AT2-antagonist sensitive potentiation of angiotensin II-induced vasoconstrictions by blockade of nitric oxide synthesis in rat renal vasculature

1. Although the actions of angiotensin II (Ang II) on renal haemodynamics appear to be mediated by activation of the AT1 receptor subtype, AT2 binding sites have also been evidenced in the adult kidney vasculature. As NO is known to mask part of the renal effects of vasoconstrictor drugs, we queried whether the Ang II-induced vasoconstrictions could occur via multiple receptor subtypes during inhibition of NO synthesis. We explored the effect of AT1 and AT2 receptor (AT-R) antagonists on Ang II-induced pressure increases during NO synthase or soluble guanylyl cyclase inhibition in rat isolated kidneys perfused in the presence of indomethacin at constant flow in a single-pass circuit. 2. In the absence of NO blockade, the AT1-R antagonist L-158809 (500 nM) antagonized the Ang II-induced vasoconstrictions, while the AT2-R antagonist PD-123319 (500 nM) had no effect. 3. Perfusing kidneys in the presence of either NO synthase inhibitors, L-NAME (100 microM) or L-NOARG (1 mM), or soluble guanylyl cyclase inhibitor, LY-83583 (10 microM), significantly increased both molar pD2 (from 9.40+/-0.25 to 10.36+/-0.11) and Emax values (from 24.9+/-3.1 to 79.9+/-4.9 mmHg) of the concentration-response curve for Ang II-induced vasoconstriction. 4. In the presence of L-NAME, 500 nM L158809 abolished the Ang II-induced vasoconstrictions whatever the concentration tested. On the other hand, 500 nM PD-123319 reversed the left shift of the concentration-response curve for Ang II (molar pD2 value 9.72+/-0.13) leaving Emax value unaffected (91.3+/-7.6 mmHg). 5. In the presence of L-NAME, the potentiated vasoconstriction induced by 0.1 nM and the augmented vasoconstriction induced by 10 nM Ang II were fully inhibited in a concentration-dependent manner by L-158809 (0.05-500 nM). By contrast, PD-123319 (0.5-500 nM) did not affect the 10 nM Ang II-induced vasoconstriction and concentration-dependently decreased the 0.1 nM Ang II-induced vasoconstriction plateauing at 65% inhibition above 5 nM antagonist. 6. Similar to PD-123319, during NO blockade the AT2-R antagonist CGP-42112A at 5 nM decreased by 50% the 0.1 nM Ang II-induced vasoconstriction and at 500 nM had no effect on 10 nM Ang II-induced vasoconstriction. 7. In conclusion, the renal Ang II-induced vasoconstriction, which is antagonized only by AT1-R antagonist in the presence of endogenous NO, becomes sensitive to both AT1- and AT2-R antagonists during NO synthesis inhibition. While AT1-R antagonist inhibited both L-NAME-potentiated and -augmented components of Ang II-induced vasoconstriction, AT2-R antagonists inhibited only the L-NAME-potentiated component.     

Effect of substrate adaptation on the microbial fermentation and microbial composition of faecal microbiota of weaning piglets studied in vitro

The in vitro cumulative gas production technique can be used to assess microbial activity of a complex community, in relation to fermentation of a particular energy source. Therefore, in combination with an in vivo study to examine the effects of two different diets for weaning piglets, microbial activities of faeces were compared from animals on the two different diets. The two diets were: CHO diet [containing added fermentable carbohydrates, including sugarbeet pulp (SBP) and wheat starch (WST)], and control diet without any added fermentable carbohydrates. Neither diet contained antibiotics or extra added copper. Twenty‐four piglets were selected from 12 litters (two per litter), weaned at 4 weeks of age (neither creep feeding nor any antibiotic treatment before and during the study), and introduced to one of the two diets. After 9 days on the diet, faecal samples were collected from selected animals, and tested for their activity in terms of gas production kinetics, and end‐products such as volatile fatty acids, ammonia and dry matter disappearance of the two test substrates SBP and WST. The bacterial diversity was also analysed before and after in vitro fermentation using denaturing gradient gel electrophoresis analysis of amplified 16S rRNA genes. There were differences both in kinetics and end‐products of the substrates. More interestingly, significant differences were detected between inocula, although mainly in terms of fermentation kinetics of the two substrates. With the CHO inoculum, SBP was fermented faster than with the control, while this effect was reversed for WST. Significantly higher diversity, as measured by DGGE fingerprint analysis, was detected in the microbial community enrichment on SBP as compared with WST at the end of fermentation. The difference between the kinetics of SBP compared with WST fermentation by faecal microbiota from the CHO diet fed piglets suggests better adaptation to SBP fermentation than to WST fermentation. The WST fermentation was more unexpected, given that a significant amount of starch is known to be fermentable by the small intestinal microbiota. It was concluded that the microbial community composition and activity in the GIT may be changed in response to diet, and that this change can be detected in vitro. Copyright © 2005 Society of Chemical Industry     

Helical-core ytterbium-doped fibre laser

An Yb-doped fibre laser with a helical core trajectory in the cladding material has been demonstrated for the first time. The laser yields 350 mW of linearly-polarised, single-spatial-mode output at 1047 nm from a multimode core of diameter, 26 /spl mu/m, and numerical aperture, 0.14, when core-pumped by an Yb:YAG laser at 1030 nm.     

A simple energy recovery circuit for high-power inverters with complete turn-on and turn-off snubbers

This paper presents and analyzes an active energy recovery circuit for the inductive turn-on snubber and capacitive turn-off snubber used on high-power gate-turn-off thyristor inverters. The circuit performs as a simple switched-mode power supply and recovers the inductive and capacitive snubbers energy induced in power inverters back into the dc rail with the aid of an extra switch. The features and operation of the proposed circuit are given and supported by PSpice simulations and experimental results.     

