Endotoxemia: an unnecessary but aggravating condition in portal hypertension?
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R Moreau
Publications and source records attributed to R Moreau.
Determinants of the Permethrin Impregnated Bednets (PIB) in the Republic of Benin: the role of women in the acquisition and utilization of PIBs.
An important aspect of malaria control strategies has been the use of prophylactic measures such as impregnated bednets; however, adoption of this strategy has been slow and uneven. This study considers the factors determining Permethrin Impregnated Bednets (PIB) use in the context of a PIB promotion project in a rural area of Benin undertaken between 1992 and 1995. Quantitative data, on socio-demographic characteristics, malaria knowledge, attitudes, and practices, were gathered from 191 households of PIB users and non-users for comparative purposes using a questionnaire format. Qualitative data were collected from 23 focus group discussion sessions and 16 semi structured interviews. Women's income, men's educational level, and women's participation in communal organizations were the principal variables distinguishing user households from non-user households. Recourse to non-western medicine and, in particular, to medicinal teas which are considered preventive or curative correlates negatively with PIB use. The qualitative data shows that informants consider exposure to the sun, especially while engaged in agriculture work, a principal cause of malaria, and that PIB adoption is not considered justified in a context where there is a quasi chronic shortage of financial resources and where confidence in the efficacy of non-western medicine prevails. Because they have primary responsibility for the health of their families and are more aware of children's vulnerability to malaria, women are more inclined than men to want to buy PIBs. However, because the household head, who is most often male, sets family consumption priorities using family income, women often have to resort to using their own income, which is often considerably lower than that of men, to buy PIBs. Support for community initiatives which are directed to women's work, linked with intensive effort to sensitize men to the mechanisms of malaria transmission and the principal groups at risk, is seen as a means to increase PIB acquisition and use.
Bedding and Linens↗
Heparin and high-density lipoprotein mediate bovine sperm capacitation by different mechanisms.
Capacitation is an important process in bovine sperm maturation and is an obligatory step prior to fertilization. Two capacitating agents, namely heparin and high-density lipoprotein (HDL), have been shown to induce sperm capacitation. A family of major proteins of bovine seminal plasma designated BSP-A1/A2, BSP-A3, and BSP-30 kDa (collectively called BSP proteins) bind to the sperm surface upon ejaculation via their membrane choline phospholipids. Our previous studies with bovine epididymal sperm showed that BSP proteins potentiate sperm capacitation induced by heparin and HDL. This study was undertaken to clarify the mechanism of capacitation induced by heparin and HDL in the presence of BSP proteins. Washed bovine ejaculated sperm were incubated with heparin (12 microg/ml) or HDL (10-160 microg/ml) in the presence of polyclonal antibodies against purified BSP proteins (anti-BSP proteins). The percentage of capacitated sperm was evaluated after the induction of the acrosome reaction (AR) with lysophosphatidylcholine. When sperm were incubated for 5 h with heparin and anti-BSP proteins (40 microg/ml), the AR level was not significantly different from control levels (16. 8 +/- 0.9% vs. 12.9 +/- 0.9%). In contrast, incubation of sperm for 8 h with HDL and anti-BSP proteins did not inhibit the AR (42.4 +/- 1.1% vs. 17.1 +/- 1.6 for the control samples). We also investigated the effect of heparin and HDL on protein tyrosine phosphorylation associated with capacitation. The tyrosine phosphorylation of a group of proteins was increased in the presence of heparin. However, HDL did not significantly stimulate protein phosphorylation. The increase in phosphorylation was correlated with an increase in the AR after the incubation with heparin but not with HDL. These results indicate that heparin and HDL mediate capacitation via different mechanisms.
1-Methyl-3-isobutylxanthine↗
Bovine seminal plasma phospholipid-binding proteins stimulate phospholipid efflux from epididymal sperm.
