Plasma BUN Research Articles

Protective effects of hydroxytyrosol on gentamicin induced nephrotoxicity in mice

BackgroundGentamicin (GM) is an effective and common antibiotic against severe gram-negative infections. However, its nephrotoxic action has limited the extent of its use. The aim of this study was to investigate the protective effects of hydroxytyrosol (HT) on gentamicin induced nephrotoxicity in mice. MethodsMale mice (n = 27) were randomly assigned to three groups: (1) Sham, (2) GM (100 mg/kg for 7 days) (3) GM + HT (2 mg/kg BW; gastric gavages, for 7 days). 24-h urine samples were collected on day 8 and then animal were anesthetized. The blood and kidney tissue samples were collected. ResultsGentamicin led to increase in plasma BUN and creatinine, fractional excretion of sodium and potassium and decrease in creatinine clearance and urine flow rate. SOD and GSH levels were reduced and MDA was increased in the GM group compared with the sham group. In GM + HT group, plasma BUN and creatinine, fractional excretion of Na, creatinine clearance and urine flow rate were decreased in contrast to GM group. Increase in SOD and GSH activity and decrease in MDA compared to GM group were seen. ConclusionsFindings suggest that HT partly protected the kidneys from gentamicin induced nephrotoxicity and it is partly due to antioxidant effect of HT.

Mitochondrial NADP+-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion Injury.

Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R. Furthermore, Idh2 gene deletion exacerbated I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells. In cultured mouse kidney proximal tubule cells, Idh2 gene downregulation enhanced the mitochondrial damage and apoptosis induced by treatment with hydrogen peroxide. This study demonstrates that Idh2 gene deletion exacerbates mitochondrial damage and tubular cell death via increased oxidative stress, suggesting that IDH2 is an important mitochondrial antioxidant enzyme that protects cells from I/R insult.

Effect of heme oxygenase-1 transduced by cell penetrating peptide PEP-1 on renal injury in rats with acute paraquat poisoning

Objective: To study the effects of heme oxygenase-1 transduced by cell penetrating peptide PEP-1 on renal injury in acute paraquat-induced rats. Methods: The fusion protein PEP-1/HO-1 was manufactured by genetic engineering methods. One hundred and twenty-six healthy adult Sprague-Dawley (SD) rats (63 male, 63 female) were randomly divided into three groups: (1) Control group: 42 rats, (2) Poisoned group: 42 rats, (3) PEP-1/HO-1 intervention group: 42 rats. The rats in Poisoned group and intervention group were treated intraperitoneally with paraquat (25 mg/kg) deliquated with normal saline. Control group rats were treated with the same way of normal saline as the others. Intervention group rats were injected 1 mg of the fusion protein PEP-1/HO-1 into the left iliac vein at 30 minutes before the administration of the paraquat. After abdominal dissection with ether anaesthesia, six rats respectively from each of three groups were taken tissue samples from kidney at 1 st、6 th、12 th、24 th、36 th、48 th、and 72 nd hour respectively. Tissue Superoxide Dismutase (SOD) activity and Malondialdehyde (MDA) content were measured, and renal tissue was quickly remained to observe the expression of Heme Oxygenase-1 (HO-1) by the method of immunohistochemistry. Blood samples were collected from the abdominal aorta for determination of Blood Urea Nitrogen (BUN) and Creatinine (Cr) concentrations in plasma. Results: To prepare high purity fusion protein PEP-1/HO-1 Successfully. The levels of the plasma Bun and Cr in Poisoned and intervention group were significantly higher than that in Control group in the six to seventy-two hours (P<0.01) ; Whereas the increases of Bun and Cr were markedly intibited in PEP-1/HO-1 intervention group, in which, the levels of Bun and Cr in the six to seventy-two hours were significantly lower than Poisoned group (P<0.05). Compared with control group, the levels of MDA in poisoned groups were increased in the one to forty-eight hours and the levels of it in groups PEP-1/HO-1 in the one to thirty-six (P<0.01 or P<0.05). The T-SOD activity of the poisoned group was decreased in the one to thirty-six hours than that of the control group (P<0.05). Compared with poisoned group, the T-SOD activity at various points in time was increased in group PEP-1/HO-1 (P<0.01). In control group, there was only very weak expressions of HO-1 in the normal renal tissue. In poisoned and intervention group, the expressions of HO-1 were significantly higher than that in control group in all time (P<0.01). The HO-1 expressions of PEP-1/HO-1 group in all time was significantly higher than that in poisoned group (P<0.01 or P<0.05). Conclusion: The HO-1 protein Can be successfully transduced into renal tissue by cell penetrating peptide PEP-1 and the transduced HO-1 protein reduces renal injury of the acute paraquat-induced rats by inhibiting lipid peroxidation response.

