Colistin is an old antibiotic used in the treatment of Gram-negative infections. It was once suspended because of its nephrotoxic effect but has since been reintroduced due to multidrug-resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the roles of caspase-associated apoptosis and caspase 1, calpain 1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it. Twenty-four rats were divided into three groups: control, colistin, and colistin plus GSPE (colistin؉GSPE). Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg of body weight/day colistin intraperitoneally for 7 days. The experiment was discontinued on the seventh day. Blood was collected for measurements of blood urea nitrogen (BUN) and creatinine levels. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and calpain 1 staining was also performed. Significant increases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed for the colistin group compared to the control group. Significant decreases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed in the colistin؉GSPE group compared to the colistin group. Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1, and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by the lowered levels of these mediators.

We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

Statins, inhibitors of cholesterol synthesis, are used to prevent cardiovascular complications. Moreover, statins have been shown to influence some cognitive functions. The modulating effects of simvastatin, one member of the statin family, on memory-related neurotransmitters and neuronal structures have also been reported. We aimed to investigate the behavioral effects of long-term simvastatin application on daily activity, psychomotor performance and spatial memory using Sprague-Dawley rats. Simvastatin (10 or 30 mg/kg/day) was administered orally to rats, in parallel with a vehicle-treated group. Daily activity test results of both simvastatin groups were found similar to the vehicle group after five weeks of simvastatin or vehicle application. Psychomotor performance was measured with the rotarod test. After 6 weeks of simvastatin or vehicle application, the vehicle-treated group stayed on the rotarod device for a shorter time compared with both simvastatintreated groups. Spatial memory was evaluated by the Barnes maze test. Four weeks of 10 mg/kg/day simvastatin application led to poorer scores on spatial memory compared to the vehicle group, but surprisingly, this effect was not seen in the 30 mg/kg/day group. Our results revealed that simvastatin administration had no significant effect on daily activity. Psychomotor performance test results suggested that simvastatin alters psychomotor behavior at higher nervous system levels. Spatial memory test results indicate that longterm simvastatin usage impairs spatial memory only at 10 mg/kg/day dose. Barnes maze; behavior; statins; brain; locomotor.Tohoku

Aim: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seedproanthocyanidin extract (GSPE) on preventing CIN. Materials and Methods: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index(AI)and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. Conclusion: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

Objectives: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. Materials and methods: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. Conclusion: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities

Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

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Objective: Demodex folliculorum and D. brevis are acari that can be found in hair follicles and sebaceous glands of the skin, especially on face of human. This study was aimed to reveal prevalance of Demodex species in faculty of health science students. Methods: Skin surface biopsy was performed in subjects who completed socio-demographic questionnaire. The samples were examined under a microscope for demodex species. Results: In this study, at least one species of demodex was found to be positive in 47.4% of 270 students. Coexistence of D. folliculorum and D. brevis was observed in most of the subjects (50.8%). In all positive cases, the presence of only Demodex folliculorum or brevis was found in 29.7% and 19.5% respectively. There was no relationship between variables and demodex prevalence. Conclusion: This study showed that demodex species infestation is a common but an ignored health problem in faculty of health science students. GirişBiyolojik sınıflandırma sistemine göre Demodeks soyu; Arachnida sınıfı, Prostigmata takımı ve Demodicidae ailesinde yer alır 1,2 . Bu soya ait Demodeks follikulorum ve D. brevis olmak üzere iki türün, insanlarda parazitik yaşam sürdüğü bilinmektedir 3 . Zorunlu parazit olan bu türler, kıl folikülleri ve derinin yağ salgılayan bezlerinde bulunur 4 . Özellikle alın ve burun bölgelerinde, ayrıca kirpik, kulak ve genital bölgelerde, omuz başı, ön kol gibi yağlı ve kıl kökü barındıran vücut bölgelerinde yerleşir 3,[5][6][7] . İnsandan insana yakın temas, tokalaşma ve öpüşme ile bulaştığı bildirilmiştir 3,7,8 .