Trimetazidine Protects from Mercury-Induced Kidney Injury.

INTRODUCTION: The presence of mercury in the environment is a worldwide concern. Inorganic mercury is present in industrial materials, is employed in medical devices, is widely used in batteries, is a component of fluorescent light bulbs, and it has been associated with human poisoning in gold mining areas. The nephrotoxicity induced by inorganic mercury is a relevant health problem mainly in developing countries. The primary mechanism of mercury toxicity is oxidative stress. Trimetazidine (TMZ) is an anti-ischemic drug, which inhibits cellular oxidative stress, eliminates oxygen-free radicals, and improves lipid metabolism. The aim of this study was to evaluate whether the administration of TMZ protects against mercuric chloride (HgCl2) kidney damage. METHODS: Adult male Wistar rats received only HgCl2 (4 mg/kg bw, sc) (Hg group, n = 5) or TMZ (3 mg/kg bw, ip) 30 min before HgCl2 administration (4 mg/kg bw, sc) (TMZHg group, n = 7). Simultaneously, a control group of rats (n = 4) was studied. After 4 days of HgCl2 injection, urinary flow, urea and creatinine (Cr) plasma levels, Cr clearance, urinary glucose, and sodium-dicarboxylate cotransporter 1 (NaDC1) in urine were determined. Lipid peroxidation (MDA) and glutathione (GSH) levels were measured in kidney homogenates. RESULTS: Rats only treated with HgCl2 showed an increase in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, and NaDC1 urinary excretion as compared with the control group and a decrease in Cr clearance. TMZHg group showed a decrease in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, NaDC1 urinary excretion, and an increase in Cr clearance when compared to the Hg group. Moreover, MDA and GSH levels observed in Hg groups were decreased and increased, respectively, by TMZ pretreatment. CONCLUSION: TMZ exerted a renoprotective action against HgCl2-induced renal injury, which might be mediated by the reduction of oxidative stress. Considering the absence of toxicity of TMZ, its clinical application against oxidative damage due to HgCl2-induced renal injury should be considered. The fact that TMZ is commercially available should simplify and accelerate the translation of the present data "from bench to bedside." In this context, TMZ become an interesting new example of drug repurposing.

Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury.

BACKGROUND: Arterial stiffness is emerging as an independent risk factor for the development of chronic kidney disease. The sodium glucose co-transporter 2 (SGLT2) inhibitors, which lower serum glucose by inhibiting SGLT2-mediated glucose reabsorption in renal proximal tubules, have shown promise in reducing arterial stiffness and the risk of cardiovascular and kidney disease in individuals with type 2 diabetes mellitus. Since hyperglycemia contributes to arterial stiffness, we hypothesized that the SGLT2 inhibitor empagliflozin (EMPA) would improve endothelial function, reduce aortic stiffness, and attenuate kidney disease by lowering hyperglycemia in type 2 diabetic female mice (db/db). MATERIALS/METHODS: Ten-week-old female wild-type control (C57BLKS/J) and db/db (BKS.Cg-Dock7m+/+Leprdb/J) mice were divided into three groups: lean untreated controls (CkC, n = 17), untreated db/db (DbC, n = 19) and EMPA-treated db/db mice (DbE, n = 19). EMPA was mixed with normal mouse chow at a concentration to deliver 10 mg kg-1 day-1, and fed for 5 weeks, initiated at 11 weeks of age. RESULTS: Compared to CkC, DbC showed increased glucose levels, blood pressure, aortic and endothelial cell stiffness, and impaired endothelium-dependent vasorelaxation. Furthermore, DbC exhibited impaired activation of endothelial nitric oxide synthase, increased renal resistivity and pulsatility indexes, enhanced renal expression of advanced glycation end products, and periarterial and tubulointerstitial fibrosis. EMPA promoted glycosuria and blunted these vascular and renal impairments, without affecting increases in blood pressure. In addition, expression of "reversion inducing cysteine rich protein with Kazal motifs" (RECK), an anti-fibrotic mediator, was significantly suppressed in DbC kidneys and partially restored by EMPA. Confirming the in vivo data, EMPA reversed high glucose-induced RECK suppression in human proximal tubule cells. CONCLUSIONS: Empagliflozin ameliorates kidney injury in type 2 diabetic female mice by promoting glycosuria, and possibly by reducing systemic and renal artery stiffness, and reversing RECK suppression.

Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse.

Quinoline-3-carboxamides (Q compounds) are immunomodulatory compounds that have shown efficacy both in autoimmune disease and cancer. We have in here investigated the impact of one such compound, paquinimod, on the development of diabetes in the NOD mouse model for type I diabetes (T1D). In cohorts of NOD mice treated with paquinimod between weeks 10 to 20 of age and followed up until 40 weeks of age, we observed dose-dependent reduction in incidence of disease as well as delayed onset of disease. Further, in contrast to untreated controls, the majority of NOD mice treated from 15 weeks of age did not develop diabetes at 30 weeks of age. Importantly, these mice displayed significantly less insulitis, which correlated with selectively reduced number of splenic macrophages and splenic Ly6Chi inflammatory monocytes at end point as compared to untreated controls. Collectively, these results demonstrate that paquinimod treatment can significantly inhibit progression of insulitis to T1D in the NOD mouse. We propose that the effect of paquinimod on disease progression may be related to the reduced number of these myeloid cell populations. Our finding also indicates that this compound could be a candidate for clinical development towards diabetes therapy in humans.

Organic anion transporter OAT3 enhances the glucosuric effect of the SGLT2 inhibitor empagliflozin.

The sodium-glucose cotransporter SGLT2 inhibitor empagliflozin (plasma protein binding ~88%) may reach its target in the brush border of the early proximal tubule by glomerular filtration and tubular secretion. Here we determined whether empagliflozin is secreted by renal tubules in mice and whether genetic knockout of the basolateral organic anion transporter 3 ( Oat3-/-) affects its tubular secretion or glucosuric effect. Renal clearance studies in wild-type (WT) mice showed that tubular secretion accounted for 50-70% of empagliflozin urinary excretion. Immunostaining indicated that SGLT2 and OAT3 localization partially overlapped in proximal tubule S1 and S2 segments. Glucosuria in metabolic cage studies was reduced in Oat3-/- vs. WT mice for acute empagliflozin doses of 1, 3, and 10 mg/kg, whereas 30 mg/kg induced similar maximal glucosuria in both genotypes. Chronic application of empagliflozin (~25 mg·kg-1 ·day-1) in Oat3-/- mice was associated with lower urinary glucose-to-creatinine ratios despite maintaining slightly higher blood glucose levels than WT. On a whole kidney level, renal secretion of empagliflozin was largely unchanged in Oat3-/- mice. However, the absence of OAT3 attenuated the influence of empagliflozin on fractional glucose excretion; higher levels of plasma or filtered empagliflozin were needed to induce similar increases in fractional renal glucose excretion. We conclude that empagliflozin is excreted into the urine to similar extent by glomerular filtration and tubular secretion. The latter can occur largely independent of OAT3. However, OAT3 increases the glucosuric effect of empagliflozin, which may relate to the partial overlap of its localization with SGLT2 and thus OAT3-mediated tubular secretion of empagliflozin in the early proximal tubule.

Bone marrow transplantation improves proximal tubule dysfunction in a mouse model of Dent disease.

