tetracycline and Necrosis

Root surface biomodification has been used to treat periodontitis and gingival recession. The rationale for this procedure is that removing the smear layer from the root surfaces exposes collagen fibers, which leads to improved healing. Although animal studies have shown promising results, human studies have been disappointing. Some experts claim that the use of low-pH biomodification agents may cause necrotizing effects, and the use of neutral-pH agents does not. However, clinical investigations generally have failed to find any improvement in clinical parameters when using such agents.

Topics: Acid Etching, Dental; Animals; Anti-Bacterial Agents; Cell Adhesion; Chelating Agents; Citric Acid; Collagen; Dental Scaling; Edetic Acid; Endotoxins; Gingival Recession; Humans; Hydrogen-Ion Concentration; Necrosis; Periodontal Diseases; Root Planing; Smear Layer; Tetracycline; Tooth Root; Wound Healing

Topics: Angiography; Animals; Blood Vessels; Bone and Bones; Bone Development; Bone Marrow; Calcification, Physiologic; Dogs; Embolism; Femur; Fractures, Bone; Methods; Microscopy, Fluorescence; Necrosis; Periosteum; Rabbits; Regional Blood Flow; Staining and Labeling; Tetracycline; Tibia; Wound Healing

Successful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy.

Topics: Alarmins; Animals; Antineoplastic Agents; Apoptosis; Bone Marrow Cells; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Proliferation; Chemokines; Cross-Priming; Dendritic Cells; Immunity; Ligands; Mice; Models, Biological; Necrosis; Neoplasms; NF-kappa B; Phagocytosis; Protein Multimerization; Tetracycline; Vaccination

Envenomation by Loxosceles spider is characterized by the development of dermonecrosis. In previous studies, we have demonstrated that increased expression/secretion of matrix metalloproteinases 2 and 9, induced by Loxosceles intermedia venom Class 2 SMases D (the main toxin in the spider venom), contribute to the development of cutaneous loxoscelism. In the present study we show that the more potent venom containing the Class 1 SMase D from Loxosceles laeta, in addition to increasing the expression/secretion of MMP2 and MMP9, also stimulates the expression of MMP7 (Matrilysin-1), which was associated with keratinocyte cell death. Tetracycline, a matrix metalloproteinase inhibitor, prevented cell death and reduced MMPs expression. Considering that L. laeta venom is more potent at inducing dermonecrosis than L. intermedia venom, our results suggest that MMP7 may play an important role in the severity of dermonecrosis induced by L. laeta spider venom SMase D. In addition, the inhibition of MMPs by e.g. tetracyclines may be considered for the treatment of the cutaneous loxoscelism.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Arthropod Proteins; Blotting, Western; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Humans; Keratinocytes; Matrix Metalloproteinase 2; Matrix Metalloproteinase 7; Matrix Metalloproteinase 9; Necrosis; Phosphoric Diester Hydrolases; Rabbits; Skin; Spider Venoms; Spiders; Tetracycline; Time Factors

Despite recovery of hemodynamics by fluid resuscitation after hemorrhage, development of the systemic inflammatory response and multiple organ dysfunction syndromes can nonetheless lead to death. Minocycline and doxycycline are tetracycline derivatives that are protective in models of hypoxic, ischemic, and oxidative stress. Our aim was to determine whether minocycline and doxycycline protect liver and kidney and improve survival in a mouse model of hemorrhagic shock and resuscitation.. Mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood followed by half the shed volume of lactated Ringer's solution containing tetracycline (10 mg/kg), minocycline (10 mg/kg), doxycycline (5 mg/kg), or vehicle. For pretreatment plus posttreatment, drugs were administered intraperitoneally prior to hemorrhage followed by second equal dose in Ringer's solution after blood resuscitation. Blood and tissue were harvested after 6 h.. Serum alanine aminotransferase (ALT) increased to 1,988 and 1,878 U/L after posttreatment with vehicle and tetracycline, respectively, whereas minocycline and doxycycline posttreatment decreased ALT to 857 and 863 U/L. Pretreatment plus posttreatment with minocycline and doxycycline also decreased ALT to 849 and 834 U/L. After vehicle, blood creatinine increased to 134 µM, which minocycline and doxycycline posttreatment decreased to 59 and 56 µM. Minocycline and doxycycline pretreatment plus posttreatment decreased creatinine similarly. Minocycline and doxycycline also decreased necrosis and apoptosis in liver and apoptosis in both liver and kidney, the latter assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) and caspase 3 activation. Lastly after 4.5 h of hemorrhage followed by resuscitation, minocycline and doxycycline (but not tetracycline) posttreatment improved 1-week survival from 38% (vehicle) to 69% and 67%, respectively.. Minocycline and doxycycline were similarly protective when given before as after blood resuscitation and might therefore have clinical efficacy to mitigate liver and kidney injury after resuscitated hemorrhage.

Topics: Alanine Transaminase; Animals; Apoptosis; Biomarkers; Caspase 3; Creatinine; Cytoprotection; Disease Models, Animal; Doxycycline; Fluid Therapy; Hemodynamics; Kidney; Liver; Male; Mice, Inbred C57BL; Minocycline; Multiple Organ Failure; Necrosis; Protective Agents; Resuscitation; Shock, Hemorrhagic; Tetracycline; Time Factors

