Treatment of congenital nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride in an adult patient

AIM: The effects of treatment with hydrochlorothiazide (HCTZ) combined with amiloride were elucidated and compared to HCTZ treatment alone and combined with acemetacin or triamterene in a Japanese adult patient with congenital nephrogenic diabetes insipidus. METHODS: The study was divided into seven periods: (1) HCTZ and acemetacin; (2) control period; (3) HCTZ; (4) a second control period; (5) HCTZ and amiloride; (6) a third control period, and (7) HCTZ and triamterene. Fluid intake, urine volume, urinary Na, K, creatinine, and osmolality and serum Na, K, Cl, CO2, and osmolality were measured, and free water clearance and proximal and distal tubular Na reabsorption rates were calculated. RESULTS: Without drug administration, the urine volume was about 8,000 ml/day. The urine volume was reduced to about 6,000 ml/day with HCTZ. A further urine volume reduction to about 5,000 ml/day was obtained with the second drug administration, and the effects were similar among the three regimens. Serum and urinary osmolality and free water clearance were also similar among the three combinations, whereas the urinary potassium excretion was the least, and the serum potassium concentration was the highest with HCTZ plus amiloride. Besides, no alkalosis was observed only with this combination. CONCLUSION: HCTZ plus amiloride may be superior to HCTZ plus acemetacin and HCTZ plus triamterene in preventing hyperkaliuria, hypokalemia, and metabolic alkalosis.     

Effects of therapeutic doses of amiloride and hydrochlorothiazide on taste, saliva and salt intake in normotensive adults

Tentative evidence suggests that hydrochlorothiazide (HCTZ)and amiloride may alter salivary function, taste sensitivityand dietary intake. The effects of these diuretics on salivaryflow and composition, taste attributes (i.e. recognition thresholds,perceived intensity ratings and preference) as well as sodiumintake were further examined in 73 normotensive adults in adouble-blind, placebo-controlled, cross-over study. Followingrandom assignments to one of three groups [5 mg twice per dayof amiloride (n = 24), 50 mg/day of HCTZ (n = 24) or placebo(n = 25)], subjects took appropriate placebos for 2 weeks, activedrug for 8 weeks and placebo for 3 weeks. Relative to baselinevalues, amiloride treatment resulted in a significant 39% decreasein stimulated salivary sodium levels and a 28% decline in NaClrecognition thresholds. HCTZ significantly stimulated sodiumintake as the sodium/creatinine ratio was {small tilde}50% higherfollowing 4 weeks of drug use relative to baseline values. Subjectswere subjectively unaware of these changes. Potential mechanismsand clinical implications of these findings are considered.     

Urinary dopamine, noradrenaline and adrenaline in type 2 diabetic patients with and without nephropathy

We measured the urinary excretions of dopamine, noradrenaline and adrenaline, their conjugated metabolites, urinary excretion of sodium and creatinine clearance simultaneously in 21 patients with Type 2 (non-insulin-dependent) diabetes and 6 normal subjects. The mean (+/- SEM) value for urinary excretion of dopamine (52.4 +/- 8.8 micrograms/day) in diabetic patients with nephropathy (Group C, n = 12) was significantly lower (P less than 0.01) than in the normal subjects (Group A, 179.7 +/- 15.5 micrograms/day) and in diabetic patients without nephropathy (Group B, n = 9, 131.5 +/- 16.5 micrograms/day). The mean values for the urinary excretions of noradrenaline and adrenaline were also significantly lower (P less than 0.01) in Group C than in Groups A and B. In addition, the mean urinary excretion of conjugated metabolite of dopamine in Group C was significantly lower (P less than 0.05) than in Group A. There was a trend toward the observation that the mean 24-h urinary excretion of sodium in Group C (121.6 less than 12.9 mEq) was lower as compared with that in Group A (140.8 +/- 8.9 mEq) or B (150.7 +/- 17.9 mEq). A multiple regression analysis revealed that the 24-h urinary excretion of dopamine correlated significantly with creatinine clearance, systolic (P less than 0.01) and diastolic (P less than 0.05) blood pressures. The results indicate that synthesis or secretion of renal dopamine might decrease with a progression of diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Non-steroidal anti-inflammatory agents, tolmetin and sulindac attenuate quinolinic acid (QA)-induced oxidative stress in primary hippocampal neurons and reduce QA-induced spatial reference memory deficits in male Wistar rats