Dent disease is a rare X-linked tubulopathy caused by mutations in the endosomal chloride-proton exchanger (ClC-5) resulting in defective receptor-mediated endocytosis and severe proximal tubule dysfunction. Bone marrow transplantation has recently been shown to preserve kidney function in cystinosis, a lysosomal storage disease causing proximal tubule dysfunction. Here we test the effects of bone marrow transplantation in Clcn5Y/- mice, a faithful model for Dent disease. Transplantation of wild-type bone marrow in Clcn5Y/- mice significantly improved proximal tubule dysfunction, with decreased low-molecular-weight proteinuria, glycosuria, calciuria, and polyuria four months after transplantation, compared to Clcn5Y/- mice transplanted with ClC-5 knockout bone marrow. Bone marrow-derived cells engrafted in the interstitium, surrounding proximal tubule cells, which showed a rescue of the apical expression of ClC-5 and megalin receptors. The improvement of proximal tubule dysfunction correlated with Clcn5 gene expression in kidneys of mice transplanted with wild-type bone marrow cells. Coculture of Clcn5Y/- proximal tubule cells with bone marrow-derived cells confirmed rescue of ClC-5 and megalin, resulting in improved endocytosis. Nanotubular extensions between the engrafted bone marrow-derived cells and proximal tubule cells were observed in vivo and in vitro. No rescue was found when the formation of the tunneling nanotubes was prevented by actin depolymerization or when cells were physically separated by transwell inserts. Thus, bone marrow transplantation may rescue the epithelial phenotype due to an inherited endosomal defect. Direct contacts between bone marrow-derived cells and diseased tubular cells play a key role in the rescue mechanism.

Pathways to reduce diabetic ketoacidosis with new onset type 1 diabetes: Evidence from a regional pediatric diabetes center: Auckland, New Zealand, 2010 to 2014.

BACKGROUND: There has been little change in the incidence of diabetic ketoacidosis (DKA) in newly diagnosed type 1 diabetes mellitus (T1DM) in children and adolescents in most developed countries. OBJECTIVES: To assess potentially modifiable antecedents of DKA in children <15 years of age with new onset T1DM. METHODS: Retrospective review of prospectively collected data from a complete regional cohort of children with T1DM in Auckland (New Zealand) from 2010 to 2014. DKA and severity were defined according to the ISPAD 2014 guidelines. RESULTS: A total of 263 children presented with new onset T1DM during the 5-year study period at 9.0 years of age (range 1.0-14.7), of whom 61% were NZ-European, 14% Maori, 13% Pacifica, and 11% other. A total of 71 patients (27%) were in DKA, including 31 mild, 20 moderate, and 20 severe DKA. DKA was associated with no family history of T1DM, higher glycated hemoglobin (HbA1c) values at presentation, self-presenting to secondary care, health care professional contacts in the 4 weeks before final presentation, and greater deprivation. Although a delay in referral from primary care for laboratory testing was common (81/216), only delay for more than 48 hours was associated with increased risk of DKA (11/22 > 48 h vs 12/59 referred at <48 h, P = .013). CONCLUSIONS: These data suggest that in addition to lack of family awareness potentially modifiable risk factors for new onset DKA include prolonged delay for laboratory testing and a low index of medical suspicion for T1DM leading to delayed diagnosis.

Eliminación renal de glucosa como tratamiento de la diabetes: de un antiguo método diagnóstico a una nueva forma de tratamiento / Glucose renal excretion as diabetes treatment: from an old diagnostic method to a new way of treatment

No disponible

A new dammarane saponin and other triterpenoids from Siolmatra brasiliensis and evaluation of the antidiabetic activity of its extract.

Context Siolmatra brasiliensis (Cogn.) Baill (Cucurbitaceae) is a climbing plant widely used for the treatment of diabetes mellitus symptoms. Objective This work evaluates the antidiabetic activity of an extract of S. brasiliensis in streptozotocin-diabetic rats and promotes the phytochemical investigation to isolate the major compounds of the same extract. Materials and methods Male Wistar rats were divided into normal (N) and diabetic rats (DC) treated with water; diabetic rats treated with 3U insulin (DI) or with 250 (DSb250) or 500 mg/kg (DSb500) of hydroalcoholic extract of the stalks of S. brasiliensis, via oral gavage, for 21 days. Physiological and biochemical parameters classically altered in diabetes were monitored. The triterpenoids were isolated from the ethyl acetate fraction under silica gel column chromatography and Sephadex-LH20 methods and their structures were determined by NMR, HR-ESI-MS and DC analysis. Results When compared with DC, DSb250 rats showed a reduction in the hyperglycemia (DC: 26.46 ± 0.69 versus DSb250: 19.67 ± 1.06 mmol/L) and glycosuria (DC: 43.02 ± 3.19 versus DSb250: 28.46 ± 2.14 mmol/24 h) and increase in hepatic glycogen (DC: 14.44 ± 1.26 versus DSb250: 22.08 ± 4.26 mg/g). Three known cucurbitacins were isolated from a hydroalcoholic extract of S. brasiliensis, i.e., cayaponosides A1, B4, D, and a new dammarane saponin 3-O-ß-d-gentiobiosyl-26-O-ß-d-glucopyranosyl-20-hydroxydammar-24-ene. The structures of these compounds were elucidated by spectral data analysis of the natural products and their acetyl derivatives. Discussion and conclusion The known cucurbitacins and/or the new identified saponin may be related with the antidiabetic activity of S. brasiliensis.

