epidermal-growth-factor and Chronic-Disease

The trend of increased survival in advanced tumors suggests the possibility of the transformation of cancer into a chronic disease. That goal will require therapeutic weapons with low toxicity that can be used chronically. Here we summarize the development of a therapeutic vaccine consisting in recombinant EGF chemically linked to a protein from Neisseria meningitides. In mice, the vaccine elicited antibodies to self-EGF and had anti-tumor activity. Clinical trials have shown that the vaccine is also immunogenic and well tolerated in humans. The vaccination produced a decrease in plasma EGF concentration. Advanced lung cancer patients eliciting high antibody titers of EGF had better survival. The vaccine can be used long term and integrated with other treatment modalities.

Topics: Animals; Autoantibodies; Bacterial Outer Membrane Proteins; Cancer Vaccines; Chronic Disease; Epidermal Growth Factor; Humans; Lung Neoplasms; Neisseria meningitidis; Treatment Outcome; Vaccines, Synthetic

Topics: Animals; Cardiotonic Agents; Chronic Disease; Epidermal Growth Factor; Heart Failure; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Myocytes, Cardiac; Signal Transduction

Asthma is increasing in prevalence in the developing world, affecting approximately 10% of the world's population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time. Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-beta is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma. This review highlights the role of transforming growth factor-beta in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-beta and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways. A fuller comprehension of the actions of transforming growth factor-beta, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.

Topics: Asthma; Chronic Disease; Epidermal Growth Factor; Epithelial Cells; Extracellular Matrix; Humans; Microscopy, Electron; Signal Transduction; Transforming Growth Factor beta

'Growth factors' is an umbrella term used to describe a variety of chemical messengers found in a wide range of tissues, which have a number of functions including the regulation of cell and tissue growth and development. Several growth factors have been proposed as ideal agents to promote wound healing. This review discusses their functions and how they can be applied in the management of chronic wounds.

Topics: Chronic Disease; Epidermal Growth Factor; Fibroblast Growth Factors; Growth Substances; Humans; Insulin-Like Growth Factor I; Interleukin-1; Platelet-Derived Growth Factor; Transforming Growth Factor beta; Wound Healing; Wounds and Injuries

Topics: Acute Disease; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Humans; Mast Cells; Nerve Growth Factors; Pancreatitis; Transforming Growth Factor beta

Topics: Chronic Disease; Epidermal Growth Factor; Fibroblast Growth Factors; Genetic Therapy; Growth Substances; Humans; Platelet-Derived Growth Factor; Signal Transduction; Skin, Artificial; Somatomedins; Transforming Growth Factor beta; Treatment Outcome; Wound Healing; Wounds and Injuries

It is proposed that chronic moderate hyperhomocysteinemia has a causal role in a number of common diseases of late life, including occlusive vascular disease, cognitive decline, senile osteoporosis and presbyopia. These diseases are seen as clinical counterparts of the main manifestations of homocystinuria (vascular occlusions of arteries and veins, mental retardation, osteoporosis and ectopia lentis, respectively) that develop only after many years of exposure to moderately elevated homocysteine (Hcy) levels. The multisystem toxicity of Hcy is attributed to its spontaneous chemical reaction with many biologically important molecules, primarily proteins. The formation of these Hcy-adducts is dependent on time and Hcy concentration and leads to loss or diminution of function of the derivatized molecules. Irreversible homocysteinylation of long-lived proteins should lead to cumulative damage and progressive clinical manifestations. Fibrillin 1 is seen as the paradigm of extracellular connective tissue proteins that are specially susceptible to Hcy (and presumably Hcy thiolactone) attack. The prominent presence of epidermal growth factor (EGF)-like domains in fibrillin and in many other extracellular proteins of the coagulation, anticoagulation, and lipoprotein transport pathways, all of which malfunction in hyperhomocysteinemia, suggests that EGF-like domains may be preferential sites of homocysteinylation.

Topics: Aging; Animals; Chronic Disease; Connective Tissue; Epidermal Growth Factor; Homocysteine; Humans; Hyperhomocysteinemia

Topics: Asthma; Bronchi; Chronic Disease; Epidermal Growth Factor; Epithelium; Fibrosis; Humans; Models, Immunological; Signal Transduction

Recent experiments have shown the healing potential of growth factors in tissue repair. Epidermal interference and fibroblast growth factors in the healing of acute and chronic tympanic membrane perforations are reviewed and discussed.

Topics: Acute Disease; Chronic Disease; Epidermal Growth Factor; Fibroblast Growth Factor 2; Growth Substances; Humans; Regeneration; Tympanic Membrane Perforation

Important role is attributed to the growth factors in the development, growth, and restitution after injury of the gastrointestinal tract. The common feature of growth factors is their ability to stimulate the growth and mitosis of quiescent cells in a nutritionally complete medium which in itself is not sufficient to initiate cell division. Epidermal growth factor prevents efficiently the experimentally induced acute gastric mucosal lesions induced by aspirin, absolute ethanol, HCl, NaCl, immobilization, and immersion and it accelerates the healing of acetic acid-induced chronic gastric and cysteamine-induced chronic duodenal ulcers. It proved to be also useful in the treatment of human gastric ulcers. Fibroblast growth factor possesses similar gastroprotective and chronic ulcer-healing properties. Its effects is much more potent than that of epidermal growth factor and that of H2-receptor blockers. The "trefoil"-peptides constitute the latest family of growth factors which are supposed to be involved in the regeneration of the normal and the ulcerated gastrointestinal mucosa. Polyamines are non-peptide growth promoting compounds present in all eukaryotic cells; their gastroprotective and ulcer-healing properties have also been published. The use of some growth factors as regenerative and angiogenic therapy could open a new, alternative way in the future management of peptic ulcer disease.

Topics: Animals; Aspirin; Chronic Disease; Duodenal Ulcer; Epidermal Growth Factor; Ethanol; Fibroblast Growth Factors; Gastric Mucosa; Humans; Polyamines; Rats; Stomach Ulcer

Polypeptide growth factors regulate cellular processes involved in wound healing. Application of exogenous growth factors can modify the healing process and, with recombinant DNA technology, growth factors can now be made in sufficient quantity to be used therapeutically. Several growth factors are showing promising results in clinical trials, especially in cases of impaired healing, such as chronic ulcers. Preclinical studies indicate that further growth factors may have therapeutic potential in a wide range of wound-healing applications. The use of specifically designed and modified growth factors, growth-factor inhibitors, and sequential and combinatorial dosing regimes offer further possibilities for enhancing wound healing.

Topics: Animals; Chronic Disease; Epidermal Growth Factor; Fibroblast Growth Factors; Growth Substances; Humans; Peptides; Platelet-Derived Growth Factor; Recombinant Proteins; Transforming Growth Factor alpha; Transforming Growth Factor beta; Ulcer; Wound Healing; Wounds and Injuries

Lipoic acid (LA) and hyperbaric oxygenation therapy (HBOT) improve chronic wound healing.. We compared the effects of LA or its enantiomer R-(+)-lipoic acid (RLA) on wound healing.. Groups LA + HBOT (L), RLA + HBOT (R) and placebo + HBOT (P). Lesion areas measured before treatment and on 20th and 40th day. The biopsies and plasma were harvested before treatment and on 7th and 14th (measurements of VEGF, vascular endothelial growth factor; EGF, epidermal growth factor, TNF-α and IL-6).. Ulcers improved more on RLA. In both L and R groups, EGF and VEFG increased in time. RLA decreased IL-6 on T7 and T14, which did not happen with LA. TNF-α levels decreased on T14 in both LA and RLA.. The improved wound healing is associated with increased EGF and VEGF and reduced plasma TNF-α and IL-6.. RLA may be more effective than LA in improving chronic wound healing in patients undergoing HBO therapy.

Topics: Aged; Aged, 80 and over; Antioxidants; Chronic Disease; Combined Modality Therapy; Diabetic Foot; Double-Blind Method; Epidermal Growth Factor; Female; Humans; Hyperbaric Oxygenation; Interleukin-6; Male; Middle Aged; Stereoisomerism; Thioctic Acid; Tumor Necrosis Factor-alpha; Wound Healing

A limited number of studies have demonstrated that some modulators of inflammation can be altered by the consumption of sweet cherries. We have taken a proteomics approach to determine the effects of dietary cherries on targeted gene expression. The purpose was then to determine changes caused by cherry consumption in the plasma concentrations of multiple biomarkers for several chronic inflammatory diseases in healthy humans with modestly elevated C-reactive protein (CRP; range, 1-14 mg/L; mean, 3.5 mg/L; normal, <1.0 mg/L). Eighteen men and women (45-61 y) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. Fasting blood samples were taken before the start of consuming the cherries (study d 7), 28 d after the initiation of cherry supplementation (d 35), and 28 d after the discontinuation (d 63). Of the 89 biomarkers assessed, cherry consumption for 28 d altered concentrations of 9, did not change those of 67, and the other 13 were below the detection limits. Cherry consumption decreased (P < 0.05) plasma concentrations of extracellular newly identified ligand for the receptor for advanced glycation end products (29.0%), CRP (20.1%), ferritin (20.3%), plasminogen activator inhibitor-1 (19.9%), endothelin-1 (13.7%), epidermal growth factor (13.2%), and IL-18 (8.1%) and increased that of IL-1 receptor antagonist (27.9%) compared with corresponding values on study d 7. The ferritin concentration continued to decrease between d 35 and 63 and it was significantly lower on d 63 than on d 7. Because the participants in this study were healthy, no clinical pathology end points were measured. However, results from the present study demonstrate that cherry consumption selectively reduced several biomarkers associated with inflammatory diseases.

Topics: Biomarkers; C-Reactive Protein; Chronic Disease; Diet; Dietary Supplements; Endothelin-1; Epidermal Growth Factor; Female; Ferritins; Fruit; Humans; Inflammation; Inflammation Mediators; Interleukin-18; Male; Middle Aged; Phytotherapy; Plant Preparations; Plasminogen Activator Inhibitor 1; Proteomics; Prunus; Receptors, Interleukin-1; Reference Values

This paper studies the healing effect of recombinant human epidermal growth factor (EGF) on chronic diabetic foot ulcers. A total of 89 patients (65 male and 24 female) aged from 36 to 82 years (average of 54) enrolled for the prospective, open-label trial, crossover study. Predetermined criteria were used for diagnosis and classification of ulcer. The average duration of ulcer was 6 months (range from 3 to 27 months) prior to study. Upon study, the ulcers were debrided and treated with hydrocolloid or composite dressing depending on the condition of the wound. If treatment effect was minimal using advanced dressing for 3 weeks, patients were crossed over to twice-a-day treatment with 0.005% EGF and advanced dressing. Among the patients, 21 patients showed improvement using hydrocolloid or composite dressing alone and 68 patients were crossed over to treatment with EGF and advanced dressing. In the EGF-treated patients, complete healing was noted in 52 patients within an average of 46 days (range from 2 to 14 weeks). Recurrence was not noted during the 6-month observation. But 5 patients showed new lesions different from the prior site. Sixteen patients required further interventions. This paper suggests that topical treatment with EGF combined with advanced dressing may have positive effects in promoting healing of chronic diabetic foot wounds.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Cross-Over Studies; Diabetic Foot; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Prospective Studies; Wound Healing

The object of this study was to compare the expression of epidermal growth factor, interleukin-1alpha, and tumor necrosis factor-alpha in chronic otitis media with or without cholesteatoma.. It has been reported that cytokines and epidermal growth factor are effective in the bone resorption process in chronic otitis media. Bone resorption can also occur in chronic otitis media without cholesteatoma. However, comparative analysis is lacking. This issue has been investigated in a blind, controlled and prospective analysis.. The activities of interleukin-1alpha, tumor necrosis factor-alpha, and epidermal growth factor were determined by commercially available enzyme-linked immunosorbent assay kits in tissue biopsy samples from 16 patients without cholesteatoma and from 23 patients with cholesteatoma (cholesteatoma epithelium). To establish a control group, external auditory canal skin was randomly collected from two groups (21 patients). The Mann-Whitney and Kruskal-Wallis tests were used for statistical analysis.. The levels of interleukin-1alpha, tumor necrosis factor-alpha, and epidermal growth factor in tissue samples from the group with cholesteatoma were significantly greater than those in the group without cholesteatoma and the control group. No correlation was observed with other clinical factors such as age, sex, and antibiotic coverage.. Higher levels of cytokines in patients with cholesteatoma confirm that the destructive behavior of cholesteatoma is likely mediated by cytokines and epidermal growth factor and is the result of keratinocyte activity. Antibiotic treatment does not affect the level of cytokine concentration in patients with chronic otitis media and cholesteatoma, although the ear discharge subsides and inflammation-related symptoms regress in some cases.

Topics: Adolescent; Adult; Biopsy; Bone Resorption; Cholesteatoma, Middle Ear; Chronic Disease; Ear, External; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Humans; Interleukin-1; Male; Middle Aged; Otitis Media; Prospective Studies; Tumor Necrosis Factor-alpha

Epidermal growth factor (EGF) is a mitogen that stimulates cell division of various cells of epidermal origin. The present study was undertaken to clarify whether the serum level of EGF is correlated with the disease activity during local therapy with dithranol in psoriasis. We examined serum EGF concentrations in acute and chronic psoriasis before and after topical treatment with dithranol and the correlation with Psoriasis Activity and Severity Index (PASI). Male patients were divided into two groups: acute psoriasis (AP, 18 cases) and chronic psoriasis (CP, 17 cases). A control group C consisted of 20 healthy male volunteers. Radioimmunoassay of EGF was performed using the reagent pack (Amersham, UK). In the CP group mean EGF was higher before treatment than in the AP and C groups, but not significantly. EGF concentration after local treatment was higher in the CP group than the AP group (P < 0.02); the AP group, however, showed statistically significant decrease of EGF after the treatment (P < 0.04). No correlation between EGF and PASI was found. Serum EGF concentration increased in 19/35 treated patients.

