Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats

Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

Background: Nitric oxide (NO) synthesis has been described in several circumventricular and hypothalamic structures in the central nervous system that are implicated in mediating central angiotensin-II (ANG-II) actions during water deprivation and hypovolemia. Neuroendocrine and cardiovascular responses, drinking behavior, and urinary excretions were examined following central angiotensinergic stimulation in awake freely-moving rats pretreated with intracerebroventricular injections of N omega-nitro-L-arginine methyl ester (L-NAME, 40 mu g), an inhibitor of NO synthase, and L-arginine (20 ug), a precursor of NO. Results: Injections of L-NAME or ANG-II produced an increase in plasma vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) levels, an increase in water and sodium intake, mean arterial blood pressure and sodium excretion, and a reduction of urinary volume. L-NAME pretreatment enhanced the ANG-II response, while L-arginine attenuated VP and OT release, thirst, appetite for sodium, antidiuresis, and natriuresis, as well as pressor responses induced by ANG-II. Discussion and conclusion: Thus, the central nitrergic system participates in the angiotensinergic responses evoked by water deprivation and hypovolemia to refrain neurohypophysial secretion, hydromineral balance, and blood pressure homeostasis.

Dietary salt restriction increases plasma lipoprotein and inflammatory marker concentrations in hypertensive patients

Background: Dietary salt restriction has been reported to adversely modify the plasma lipoprotein profile in hypertensive and in normotensive subjects. We investigated the effects of the low sodium intake (LSI) on the plasma lipoprotein profile and on inflammation and thrombosis biomarkers during the fasting and postprandial periods. Methods: Non-obese, non-treated hypertensive adults (n=41) were fed strictly controlled diets. An initial week on a control diet (CID, Na=160 mmol/day) was followed by 3 weeks on LSI (Na=60mmol/day). At admission and on the last day of each period, the 24-h ambulatory blood pressure was monitored and blood was drawn after an overnight fasting period and after a fat-rich test meal. Results: The dietary adherence was confirmed by 24-h urinary sodium excretion. Fasting triglyceride (TG), chylomicron-cholesterol, hsC-reactive protein (CRP), tumor necrosis factor-a (TNF-alpha). interleukin-6 (IL-6) concentrations, renin activity, aldosterone, insulin, and homeostasis model assessment insulin resistance (HOMA-IR) Values were higher, but non-esterified fatty acids (NEFA) were lower on LSI than on CD. For LSI, areas under the curve (AUC) of TG, chylomicron-cholesterol, apoB and the cholesterol/apoB ratio were increased, whereas AUC-NEFA was lowered. LSI did not modify body weight, hematocrit, fasting plasma cholesterol, glucose, adiponectin, leptin, fibrinogen and factor VII (FVII), and AUC of lipoprotein lipase and of lipoprotein remnants. Conclusion: LSI induced alterations in the plasma lipoproteins and in inflammatory markers that are common features of the metabolic syndrome. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system

A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy, Blood pressure, heart rate, fetuses and dams` body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the US group than in the NS and HS groups. The PRA was greater in IS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of angiotensins I and II were lower in the HS group than in the ISIS and IS groups. Placental angiotensin receptor type 1 (AT(1)) gene expression and levels of thiobarbituric acid reactive substances (TBARS) were higher in HS dams, as were uterine blood flow and cardiac output. The degree of salt intake did not influence plasma sodium, potassium or creatinine. Although fractional sodium excretion was higher in HS dams than in NS and LS dams, fractional potassium excretion was unchanged. In conclusion, findings from this study indicate that the reduction in fetal weight in response to salt restriction during pregnancy does not involve alterations in uterine-placental perfusion or the RAS. Moreover, no change in fetal weight is observed in response to salt overload during pregnancy. However, salt overload did lead to an increase in placental weight and uterine blood flow associated with alterations in maternal plasma and placental RAS. Therefore, these findings indicate that changes in salt intake during pregnancy lead to alterations in uterine-placental perfusion and fetal growth. (C) 2008 Elsevier Inc. All rights reserved.

