tacrolimus and Cicatrix

Atopic dermatitis, also known as atopic eczema, is a chronic pruritic skin condition affecting approximately 17.8 million persons in the United States. It can lead to significant morbidity. A simplified version of the U.K. Working Party's Diagnostic Criteria can help make the diagnosis. Asking about the presence and frequency of symptoms can allow physicians to grade the severity of the disease and response to treatment. Management consists of relieving symptoms and lengthening time between flare-ups. Regular, liberal use of emollients is recommended. The primary pharmacologic treatment is topical corticosteroids. Twice-daily or more frequent application has not been shown to be more effective than once-daily application. A maintenance regimen of topical corticosteroids may reduce relapse rates in patients who have recurrent moderate to severe atopic dermatitis. Pimecrolimus and tacrolimus are calcineurin inhibitors that are recommended as second-line treatment for persons with moderate to severe atopic dermatitis and who are at risk of atrophy from topical corticosteroids. Although the U.S. Food and Drug Administration has issued a boxed warning about a possible link between these medications and skin malignancies and lymphoma, studies have not demonstrated a clear link. Topical and oral antibiotics may be used to treat secondary bacterial infections, but are not effective in preventing atopic dermatitis flare-ups. The effectiveness of alternative therapies, such as Chinese herbal preparations, homeopathy, hypnotherapy/biofeedback, and massage therapy, has not been established.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Bacterial Infections; Calcineurin Inhibitors; Cicatrix; Complementary Therapies; Dermatitis, Atopic; Dermatologic Agents; Diagnosis, Differential; Dose-Response Relationship, Drug; Emollients; Histamine Antagonists; Humans; Phototherapy; Pruritus; Skin; Tacrolimus

Numerous treatments have been described for the treatment and prevention of scars, but the optimal management strategy is yet to be defined. In this article we present and evaluate new opportunities for the treatment and prevention of hypertrophic scars, keloids, and atrophic scars. Clinical, animal, and in vitro studies reporting novel techniques for the treatment and prevention of scarring were identified primarily from the MEDLINE/PubMed database. We found that a variety of new treatments exist with potential effectiveness for the treatment of hypertrophic scars and keloids, including interferon, imiquimod 5% cream, tacrolimus, botulinum toxin, 5-fluorouracil, bleomycin, and verapamil. For atrophic scars, different types of lasers represent modern treatment modalities with satisfactory results. Several agents have been reported to be effective in reducing scarring in vitro and in animal studies, representing potential opportunities for scarring management. We conclude that several novel modalities may be potential therapies for scarring.

Topics: Bleomycin; Botulinum Toxins, Type A; Celecoxib; Cicatrix; Fluorouracil; Humans; Immunosuppressive Agents; Laser Therapy; Neuromuscular Agents; Pyrazoles; Sulfonamides; Tacrolimus; Verapamil

Topics: Acne Vulgaris; Atrophy; Cicatrix; Connective Tissue Diseases; Erythema; Humans; Tacrolimus; Treatment Outcome

Frontal fibrosing alopecia (FFA) describes the scarring, band-like recession of the frontotemporal hairline. Treatment is difficult, and currently, no evidence-based therapy exists. The purpose of this study is to report clinical features and treatment responses in a large cohort of patients with FFA. The authors analyzed a series of 72 patients with a clinical or histologic diagnosis of FFA. A total of 70 patients were female (97.2%), and 2 were male (2.8%). In females, the first onset of FFA was postmenopausal in 81.4% (

Topics: Adult; Aged; Aged, 80 and over; Alopecia; Cicatrix; Dermatologic Agents; Drug Therapy, Combination; Eyebrows; Female; Fibrosis; Forehead; Glucocorticoids; Humans; Male; Middle Aged; Retrospective Studies; Tacrolimus

To investigate the effect of tacrolimus on the proliferation of fibroblasts after glaucoma surgery.. Biopsy was applied in this study. Under aseptic conditions, tissues were collected from rabbits, cut into small pieces and cultured. Morphology of fibroblasts was observed under a microscope. Features of fibroblasts were identified via immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Western blotting and RT-PCR were performed to detect the expressions of related proteins after treatment. Flow cytometry and cell counting kit-8 (CCK-8) assay were employed to examine the proliferation of human Tenon's capsule fibroblasts (HTFs) after tacrolimus treatment.. Tacrolimus decreased the levels of survivin and α-smooth muscle actin (α-SMA) after transforming growth factor-β (TGF-β) treatment. Besides, it inhibited proliferation and induced apoptosis of HTFs.. Tacrolimus reduces proliferation and promotes apoptosis of HTFs by inhibiting the expression of survivin, which may be a strategy for treating hypertrophic scar after glaucoma surgery.