Effects of self-monitoring of glucose on distress and self-efficacy in people with non-insulin-treated Type 2 diabetes: a randomized controlled trial.

AIMS: To investigate the effects of self-monitoring of glucose in blood or urine, on diabetes-specific distress and self-efficacy, compared with usual care in people with non-insulin-treated Type 2 diabetes mellitus. METHODS: One hundred and eighty-one participants with non-insulin-treated Type 2 diabetes mellitus [diabetes duration ≥ 1 year, age 45-75 years, HbA1c ≥ 53.0 mmol/mol (7.0%), self-monitoring frequency < 3 times in the previous year] were randomly assigned to blood self-monitoring (n = 60), urine self-monitoring (n = 59) or usual care (n = 62). Primary outcomes were between-group differences in diabetes-specific distress [Problem Areas in Diabetes scale (PAID)] and self-efficacy [Confidence in Diabetes Self-Care questionnaire (CIDS-2)] after 12 months. Secondary outcomes included changes in HbA1c , treatment satisfaction and depressive symptoms. RESULTS: There were no statistically significant between-group differences in changes in PAID and CIDS-2 after 12 months. Mean difference in PAID between blood monitoring and control was -2.2 [95% confidence interval (CI) -7.1 to 2.7], between urine monitoring and control was -0.9 (95% CI -4.4 to 2.5) and between blood monitoring and urine monitoring was -2.0 (95% CI -4.1 to 0.1). Mean difference in CIDS-2 between blood monitoring and control was 0.6 [95% CI (-2.0 to 2.1), between urine monitoring and control was 2.8 (95% CI -2.3 to 7.9)] and between blood monitoring and urine monitoring was -3.3 (95% CI -7.9 to 1.3). No statistically significant between-group differences in change in any of the secondary outcome measures were found. CONCLUSIONS: This study did not find statistical or clinical evidence for a long-term effect of self-monitoring of glucose in blood or urine on diabetes-specific distress and self-efficacy in people with moderately controlled non-insulin-treated Type 2 diabetes mellitus. (Current Controlled Trials ISRCTN84568563).

Application and opportunities of pulses in food system: a review.

Pulses are highly nutritious seeds of pod-bearing leguminous plants, specifically dry peas, lentils, and chickpeas. US farmers harvest about 2.6 million pounds of pulses every year but 75% of this is being exported internationally because of its increased consumption in the developing countries. In the current scenario, increasing costs of production, bad economy, and fluctuating food commodity prices have made a strong case for US producers to seek opportunities to increase domestic consumption of pulses through value-added products. Pulses are the richest sources of plant proteins and provide approximately 10% of the total dietary requirements of the proteins world over. Pulses are also high in dietary fibers and complex carbohydrates leading to low GI (glycemic index) foods. Pulses help to lower cholesterol and triglycerides as leguminous fibers are hypoglycosuria because of consisting more amylose than amylopectin. Pulses provide tremendous opportunities to be utilized in the processed foods such as bakery products, bread, pasta, snack foods, soups, cereal bar filing, tortillas, meat, etc. These show excellent opportunities in frozen dough foods either as added flour or as fillings. Pulses in view of their nutrient profile, seem to be ideal for inclusion in designing snack foods, baby, and sports foods.

Validation of a novel method for determining the renal threshold for glucose excretion in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus.