Cyclin D1 is important for pancreatic cancer growth. Our aim was to determine the effects of cyclin D1 inhibition on the growth of established pancreatic tumors.. PANC-1 cells harboring cyclin D1 antisense cDNA in a tetracycline-inducible vector system were prepared. The effects of cyclin D1 inhibition after tumor development were characterized in a mouse model.. In vitro removal of tetracycline induced cyclin D1 antisense cDNA expression and inhibited cyclin D1 expression and cyclin D1-associated kinase activity as well as anchorage-dependent and -independent growth. After establishment of xenograft tumors in the presence of tetracycline (2 mg/mL) in the drinking water, animals were assigned to either control (tetracycline remained in the drinking water) or to the group without tetracycline for which tetracycline was removed from the drinking water. Tumor growth was significantly inhibited after removal of tetracycline. Microscopic analysis revealed that the area of central necrosis was significantly increased in the group without tetracycline paralleled by a reduction of the vital peripheral area of proliferating cells.. Our results confirmed that cyclin D1 plays an important role in the growth of pancreatic cancer cells and may be an attractive molecular target for the treatment of human pancreatic cancer.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Cyclin D1; DNA, Antisense; Female; Gene Expression Regulation; Genes, Reporter; Genetic Therapy; Humans; Mice; Mice, Nude; Necrosis; Pancreatic Neoplasms; Tetracycline; Time Factors; Transfection; Tumor Burden; Xenograft Model Antitumor Assays

This study aimed to evaluate by the intra-osseous implant technique the most commonly used materials for pulp therapy in pediatric dentistry: calcium hydroxide (CH), Guedes Pinto paste and CTZ paste, according to FDI (1980) and ANSI/ADA (1982) recommendations. Thirty guinea pigs, 10 for each material, divided into experimental periods of 4 and 12 weeks received one implant on each side of the lower jaw symphysis. The external lateral tube wall served as control for the technique. At the end of the observation periods, the animals were euthanized and specimens were prepared for routine histological examination. It was observed that CH and CTZ paste induced severe inflammation, a large amount of necrotic tissue, lymphocytes, foreign body cells and bone resorption, while Guedes Pinto Paste induced little or no inflammation in the 4-week observation period. After 12 weeks, the reactions to CH and Guedes Pinto paste were also absent/mild, presenting a general pattern of replacement by recently formed bone tissue while a moderate to severe inflammatory response was observed with CTZ paste. Guedes Pinto paste presented acceptable biocompatibility levels in both analyzed periods; CH only showed acceptable biocompatibility in the 12-week period while CTZ paste showed no biocompatibility in both periods. Among the tested materials, only Guedes Pinto paste presented an acceptable biocompatibility.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Biocompatible Materials; Bone Resorption; Calcium Hydroxide; Chloramphenicol; Drug Combinations; Eugenol; Giant Cells, Foreign-Body; Guinea Pigs; Hydrocarbons, Iodinated; Lymphocytes; Macrophages; Mandible; Necrosis; Neutrophils; Osteitis; Osteogenesis; Prednisolone; Rifamycins; Root Canal Filling Materials; Tetracycline; Time Factors; Zinc Oxide

The venom of Loxosceles spiders produces severe dermonecrotic damage, intravascular hemolysis, systemic alterations and risk of death. Clostridium perfringens is present in the microbial flora of the fangs and venom glands of Loxosceles intermedia. Its inoculation with the venom may infect the wound site and exacerbate the dermonecrotic damage. This anaerobic bacterium is widely distributed in nature and capable of damage with similar characteristics and severity to the spider venom. In this study we isolated and characterized species of Clostridium from the fangs and venom glands of Loxosceles laeta, including C. perfringens. The sensitivity patterns of different isolates of C. perfringens were evaluated by minimum inhibitory concentration against penicillin, ampicillin, erythromycin, gentamicin, chloramphenicol, clindamycin and tetracycline, under anaerobic conditions, using the method of microdilution in broth. Strain C. perfringens H28 showed resistance to penicillin, ampicillin, tetracycline and chloramphenicol. Resistance to penicillin and ampicillin was mediated by beta-lactamase. In vivo evaluation of dermonecrosis in rabbits using L. laeta venom co-inoculated with isolate C. perfringens H28 produced an increase in the area of dermonecrotic lesions in the presence of penicillin and tetracycline, but not with gentamicin. Antibiotic therapy Loxosceles poisoning should be re-evaluated, considering the existence of multi-resistant strains of C. perfringens.

Topics: Animals; Anti-Bacterial Agents; Antivenins; beta-Lactamases; Clostridium perfringens; Exocrine Glands; Gene Expression; Injections, Intradermal; Male; Necrosis; Penicillin Resistance; Penicillins; Phosphoric Diester Hydrolases; Rabbits; Skin; Spider Bites; Spider Venoms; Spiders; Tetracycline; Tetracycline Resistance; Tooth

Graft failure after liver transplantation may involve mitochondrial dysfunction. We examined whether prevention of mitochondrial injury would improve graft function. Orthotopic rat liver transplantation was performed after 18 hours' cold storage in University of Wisconsin solution and treatment with vehicle, minocycline, tetracycline, or N-methyl-4-isoleucine cyclosporin (NIM811) of explants and recipients. Serum alanine aminotransferase (ALT), necrosis, and apoptosis were assessed 6 hours after implantation. Mitochondrial polarization and cell viability were assessed by intravital microscopy. Respiration and the mitochondrial permeability transition (MPT) were assessed in isolated rat liver mitochondria. After transplantation with vehicle or tetracycline, ALT increased to 5242 U/L and 4373 U/L, respectively. Minocycline and NIM811 treatment decreased ALT to 2374 U/L and 2159 U/L, respectively (P < 0.01). Necrosis and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) also decreased from 21.4% and 21 cells/field, respectively, after vehicle to 10.1% and 6 cells/field after minocycline and to 8.7% and 5.2 cells/field after NIM811 (P < 0.05). Additionally, minocycline decreased caspase-3 activity in graft homogenates (P < 0.05). Long-term graft survival was 27% and 33%, respectively, after vehicle and tetracycline treatment, which increased to 60% and 70% after minocycline and NIM811 (P < 0.05). In isolated mitochondria, minocycline and NIM811 but not tetracycline blocked the MPT. Minocycline blocked the MPT by decreasing mitochondrial Ca(2+) uptake, whereas NIM811 blocks by interaction with cyclophilin D. Intravital microscopy showed that minocycline and NIM811 preserved mitochondrial polarization and cell viability after transplantation (P < 0.05).. Minocycline and NIM811 attenuated graft injury after rat liver transplantation and improved graft survival. Minocycline and/or NIM811 might be useful clinically in hepatic surgery and transplantation.