Topics: Actins; Animals; Apoptosis; Cell Proliferation; Cells, Cultured; Cicatrix; Fibroblasts; Glaucoma; Humans; In Vitro Techniques; Rabbits; Survivin; Tacrolimus; Tenon Capsule; Transforming Growth Factor beta

Frontal fibrosing alopecia (FFA) is a lichen planopilaris-variant scarring alopecia that has rarely been described in men.. To characterize the clinicopathologic findings of FFA in men by studying a series of 7 male patients.. We conducted a retrospective review of all cases of male patients with FFA at the Mayo Clinic from 1992 to 2016.. Seven male patients with FFA were identified. The frontal scalp (in 6 of 7 patients), sideburns (in 4 of 7), and temporal scalp (in 4 of 7) were most frequently involved. Three patients had involvement of the eyebrows. One patient had hair loss of the upper cutaneous lip. All patients had biopsy evidence of lichen planopilaris. None of the patients had associated autoimmune or thyroid disease. Two patients had hypogonadism upon testosterone studies.. Limitations include small sample size and varied follow-up.. Although most often reported among postmenopausal women, FFA also occurs among men. The clinical and histopathologic characteristics of FFA in men parallel those described in women with FFA. Unique areas of involvement in men include sideburns and facial hair. Concomitant mucocutaneous lichen planus, autoimmune disease, and thyroid disease are infrequent among men with FFA. Distribution of hair loss and associated hormonal abnormalities aid in the recognition of FFA in men.

Topics: Adult; Aged; Alopecia; Anti-Inflammatory Agents; Cheek; Cicatrix; Clobetasol; Dermatologic Agents; Eyebrows; Forehead; Humans; Hydroxychloroquine; Lichen Planus; Male; Middle Aged; Retrospective Studies; Scalp; Tacrolimus

Scar formation after injured peripheral nerve repair is a significant clinical problem because it prevents nerve regeneration. The aim of this study was to investigate and compare the effects of hyaluronic acid (HA) and tacrolimus (FK506) on peripheral nerve regeneration in rabbits after the drugs were topically applied at the site of nerve repair.. Thirty adult male European rabbits (Oryctolagus cuniculus), ranging in weight from 2.5 to 3 kg, were randomly assigned to three groups: the HA and FK506 groups comprised the experimental groups, while the saline group served as the control. At week 12, macroscopic and microscopic evaluations were performed and analyzed.. In general, the macroscopic evaluations (skin and muscle fascia closure and nerve adherence), microscopic evaluations (cellular components, scar tissue formation index, and histomorphological organization), and measurements of nerve diameter and gastrocnemius muscle wet weight demonstrated the positive effects of topical application of these pharmacological agents (HA and FK506); HA and FK506 prevented scar formation and enhanced nerve regeneration. No significant differences in the parameters described above were observed between the HA and FK506 groups (P > 0.05). However, significant differences were observed between both the HA and FK506 groups and the saline group (P < 0.05).. Based on our findings, topical application of HA and FK506 exhibits equally positive effects, preventing perineural scar formation and enhancing nerve regeneration after peripheral nerve repair.