CONTEXT: The stepwise hyperglycemic clamp procedure (SHCP) is the gold standard for measuring the renal threshold for glucose excretion (RT(G)), but its use is limited to small studies in specialized laboratories. OBJECTIVE: The objective of the study was to validate a new method for determining RT(G) using data obtained during a mixed-meal tolerance test (MMTT) in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus (T2DM). DESIGN: This was an open-label study with 2 sequential parts. SETTING: The study was performed at a single center in Germany. PATIENTS: Twenty-eight subjects with T2DM were studied. INTERVENTIONS: No treatment intervention was given in part 1. In part 2, subjects were treated with canagliflozin 100 mg/d for 8 days. In each part, subjects underwent an MMTT and a 5-step SHCP on consecutive days. MAIN OUTCOME MEASURES: For both methods, RT(G) was estimated using measured blood glucose (BG) and urinary glucose excretion (UGE); estimated glomerular filtration rates were also used to determine RT(G) during the MMTT. The methods were compared using the concordance correlation coefficient and geometric mean ratios. RESULTS: In untreated and canagliflozin-treated subjects, the relationship between UGE rate and BG was well described by a threshold relationship. Good agreement was obtained between the MMTT-based and SHCP-derived RT(G) values. The concordance correlation coefficient (for all subjects) was 0.94; geometric mean ratios (90% confidence intervals) for RT(G) values (MMTT/SHCP) were 0.93 (0.89-0.96) in untreated subjects and 1.03 (0.78-1.37) in canagliflozin-treated subjects. Study procedures and treatments were generally well tolerated in untreated and canagliflozin-treated subjects. CONCLUSIONS: In both untreated and canagliflozin-treated subjects with T2DM, RT(G) can be accurately estimated from measured BG, UGE, and estimated glomerular filtration rates using an MMTT-based method.

Continuous subcutaneous hydrocortisone infusion (CSHI) in a young adolescent with congenital adrenal hyperplasia (CAH).

Congenital adrenal hyperplasia (CAH) is an autosomal recessive enzymatic defect caused by mutations or deletions of the cytochrome P450 21-hydroxylase CYP21 gene. Oral therapy with glucocorticoids and mineralcorticoids is administered to prevent adrenal crisis and to control hyperandrogenism. During puberty this type of therapy is difficult to manage owing to physiological and hormonal changes and poor compliance. We describe a case of a pubertal boy affected by CAH, in whom continuous subcutaneous infusion of hydrocortisone led to improved metabolic control and compliance.

Intravenous immunoglobulins exposed to heme (heme IVIG) are more efficient than IVIG in attenuating autoimmune diabetes.

Intravenous immunoglobulins (IVIG) are known to have a therapeutic effect in some autoimmune diseases. We examined the effect of IVIG and heme-exposed IVIG on the development of immune mediated diabetes induced in C57BL/6 mice by multiple low doses of streptozotocin. IVIG were used in a dose of 200mg/kg daily for 15 days. Treatment with IVIG resulted in significant attenuation of diabetes induction as evaluated by glycemia, glycosuria and HbA1c level. Interestingly, heme-exposed IVIG had a still stronger antidiabetogenic effect. Serum levels of proinflammatory cytokines TNF-α, IFN-γ and IL17 were lower in IVIG treated animals when compared with controls, while IL10 level was higher. The number of CD4(+)Foxp3(+) cells was higher in pancreatic lymph nodes of heme-exposed IVIG treated mice. Our results show that IVIG may downregulate diabetes induction possibly by favouring induction of T regulatory cells and suggest enhanced effect upon heme-binding to IVIG.

Antidiabetic and antioxidant potential of ß-sitosterol in streptozotocin-induced experimental hyperglycemia.

BACKGROUND: Oxidative stress, produced under diabetic conditions, may cause tissue damage. Although several drugs are currently available for the treatment of diabetes, their continued use may cause unwanted side effects. The aim of the present study was to evaluate the antioxidant potential of ß-sitosterol (BS), a phytosterol from Solanum surattense, using an experimental model for diabetes-induced oxidative damage. METHODS: The effects of 21 days treatment with BS (10, 15 and 20 mg/kg, p.o.) on blood, serum, and tissue biochemical parameters were evaluated in control and streptozotocin-induced diabetic rats. Nine experimental groups, including a control group, a diabetic group, and BS- and glibenclamide-treated diabetic groups, were evaluated. RESULTS: All three dose levels dose dependently resulted in decreases in glycated hemoglobin, serum glucose, and nitric oxide, with concomitant increases in serum insulin levels. Furthermore, treatment with BS doses also increased pancreatic antioxidant levels, with a concomitant decrease in thiobarbituric acid-reactive substances. CONCLUSIONS: ß-Sitosterol has promising antidiabetic as well as antioxidant effects and may be considered in clinical studies for drug development.