Several studies have shown that sperm capacitation was accompanied by a change in the lipid composition of the sperm membrane. In cattle, the major proteins of (bovine)seminal plasma (BSP proteins: BSP-A1/A2, BSP-A3, and BSP-30-kDa) potentiate sperm capacitation induced by high-density lipoprotein (HDL). Our recent studies indicate that these proteins and HDL stimulate sperm cholesterol efflux during capacitation. In order to gain more insight into the mechanisms of BSP-mediated sperm capacitation, we studied whether or not BSP proteins induce phospholipid efflux from epididymal sperm membrane. By direct determination of choline phospholipids on unlabeled epididymal sperm, the results show that sperm incubated in the presence of BSP-A1/A2 protein lost 34.4% of their choline phospholipids compared with the control (11.5%). Similar results were obtained using labeled epididymal sperm. Labeling was carried out by incubating washed epididymal sperm for 1 h with medium containing [(3)H]palmitic acid. The majority of the label was incorporated into sperm phosphatidylcholine. Studies of sperm phospholipid efflux were done by incubating the labeled sperm with purified BSP proteins, delipidated BSA, or bovine seminal ribonuclease (RNase, control protein). When labeled ([(3)H]phospholipid) epididymal sperm were incubated with BSP proteins (20-120 microg/ml) for 8 h, the sperm lost [(3)H]phospholipid in a dose-dependent manner (maximum efflux of approximately 30%). After the incubation with BSP proteins, the efflux particles were fractionated by size-exclusion chromatography. Analysis of the fractions obtained showed that the [(3)H]phospholipid was associated with BSP proteins. BSA (6 mg/ml) stimulated a specific phospholipid efflux of approximately 22%. In contrast, bovine RNase (120 microg/ml) did not stimulate phospholipid efflux. These results indicate that BSP proteins participate in the sperm cholesterol and phospholipid efflux that occurs during capacitation.
Animals↗
Relation between severity of liver disease and renal oxygen consumption in patients with cirrhosis.
BACKGROUND: Worsening cirrhosis may lead to increased renal O2 metabolism caused by activation of neurohumoral antinatriuretic substances. AIMS: To evaluate the relation between the severity of liver disease, sodium excretion, and neurohumoral antinatriuretic substances on the one hand and renal O2 metabolism on the other in patients with cirrhosis. METHODS: Renal O2 consumption and haemodynamics as well as plasma concentrations of noradrenaline, renin, and aldosterone were measured. Investigations were performed in 14 patients with Pugh's grade A, 43 with grade B, and 29 with grade C liver disease. RESULTS: Renal O2 consumption significantly increased with the severity of cirrhosis (grade A, 8.9 (1.6); grade B, 15.5 (1.3); grade C, 18.0 (1.5) ml/min/m2). Plasma concentrations of noradrenaline, renin, and aldosterone significantly increased while mean arterial presssure and systemic vascular resistance significantly decreased with the severity of the disease. A significant inverse correlation was found between renal O2 consumption and sodium excretion. A significant direct correlation was found between plasma levels of noradrenaline and aldosterone on the one hand and renal O2 consumption on the other. Renal blood flow and the glomerular filtration rate did not differ significantly between patients with grade C and grade A or B disease. CONCLUSIONS: This study shows for the first time that, in patients with cirrhosis, worsening of the disease is associated with an increase in renal O2 consumption. The results suggest that increased renal O2 consumption is due to renal tubular sodium retention caused by increased levels of neurohumoral antinatriuretic substances. This neurohumoral activation is related to cirrhosis induced vasodilation.
Adult↗
[Nitric oxide, vasodilatation and cirrhosis: a double (dys)equilibrium].
Explore the source record for details and available documents.
Animals↗
[Management of patients with cirrhosis and ascites].
Explore the source record for details and available documents.
Ascites↗
Pathophysiology of portal hypertension.
Explore the source record for details and available documents.
Blood Volume↗
Relationship between vascular reactivity in vitro and blood flows in rats with cirrhosis.
In cirrhosis there is a hyperdynamic circulation, which occurs mainly in the systemic and splanchnic regions. Using isolated-vessel models, previous studies have shown reduced aortic reactivity to vasoconstrictors in rats with cirrhosis. The aim of the present study was to evaluate and compare the vascular responsiveness to phenylephrine in arterial rings and the blood flows from different regions in rats with cirrhosis and controls. Reactivity was studied in isolated thoracic aortic, superior mesenteric arterial and carotid arterial rings from sham-operated and bile-duct-ligated rats by measuring the cumulative concentration-dependent tension induced by phenylephrine (10(-9)-10(-4) M). Blood flows were measured by the radioactive microsphere method. In rats with cirrhosis, a significant hyporeactivity to phenylephrine was observed in both the aorta and the superior mesenteric artery compared with the corresponding arteries of normal rats. This hyporesponsiveness was corrected by N(omega)-nitro-L-arginine (0.1 mM). In contrast, carotid artery reactivity and the responses to N(omega)-nitro-L-arginine were similar in the cirrhotic and control groups. In each case, cardiac output and mesenteric arterial blood flow were significantly higher in cirrhotic than in normal rats. Cerebral blood flows were not significantly different between the two groups. In cirrhotic rats, arterial hyporeactivity may be a consequence of increased regional blood flow and increased production of nitric oxide.