PS 10-03 EFFECTS OF LCZ696 ON BLOOD PRESSURE AND RENAL INJURY IN TYPE 2 DIABETIC RATS WITH OVERT PROTEINURIA

Objective: Clinical studies have indicated that LCZ696, an angiotensin receptor-neprilysin inhibitor, exerts beneficial effects in patients with heart failure. Here, we aimed to examine the effect of LCZ696 on blood pressure and renal injury in type 2 diabetic Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats with overt proteinuria. Design and Method: In OLETF rats, vehicle (n = 10), valsartan (30 mg/kg/day, n = 10), LCZ696 (68 mg/kg/day, n = 9) or valsartan plus hydralazine (3 mg/kg/day, n = 10) was treated from 56 to 80 weeks of age. Results: At baseline (56-week-old), diabetic OLETF rats showed hypertension, overt proteinuria, glomerular injury (glomerular PAS positive area) and tubulointerstitial fibrosis (Sirius Red-positive area). At 80-week-old, vehicle-treated OLETF rats showed developed hypertension and proteinuria, severe glomerular injury and tubulointerstitial fibrosis, and increases in plasma BUN and creatinine levels. Treatment with LCZ696 or valsartan plus hydralazine similarly caused greater blood pressure reduction than valsartan. On the other hand, LCZ696 caused greater reductions in proteinuria, glomerular injury and tubulointerstitial fibrosis than valsartan or valsartan plus hydralazine. LCZ696 also prevented the increases in plasma BUN and creatinine levels. Conclusions: These data suggest that LCZ696 elicits a reno-protective effect in type 2 diabetes with hypertension and nephrotic-range proteinuria.

Pathomorphological changes of flunixin meglumine toxicity in layer chicks

The aim of the 21 day toxicity study was to evaluate the pathomorphological effect of flunixin meglumine in layer chicks. The chicks of Group I were kept as control while groups II, III and IV were fed with diet containing flunixin meglumine @ 10 ppm, 25 ppm and 50 ppm respectively for 21 days. Clinical signs viz. anorexia, dullness,lethargy, lameness and uneven growth were noticed in chicks of treatment groups III and IV only. Maximum mortality was observed in group IV (12%) followed by group III (4%). A dose dependant reduction in body weight was observed in all the treatment groups. The mean values of Kidney: Body weight ratio was significantly increased in group IV. The plasma uric acid, creatinine and BUN values were significantly increased in group III whereas increase in group IV was highly significant. Grossly, there was deposition of chalky white urates on serosal surface of kidney, heart and liver in chicks of group IV which died during experiment. Microscopically, lesions were characterized by varying degrees of congestion, haemorrhages, degeneration, necrosis and deposition of urate crystals in visceral organs of group III and group IV chicks. The intensity and distribution of pathological lesions were more severe in chicks of group IV, followed by chicks of group III. The overall lesions gave an impression that flunixin meglumine was nephrotoxic in nature.

Adipocytes play an etiological role in the podocytopathy of high-fat diet-fed rats.

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.