Neonatal Handling Reduces Renal Function in Adult Rats

Background/Aims: To evaluate the effects of neonatal handling on hydroelectrolytic balance in adult rats. Methods: The litters were divided into two groups: nonhandled and handled. The procedure consisted of handling the pups for 1 min/day in the first 10 days postnatally. When adults, animals had their body weight verified and were housed in individual metabolic cages. After a 24-hour period, urine samples were collected and the urinary and water intake volumes measured. Blood samples to determine osmolality, aldosterone, corticosterone, angiotensin II, creatinine, urea, sodium and potassium levels were collected. The kidneys were removed for histological assessment. Urinary osmolality, sodium, urea and creatinine were also measured and the creatinine clearance (CC) calculated. Results: No difference between groups was found in the body weight. Handled animals showed a reduction in the total kidney wet weight, water intake, urinary volume, CC, plasma angiotensin II, corticosterone and aldosterone when compared to the nonhandled and an increase in the urinary osmolality and sodium excretion fraction. No differences in serum potassium and no evidence of structural changes were demonstrated by histological analysis. Conclusion: Neonatal handling induced long-lasting effects decreasing renal function without evidence of kidney structural changes. Copyright (c) 2009 S. Karger AG, Basel

Dipeptidyl peptidase IV inhibition downregulates Na(+)-H(+) exchanger NHE3 in rat renal proximal tubule

In the microvillar microdomain of the kidney brush border, sodium hydrogen exchanger type 3 (NHE3) exists in physical complexes with the serine protease dipeptidyl peptidase IV (DPPIV). The purpose of this study was to explore the functional relationship between NHE3 and DPPIV in the intact proximal tubule in vivo. To this end, male Wistar rats were treated with an injection of the reversible DPPIV inhibitor Lys [Z(NO(2))]-pyrrolidide (I40; 60 mg center dot kg(-1)center dot day(-1) ip) for 7 days. Rats injected with equal amounts of the noninhibitory compound Lys[ Z(NO(2))]-OH served as controls. Na(+) -H(+) exchange activity in isolated microvillar membrane vesicles was 45 +/- 5% decreased in rats treated with I40. Membrane fractionation studies using isopycnic centrifugation revealed that I40 provoked redistribution of NHE3 along with a small fraction of DPPIV from the apical enriched microvillar membranes to the intermicrovillar microdomain of the brush border. I40 significantly increased urine output ( 67 +/- 9%; P < 0.01), fractional sodium excretion ( 63 +/- 7%; P < 0.01), as well as lithium clearance ( 81 +/- 9%; P < 0.01), an index of end-proximal tubule delivery. Although not significant, a tendency toward decreased blood pressure and plasma pH/HCO(3)(-) was noted in I40-treated rats. These findings indicate that inhibition of DPPIV catalytic activity is associated with inhibition of NHE3-mediated NaHCO(3) reabsorption in rat renal proximal tubule. Inhibition of apical Na(+) -H(+) exchange is due to reduced abundance of NHE3 protein in the microvillar microdomain of the kidney brush border. Moreover, this study demonstrates a physiologically significant interaction between NHE3 and DPPIV in the intact proximal tubule in vivo.

Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats

Objectives The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). Methods Sitagliptin (40 mg/kg twice daily) was given by oral gavage to young (Y-SHR + IDPPIV) and adult (A-SHR R IDPPIV) SHRs for 8 days. Kidney function was assessed daily and compared with age-matched vehicle-treated SHR (Y-SHR and A-SHR) and with normotensive Wistar-Kyoto rats (Y-WKY and A-WKY). Arterial blood pressure was measured in these animals at the end of the experimental protocol. Additionally, Na(+)/H(+) exchanger isoform 3 (NHE3) function and expression in microvilli membrane vesicles were assessed in young animals. Results Mean arterial blood pressure of Y-SHR + IDPPIV was significantly lower than that of Y-SHR (104 +/- 3 vs. 123 +/- 5 mmHg, P < 0.01) and was similar to Y-WKY (94 +/- 4 mmHg, P > 0.05). Compared to Y-SHR, Y-SHR + IDPPIV exhibited enhanced cumulative urinary flow and sodium excretion and decreased NHE3 activity and expression in proximal tubule microvilli. In the A-SHR, sitagliptin treatment had no significant effect on either renal function or arterial blood pressure. Conclusion Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule. J Hypertens 29:520-528 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Na(+), K(+)-ATPase activity in gill microsomes from the blue crab, Callinectes danae, acclimated to low salinity: Novel perspectives on ammonia excretion