Accumulating evidence suggests that anti-inflammatory agents and antioxidants have neuroprotective properties and may be beneficial in the treatment of neurodegenerative disorders. In the present study, the possible neuroprotective properties of tolmetin and sulindac were investigated using quinolinic acid (QA)-induced neurotoxicity as well as behavioral studies. QA, a metabolite of the tryptophan-kynurenine pathway, significantly induces lipid peroxidation, superoxide anion generation and decreases cell viability in primary hippocampal neurons established from one day old rat pups. However, co-incubation of the neurons with tolmetin or sulindac markedly reduces oxidative stress and enhances cell viability. Animals were trained in a Morris water maze for four consecutive days and thereafter received 0.6 micromol of QA intrahippocampally. The animals were divided into groups and were treated with either tolmetin or sulindac (5 mg/kg twice a day for five days). During test trials, the time taken for each rat to find the submerged platform was recorded over a period of two weeks. Animals were thereafter sacrificed and the hippocampi analyzed for protein carbonyl and glutathione content. The results show that both sulindac and tolmetin reduce the QA-induced spatial memory deficit and sulindac treated animals respond better in the water maze compared to the tolmetin treated animals. Both agents also reduce protein oxidation in rat hippocampus and attenuate the decrease in hippocampal glutathione content induced by QA. This study indicates that the antioxidant properties of tolmetin and sulindac may be beneficial in the treatment of neurodegenerative disorders such as Alzheimer's disease.     

Anionic salts and dietary 25-hydroxyvitamin D stimulate calcium availability in steers

The influence of feeds containing varying dietary cation–anion differences (DCADs) with and without supplements of 25-hydroxyvitamin D (25(OH)D) on urine pH and excretion of macro minerals was determined in fistulated crossbred steers (mean live weight 315 ± 45 kg). A basal forage diet comprising lucerne hay and wheat chaff was used, to which varying quantities of MgCl₂ or K₂CO₃ were added to achieve four levels of DCAD: −300, 50, 150 or 250 mEq/kg dry matter (DM). Steers were allocated to one of six treatments, one treatment for each diet and a further treatment for both the 50 and 150 mEq/kg DCAD diets, which were supplemented with 25(OH)D at a rate of 3 mg/steer per day. Urine pH from steers offered the diets comprising DCADs of 50, 150 and 250 mEq/kg ranging from 8.3 to 8.8. In treatments not containing 25(OH)D with DCADs of 50 to 250 mEq/kg, there were no significant differences in urine pH or Ca excretion. However, steers offered the diet with a DCAD of −300 mEq/kg DM produced urine with a significantly lower pH (6.5 to 7.5). Daily output of Ca in urine was also significantly higher from steers given this diet. Supplementation with 25(OH)D significantly increased urinary Ca excretion from steers offered diets of DCADs 50 and 150 mEq/kg DM. Estimates of daily urinary Ca excretion, calculated using the ratio of creatinine to Ca in ‘spot’ urine samples, were less variable than those based on total collection (residual mean square of 0.54 and 0.63, respectively).     