Animals↗
Cl- absorption across the thick ascending limb is not altered in cystic fibrosis mice. A role for a pseudo-CFTR Cl- channel.
The cortical thick ascending limb (CTAL) absorbs Cl- via a Na+-K+-Cl- cotransport at the apical membrane and several Cl- channels at the basolateral membrane, including a 9-pS channel having several properties of the cystic fibrosis transmembrane conductance regulator (CFTR). Having checked that CFTR mRNA is present in the mouse CTAL, we investigated whether this channel is a CFTR molecule by applying the patch-clamp technique to CTALs microdissected from CFTR knockout mice (cftrm1Unc). The 9-pS channel was active in cell-attached patches from tubules of mice homozygous for the disrupted cftr gene [CFTR (-/-)] at the same frequency and with the same activity (NPo) as in normal [CFTR (+/+)] or heterozygous [CFTR (+/-)] mice. The conductive properties of the channel, studied on inside-out patches, were identical in CFTR (-/-), CFTR (+/+), and CFTR (+/-) tubules, as were the sensitivities to internal pH and internal ATP, two typical features of this channel. In addition, the Cl- absorption in isolated, microperfused CTALs and the Na+-K+-Cl- cotransport activity were identical in CFTR (-/-), CFTR (+/+), and CFTR (+/-) mice. These results show that the 9-pS Cl- channel is distinct from CFTR, and that the CFTR protein has no influence on the Cl- absorption in this part of the renal tubule.
Adenosine Triphosphate↗
Fish acquired ascorbic acid synthesis prior to terrestrial vertebrate emergence.
Explore the source record for details and available documents.
Animals↗
Body pool and synthesis of ascorbic acid in adult sea lamprey (Petromyzon marinus): an agnathan fish with gulonolactone oxidase activity.
Although many vertebrates can synthesize ascorbic acid (vitamin C), it is still unclear from the evolutionary perspective when the ability to synthesize the vitamin first appeared in the animal kingdom and how frequently the trait has been lost. We report here ascorbic acid biosynthesis ability in sea lamprey (Petromyzon marinus) which represent the most ancient vertebrate lineage examined thus far for presence of gulonolactone oxidase, the enzyme catalyzing the terminal step in biosynthesis of vitamin C. This finding supports the view that the ancestors of living vertebrates were not scurvy prone and that the loss of gulonolactone oxidase activity subsequently occurred several times in vertebrate phylogeny. Adult sea lamprey allocate significant amounts of ascorbic acid to the gonads to guaranty high-quality gametes. Tissue stores of ascorbate were maintained by de novo synthesis (1.2-1.3 mg of ascorbic acid/300-g sea lamprey per day at 15 degrees C) while sea lamprey fast during spawning migration. We estimate that the in vivo daily renewal rate of ascorbate is 4-5% of the whole-body ascorbate pool based on measurement of its biosynthesis and concentration in the whole animal.
Journal Article↗
Type II domains of BSP-A1/-A2 proteins: binding properties, lipid efflux, and sperm capacitation potential.
Bovine seminal plasma contains a family of major proteins (collectively called 1BSP proteins) that potentiate sperm capacitation by binding to capacitation factors such as heparin and by stimulating sperm membrane cholesterol efflux. Here, we investigated the structure-function relationship of type II domains of BSP proteins. We isolated from a tryptic digest of citraconylated BSP-A1/-A2 proteins the intact second type II domain (domain b or Db). Similar to native protein, Db bound to heparin-Sepharose, p-aminophenylphosphorylcholine-Agarose and liposomes containing phosphatidylcholine. When assessed for biological function, Db did not stimulate cholesterol efflux from human fibroblasts, a cell model for lipid efflux studies, and from bovine spermatozoa, or potentiate bovine sperm capacitation induced by heparin and high-density lipoproteins. Therefore, type II motifs of BSP proteins represent binding units for sperm membrane choline phospholipids and heparin but the second type II domain of BSP-A1/-A2 alone is not sufficient to stimulate lipid efflux nor is sufficient to potentiate bovine sperm capacitation. Thus, the presence of both type II domains in BSP proteins is essential for the expression of functional properties, namely lipid efflux and sperm capacitation.