Topics: Acute Disease; Administration, Cutaneous; Administration, Topical; Anthralin; Anti-Inflammatory Agents; Chronic Disease; Epidermal Growth Factor; Humans; Male; Psoriasis; Severity of Illness Index; Treatment Outcome

Topics: Acute Disease; Adult; Biomarkers; Chronic Disease; Epidermal Growth Factor; Humans; Male; Prognosis; Psoriasis; Reference Values; Severity of Illness Index

Epidermal growth factor is an important modulator of cell growth, and its role in normal wound healing is well documented. Epidermal growth factor receptors have been identified in tympanic membranes of different animals. The ability of epidermal growth factor to promote healing of tympanic membrane perforations has recently been shown in experimental animals. We performed a double-blind, placebo-controlled study of the effect of epidermal growth factor applied locally on the tympanic membrane for 1 week in patients with chronic perforations. Seventeen adult patients took part in the study, eight in the epidermal growth factor group and nine in the placebo group. Three placebo-treated patients were later treated with epidermal growth factor, and five patients received repeated epidermal growth factor treatment. Perforation size was measured as a percentage of the tympanic membrane area before and at least 1 month (mean, 2.6 months) after treatment. One perforation in the placebo group healed completely, but none of the epidermal growth factor-treated perforations closed. Perforations became slightly smaller in both groups (mean decrease, 0.3% and 2.7% for epidermal growth factor and placebo, respectively), but these changes in size were not statistically significant for either group. At otomicroscopy, a proliferation reaction with thickening of the tympanic membrane and pseudomembrane formation at the perforation edge could be seen in some ears. Histologically, a sample from one epidermal growth factor-treated ear demonstrated signs of hypertrophic epithelium when compared with the morphology of a placebo-treated tympanic membrane. The only complications were two mild infections in the placebo group. Hearing remained stable after epidermal growth factor treatment.

Topics: Administration, Topical; Adult; Audiometry, Pure-Tone; Bacterial Infections; Cell Division; Chronic Disease; Double-Blind Method; Ear Diseases; Epidermal Growth Factor; Epithelium; Female; Follow-Up Studies; Hearing; Humans; Hypertrophy; Male; Microscopy; Placebos; Tympanic Membrane; Wound Healing

We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing.

Topics: Administration, Cutaneous; Adult; Aged; Arthritis, Rheumatoid; Burns; Chronic Disease; Diabetes Mellitus, Type 2; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Pilot Projects; Postoperative Complications; Prospective Studies; Silver Sulfadiazine; Skin Ulcer; Wound Healing

In this study we aimed to investigate epidermal growth factor (EGF), interleukin (IL1)-α and IL-6 levels, and hematological parameters in the serum samples of patients with chronic cholesteatomatous otitis media (CCOM). This prospective included 40 patients who underwent surgery due to CCOM between June 2020 and May 2021. The stage of middle ear cholesteatoma was determined on each chart using the EAONO/JOS system. The control group comprised of 30 adults who were scheduled for septoplasty over the same period in our hospital, had no otological complaints, and had normal otological findings. The demographic, clinical, and laboratory data of the patients were obtained from the electronic medical record system of our hospital. The serum EGF, IL1-α and IL-6 levels, and hematological parameters (neutrophil-lymphocyte ratio (NLR) and mean platelet volume (MPV)) were compared between the CCOM and control groups. Seven patients had Stage 1 and 33 patients had Stage 2 middle ear cholestatoma. There was no statistically significant difference between the CCOM and control groups in terms of age and gender (p=0.092 and p=0.616, respectively). The serum EGF and IL1-α levels of the CCOM group were statistically significantly higher than those of the control group (p=0.047 and p=0.013, respectively). No statistically significant difference was observed in the serum IL-6 levels of the CCOM and control groups (p=0.675). There was also no significant difference between the CCOM and control groups in terms of the mean NLR and MPV values ​​(p=0.887 and p=0.164, respectively). There was no significant difference between the Stage 1 and Stage 2 cholesteatoma subgroups in terms of the mean EGF, IL1-α, IL-6 levels (p=0.204, p=0.557 and p=0.613, respectively), and the mean NLR and MPV values (p=0.487, p=0.439, respectively). Increased serum EGF and IL1-α levels in patients with CCOM suggest that these cytokines may play a role in cholesteatomatous epithelial hyperproliferation.

Topics: Adult; Cholesteatoma, Middle Ear; Chronic Disease; Epidermal Growth Factor; Humans; Interleukin-1alpha; Interleukin-6; Lymphocytes; Mean Platelet Volume; Neutrophils; Nigeria; Otitis Media; Prospective Studies; Retrospective Studies

Induction of intrinsic liver regeneration is an unmet need that can be achieved by temporally activating key hepatocyte regenerative pathways. Here, we establish an efficient, safe, non-integrative method to transiently express hepatocyte-growth-factor (HGF) and epidermal-growth-factor (EGF) in hepatocytes via nucleoside-modified, lipid-nanoparticle-encapsulated mRNA (mRNA-LNP) delivery in mice. We confirm specific hepatotropism of mRNA-LNP via intravenous injection of firefly luciferase encoding mRNA-LNP, with protein expression lasting about 3 days. In the liver, virtually all hepatocytes are transfected along with a subpopulation of endothelial and Kupffer cells. In homeostasis, HGF mRNA-LNP efficiently induce hepatocyte proliferation. In a chronic liver injury mouse model recapitulating non-alcoholic fatty liver disease, injections of both HGF and EGF mRNA-LNP sharply reverse steatosis and accelerate restoration of liver function. Likewise, HGF and EGF mRNA-LNP accelerate liver regeneration after acetaminophen-induced acute liver injury with rapid return to baseline ALT levels. This study introduces mRNA-LNP as a potentially translatable safe therapeutic intervention to harness liver regeneration via controlled expression of endogenous mitogens in vivo.

Topics: Acetaminophen; Animals; Cell Proliferation; Chronic Disease; Disease Models, Animal; Epidermal Growth Factor; Female; Green Fluorescent Proteins; Hepatocyte Growth Factor; Hepatocytes; Homeostasis; Injections; Lipids; Liver; Liver Function Tests; Liver Regeneration; Mice, Inbred C57BL; Nanoparticles; Nucleosides; RNA, Messenger

Previous studies have demonstrated that neurotrophic factors may play a critical role in the severity of clinical symptoms in schizophrenia. However, it remains unknown whether serum levels of epidermal growth factor (EGF) in schizophrenia are similar to those observed in the case of other neurotrophic factors. Therefore, we compared serum EGF concentrations in first-episode drug-naive (FEP) patients and medicated chronic schizophrenic patients with healthy controls in order to explore whether EGF levels are related to psychopathological symptoms. We measured the serum levels of EGF in 78 first-episode medication-naive schizophrenia patients, 76 medicated chronic schizophrenic patients, and 75 healthy controls using the sandwich ELISA method. Disease severity were measured using the positive and negative syndrome scale (PANSS). Serum EGF levels showed a significant decrease in schizophrenia patients in comparison to healthy subjects. Serum EGF levels in FEP patients are indistinguishable from chronic cases. EGF levels were related to PANSS general symptom subscales in both FEP never-medicated and medicated patients. It is interesting that serum EGF levels were negatively correlated with the PANSS cognitive subscales, with the exception of the patients with chronic schizophrenia. Our preliminary results indicated that EGF may play a role in this illness and that it could be used as a potential biomarker of disease severity. Moreover, EGF may be associated with cognitive subscales of PANSS in FEP patients. Future studies should investigate the relationship between EGF and cognitive function as measured using standardized neuropsychological assessments to identify potential biomarkers related with cognition.

Topics: Adolescent; Adult; Chronic Disease; Epidermal Growth Factor; Female; Humans; Male; Psychopathology; Schizophrenia; Schizophrenic Psychology; Young Adult

The present study investigated the potent therapeutic effects of Ruscogenin, main steroid sapogenin of traditional Chinese plant called 'Ophiopogon japonicas', on chronic ulcer model established with acetic acid in rats.. 24 rats were attenuated to the sham (2 ml/kg/day isotonic solution), control (untreated ulcer) and treatment (3 ml/kg/day ruscogenin) groups. After treatment for 2 weeks, gastric tissues were collected and prepared for light microscopic (H&E), immunohistochemical (Collagen I, III and IV) and biochemical analysis [Epidermal growth factor (EGF), Prostaglandin E2 (PGE2), Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 and 8 (IL-6 and IL-8), Lipid Peroxidase (LPO), Myeloperoxidase (MPO), Glutathione (GSH) and Glutathione Peroxidase (GSH-Px)] and transmission electron microscopy (TEM).. Macroscopic scoring showed that the ulceration area of ruscogenin-treated group decreased compared with control group. Immunohistochemical analysis revealed ruscogenin ameliorated and restored the levels of Collagen I and IV to the levels of sham group. Tissue levels of EGF and PGE2 enhanced significantly in untreated ulcer group while were higher in treated ulcer group than the control group. TNF-α, IL-6, IL-8, LPO, MPO levels increased significantly in control group whereas decreased in treated rats after ruscogenin treatment. However, levels of GSH and GSH-Px increased significantly in treatment group. TEM showed chief cells and parietal cells of ulcer group having degenerated organelles while ruscogenin group had normal ultrastructure of cells.. There are potent anti-inflammatory and anti-oxidant effects of ruscogenin on gastric ulcer and may be successfully used as a safe and therapeutic agent in treatment of peptic ulcer.

Topics: Animals; Chronic Disease; Collagen; Cytokines; Dinoprostone; Disease Models, Animal; Epidermal Growth Factor; Female; Microscopy, Electron, Transmission; Ophiopogon; Parietal Cells, Gastric; Peroxidases; Phytotherapy; Rats, Sprague-Dawley; Spirostans; Stomach Ulcer; Tumor Necrosis Factor-alpha

The etiology of non-healing ulcers depends on both systemic and local factors. The introduction of advanced dressing, negative wound therapy and compression therapy have undoubtedly improved clinical outcomes. The principal aim of study was to demonstrate the efficacy of dermal micrografts in the treatment of ulcers with different etiologies. The second aim was to investigate in vitro the action of micrografts in the regenerative process.. The dermal micro-grafts were obtained from mechanical disaggregation of small pieces of skin tissue through a medical device called Rigeneracons.. We observed in vivo the ability of dermal autologous micrografts to improve the healing of venous, diabetic, pressure and post-traumatic ulcers after few week of treatment accomplished in general with a better quality of life for the patients. In vitro results showed that these micrografts express mesenchymal stem cells (MSCS) marker such as CD34, CD73, CD90 and CD105, and are able to form a viable and proliferative biocomplex with collagen sponge. Finally, the site of ulcers displayed a different expression of epidermal growth factors, insulin-like growth factors, platelet-derived growth factors and their receptors and tumor necrosis factor-β with respect to healthy skin samples.. We reported a good outcome for the treatment of chronic ulcers using dermal autologous micrografts. Finally, we suggest that the positivity to MSCs markers and the ability to interact with a scaffold can play a key role in their regenerative properties.

Topics: 5'-Nucleotidase; Aged; Aged, 80 and over; Antigens, CD34; Autografts; Biomarkers; Chronic Disease; Dermis; Epidermal Growth Factor; ErbB Receptors; Gene Expression; Humans; Mesenchymal Stem Cells; Middle Aged; Platelet-Derived Growth Factor; Receptors, Platelet-Derived Growth Factor; Regeneration; Regenerative Medicine; Reverse Transcriptase Polymerase Chain Reaction; Skin Transplantation; Skin Ulcer; Treatment Outcome

That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model.. A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle.. The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks.. The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration.. This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

Topics: Animals; Chronic Disease; Drug Delivery Systems; Epidermal Growth Factor; Fibroblast Growth Factor 2; Heparin-binding EGF-like Growth Factor; Hydrogels; Male; Mice; Mice, Inbred CBA; Polymers; Tympanic Membrane Perforation; Wound Healing

Chronic pain is a debilitating condition with unknown mechanism. Nociceptive sensitivity may be regulated by genetic factors, some of which have been separately linked to neuronal progenitor cells and neuronal differentiation. This suggests that genetic factors that interfere with neuronal differentiation may contribute to a chronic increase in nociceptive sensitivity, by extending the immature, hyperexcitable stage of spinal cord neurons. Although adult rodent spinal cord neurogenesis was previously demonstrated, the fate of these progenitor cells is unknown. Here, we show that peripheral nerve injury in adult rats induces extensive spinal cord neurogenesis and a long-term increase in the number of spinal cord laminae I-II neurons ipsilateral to injury. The production and maturation of these new neurons correlates with the time course and modulation of nociceptive behaviour, and transiently mimics the cellular and behavioural conditions present in genetically modified animal models of chronic pain. This suggests that the number of immature neurons present at any time in the spinal cord dorsal horns contributes to the regulation of nociceptive sensitivity. The continuous turnover of these neurons, which can fluctuate between normal and injured states, is a dynamic regulator of nociceptive sensitivity. In support of this hypothesis, we find that promoters of neuronal differentiation inhibit, while promoters of neurogenesis increase long-term nociception. TrkB agonists, well-known promoters of nociception in the short-term, significantly inhibit long-term nociception by promoting the differentiation of newly produced immature neurons. These findings suggest that promoters of neuronal differentiation may be used to alleviate chronic pain.

Topics: Aging; Animals; Biomarkers; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Proliferation; Chronic Disease; Constriction, Pathologic; Epidermal Growth Factor; Fibroblast Growth Factor 2; Male; Neural Stem Cells; Neurogenesis; Neurons; Nociception; Rats, Sprague-Dawley; Spinal Cord; Time Factors

Topics: Adrenal Cortex Hormones; Adrenergic alpha-2 Receptor Agonists; Adult; Aged; Aged, 80 and over; Airway Obstruction; Airway Remodeling; Asthma; Chronic Disease; Elasticity; Epidermal Growth Factor; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Lung; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Pulmonary Emphysema; Radiography

Rehabilitation is the only treatment option for chronic stroke deficits, but unfortunately, it often provides incomplete recovery. In this study, a novel combination of growth factor administration and rehabilitation therapy was used to facilitate functional recovery in a rat model of cortical stroke.. Ischemia was induced via injection of endothelin-1 into the sensorimotor cortex. This was followed by either a 2-week infusion of epidermal growth factor and erythropoietin or artificial cerebrospinal fluid into the ipsilateral lateral ventricle. Two weeks after ischemia, animals began an 8-week enriched rehabilitation program. Functional recovery was assessed after ischemia using the Montoya staircase-reaching task, beam-traversing, and cylinder test of forelimb asymmetry.. The combination of growth factor infusion and rehabilitation led to a significant acceleration in recovery in the staircase task. When compared with controls, animals receiving the combination treatment attained significant recovery of function at 4 weeks after stroke, whereas those receiving rehabilitation alone did not recover until 10 weeks. Significant recovery was also observed on the beam-traversing and cylinder tasks.. Combining behavioral rehabilitation with growth factor infusion accelerates motor recovery. These data suggest a promising new avenue of combination therapies that may have the potential to reduce the rehabilitation time necessary to recover from sensorimotor deficits arising from stroke.