Developmental toxicity evaluation of ibuprofen and tolmetin administered in triple daily doses to Wistar CRL:(WI)WUBR rats

BACKGROUND: Ibuprofen and tolmetin are popular non-steroidal anti-inflammatory drugs. Previous animal studies taken with single daily doses showed their good prenatal tolerability. However, since both cyclooxygenase (COX) inhibitors have a short half-life, the current report presents drug developmental effects after triple daily doses administration, as they are used in human. METHODS: Drugs were separately, orally dosed to pregnant rats triple daily 8 hr apart from day 8 to 21 (GD=1-plug day). The total daily doses were set at 25.5, 255.0, and 600.0 mg/kg for ibuprofen and 25.5, 255.0, and 2550.0 mg/kg for tolmetin. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. RESULTS: Maternal toxicity and intrauterine growth retardation were found in groups exposed to the highest doses of both drugs. An increase of external variations was reported in groups exposed to the middle and highest dose of ibuprofen and to the highest dose of tolmetin. Skeletal variations were significantly different only in litters treated with the highest doses of the drugs. Pooled statistical analysis showed a higher incidence of midline and ventricular septal (VSD) defect in rat fetuses exposed to COX inhibitors when compared with historical control data. For ibuprofen, the influence on VSD was similar to aspirin. CONCLUSION: Both COX inhibitors were toxic to dams in the highest doses evaluated, which caused a significantly greater incidence of intrauterine growth retardation and developmental variations.     

Amiloride is an ineffective conditioned stimulus in taste aversion learning in C57BL/6J and DBA/2J mice

The epithelial sodium channel (ENaC) blocker amiloride has been shown to increase the behaviorally measured NaCl detection threshold in mice. In this study, a conditioned taste aversion (CTA) paradigm was used to examine whether 100 microM amiloride has a perceptible taste that could contribute to this observed decrease in behavioral responsiveness. Eighty-four C57BL/6J (B6) and 64 DBA/2J (D2) mice were divided into eight groups (n=8-12 per group), in which half received an injection of 0.15 M LiCl (2 mEq/kg) and the other half an equivalent saline injection, in three conditioning trials. The four conditioned stimuli were 100 microM amiloride hydrochloride, water, 0.1 and 0.3 M NaCl. Neither strain demonstrated acquisition of a CTA to amiloride in a brief-access (BA) taste test (5 s trials in the gustometer). Although 0.3 M NaCl is inherently aversive, its pairing with LiCl led to significantly further decreases in licking during the BA test on salt trials in both strains. The D2 strain clearly avoided 0.1 M NaCl, whereas avoidance of this stimulus was more equivocal in B6 mice. The inefficacy of amiloride to serve as a conditioned stimulus in taste aversion learning involving three LiCl pairings suggests that the effects of this ENaC blocker on taste-related behavioral responses to NaCl are likely due to its pharmacological interference with sodium taste transduction.     

Genital lesions in male red fronted gazelles (Gazella rufifrons) experimentally infected with Trypanosoma brucei and the effect of melarsamine hydrochloride (Cymelarsan®) and diminazene aceturate (Berenil®) in its treatment