Topics: Adenosine Diphosphate; Alanine Transaminase; Animals; Anti-Bacterial Agents; Apoptosis; Calcium; Cyclosporine; Graft Survival; Liver; Liver Transplantation; Male; Minocycline; Mitochondria; Mitochondrial Diseases; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Necrosis; Rats; Rats, Inbred Lew; Reperfusion Injury; Tetracycline

Tight regulation of the therapeutic gene expression is critical in gene therapy. In this report, a doxycycline (Dox)-regulated retrovirus-mediated gene expression system was used to study the effects of suicide gene therapy on human breast cancer cell line MCF-7 and the nude mice model of implanted human breast cancer. To render the expression of suicide gene under control, we used two pseudoviruses simultaneously, RevTRE/HSVtk and RevTet-On, to infect MCF-7 cells or xenografts of nude mice. When infected by the pseudoviruses and followed by Dox and Ganciclovir (GCV) treatment, MCF-7 cells were arrested at S phase and the growth was suppressed. We then evaluated the antitumor efficiency of this system in vivo through studying the mice bearing human breast cancer xenografts. Compared with control groups, the HSVtk mRNA level increased significantly in tumor tissues, mass of the tumors shrank remarkably, and tumor necrosis features occurred after treatment with Dox and GCV. These data suggest that suicide gene therapy using the Dox-induced Tet-On-controlled HSVtk gene expression system is a feasible method to treat human breast cancer.

Topics: Animals; Breast Neoplasms; Bystander Effect; Cell Line, Tumor; Doxycycline; Female; Ganciclovir; Gene Expression Regulation, Neoplastic; Genes, Transgenic, Suicide; Genetic Therapy; Genetic Vectors; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Necrosis; Protein Synthesis Inhibitors; Retroviridae; Tetracycline; Thymidine Kinase; Transfection; Transplantation, Heterologous

Topics: Anti-Bacterial Agents; Chronic Disease; Debridement; Female; Fluorescent Dyes; Humans; Mandible; Mandibular Diseases; Middle Aged; Necrosis; Osteomyelitis; Staining and Labeling; Tetracycline; Ultraviolet Rays

Idiopathic dilated cardiomyopathy (DCM), ventricular systolic dysfunction and chamber dilatation are accompanied by architectural remodeling, wall thinning and cardiac myocyte slippage. Recent work has demonstrated an association between collagen degradation and an increased expression of matrix metalloproteinases (MMPs). Accordingly, we have sought to correlate (a) collagen degradation with MMP elevations and, (b) assay the neutralizing potential of a known inhibitor of MMP, tetracycline on MMPs in DCM.. Assessment of LV volume and shape by 2-D echocardiography was performed. Light microscopic assessment of histopathology in picrosirius red stained biopsy samples of 11 DCM patients and six post-transplant patients was performed. Zymographic estimation of MMP activity and influence of tetracycline on MMP activity was assessed.. Small amount of interstitial collagen was noted in the control group, whereas in the DCM hearts, chamber dilatation was associated with areas of scanty myocyte necrosis, islands of excess collagen, and focal areas of absent or scanty collagen with intact myocytes. In cardiomyopathic tissue, collagenase activity was markedly elevated at 63% compared with 8% in post-transplant tissue. Tetracycline at a concentration of 285+/-10 microM (IC50) inhibited collagenase activity by 50% in cardiomyopathic tissue.. Areas of focal interstitial collagen accumulation were accompanied by collagen fiber lysis and increased collagenase activity in dilated cardiomyopathy. This enhanced collagenolytic activity found in endomyocardial biopsy tissue was inhibited by tetracycline. The non-antibiotic property of tetracycline may be of potential value in the prevention of ventricular dilatation in idiopathic dilated cardiomyopathy.

Topics: Adult; Biomarkers; Cardiomyopathy, Dilated; Collagen; Collagenases; Echocardiography; Electrophoresis, Polyacrylamide Gel; Female; Fibrosis; Heart Diseases; Heart Transplantation; Humans; Inhibitory Concentration 50; Male; Matrix Metalloproteinases; Middle Aged; Myocardium; Necrosis; Tetracycline; Time Factors

We used vital staining with tetracycline to detect viability of bone at the bone-cement interface in 11 stable ICLH femoral surface replacement prostheses that were retrieved at revision surgery for acetabular loosening. The resected femoral heads were processed for undecalcified ground sections with the prostheses in situ. All sections showed direct bone-to-cement contacts. Bone in direct contact with or close to the cement sometimes showed an abnormal staining, indicating that the bone was not fully mineralized. Areas with fluorescence were observed within all femoral heads but never in direct bone-to-cement contact. From this study, we conclude that the mechanical stability of these cemented femoral surface replacement prostheses depends mainly on the original bone present at the time of primary operation.

Topics: Acetabulum; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Bone Cements; Bone Resorption; Female; Femur Head; Hip Prosthesis; Humans; Male; Middle Aged; Necrosis; Prosthesis Failure; Reoperation; Staining and Labeling; Tetracycline

Chemical ablation of the gallbladder might avoid the need for surgery in elderly, unfit patients. This study examined the efficacy of various chemicals in destroying gallbladder mucosa.. Ninety-five per cent ethanol, 3 per cent sodium tetradecyl sulphate (STD), trifluoroacetic acid (TFA) 2 mol/l, tetracycline 50 mg/ml, 30 and 50 per cent phenol, and a mucosal exfoliant solution (compound ethylene diamine tetra-acetic acid) were tested for gallbladder ablation in rabbits. Histology was obtained 8 weeks after exposure to these chemicals.. Thirty per cent phenol, tetracycline, TFA and ethanol when used as single agents were moderately effective in causing complete gallbladder mucosal obliteration, 50 per cent phenol caused a macroscopic burn of the entire gallbladder. The mucosal exfoliant solution and STD on their own did not cause mucosal destruction but had significantly enhanced efficacy when combined with 95 per cent ethanol, allowing reliable mucosal destruction with a 5-min contact duration.. Ninety-five per cent ethanol and STD after pretreatment with a mucosal exfoliant solution may be the combination of choice for in situ gallbladder mucosal ablation.