Topics: Animals; Chronic Disease; Disease Models, Animal; Endothelin-1; Epidermal Growth Factor; Erythropoietin; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Stroke; Stroke Rehabilitation

Chronic allograft injury remains a major problem in clinical kidney transplantation and different growth factors participate in its development. Epidermal growth factor (EGF) affects cell proliferation and mitogenesis through its tyrosine kinase receptor. Erlotinib is an orally administered tyrosine kinase inhibitor used in clinical oncology to inhibit EGF signaling. We investigated its effect on the development of chronic allograft injury in an experimental kidney transplantation model.. Kidney transplantations were performed between Dark Agouti and Wistar Furth rats. Recipients were immunosuppressed either with cyclosporine A (CsA, 1.5 mg/kg/day subcutaneously) or with CsA and erlotinib (10 mg/kg/day orally). Kidney grafts were harvested after 5 and 90 days for histology and immunohistochemistry. Aorta denudation model was used for the erlotinib dose response study to define the optimal dose for the transplantation study.. Epidermal growth factor expression was increased in CsA-treated allografts which developed intense chronic changes on day 90. Erlotinib ameliorated neointimal formation in the dose response study. In addition, erlotinib decreased chronic rejection changes and maintained better graft function in kidney transplantation model. Late posttransplant EGF and EGF receptor levels were reduced with erlotinib.. Based on these findings, EGF mediates in part the development of chronic allograft injury. Its inhibition with erlotinib prevents chronic rejection and maintains better allograft function. Therefore, EGF blocking by erlotinib provides a novel pathway to prevent chronic allograft injury.

Topics: Animals; Aorta; Chronic Disease; Epidermal Growth Factor; Erlotinib Hydrochloride; Graft Rejection; Immunohistochemistry; Kidney; Kidney Transplantation; Male; Quinazolines; Rats; Rats, Wistar; Transplantation, Homologous

To evaluate the changes of epidermal growth factor (EGF) in serum before and after endoscopic surgery in patients with chronic sinusitis, and then to explore its clinical significance.. Serum was collected before and after operation and EGF concentrations were measured by the radioimmunoassay at different times.. EGF levels in patients with chronic sinusitis (1.24 +/- 0.41) microg/L were higher than that in control group (0.92 +/- 0.23) microg/L, but there were no significantly difference between them (P > 0.05). The concentrations of EGF were reduced after surgery, and the lowest were evaluated after 4 weeks. Significant difference of EGF concentrations were found between before and 4 weeks after operation (P < 0.01). The concentration of EGF were raised 6 weeks after surgery, and returned to normal after 8 weeks.. The changes of EGF in serum before and after endoscopic surgery may relate with the epithelization process of sinus mucosa after endoscopic surgery.

Topics: Adult; Case-Control Studies; Chronic Disease; Endoscopy; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Sinusitis; Treatment Outcome; Young Adult

Coexistence of pulmonary tuberculosis (TB) and lung cancer in clinic poses significant challenges for the diagnostic and treatment of both diseases. Although association of chronic inflammation and cancer is well-documented, causal relationship between TB infection and lung cancer are not understood. We present experimental evidence that chronic TB infection induces cell dysplasia and squamous cell carcinoma (SCC) in a lung-specific manner. First, squamous cell aggregates consistently appeared within the lung tissue associated with chronic TB lesions, and in some cases resembled SCCs. A transplantable tumor was established after the transfer of cells isolated from TB lung lesions into syngeneic recipients. Second, the (Mycobacterium tuberculosis) MTB-infected macrophages play a pivotal role in TB-induced carcinogenesis by inducing DNA damage in their vicinity and by the production of a potent epidermal growth factor epiregulin, which may serve as a paracrine survival and growth factor responsible for squamous metaplasia and tumorigenesis. Third, lung carcinogenesis during the course of chronic TB infection was more pronounced in animals with severe lung tissue damage mediated by TB-susceptibility locus sst1. Together, our experimental findings showed a causal link between pulmonary TB and lung tumorigenesis and established a genetic model for further analysis of carcinogenic mechanisms activated by TB infection.

Topics: Animals; Antitubercular Agents; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Chronic Disease; Disease Models, Animal; Epidermal Growth Factor; Epiregulin; Female; Gene Expression; Genetic Predisposition to Disease; Host-Pathogen Interactions; Isoniazid; Lung; Lung Neoplasms; Macrophages; Male; Mice; Mice, Congenic; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred Strains; Mycobacterium tuberculosis; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Tuberculosis, Pulmonary

It has been demonstrated that parotid glands of rats infected with Trypanosoma cruzi present severe histological alterations; changes include reduction in density and volume of the acini and duct systems and an increase in connective tissue. We evaluated the association between morphological changes in parotid glands, circulating testosterone levels and epidermal growth factor receptor (EGF-R) expression in experimental Chagas disease in rats. Animals at 18 days of infection (acute phase) showed a significant decrease in body weight, serum testosterone levels and EGF-R expression in the parotid gland compared with a control group. Since decreases in body weight could lead to a reduction in circulating testosterone concentration, we believe that the reduction in EGF-R expression in parotid glands of infected rats is due to alterations in testosterone levels and atrophy of parotid glands is caused by changes in EGF-R expression. Additionally, at 50 days (chronic phase) of infection parotid glands showed a normal histological aspect likely due to the normalization of the body weight. These findings suggest that the testosterone-EGF-R axis is involved in the histological changes.

Topics: Acute Disease; Animals; Chagas Disease; Chronic Disease; Epidermal Growth Factor; Male; Parotid Gland; Rats; Rats, Sprague-Dawley; Testosterone; Time Factors; Trypanosoma cruzi; Weight Loss

Office treatment for chronic tympanic membrane (TM) perforations has limitations, and alternative methods to myringoplasty are sometimes needed. Serum lacks antigenicity and contains a large variety of growth factors known to modulate proliferation of various tissues to promote wound healing effects. Our purpose was to evaluate the feasibility of autologous serum eardrops therapy with a chitin membrane for closing TM perforations.. In the outpatient clinic, the perforation margin was cauterized with silver nitrate, and the perforation was covered with a chitin membrane. Patients were instructed to apply autologous serum eardrops daily. Patients were examined every 2 weeks, and the procedure was repeated.. We treated 19 sequential patients with chronic TM perforation in 1 ear between October 2005 and September 2007. Closure of the TM was achieved in 11 (58%) of 19 ears, and reduction of the perforation size was observed in 2 ears (11%). Closure rates for small, medium, and large perforations were 57 (8 of 14), 0 (0 of 1), and 75% (3 of 4), respectively. Closure rates for perforations attributable to intratympanic dexamethasone treatment, after myringoplasty and chronic otitis media were 67 (2 of 3), 67 (2 of 3), and 54% (7 of 13), respectively. Time for closure took from 15 to 175 days, with an average of 68 days (5.9 clinic visits). During autologous serum eardrop therapy with a chitin membrane, no remarkable side effects in the treated ears were observed. Measurement of the concentration of the epidermal growth factor, transforming growth factor beta1, fibronectin, and interleukin 6 in the serum showed no decrease in 14 days, suggesting activity remained stable in that period.. Autologous serum eardrops therapy with a chitin membrane, which requires no surgical intervention, was found to be a promising office-based technique for the closure of chronic TM perforations because of its ease, safeness, and feasibility. However, additional studies are needed to independently analyze the specific benefits of the serum drops and the chitin membrane.

Topics: Administration, Topical; Adolescent; Aged; Chitin; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Fibronectins; Humans; Interleukin-6; Male; Middle Aged; Polymers; Serum; Transforming Growth Factor beta1; Tympanic Membrane Perforation; Young Adult

Neurotrophic factors (NFs) play a pivotal role in the development of the central nervous system. They are thus also suspected of being involved in the etiology of schizophrenia. Previous studies reported a decreased level of serum brain-derived neurotrophic factor (BDNF) in schizophrenia, whereas the association of epidermal growth factor (EGF) with this illness remains controversial. Using a two-site enzyme immunoassay, we conducted the simultaneous measurement of serum BDNF and EGF levels in a group of patients with chronic schizophrenia (N=74) and a group of normal controls matched in age, body mass index, smoking habit and sex (N=87). We found that, compared to normal controls, patients with chronic schizophrenia exhibited lower serum levels of both BDNF and EGF across all ages examined (21-59 years). The serum levels of BDNF and EGF were negatively correlated in the controls (r=-0.387, P=0.0002) but not in the patients. Clinical parameters such as duration of illness and psychiatric rating scale also showed no robust correlations with the NF levels. Collectively, these results suggest that pervasive, abnormal signaling of NFs underlies the pathophysiology of chronic schizophrenia.

Topics: Adult; Brain-Derived Neurotrophic Factor; Chronic Disease; Epidermal Growth Factor; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Schizophrenia; Statistics, Nonparametric

Chronic renal disease is characterized by declining renal function, loss of intrinsic renal cells, and their replacement with fibrotic tissue. This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor beta(1) (TGFbeta(1)) mRNA (P<0.05). Conversely, a 1 U increase in epidermal growth factor (EGF) mRNA was associated with a 47% decrease in tubulointerstitial apoptosis (P<0.05). Tubulointerstitial injury was correlated with increased TGFbeta(1) and tumour necrosis factor alpha (TNFalpha) mRNA (P<0.005) and decreased EGF mRNA (P<0.05). Additionally, for a 10 U decrease in the glomerular filtration rate there was an estimated increase of 5 and 10% in TGFbeta(1) and TNFalpha mRNA, respectively (P<0.05), whereas EGF mRNA decreased by an estimated 15% (P<0.005). Therefore dysregulation of cytokine/growth factor expression plays a central role in the progression of chronic renal disease through contribution to renal cell loss, tubulointerstitial injury, and renal dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Apoptosis; Biomarkers; Biopsy; Chronic Disease; Epidermal Growth Factor; Female; Gene Expression; Gene Expression Regulation; Glomerular Filtration Rate; Humans; Intercellular Signaling Peptides and Proteins; Kidney; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Proteinuria; RNA, Messenger; Transforming Growth Factor beta1; Treatment Outcome; Tumor Necrosis Factor-alpha

This case report describes the first successful use of recombinant human epidermal growth factor (rh-EGF) in radiation-induced chronic wound of bone and skin which remains to be difficult to treat. Such wound on the chest of a 59-year-old female patient is presented lasting 3 years despite flap surgery and conventional treatment. The treatment with rh-EGF achieved healing within 16 weeks but further study to evaluate its potential for radiation-induced chronic wounds is warranted.

Topics: Breast Neoplasms; Chronic Disease; Epidermal Growth Factor; Female; Humans; Middle Aged; Radiation Injuries; Recombinant Proteins; Ulcer; Wound Healing

To investigate the expression of epidermal growth factor receptor (EGFR) messenger RNA (mRNA) in human sinus mucosa and to compare the expression of EGFR and EGF among patients with chronic rhinosinusitis (CRS), patients with CRS and nasal polyposis (CRS/NP), and a healthy control group.. Maxillary sinus ostia mucosa was harvested from patients undergoing endoscopic sinus surgery for CRS or CRS/NP and from patients undergoing surgery for non-CRS pathologic conditions (control group). The samples were analyzed using semiquantitative reverse transcription-polymerase chain reaction to detect mRNA of EGFR. Hematoxylin-eosin staining and immunofluorescent staining were used to localize EGFR and EGF in the sinus mucosa.. Academic research.. Three groups (CRS, CRS/NP, and control), each with 10 subjects, were enrolled in the present study.. Area ratios of positive cells in the epithelia were compared among the CRS, CRS/NP, and control groups. In addition, eosinophils were counted in the subepithelial connective tissue in the 3 groups.. The level of EGFR mRNAs in the sinus mucosa of the CRS and CRS/NP groups was statistically significantly increased compared with that in the control group (P < .01), and no statistically significant difference was found between the sinus mucosa of the CRS group and that of the CRS/NP group (P < .01). On hematoxylin-eosin staining, hyperplasia and metaplasia of epithelial goblet cells were present in the sinus mucosa of the CRS and CRS/NP groups. Epidermal growth factor receptor was mainly expressed in goblet cells and basal cells and was weakly expressed in ciliated cells, while EGF expression was located in epithelial cells and in some inflammatory cells but not in goblet cells. In the control group, expression of EGFR and EGF was lower compared with that in the CRS and CRS/NP groups. No statistically significant area ratios of positive cells differences in staining of EGFR and EGF were found between the CRS group and the CRS/NP group (P > .05), whereas statistically significant differences were found between the control group and the 2 CRS groups (P < .01). The number of eosinophils was statistically significantly increased in the CRS/NP group compared with that in the CRS group (P < .01).. Up-regulation of the EGFR cascade may have an important role regarding mucus production in the sinus mucosa of patients with CRS and CRS/NP associated with hyperplasia and metaplasia of epithelial goblet cells.