A functional role for complement receptor C5L2 in the pathogenesis of renal ischemia-reperfusion injury

The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The two receptors for C5a, C5aR and C5L2, are expressed on leukocytes as well as in the kidney. Extensive evidence shows that C5aR inhibition protects kidneys from IR injury, but the role of C5L2 in IR injury has not been studied so far. Therefore, WT, C5aR−/− and C5L2−/− mice were subjected to 40 min of bilateral renal ischemia, followed by reperfusion for 1, 3 or 7 days. It was found that C5L2−/− mice were protected against IR injury, resulting in significant lower plasma creatinine and BUN levels, and reduced acute tubular necrosis. Next, an in vivo migration study, where WT, C5aR−/− and C5L2−/− mice were injected intraperitoneally with complement ligands, revealed that C5L2 is not involved in leukocyte migration. To investigate the contribution of renal-expressed C5L2 versus leukocyte-expressed C5L2 to renal IR injury, bone marrow chimeras were created. Our data show that renal-expressed C5L2 and leukocyte-expressed C5L2 mediate IR injury-induced renal dysfunction. Therefore, C5L2 is a functional receptor in renal IR injury rather than a simple decoy receptor. For that reason, next to C5aR, C5L2 is a potential target for intervention during renal IR injury.

Comparative efficacy of passive and mechanical fan-pad cooling system for microclimate modification and welfare in broiler production

Efficacy of passive cooling vis-à-vis mechanical fan-pad cooling system was assessed for microclimate modification to alleviate heat stress and improving growth performance and welfare of broilers. Cooling treatments comprised of Tc (control without any cooling system), TJSC passive cooling (jute sheet roof shading and curtains with gravity flow sprinklers), TGSC passive cooling (green sheet roof shadings and curtains with gravity flow sprinklers) and TFP (fan pad mechanical cooling systems). The results of shed microclimate indicated that maximum ambient temperature, temperature humidity index (THI) and duration and level of heat stress in control were significantly higher than passive (TJSC and TGSC) and mechanical (TFP) cooling group. Growth performance and feed efficiency, in both passive (TJSC and TGSC) and mechanical cooling (TFP) were significantly better than control. However, growth performance and feed efficiency of chicks was significantly higher in TFP than chicks in passive (TJSC and TGSC) cooling groups. In passive cooling systems (TJSC and TGSC), the plasma catalase, glutathione peroxidase (GPx) and BUN were significantly lower than control (Tc) but significantly higher than mechanical cooling (TFP) system. The stress related behavioural activities, panting, preening, scratching and wing flapping were significantly higher in control as than in cooling system. It was concluded that passive cooling system can be an environment friendly and energy independent alternate to intensive mechanical cooling system to reduce heat stress and improve growth and welfare in broiler production.

Nephroprotective and antioxidant effect of aqueous leaf extract of Costus Afer Ker gawl on cyclosporin-a (Csa) induced nephrotoxicity

BackgroundOxidative stress (OS) has been linked to the pathology of a variety of chronic and degenerative diseases. Medicinal plants contain bioactive compounds which are capable of preventing and fighting these diseases. The nephroprotective and antioxidant properties of the aqueous leaf extract of Costus afer (C.afer) against cyclosporine A CsA - induced nephrotoxicity in Wistar albino rats were investigated.MethodsSix groups of five weight-matched animals each, were used for the study. The first and second groups served as normal and toxic control and were given olive oil and CsA (50 mg/kg b.w.) orally respectively while groups 3, 4, 5 and 6 ingested 375, 750 and 1125 mg/kg b.w. aqueous leaf extract and 100 mg/kg b.w. of the Silymarin respectively one hour prior to administration of CsA 50 mg/kg b.w.ResultsTreatment with C. afer extract at doses of 375, 750 and 1125 mg/kg prevented the CsA induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly (p < 0.05) reduced plasma creatinine, BUN, K+ and renal malondialdehyde (MDA). Furthermore, all the doses were able to induce a significant increment (P < 0.05) of renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity, catalase(CAT), glutathione-S-tranferase (GST), serum electrolytes (Na+ and HCO3−), body and kidney weight. The nephroprotective effects of C.afer extract were confirmed by a reduced severity of renal cellular damage.ConclusionAqueous leaf extract of C.afer has a protective role against CsA- induced nephrotoxicity probably mediated through its antioxidant properties.