Thirty red fronted gazelles (Gazella rufifrons) were used to assess the genital lesions associated with trypanosomosis and the efficacy of melarsamine hydrochloride (Cymelarsan^®) and diminazene aceturate (Berenil^®) in the treatment of the condition. The animals were divided into 6 equal groups (A-F). Animals in groups A-E were infected with Trypanosoma brucei, and later treated on day 8 post infection (p.i.) with either melarsamine hydrochloride (Cymelarsan^®) at 0.3 mg/kg (Group A) and 0.6 mg/kg (Group B) or diminazene aceturate (Berenil^®) at 3.5 mg/kg (Group C) and 7.0 mg/kg (Group D). Animals in group E remained untreated while group F served as healthy controls. Parasitaemia was established by day 8 p.i. in all infected groups and eliminated by day 16 following treatment on day 8 p.i. with melarsamine hydrochloride (Cymelarsan^®) (Groups A and B) or diminazene aceturate (Berenil^®) (Group D). On the other hand, diminazene aceturate treatment (Berenil^®) on day 8 p.i. at 3.5 mg/kg (Group C) caused a temporary disappearance of parasites from the circulation by day 16 p.i. but there was a relapse parasitaemia on day 44 with a peak count of 500 ± 2.79 × 10³ parasites/μL of blood by day 52 p.i. In the infected/untreated group (E), parasitaemia fluctuated but attained the same peak as Group C by day 52 p.i. Increase in body temperatures (40.5 ± 3.16 - 42.8 ± 3.25 °C) occurred during the first wave of parasitaemia but declined to pre-infection values from day 28 p.i. in Groups A, B and D. In Groups C and E, there was a second wave of parasitaemia (P < 0.05) with peak counts of 42.4 ± 0.81 × 10³/μL and 41.8 ± 0.80 × 10³/μL respectively by day 52 p.i. A significant (P < 0.05) decline in packed cell volume was also noted by day 52 p.i. The major clinical signs observed in Groups C and E were pyrexia, inappetance, emaciation, anaemia, dullness, starry hair coat, pallor of buccal and ocular mucous membranes. Similarly, in Groups C and E, the testicles appeared oedematous and painful to touch with degenerative changes, morphological sperm abnormalities and oligospermia with 2.0% and 0% sperm reserves respectively. Sperm reserve was 100% in Groups A, B and D. It is therefore, concluded that trypanosomosis can cause serious infertility in male red fronted gazelles and that early treatments with melarsamine hydrochloride (Cymelarsan^®) at 0.3 and 0.6 mg/kg body weight or diminazene aceturate (Berenil^®) at 7.0 mg/kg body weight may prevent such effects.     

Acute effect of hydrochlorothiazide on renal calcium and magnesium handling in postmenopausal women

A single 50 mg dose of hydrochlorothiazide (HCTZ) decreases the urinary excretion of calcium (U(Ca)V), clearance (C(Ca)) and fractional excretion (FE(Ca)) of calcium. This is accompanied by an increase of total calcium and ionized calcium (Ca2+) concentrations in the serum. On the other hand, HCTZ increases fractional excretion of magnesium (FE(Mg)) and decreases serum Mg2+ concentrations. Moreover, HCTZ decreases markedly clearance of phosphate (C(Pi)) and fractional excretion of phosphate (FE(Pi)) and increases serum phosphate (Pi) concentrations in healthy postmenopausal women. It is concluded that intrinsic renal cellular control promptly uncouples calcium and magnesium tubular reabsorption even without K+ depletion.     

Effects of recombinant human extracellular-superoxide dismutase type C on myocardial reperfusion injury in isolated cold-arrested rat hearts.

The efficacy of recombinant human extracellular-superoxide dismutase type C (EC-SOD C) on myocardial reperfusion injury was explored in hypothermically arrested rat hearts, as was its site of action. Forty isolated working rat hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. The hearts were arrested by the administration of 10 mL of cold perfusate at the onset of ischemia. At the same time, they were randomly assigned to one of five groups; A: cold perfusate only; B: cold perfusate + EC-SOD C 10.4 mg/L (30,000 U/L); C: cold perfusate+bovine CuZn-SOD 7.5 mg/L (30,000 U/L); D: cold perfusate + EC-SOD C 10.4 mg/L + heparin 50,000U/L; E: cold perfusate + heparin 50,000 U/L. Heparin was given to prevent binding of EC-SOD C to endothelial cell surfaces. Left ventricular function was studied before ischemia and at the end of reperfusion. Percent recovery of maximal left ventricular dP/dt after reperfusion was more pronounced in group B (109 +/- 24%; p less than .05) than in groups A (42 +/- 40%), C (47 +/- 36%), D (44 +/- 33%) and E (58 +/- 25%). Likewise, percent recovery of the double product (heart rate x systolic left ventricular pressure) was better in group B (104 +/- 18%; p less than .05) than in the other groups (A: 47 +/- 37%, C: 49 +/- 36%, D: 50 +/- 35%, E: 69 +/- 31%). Compared to the preischemic level, creatine kinase increased significantly in the coronary effluent after reperfusion in groups A, C, D, and E, but not in group B. The results suggest that EC-SOD C, which attaches to the endothelial cell surfaces, might be particularly effective as protection against myocardial reperfusion injury when given together with cardioplegic solution.     