Crocin attenuates cisplatin-induced renal oxidative stress in rats.

Reactive oxygen species (ROS) and oxidative damage are the most important factors in cisplatin-induced acute renal failure. This study examined the protective effects of crocin against cisplatin-induced renal oxidative stress in rat. Animals were divided into five groups (n=6). Group 1 received normal saline (2 ml/day, i.p.). Group 2 received a single dose of cisplatin (5mg/kg, i.p.). Groups 3-5 received crocin (100, 200, and 400mg/kg, i.p., respectively) for four consecutive days beginning 1-h before a single dose of cisplatin (5mg/kg) on day 1. On day 5, blood samples were drawn and kidneys were removed for histopathological, biochemical and RT-PCR examinations. Twenty four hours urinary chemistries were measured. Blood urea and creatinine and urinary glucose and protein concentrations in crocin-treated groups were significantly lower compared to the cisplatin-treated group. Histopathological studies showed massive damage in the S(3) segment of proximal tubules in cisplatin-treated group but not in crocin-treated groups. Crocin treatment resulted in a significant reduction in malondialdehyde (MDA) concentration and produced a significant elevation in total thiol and glutathione peroxidase concentrations. There was a significant elevation in the mRNA expression of glutathione peroxidase in crocin-treated groups. The results suggest that crocin attenuates cisplatin-induced renal oxidative stress in rats.

Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses.

REASONS FOR PERFORMING STUDY: The frequently sampled i.v. glucose tolerance test (FSIGTT) is used to evaluate glucose and insulin dynamics in horses, but it has not been determined whether urinary glucose spilling (UGS) affects results. HYPOTHESIS: UGS occurs in horses during the FSIGTT and this problem can be minimised by adjusting the dextrose and insulin dosages used. METHODS: Six mature mares were included in this study. In the first phase, 6 FSIGTT procedures were performed in each horse to evaluate 6 different dextrose dosages. Six different insulin dosages were evaluated during the second phase of the study after administration of 300 mg/kg bwt dextrose. Area under the glucose (AUCg) and insulin (AUCi) curves were calculated and minimal model analyses performed. UGS was measured in the third and fourth phases of the study during the combined glucose insulin test and established FSIGTT. A new FSIGTT was developed and evaluated. RESULTS: Positive linear effects of dextrose dosage on AUCg, AUCi and acute insulin response to glucose were detected, with AUCg reaching a plateau at doses > or =200 mg/kg bwt. Insulin dosage had an inverse linear effect on AUCg, but other values remained unaffected. UGS occurred during all 3 tests and was the highest for the established FSIGTT and the lowest for the new FSIGTT. The type of FSIGTT performed did not affect minimal model results. CONCLUSIONS: Results indicate that the dextrose dosage of 300 mg/kg bwt used in the established FSIGTT is too high. UGS can be reduced by lowering the dextrose dosage to 100 mg/kg bwt. POTENTIAL RELEVANCE: A new FSIGTT involving the administration of 100 mg/kg bwt dextrose followed by 20 mu/kg bwt insulin 20 min later is recommended for use in horses because this test provides adequate data for minimal model analysis while minimising UGS.

Mechanism of Cd-induced inhibition of Na-glucose cotransporter in rabbit proximal tubule cells: roles of luminal pH and membrane-bound carbonic anhydrase.