Short communication: Production performance and plasma metabolites of dairy ewes in early lactation as affected by chitosan

The objective of this study was to evaluate the effects of chitosan (CHI) supplementation on production performance and blood parameters in dairy ewes. Twenty-four multiparous Latxa dairy ewes at d 16 of lactation were divided into two groups of 12 ewes each. Ewes were fed one of two experimental concentrates (0.840 kg dry matter/d), control or supplemented with 1.2% CHI, on a dry matter basis. Ewes also had free access to tall fescue hay, water, and mineral salts. The experimental period lasted for 25 d, of which the first 14 d were for treatment adaptation and the last 11 d for measurements and samplings. Supplementation with CHI decreased total (p=0.043) and fescue (p=0.035) dry matter intake (DMI), but did not affect concentrate DMI. Supplementation with CHI, moreover, increased plasma glucose (p=0.013) and BUN concentrations (p=0.035), but did not affect those of non-esterified fatty acids. Dietary supplementation with CHI, however, did not affect milk yield, 6.5% FCM, milk composition, or BW, but it improved dietary apparent efficiency by increasing the milk yield-to-DMI (p=0.055) and 6.5% FCM-to-DMI (p=0.045) ratios. In conclusion, dietary supplementation of chitosan maintained ewe performance while reducing feed intake and improving dietary apparent efficiency.

Macrophage-derived tumor necrosis factor-α mediates diabetic renal injury

Monocyte/macrophage recruitment correlates strongly with the progression of diabetic nephropathy. Tumor necrosis factor-alpha (TNF-α) is produced by monocytes/macrophages but the direct role of TNF-α and/or macrophage-derived TNF-α in the progression of diabetic nephropathy remains unclear. Here we tested whether inhibition of TNF-α confers kidney protection in diabetic nephropathy via a macrophage-derived TNF-α dependent pathway. Compared to vehicle-treated mice, blockade of TNF-α with a murine anti-TNF-α antibody conferred kidney protection in Ins2Akita mice as indicated by reductions in albuminuria, plasma creatinine, histopathologic changes, kidney macrophage recruitment and plasma inflammatory cytokine levels at 18 weeks of age. To assess the direct role of macrophage-derived TNF-α in diabetic nephropathy, we generated macrophage specific TNF-α deficient mice (CD11bCre/TNF-αFlox/Flox). Conditional ablation of TNF-α in macrophages significantly reduced albuminuria, the increase in plasma creatinine and BUN, histopathologic changes and kidney macrophage recruitment compared to diabetic TNF-αFlox/Flox control mice after 12 weeks of streptozotocin-induced diabetes. Thus, production of TNF-α by macrophages plays a major role in diabetic renal injury. Hence, blocking TNF-α could be a novel therapeutic approach for treatment of diabetic nephropathy.

Pathomorphological study of Flunixin meglumine toxicity in broiler chicks

The aim of the present study was to evaluate the toxicopathological effects of flunixinmeglumine in broiler chicks. The chicks of group I were kept as control while group II, III and IV were fed with diet containing flunixinmeglumine @ 10 ppm, 25 ppm and 50 ppm, respectively for 21 days. Clinical signs viz., dullness, depression, anorexia, shifting lameness, unthriftiness with ruffled feather, drooping of the wings and lethargy with shrunken eyes were noticed in birds of treatment group III and IV only. Maximum mortality was observed in group IV (48%) followed by group III (20%) and group II (4%). A dose dependent reduction in body weight was observed in all treatment groups. The mean values of kidney: body weight ratio was significantly increased in all treatment groups. The plasma uric acid values were significantly increased in treatment group II whereas highly significantly increased in group III and IV. The plasma creatinine and BUN values were significantly increased in treatment group III, whereas, highly significantly increased in group IV. Grossly, chalkywhiteurate deposits of varying degree on mucosal or serosal surface and parenchyma of visceral organs and joints were observed in chicks that died during experiment from treatment group III and IV. Microscopically, the lesions were characterized by congestion, haemorrhages, degeneration, necrosis and deposition of urate crystals in visceral organs. The overall lesions gave an impression that flunixinmeglumine was nephrotoxic in nature and causes similar toxicity in broiler chicks as diclofenac does in vultures.