Evaluation of Bilayer Tablet Machines—A Case Study

Four bilayer tablet compression machines were evaluated for their suitability for compression of a specific bilayer tablet formulation. Tablet machines evaluated were: Manesty (Model No. BB4), Manesty (Model No. Rotappress), Fette (Model No. P3102) and Kilian (Model No. 51AST-ZS) tablet presses. The tablet delamination tendency was the primary acceptance criteria for the evaluation of tablet press performance. The compression force on layer I was found to be the major factor influencing tablet delamination. It was found that the Kilian press was best suited for the compression of the model bilayer tablet formulation. The Kilian press is equipped with a special sampling device for layer I which allows additional compression force to be applied on layer I only at the time of weight sampling. The sampling device then returns to the original set points after sampling is completed. This feature maintains the compression force on layer I to a minimum during routine compression. Data indicated that the compression force on layer I and the compression zone in the die cavity of layer II were two factors needing to be controlled in order to yield bilayer tablets with acceptable physical characteristics.     

Complement C6 and C2 biosynthesis in syngeneic PVG/c- and PVG/c+ rat strains

A PVG rat with total deficiency of C6 and partial deficiency of C2 (PVG/c-), and a syngeneic control strain (PVG/c+), were used to study the production of extrahepatically synthesized complement. Livers of complement deficient rats were transplanted in sufficient rats (Tx-L). The C6 and C2 levels in Tx-L rats declined within 2 days to 25% and 30%, respectively, and remained stable for more than 6 weeks. To investigate the contribution of C6 synthesis by the liver, C6 sufficient livers were grafted in deficient rats (Tx + 1). After an initial increase, with maximum C6 levels of 119% at 10 days following transplantation, the C6 levels decreased gradually and C6 was no longer detectable 28 days after transplantation. This decline in C6 levels was dependent on antibody production against C6. No significant change in the C3, C4, factor H and factor B levels was observed. Expression of C6 mRNA in the grafted PVG/c+ sufficient liver was comparable to the expression of C6 mRNA in control PVG/c+ livers while C6 mRNA expression in the transplanted PVG/ c- liver and the control PVG/c- liver was lower. In conclusion, it was demonstrated in vivo that not only C6 but also C2 is synthesized extrahepatically in PVG/c rats.     

A candidate Ross River virus vaccine: preclinical evaluation

A killed Ross River virus vaccine is being developed in an effort to prevent the, ca 5000 cases of epidemic polyarthritis which occur in Australia each year. The symptoms of epidemic polyarthritis commonly last 30-40 weeks and 25% of patients have symptoms for a year or more. There is no cure. Although there was some strain to strain variation, particularly after a single injection, outbred and inbred strains of mice all produced significant levels of anti-Ross River virus antibody after intramuscular (i.m.) injection with 24 h BEI inactivated, sucrose gradient purified, Ross River virus vaccine. Mice immunized i.m. with two 20 micrograms doses of vaccine or live virus produced similar levels of neutralizing antibody but the reaction of IgG 2a and IgG 2b antibody from these two groups of mice to Ross River virus proteins in western blots differed. Antibody from BALB/c mice immunized with this vaccine neutralized all strains of Ross River virus tested, in vitro, albeit to different degrees.     

Adrenomedullary secretion of epinephrine is increased in mild essential hypertension

To assess whether patients with mild essential hypertension have excessive activities of the sympathoneuronal and adrenomedullary systems, we examined total body and forearm spillovers and norepinephrine and epinephrine clearances in 47 subjects with mild essential hypertension (25 men, 22 women, aged 38.1 +/- 6.7 years) and 43 normotensive subjects (19 men, 24 women, aged 36.5 +/- 5.9 years). The isotope dilution method with infusions of tritiated norepinephrine and epinephrine was used at rest and during sympathetic stimulation by lower body negative pressure at -15 and -40 mm Hg. Hypertensive subjects had a higher arterial plasma epinephrine concentration (0.20 +/- 0.01 nmol.L-1: mean +/- SE) than normotensive subjects (0.15 +/- 0.01) (P < .01). The increased arterial plasma epinephrine levels appeared to be due to a higher total body epinephrine spillover rate in the hypertensive subjects (0.23 +/- 0.02 nmol.min-1.m-2) than the normotensive subjects (0.18 +/- 0.01) (P < .05) and not to a decreased plasma clearance of epinephrine. The arterial plasma norepinephrine level, total body and forearm norepinephrine spillover rates, and plasma norepinephrine clearance were not altered in the hypertensive subjects. The responses of the catecholamine kinetic variables to lower body negative pressure were not consistently different between normotensive and hypertensive individuals. These data indicate that individuals with mild essential hypertension (1) have elevated arterial plasma epinephrine concentrations that are due to an increased total body epinephrine spillover rate, indicating an increased adrenomedullary secretion of epinephrine; (2) have no increased generalized sympathoneuronal activity and no increased forearm norepinephrine spillover; and (3) have similar responses of both the sympathoneuronal and adrenomedullary systems to sympathetic stimulation by lower body negative pressure.     

The Internet versus the telephone: What is telehealth anyway?

How extensive is health care service delivery via the Internet? Should all practicing professional psychologists immediately acquire audio and video Internet capability so they can interact with their patients via this modality? Five hundred and ninety-six practicing psychologists responded to a survey about their use of the telephone and the Internet in their professional practices. Use of the telephone in the delivery of clinical services was nearly universal. However, only 2% of respondents had utilized the Internet or satellite technology in the delivery of health care. Nonetheless, routine use of such technology in service delivery is expected to increase as the technology becomes more universally available and regularly used. (PsycINFO Database Record (c) 2010 APA, all rights reserved)