PLGA-5-氟尿嘧啶缓释微球治疗结直肠癌裸鼠的探讨

目的研究PLGA-5-氟尿嘧啶缓释微球瘤周给药对结直肠癌移植瘤的治疗效果。方法将60只结直肠癌荷瘤鼠随机分为6组,每组10只。A、B组瘤周注射PLGA-5-氟尿嘧啶缓释微球,5-氟尿嘧啶剂量分别为200mg/kg和100 mg/kg;C、D组瘤周注射5-氟尿嘧啶注射液,5-氟尿嘧啶剂量分别为200 mg/kg和100 mg/kg;E组瘤周注射PLGA微球,800 mg/kg;F组不给予任何治疗。于0、3、6、9、12、15d观察裸鼠生存状况、称体重、测量肿瘤大小。15d时处死动物,称瘤重,计算抑瘤率,绘制肿瘤生长曲线;取血行白细胞计数、肝肾功能检查。结果A、B组肿瘤生长曲线平缓,15 d时A、B组肿瘤体积与C、D、E、F组比较,结果差异有显著性,C、D组肿瘤体积与E、F组比较差异无显著性;A、B组抑瘤率分别为75%和62%,与C、D组比较,结果差异有显著性;A、B、C、D、E组体重在0 d及15 d与F组比较,差异无显著性,15 d时各组白细胞计数及肝肾功能检查值均在正常范围。结论PLGA-5-氟尿嘧啶缓释微球瘤周给药能有效抑制结直肠癌移植瘤的生长,且无明显的毒副作用。     

辛伐他汀对大鼠肺纤维化及其内皮间质变过程的影响*

目的: 观察辛伐他汀对大鼠肺纤维化及其内皮间质变(EnMT )过程中VE-钙粘素(VE-cad)、波形蛋白(VIM)、α-平滑肌蛋白(α-SMA)表达的影响。方法: 健康雄性SD大鼠60只,随机分为对照组(A组)、造模组(B组)、辛伐他汀5 mg治疗组(C组)、辛伐他汀10 mg治疗组(D组),每组各15只。博来霉素(BLM)按5 mg/kg剂量一次性气管内灌注复制博莱霉素致大鼠肺纤维化模型,从造模第1日起C、D 组每天分别胃内灌注辛伐他汀混悬液5 mg /(kg·d)及辛伐他汀混悬液10 mg /(kg·d),A组和B 组每天胃内灌注等体积生理盐水10 ml /(kg·d)。于造模第7、14和28 日随机处死各组大鼠5只。Masson染色观察大鼠肺组织形态变化;碱性水解法检测肺组织中羟脯氨酸(HYP)含量;免疫组化法测定各组大鼠肺组织血管新生微血管密度(MVD);免疫组化和逆转录-聚合酶链反应法测定各组肺组织中VE-Cad、VIM及α-SMA蛋白和mRNA的表达水平。结果: ①与A组相比,B、C、D组各时间点肺组织HYP和MVD水平、VIM、α-SMA的mRNA和蛋白表达水平均明显升高(P均＜0.05),且以28 d达最高;而相应时间点VE-Cad 的mRNA和蛋白表达水平均明显降低(P均＜0.05),且以28 d达最低。②与B组相比,C、D组HYP和MVD水平、VIM、α-SMA的mRNA和蛋白表达水平均有降低(P均＜0.05),以D组28 d下降最明显;而相应时间点VE-Cad 的mRNA和蛋白表达水平均有升高(P均＜0.05),以D组28 d升高最明显。结论: 辛伐他汀可减轻大鼠肺纤维化,其机制可能与增强VE-cad表达,降低VIM及α-SMA表达,减少EnMT 发生有关。     