Prediction of mortality in hip fracture patients: role of routine blood tests.

To assess the mortality predictive value of routine blood tests in patients with hip fracture. In a retrospective descriptive study, medical records of 204 hip fractured patients with the age of 60 or older who were admitted to the Department of Orthopedics was considered regarding routine laboratory tests. Predictive values of these tests were assessed using receiver operating characteristic curve (ROC). The incidence of death due to hip fracture was 24%. The mortality rate was significantly increased with age > 65 (OR= 15). There was no significant difference between mortality in regards to gender. High plasma BUN (more than 20 mg/dl) and creatinine (more than 1.3 mg/dl) significantly increased the chance of mortality. [OR= 3.0 and OR=2.5 for BUN and creatinine, respectively]. Patients' mortality did not show any correlation with sodium and potassium plasma levels and blood hemoglobin. There is direct correlation between plasma levels of BUN and creatinine and 3-month mortality after hip fractures. Patients with high plasma levels of BUN were three times more likely to die than those with normal BUN. Also, patients with high plasma creatinine levels were 2.5 times more likely to die than those who had normal values. Mortality was also associated with increasing age but did not vary with gender. Patients aging more than 65 were 15 times more likely to die following a hip fracture than those with younger age.

Toxicopathological studies of flunixinmeglumine in broiler chicks

The aim of the present study was to evaluate the toxicopathological effects of flunixinmeglumine in broiler chicks. The chicks of Group I were kept as control while groups II, III and IV were fed with diet containing flunixinmeglumine @ 10 ppm, 25 ppm and 50 ppm respectively for 21 days. Clinical signs viz. dullness, depression, anorexia, shifting lameness, unthriftiness with ruffled feather, drooping of the wings and lethargy with shrunken eyes were noticed in birds of treatment groups III and IV only. Maximum mortality was observed in group IV (48%) followed by group III (20%) and group II (4%). A dose dependent reduction in body weight was observed in all treatment groups. The mean values of kidney: body weight ratio was significantly increased in all treatment groups. The plasma uric acid values were significantly increased in group II whereas, increase in group III and IVwas highly significant. The plasma creatinine and BUN values were significantly increased in group III whereas highly significant increase in group IV was observed. Grossly, chalkywhiteurate deposits of varying degree on mucosal and/or serosal surfaces, parenchyma of visceral organs and joints were observed in chicks that died during experiment from groups III and IV. Microscopically, the lesions were characterized by congestion, haemorrhages, degeneration, necrosis and deposition of urate crystals in visceral organs. The overall lesions gave an impression that flunixinmeglumine was nephrotoxic in nature and causes similar toxicity in broiler chicks as diclofenac does in vultures.

Complement Activation May Trigger the Onset of Thrombotic Thrombocytopenic Purpura in Patients with Severe ADAMTS13 Deficiency