Topics: Administration, Topical; Animals; Cicatrix; Hyaluronic Acid; Male; Models, Animal; Nerve Regeneration; Rabbits; Sciatic Nerve; Tacrolimus

Discoid lupus erythematosus (DLE) is a chronic variant of cutaneous lupus erythematosus, an autoimmune inflammatory disorder of the skin. Lesions are often localized to the scalp and can result in permanent scarring, disfiguration, and irreversible alopecia. Although DLE usually responds to topical or intralesional corticosteroids and/or oral antimalarials, some DLE is resistant to these treatments or adverse effects limit their effectiveness.. Three patients with treatment-refractory, biopsy-proved DLE were prescribed a novel, off-label preparation of tacrolimus lotion, 0.3%, in an alcohol base as an adjunct to oral antimalarial therapy. All 3 patients demonstrated improvement in lesion severity and hair regrowth with the use of this regimen after 3 months and continued improvement thereafter. We report a retrospective analysis of these 3 cases.. This report is, to our knowledge, the first mention of tacrolimus being used in a lotion formulation to treat DLE lesions, resulting in hair regrowth. Topical tacrolimus lotion, 0.3%, in an alcohol base may be a potential therapeutic option for patients with DLE that is refractory to first-line therapies and who risk late-stage disease with permanent scarring alopecia.

Topics: Administration, Topical; Adult; Alopecia; Cicatrix; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Discoid; Middle Aged; Retrospective Studies; Tacrolimus; Treatment Outcome

Stem cell therapy has shown promise in treating a variety of pathologies including skin wounds, but practical applications remain elusive. Here, we demonstrate that endogenous stem cell mobilization produced by AMD3100 and low-dose tacrolimus is able to reduce by 25% the time of complete healing of full-thickness wounds created by surgical excision. Equally important, healing was accompanied by reduced scar formation and regeneration of hair follicles. Searching for mechanisms, we found that AMD3100 combined with low-dose tacrolimus mobilized increased number of lineage-negative c-Kit+, CD34+, and CD133+ stem cells. Low-dose tacrolimus also increased the number of SDF-1-bearing macrophages in the wound sites amplifying the "pull" of mobilized stem cells into the wound. Lineage tracing demonstrated the critical role of CD133 stem cells in enhanced capillary and hair follicle neogenesis, contributing to more rapid and perfect healing. Our findings offer a significant therapeutic approach to wound healing and tissue regeneration.

Topics: Animals; Benzylamines; Cell Lineage; Cicatrix; Cyclams; Disease Models, Animal; Drug Synergism; Hair Follicle; Hematopoietic Stem Cell Mobilization; Heterocyclic Compounds; Immunosuppressive Agents; Mesenchymal Stem Cells; Mice, Inbred C57BL; Mice, Knockout; Rats, Inbred Strains; Receptors, CXCR4; Regenerative Medicine; Skin; Tacrolimus; Wound Healing

To evaluate bladder histology in healing and biochemical analysis of rats with single kidney in ischemia/reperfusion, treated with tacrolimus.. Fifty rats randomized into five groups. Three rats died in surgery, 47 rats divided in groups: Control (non-operated, n=10), Sham (operated without drugs, n=8), T1 (operated + tacrolimus 1mg/kg, n=10), T2 (operated + tacrolimus 0.1 mg/kg, n=10), T3 (operated + tacrolimus 10mg/kg, n=9). The surgery was: laparotomy, right nephrectomy, left kidney ischemia/reperfusion, cystotomy followed by bladder suture. After that, rats were submited to gavage daily (Control and Sham with saline solution. T1, T2, T3 with tacrolimus in doses already mentioned). On the 14th day, after death induction, cystectomy was performed and bladder was histologicaly analysed. The serum urea, creatinine and tacrolimus were analysed too.. There was difference in serum tacrolimus in T3 compared to the other groups (p<0.05). There was higher doses of creatinine in T3 group and higher urea in groups with tacrolimus. There were significant differences among all histologic variables comparing groups with and without tacrolimus (p<0.05).. Tacrolimus associated with ischemia/reperfusion is nephrotoxic, suppresses inflammation and seems to delay the healing bladder.