Topics: Animals; Ethanol; Female; Gallbladder; Necrosis; Pilot Projects; Rabbits; Sclerosing Solutions; Sodium Tetradecyl Sulfate; Tetracycline; Trifluoroacetic Acid

Apoptosis and necrosis, two morphologically distinct forms of cell death, can be induced by common stimuli depending on the doses and the cell type. This study compares the protective effect of oncoprotein Bcl-2 and of the small stress protein Hsp27 on these two types of cell death. We use rat embryo fibroblasts conditionally immortalized by the tsA58 mutant of SV40 large T antigen as parental cells to develop cell lines carrying inducible bcl-2 or hsp27 genes. Two apoptotic stimuli were used: shift to the restrictive temperature that induced p53-mediated apoptosis and treatment with low doses of hydrogen peroxide. Necrosis was induced by high doses of hydrogen peroxide. Although Bcl-2 and Hsp27 protect these cells from necrotic death, only Bcl-2 appears capable of preventing apoptotic death. Bcl-2 protection is not mediated by a negative effect on the induction of the p53 responsive genes bax or waf1 but it slows down at least two stages of apoptosis: decrease of mitochondrial membrane potential and subsequent morphological changes. In contrast, although Hsp27 has been recently shown to inhibit apoptosis induced by various stimuli, its overexpression has no effect on apoptosis in this cell system. It should be also noticed that the apoptotic stimuli (temperature shift or hydrogen peroxide treatment) induce Hsp27, but not Bcl-2 accumulation suggesting that, in parental cells, Hsp27 might already provide some protection. However, taken together these results suggest that Hsp27, as well as Bcl-2, acts at several levels to inhibit cell death, but that their protective functions only partially overlap.

Topics: Animals; Antigens, Viral, Tumor; Apoptosis; Cell Line; Cell Line, Transformed; Cell Membrane; Cell Survival; Embryo, Mammalian; Fibroblasts; Heat-Shock Proteins; Hydrogen Peroxide; Kinetics; Membrane Potentials; Mitochondria; Necrosis; Proto-Oncogene Proteins c-bcl-2; Rats; Recombinant Proteins; Simian virus 40; Tetracycline; Transfection

Interleukin-4 (IL-4) has been demonstrated to possess anti-tumourigenic properties in vivo which is initially attributed to the infiltration of eosinophils proposed to occur by IL-4 binding to its receptors on endothelial cells, thereby mediating eosinophil adhesion. We have investigated whether the binding of IL-4 to receptors on endothelial cells could elicit other biological responses which may also play a role in tumour inhibition, such as angiogenesis. We have demonstrated that mouse IL-4 (mIL-4) down-regulates the expression of one of the receptors for VEGF, VEGF-R2, on endothelial cells in vitro. By generating stable transfectants of C6 glioma cells that express mIL-4 under a tetracycline-responsive promoter system, we were able to apply tight regulatory control of mIL-4 expression in vivo. Subcutaneous implantation of mIL-4/C6 cell lines in nu/nu mice revealed that tumour growth is inhibited by mIL-4 expression. mIL-4-expressing tumours were demonstrated to have a reduced level of vascularisation compared with controls, in addition to a high degree of eosinophil infiltration. Our results suggest that mIL-4 has bimodal biological roles in potentiating tumour inhibition in athymic mice: the suppression of angiogenesis and the augmentation of the host local immune response.

Topics: Animals; Brain Neoplasms; Cell Division; Cloning, Molecular; DNA, Complementary; Endothelial Growth Factors; Endothelium; Eosinophils; Female; Genetic Vectors; Glioma; Interleukin-4; Lymphokines; Male; Mice; Mice, Nude; Necrosis; Neovascularization, Pathologic; Rats; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Tetracycline; Transfection; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Drug-induced pemphigus represents a diagnostic challenge, as usually no clinical feature differentiates it from its idiopathic counterpart. It was suggested recently that some histologic features may assist in diagnosing drug-associated diseases. The purpose of the study was to determine whether the histologic criteria suggested in the literature are specific enough to arouse suspicion of drug-induced pemphigus. Biopsy specimens of drug-induced and idiopathic pemphigus were reviewed by five dermatologists with no clinical data available about the patients. The sections were assessed to the presence of spongiosis with eosinophils, vacuolar degeneration, and the degree of acantholysis and cleavage level. Using the suggested criteria, the reviewers were unable to confirm a diagnosis of drug-induced pemphigus. It is advisable to consider drug etiology in every case of newly diagnosed pemphigus based on clinical criteria an detailed drug consumption history, as histologic features do not differentiate between drug-associated and idiopathic disease.

Topics: Acantholysis; Adult; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Cloxacillin; Diagnosis, Differential; Dipyrone; Drug Eruptions; Drug Therapy; Eosinophils; Female; Humans; Keratinocytes; Male; Medical History Taking; Middle Aged; Necrosis; Pemphigus; Penicillins; Tetracycline; Vacuoles

Acute self-limited liver disease has been associated with tetracycline use. However, severe prolonged cholestatic hepatitis and bile duct paucity have not been previously attributed to tetracyclines. Hepatitis, characterized by prolonged jaundice, severe pruritus, and moderate increased transaminase values, occurred within 2 months of ingesting tetracyclines in two female patients. Serum bilirubin levels normalized 12 and 34 months after tetracycline ingestion. Liver histology revealed bile duct paucity, severe cholestasis, and minimal necrosis and inflammation. Tetracyclines may infrequently induce bile duct paucity and prolonged, severe, and reversible cholestasis.