Thrombotic thrombocytopenic purpura (TTP), a potential fatal syndrome, is often associated with severe deficiency of plasma ADAMTS13 activity, either resulting from ADAMTS13 mutations or acquired anti-ADAMTS13 autoantibodies that inhibit plasma ADAMTS13 activity. Patients with severe ADAMTS13 do not always have TTP signs and symptoms, which often occur following infections or inflammatory responses. The mechanism of TTP flare is not fully understood. In the present study, complement activation markers (iC3b, C5b, Bb, and C4b) were determined by enzyme-linked absorbent assays (ELISA) in the initial plasmas (prior to plasma exchange) of 20 patients with acquired TTP with severe ADAMTS13 deficiency (less than 20% of normal) and plasmas from 20 healthy controls. Of 20 TTP patients, 19 exhibited positive inhibitor in the 50:50 mixing study. Plasma levels of iC3b (1,000 ± 1,062 ng/ml), sC5b-9 (1,342±867 ng/ml), and Bb (38.2±47.7 ng/ml), as well as C4b (74.3±49.5 ng/ml) in acquired TTP patients were significantly higher than those in healthy controls (p value less than 0.01) These results indicate that complement activation in both classic and alternative pathways is a common phenomenon in patients with acquired autoimmune TTP. To demonstrate the causative effect of complement activation in TTP, we turned to our Adamts13 null mice. C57BL/6 (Adamts13-/-) mice are resistant to the development of spontaneous and Shigatoxin-induced TTP syndrome. When injected with a murine specific monoclonal antibody against complement factor H (CFH) (800 micro grams/mouse), which inhibits binding of circulating CFH to endothelial cells and C3b, Adamts13-/- mice (C57BL/6) developed more severe thrombocytopenia and anemia than wild type mice did within 6 days without additional challenge. However, renal insufficiency manifested by the increase of plasma BUN concentration was similar in both groups (Fig. 1). These results indicate that complement activation through an alternative pathway, following antibody-mediated inhibition of CFH or other complement regulatory components, may trigger the onset of TTP in light of severe ADAMTS13 deficiency. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Novel Hg2+-induced nephropathy in rats and mice lacking Mrp2: evidence of axial heterogeneity in the handling of Hg2+ along the proximal tubule.

The role of the multi-resistance protein 2 (Mrp2) in the nephropathy induced by inorganic mercuric mercury (Hg(2+)) was studied in rats (TR(-)) and mice (Mrp2(-/-)), which lack functional Mrp2, and control animals. Animals were exposed to nephrotoxic doses of HgCl2. Forty-eight or 24 hours after exposure, tissues were harvested and analyzed for Hg content and markers of injury. Histological analyses revealed that the proximal tubular segments affected pathologically by Hg(2+) were significantly different between Mrp2-deficient animals and controls. In the absence of Mrp2, cellular injury localized almost exclusively in proximal tubular segments in the subcapsular (S1) to midcortical regions (early S2) of the kidney. In control animals, cellular death occurred mainly in the proximal tubular segments in the inner cortex (late S2) and outer stripe of the outer medulla (S3). These differences in renal pathology indicate that axial heterogeneity exists along the proximal tubule with respect to how mercuric ions are handled. Total renal and hepatic accumulation of mercury was also greater in animals lacking Mrp2 than in controls, indicating that Mrp2 normally plays a significant role in eliminating mercuric ions from within proximal tubular cells and hepatocytes. Analyses of plasma creatinine, BUN, and renal expression of Kim-1 and Ngal tend to support the severity of the nephropathies detected histologically. Collectively, our findings indicate that a fraction of mercuric ions is normally secreted by Mrp2 in early portions of proximal tubules into the lumen and then is absorbed downstream in straight portions, where mercuric species typically induce toxic effects.

Diabetic cardiomyopathy in medical examination patients with impaired glucose tolerance and Type 2 diabetes

To investigate the change of diabetic cardiomyopathy in patients with impaired glucose tolerance (IGT) and Type 2 diabetes (T2DM) and its influencing factors. Patients with IGT and T2DM were divided into an IGT group (n=314), a T2DM group (n=368) and an NC group (400 normal subjects). The left ventricular ejection fractions (LVEF) and the interventricular septal depth (IVSd) were measured by Doppler echocardiography. The general information and blood biochemistry were also collected during the corresponding time period. Compared with the NC group, waist circumference (WC), bodymass index (BMI), premature family history of cardiovascular disease, the serum levels of fasting plasma glucose (FPG), HbA1c, TC, TG, hyperlipidemia, BUN and Cr significantly increased (P<0.01) in the IGT and T2DM groups. Compared with the NC group and the IGT group, the LVEF significantly decreased (P<0.01) and the IVSd significantly increased (P<0.01) in the T2DM group. The LVEF and IVSd did not have obvious difference between the NC group and the IGT group. Pearson correlation analysis showed a negative correlation between LVEF and HbA1c, TC and duration of disease (P<0.01); but a positive correlation between IVSd and WC, BMI, HbA1c and duration of disease, and a negative correlation between IVSd and HDL (P<0.05). In the multiple linear stepwise regression, HbA1c and duration of disease showed a significant association with both LVEF and IVSd (P<0.05). T2DM has a close association with cardiomyopathy. HbA1c and duration of disease are the independent predictors for LVEF and IVSd.