Ciprofloxacin concentrations in serum, bone and bone marrow of rabbits

Ciprofloxacin concentrations were determined in serum, bone and bone marrow of rabbits. Four experimental groups of animals were examined: group A (n = 6) received a dosage of 60 mg/kg/day intramuscularly for 4 weeks, groups B (n = 6), C (n = 15) and D (n = 15) received dosages of 120 mg/kg/day subcutaneously for 2 days, 2 weeks, and 4 weeks, respectively. In the kinetic portion of the study, peak serum concentrations of ciprofloxacin measured at the 15 min sampling time were: 2.61 +/- 0.27 micrograms/ml in the 60 mg/kg/day group (group A) and 3.24 +/- 0.78 micrograms/ml in the 120 mg/kg/day group (group B). At necropsy, rabbits in group A had mean ciprofloxacin concentrations of 3.60 +/- 2.27 micrograms/ml in serum, 2.24 +/- 1.19 micrograms/g in marrow and 1.19 +/- 0.44 micrograms/g in bone. Rabbits in group B achieved mean levels of 4.02 +/- 1.23 micrograms/ml in serum, 2.48 +/- 0.79 micrograms/g in marrow, and 1.35 +/- 0.40 micrograms/g in bone. Rabbits in group C achieved mean levels of 5.65 +/- 2.16 micrograms/ml in serum, 3.74 +/- 1.33 micrograms/g in marrow and 1.92 +/- 0.94 micrograms/g in bone. Rabbits in group D achieved mean levels of 7.24 +/- 2.50 micrograms/ml in serum, 4.48 +/- 1.68 micrograms/g in marrow, and 1.93 +/- 0.54 micrograms/g in bone. Differences between mean values for the four experimental groups were not statistically significant.     

Evaluation of inflammatory biomarkers associated with oxidative stress and histological assessment of magnetic therapy on experimental myopathy in rats

The effect of pulsed electromagnetic field (PEMF) therapy, also called magnetic therapy, upon inflammatory biomarkers associated with oxidative stress plasma fibrinogen, nitric oxide (NO), L-citrulline, carbonyl groups, and superoxide dismutase (SOD) was evaluated through histological assessment, in rats with experimental myopathy.

The groups studied were: (A) control (intact rats that received PEMF sham exposures); (B) rats with myopathy and sacrificed 24 h later; (C) rats with myopathy; (D) rats with myopathy and treated with PEMF; and (E) intact rats treated with PEMF. Groups A, C, D, and E were sacrificed 8 days later. Myopathy was induced by injecting 50 μl of 1% carrageenan λ (type IV) once sub-plantar. Treatment was carried out with PEMF emitting equipment with two flat solenoid disks for 8 consecutive days in groups D and E, at 20 mT and 50 Hz for 30 min/day/rat. The biomarkers were determined by spectrophotometry. The muscles (5/8) were stained with Hematoxylin-Eosin and examined by optic microscopy. Quantitative variables were statistically analyzed by the Fisher test, and categorical applying Pearson's Chi Squared test at p < 0.05 for all cases.

In Groups B and C, the biomarkers were significantly increased compared to A, D, and E groups: fibrinogen (p < 0.001); NO, L-citrulline and carbonyl groups (p < 0.05); SOD (p < 0.01) as well as the percentage of area with inflammatory infiltration (p < 0.001).

PEMF caused decreased levels of fibrinogen, L-citrulline, NO, SOD, and carbonyl groups and significant muscle recovery in rats with experimental myopathies.     

Comparative efficacy of ivermectin and levamisole for reduction of migrating and encapsulated larvae of Baylisascaris transfuga in mice