Topics: Adult; Bile Ducts; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Liver; Middle Aged; Necrosis; Tetracycline

Four cows and a calf with non-suppurative limb cellulitis were observed subsequently to suffer skin necrosis and sloughing in the affected limbs, either on or distal to the metacarpus or metatarsus. In comparison with six cows with suppurative Corynebacterium pyogenes limb cellulitis, topical therapy or the cases with skin necrosis and sloughing was adequate and the prognosis was good, when compared with the rigorous systemic therapy applied to the cows with suppurative cellulitis, some of which died. The skin necrosis and sloughing resulting from limb cellulitis seemed to be encouraged by the paucity of tissue between the skin and the bone, by the poor vascularity of the area, and by the causative bacteria.

Topics: Administration, Topical; Animals; Cattle; Cattle Diseases; Cellulitis; Debridement; Extremities; Female; Necrosis; Ointments; Povidone-Iodine; Prognosis; Skin; Tetracycline; Treatment Outcome

The connective tissue reactions to 3% tetracycline ointment were studied in 14 Sprague-Dawley white male rats. Using polyethylene tubes, the ointment was implanted subcutaneously in the pouches surgically created on the backs of the experimental group. Empty tube implants, tubes with the vehicle (vaseline/lanolin), and a sham operation (surgical pouches with no implant) served as controls. The animals were killed on day 14 and tissue blocks were taken containing the tubes and a generous amount of the peripheral connective tissue. The connective tissue surrounding the tube opening furthest from the surgical incision was histologically examined for the severity of tissue reaction (STR), the number of inflammatory cell infiltrates (II), and the spread of the reaction area (RSI). The data were statistically analyzed. The sham operation group showed minimal inflammatory response. All three parameters (STR, II, RSI) were significantly greater in the tetracycline group when compared with the empty tube group at 0.05 level of significance. There were significant differences between the mean values of the STR and RSI scores in the tetracycline and vehicle groups (groups 1 and 2). The vehicle group (group 2) had significantly higher STR and II values than the empty tube group (group 3); however, the RSI scores were not statistically different. Necrosis was observed in the reaction site in group 1 and vacuole-containing macrophages were noted in groups 1 and 2. This study, although an animal investigation, questions the use of topical 3% tetracycline ointment on sutured surgical flaps.

Topics: Animals; Connective Tissue; Inflammation; Lanolin; Male; Necrosis; Ointment Bases; Petrolatum; Polyethylenes; Prostheses and Implants; Rats; Rats, Inbred Strains; Skin; Tetracycline

Fifteen patients with toxic epidermal necrolysis (TEN) were studied. In all of them the TEN was related to drug ingestion and believed to be drug-induced. The drugs implicated include pyrazolone derivatives, allopurinol, barbiturates, tetracycline, phenytoin, and penicillamine. Possible etiologic co-factors are infections, cancer, and the systemic lupus erythematosus diathesis. The extent of skin loss varied from 25% to almost 100% involvement of the total body surface. Seven of the fifteen patients had more than 75% epidermal loss. Three deaths were recorded (20%). From observations on these fifteen patients it was found that a single drug can cause two "reaction" patterns, namely, Stevens-Johnson syndrome (or erythema multiforme) and TEN, at the same time or at different times in one and the same patient. It is stressed that from the prognostic and therapeutic viewpoints patients with TEN may be equated to patients with extensive partial-thickness burns and should be treated in a burn unit.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antipyrine; Barbiturates; Burns; Child; Diagnosis, Differential; Drug Eruptions; Female; Humans; Male; Middle Aged; Necrosis; Penicillamine; Phenytoin; Syndrome; Tetracycline

Liposomes accumulate is ischaemic rat intestine 24 h after mesenteric occlusion. The accumulation of liposomal components is shown to depend on necrotic or allied alterations in cell integrity/function associated with chronic ischaemia. Moreover, not all liposomal components accumulate at sites of infarction. It is concluded therefore that liposomes are likely to be of little value in the diagnosis and management of ischaemic disorders.

Topics: Animals; Etidronic Acid; Hydrocortisone; Intestines; Ischemia; Liposomes; Male; Necrosis; Pharmaceutical Vehicles; Rats; Tetracycline; Time Factors

The lethal effects of the fluorinated ether anesthetics fluroxene (2,2,2-trifluoroethyl vinyl ether) and its ethyl (TFEE) and allyl analogues in male Wistar rats have previously been demonstrated to be potentiated by specific hepatic microsomal cytochromes P-450, and mediated by the common metabolite 2,2,2-trifluoroethanol (TFE). We report here that administration of lethal combinations of anesthetic and cytochrome P-450-inducing agents or of lethal doses of TFE (0.21 g/kg and higher) to rats caused decreased white blood cell counts, necrosis of sternum bone marrow cells and lymphocytes in the thymic cortex, and resulted in Escherichia coli contamination of the blood, lungs, liver, and kidneys of treated rats. Control animals in identical environments were free of bacterial contamination. Pretreatment of rats with the antibiotic tetracycline-HCl in the drinking water (0.6 g/liter) from 24 hr before anesthetic or TFE administration significantly diminished the mortality. With TFEE and beta-naphthoflavone induction, mortality was reduced from 85 to 30% by the antibiotic. However, the antibody plaque assay following immunization with sheep erythrocytes indicated that the primary humoral immune response to a thymus-dependent antigen was not impaired in treated rats. These results considered together indicate that metabolic formation of TFE from the anesthetic agents produced a decreased host resistance with subsequent increased susceptibility to bacterial infection. If not administered the antibiotic, the animals succumbed to the infection.