This investigation provides an extensive characterization of the modulation by ATP, Mg(2+), Na(+), K(+) and NH(4)(+) of a gill microsomal (Na(+),K(+))-ATPase from Callinectes danae acclimated to 15 parts per thousand salinity. Novel findings are the lack of high-affinity ATP-binding sites and a 10-fold increase in enzyme affinity for K(+) modulated by NH4+, discussed regarding NH4+ excretion in benthic marine crabs. The (Na(+),K(+))-ATPase hydrolyzed ATP at a maximum rate of 298.7 +/- 16.7 nmol Pi min(-1) mg(-1) and K(0.5) = 174.2 +/- 9.8 mmol L(-1) obeying cooperative kinetics (n(H) = 1.2). Stimulation by sodium (V = 308.9 +/- 15.7 nmol Pi min(-1) mg(-1), K(0.5) = 7.8 +/- 0.4 mmol L(-1)), magnesium (299.2 +/- 14.1 nmol Pi min(-1) mg(-1), K(0.5) = 767.3 +/- 36.1 mmol L(-1)), potassium (300.6 +/- 153 nmol Pi min(-1) mg(-1), K(0.5) = 1.6 +/- 0.08 mmol L(-1)) and ammonium (V = 345.1 +/- 19.0 nmol Pi min(-1) mg(-1), K(0.5) = 6.0 +/- 0.3 mmol L(-1)) ions showed site-site interactions. Ouabain inhibited (Na(+),K(+))-ATPase activity with K(1) = 45.1 +/- 2.5 mu mol L(-1), although affinity for the inhibitor increased (K(1) = 22.7 +/- 1.1 mu mol L(-1)) in 50 mmol L(-1) NH(4)(+). Inhibition assays using ouabain plus oligomycin or ethacrynic acid suggest mitochondrial F(0)F(1)- and K(+)-ATPase activities, respectively. Ammonium and potassium ions synergistically stimulated specific activity up to 72%, inferring that these ions bind to different sites on the enzyme molecule, each modulating stimulation by the other. (C) 2009 Elsevier Inc. All rights reserved.

Evaluation of hepatobiliary excretion and enterobiliary reflux in rats with biliary obstruction submitted to bilioduodenal or biliojejunal anastomosis

Bilioduodenal and biliojejunal anastomoses are effective for the treatment of biliary obstruction. The objective of this study was to compare the effects of these anastomoses on hepatobiliary excretion and enterobiliary reflux. Enterobiliary reflux and biliary excretion were evaluated respectively after oral administration of technetium (Tc-99m) in combination with sodium phytate and intravenous infusion of Tc-99m with diisopropyl-iminodiacetic acid. Enterobiliary reflux occurred to an equal degree in the bilioduodenal and biliojejunal groups. Maximum hepatic activity time (T-max) and radiotracer clearance half-time (T-1/2) were similar in both groups. However, when compared with that found for the sham-operated group, T-max, and T-1/2 were higher in the biliojejunal group (P = 0.02 and P = 0.01, respectively). Histopathological analysis showed marked reduction in ductal proliferation in both groups. These data undermine the theoretical advantages attributed to biliojejunal anastomosis and further the understanding of the pathophysiology of cholangitis that occurs even with patent anastomosis.