Growth, nutrition and immune function of breast‐fed infants and infants fed formula with added osteopontin (623.14)

Breast milk contains a high concentration of OPN, which affects immune function. In contrast, infant formula is low in OPN. We performed an RCT in Shanghai to evaluate effects of adding bovine OPN to formula. Mothers chose to either breast‐(BF) or formula‐feed their infant. Formula‐fed infants received: formula (FF), formula with 65 mg/L (F65) or 130 mg/L (F130) OPN. Anthropometry was registered monthly and venous blood samples were taken at 1, 4 and 6 mo of age. Hematology (RBCs, Hb, ferritin), immune parameters (FACS analysis, cytokines), plasma amino acids and BUN were analyzed. Antibody response to DPT vaccination was also used as a measure of immune function. Formulas were well tolerated and there were no significant differences in formula intake or growth among the formula‐fed groups. Repeated measures analysis showed a higher % of T‐lymphocytes and T‐regulatory cells in infants fed F130 than infants fed the other formulas. FF infants had significantly higher levels of TNF‐α than those fed F65 or F130 and BF infants. IL‐6 levels were lower in infants fed F130 than infants fed the other formulas and IL‐10 levels highest in the FF group. These results suggest that addition of OPN to infant formula changes immune function and cytokine responses of FF infants and makes them more similar to BF infants.

Elucidating the role of a renal proximal tubule‐specific olfactory receptor (892.42)

Olfactory receptors (ORs) are seven transmembrane domain G protein‐coupled chemosensors that detect odorants in the nose. We previously reported that OR signaling plays a role in the kidney (PNAS 2009), and to date we have identified 9 renal ORs. One of these is Olfr1393, which is widely expressed in a number of tissues, including kidney (by RT‐PCR screen). Using reverse‐transcribed RNA from microdissected renal segments, we found that Olfr1393 is exclusively expressed in the proximal tubule (PT; S1, S2 and S3). Like the majority of ORs, Olfr1393 is an orphan receptor with no known ligand. To screen for ligands, we cloned this receptor from the kidney and expressed it in HEK293T cells after optimizing conditions to allow for surface expression. We comprehensively screened over 1400 chemicals, and found that Olfr1393 detects preconstrained cyclic molecules containing either a carbonyl or alcohol group. We also found that when stably expressed in polarized MDCK cells, Olfr1393 localizes to the apical PM yet is excluded from the primary cilia. To determine the function of this receptor, we generated knockout (KO) mice. At baseline, KO mice appear to be in homeostatic balance based on plasma electrolytes, BUN, creatinine, urinalysis, and blood pressure measurements ‐ in future studies, we will challenge WT and KO mice with Olfr1393 ligands to ascertain how PT and renal function are regulated by Olfr1393.Grant Funding Source: Supported by: NIDDK and ASN

Average Daily Gain, AST and Blood Nitrogen Urea (BUN) Responses of Bali Beef on Cocoa Waste Extract Supplement

the research aimed to identify blood plasma AST, BUN, Triglyceride and average daily gain (ADG) responses of Bali beef on cocoa pod husk (CPH) extracts supplementations. 15 males of Bali beef in fattening premises were divided according to feed treatments; group A1 with normal feed; A2 CPH meal (CPH-M); A3= CPH crud (CPH-CE); A4= high theobromine CPH (CPH-T); A5= high polyphenol CPH (CPH-P). Blood collection and body weighting held one day before treatment (B1); B2= 24 h; B3= 14 d; B4= 28 d; 42 d later. Result show that there was no significant difference in ADG values within all treatments, although the control and CPH-P had higher ADG at 14–56d of treatment. The blood AST activity were same (P>0.05) in control, CPH-M and CPH-C and significantly higher (P<0.05) than CPH-T and CPH-P Thus preliminary parameters implied that utilizing of CPH as feed for Bali beef didn’t indicate any negative effect.