Topics: Animals; Blood Urea Nitrogen; Cicatrix; Creatinine; Immunosuppressive Agents; Ischemia; Kidney; Male; Models, Animal; Nephrectomy; Random Allocation; Rats, Wistar; Reperfusion Injury; Tacrolimus; Urinary Bladder; Wound Healing

We previously demonstrated that FK506, a generally applied immunosuppressant in organ transplantation, could promote peripheral nerve regeneration through reducing scar formation. However, little is known about how FK506 reduces scar formation. Herein we investigated the influence of FK506 on fibroblast proliferation and its correlation with scar formation after sciatic nerve injury in rats, and further explored the effect of FK506 on fibroblast proliferation and apoptosis in vitro. Masson staining and immunohistochemistry revealed that scar area and fibroblast number in the nerve anastomosis of sciatic nerve-injured rats were significantly reduced after FK506 administration. The scar area had a significant positive correlation with the fibroblast number, as detected by linear correlation analysis. CCK-8 assay and flow cytometry indicated that FK506 also inhibited proliferation and induced apoptosis of fibroblasts in vitro. It was primarily phosphorylation of JNK and ERK that were activated during the apoptosis of fibroblast. Pretreatment of cells with JNK inhibitor, SP600125, or ERK inhibitor, PD98059, could inhibit FK506-induced fibroblast apoptosis, respectively. Moreover, simultaneous application of both inhibitors had additive roles in cell protection from apoptosis. These results suggest that FK506-induced fibroblast apoptosis contributes to the suppression of fibroblast proliferation and then results in the reduction of scar formation in sciatic nerve-injured rat, and that JNK and ERK are involved in FK506-induced fibroblast apoptosis.

Topics: Anastomosis, Surgical; Animals; Anthracenes; Apoptosis; Caspase 3; Cell Proliferation; Cells, Cultured; Cicatrix; Cytochromes c; Cytoprotection; Extracellular Signal-Regulated MAP Kinases; Fibroblasts; Flavonoids; Immunosuppressive Agents; JNK Mitogen-Activated Protein Kinases; Male; Phosphorylation; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Tacrolimus

There was no previous study about topical application of tacrolimus (FK506) could inhibit fibroblast proliferation and prevent epidural scar adhesion after laminectomy. We intended to illustrate the effect of FK506 on inhibiting fibroblast proliferation and preventing epidural scar adhesion after laminectomy in rat model. In our study, seventy-two rats were randomly divided into four groups (0.1mg/ml group, 0.05 mg/ml group, 0.01 mg/ml group and control group). Laminectomy was performed at Lumbar-1 level, and then different concentrations of FK506 and saline were applied to the laminectomy sites. Four weeks later the rats were killed and the epidural adhesion was evaluated. Macroscopic assessment, hydroxyproline content analysis, histological analysis and mRNA measurements were used to evaluate the effect of FK506 on reducing epidural scar adhesion. The results showed that FK506 could prevent epidural scar adhesion in a dose-dependent manner. Little epidural adhesions were seen in the laminectomy sites treated with 0.1mg/ml FK506. The hydroxyproline content, the number of fibroblasts, the mRNA expression level of IL-2 and TGF-β1 in 0.1mg/ml FK506 group were significantly less than those of 0.05 mg/ml FK506 group, 0.01 mg/ml FK506 group and control group. However, dense epidural adhesions were found in 0.01 mg/ml FK506 group and control group. The hydroxyproline content and the number of fibroblasts in 0.01 mg/ml group showed no significant difference compared with those of control group. In conclusion, topical application of 0.1mg/ml FK506 could inhibit fibroblast proliferation and prevent epidural scar adhesion after laminectomy in rat model.

Topics: Administration, Topical; Animals; Cell Proliferation; Cicatrix; Disease Models, Animal; Dose-Response Relationship, Drug; Epidural Space; Fibroblasts; Gene Expression Regulation; Immunosuppressive Agents; Interleukin-2; Laminectomy; Male; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tacrolimus; Tissue Adhesions; Transforming Growth Factor beta1