Bioavailability of fluoride administered as sodium fluoride or monofluorophosphate to humans

A double-bind cross-over study was conducted on four healthy subjects, aged 19-29 years, in order to determine the relative bioavailability and other pharmacokinetics features of fluoride (F) after single oral administration in fasting conditions of 2 mg F as sodium F (NaF) or sodium monofluorophosphate (MFP). The bioavailability was evaluated on the basis of the plasma levels and of the urinary excretion of F. Blood was sampled before and during the 8 h after the administration of the test solutions. For F excretion urine was sampled 12 h before the study and over the 8 h after the administration. Data were tested for statistically significant differences by ANOVA and Tukey`s post hoc tests, and also by Student`s t-test (p < 0.05). For the two formulations, the pharmacokinetics of F in plasma was characterized by a rapid absorption and by a peak (C-max = 0.1 mu g/mL) which was reached 20 min after administration, followed by a biphasic elimination. In the 8 h following the administration the urinary excretion of F accounted for 35-41% of the administered dose, without significant differences between the two formulations. The AUCs (+/- S.D.) for NaF and MFP were 21.15 (+/- 0.58) and 19.04 (+/- 1.75) min mu g mL(-1), respectively, and were not significantly different (p = 0.079). Based on the AUC and C-max of F in plasma and on the urinary excretion of F during the 8 h following administration, the relative bioavailabilities of the two F formulations were equivalent. (c) 2008 Elsevier B.V. All rights reserved.

Comparison of physical and mechanical properties of microwave-polymerized acrylic resin after disinfection in sodium hypochlorite solutions

This study evaluated the color stability, surface roughness and flexural strength of a microwave-polymerized acrylic resin after immersion in sodium hypochlorite (NaOCl), simulating 20 min of disinfection daily during 180 days. Forty disk-shaped (15 x 4 mm) and 40 rectangular (65 x 10 x 3 mm) specimens were prepared with a microwave-polymerized acrylic resin (Onda-Cryl). Specimens were immersed in either 0.5% NaOCl, 1% NaOCl, Clorox/Calgon and distilled water (control). Color measurements were determined by a portable colorimeter. Three parallel lines, separated by 1.0 mm, were registered on each specimen before and after immersion procedures to analyze the surface roughness. The flexural strength was measured using a 3-point bending test in a universal testing machine with a 50 kgf load cell and a crosshead speed of 1 mm/min. Data were analyzed statistically by ANOVA and Tukey's test (?=0.05). There was no statistically significant differences (p>0.05) among the solutions for color, surface roughness and flexural strength. It may be concluded that immersion in NaOCl solutions simulating short-term daily use during 180 days did not influence the color stability, surface roughness and flexural strength of a microwave-polymerized acrylic resin.

Influence of sodium hypochlorite and edta on the microtensile bond strength of a self-etching adhesive system

Chemical substances used during biomechanical preparation of root canals can alter the composition of dentin surface and affect the interaction with restorative materials. OBJECTIVE: The purpose of this study was to evaluate the microtensile bond strength (µTBS) of a self-etching adhesive system to dentin irrigated with sodium hypochlorite (NaOCl) and ethylenediaminetetraacetic acid (EDTA). MATERIAL AND METHODS: Thirty human third molars were sectioned 3 mm below the occlusal surface, polished with 600- to 1200-grit silicon carbide papers, and randomly divided into 3 groups: G1 (control): no irrigating solution; G2: 1% NaOCl; and G3: 1% NaOCl followed by the application of 17% EDTA. The specimens received the self-etching adhesive system (XENO III - Dentsply), restored with microhybrid composite resin (Z250 - 3M ESPE), sectioned and trimmed to create 4 hourglass-shaped slabs of each tooth. The slabs were tested in microtensile strength in a universal testing machine (Emic DL 2000) at a crosshead speed of 0.5 mm/min until fracture. The results were analyzed statistically by ANOVA and Newman-Keuls test. RESULTS: Mean µTBS values and standard deviations in MPa were: G1 = 11.89 ± 4.22; G2 = 19.41 ± 5.32; G3 = 11.34 ± 4.73. 1% NaOCl increased the adhesive resistance significantly (p<0.001/F=22.5763). The application of 1% NaOCl/17% EDTA resulted in statistically similar µTBS to the control group. CONCLUSIONS: None of the irrigants affected negatively the µTBS of XENO III to dentin. The use of 1% NaOCl alone resulted in higher bond strength than the other treatments. The combination of 1% NaOCl and 17% EDTA produced similar bond strength to that of untreated dentin.