Topics: Case-Control Studies; Chronic Disease; Eosinophils; Epidermal Growth Factor; ErbB Receptors; Humans; Leukocyte Count; Nasal Mucosa; Nasal Polyps; Rhinitis; RNA, Messenger; Sinusitis

Epidermal growth factor (EGF) is predominantly secreted by salivary glands and activates Na(+)/H(+) exchanger-1 (NHE-1), which regulates intracellular pH (pH(i)). We investigated the roles of EGF and NHE-1 in esophageal epithelial defense against acid using human esophageal epithelial cell lines and a rat chronic esophagitis model. Esophageal epithelial cells were incubated with acidified medium in the absence or presence of EGF. Cell viability and changes in pH(i) were measured. Chronic acid reflux esophagitis was induced in rats with and without sialoadenectomy. Esophageal lesion index, epithelial proliferation, and expression of EGF receptors and NHE-1 were examined. EGF protected esophageal epithelial cells against acid in a dose-dependent manner, and the cytoprotective effect of EGF was completely blocked by treatment with NHE-1 inhibitors. Tyrosine kinase, calmodulin, and PKC inhibitors significantly inhibited cytoprotection by EGF, whereas MEK, phosphatidylinositol 3-kinase, and PKA inhibitors had no effect. EGF significantly increased pH(i) recovery after NH(4)Cl pulse acidification, and this increase in pH(i) recovery was significantly blocked by inhibitors of calmodulin and PKC. Sialoadenectomy led to an increase in the severity of chronic esophagitis but affected neither epithelial proliferation nor expression of EGF receptors. Expression of NHE-1 mRNA was increased in esophagitis and upregulated in rats with sialoadenectomy. The increasing severity of esophagitis in rats with sialoadenectomy was prevented by exogenous administration of EGF. In conclusion, EGF protects esophageal epithelial cells against acid through NHE activation via Ca(2+)/calmodulin and the PKC pathway. Deficiency in endogenous EGF is associated with increased severity of esophagitis. EGF and NHE-1 play crucial roles in esophageal epithelial defense against acid.

Topics: Animals; Cell Line; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Epidermal Growth Factor; Epithelium; Esophagitis, Peptic; Esophagus; Humans; Hydrogen-Ion Concentration; Male; Rats; Rats, Wistar; Sodium-Hydrogen Exchangers

Duck hepatitis B virus (DHBV) replication is up-regulated by cell cycle during the early infection of primary duck but the effect of cell cycle on DHBV replication in chronically infected hepatocyte is not known.. Hepatocytes obtained from DHBV congenitally infected embryos were used. Cell proliferation was controlled by addition of liver growth factors and the impact on viral replication analyzed.. EGF induced cell proliferation is associated with a slight increase in CCC DNA synthesis and a decrease in viral transcription. Conversely, TGFbeta blocked cell cycle progression, diminished CCC DNA synthesis but increased viral transcription.. Cell proliferation decreases DHBV transcription but this effect seems to be compensated by an opposite effect on the synthesis of CCC DNA resulting in a global moderate effect on viral replication. Our results also indicate that after division of chronically infected hepatocytes both daughter cells are infected, confirming that liver regeneration is not sufficient to induce CCC DNA eradication as suggested by the lack of effect of some long term anti-HBV therapies.

Topics: Animals; Cell Division; Chick Embryo; Chronic Disease; DNA, Viral; Ducks; Epidermal Growth Factor; Gene Expression Regulation, Viral; Hepadnaviridae Infections; Hepatitis B Virus, Duck; Hepatitis, Viral, Animal; Hepatocytes; Liver Regeneration; RNA, Viral; Transcription, Genetic; Transforming Growth Factor beta; Virus Replication

Strong interest exists about the biomolecular basis of the chronic liver diseases due to viral infections. It seems to be very interesting because of their evolutive potential. In this context the study of oncogenes and oncoproteins could be interesting as prognostic factors for chronic viral diseases of the liver. In this study the authors show the results obtained about EGF and p62 expression in 39 selected patients with cirrhosis and 3 different chronic viral hepatitis (persistent, lobular, and active).

Topics: Biomarkers, Tumor; Biopsy; Chronic Disease; Epidermal Growth Factor; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis, Viral, Human; Hepatocytes; Humans; Liver; Liver Cirrhosis; Prognosis; Proto-Oncogene Proteins c-myc; Receptor, ErbB-2

To study the pathologic change and molecular regulation in cell proliferation and apoptosis of gastric mucosa in rats with chronic atrophic gastritis (CAG), and evaluate the possible mechanisms.. Rats were administered with 60% alcohol or 2% salicylate sodium, 20 mmol/L deoxycholate sodium and 0.1% ammonia water to establish chronic atrophic gastritis (CAG) models. The gastric specimens were prepared for microscopic view with hematoxylin and eosin (H-E) and alcian blue (A-B) stain. The number of infiltrated inflammatory cells, the thickness of the mucosa gland layer (microm) and the number of gastric glands were calculated. The damage of barrier in mucosa with erosion or ulceration, and the thickness of mucin were examined by scanned electron microscope (SEM). The levels of PGE(2), EGF (epiderminal growth factor) and gastrin in the serum were measured with radioimmunoassay or ELISA method. The immunohistochemistry method was used to observe the number of G cells, the expression of protein of EGFR (EGF receptor), C-erbB-2, p53, p16 and bcl-2 in gastric tissue.. Under SEM observation, the gastric mucosa was diffused erosion or ulceration and the thickness of mucin was decreased. Compared with normal rats, the grade of inflammatory cell infiltration in CAG rats was elevated, whereas the thickness and number of gastric gland were significantly lower (P<0.05). Compared with normal level of (0.61+/-0.28) microg/L, EGF in CAG (2.24+/-0.83) microg/L was significantly higher (P<0.05). The levels of PGE(2) and gastrin in serum were significantly lower in CAG rats than that in normal rats (P<0.05). Immunohistochemistry detection showed that the number of G cell in antrum was lower in CAG group (P<0.05). Immuno-stain showed EGFR protein expression in the basal and bilateral membrane, and the cytoplasma in atrophic gastric gland, while negative expression was observed in normal gastric epithelial cells. Positive staining of p53 and p16 protein was localized in the nucleus of epithelial cells. The former was higher positively expressed in atrophic gland, while the later was higher positively stained in normal gastric tissue. bcl-2 protein was positively stained in the cytoplasma in atrophic gastric gland, while very weakly stained in normal gastric tissue.. The pathological findings in gastric gland accorded with the Houston diagnostic criteria of antrum-predominant CAG. CAG in rats was related with the damage of barrier in gastric mucosa and the misbalance of cell proliferation and apoptosis. There was high protein expression of oncogene, while inhibitor of suppressor gene in CAG rats indicated high trend of carcinogenesis.

Topics: Animals; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Immunohistochemistry; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Tumor Suppressor Protein p53

Epidermal growth factor receptor (EGFR) activation, which plays an important role in regulating intestinal ion transport, can alleviate clinical symptoms such as diarrhea in patients with ulcerative colitis and promote mucosal restitution in animal models of colitis. Here, we investigate whether EGFR can regulate colonic ion transport in the setting of colitis.. Distal colon from control mice and mice with colitis was retained for immunohistochemistry or mounted in Ussing chambers. Ion transport responses across the tissues to the calcium agonist carbachol and the adenosine 3',5'-cyclic monophosphate agonist forskolin were measured with or without epidermal growth factor (EGF) pretreatment.. EGF pretreatment of normal colonic mucosa inhibited ion transport responses to carbachol and forskolin but potentiated the reduced ion transport responses seen in dextran sulfate sodium (DSS)-treated and mdr1a knockout mouse colon. Ion substitution studies and the sodium transport inhibitor amiloride showed that sodium movement primarily accounted for the potentiating effect of EGF in DSS-treated tissues, despite decreased sodium channel expression. EGF potentiation of transport responses in DSS-treated colon was completely blocked by the cytoskeletal disruptor cytochalasin D and the phosphatidylinositol 3-kinase inhibitor wortmannin, whereas the novel and conventional protein kinase C isoform inhibitor Gö6850 and the extracellular signal-regulated kinase inhibitor PD98059 partially reduced EGF effects. EGFR epithelial distribution and transforming growth factor alpha expression were also altered in DSS-treated tissues.. Chronic inflammation uncovers a potentiating effect of EGFR activation on epithelial electrogenic sodium absorption that would be expected to ameliorate diarrheal symptoms associated with colitis.

Topics: Animals; Biopsy, Needle; Blotting, Western; Chronic Disease; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Epidermal Growth Factor; Epithelial Cells; Immunohistochemistry; Intestinal Mucosa; Ion Transport; Male; Mice; Mice, Inbred BALB C; Probability; Reference Values; Sensitivity and Specificity; Sodium Channels

To determine whether men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have urine markers previously described for patients with interstitial cystitis (IC; presence of antiproliferative factor [APF] activity, decreased levels of heparin-binding epidermal growth factor-like growth factor [HB-EGF], and increased levels of epidermal growth factor).. Clean catch urine specimens were collected from 41 symptomatic patients with CP/CPPS, 36 asymptomatic men without bladder disease who served as the control group, and 24 men with IC. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells. HB-EGF and epidermal growth factor levels were determined by enzyme-linked immunosorbent assay.. Men with CP/CPPS did not differ significantly from asymptomatic controls for any of the three markers tested (P >0.49). In contrast, APF activity was present significantly more often and HB-EGF levels were significantly lower in the urine specimens from men with IC than in the specimens from controls or patients with CP/CPPS (P <0.00001 for all four comparisons). Although the epidermal growth factor levels also tended to be higher in the urine from patients with IC than in the urine from controls, the difference did not reach statistical significance (P = 0.06).. These findings indicate that at least two of the urine biomarkers previously identified in women with IC (presence of APF activity and decreased levels of HB-EGF) are also found in men with IC, but not in men with CP/CPPS. This finding suggests that IC and CP/CPPS may be two different disorders with distinct pathophysiologies. It also confirms the utility of the presence of APF activity and HB-EGF levels as markers for IC in men, as well as in women, with this disorder.

Topics: Adolescent; Adult; Aged; Biomarkers; Cells, Cultured; Chronic Disease; Cystitis, Interstitial; DNA Replication; Epidermal Growth Factor; Growth Inhibitors; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Pelvic Pain; Urothelium

Growth factors produced by airway epithelial cells may be important in the pathogenesis of subepithelial fibrosis, a distinctive lesion of chronic human asthma.. To examine the relationship between the development of subepithelial fibrosis and the expression of transforming growth factor-beta 1 (TGF-beta 1) and ligands for the epidermal growth factor receptor.. BALB/c mice sensitized to ovalbumin were chronically challenged by inhalation of low levels of antigen, leading to development of subepithelial fibrosis and other changes of airway wall remodelling. Growth factor expression was assessed by immunohistochemistry and enzyme immunoassay.. Allergic sensitization directly correlated with airway epithelial expression of both the cleaved, potentially biologically active form of TGF-beta 1 and of amphiregulin in response to allergen challenge. Accumulation of TGF-beta 1 was related to remodelling of the airway wall in chronic asthma, whereas expression of amphiregulin did not exhibit a similar relationship. Production of epithelial cell-derived TGF-beta 1 appeared to be regulated by IL-13, while both IL-13 and CD4(+) T cells regulated accumulation of TGF-beta 1. In contrast to results reported in high-level exposure models of airway fibrosis, eosinophils did not appear to be a significant source of TGF-beta 1.. Airway epithelial cell-derived TGF-beta 1 has a potentially crucial role in the development of airway wall remodelling in asthma. Immunological mechanisms may regulate the release and accumulation of TGF-beta 1.

Topics: Allergens; Amphiregulin; Animals; Asthma; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Chronic Disease; Disease Models, Animal; EGF Family of Proteins; Epidermal Growth Factor; Epithelial Cells; Female; Fibrosis; Glycoproteins; Immunoenzyme Techniques; Intercellular Signaling Peptides and Proteins; Interleukin-13; Ligands; Mice; Mice, Inbred BALB C; Ovalbumin; Respiratory Mucosa; Trachea; Transforming Growth Factor beta; Transforming Growth Factor beta1

Transforming growth factor-alpha (TGF-alpha), which binds to epidermal growth factor receptors (EGF-R), stimulates esophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. The aim of the present study was to examine epithelial proliferation and dynamics of TGF-alpha and EGF-R gene and protein expression in rat chronic acid reflux esophagitis.. Gastric acid reflux esophagitis was induced in Wistar rats by ligating the transitional region between the forestomach and the glandular portion, and by covering the duodenum near the pyloric ring with a small piece of an 18Fr Nélaton catheter. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake. Expression of TGF-alpha and EGF-R mRNA and protein was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry.. Esophageal lesions were observed in the lower and middle esophagus. Histologically, a significant increase in mucosal thickening with elongation of lamina propria papillae and basal cell hyperplasia was observed. The BrdU labeling index was significantly increased from 2.7 +/- 1.0 in normal mucosa and 2.8 +/- 1.2 in background mucosa adjacent to the esophageal lesion, to 60.3 +/- 32.7 in the lesions of chronic esophagitis. Expression of TGF-alpha and EGF-R mRNA in the esophageal lesion significantly increased compared to those in the control and background tissue, whereas treatment with rabeprazole significantly inhibited increases in TGF-alpha and EGF-R mRNA expression. According to immunohistochemical study, TGF-alpha and EGF-R revealed strong expression in esophageal lesions compared with control and background mucosa. The superficial layer of the esophagus was strongly positive for TGF-alpha and most cells in regions of basal hyperplasia had a positive reaction for EGF-R in the esophagitis lesion.. Epithelial proliferation and expression of TGF-alpha and EGF-R were significantly increased in rat chronic reflux esophagitis. Activation of TGF-alpha and EGF-R genes in response to acid reflux may facilitate rapid mucosal healing by stimulating epithelial proliferation. These results suggest that TGF-alpha and EGF-R play crucial roles in rat chronic reflux esophagitis.