Amino Acid Sequence↗
Acute and chronic haemodynamic effects of naftazone in portal hypertensive rats.
It has been demonstrated that hyperproduction of nitric oxide (NO) plays a major role in the vasodilatation of cirrhosis; thus, the vasodilatation might be reversed by an inhibition of NO production. Experimental studies in isolated aortic rings showed that naftazone inhibits the effects of NO production. The aim of this study was to evaluate the haemodynamic effects of acute and chronic administration of naftazone in rats with portal hypertension. Haemodynamic values were measured either before and 10 min after intravenous administration of 432 microg/kg of naftazone or after 4 days of oral administration of 10 mg/kg per day. Acute administration of naftazone significantly reduced portal pressure in portal vein-stenosed and cirrhotic rats. This reduction was related to a decrease in the resistance of the liver and collateral circulation and it was associated with an increased cardiac output. Oral administration of naftazone significantly decreased portal pressure in rats with portal vein stenosis; this decrease depended on a significant reduction of portal blood flow. In both groups, arterial pressure did not change significantly. These haemodynamic effects differed from those observed following prazosin or propranolol administration. However, these effects were similar but less marked than those observed following N-nitro-L-arginine administration in systemic and splanchnic arterial territories. In conclusion, acute and oral administration of naftazone significantly reduces portal pressure by two different mechanisms in portal hypertensive rats. The exact mechanism has, however, to be elucidated.
Animals↗
Beneficial hemodynamic effects of bosentan, a mixed ET(A) and ET(B) receptor antagonist, in portal hypertensive rats.
In patients with cirrhosis, the plasma level of endothelin, a potent vasoconstrictor peptide, is elevated, and endothelin plays a role in increased intrahepatic vascular resistance. Thus, the aim of this study was to evaluate the hemodynamic effects of bosentan, a mixed ET(A) and ET(B) endothelin receptor antagonist in three models of portal hypertension. In all groups of rats, endothelin (2 microg/kg intravenously) administration significantly increased intrahepatic vascular resistance. In rats with secondary biliary cirrhosis, bosentan (30 mg/kg) significantly reduced portal pressure from 14.6 +/- 1.2 to 12.1 +/- 0.6 mm Hg, while portal blood flow and cardiac output increased by 45% and 57%, respectively. Thus, hepatocollateral vascular resistance decreased significantly from 177 +/- 19 to 101 +/- 9 dyn x s x cm(-5) x 10(-3). Similar results were observed in rats with CCl4-induced cirrhosis. In isolated perfused cirrhotic rat livers, bosentan (1 to 100 micromol/L) had no significant effect on hepatic vascular resistance. In portal vein-stenosed rats, bosentan administration significantly decreased portal pressure from 13.1 +/- 0.6 to 11.4 +/- 0.5 mm Hg by reducing portosystemic vascular resistance, because bosentan had no effect on vascular resistance of normal rat liver. In conclusion, bosentan administration decreased portal pressure in vivo by reducing hepatocollateral vascular resistance in rats with cirrhosis. Thus, mixed endothelin receptor antagonists might be a new approach in the pharmacological treatment of portal hypertension.
Animals↗
Effects of protein kinase C modulators on Na+/K+ adenosine triphosphatase activity and phosphorylation in aortae from rats with cirrhosis.