Topics: Anesthetics; Animals; Bacterial Infections; Ethers; Ethyl Ethers; Immunity; Leukocyte Count; Liver; Lymphatic System; Male; Necrosis; Rats; Rats, Inbred Strains; Tetracycline; Trifluoroethanol

Topics: Absorption; Animals; Kinetics; Muscles; Muscular Diseases; Necrosis; Rats; Sarcoma, Experimental; Technetium; Tetracycline; Time Factors

Methods currently used to quantitate myocardial damage and necrosis produced by chemicals are usually time consuming and subjective. These studies were conducted to evaluate the utility of 3H-tetracycline as a means of quantitating myocardial necrosis produced by isoproterenol. Male, Sprague-Dawley derived rats (180-200 g) were treated with (+/-)-isoproterenol HCl (0.1-100 mg/kg, s.c.) or equivalent volumes of saline. After 90 minutes, all rats received 50 uCi/kg of 3H-tetracycline. Rats were sacrificed 3 hours after 3H-tetracycline administration and the hearts were removed and rinsed free of blood. The degree of radioactivity of the heart as determined by liquid scintillation counting was directly proportional to the dose of isoproterenol. Propranolol pretreatment decreased the accumulation of radioactivity in a dose-dependent fashion. Determination of 3H-tetracycline accumulation appears to be a rapid and reliable method for quantitating isoproterenol-induced myocardial necrosis.

Topics: Animals; Cardiomyopathies; Dose-Response Relationship, Drug; Isoproterenol; Male; Myocardium; Necrosis; Propranolol; Rats; Tetracycline

Considering the diagnostic significance of a few 99mTc-chelates in the diagnosis of myocardial infarct, we have recently developed a necrosis model in tissue culture obtained from mammalian cells, where the dead cells showed enhanced binding of 99mTc-tetracycline like the necrotic cells of infarcted myocardium. Technical details of the principles of labeling, fixing, washing and drying, dipping in emulsion, exposure, development and staining of mammalian cells have been described. Considering the short half-life of 99mTc-radioisotope, the recently available techniques have been modified to make autoradiography possible in a reasonably short period of time. Technetium-99m in different physical and chemical states is playing a very important role in a variety of diagnostic procedures. The autoradiography of 99mTc-labeled cells and tissue will shed further light on the mechanism of cellular uptake and subcellular distribution in normal and pathologic states. Presently no information is available regarding autoradiography with 99mTc-chelates of mammalian cells obtained from tissue culture.

Topics: Autoradiography; Myocardial Infarction; Necrosis; Technetium; Tetracycline

Fluoride-18 scintigraphy is a simple, safe method for evaluating perfusion to bone, and obviates objections to earlier techniques. The scintillation camera with positron detection represents a unique instrumentation system because of its tomographic effect, relative insensitivity to vascular radioactivity in the surrounding skeleton, and excellent spatial resolution despite low counting efficiency. In 75 patients with avascular disorders about the hip, knee, elbow, foot and hand, the impressions obtained from fluoride-18 scintigraphy were correlated with clinical findings and roentgenograms and when possible confirmed by tetracycline labeling and histological examination. Fluoride-18 scintigraphy was useful: in determining the vascularity of the femoral head following femoral neck fractures; in determining results of treatment; and in diagnosing early the various avascular necrotic disorders of the bone.

Topics: Adolescent; Aged; Bone and Bones; Bone Diseases; Child; Female; Femoral Neck Fractures; Fluorescence; Fluorine; Humans; Male; Necrosis; Osteochondritis; Radioisotopes; Radionuclide Imaging; Tetracycline; Wrist Injuries

An epizootic of reptilian amebiasis seems to have caused the death of 15 to 16 large and valuable captive snakes (boas, pythons, and anacondas) occupying one of 5 large display dioramas in the Steinhart Aquarium of the California Academy of Science, Golden Gate Park, San Francisco. Subsequent review of previous snake deaths in the colony indicated that of 464 snakes that had died since early 1969, 89 snakes had intestinal or hepatic lesions, and 80 of these snakes had pathologic features which involved severe intestinal ulceration, hemorrhage, and massive enteritis, with or without hepatic necrosis and destruction, condition compatible with Entamoeba invadens infection. The present epizootic began in November, 1972, with the death by acute enteritis of a red-tailed boa constrictor (Boa constrictor amarali) and was followed by the loss of 15 other large boids and pythonids. The affected snakes became immobile, refused to feed, and began to die 10 weeks after the death of the red-tailed boa. Seven boa constrictors, 4 pythons, and 4 anacondas from the same diorama died during the ensuing 10 weeks. Entamoeba invadens trophozoites were identified in the stool of the remaining living snake, a 3-m boa constrictor, and in the liver and the intestinal tissue of 1 of the dead boas examined microscopically. The parasite was also found in the stool of a giant Burmese python (Python molurus bivittatus) that died in the adjacent diorama and in the tissues of a blue-tongued skink (Tiliqua scincoides), separately housed, that died of enteritis during this period. Amebic cysts were recovered from turtle and alligator fecal samples taken from a central "swamp," or reservoir, draining the dioramas, water that is returned to the snake display areas after passage through a biological sand-gravel filter and ultraviolet radiation exposure. Cultures from these stools were positive and proved lethal to an experimentally infected boa constrictor. Treatment of the surviving snake in the affected diorama with metronidazole at the dose rate of 275 mg/kg proved rapidly effective; toxicosis was not observed. Other snakes and lizards suspected of having the infection were similarly treated and returned to normal behavior and feeding patterns. Epidemiologic considerations review the probable mode of introduction and spread of this highly lethal snake pathogen and recommendations are made for avoiding infection, prophylactic treatment, and handling of similar epizootics when they do occur

Topics: Amebiasis; Animals; Animals, Zoo; Emetine; Entamoebiasis; Enteritis; Gastroenteritis; Inflammation; Intestines; Kidney; Liver; Metronidazole; Necrosis; Snakes; Tetracycline

Topics: Animals; Body Weight; Castration; Cornea; Diet; Eye; Kidney; Liver; Male; Mycotoxins; Necrosis; Penicillium; Prednisolone; Rats; Reserpine; Scrotum; Skin; Stomach; Tetracycline; Time Factors; Tripelennamine

Topics: Cell Line; Chlortetracycline; Demeclocycline; Liver; Necrosis; Oxytetracycline; Technetium; Tetracycline

