Oral candidiasis is one of the earliest and most frequent complications of a failing immune system in HIV-infected individuals. For several years, oral candidiasis has been treated effectively with azole drugs, the one most frequently used is fluconazole. Unfortunately, extensive use of the drug for treatment and prophylaxis has led to treatment failure in an increasing number of patients. In most of these cases, strains of C. albicans isolated from the infection are less susceptible to fluconazole. The development of azole resistance in strains of C. albicans has been studied biochemically and more recently with molecular techniques. One excellent example of the development of azole resistance in C. albicans has been documented in a series of 17 C. albicans isolates from a single patient over a 2-year period. During this time, the patient experienced 14 episodes of oral candidiasis and was treated with increasing doses of fluconazole. Molecular and biochemical analyses confirms that the isolates are the same strain of C. albicans and that the resistance in these isolates is stable over 600 generations, suggesting that the changes in this strain are genetic in nature. In addition, the development of resistance is correlated with the identification of a substrain or variant of the original strain, as identified by restriction fragment length polymorphism (RFLP) analysis with the moderately repetitive probe, Ca3. The analysis of this series of isolates demonstrates that azole drug resistance is associated with several small genetic changes, each of which contributes to the overall resistance of the strain. Clearly, continual use of azole drugs by a patient can select for genetic changes that render oral candidiasis refractory to treatment.

Studies have shown that dietary caloric restriction (CR) without malnutrition can increase longevity.This study aims to evaluate the protective effects of CR on oxidative stress, lipid peroxidation and inflammatory cytokines in the kidney of streptozotocin-induced diabetic rats. Forty 12-week old male Wistar rats, weighing 250-275 g, were randomly divided into 4 groups. Two groups were subjected to 30 % caloric restriction and the other two to ad libitum feeding for 9 weeks. Diabetes was induced at the 10th week by a single intraperitoneal injection of streptozotocin (35 mg/kg body weight) to one caloric restricted and one ad libitum group. At sacrifice, 2 weeks after the induction of diabetes, the severe hyperglycemia in the kidney of diabetic rats fed ad libitum correlated with increases in organ weight, malondialdehyde (MDA), triglyceride (TG), oxidized glutathione (GSSG) and reactive oxygen species (ROS) concentrations, superoxide dismutase (SOD) and catalase (CAT) activities and decreased glutathione reductase (GR) and glutathione peroxidase (GPx) activities, reduced glutathione (GSH) levels and GSH/GSSG ratios. Decreased levels of tumor necrosis factor-alpha (TNF -α), interleukin 1β (IL -1β) and interleukin -6 (IL -6) were also observed in these diabetic kidneys and these were postulated to be indicative of proteinuria. Caloric restriction was able to significantly reduce ROS, MDA and GSSG concentration as well as the activities of SOD and CAT under diabetic conditions. Moreover, CR produced significant increases in GPx and GR activities, GSH concentration and the GSH/GSSG ratio as well as significant increases in IL-1β, IL-6 and TNFα concentrations. Additionally, non-significant decreases were exhibited in the concentrations of glucose, TG and GSSG in the diabetic animals under CR. It can be concluded that caloric restriction significantly improved antioxidant status, lipid peroxidation and restored the cytokine levels to near normalcy. This study has demonstrated that these pathophysiological alterations caused by disturbed glucose homeostasis are reversed by caloric restriction and thus CR may have therapeutic/preventive potential towards the development of diabetic nephropathy.