Involvement of oxidative stress in bee venom-induced inhibition of Na+/glucose cotransporter in renal proximal tubule cells

1. The present study was conducted to examine the involvement of oxidative stress in bee venom-induced inhibition of the Na+/glucose cotransporter (alpha-methyl-d-glucopyranoside (alpha-MG) uptake), a typical functional marker of proximal tubules, in primary cultured rabbit renal proximal tubule cells (PTC). 2. Bee venom (> or = 1 microg/mL) increased lipid peroxide (LPO) formation over 30 min. The increase in [(3)H]-arachidonic acid (AA) release and LPO formation and the inhibition of alpha-MG uptake induced by bee venom (1 microg/mL) and melittin (a major component of bee venom; 0.5 microg/mL) were blocked by N-acetyl-l-cysteine, vitamin C and vitamin E, anti-oxidants. 3. Bee venom- and melittin-induced increases in LPO formation and inhibition of alpha-MG uptake were significantly prevented by mepacrine and AACOCF(3), phospholipase A(2) inhibitors. In addition, nordihydroguaiareic acid (a lipoxygenase inhibitor) and econazole (a cytochrome P-450 epoxygenase inhibitor), but not indomethacin (a cyclo-oxygenase inhibitor), prevented bee venom- and melittin-induced increases in LPO formation and inhibition of alpha-MG uptake. 4. Nordihydroguaiareic acid prevented bee venom- and melittin-induced increases in Ca(2+) uptake. Moreover, anti- oxidants significantly prevented bee venom- and melittin-induced increases in Ca(2+) uptake. 5. In conclusion, bee venom inhibits alpha-MG uptake via the phospholipase A(2)-oxidative stress-Ca(2+) signalling cascade in primary cultured rabbit renal proximal tubule cells.     

The water-soluble fraction (<10 kD) of bee venom (Apis mellifera) produces inhibitory effect on apical transporters in renal proximal tubule cells

Human envenomation caused by bee stings has been reported to cause acute renal failure and the pathogenetic mechanisms of these renal functional changes are still unclear. Bee venom is also a complex mixture of enzymes and proteins. Thus, this study was conducted to examine the effects of bee venom (BV, Apis mellifera) fractions on apical transporters' activity and its related signal pathways in primary cultured renal proximal tubule cells. Whole BV was extracted into three fractions according to solubility [a water-soluble fraction (BVA), an ethylacetate-soluble fraction (BVE), and a hexane-soluble fraction (BVH)]. BVA fraction was further separated to three portions according to molecular weights: BF1 (>20 kD), BF2 (10-20 kD), and BF3 (<10 kD). Each fraction was treated to the PTCs to the ratio of BV (1 microg/ml). BVA (930 ng/ml) significantly decreased cell viability, but BVH (27 ng/ml) and BVE (43 ng/ml) did not. BF3 (710 ng/ml) among BVA fractions predominantly decreased cell viability and inhibited alpha-methyl-D-glucopyranoside (alpha-MG), phosphate (Pi), and Na(+) uptake. In addition, BF3 increased [(3)H] arachidonic acid release, lipid peroxide formation, and Ca(2+) uptake. These effects of BF3 were blocked by mepacrine and AACOCF(3) (phospholipase A(2) inhibitors) or N-acetylcysteine, vitamin C, and vitamin E (antioxidants). In conclusion, BF3 (<10 kD) among BV fractions is the most effective portion in BV-induced inhibition of alpha-MG, P(i), and Na(+) uptake and these effects of BF3 are associated with phospholipase A(2)-oxidative stress-Ca(2+) signal cascade in the primary cultured rabbit renal proximal tubule cells.     

Secondary thrombocytosis

To estimate the incidence and causes of secondary thrombocytosis in children, a 12 month study of all patients attending a children's hospital and discovered to have a platelet count over two times the upper normal limit (> 800 x 10(9)/l) was undertaken. Data so obtained were analysed both separately and together with those from two previous studies to gain as broad a perspective as possible. Of 7916 children who had platelet counts during the study period, 36 (0.5%) produced a value > 800 x 10(9)/l; there were 19 boys and 17 girls. There was a preponderance of young infants (median age 13 months). Twenty seven of the 36 had some sort of associated infection, bacterial in 18 and viral in nine. The other nine were either recovering from anti-neoplastic chemotherapy (n = 6), were post-operative (n = 2), or simply iron deficient (n = 1). Combining these patients with those described in previous studies allowed a review of 139 unselected children with very high platelet counts. Fifty three (38%) had infections, 29 (20%) had traumatic or surgical tissue damage, 16 (11%) had malignant disease undergoing chemotherapy or surgery, and 13 (9%) had connective tissue or autoimmune disorders. Secondary thrombocytosis is not rare and is most frequently seen in very young infants after infection. It can arise in a wide variety of other circumstances including rebound from myelosuppression, iron lack, or as part of an acute phase response. It is clinically unimportant in terms of morbidity and requires no treatment other than that for the primary condition.     

Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia

Two children with acute lymphoblastic leukaemia (ALL) taking daily 6-mercaptopurine as part of a national UK therapeutic trial repeatedly developed profound myelosuppression on 25% of the standard protocol dose. Both were found to have undetectable intracellular activity of thiopurine methyltransferase (TPMT), an enzyme controlling one of the major alternative catabolic pathways of 6-mercaptopurine, and both produced higher concentrations of cytotoxic drug metabolites at 10-25% of the protocol dose than other patients taking 100%. It is supposed that these patients represent the 0.33% of the normal population constitutionally lacking TPMT. It is important to recognise such individuals both to avoid fatal bone marrow failure through inadvertent overdosage, and to be reassured that an adequate drug effect can be achieved at around 10% of the standard dose.     

Multiple myeloma: evaluation by CT

Although patients who have multiple myeloma usually have straightforward clinical symptoms and corroborative radiographs, in some instances, these patients will present atypically, with symptoms suggesting active disease but radiographs that are normal or nonspecific. We reviewed the records of 32 patients who had documented multiple myeloma and had undergone CT examinations, assessing the value of those examinations. Although CT is not indicated in all patients who have multiple myeloma, it is especially useful in patients who have bone pain and normal or nonspecific radiographs. CT provided confirmatory information in all cases in which lesions were seen on radiographs. CT also frequently demonstrated a greater extent of disease than could be appreciated on the radiographs.     

Looped silk tie: surgical technique for management of the renal vein during laparoscopic live-donor nephrectomy

Laparoscopic live-donor nephrectomy has revolutionized the field of kidney transplantation and has been adopted in many tertiary centers as the method of choice in procuring kidneys. While standard techniques for laparoscopic live-donor nephrectomy have been well described in the literature, there continues to be ample discussion about renal-vein ligation. Endo-GIA and other commonly used vascular stapling devices can be costly and prone to mechanical failures and may not be applicable in certain anatomic situations. Vascular clips, although simple to use for arteries, are difficult to apply to large renal veins. To address these issues, we describe a simple, cost-effective method of control that can be used for both right and left renal veins, using a loop constructed from a 0 silk tie.     

Material sensitivity study on lumbar motion segment (L2-L3) under sagittal plane loadings using probabilistic method

OBJECTIVE: In this study, the probabilistic responses of a three-dimensional finite element L2-L3 motion segment, with and without posterior elements, tested under sagittal plane loadings, are presented. Understanding the effect of biologic uncertainties and variations on the biomechanical response provides an insight into spinal behavior under normal and degenerated conditions. METHODS: The biologic variability of 19 spinal components (nucleus, annulus, ligament, cortical/cancellous bone, endplate, and ligaments) in the motion segment was incorporated using statistical distributions into the model. A total of 2000 runs were performed using Monte Carlo probabilistic algorithms to compute the probabilistic response. RESULTS: This study establishes the relative importance of the spinal components in resisting the loading modes. The results show that for an intact motion segment, posterior ligaments are more dominant than intervertebral disc in resisting flexion moment. In extension, the capsular ligaments were found to be the most influential parameter. The intervertebral disc (ie, nucleus and annulus) affects the angular response of the disc body segment more than the hard tissues (ie, cortical and cancellous bone). CONCLUSIONS: The application of the probabilistic analysis provides a new approach whereby the influences of inherent uncertainties and variations in biologic structures can be studied and the biomechanical response assessed.     

Simultaneous bilateral retrograde intrarenal surgery for bilateral complex upper tract stone disease

Recent advances in retrograde endoscopy have greatly expanded the role of minimally invasive surgery in addressing upper tract stone disease. In an attempt to decrease patient morbidity further, we present our initial experience with simultaneous bilateral retrograde intrarenal surgery in a patient with complex bilateral upper tract stones.