Protein kinase C (PKC) modulates the activity and phosphorylation of the catalytic alpha-subunit of sodium-potassium-adenosine triphosphatase (Na+/K+ ATPase) in normal arteries. Because PKC is altered in cirrhotic aortae, Na+/K+ ATPase may also be altered in these arteries. The aim of the present study was to investigate alpha-subunit activity and phosphorylation in aortae from normal and cirrhotic rats, under baseline conditions and during exposure to PKC modulators. Alpha-subunit activity was assessed by measuring the amount of 32P released by hydrolysis of [gamma-32P]ATP in freshly isolated cell membranes (in the absence of PKC modulators only) and membrane depolarization caused by ouabain-induced alpha-subunit inhibition in isolated aortae (in the absence and presence of PKC modulators). Alpha-subunit phosphorylation was assessed by incorporation of 32P into alpha-subunits. Staurosporine, a PKC inhibitor, and phorbol 12,13-dibutyrate (PDBU), a PKC activator, were used. In addition, alpha-subunit expression was studied by Western blot analysis. In the absence of PKC modulators, the amount of 32P released by hydrolysis of [gamma-32P]ATP and ouabain-induced membrane depolarization were significantly lower in cirrhotic than in normal aortae. Staurosporine suppressed ouabain-induced membrane depolarization in cirrhotic and normal arteries. Ouabain-induced membrane depolarization was similar in cirrhotic aortae exposed to PDBU and in normal arteries studied under baseline conditions. Alpha-subunit phosphorylation was significantly lower in cirrhotic than in normal aortae, in aortae under baseline conditions, and in arteries exposed to staurosporine. Phosphorylation of the alpha-subunit was similar in cirrhotic aortae exposed to PDBU and in normal arteries under baseline conditions. Western blot analysis showed that the amount of alpha-subunit did not significantly differ between cirrhotic and normal aortae. In conclusion, a decrease in baseline Na+/K+ ATPase alpha-subunit activity occurs in aortae from cirrhotic rats as a result of reduced basal PKC activity. This PKC-dependent decreased alpha-subunit activity may be caused by a reduction in PKC-induced alpha-subunit phosphorylation.
Animals↗
Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome.
BACKGROUND/AIMS: A treatment to induce a sustained increase in glomerular filtration rate in patients with hepatorenal syndrome has not yet been identified. Thus, the aim of the present study was to investigate the effects of terlipressin for 2 days on the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome. METHODS: A double-blind, cross-over randomized study was performed in nine patients. Patients received terlipressin (2 mg/day for 2 days) and a placebo for 2 days in a randomized order. RESULTS: Terlipressin administration significantly increased creatinine clearance (from 15+/-2 ml/min to 27+/-4 ml/min) and urine output (from 628+/-67 ml/day to 811+/-76 ml/day), but did not significantly change urinary sodium concentrations. Urinary sodium excretion was not significantly different after placebo administration (0.6+/-0.1 mmol/24 h) and terlipressin administration (9.3+/-7.2 mmol/24 h). Terlipressin administration significantly decreased plasma concentrations of renin and aldosterone but not atrial natriuretic peptide levels. Placebo elicited no significant effects. CONCLUSIONS: This study shows that 2-day terlipressin administration increases the glomerular filtration rate in patients with cirrhosis and hepatorenal syndrome.
Atrial Natriuretic Factor↗
Protein kinase C alterations in aortic vascular smooth muscle cells from rats with cirrhosis.
BACKGROUND/AIMS: Alterations in signal transduction in vascular smooth muscle cells may contribute to vascular hyporeactivity in cirrhosis. Protein kinase C plays a role in vascular cell contraction by modifying contractile proteins and intracellular [Ca2+] homeostasis. The aim of this study was to examine the vascular reactivity and expression of protein kinase Calpha in aortae from rats with cirrhosis. METHODS: The contractile response to phorbol ester, a protein kinase C activator, was evaluated in endothelium-denuded aortic rings from normal and cirrhotic rats. Protein kinase Calpha expression was determined by Western blot analysis. RESULTS: Maximal contraction was significantly less marked in cirrhotic (1.24+/-0.24 g) than in control (3.43+/-0.27 g) aortae. Phorbol myristate-acetate-induced contraction was dependent on extracellular [Ca2+] concentrations, as shown by a reduction in maximal contraction when control and cirrhotic aortic rings were exposed to a Ca2+-free medium. Increasing the intracellular [Ca2+], by incubation with a Ca2+ ionophore, significantly increased the maximal contraction induced by phorbol myristate-acetate in cirrhotic but not in control rat aortae. Protein kinase Calpha expression was significantly lower in aortae in cirrhotic than in control rats. CONCLUSION: These results confirm alterations in protein kinase C in aortae from cirrhotic rats.
Animals↗