amphotericin-b and Osteoarthritis

This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months time-lapse, in order to assess two end-points. Clinical, synovial, radiological and ultrasonographic follow-up was performed. At six months, animals were euthanized and both carpi were assessed by magnetic resonance imaging (MRI), gross anatomy, histopathology, histochemistry and gene expression.. Clinical and synovial inflammatory signs were quicker reduced in MSC-treated groups and repeated allogeneic administration did not produce adverse reactions, but MSC-primed group showed slight and transient local inflammation after second injection. Radiology and MRI did not show significant differences between treated and control groups, whereas ultrasonography suggested reduced synovial effusion in MSC-treated groups. Both MSC-treated groups showed enhanced cartilage gross appearance at two compared to six months (MSC-naïve, p < 0.05). Cartilage histopathology did not reveal differences but histochemistry suggested delayed progression of proteoglycan loss in MSC-treated groups. Synovium histopathology indicated decreased inflammation (p < 0.01) in MSC-primed and MSC-naïve at two and six months, respectively. At two months, cartilage from MSC-primed group significantly (p < 0.05) upregulated collagen type II (COL2A1) and transforming growth factor (TGF)-β1 and downregulated cyclooxygenase-2 and interleukin (IL)-1β. At six months, MSC-treatments significantly downregulated TNFα (p < 0.05), plus MSC-primed upregulated (p < 0.05) COL2A1, aggrecan, cartilage oligomeric protein, tissue inhibitor of metalloproteinases-2 and TGF-β1. In synovium, both MSC-treatments decreased (p < 0.01) matrix metalloproteinase-13 expression at two months and MSC-primed also downregulated TNFα (p < 0.05) and IL-1β (p < 0.01).. Both MSC-treatments provided beneficial effects, mostly observed at short-term. Despite no huge differences between MSC-treatments, the findings suggested enhanced anti-inflammatory and regulatory potential of MSC-primed. While further research is needed to better understand these effects and clarify immunogenicity implications, these findings contribute to enlarge the knowledge about MSC therapeutics and how they could be influenced.

Topics: Amphotericin B; Animals; Horse Diseases; Horses; Inflammation; Interferon-gamma; Male; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Synovial Membrane; Tumor Necrosis Factor-alpha

Invasive candidiasis is rare in children after the neonatal period, but can occur in children with (secondary) immunodeficiency with a damaged gastrointestinal or skin barrier, or when receiving antibiotics. A 10-month-old girl was diagnosed as suffering from cystic fibrosis (CF) when showing failure to thrive, pulmonary symptoms and hypoproteinaemia. At that time, Candida albicans was identified from blood culture and treated intravenously with liposomal amphotericin B for 13 days. Six weeks later, the girl presented with osteoarticular infection of the left knee caused by C. albicans. The infection showed insufficient response to therapy with liposomal amphotericin B, but the patient recovered after therapy with fluconazole and flucytosine. Follow-up over 4 years revealed no sequelae. In conclusion, invasive Candida infections may occur in patients with CF, and preventive measures might be considered in patients at risk. In the case of an invasive infection, prolonged treatment with a combination of antifungal drugs may be required.

Topics: Amphotericin B; Antifungal Agents; Candida albicans; Candidemia; Candidiasis, Invasive; Cystic Fibrosis; Female; Fluconazole; Flucytosine; Humans; Infant; Osteoarthritis; Treatment Outcome

The authors report a case of candidal arthritis and osteomyelitis in a five-month-old child. Parenteral nutrition with central catheter, broad-spectrum antibiotherapy, repeated gastrointestinal surgery are the main risk factors. The prognosis for this bone and joint infection is favourable. Using 5-fluorocytosine alone is not recommended because of rapid gain of resistant various pathogenic fungi and the risk of therapeutic failure.

Topics: Amphotericin B; Candidiasis; Drug Therapy, Combination; Fluorouracil; Humans; Iatrogenic Disease; Infant; Male; Osteoarthritis; Risk Factors

Of 38 heroin addicts treated for systemic candidal infections, 36 had metastatic cutaneous lesions (deep-seated scalp nodules and pustulosis in hairy zones), 15 had ocular localizations (mainly chorioretinitis), and 10 had osteoarticular involvement (vertebrae, costal cartilage, knees, and sacroiliac). Such cutaneous lesions have not previously been described in classical systemic candidiasis; we also observed hair invasion by candidal hyphae. Candida albicans was the exclusive species isolated, in contrast to other visceral candidiases in heroin addicts. All isolates were sensitive to amphotericin B, flucytosine, and ketoconazole. Thirty-one visceral localizations were treated only with ketoconazole. Results were favorable in 15 of 18 cutaneous, 6 of 6 ocular, and 4 of 7 osteoarticular cases of involvement. This outbreak coincided with introduction of a new heroin on the drug market in the Paris area. C. albicans was not isolated from the drug. Pathogenesis of this syndrome is unclear.

Topics: Adult; Aged; Amphotericin B; Bone Diseases; Candida albicans; Candidiasis; Candidiasis, Cutaneous; Eye Diseases; Female; Flucytosine; France; Heroin Dependence; Humans; Joint Diseases; Ketoconazole; Male; Middle Aged; Osteoarthritis; Scalp; Syndrome

Topics: Adult; Amphotericin B; Antifungal Agents; Arthritis, Infectious; Candida albicans; Candidiasis; Catheterization; Cytosine; Female; Flucytosine; Humans; Immunosuppressive Agents; Kidney Transplantation; Osteoarthritis; Transplantation, Homologous