After acute coronary occlusion in primates, the time period during which reperfusion results in significant salvage of reversibly injured myocardium was investigated. In 23 monkeys, the left anterior descending coronary artery was occluded from 1 to 6 h; and in 5 others, occlusion was maintained for the 1-wk study. Unipolar epicardial electrocardiograms were monitored from mapping points on the anterior and lateral left venticle. S-T segment elevation (S-T upward arrow) and R + S wave amplitude (RS) were measured before occlusion and at regular intervals during occlusion and reperfusion. Summated S-T upward arrow (SigmaS-T upward arrow) and summated RS (SigmaRS), computed for mapping points demonstrating greater than 2 mV S-T upward arrow, were used as serial measures of electrical injury. SigmaS-T upward arrow peaked within 2-h postocclusion and then gradually declined throughout the period of occlusion suggesting the progress of infarction within the area of injury. After reperfusion SigmaS-T upward arrow rapidly declined to near cnotrol values indicating the extent of reversible injury. During the period of occlusion, the magnitude of voltage loss in SigmaS-T upward arrow as a percent of maximum SigmaS-T upward arrow was proportional to the duration of occlusion, though the rate of loss decreased with increasing time of occlusion. Reperfusion after 6 h of occlusion resulted in reversal of only a small remaining component of the maximum current of injury. The voltage decrease in SigmaRS (from control values) was proportional to the duration of occlusion, though the decrease was accelerated during the first 2-h postocclusion. Whereas reperfusion interrupted the decline in SigmaRS, a consistent increase in SigmaRS postreperfusion was observed only after occlusion of 1 h. With respect to reperfusion groups, significance in SigmaS-T upward arrow voltage loss as a percent of maximum SigmaS-T upward arrow was demonstrated between 2-h and 4-h, 4- and 6-h, and 6-h and chronically ligated animals. Significance in SigmaRS voltage loss as a percent of control SigmaRS was demonstrated between 2- and 4-h, and 4- and 6-h reperfusion groups. Hearts were excised at 7 days for histological assessment of infarct size. Planimetric determination of left ventricular areas and areas of necrosis using slides made from 10 serial cross sections were used in estimating the percent of left ventricle infarcted. A significant reduction in infarct size was demonstrated between reper

Topics: Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Electric Injuries; Electrocardiography; Fluorescence; Heart Ventricles; Ligation; Macaca fascicularis; Models, Biological; Myocardial Infarction; Necrosis; Tetracycline; Time Factors; Tourniquets

Topics: Acute Kidney Injury; Adult; Blood Coagulation Tests; Bronchopneumonia; Cytoplasm; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Hepatic Encephalopathy; Humans; Liver; Liver Function Tests; Necrosis; Pneumonia; Pregnancy; Respiratory Insufficiency; Seizures; Tetracycline; Time Factors; Twins; Uric Acid

Topics: Age Factors; Animals; Cartilage, Articular; Dogs; Epiphyses; Femur Head; Femur Neck; Hip; Hip Joint; Humans; Ischemia; Necrosis; Osteochondritis; Prognosis; Rabbits; Radiography; Swine; Tetracycline

Topics: Actinobacillus; Actinobacillus Infections; Animals; England; Kidney; Kidney Cortex; Kidney Medulla; Necrosis; Swine; Swine Diseases; Tetracycline

Topics: Adult; Aged; Agranulocytosis; Aminopyrine; Antineoplastic Agents; Candidiasis, Oral; Dentin; Drug Hypersensitivity; Female; Gingival Hyperplasia; Humans; Hydantoins; Mouth; Mouth Diseases; Mouth Mucosa; Necrosis; Palate; Penicillins; Phenylbutazone; Tetracycline; Thrombocytopenia

Topics: Adipose Tissue; Animals; Bone Development; Cartilage; Epiphyses; Femur; Fluorescence; Hematoma; Necrosis; Postoperative Complications; Rabbits; Radiography; Recurrence; Synostosis; Tetracycline; Time Factors; Transplantation, Heterologous; Waxes

Topics: Adolescent; Adult; Cephalosporins; Chloramphenicol; Chronic Disease; Culture Media; Enterococcus faecalis; Erythromycin; Female; Femoral Fractures; Femur Head; Humans; Hypertonic Solutions; Kanamycin; L Forms; Male; Microbial Sensitivity Tests; Middle Aged; Necrosis; Osteomyelitis; Penicillins; Polymyxins; Proteus; Radiography; Staphylococcal Infections; Staphylococcus; Tetracycline; Vancomycin

Topics: Animals; Carcinoma 256, Walker; Edetic Acid; Kidney; Liver; Male; Microscopy, Fluorescence; Necrosis; Rats; Spleen; Tetracycline

Topics: Antibodies; Bacteria; Bone Diseases; Child, Preschool; Female; Gentamicins; Granuloma; Humans; Lymphatic Diseases; Male; Necrosis; Tetracycline; Tonsillitis

Topics: Animals; Chlorpromazine; Cysteine; Injections, Intraperitoneal; Ischemia; Liver Diseases; Necrosis; Rats; Tetracycline

Topics: Adult; Biopsy; Chronic Disease; Humans; L Forms; Male; Necrosis; Pharyngitis; Stomatitis, Aphthous; Streptococcal Infections; Tetracycline; Triamcinolone Acetonide

Topics: Animals; Burns; Coloring Agents; Diagnosis, Differential; Hydrogen-Ion Concentration; Male; Necrosis; Rats; Skin; Staining and Labeling; Tetracycline

Topics: Adult; Age Factors; Anemia, Sickle Cell; Bone Diseases; Female; Femoral Fractures; Femur Head; Fluorescence; Follow-Up Studies; Humans; Male; Microscopy, Polarization; Middle Aged; Necrosis; Osteogenesis; Radiography; Sex Factors; Synovial Fluid; Synovitis; Tetracycline; Uric Acid; X-Ray Diffraction

