minocycline and Fibrosis

Donor-derived infections with multidrug-resistant gram-negative bacteria are associated with poor outcomes, in part because of limited treatment options. Here, we describe a case of donor-derived, disseminated infection with colistin-resistant, carbapenemase-producing Klebsiella pneumoniae in a liver transplant recipient that was cured with addition of intravenous fosfomycin to a multidrug regimen, in conjunction with aggressive surgical source control. Intravenous fosfomycin represents a promising adjunctive agent for use in treatment of extensively drug-resistant infections in immunocompromised hosts.

Topics: Aged; Allografts; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fibrosis; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Liver Transplantation; Microbial Sensitivity Tests; Minocycline; Tigecycline

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 endodontic regenerative procedure (ERP), which is an alternative to calcium hydroxide-induced apexification, involves the use of a triple antibiotic paste (TAP) as a dressing material. The aim of this study was to evaluate the response of rat subcutaneous tissue to implanted polyethylene tubes that were filled with TAP or calcium hydroxide.. Thirty rats received 2 individual implants of polyethylene tubes filled with TAP or calcium hydroxide paste (CHP) and another empty tube as a control. Thirty additional rats received 2 individual implants consisting of polyethylene tubes filled with dressing material carriers (macrogol and propylene glycol) and a sham procedure. After 7, 15, 30, 60, and 90 days, 12 animals were euthanized, and the tubes and surrounding tissue were removed and processed for histology by using glycol methacrylate and stained with hematoxylin and eosin. The histological score ranged from 0 to 3 depending on the content of inflammatory cells; the fibrous capsule was considered thin or thick, and necrosis and calcification were recorded as present or absent. The results were analyzed using the Kruskal-Wallis test.. Both dressing materials induced moderate reactions at 7 and 15 days. These reactions were similar to the control (P > .05) and reduced in intensity (to mild) from day 30 onward (P > .05). The carriers did not interfere with the reaction of the dressing materials.. TAP and CHP were biocompatible over the different experimental periods examined.

Topics: Animals; Anti-Bacterial Agents; Apexification; Biocompatible Materials; Calcinosis; Calcium Hydroxide; Ciprofloxacin; Drug Carriers; Drug Combinations; Fibrosis; Lymphocytes; Macrophages; Male; Materials Testing; Metronidazole; Minocycline; Necrosis; Polyethylene Glycols; Rats; Rats, Wistar; Regeneration; Root Canal Filling Materials; Subcutaneous Tissue; Time Factors; Tooth, Nonvital

Renal fibrosis is a common finding in progressive renal diseases. Matrix metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type (MMP-2⁺/⁺) mice by unilateral ureteral obstruction (UUO). Renal histopathology, EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during the development of interstitial fibrosis. UUO-renal fibrosis was also induced in MMP-2 deficient (MMP-2⁻/⁻) and MMP-2⁺/⁺ mice treated with minocycline (inhibitor of MMPs). In MMP-2⁺/⁺ mice, MMP-2 and MMP-9 were expressed in damaged tubules, and their activities increased in a time-dependent manner after UUO. Interstitial fibrosis was noted at day 14, with deposition of types III and I collagens and expression of markers of mesenchymal cells (S100A4, vimentin, α-smooth muscle actin, and heat shock protein-47) in damaged tubular epithelial cells, together with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated molecules (ILK, TGF-β1, Smad, Wnt, β-catenin, and Snail). In contrast, the kidneys of MMP-2⁻/⁻ mice and minocycline-treated MMP-2⁺/⁺ mice showed amelioration of renal fibrosis with reduced expression of markers of mesenchymal cells in tubular epithelial cells, inhibition of upregulated EMT-associated molecules, and suppression of macrophage infiltration. The results suggested that MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the induction of EMT and macrophage infiltration. Inhibition of MMPs may be beneficial therapeutically in renal fibrosis.

Topics: Animals; Collagen; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Histocytochemistry; Kidney Diseases; Kidney Tubules; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Transgenic; Minocycline; Phenotype; RNA, Messenger; S100 Calcium-Binding Protein A4; S100 Proteins; Ureteral Obstruction

The ideal thoracoscopic pleurodesis method for preventing recurrence of spontaneous pneumothorax remains controversial. This study was conducted to compare the patterns, effects, and thoracic volume changes achieved using a variety of thoracoscopic procedures in rabbits.. Thirty-six New Zealand White rabbits were randomly assigned to undergo the following thoracoscopic procedures in the left hemithorax: (a) parietal pleural abrasion; (b) minocycline instillation; (c) combination of abrasion and minocycline; or (d) examination alone. The rabbits were euthanatized 30 days after the operation to determine pleurodesis score, area of greatest adhesion, thoracic volume change, and histopathological findings.. Grossly, pleural abrasion produced moderate localized apical pleural symphysis with no obvious thoracic volume change. Minocycline instillation induced moderate generalized pleurodesis with a significant decrease in thoracic volume. The combination of abrasion and minocycline instillation produced the greatest generalized pleurodesis as well as a significant decrease in thoracic volume. On microscopic examination, the combination procedure produced the greatest inflammation and fibrosis of the visceral and parietal pleura. Increased intensity of pleurodesis score as well as pleural inflammation and fibrosis is associated with decreased thoracic volume.. Thoracoscopic pleurodesis achieved using pleural abrasion and minocycline instillation induced different patterns of pleurodesis, and a combination of each method generated a synergy and produced a better pleurodesis. However, as the generalization and intensity of the pleurodesis were inversely associated with thoracic volume, the optimal method should be determined on an individual basis according to the clinical situation.

Topics: Animals; Fibrosis; Minocycline; Pleura; Pleurodesis; Pneumothorax; Rabbits; Thoracoscopy; Thorax

Eighteen adult pigs (Sus scrofa) underwent thoracoscopy and were placed into one of three groups: no sclerosant, talc pleurodesis, or minocycline pleurodesis.. Animals were then sacrificed at matched time intervals. Gross inspection of the pleural cavity estimated percentage of pleural symphysis (>25% was considered substantial) and allowed assignment of a pleurodesis score based on a scale described by Bresticker. Microscopic examination evaluated degree of fibrosis as mild, moderate, or severe.. The talc group had significantly better pleurodesis than the minocycline group as determined by (1) the proportion of animals with substantial surface pleural symphysis (5/6 vs 1/6, p < 0.01), (2) a higher pleurodesis score (3 vs 1.3, p < 0.05), and (3) the proportion of animals with moderate fibrosis (5/6 vs 0/6, p < 0. 01).. The authors conclude that instillation of aerosolized talc produces significantly better fibrosis and pleural symphysis than atomized minocycline in this animal model.

Topics: Animals; Fibrosis; Minocycline; Pleura; Pleurodesis; Swine; Talc; Thoracoscopy; Tissue Adhesions