WITHDRAWN: Assessment of the activity of posaconazole against azole-resistant Aspergillus species studied in an in vitro pharmacokinetic/pharmacodynamic model.

Ahead of Print article withdrawn by publisher.

The impact of low alcohol consumption on the liver and inflammatory cytokines in diabetic rats.

BACKGROUND: Diabetes mellitus (DM) and alcohol consumption is still one of the important research models that simulate variable clinical conditions and metabolic diseases, such as alcoholic liver diseases. OBJECTIVES: The aim of this study was to evaluate the long-term cumulative effects of low alcohol consumption on the liver tissue, biochemical assays and some inflammatory cytokines in experimentally-induced DM rats. MATERIAL AND METHODS: Ethanol was administered in the drinking water (3% v/v) for 30 days to adult male Sprague-Dawley rats, with or without DM induced by streptozocin injection. Histological and biochemical parameters as well as some inflammatory cytokines - interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor alpha (TNF-α) - were measured. RESULTS: A significant increase in blood glucose level in the combination group was accompanied by a significant decrease in plasma insulin (p < 0.001 vs controls). Hepatic histopathology of the combination group revealed steatosis and fibrosis in addition to a significant increase in the gamma-glutamyltransferase (γ-GT) and alkaline phosphatase (ALP) levels (p < 0.05 and p < 0.001, respectively). A non-high-density lipoprotein (HDL) lipid profile (total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL)) revealed a significant increase in comparison to controls (p < 0.05), while HDL showed no significant change. The IL-4 and IL-6 levels were significantly higher (p < 0.05), while IL-10 and TNF-α revealed non-significant changes. CONCLUSIONS: Depletion of the hyperglycemic response in the case of low alcohol consumption in DM rats was associated with elevated plasma cytokines, especially IL-6 and IL-4, which could be a part of a host defense mechanism to repair the hepatic and pancreatic damage through this inflammatory process. The severe liver damage under insult of low alcohol consumption and DM could serve as inhibitory factors in gluconeogenesis and glycogenolysis, with little or no impact on insulin levels.

Addressing the Challenges of Tuberculosis: A Brief Historical Account.

Tuberculosis (TB) is a highly contagious disease that still poses a threat to human health. Mycobacterium tuberculosis (MTB), the pathogen responsible for TB, uses diverse ways in order to survive in a variety of host lesions and to subsequently evade immune surveillance; as a result, fighting TB and its associated multidrug resistance has been an ongoing challenge. The aim of this review article is to summarize the historical sequence of drug development and use in the fight against TB, with a particular emphasis on the decades between World War II and the dawn of the twenty first century (2000).

Oral Candida in Patients with Fixed Orthodontic Appliance: In Vitro Combination Therapy.

BACKGROUND: Fixed orthodontic appliance (FOA) increases the cariogenic microorganisms of mouth including candida. The aim was to evaluate the pharmacodynamic effects of some antibacterial drugs in combination with most applicable antifungal agents on candida isolated from patients with FOA. METHODS: Three antifungal agents (amphotericin B (AMB), ketoconazole (KET), and itraconazole (ITZ)) and three antibacterial drugs (ciprofloxacin (CIP), doxycycline (DOX), and metronidazole (MET)) with serial concentrations have been used and microdilution broth method has been done for single and combination therapy, then fungal growth was assessed spectrophotometrically, and the combinations were evaluated by bliss independent analysis. RESULTS: According to bliss independent interaction, the synergistic interactions depended on ΔE values that showed the best for CIP was with AMB (ΔE = 55.14) followed with KET (ΔE = 41.23) and lastly ITR (ΔE = 39.67) at CIP = 150 mg/L. DOX was optimal with KET (ΔE = 42.11) followed with AMB (ΔE = 40.77) and the lowest with ITR (ΔE = 9.12) at DOX = 75 mg/L. MET is the best with AMB (ΔE = 40.95) and then with ITR (ΔE = 35.45) and finally KET (ΔE = 15.15) at MET 200 mg/L. Moreover, usage of higher concentrations of antibacterial agents revealed inhibitory effects. CONCLUSION: This study uncovers the optimum antibiotic combination therapy against cariogenic candida with FOA by usage of low therapeutic concentrations.