Topics: Animals; Bile Ducts; Body Weight; Cecum; Cholangitis; Culture Media; Diet; Epididymis; Food Microbiology; Guinea Pigs; Hepatitis; Hyperplasia; Liver; Male; Mycotoxins; Necrosis; Penicillium; Plant Poisoning; Rats; Scrotum; Stomach Diseases; Tetracycline; Zea mays

Topics: Adult; Biopsy; Bone Regeneration; Female; Humans; Ilium; Male; Microradiography; Microscopy, Fluorescence; Necrosis; Osteitis; Sclerosis; Spondylitis, Ankylosing; Tetracycline

Topics: Animals; Coronary Vessels; Female; Fluorescence; Heart Diseases; Hydrocortisone; Ligation; Myocardial Infarction; Myocardium; Necrosis; Oils; Rats; Tetracycline

Topics: Animals; Clostridium; Clostridium Infections; Guinea Pigs; Mice; Necrosis; Rabbits; Radiation Effects; Tetracycline

Topics: Diabetes Complications; Foot; Gangrene; Humans; Leg; Leg Ulcer; Necrosis; Tetracycline

Topics: Animals; Cecum; Chlortetracycline; Colon, Sigmoid; Cricetinae; Diarrhea; Drug Hypersensitivity; Epithelium; Intestine, Large; Necrosis; Oxytetracycline; Tetracycline; Vascular Diseases

Topics: Alanine Transaminase; Animals; Chemical and Drug Induced Liver Injury; Fatty Liver; Female; Liver Diseases; Male; Necrosis; Ornithine Carbamoyltransferase; Perfusion; Rats; Tetracycline

Topics: Adolescent; Adrenal Glands; Fatty Liver; Female; Humans; Necrosis; Pancreas; Pregnancy; Pregnancy Complications; Pyelonephritis; Tetracycline

Topics: Clostridium perfringens; Colectomy; Colitis; Digitalis Glycosides; Female; Humans; Hydrocortisone; Ileostomy; Middle Aged; Necrosis; Tetracycline

Topics: Adult; Enteral Nutrition; Fracture Fixation; Humans; Male; Mandibular Fractures; Maxillary Fractures; Maxillofacial Injuries; Metals; Neck Injuries; Necrosis; Osteomyelitis; Radiography; Skin Transplantation; Spinal Injuries; Splints; Stainless Steel; Surgery, Plastic; Tetracycline; Tracheotomy

Topics: Adolescent; Chlorpheniramine; Dexamethasone; Diphenhydramine; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Hydrocortisone; Male; Methoxamine; Necrosis; Norepinephrine; Pentobarbital; Purpura; Tetracycline

Topics: Animals; Female; Glycosuria, Renal; Hemoglobins, Abnormal; Hemoglobinuria; Kidney Tubules; Necrosis; Rats; Tetracycline

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Blood Coagulation Disorders; Diagnosis; Drug Therapy; Fibrinolysis; Humans; Ischemia; Necrosis; Pathology; Prednisone; Promethazine; Purpura; Purpura Fulminans; Tetracycline

Topics: Adrenocorticotropic Hormone; Ascorbic Acid; Blood Coagulation Disorders; Diagnosis; Drug Therapy; Fibrinolysis; Humans; Ischemia; Necrosis; Pathology; Prednisone; Promethazine; Purpura; Purpura Fulminans; Tetracycline

Topics: Anti-Bacterial Agents; Bacitracin; Bone Marrow Diseases; Drug Eruptions; Gastrointestinal Diseases; Kanamycin; Kidney Diseases; Liver Diseases; Necrosis; Neomycin; Neurologic Manifestations; Penicillins; Pharmacology; Polymyxins; Ristocetin; Streptomycin; Tetracycline; Toxicology; Vancomycin; Vestibule, Labyrinth

Topics: Ammonium Compounds; Chlorides; Fluorescence; Heparin Antagonists; Ischemia; Kidney; Kidney Diseases; Kidney Tubules; Mercury; Necrosis; Pathology; Potassium; Quaternary Ammonium Compounds; Rats; Research; Serine; Tetracycline; Toxicology

Topics: Amides; Calcium; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chloroform; Edetic Acid; Fluorescence; Formates; Hepatitis; Hepatitis A; Metabolism; Necrosis; Pathology; Pharmacology; Promethazine; Rats; Research; Sulfhydryl Compounds; Tetracycline; Toxicology

Topics: Animals; Benz(a)Anthracenes; Carcinoma, Squamous Cell; Female; Fluorescence; In Vitro Techniques; Injections, Intramuscular; Leukemia, Experimental; Male; Mammary Neoplasms, Experimental; Necrosis; Neoplasms, Experimental; Ovarian Neoplasms; Rabbits; Rats; Tetracycline

Topics: Anesthesia; Atropine; Barbiturates; Chemical and Drug Induced Liver Injury; Colonic Neoplasms; Halothane; Hepatitis; Massive Hepatic Necrosis; Necrosis; Neomycin; Phenazocine; Postoperative Complications; Promethazine; Sigmoidoscopy; Surgical Procedures, Operative; Tetracycline; Toxicology

Topics: Aspartate Aminotransferases; Dogs; Glycosuria; Kidney Diseases; Kidney Function Tests; Kidney Tubules; Necrosis; Pathology; Proteinuria; Rats; Research; Tetracycline; Toxicology; Urine

Topics: Anaphylaxis; Animals; Fluorescence; Histological Techniques; In Vitro Techniques; Kidney Diseases; Kidney Tubules; Necrosis; Pituitary Hormones, Posterior; Rats; Tetracycline

Topics: Anti-Bacterial Agents; Dermatology; Humans; Hydrocortisone; Necrosis; Skin Diseases; Stevens-Johnson Syndrome; Tetracycline

Topics: Anti-Bacterial Agents; Burns; Fluorescence; Humans; Inflammation; Ischemia; Myocardial Infarction; Necrosis; Neoplasms; Tetracycline

Topics: Anti-Bacterial Agents; Fluorescence; Necrosis; Tetracycline; Tetracyclines