The comparative efficacy of 2 anthelmintics (ivermectin and levamisole) against Baylisascaris transfuga migrating and encapsulated larvae was studied in mice. A total of 60 BALB/c mice inoculated each with about 1,000 embryonated B. transfuga eggs were equally divided into 6 groups (A-F) randomly. Mice of groups A and B were treated with ivermectin and levamisole, respectively, on day 3 post-infection (PI). Mice of groups A-C were killed on day 13 PI. Similarly, groups D and E were treated with ivermectin and levamisole, respectively, on day 14 PI, and all mice of groups D-F were treated on day 24 PI. The groups C and F were controls. Microexamination was conducted to count the larvae recovering from each mouse. The percentages of reduction in the number of migrating larvae recovered from group A (ivermectin) and B (levamisole) were 88.3% and 81.1%, respectively. In addition, the reduction in encapsulated larvae counts achieved by ivermectin (group D) and levamisole (group E) was 75.0% and 49.2%, respectively. The results suggested that, to a certain extent, both anthelmintics appeared to be more effective against migrating larvae than encapsulated larvae. However, in the incipient stage of infection, ivermectin may be more competent than levamisole as a larvicidal drug for B. transfuga.     

Postprandial Hypertriglyceridemia Predicts Development of Insulin Resistance Glucose Intolerance and Type 2 Diabetes

Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) have been found to be associated with postprandial hypertriglyceridemia (PPHTg). However, whether PPHTg can cause IR and diabetes is not clear. We therefore investigated the role of PPHTg in development of T2DM in rat model of T2DM. 96 male Wistar rats were randomized into four groups (24 rats each). Control Group A, high sucrose diet (HSD) Group B, HSD+Pioglitazone (10mg/kg/day) Group C and HSD+Atorvastatin (20mg/kg/day) Group D. Fat and glucose tolerance tests were done at regular intervals in all groups besides insulin and body weight measurement. At 26 weeks, low dose streptozotocin (15mg/kg,i.p.) was given to half of the rats. All rats were followed up till 48 weeks. PPHTg developed as early as week 2 in Group B and stabilized by week 14. Group B displayed highest PPHTg compared to other groups. Atorvastatin treatment (Group D) abolished PPHTg which became comparable to controls, pioglitazone treatment partially blunted PPHTg resulting in intermediate PPHTg. Group B with highest PPHTg showed highest subsequent IR, glucose intolerance (GI) and highest incidence of prediabetes at week 26 and diabetes at week 34 and 46 compared to other groups. Group D rats displayed lower IR, GI, low incidence of prediabetes and diabetes at these time points compared to Groups B and C. ROC analysis showed that triglyceride area under the curve of each time point significantly predicts the risk of diabetes. Present study provides the evidence that PPHTg predicts the development of IR, GI and T2DM in rat model of diet induced T2DM.     

A modification of the Detter and Klingmüller's method for urinary alpha- and beta-pregnanediol and pregnanetriol determination: excretion patterns in men and in women during the normal menstrual cycle.

This report describes the modification of Detter and Klingmüller's method for the determination of urinary alpha- and beta-pregnanediol and pregnanetriol by means of thin -layer chromatography. The modifications were as follows: 1. The addition of formol prior to hydrolysis to prevent pigments penetration into urinary extracts. 2. The use of Kieselgel HF 254+366 nach Stahl (E. Merck, Darmstadt) which allows to localize the spots under UV-light at 366 nm without the use of colour reagents. The results concerning accuracy, sensitivity, precision and specificity in the modification described are profitable. Using this method in 7 healthy women (aged 28-37) with normal menstrual cycles the urinary excretion of alpha- and beta-pregnanediol and pregnanetriol were evaluated every second day (starting the 6th day of the cycle). The maximum of excretion of alpha- and beta-pregnandiol appeared on day 20 of the cycle, with the mean (+/- S.D.) 1.27 +/- 0.37 mg/24hr and 2.97 +/- 0.80 mg/24hr for alpha- and beta-pregnanediol, respectively. Mean values of pregnantriol were at the same level and ranged from 0.25 to 1.42 mg/24 hr. Single determination of these compounds in 8 healthy men (aged 19-42) revealed the mean excretion values (+/- S.D.) 0.96 +/- 0.17 mg/24 hr, 1.24 +/- 0.40 mg/24 hr, 1.12 +/- 0.65 mg/24 hr for alpha- and beta-pregnanediol and pregnanetriol, respectively.     