Topics: Amino Acid Sequence; Analysis of Variance; Animals; Blotting, Western; Chronic Disease; Disease Models, Animal; Epidermal Growth Factor; Epithelial Cells; ErbB Receptors; Esophagitis, Peptic; Esophagus; Gastrointestinal Hemorrhage; Gene Expression; Immunoenzyme Techniques; Ligation; Male; Molecular Sequence Data; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor alpha

A prominent pathological feature of murine autoimmune gastritis is a pronounced mucosal hypertrophy. Here, we examined factors that may be responsible for inducing this hypertrophy. Because gastrin is known to be both an inducer of gastric mucosal cell proliferation and is elevated in autoimmune gastritis, mice deficient in gastrin were thymectomised at day 3 and assessed for autoimmune gastritis. Gastrin-deficient mice showed all the characteristic features of murine autoimmune gastritis, including gastric unit hypertrophy due to hyperproliferation and accumulation of immature epithelial cells, decreases in the number of zymogenic and parietal cells, and autoantibodies to the gastric H+/K+-ATPase. Hence, gastrin is not required for either the establishment of chronic gastritis or development of the typical pathological features of this disease. We also examined mRNA levels of a number of gastric mucosal growth factors in RNA samples from mice with hypertrophic autoimmune gastritis. Members of the Reg family, RegIIIbeta and RegIIIgamma, were greatly elevated in mice with hypertrophic gastritis, whereas RegI and amphiregulin (an EGF receptor ligand) were more modestly and/or inconsistently induced. These data demonstrate that induction of gastric mitogenic factors, such as members of the Reg family, can be achieved in inflammatory situations by gastrin-independent pathways. Members of the Reg family, in particular RegIIIbeta and RegIIIgamma, are good candidates to be involved in inducing the mucosal hyperproliferation in autoimmune gastritis. These findings are likely to be of relevance to other gastric inflammatory conditions.

Topics: Amphiregulin; Animals; Autoantibodies; Autoimmune Diseases; Chronic Disease; EGF Family of Proteins; Epidermal Growth Factor; ErbB Receptors; Gastric Mucosa; Gastrins; Gastritis; Gene Expression; Glycoproteins; Growth Substances; H(+)-K(+)-Exchanging ATPase; Heparin-binding EGF-like Growth Factor; Hypertrophy; Intercellular Signaling Peptides and Proteins; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Proteins; RNA, Messenger; Transforming Growth Factor alpha

To investigate the mechanism of isinglass in the prevention and treatment of chronic atrophic gastritis (CAG) in rats.. Animal models of SD rats with CAG were made in accordance with the previous experience of combined administration of 60% ethanol, 20 mmol x L(-1) sodium deoxycholate and 0.1% ammonia water. In prevention groups, sucralfate and isinglass were used as preventive therapy while CAG rat model was being made. In the reverse groups, sucralfate and isinglass were used to treat rats after establishment of CAG rat model. Finally all the rats were executed. Then the length of the proliferation zone of the gastric mucosa and serum epidermal growth factors (EGF) and growth hormones (GH)level were studied.. In isinglass prevention groups and high dose isinglass reverse group, the length of the proliferation zone of the gastric mucosa was very close to that in normal control group (P > 0.05), much better than model control group (P < 0.01). In low dose isinglass reverse group, it was lower than that in normal control group (P < 0.01), but much better than model control group (P < 0.01). In both prevention and reverse groups, serum EGF level was higher than that in normal (P < 0.01) and model control group (P < 0.05). Serum GH level was the same in every group (P > 0.05).. The mechanism of isinglass in the prevention and treatment of CAG rats lies in revitalizing and proliferating gastric mucosal cells by stimulating endogenous EGF secretion.

Topics: Animals; Chronic Disease; Dose-Response Relationship, Drug; Epidermal Growth Factor; Female; Gastritis, Atrophic; Gelatin; Growth Hormone; Materia Medica; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley

The epidermal growth factor receptor (EGF-R) system plays a crucial role in mucus production in vitro and in rats. However, the role of the EGF-R system in humans is not known. We compared the localization of EGF-R and its ligands (epidermal growth factor and transforming growth factor alpha) in the epithelia of sinuses with chronic sinusitis and in those of healthy controls. Immunohistochemical techniques were employed to identify the presence of EGF-R and its ligands in the sinus mucosa. We found EGF-R in goblet cells, basal cells, and submucosal gland cells, but not in ciliated cells. Immunoreactivity for both epidermal growth factor and transforming growth factor alpha was found in the epithelial cells and inflammatory cells and in some submucosal gland cells. There was stronger staining of EGF-R and its ligand proteins in chronic sinusitis specimens than in controls. The interrelated localization of EGF-R and its ligands suggests a role in mucus production in the epithelium of the sinus mucosa.

Topics: Adult; Case-Control Studies; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Female; Goblet Cells; Humans; Hyperplasia; Immunohistochemistry; Ligands; Male; Maxillary Sinusitis; Metaplasia; Middle Aged; Mucus; Neutrophil Activation; Tomography, X-Ray Computed; Transforming Growth Factor alpha; Tumor Necrosis Factor-alpha

Patients with graft-versus-host disease (cGVHD) suffer from oral dryness and increased levels of oral infections and mucosal pathologies. The purpose of the current study was dual: 1) to investigate the salivary functional (sialometry) and compositional (sialochemistry) alterations induced by the disease during a 12-month period following the onset of the disease; and 2) to evaluate the effect of Salagen 30 mg/d on the salivary biochemical and immunological composition in cGVHD patients. Significant higher concentrations of salivary sodium (Na), magnesium (Mg), total protein (TP), albumin (Alb), epidermal growth factor (EGF), and total IgG accompanied by a concomitant increase in total IgA that did not reach significant value was observed in cGVHD patients in comparison with controls at both resting and stimulated conditions (p < 0.05) while salivary levels of potassium (K), calcium (Ca), and phosphate (P) were not altered. Two weeks of oral Salagen 30 mg/d resulted in normalization of the salivary biochemical and immunological compositional alterations in the cGVHD patients. Oral pilocarpine was able to reduce and normalize the elevated levels of Na, Mg, TP, Alb, EGF, IgG, and IgA salivary concentrations at both resting and stimulated conditions. The ability of oral pilocarpine to normalize and reverse salivary biochemical and immunological alterations induced by cGVHD is parallel to its stimulatory effect on salivary flow rates, as we previously showed. As the biochemical and immunological composition of the saliva results in its antimicrobial protective characteristics, the ability of oral pilocarpine (Salagen) to abrogate cGVHD salivary gland abnormalities may be of clinical importance.

Topics: Adolescent; Adult; Albumins; Cations; Chronic Disease; Epidermal Growth Factor; Female; Follow-Up Studies; Graft vs Host Disease; Hematologic Neoplasms; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; Pilocarpine; Rheology; Saliva; Salivary Proteins and Peptides; Salivation; Xerostomia

In both pancreatic cancer and chronic pancreatitis, there is enhanced expression of mitogenic growth factors and their tyrosine kinase receptors, which have the capacity to activate mitogen-activated protein kinase (MAPK). In view of the important role of MAPK kinase phosphatase (MKP)-1 in the regulation of MAPK activation, the expression and functional role of MKP-1 was analyzed.. Pancreatic tissues were analyzed by Northern blotting, Western blotting, and immunohistochemistry. Pancreatic cancer cells were transfected with a full-length MKP-1 antisense construct. Growth characteristics and tumorigenicity in vivo and the effects of mitogenic growth factors on cell growth and MAPK activation were determined in transfected and control cells.. MKP-1 messenger RNA (mRNA) levels were increased in pancreatic cancer and chronic pancreatitis (CP) tissues. Moderate to strong MKP-1 immunoreactivity was present in the cancer cells, ductal cells of pancreatic intraepithelial neoplasia, and in tubular complexes in CP. Down-regulation of MKP-1 resulted in decreased anchorage-dependent and -independent growth of pancreatic cancer cells, and decreased tumorigenicity in a nude mouse tumor model. MKP-1 down-regulation led to decreased proliferation and sustained MAPK activation in response to mitogens.. Suppression of MKP-1 expression reduces the tumorigenicity of pancreatic cancer cells in vivo, suggesting that MKP-1 contributes to enhanced mitogenic signaling in pancreatic cancer cells.

Topics: Adolescent; Adult; Aged; Cell Cycle Proteins; Chronic Disease; Down-Regulation; Dual Specificity Phosphatase 1; Epidermal Growth Factor; Female; Gene Expression Regulation, Enzymologic; Humans; Immediate-Early Proteins; JNK Mitogen-Activated Protein Kinases; Male; Middle Aged; Mitogen-Activated Protein Kinases; Pancreas; Pancreatic Neoplasms; Pancreatitis; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 1; Protein Tyrosine Phosphatases; RNA, Messenger; Transfection; Tumor Cells, Cultured

The AP-1 transcription factor, composed of Jun and Fos proteins, plays a crucial role in the fine tuning of cell proliferation. We showed previously that AP-1 complexes are activated during the proliferative response that parallels the development of renal lesions after nephron reduction, but little is known about the specific role of individual Jun/Fos components in the deterioration process. Here we used JunD knockout (JunD-/-) mice and an experimental model of chronic renal injury (75% nephron reduction) to explore the role of JunD. Nephron reduction resulted in an initial compensatory growth phase that did not require JunD. JunD, however, was essential to inhibit a second wave of cell proliferation and to halt the development of severe glomerular sclerosis, tubular dilation, and interstitial fibrosis. We show that the effects of junD inactivation are not cell autonomous and involve upregulation of the paracrine mitogen, TGF-alpha. Expression of a transgene (REM) encoding a dominant negative isoform of the EGFR, the receptor for TGF-alpha, prevented the second wave of cell proliferation and the development of renal lesions in bitransgenic JunD-/-/REM mice. We propose that JunD is part of a regulatory network that controls proliferation to prevent pathological progression in chronic renal diseases.

Topics: Animals; Cell Division; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Humans; Kidney; Kidney Diseases; Mice; Mice, Knockout; Mitogens; Paracrine Communication; Proto-Oncogene Proteins c-jun; Signal Transduction; Transcription Factor AP-1; Transforming Growth Factor alpha; Up-Regulation

To investigate the expression and location of epidermal growth factor (EGF) and its receptor (EGFR) in dermal chronic ulcers and normal skin in order to explore their influence on ulcer formation.. The expression intensity and distribution of EGF and EGFR were detected with pathological method and immunohistochemistry method in 8 cases of dermal ulcers, 8 cases of edge of ulcer and 8 cases of normal skin.. The Positive signals of EGF could be found in epidermal cells, endothelial cells and some fibroblasts; EGFR was principally located in the cytoplasm and cellular membrane of these cells mentioned above in normal skin. From normal skin, edge of ulcer to ulcerative tissues, the protein contents of EGF and EGFR were decreased progressively. In ulcerative tissues, EGF was mostly distributed in monocytes and macrophages while EGFR was chiefly sited in monocytes. When compared with normal skins, the protein expression of EGF and EGFR was notably reduced in ulcerative tissues (both P<0.01). The positive cellular ratios of two proteins were reduced to (7.1+/-5.2) % and (8.8+/-5.5) % of those in normal skin respectively (all P<0.01).. The formation of dermal chronic ulcers is closely associated with the reduction of EGF and EGFR protein expression which may lead to binding obstruction between EGF and its receptor.

Topics: Adult; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunohistochemistry; Male; Middle Aged; Skin; Skin Ulcer

To observe the effect of recombinant human epidermal growth factor (rhEGF) on healing of chronic ulcer wound.. From January 1999 to January 2001, twenty-six patients with chronic wounds were adopted in this study. Among them, there were 17 males and 9 females, aged from 12 to 61 years. The area of the chronic wound varied from 3 cm x 3 cm to 5 cm x 8 cm and the disease course was 7 to 16 days. These patients were treated with rhEGF in the way of sprinkling locally (400 U/10 cm2). Another 26 patients with chronic wounds were adopted as the control group and were treated with 0.9% saline in the same way. The healing time of wounds and the local and systemic reactions of patients were observed.. The healing time of chronic wounds was shorter obviously to about 7 days with rhEGF than that of the control group and there was significant difference between the two groups(P < 0.01).. rhEGF can obviously promote the healing of chronic ulcer wound.

Topics: Adolescent; Adult; Child; Chronic Disease; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Recombinant Proteins; Skin Ulcer

Chronic graft-versus-host disease (cGVHD) is a complex clinical entity with various target organs, including the salivary glands. Oral pilocarpine (Salagen(R)), 30 mg/day, can ameliorate cGVHD-induced xerostomia and improve the flow rate from the major salivary glands. The purpose here was to evaluate the effect of this drug at 30 mg/day on salivary biochemical and immunological composition in cGVHD patients. Significantly higher concentrations of salivary sodium (Na), magnesium (Mg), total protein, albumin, epidermal growth factor (EGF) and total IgG, accompanied by a concomitant increase in total IgA which did not reach significance, were observed in cGVHD patients in comparison with controls, in both resting and stimulated conditions (p < 0.05), while salivary potassium, calcium and phosphate were not altered. Two weeks of oral pilocarpine, at 30 mg/day, resulted in normalization of the altered salivary biochemical and immunological composition in the cGVHD patients. Oral pilocarpine was able to reduce and normalise the elevated Na, Mg, total protein, albumin, EGF, IgG and IgA concentrations in both resting and stimulated conditions. The ability of oral pilocarpine to normalise and reverse the salivary biochemical and immunological alterations induced by cGVHD parallels its known stimulatory effect on salivary flow rates. As the biochemical and immunological composition of saliva provides its protective antimicrobial characteristics, the ability of pilocarpine to abrogate cGVHD salivary gland abnormalities may be of clinical significance.

Topics: Administration, Oral; Albumins; Calcium; Chronic Disease; Epidermal Growth Factor; Graft vs Host Disease; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Magnesium; Muscarinic Agonists; Phosphates; Pilocarpine; Potassium; Saliva; Salivary Proteins and Peptides; Secretory Rate; Sodium; Statistics as Topic; Xerostomia

Biodegradable microspheres containing recombinant human epidermal growth factor (rhEGF) were prepared using poly(L-lactic acid) by a solvent evaporation method based on multiple w/o/w emulsion. Encapsulation efficiency and initial release were influenced by the amount of polymer, inner water phase volume and osmotic pressure difference between inner water phase and outer water phase. The effect of osmotic pressure difference between inner water phase and outer water phase in w/o/w emulsion on particle size, porosity and in vitro release of rhEGF from microspheres were also studied. Microspheres prepared with the optimized osmotic pressure, polymer amount and inner water volume produced 21% initial release on the first day with 92% encapsulation efficiency. The blood concentration of rhEGF was maintained at constant levels for 9-11 days after a single subcutaneous (s.c.) administration of rhEGF microspheres. The gastric ulcer healing effect of a single s.c. administration of rhEGF microspheres was increased 1.44-fold compared with twice a day s.c. administration of rhEGF saline solution after 11 days. The enhanced curative ratio of rhEGF loaded microspheres may be due to the optimized osmotic pressure, high encapsulation efficiency and sustained release pattern.

