Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

Tamm-Horsfall protein (THP) is thought to protect against calcium oxalate monohydrate (COM) stone formation by inhibiting COM aggregation. Several studies reported that stone formers produce THP with reduced levels of glycosylation, particularly sialic acid levels, which leads to reduced negative charge. In this study, normal THP was treated with neuraminidase to remove sialic acid residues, confirmed by an isoelectric point shift to higher pH. COM aggregation assays revealed that desialylated THP (ds-THP) promoted COM aggregation, while normal THP inhibited aggregation. The appearance of protein aggregates in solutions at ds-THP concentrations ≥1 μg/mL in 150 mM NaCl correlated with COM aggregation promotion, implying that ds-THP aggregation induced COM aggregation. The aggregation-promoting effect of the ds-THP was independent of pH above its isoelectric point, but was substantially reduced at low ionic strength, where protein aggregation was much reduced. COM aggregation promotion was maximized at a ds-THP to COM mass ratio of ~0.025, which can be explained by a model wherein partial COM surface coverage by ds-THP aggregates promotes crystal aggregation by bridging opposing COM surfaces, whereas higher surface coverage leads to repulsion between adsorbed ds-THP aggregates. Thus, desialylation of THP apparently abrogates a normal defensive action of THP by inducing protein aggregation, and subsequently COM aggregation, a condition that favors kidney stone formation.     

生姜提取物6-姜酚对对乙酰氨基酚致小鼠肝脏毒性的保护作用

目的：研究生姜提取物6-姜酚对对乙酰氨基酚致小鼠肝脏毒性的保护作用。方法：实验组小鼠在腹腔注射对乙酰氨基酚（900mg／kg）30min后,分别给予6-姜酚（30mg／kg）或标准对照药水飞蓟素（25mg／kg）。注射对乙酰氨基酚4h后处死小鼠,检测血清中天冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶活性,总胆红素的含量及肝匀浆中脂质过氧化及抗氧化情况,如超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、谷胱甘肽转移酶活性及还原型谷胱甘肽含量。结果：与对照组相比,6-姜酚及水飞蓟素均能显著降低对乙酰氨基酚引起的小鼠血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶活性及总胆红素含量的升高（P〈0．05）。此外,6-姜酚及水飞蓟素有效控制了肝脏内丙二醛的形成及各种抗氧化酶的降低（P〈0．05）。结论：本研究的结果证实了6-姜酚具有与水飞蓟素相当的保肝作用。     

Livedo Reticularis Due to Pellagra in a Two Year Old Child

A two-year-old girl child was admitted with complaints of diarrhoea of one week duration in the paediatric ward. She was referred to the skin OPD for gradually progressive skin rashes on both lower limbs noticed since two days. Dermatological examination revealed finding of livedo reticularis. Dietary history revealed maize forming a significant portion of the child''s diet since the age of nine months. The child was treated with a course of Niacin in the form of Nicotinamide 50 mg twice a day for 4 weeks and the parents were advised not to give her maize in the diet. The skin lesions and diarrhoea regressed in duration of two weeks. This is probably the first time that a case of pellagra causing livedo is being reported, that too in a child.     

A Case of Extensive Multifocal Tuberculosis Verrucosa Cutis

Tuberculosis is probably as old as the human race itself. Cutaneous tuberculosis constitutes a very small proportion of extra pulmonary tuberculosis. Extensive, multifocal involvement of cutaneous tuberculosis is a very rare manifestation. We report one such case of extensive, multifocal tuberculosis verrucosa cutis in a 30-year-old immunocompetent male patient in the absence of any primary tubercular focus.     

Counteracting adriamycin-induced oxidative stress by administration of N-acetyl cysteine and vitamin E.

Adriamycin (ADR), a cytotoxic antineoplastic drug, is used in the treatment of various solid tumors. However, its efficacy continues to be challenged by significant toxicities including nephrotoxicity. In the present study, the effects of N-acetyl cysteine (NAC) and vitamin E, known antioxidants, were investigated on ADR-induced peroxidative damage in rat kidney. Adult male albino rats of Wistar strain were administered ADR as a single dose (10 mg/kg body weight, i.v.). Histopathological studies indicated that ADR-treated kidney sections show focal tubular necrosis and casts. ADR-injected rats showed a significant decline in the activities/levels of enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and non-enzymic antioxidants (thiols, vitamin C and vitamin E) with high malondialdehyde levels. The extent of nephrotoxicity was evident from the increased activities of urinary marker enzymes (alkaline phosphatase, lactate dehydrogenase and gamma-glutamyltransferase). Treatment with NAC and vitamin E (50 mg/kg b.w., i.p.) 1 day prior to ADR administration maintained near normal activities of the enzymes, significantly reduced lipid peroxidation and prevented the necrosis caused by ADR, thereby proving to be an effective thiol replenishing agent and antioxidant.     

Detection of endothelial nitric oxide synthase and NADPH-diaphorase in experimentally induced hyperoxaluric animals

Nitrosative stress plays a role in calcium oxalate stone formation, as nitrosated proteins have been identified in stone formers. Nitric oxide (NO), the common precursor for reactive nitrogen species, is synthesized in the juxtaglomerular apparatus of the kidneys. The present study is aimed to determine the role of nitric oxide synthase (NOS) in an experimental hyperoxaluric condition by histological and biochemical techniques. Hyperoxaluria was induced by 0.75% ethylene glycol in drinking water. L-arginine (L-arg) was supplemented at a dose of 1.25 g/kg body weight orally for 28 days. Nitric oxide metabolites (NOx), protein content in the urine and lipid peroxidation in the kidney were determined at the end of the experimental period. Histopathological examination of the rat kidneys was then carried out. NADPH-diaphorase and eNOS expression studies were carried out in control and hyperoxaluric rat kidneys using histochemical and immunohistochemical techniques. Significant amounts of NOx were present in the urine of hyperoxaluric animals when compared to control rats. Histopathological examinations revealed membrane injury, tubular dilatation and edema in the hyperoxaluric rats, whereas co-supplementation of L-arg to the hyperoxaluric rats significantly reduced these changes. The results of histochemical analysis for NADPH-diaphorase staining demonstrate the role of NOS in hyperoxaluric rats. Hyperoxaluric rats showed intense staining for NADPH-diaphorase when compared to control and L-arg co-supplemented hyperoxaluric rats. Immunohistochemical demonstration confirmed that eNOS expression was markedly increased in L-arg supplemented rats, when compared to EG treated rat kidney sections. Thus, from the present study, we conclude that supplementation of L-arg to the hyperoxaluric animals minimizes the cellular injury mediated by ethylene glycol, prevents oxidative/nitrosative damage to the membranes and reduces the incidence of calcium oxalate stone formation.