BACKGROUND/AIMS: We have previously reported that a complex of cadmium-metallothionein (Cd-MT) directly affects the apical Na-glucose cotransporter on the luminal side in proximal tubules, suggesting that Cd-MT is more toxic than CdCl(2) in causing tubulopathy. To find the potential mechanisms, we evaluated the effect of luminal pH alteration and carbonic anhydrase (CA) inhibition on Cd-MT-induced reduction of glucose-dependent transmural voltage in rabbit S2 segments perfused in vitro. METHODS: Before and after the addition of Cd-MT (1 microg Cd/ml) to the lumen, the deflections of transmural voltage upon the elimination of glucose from the perfusate (DeltaVt(glu)) were measured as a parameter of activity of the Na-glucose cotransporter. RESULTS: During perfusion with a control solution of pH 7.4, the DeltaVt(glu) significantly decreased after addition of Cd-MT for 10 min. A reduction in pH to 6.8 significantly shortened the time needed to reduce the DeltaVt(glu) to <5 min, whereas an increase of pH to 7.7 significantly prolonged the time to >20 min. Furthermore, simultaneous addition of acetazolamide with control perfusate prevented the reduction. P-Fluorobenzyl-aminobenzolamide (pFB-ABZ), a membrane-impermeable CA inhibitor, added to the lumen also completely prevented the reduction in DeltaVt(glu). In rabbits with chronic Cd exposure, acetazolamide prevented the glucosuria. CONCLUSION: Cd-MT-induced inhibition of Na-glucose cotransporter activity in the S2 segment strongly depends on luminal pH, and that an increase in pH by inhibition of luminal membrane-bound CA is useful to prevent renal Cd toxicity.

Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats.

BACKGROUND: The major side effect of cisplatin, used in some tumours, is nephrotoxicity. Reactive oxygen species and oxidative damage are the most important factors in cisplatin-induced acute renal failure. The main purpose of this study is to investigate the protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rat. METHODS: In this study, animals were randomly divided into 5 groups (6 each). Group one received normal saline (2 ml/day, i.p.). Group two received a single dose of cisplatin (5 mg/kg, i.p.). Groups 3 to 5 received crocin (100, 200 and 400 mg/kg, i.p., respectively, for 4 consecutive days one hour before a single dose of cisplatin (5 mg/kg) only at the first day. Blood samples were taken out (on the fifth day) for measuring the level of urea and creatinine. The kidneys were removed for histopathological and biochemical examinations. Furthermore, 24-hour urinary factors were measured. RESULTS: Blood urea, creatinine and urinary glucose and protein concentrations in crocin-treated groups were significantly lower than those of cisplatin-treated group in a dose-dependent manner. Histopathological studies showed a massive damage in S3 segment of proximal tubules in cisplatin-treated group. No damage was observed in crocin-treated groups. Crocin treatment resulted in a significant and dose-dependent reduction in malondialdehyde concentration as compared to the cisplatin-treated group. Moreover, crocin produced a significant elevation in total thiol and glutathione peroxidase concentrations, as compared with cisplatin-treated group. CONCLUSION: The results of the present study suggest that crocin has a protective effect against cisplatin-induced acute renal failure and relative oxidative stress.

How self management therapy can improve quality of life for diabetic patients.

Self-control led therapy is vital in the treatment of insulin dependent diabetes mellitus (IDDM), allowing as it does, correct insulin therapy, a reduction in hospitalisation and modification of therapy for individual needs in relation to various factors. Undoubtedly it is the responsibility of the diabetes team (doctors, nurses, dietician, psychologist and social assistant) to instruct the patient and help him/her in this new situation. The patient must learn to live and develop normally, participating to the full in school, at work and in all social situations, by fully understanding how to manage the illness autonomously and how to prevent short and long-term complications. Thus, the team must set objectives: making the patient aware of his condition, giving him the knowledge of what to do and how to do it. In this way, quality of life can be improved for patients affected by this chronic illness and they can understand how to face the future with realistic optimism. Modern technology has brought many novelties into the diabetes field, such as the ever smaller and more accurate glucose meters, or finger-prick devices requiring minimal quantities of blood. They represent another step towards a less invasive or disruptive approach in the management of diabetes. Non-specialist press articles may raise false hopes, above all about new research in the field of diabetes, but at least they also raise awareness on a problem of national interest, i.e. insulin dependent diabetes mellitus.