Topics: Animals; Chronic Disease; Epidermal Growth Factor; Lactic Acid; Male; Microscopy, Electron, Scanning; Microspheres; Osmotic Pressure; Particle Size; Polyesters; Polymers; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Stomach Ulcer

Topics: Animals; Animals, Genetically Modified; Chronic Disease; Disease Progression; Epidermal Growth Factor; ErbB Receptors; Growth Substances; Humans; Ischemia; Kidney Diseases; Kidney Tubules; Nephrectomy

Helicobacteria pylori infection of gastroduodenal mucosa is strongly associated with gastritis and peptic ulcer disease. The aims of the present study were to compare the gastroduodenal mucosal levels of epidermal growth factor (EGF) and its receptor (EGFR) among H. pylori-negative controls and H. pylori infected patients with chronic active gastritis or gastroduodenal ulcer before and after H. pylori eradication.. The protein levels of EGF in mucosal tissues and saliva were determined by a solid-phase enzyme-linked immunosorbent assay (ELISA). Repeat transcription-polymerase chain reaction and the following polymerase chain reaction ELISA were employed to examine the mucosal EGFR mRNA expression.. Mucosal injury and H. pylori infection increased EGF protein levels and EGFR mRNA expression in the antral mucosa. The concentration of EGF in saliva was not affected by mucosal damage or H. pylori infection. Successful H. pylori eradication normalized the EGFR mRNA back to its basal level 6 weeks after treatment. However, after unsuccessful eradication their high levels in the antrum persisted. All patients experienced ulcer healing after drug treatment, regardless of H. pylori eradication.. Mucosal damage increased the expression of EGF protein and EGFR mRNA in the gastric mucosa. H. pylori could induce the expression of EGFR but not the EGF in the antral mucosa. The expression of EGFR could be a contributing factor for ulcer healing in patients with H. pylori infection.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Chronic Disease; Duodenal Ulcer; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; ErbB Receptors; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Polymerase Chain Reaction

Topics: Biomarkers; Chronic Disease; Endothelial Growth Factors; Epidermal Growth Factor; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Lung Diseases; Lymphokines; Respiratory Distress Syndrome, Newborn; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Growth factors important to lung growth and fibrosis have been poorly studied in chronic lung disease (CLD) of prematurity. Epidermal growth factor (EGF) promotes epithelial cell maturation, and vascular endothelial growth factor (VEGF) is important in angiogenesis. The concentration of these growth factors was determined in 111 bronchoalveolar lavage fluid (BALF) samples from 35 ventilated infants: 13 developed CLD (median gestation 27 weeks, birthweight 820 g), 16 developed and recovered from respiratory distress syndrome (RDS) (31 weeks, 1,415 g) and six control infants (33 weeks, 2,075 g) were ventilated for nonpulmonary reasons. At birth, EGF in BALF from the CLD and RDS infants was lower than in the control infants (control versus CLD, 7.3 versus 0.0 pg x mL(-1), p<0.01; control versus RDS, 7.3 versus 5.0, p=0.08). EGF increased in all groups with a more rapid increase in control infants. A close relationship was noted between BALF EGF and gestational age (R=0.73). VEGF was undetectable at birth but increased at a similar rate in all three groups and did not correlate with gestation. In conclusion, these data suggest that epidermal growth factor is closely correlated to gestation and that it may predispose preterm infants to develop chronic lung disease.

Topics: Bronchoalveolar Lavage Fluid; Chronic Disease; Endothelial Growth Factors; Epidermal Growth Factor; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lymphokines; Male; Protein Isoforms; Respiratory Distress Syndrome, Newborn; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The results of this study show that routine measurements of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) cannot improve screening for pancreatic cancer despite the frequently present tissue overexpression. Both values fail to reveal this malignancy in a serum test. Patients with chronic pancreatitis exhibit no or very low concentrations of EGF. In cases where preoperative diagnosis is difficult the noninvasive EGF and EGF-R serum measurements may be helpful in discriminating between pancreatic cancer and chronic pancreatitis.. EGF and EGF-R are frequently overexpressed in the tissue of patients suffering from ductal pancreatic cancer and to lesser degree in patients with chronic pancreatitis. The aim of this study was to determine the value of serum measurements in these patients to detect malignant pancreatic disease. In cases of pancreatic cancer, the tissue expression of EGF and EGF-R was evaluated by immunohistochemistry.. Thirty-five patients with chronic pancreatitis and 31 patients with pancreatic cancer were evaluated; 71 patients admitted for routine surgery (hernia repair, cholecystectomy, goiter surgery) served as controls.. EGF and EGF-R values were not significantly different in pancreatic cancer as compared to controls and did not correlate with other tumor markers (CA 19-9, carcinoembryonic antigen [CEA], tumor polypeptide antigen [TPA]) or with the stage of the disease. Fourteen patients (67%) with pancreatic cancer displayed tissue overexpression for EGF and 11 patients for EGF-R (52%). These patients, however, also failed to exhibit any significant pathological changes in serum concentration. In chronic pancreatitis, EGF and EGF-R were significantly decreased as compared to pancreatic cancer and controls. This was an unexpected finding. There was a positive correlation to clinical exocrine insufficiency.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunohistochemistry; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis

Long-term survival of small bowel transplants is hampered by chronic rejection. Epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta) have opposing, regulatory roles in normal intestinal physiology and may be involved in the pathogenesis of chronic intestinal rejection. Our aim was to investigate the expression of EGF and TGF-beta1 in chronically rejecting small bowel transplants. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination; Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA rats. PreproEGF and TGF-beta1 gene expression was evaluated by northern blot analysis of the ileum RNA and standardized against glyceraldehyde-3-phosphate-dehydrogenase expression. Allografts demonstrated functional impairment and histological features of chronic rejection, whereas isografts appeared normal. Allografts demonstrated a significant reduction of EGF mRNA when compared to DA isografts. No significant changes were detected in TGF-beta1 expression in either allogeneic or syngeneic grafts. In conclusion, this study demonstrates reduced preproEGF and preserved TGF-beta1 gene expression in chronically rejecting small bowel transplants.

Topics: Analysis of Variance; Animals; Blotting, Northern; Chronic Disease; Disease Models, Animal; Epidermal Growth Factor; Gene Expression Regulation; Graft Rejection; Intestine, Small; Male; Rats; Rats, Inbred Strains; RNA, Messenger; Statistics, Nonparametric; Transforming Growth Factor beta

Helicobacter pylori (H. pylori) infection has been linked to gastric cancer. The factors that promote carcinogenesis remain unknown. Epidermal growth factor (EGF) has been shown to be a potent epithelial mitogen and oncoprotein when sustained over expression occurs. Our aim was to compare gastric mucosal levels of EGF and its receptor (EGFR) among controls, H. pylori infected subjects, and subjects following H. pylori eradication using quantitative flow cytometric analysis.. Patients referred for evaluation of dyspepsia underwent EGD and six antral biopsies were performed (two each for rapid urease testing (RUT), histopathology, and flow cytometry). Controls were those found to be H. pylori negative while subjects had confirmed infection. The study patients were treated, then had repeat EGD with biopsies.. There were 17 controls and 28 cases. Mean EGF and EGFR values were 2.69 and 2.46 for controls and 4.67 and 4.64 for subjects. Subjects' mean EGF was 73% higher (p = .035) and EGFR was 88% higher (p = 0.029) than controls. After treatment, the subjects' mean values declined 55% (p = 0.0001) for EGF and 40% (p = 0.002) for EGFR. Three subjects had persistent infection and showed no change in their EGF/EGFR levels. No difference was found among factor levels with respect to endoscopic findings.. Both EGF and EGFR from gastric antral biopsies are increased nearly 2-fold in infection with H. pylori. Infection eradication reduces levels of both factors to those of controls. One major pathogenic mechanism for gastric mucosal hyperproliferation and possibly carcinogenesis related to H. pylori may be the over expression of EGF and increased receptor density of EGFR on gastric mucosal cells.

Topics: Adult; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Bismuth; Chronic Disease; Drug Therapy, Combination; Epidermal Growth Factor; ErbB Receptors; Female; Flow Cytometry; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Organometallic Compounds; Prospective Studies; Salicylates

Cholesteatoma in children is generally considered to be more aggressive and destructive than in adults. Each otologic surgeon has experienced widely extended cholesteatomas in children with large pneumatized mastoid processes. In this paper, we want to present clinical and experimental observations which imply that the destructive potential in children is similar to that in adults. Factors and observations that have led to the assumption that cholesteatoma in children is more aggressive will be discussed. Based on our experience and the literature, we tried to distill the current and leading thoughts concerning this intriguing entity.

Topics: Adolescent; Adult; Child; Child, Preschool; Cholesteatoma, Middle Ear; Chronic Disease; Ear Canal; Epidermal Growth Factor; Fibroblast Growth Factor 2; Humans; Immunohistochemistry; Infant; Ki-67 Antigen; Otitis Media, Suppurative; Skin; Transforming Growth Factor alpha

Obstructive nephropathy is a primary cause of renal failure in infancy. Chronic unilateral ureteral obstruction (UUO) in the neonatal rat results in reduced renal expression of epidermal growth factor (EGF), renal tubular epithelial (RTE) cell apoptosis and interstitial fibrosis. We wished to determine whether these changes could be prevented by exogenous administration of EGF.. Thirty-three Sprague-Dawley rats underwent UUO within the first 48 hours of life, and received daily injections of either EGF (0.1 mg/kg/day) or saline (control) for the following seven days, after which obstructed and intact opposite kidneys were removed for study. These were compared to 11 sham-operated rats that received either no injections, EGF injections, or saline injections. Renal cell proliferation was determined by proliferating cell nuclear antigen, apoptosis was measured by the TUNEL technique, and the distribution of vimentin, clusterin, transforming growth factor-beta 1 (TGF-beta 1), and alpha-smooth muscle actin were determined by immunohistochemistry. Tubular dilation, tubular atrophy, and interstitial collagen deposition were quantitated by histomorphometry.. Compared to controls, EGF treatment increased RTE cell proliferation in the obstructed kidney by 76%, decreased apoptosis by 80%, and reduced vimentin, clusterin and TGF-beta 1 immunostaining (all P < 0.05). EGF treatment reduced tubular dilation by 50%, atrophic tubules by 30%, and interstitial fibrosis by 50% (all P < 0.05). There was no significant effect of EGF on renal alpha smooth muscle actin distribution. There was no effect of saline or EGF injections on kidneys from sham-operated rats for any of the parameters studied.. We conclude that EGF stimulates RTE cell proliferation and maturation and reduces apoptosis in the neonatal rat kidney subjected to chronic UUO. These effects may contribute to the reduction in tubular dilation, tubular atrophy, and interstitial fibrosis. By preserving renal development, administration of EGF attenuates the renal injury resulting from chronic UUO.

Topics: Animals; Animals, Newborn; Apoptosis; Cell Division; Chronic Disease; Clusterin; Complement Inactivator Proteins; Epidermal Growth Factor; Fibrosis; Glycoproteins; Kidney; Kidney Tubules; Ligation; Molecular Chaperones; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta; Ureter; Ureteral Obstruction; Urothelium; Vimentin

Topics: Aged; Chronic Disease; Cytokines; Epidermal Growth Factor; Female; Humans; Leg Ulcer; Risk Factors; Wound Healing

We assessed whether transforming growth factor-beta (TGF-beta), a fibrogenic growth factor, may be involved in remodeling of asthma and chronic bronchitis; its expression was compared with that of epidermal growth factor (EGF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in bronchial mucosal biopsies from 13 normal subjects, 24 asthmatics, and 19 patients with chronic bronchitis. TGF-beta immunoreactivity was highly increased in epithelium and submucosa of those with bronchitis and to a lesser extent in asthmatics. By comparison, with normal subjects, EGF immunoreactivity was significantly increased in the epithelium of bronchitic subjects and submucosa of asthmatics, and, GM-CSF immunoreactivity was increased in both epithelial and submucosal cells of asthmatics and to a lesser extent in submucosa of bronchitics. A significant correlation was found between the number of epithelial or submucosal cells expressing TGF-beta in both asthma and chronic bronchitis and basement membrane thickness and fibroblast number. No such correlation was found for EGF or GM-CSF. in situ hybridization for TGF-beta 1 mRNA confirmed the results obtained by immunohistochemistry. By combining in situ hybridization and immunohistochemistry, it was found that eosinophils and fibroblasts were synthetizing TGF-beta in asthma and bronchitis. These data suggest that TGF-beta, but not EGF or GM-CSF, is involved in airways remodeling in asthma and chronic bronchitis.

Topics: Adolescent; Adult; Aged; Asthma; Biopsy; Bronchi; Bronchitis; Chronic Disease; Epidermal Growth Factor; Epithelium; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunohistochemistry; In Situ Hybridization; Middle Aged; Mucous Membrane; Transforming Growth Factor beta

This study examined the relationship between healing of acetic acid-induced chronic gastric ulcer and connexin formation. In addition, the effect of anti-ulcer drugs on ulcer healing and the presence of connexin was investigated. In a rat model, acetic acid-induced gastric ulcers were healed without administration of drugs after 14 days. Appearance of an electrophoretic connexin 32 band was observed 7 days after ulcer induction. Administration of cimetidine (3 mg/day) promoted ulcer healing, i.e., ulcers were healed 12 days after ulcer induction, 2 days earlier than the control. The appearance of a connexin 32 band in electrophoresis was observed on the fourth day after ulcer induction. Administration of cimetidine at a higher dose further promoted ulcer healing and the connexin 32 band was more strongly visible. After administration of i.p. 2 nM EGF, acetic acid-induced gastric ulcers were healed 12 days after ulcer induction and the appearance of connexin 32 was observed on the fourth day after induction. These results indicate that connexin 32 is related to the healing of acetic acid-induced gastric ulcers.