Frontal fibrosing alopecia (FFA) is a type of scarring hair loss primarily observed in postmenopausal women and characterized by fronto-tempero-parietal hairline recession, perifollicular erythema, and loss of eyebrows. The incidence is unknown, but the number of women presenting with this condition has significantly increased in recent years. No effective therapy has been established.. The purpose of this study is to present pertinent demographic and clinical findings of patients with FFA seen at an academic hair loss clinic and their responses to various therapeutic interventions.. Patients seen at the Duke University Hair Disorders Research and Treatment Center, Durham, NC, between 2004 and 2011 who met FFA inclusion criteria and signed an informed consent form for participation in the Duke University Hair Disorders Research and Treatment Center database were included in this review.. Nineteen female patients with FFA met our inclusion criteria, the majority of whom were white and postmenopausal. A number of treatments, including topical and intralesional steroids, antibiotics, and immunomodulators, were used with disappointing results in most patients. However, the majority of patients on dutasteride experienced disease stabilization.. This was a retrospective review and outside clinic records were occasionally incomplete.. FFA is an increasingly common form of scarring hair loss, but the origin remains unknown. Without clear understanding of the pathogenesis and evolution of this condition, it is not surprising that treatments to date have been minimally or not effective. At our institution, dutasteride was most effective in halting disease progression, although no therapy was associated with significant hair regrowth.

Topics: 5-alpha Reductase Inhibitors; Adult; Aged; Alopecia; Anti-Bacterial Agents; Azasteroids; Cicatrix; Dutasteride; Enzyme Inhibitors; Eyebrows; Female; Fibrosis; Forehead; Hospitals, University; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lichen Planus; Methotrexate; Middle Aged; Minocycline; Osteoporosis, Postmenopausal; Retrospective Studies; Scalp; Tacrolimus; Treatment Outcome

The most common cause of late kidney transplant failure is insidiously progressive renal dysfunction associated with organ scarring and fibrosis. Advanced donor age, delayed graft function, calcineurin toxicity and repeated acute rejection episodes are risk factors for this pathophysiology.. We employed 3, 12 and 24 months surveillance renal biopsies, scored using the Chronic Allograft Damage Index (CADI), with periodic estimates of glomerular filtration rate (eGFR) to assess the effect of a steroid-free maintenance immunosuppression regimen on allograft histology and function. Ninety-one patients were induced with Alemtuzumab and then treated with mycophenolate sodium and low trough concentrations of tacrolimus.. Fifty-six of 91 patients followed for 24 months showed no clinical rejection and in 16 more only minimal histological or borderline changes as defined by Banff criteria were observed. Histologically acute rejection was observed in 14 patients including two detected on surveillance biopsy. Five patients refused biopsies but showed stable eGFR for 24 months. Graft histopathology in the group with no rejection did not worsen. In contrast, nearly half the patients with acute rejection showed progression of CADI scores and a total of four grafts were lost over the 2 years. The 16 patients with borderline rejection changes exhibited stable glomerular filtration rate throughout, but 12.5% showed progression of CADI scores in the 12- to 24-month period.. Following Alemtuzumab induction and in conjunction with low-dose tacrolimus and mycophenolate, continuous steroid therapy was not required to prevent progressive injury or preservation of graft function in patients without biopsy-proven acute rejection. Scored surveillance renal biopsies provide a useful tool to monitor transplanted kidneys.

Topics: Adult; Alemtuzumab; Antibodies, Monoclonal, Humanized; Biopsy; Calcineurin Inhibitors; Cicatrix; Dose-Response Relationship, Drug; Female; Fibrosis; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Longitudinal Studies; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Risk Factors; Tacrolimus; Transplantation, Homologous

The purposes of this study were to investigate the effects of topically administrated Tacrolimus and Octreotide on modulation of postoperative scarring in experimental glaucoma filtration surgery and to compare the antifibrotic properties of these agents with mitomycin-C (MMC).. A total of 28 New Zealand rabbits weighing 2.5-3 kg were randomly divided into a surgical control (SC) group and three experimental groups. Standard filtration surgeries were performed on the right eyes of all the rabbits. The rabbits in the SC group received only vehicle after the surgeries, whereas the rabbits in the three experimental groups were treated either with 0.4 mg/mL MMC during the surgery (MMC group) or with 0.3 mg/mL Tacrolimus drop four times a day (TT group) or with 10 µg/mL Octreotide drop three times a day (OT group) for 14 days. The animals were killed on day 14, eyes were enucleated and histologically and immunohistochemically analyzed.. In SC group mean fibroblast, mononuclear cell number and fibroblast growth factor-β (FGF-β), transforming growth factor-β (TGF-β) immunostaining intensity was higher than all treatment groups. In OT group mean fibroblast number was lesser than MMC (p < 0.01) and TT (p < 0.05) group. In TT group mean fibroblast number was lesser than MMC group (p < 0.05). Mean mononuclear cell number was similar between MMC, OT and TT groups (p > 0.05). In MMC, OT and TT groups mean TGF-β and FGF-β immunostaining intensity was similar (p > 0.05).. Topically administration of Tacrolimus and Octreotide effectively reduced the subconjuntival scarring response 2 weeks after experimental glaucoma filtration surgery.

