Rosiglitazone,peroxisome proliferator receptor-gamma agonist,ameliorates gentamicin-induced nephrotoxicity in rats

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe gram-negative infections. Reactive oxygen spaces (ROS) are important mediators of gentamicin-induced nephrotoxicity. Peroxisome proliferator-activated receptors (PPARs) have different activities including antioxidant properties. This study was performed to investigate the protective role of PPAR-γ agonist against GEN-induced nephrotoxicity. Male Wistar Albino rats were randomly divided into the following four groups, each of which consisted of six animals: (1) control; (2) intraperitoneally injected with GEN for 14 consecutive days (100 mg/kg/day); (3) treatment with rosiglitazone (RSG) via nasogastric gavage (10 mg/kg/daily for 14 days); (4) treatment with GEN + RSG combination for 14 day. Rats were decapitated on the 15th day and kidneys were removed. Urine was collected for every 24 h for the determination of daily urine volume. Urea, creatinine, Na⁺ and K⁺ levels were measured in blood. Malondialdehyde (MDA), reduced glutathion (GSH), and nitric oxide (NO) levels along with glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were determined in the renal tissue. Changes in body weight were recorded. GEN treatment was found to cause nephrotoxicity as evidenced by elevation of serum urea and creatinine levels. Renal impairment was also assessed by the renal histology. The significant decrease in GSH and increases in MDA and NO levels as well as a decrease in GSH-Px, CAT, and SOD activities indicated that GEN-induced renal damage was mediated through oxidative reactions. On the other hand, RSG administration protected kidney tissue against GEN-induced and free radical-mediated oxidative renal damage in rats.     

Rosuvastatin protects tissue perfusion in the experimental testicular torsion model

Recently, anti-inflammatory and tissue protective effects of statins have been shown independent from its anti-hyperlipidemic effect. It has been shown that one of the statins, rosuvastatin, may reduce ischemia/reperfusion (I/R)-induced tissue injury in the brain, intestines, and heart. We planned an experimental study to evaluate the effect of rosuvastatin on I/R injury encountered after the detorsion of the testicular torsion. Rats were divided into three groups. In group 1, testis basal blood flow (basal value) was measured with LASER Doppler flowmeter (LDF). Testis was relocated into the scrotum without torsion. Two and 3 h after the basal measurement, testis was brought out from the same incision, and the second (second value) and third (third value) testicular blood flow measurements were done, respectively. In group 2, after the measurement of basal value testicular torsion was created. Second and third value measurements were obtained with LDF at the end of the 2 h of testicular torsion just before the detorsion and 1 h after detorsion. In group 3, same procedures in torsion/detorsion group were repeated in this group, but 10 mg/kg rosuvastatin was injected intraperitoneally 30 min before detorsion. Second values in groups 2 and 3 were significantly lower than group 1. Third values were significantly low in group 2 compared to groups 1 and 3. Regarding the third measurement, there was no significant difference between the groups 1 and 3. Tissue injury is closely related with condition of microvascular perfusion after I/R. Rosuvastatin can protect tissue perfusion in the experimental testicular torsion model.     

Evidence for waning of latency in a cohort study of tuberculosis

Background  

To investigate how the risk of active tuberculosis disease is influenced by time since original infection and to determine whether the risk of reactivation of tuberculosis increases or decreases with age.     

Intra-left ventricular systolic asynchrony in patients with overt hyperthyroidism

Hyperthyroidism causes a variety of adverse effects on the cardiovascular system. Left ventricular (LV) asynchrony is defined as loss of the simultaneous peak contraction of corresponding cardiac segments. The aim of this study was to assess systolic asynchrony in patients with overt hyperthyroidism. Asynchrony was evaluated in 27 patients with overt hyperthyroidism and 21 controls. All the patients and controls were subjected to a tissue synchronization imaging (TSI). The time to regional peak systolic tissue velocity (Ts) in LV by the six-basal-six-mid-segmental model was measured on ejection phase TSI images and four TSI parameters of systolic asynchrony were computed. All TSI parameters of LV asynchrony increased in hyperthyroid patients compared to controls: the standard deviation (SD) of the 12 LV segments Ts (35.7±14.4 vs 20.1±10.1, P<0.0001); the maximal difference in Ts between any 2 of the 12 LV segments (111.9±40.7 vs 65.9±30.7, P<0.0001); the SD of the 6 basal LV segments (31.2±18.2 vs 16.8±9.7, P=0.01); and the maximal difference in Ts between any 2 of the 6 basal LV segments (76.6±42.0 vs 44.4±25.7, P=0.005). Patients with overt hyperthyroidism present evidence of LV asynchrony by TSI.     