Effects of sodium depletion and orthostasis on plasma and urinary vasopressin in normal subjects

We investigated the effects of sodium depletion and orthostasis on the plasma concentration and urinary excretion of vasopressin (AVP) in eight normal female subjects. After 4 days on a sodium controlled diet (130 mEq/day), the subjects were placed on a low sodium diet (30 mEq/day) for 3 days and 120 mg of furosemide was administered orally on the first day of the low sodium regimen. Sodium depletion in the present study reduced body weight by 1.6 kg and increased hematocrit by 3.5%. A significant (p less than 0.05) increase in plasma AVP and a significant (p less than 0.05) decrease in 24-h urinary excretion of AVP were observed during sodium depletion. One-hour ambulation significantly increased plasma AVP in both control and sodium depleted phases (p less than 0.01). The percent change in plasma AVP tended to correlate with that in mean blood pressure in the control phase (r = 0.69, 0.05 less than p less than 0.1), and significantly correlated in the sodium depleted phase (r = 0.86, p less than 0.01). The present results suggest that AVP may play an important role in the maintenance of blood pressure during orthostasis in the sodium depleted state.     

Antihypertensive and bilateral renal responses to diuretics in 2-kidney, 1-clip Goldblatt hypertensive rats

Experiments were conducted to assess the effect of furosemide or amiloride alone and a combination of both agents on each kidney in anesthetized 2-kidney, 1 clip Goldblatt hypertensive rats (n = 25). Intravenous infusion of furosemide alone (1.02 mg/kg.hr) significantly reduced the blood pressure by 14 +/- 5 mmHg. There were 6- to 10-fold increases in water, absolute sodium and fractional sodium excretions and a 2-fold increase in potassium excretion in the nonclipped kidney. A smaller but significant increase in the excretory function was also observed in the clipped kidney. There was no significant change in GFR of both kidneys. Indomethacin pretreatment (2 mg/kg) failed to significantly alter the vasodepressor and renal responses to furosemide in both hypertensive and normal rats. Removal of the renal artery clip from the hypertensive rats reduced the blood pressure by 12 +/- 3 mmHg and enhanced the function of the ipsilateral, unclipped kidney. Subsequent administration of furosemide further increased the excretory response. Administration of amiloride alone (2.4 mg/kg.hr) or with furosemide into hypertensive rats reduced the arterial pressure and increased excretion rates of urine flow and urinary sodium. Potassium excretion rate decreased bilaterally in amiloride treated rats but did not alter significantly in rats which received a combination of amiloride and furosemide. These results indicate that diuretics ameliorate the excretory function of both the stenotic kidney and the nonstenotic kidney and that the improvement of the kidney function is independent of prostaglandin. Furthermore, removal of the stenosis accentuates the beneficial effect of diuretics on the kidney.     

Influence of bacteriocin in the control of Escherichia coli infection of broiler chickens in Nigeria

One hundred broiler chickens were divided into four groups. Group A was untreated and challenged with E. coli 02:KH6; group B was infected and treated with bacteriocin in their drinking water; group C was infected and treated by administration of Lactobacillus plantarum F1 culture in skimmed milk, and group D acted as a control. Their weight, feed intake, clinical signs, microscopic lesions, E. coli re-isolation and serum biochemistry were compared. Groups B and C showed fewer symptoms and gross lesions than those from group A, while body weight and feed intakes were similar to the control group. E. coli 02:KH6 was re-isolated in 60% of the livers from group A, compared to 8 and 12% of the livers from group B and C respectively. There was significant increase in the levels of total protein (3.78 ± 0.05 g/100 ml) and globulins (2.53 ± 0.03 g/100 ml) in group A compared to groups B and C. The cholesterol levels in group A (112.56 ± 0.15 mg/100 ml) were significantly reduced compared to those of groups B and C which had 127.25 ± 0.14 and 128.73 ± 0.13 mg/100 ml respectively. The study provides evidence of the potential therapeutic efficacy of bacteriocin in the control of an experimental E. coli infection in broiler chickens.