Topics: Administration, Topical; Alkylating Agents; Animals; Cicatrix; Conjunctival Diseases; Disease Models, Animal; Fibroblast Growth Factor 2; Fibroblasts; Fibrosis; Filtering Surgery; Glaucoma; Immunoenzyme Techniques; Immunosuppressive Agents; Leukocyte Count; Mitomycin; Octreotide; Ophthalmic Solutions; Postoperative Complications; Rabbits; Tacrolimus; Transforming Growth Factor beta

Postlaminectomy epidural fibrosis is the formation of scar tissue over the dura mater following posterior spinal surgery. This devastating complication is responsible for the substantial amount of failed back syndromes. MATERIAL and. Twenty male Wistar-Albino rats each weighing 350-400 grams were used. Following L3-L5 laminectomy, the rats were randomly divided into 2 groups, with 10 rats in each group. In the control group, only a laminectomy was performed. In the drug group, 5 mg/ml tacrolimus was topically applied with a cotton pad soaked with the drug solution for 5 minutes. The animals were killed on the 30th postoperative day injecting a lethal dose (250 mg/kg) of pentobarbital and the involved dural segments were removed for histopathological and ultrastructural evaluations.. Epidural scar thickness and the density were significantly lower in the animals treated with tacrolimus than those of the control group.. Promising evidence regarding the anti-scar potential of tacrolimus merits further research to optimize the dosage and the usage of the drug.

Topics: Administration, Topical; Animals; Cell Movement; Cicatrix; Disease Models, Animal; Dura Mater; Epidural Space; Failed Back Surgery Syndrome; Fibroblasts; Fibrosis; Immunosuppressive Agents; Laminectomy; Lumbar Vertebrae; Male; Microscopy, Electron; Neurosurgical Procedures; Postoperative Complications; Rats; Rats, Wistar; Spinal Canal; Tacrolimus; Treatment Outcome

Brain injury is often associated with proliferation and hypertrophic response of glial cells (reactive gliosis). We have previously reported immunosuppressant effects on survival of glioma cells and adult reactive astrocytes. In the present study, we demonstrate growth-inhibitory effect of FK506 on cortical astrocytes from newborn rats. FK506 inhibits Erk and PI-3K/Akt signaling, two crucial pro-survival pathways. The levels of phosphorylated Akt and p42/44 Erk decline in few hours after FK506 addition. Furthermore, in FK506-treated astrocyte cultures the levels of mRNA encoding PDGF, bFGF, and CNTF decreased. Downregulation of growth factor expression by FK506 may play a role in the inhibition of mitogenic/hypertrophic responses. FasL mRNA level was elevated and interaction of FasL with Fas receptor expressed in astrocytes may trigger cell death. Interestingly, expression of BDNF increased in a dose-dependent manner in FK506-treated astrocytes. Upregulation of BDNF mRNA and protein level in astrocytes exposed to FK506 may underlie neuroprotective action of FK506.

Topics: Animals; Animals, Newborn; Astrocytes; Brain Injuries; Brain-Derived Neurotrophic Factor; Cell Survival; Cells, Cultured; Cicatrix; Dose-Response Relationship, Drug; Down-Regulation; Fas Ligand Protein; Gene Expression Regulation; Gliosis; Growth Substances; Immunosuppressive Agents; Membrane Glycoproteins; Mitogen-Activated Protein Kinases; Neuroprotective Agents; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction; Tacrolimus; Up-Regulation