Topics: Acetic Acid; Animals; Anti-Ulcer Agents; Chronic Disease; Cimetidine; Connexins; Epidermal Growth Factor; Gap Junction beta-1 Protein; Gastric Mucosa; Male; Rats; Rats, Wistar; Stomach Ulcer; Time Factors

The purpose of this study was to investigate the role of growth-related peptides in the impairment of renal growth and development resulting from unilateral ureteral obstruction (UUO) in the neonatal rats.. Sprague-Dawley rats underwent UUO or sham-operation in the first 48-hours of life, and kidneys were harvested 1 to 28 days later. Renal messenger RNA (mRNA) was quantitated for renin, transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF). Renal interstitial volume was measured in Masson-trichrome-stained sections, and renin and alpha-smooth muscle actin (alpha-SM actin) distribution were determined by immunocytochemistry.. The normal developmental increase in renal mass and DNA content were suppressed in ipsilateral UUO and increased in the intact opposite kidney. Renal interstitial volume was increased more than 10-fold by ipsilateral UUO. Unilateral ureteral obstruction resulted in a sustained increased in ipsilateral renal renin mRNA and persistence of fetal renin distribution. Renin in the contralateral kidney was suppressed. Transforming growth factor-beta 1 expression increased progressively in the obstructed kidney, but decreased after 7 days in sham-operated kidneys. While renal EGF expression was undetectable in the normal sham kidney during the first 3 days of life, it increased steadily with maturation. However, EGF expression remained suppressed in the obstructed kidney. Whereas alpha-SM actin disappeared from the interstitium of normal rat kidneys by 15 days of age, it persisted in the obstructed neonatal kidney.. As revealed by changes in expression of growth-related peptides, neonatal UUO delays ipsilateral renal development, which may contribute to impaired renal growth.

Topics: Actins; Animals; Animals, Newborn; Chronic Disease; Epidermal Growth Factor; Gene Expression Regulation; Kidney; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger; Time Factors; Transforming Growth Factor beta; Ureteral Obstruction

Topics: Biopsy; Blood Pressure; Chronic Disease; Drug Therapy, Combination; Epidermal Growth Factor; Fibroblast Growth Factor 2; Graft Rejection; Growth Substances; Humans; Immunosuppressive Agents; Interleukin-1; Kidney Transplantation; Platelet-Derived Growth Factor; Polymerase Chain Reaction; Proteinuria; RNA, Messenger; Transcription, Genetic; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

This study was designed to evaluate the concentration and the regional distribution of TGF-alpha and EGF in normal and portal hypertensive human gastric mucosa. To this end we measured by RIA the gastric and duodenal concentration of TGF-alpha and EGF in subjects with chronic hepatitis, who had normal gastric endoscopic appearance, and in patients with liver cirrhosis with and without congestive gastropathy. Our results show that TGF-alpha concentration is significantly higher than EGF concentration in both the stomach and duodenum. No significant regional differences in the distribution of the two peptides were found. Moreover, the gastroduodenal tissue levels of TGF-alpha were comparable in subjects with and without hypertensive gastropathy. EGF gastric concentration was not altered in patients with congestive gastropathy. However, EGF duodenal tissue levels were significantly lower in patients with liver cirrhosis than in noncirrhotic subjects. We speculate that the higher level of TGF-alpha in the gastroduodenal mucosa may support the hypothesis that TGF-alpha and not EGF is the major physiological ligand for TGF-alpha/EGF receptor in the intact gut. Furthermore, the lower duodenal concentration of EGF in cirrhotics might partially explain the increased susceptibility of cirrhotic patients to duodenal ulcer.

Topics: Adult; Aged; Biopsy; Chronic Disease; Duodenum; Epidermal Growth Factor; Female; Gastric Mucosa; Humans; Hypertension, Portal; Intestinal Mucosa; Liver Diseases; Male; Middle Aged; Radioimmunoassay; Reference Values; Stomach Diseases; Transforming Growth Factor alpha

Chronic tympanic membrane (TM) perforation is a common problem worldwide. Recent reports have shown epidermal growth factor (EGF) to stimulate healing in approximately 80% of chronic TM perforations in chinchillas when applied in three doses over 1 week. The objective of this controlled study is to evaluate the efficacy of long-term EGF in the closure of TM perforations. Chronic chinchilla TM perforations were treated with EGF for up to 6 weeks. One hundred percent (17 of 17) of treatment group perforations completely healed. However, two new findings with this long dosing scheme were reperforation on long-term follow-up and three TMs with cholesteatomas. It is likely that reperforation was due to a progressive thinning seen with prolonged EGF application. Long-term EGF use is not recommended for the treatment of TM perforations because of possible wound healing impairment and possible cholesteatoma induction.

Topics: Animals; Chinchilla; Cholesteatoma, Middle Ear; Chronic Disease; Drug Administration Schedule; Endoscopy; Epidermal Growth Factor; Follow-Up Studies; Gelatin Sponge, Absorbable; Longitudinal Studies; Placebos; Recurrence; Rupture; Sodium Chloride; Time Factors; Tympanic Membrane; Wound Healing

Topics: Chronic Disease; Epidermal Growth Factor; Gastrointestinal Diseases; Humans; Intercellular Signaling Peptides and Proteins; Mucins; Muscle Proteins; Neuropeptides; Parasympatholytics; Peptides; Remission, Spontaneous; Trefoil Factor-2; Trefoil Factor-3; Ulcer

Epidermal growth factor (EGF) is a fibrogenic cytokine with a possible role in chronic damage. EGF is also involved in tubular regenerative response to injury. This study investigates the expression and distribution of EGF in a rat model of renal allograft rejection. EGF was localised in control kidneys to distal convoluted tubules (DCT) and thick ascending loop of Henle (TAL). Five days post-transplantation EGF was diffusely distributed. In chronic rejection at one, three and six months, damaged areas of allografts demonstrated faint diffuse EGF staining, while well-preserved areas exhibited the normal distribution pattern. PreproEGF mRNA was significantly reduced (P < 0.01) in acute rejection and in chronic rejection at three months to 28% and 51% of normal, respectively. At six months values ranged from 16% to 166% of normal kidneys, and were inversely correlated with tubular damage (P < 0.01). PreproEGF mRNA was localized to DCT and TAL in controls and in well preserved areas of the tissue in chronic rejection. Thus, EGF would not appear to contribute to the development of injury in chronic renal rejection. It may instead exert a protective effect on tubular structures.

Topics: Acute Disease; Animals; Chronic Disease; Epidermal Growth Factor; Gene Expression; Graft Rejection; Immunohistochemistry; In Situ Hybridization; Kidney Transplantation; Kidney Tubules, Distal; Loop of Henle; Male; Protein Precursors; Rats; Rats, Inbred Strains; RNA, Messenger; Tissue Distribution; Transplantation, Homologous

In an earlier study, epidermal growth factor (EGF) was shown to be effective in healing chronic tympanic membrane (TM) perforations in the chinchilla. The original protocol required rimming of the perforation's epithelial edge, application of a paper patch, placement of a Gelfoam pledget, and then administration of EGF solution. To develop a simple outpatient method of healing chronic TM perforations, an attempt was made to simplify the treatment protocol while preserving efficacy. In the modified experimental protocol, a large Gelfoam pledget was placed over the chronic perforation in contact with the residual TM, without mechanical disruption of the perforation edge or use of a paper patch. Then EGF in phosphate buffered saline (PBS) was applied to the Gelfoam pledget (50 microL of 0.5 mg EGF/mL PBS). A series of control ears received Gelfoam pledgets and PBS. Complete closure of the TM perforation was achieved in 80 percent (12/15) of treated ears but in only 20 percent (3/15) of controls (p < 0.01), results similar to those obtained with the original protocol. At long-term follow-up, 4 to 9 months after treatment, EGF-healed TMs were histologically similar to normal TMs, both in their overall thickness and in the relative proportions of the three component layers. In contrast, the few spontaneously healed TMs from the control group were less than half the thickness of normal TMs. To ascertain the optimal EGF concentration for therapeutic effect, a dose ranging study was undertaken.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Chi-Square Distribution; Chinchilla; Chronic Disease; Epidermal Growth Factor; Male; Myringoplasty; Organ of Corti; Recombinant Proteins; Tympanic Membrane Perforation; Wound Healing

Cripto is a 188 amino-acid protein containing a central segment that shares amino-acid sequence homology with epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). The EGF receptor, EGF and TGF-alpha are expressed in the normal human pancreas, and are over-expressed in human pancreatic cancer. Therefore, in the present study we sought to determine whether cripto is found in the normal human pancreas and whether its expression is altered in pancreatic cancer. Because chronic pancreatitis (CP) is associated with interstitial fibrosis similar to that observed in pancreatic cancer, we also examined cripto expression in pancreatic tissues from patients with CP. In the normal pancreas, cripto immunoreactivity was found at moderate levels in most ductal cells and was present very faintly in a rare acinar cell. In 26 of 58 pancreatic cancers, cripto immunoreactivity was present in many cancer cells. Its presence was associated with advanced tumor stage, but not with shorter post-operative survival. Cripto was also present in acinar and ductal cells adjacent to the cancer cells, and in many ductal atrophic acinar cells in the CP samples. Northern blot analysis revealed a marked increase in cripto mRNA levels in the cancer and CP samples. By densitometry, there was a 11- and 4-fold increase in cripto mRNA levels in pancreatic cancer and CP respectively. Southern blot analysis did not reveal an increase in gene copies encoding cripto either in cancer or in CP. These findings indicate that cripto expression may contribute to disease progression in pancreatic cancer, and implicate cripto in the histopathological alterations that occur in the pancreas both in cancer and in CP.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Blotting, Northern; Blotting, Southern; Chronic Disease; Epidermal Growth Factor; Female; GPI-Linked Proteins; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Male; Membrane Glycoproteins; Middle Aged; Neoplasm Proteins; Pancreas; Pancreatic Neoplasms; Pancreatitis

The expression of oncogene products and growth factors (epidermal growth factor, transforming growth factor-beta, erbB-2, ras p 21, and c-myc) in gallbladder cancer and chronic cholecystitis was measured by immunohistochemical staining on paraffin-embedded serial sections. Expression of these products was graded according to staining intensity in an area of positively stained cells. This study reports the detection of oncogene products and growth factors in cholecystitis as well as in early and late gallbladder cancer. The multiexpression of oncogene products and growth factors was greater for both gallbladder cancer groups as compared with the cholecystitis group. The percentage of epidermal growth factor positivity diminished with increased proportion of interstitial tissue and, conversely, the percentage of transforming growth factor positivity increased with increased proportion of interstitial tissue. The proportion of ras positivity was significantly greater in both early and advanced cholecystic cancer as compared with cholecystitis, but also was considerable even for cholecystitis. These results suggest that various oncogenes may have significant roles in gallbladder cancer and that collagen synthesis is reduced by epidermal growth factor and enhanced by transforming growth factor-beta.

Topics: Cholecystitis; Chronic Disease; Epidermal Growth Factor; Gallbladder Neoplasms; Gene Expression; Growth Substances; Humans; Immunohistochemistry; Oncogene Protein p21(ras); Oncogene Proteins; Oncogene Proteins, Viral; Proto-Oncogene Proteins c-myc; Receptor, ErbB-2; Transforming Growth Factor beta

Topics: Animals; Chronic Disease; Epidermal Growth Factor; Gene Expression; Graft Rejection; Immunohistochemistry; In Situ Hybridization; Kidney Transplantation; Rats; Tissue Distribution; Transplantation, Homologous

Kidneys of newborn (but not adult) mice are normally high permissive for polyomavirus (Py) infection and readily establish persistent infections. We have proposed that ongoing cellular differentiation, which occurs in newborn mice, may be necessary for a high level of in vivo Py replication (R. Rochford, J. P. Moreno, M. L. Peake, and L. P. Villarreal, J. Virol. 66:3287-3297, 1992). This cellular differentiation requirement may also be necessary for the reactivation of a persistent Py kidney infection and could provide an alternative to the accepted view that reactivation results from immunosuppression. To examine this proposal, the ability of adult BALB/c mouse kidneys to support primary acute Py infection or to reactivate previously established persistent Py infections after kidney-specific damage was investigated. Kidney damage was induced by both chemical (glycerol, cisplatin, or methotrexate) and mechanical (through renal artery clamping to produce unilateral renal ischemia) treatments. We also examined the effects of epidermal growth factor (EGF), which enhances the rate of kidney regeneration, on Py replication. Using histopathologic techniques, in situ hybridization for Py DNA, and immunofluorescence for Py VP1 production, we established that both chemical damage and damage through renal artery clamping of adult kidneys promoted high levels of primary Py replication in these normally nonpermissive cells. This damage also promoted the efficient reactivation of Py replication from persistently infected kidneys, in the absence of immunosuppression. EGF treatment significantly increased acute Py replication and also reactivation in damaged kidneys. These results support the view that ongoing cellular division and differentiation may be needed both for high levels of acute Py replication and for reactivation of persistent infections in vivo.

Topics: Acute Disease; Animals; Capsid; Capsid Proteins; Chronic Disease; Cisplatin; Epidermal Growth Factor; Epithelium; Fluorescent Antibody Technique; Glycerol; Ischemia; Kidney Tubules; Methotrexate; Mice; Mice, Inbred BALB C; Polyomavirus; Tumor Virus Infections; Virus Activation

We carried out the following three experiments to clarify the mechanism of hepatocarcinogenesis in Long-Evans Cinnamon (LEC) rats. (1) Sensitivity to diethylnitrosamine (DEN): LEC rats (8 and 25 weeks old) without and with hepatitis and age-matched F344 rats were administered an intraperitoneal injection of a low dose of DEN. Eight weeks after the injection, the numbers of glutathione-S-transferase placental-form (GST-P)-positive foci in the 33-week-old LEC rat liver were significantly higher than those in the livers of the other three groups of rats. (2) Potential for unscheduled DNA synthesis (UDS): Isolated hepatocytes of 25-week-old LEC rats with chronic hepatitis showed about one-third the level of UDS induced by UV irradiation, as compared to that of age-matched F344 rats, while no significant difference was found between the UDS of isolated hepatocytes of 8-week-old LEC rats and age-matched F344 rats. (3) Potential for proliferation: Isolated hepatocytes from 8-week-old LEC rats responded well to epidermal growth factor (EGF) in culture, to almost the same degree as F344 rat hepatocytes, while a remarkable decrease in the responsiveness of hepatocytes isolated from 25-week-old LEC rats to EGF was found. These results suggested that LEC rat hepatocellular carcinoma could be naturally initiated after the onset of hepatitis by carcinogens contaminating food and the environment, probably due to the reduction of DNA repair activity, after which initiated hepatocytes selectively proliferate in response to growth stimuli endogenously produced as a result of continuous loss of hepatocytes (chronic hepatitis), because of a decrease in growth activity of non-initiated hepatocytes.