The value of XPD and XRCC1 genotype polymorphisms to predict clinical outcome in metastatic colorectal carcinoma patients with irinotecan-based regimens

Background  

Previous studies have suggested that DNA repair enzyme polymorphisms may bear prognostic value in metastatic colorectal carcinoma (MCRC).     

Spontaneous endogenous hypermelatoninemia: a new disease?

Melatonin, a major photoperiod-dependent hormone, regulates circadian rhythms and biological rhythms and acts as a prominent sleep promoter. Symptoms related to hypermelatoninemia have been reported in individuals supplemented with melatonin. However, spontaneous endogenous hypermelatoninemia has not been reported previously. A 6-year-old girl previously diagnosed with Shapiro's syndrome was admitted to our hospital on several occasions during a 1-year period with complaints of altered consciousness, syncope, hypothermia and episodes of sweating. The episodes occurred daily and during sleep and lasted for 1-6 h. During these episodes, she sweated profusely and felt faint and her skin was pale and cool. Other complaints included recurrent abdominal pain, urge incontinence and myopia. She was shown to have hypermelatoninemia (>1,000 pg/ml, normal range 0-150 pg/ml) during these episodes. The duration of her attacks decreased with phototherapy and she was successfully treated with propranolol. To our knowledge, this is the first case of hypermelatoninemia without any detectable organic pathology. We did not determine the exact mechanism of hypermelatoninemia in this patient; however, it might have been related to irregular control of pinealocytes by the suprachiasmatic nucleus or related pathways. Hypermelatoninemia should be considered in patients with spontaneous periodic hypothermia and hyperhidrosis, and also in patients with Shapiro's syndrome.     

The design and cytotoxic evaluation of some 1-aryl-3-isopropylamino-1-propanone hydrochlorides towards human Huh-7 hepatoma cells

A series of 1-aryl-3-isopropylamino-1-propanone hydrochlorides 1 and a related heterocyclic analog 2 as candidate antineoplastic agents were prepared and the rationale for designing these compounds is presented. A specific objective in this study is the discovery of novel compounds possessing growth-inhibiting properties of hepatoma cells. The compounds in series 1 and 2 were prepared and their structures established unequivocally. X-ray crystallography of two representative compounds 1d and 1g were achieved. Over half of the compounds are more potent than 5-fluorouracil which is an established drug used in treating liver cancers. QSAR evaluations and molecular modeling studies were undertaken with a view to detecting some physicochemical parameters which govern cytotoxic potencies. A number of guidelines for amplification of the project have been formulated.     

Prenatal TCDD in mice increases adult autoimmunity

Two immunologically different mouse strains, C57BL/6 and SNF₁, were exposed to a mid-gestation dose of TCDD. The C57BL/6 mouse has a high-affinity aryl hydrocarbon receptor (AhR) and is sensitive to TCDD. The SNF₁ mouse has a low-affinity AhR but spontaneously develops autoimmune nephritis. Autoreactive Vβ⁺CD4⁺17a and Vβ⁺CD3⁺ T cells were increased at 24-weeks-of-age in offspring of C57BL/6 mice, more so in females than males. The cytokine IFN-γ was elevated in the females, while IL-10 was elevated in males. Phenotypic changes in B-lineage cells were present in bone marrow and spleen, and circulating autoantibodies were increased after prenatal TCDD. Kidneys of males showed significant anti-IgG and anti-C3 deposition, suggesting early-stage autoimmune disease. The SNF₁ offspring similarly showed increased peripheral Vβ⁺ cells in the females, increased autoantibody production in both sexes, and increased IFN-γ production in females. Male SNF₁ mice had increased anti-IgG and anti-C3 deposition in kidneys. Both mouse models therefore showed clear signatures of enhanced autoimmunity after prenatal TCDD.