Shelf-life of a 2.5% sodium hypochlorite solution as determined by arrhenius equation

Accelerated stability tests are indicated to assess, within a short time, the degree of chemical degradation that may affect an active substance, either alone or in a formula, under normal storage conditions. This method is based on increased stress conditions to accelerate the rate of chemical degradation. Based on the equation of the straight line obtained as a function of the reaction order (at 50 and 70 ºC) and using Arrhenius equation, the speed of the reaction was calculated for the temperature of 20 ºC (normal storage conditions). This model of accelerated stability test makes it possible to predict the chemical stability of any active substance at any given moment, as long as the method to quantify the chemical substance is available. As an example of the applicability of Arrhenius equation in accelerated stability tests, a 2.5% sodium hypochlorite solution was analyzed due to its chemical instability. Iodometric titration was used to quantify free residual chlorine in the solutions. Based on data obtained keeping this solution at 50 and 70 ºC, using Arrhenius equation and considering 2.0% of free residual chlorine as the minimum acceptable threshold, the shelf-life was equal to 166 days at 20 ºC. This model, however, makes it possible to calculate shelf-life at any other given temperature.

Rheology of decane/water and triglyceride/water emulsions stabilized by β-casein and sodium caseinate

β-Casein and sodium caseinate stabilized emulsions were produced and had their rheological properties investigated as a function of the nature of the oil phase, ionic strength and pH. Oil phases of distinct structural characteristics, namely decane and vegetable oil of high triglyceride content, were assayed. The former was much more effectively emulsified than the latter. Effects of pH and ionic strength were minor. Emulsion rheological properties were strikingly distinct in each case, with viscoelastic, solid-like structures being formed with decane (G' >> G"), differently from what is observed for samples containing triglycerides as the oil phase, in which viscoelasticity was not even apparent. The relevance of the spatial features of the oil phase structure in the development of the emulsion viscoelastic character is discussed. Factors responding for the system distinct behaviour possibly reside at the emulsion droplet interface, unapproachable by optical microscopy, rather than on aspects related to particle size or shape.

Productive performance and milk protein fraction composition of dairy cows supplemented with sodium monensin

The objective of this work was to evaluate the levels of sodium monensin on lactating cows and their effects on productive performance and milk protein fraction composition. It was used 12 Holstein cows, distributed in four balanced 3 × 3 Latin squares, and fed three diets: one control without monensin, and two diets with monensin at the levels of 24 or 48 mg/kg DM added to the concentrate. Milk production was daily measured throughout the entire experimental period. The samples used for analysis of milk composition were collected on two alternated days from the two daily milking. Non-protein nitrogen, total nitrogen and non-casein nitrogen contents were directly evaluated in the milk, and casein, whey protein and true protein contents were indirectly determined. The use of monensin in the rations reduced dry matter and nutrient intake, especially when diet with 48 mg/kg of dry matter was given. The ration with 24 mg/kg of DM increased milk production, with or without correction, and also fat and lactose yield, and it improved productive efficiency. The levels of monensin in the ratios did not influence contents of milk crude protein, non-protein nitrogen, non-casein nitrogen, true protein, casein, casein/true protein ratio, whey protein, and of all those fractions expressed as percentage of crude protein. The utilization of monensin in the ratio at the dose of 24 mg/kg of DM influences positively the productive performance of lactating cows, and it does not influence the composition of milk protein fractions.