Topics: Animals; Carcinoma, Hepatocellular; Cell Division; Chronic Disease; Diethylnitrosamine; DNA; Epidermal Growth Factor; Glutathione Transferase; Hepatitis, Animal; Liver; Male; Rats; Rats, Inbred F344; Rats, Mutant Strains; Ultraviolet Rays

Topics: Administration, Topical; Becaplermin; Chronic Disease; Epidermal Growth Factor; Humans; Platelet-Derived Growth Factor; Pressure Ulcer; Proto-Oncogene Proteins c-sis; Recombinant Proteins

The effect of a proton pump inhibitor, omeprazole (OPZ), in combination with mouse epidermal growth factor (EGF), on the healing of chronic gastric ulcers induced by acetic acid in submandibular glands removed rats (SMR rat) was investigated. Four separate groups of SMR rats were orally administered 1 ml of distilled water (control), 100 mg/kg of OPZ alone (OPZ), 5 micrograms/kg of mouse EGF alone (EGF), or combination with (EGF + OPZ) twice daily. Two weeks later, ulcer areas of four groups were measured and expressed as the ulcer index (UI). The UI of the OPZ and EGF + OPZ group was significantly reduced as compared with that of the control. Furthermore, the UI of the EGF + OPZ group was significantly smaller than that of the EGF group. The present study indicates that the proton pump inhibitor promotes healing of chronic gastric ulcers in SMR rats and the effect of the proton pump inhibitor is enhanced by administration of mouse EGF.

Topics: Acetates; Acetic Acid; Adenosine Triphosphatases; Animals; Chronic Disease; Drug Therapy, Combination; Epidermal Growth Factor; Gastric Mucosa; Glycoproteins; H(+)-K(+)-Exchanging ATPase; Mice; Omeprazole; Rats; Stomach Ulcer; Submandibular Gland

Plasma concentrations of Epidermal Growth Factor (EGF) in healthy control persons do not change significantly during adult lifetime and no diurnal changes could be detected. In addition, no alterations of plasma EGF concentrations occur during acute and chronic stress and in all three trimesters of pregnancy. Thus, the previously suggested theories that EGF might play a causative role in the activation of the hypothalamic-pituitary adrenal axis during the stress reaction and in the prevention of peptic ulcers in pregnancy could not be confirmed by the present data.

Topics: Acute Disease; Adolescent; Adult; Aged; Aging; Chronic Disease; Epidermal Growth Factor; Exercise; Female; Humans; Male; Middle Aged; Pregnancy; Reference Values; Stress, Physiological

Topics: Chronic Disease; Epidermal Growth Factor; Humans; Wound Healing; Wounds and Injuries

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.

Topics: Adenocarcinoma; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Fetus; Humans; Immunoenzyme Techniques; Pancreas; Pancreatic Neoplasms; Pancreatitis; Staining and Labeling; Transforming Growth Factor alpha

Sucralfate prevents the formation of acute gastric lesions induced by various ulcerogens and enhances the healing of chronic gastroduodenal ulcerations, but the mechanism of these effects has not been fully explained. This study was designed to determine the importance of intragastric pH in the sucralfate-induced gastroprotection against 100% ethanol, acidified aspirin, taurocholate, or stress, and in the healing of chronic gastroduodenal ulcerations induced by acetic acid. Sucralfate acidified to pH 2.0 showed significantly stronger protective activity against all four irritants, its protective potency against 100% ethanol being about eight times greater and the duration of the protection about four times longer than those obtained with sucralfate at its pH of 5.0. Pretreatment with indomethacin to suppress mucosal generation of prostaglandin or the removal of salivary glands to eliminate the endogenous source of epidermal growth factor failed to affect sucralfate-induced gastroprotection. In contrast, the rate of healing of chronic gastric ulcerations was significantly delayed by indomethacin or sialoadenectomy; but sucralfate enhanced the healing, and a marked inhibition of gastric acid secretion by ranitidine did not eliminate this enhancement. We conclude that the protective activity of sucralfate depends on the presence of acid milieu in the stomach, but that the ulcer-healing effects of this drug occur even after a marked inhibition of gastric acid secretion.

Topics: Animals; Chronic Disease; Combined Modality Therapy; Disease Models, Animal; Drug Therapy, Combination; Epidermal Growth Factor; Female; Gastric Acid; Gastric Mucosa; Hydrogen-Ion Concentration; Indomethacin; Male; Peptic Ulcer; Prostaglandins E; Ranitidine; Rats; Rats, Inbred Strains; Salivary Glands; Sucralfate; Wound Healing

Epidermal growth factor (EGF) receptors were detected in plasma membrane preparations of equine hoof wall laminar tissue at concentrations comparable to that of equine liver. Scatchard analysis of the equilibrium binding data suggested the presence of two classes of EGF binding sites in most of the controls (plasma membranes from clinically normal horses); a high-affinity class and a more numerous low-affinity class. The dissociation constant of the low-affinity class of EGF-specific receptors (KD = 1 x 10(-9)M) is in reasonable agreement with other values established for the EGF receptor. The variability between individual estimates for the KD of the high-affinity receptor class precluded an accurate estimate for those sites. A possible explanation is discussed. The high-affinity binding sites were uniformly absent in plasma membranes prepared from horses affected by chronic laminitis. Autoradiographic analysis localised the EGF receptors primarily to the secondary epidermal laminae, with an apparent greater density over the proliferative basal keratinocytes. Little label was associated with the dermal or the keratinised primary epidermal laminae. Tissue from horses with chronic laminitis had EGF receptors located uniformly over the hyperplastic epidermal keratinocytes. These data suggest that an EGF-mediated response may be involved in the hyperproliferative response that is characteristic of chronic laminitis.

Topics: Animals; Autoradiography; Binding Sites; Binding, Competitive; Cell Membrane; Chronic Disease; Epidermal Growth Factor; ErbB Receptors; Foot Diseases; Hoof and Claw; Horse Diseases; Horses; Ischemia; Liver; Spleen

A heterologous radioreceptor binding assay (RRA) has been developed capable of detecting nanogram amounts of epidermal growth factor (EGF) receptor-binding activity in equine urine. The binding parameters of [125I]mEGF (murine EGF) to EGF receptors on equine plasma membranes are in good agreement with values from other EGF-RRA systems. The dissociation constant estimated from equilibrium methods (KD = 4 X 10(-10) M) is in reasonable agreement with that determined from the rate constants (KD = 6 X 10(-10) M) and is in good agreement with values determined in other species. The assay is specific for equine EGF (eEGF) receptor-binding activity and capable of detecting less than 0.34 nM eEGF receptor-binding activity in urine. Equine EGF receptor-binding activity in equine urine form adult horses varied widely between samples (8.5 +/- 6.5 nM). This variability was somewhat reduced when values were adjusted for dilutional effects using urine creatinine as an indicator (3.6 +/- 2.0 nanomoles/g creatinine). No significant differences were demonstrated between the means of EGF binding activity concentrations in clinically normal horses and horses affected by chronic laminitis.

Topics: Animals; Binding, Competitive; Chromatography, High Pressure Liquid; Chronic Disease; Creatinine; Cross Reactions; Epidermal Growth Factor; ErbB Receptors; Foot Diseases; Hoof and Claw; Horse Diseases; Horses; Predictive Value of Tests; Radioligand Assay

Cells staining for immunoreactive human epidermal growth factor were sought in the lungs and tracheas of human fetuses from 8 to 24 weeks of gestation. Lungs of liveborn infants from 25 to 40 weeks of gestation (stillborn to 7 months postnatal life), both with and without lung pathology, were also studied. In the early fetal trachea (12 to 15 weeks), many nonciliated cells immunostained for immunoreactive human epidermal growth factor in the lining epithelium. By 16 weeks of gestation this widespread staining was replaced by stained nonciliated single cells or small clusters of cells which were identifiable until 24 weeks. In the few tracheas which were available from liveborn infants who died without evidence of lung disease, stained cells were seldom identified in the lining epithelium after 24 weeks of gestation. In contrast, from 18 weeks until term, tracheal submucosal glands contained scattered cells which immunostained for immunoreactive human epidermal growth factor but which did not appear to be classical mucous cells. Beginning at 20 weeks of gestation, positively staining cells were found occasionally in bronchial lining epithelium, but more often in bronchial submucosal glands. Immunostained cells were never identified in bronchiolar epithelium in normal fetal or newborn lungs. In liveborn infants from 24 weeks onward who developed lung disease, many tracheas were severely damaged. In the presence of extensive denudation of the mucosa or the development of squamous metaplasia, immunostained cells were rarely seen in the lining epithelium. However, even under these conditions stained glandular cells could usually be identified. Stained cells were also present in the necks of those tracheal glands from which new epithelial lining cells appeared to be migrating onto denuded surfaces. Immunostained cells in the bronchial lining epithelium of infants with chronic lung disease were infrequent, just as they were in the fetus, but bronchial submucosal glands contained positively stained cells similar to those in tracheal glands. The appearance and distribution of immunostained cells were similar in the tracheal and bronchial submucosal glands in both normal subjects and those with all stages of lung disease. In contrast to the bronchioles of fetuses and infants without lung pathology, the bronchiolar epithelium of infants with chronic lung disease contained immunostained cells. Immunostained cells were found in areas of migrating dysplastic cells in r

Topics: Acute Disease; Bronchopulmonary Dysplasia; Chronic Disease; Embryonic and Fetal Development; Epidermal Growth Factor; Female; Humans; Hyaline Membrane Disease; Infant, Newborn; Lung Diseases; Male; Middle Aged; Respiratory System; Retrospective Studies

Sucralfate exhibits gastroprotective properties in laboratory animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether or not epidermal growth factor (EGF), which also has gastroprotective and ulcer-healing properties, contributes to the action of sucralfate in rat stomach. It was confirmed that sucralfate, like 16,16-dimethyl prostaglandin E2, protects the gastric mucosa against ethanol damage and increases mucosal generation of prostaglandins. Removal of the endogenous source of EGF (sialoadenectomy) did not abolish the protective and prostaglandin-stimulating effects of sucralfate. Exogenous EGF and 16,16-dimethyl prostaglandin E2 were also protective in rats with intact and removed salivary glands. Sucralfate, like EGF, enhanced the healing of chronic gastric and duodenal ulcerations induced by serosal application of acetic acid. Sucralfate was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer areas. Thus, the peptide is available locally in high concentrations to accelerate tissue repair and the healing process in ulcerated mucosa. The ulcer-healing effects of sucralfate were reduced with sialoadenectomy and partially restored with oral administration of EGF. It was concluded that EGF is not essential for the gastroprotection induced by sucralfate, but seems to play an important role in the ulcer-healing action of this drug.

Topics: 16,16-Dimethylprostaglandin E2; Acetates; Acetic Acid; Acute Disease; Animals; Chronic Disease; Dinoprostone; Epidermal Growth Factor; Ethanol; Gastric Mucosa; Male; Peptic Ulcer; Rats; Rats, Inbred Strains; Submandibular Gland; Sucralfate; Wound Healing

The authors examined the influence of pregnancy on the healing of chronic gastric and duodenal ulcers in connection with pregnancy-induced changes of growth parameters of gastric-duodenal mucosa and changes in the level of endogenic EGF. Besides, the level of EGF was lowered by the resection of submandibular glands (sialadenectomy). Pregnancy caused an increase in the speed of the healing of gastric and duodenal ulcers, this effect being the result of the appearance of hyperplastic changes in the gastric-duodenal mucosa. This hyperplasia was the result of the increase in the level of endogenic EGF. Sialadenectomy decreased the level of EGF in the blood serum preventing total pregnancy hyperplasia of the mucosa in the stomach and partly in the duodenum, which resulted in the total abolition of favourable influence of pregnancy on the healing of gastric ulcers and reduction of the influence of pregnancy on the healing of duodenal ulcers. The results obtained show that the gastric and duodenal mucosa during pregnancy has an increased ability to regenerate, this ability resulting from the hyperplasia of the mucosa taking place in pregnancy, which is the effect of an increase in the level of endogenic EGF.

Topics: Chronic Disease; Duodenal Ulcer; Epidermal Growth Factor; Female; Humans; Pregnancy; Pregnancy Complications; Stomach Ulcer; Wound Healing

The effect of extirpation of the submandibular glands, an exocrine organ for epidermal growth factor/urogastrone (EGF/URO), and the effect of oral administration of synthetic human (EGF/URO) on healing of chronic gastric ulcers in rats has been investigated. Removal of the submandibular glands delayed healing of chronic gastric ulcers when examined after 50, 100, and 200 days. Oral administration of synthetic human EGF/URO stimulated gastric ulcer healing when examined after 25 and 50 days of treatment. The effect of synthetic human EGF/URO was comparable with that of cimetidine. The combined administration of synthetic human EGF/URO and cimetidine further increased healing of gastric ulcers compared with administration of each substance. Neither synthetic human EGF/URO, nor removal of the submandibular glands had any influence on gastric acid secretion. This study showed that the submandibular glands influence healing of chronic gastric ulcers and suggest that EGF/URO participate in healing of chronic gastric ulcers in rats.

Topics: Animals; Chronic Disease; Cimetidine; Combined Modality Therapy; Epidermal Growth Factor; Female; Gastric Acid; Rats; Rats, Inbred Strains; Stomach Ulcer; Submandibular Gland