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G Cros

Publications and source records attributed to G Cros.

At least 19 recordsLinked to original sources
PubMed2006

Methanol extract of Terminalia superba induces endothelium-independent relaxation of rat thoracic aorta.

Terminalia superba is highly regarded in some parts of Cameroon in traditional medical practice. We have studied the vasorelaxant effects of the stem bark methanol extract of T. superba on rat vascular smooth muscle. The results demonstrated that T. superba extract provoked a time-dependent relaxation of aortic rings precontracted with norepinephrine (10(-6) M). The vasorelaxant effect of the plant extract was not affected by endothelium removal or by pretreatment with indomethacin or N(W)-nitro-Larginine methyl ester (L-NAME). T. superba extract did not significantly, affect the contraction induced by 30 mM or 60 mM KCl as compared to those induced by NE. Relaxations elicited by T. superba extract were markedly reduced by glibenclamide, a putative blocker for K(ATP) channels and by tetraethylammonium, the non-specific K+ channel inhibitor. T. superba caused a time- and concentration-dependent relaxation of the rat aortic rings that were inhibited by charybdotoxin and iberotoxin but not by apamin. These finding indicate that T. superba extract at least partially relaxes the rat aorta by activating K+ channels, mainly KATP channels and large-conductance Ca2+ -activated K+ channels in rat aorta.

Animals↗
PubMed2002

Influence of food and diabetes on pharmacokinetics of sodium tungstate in rat.

In this paper, the influence of food and diabetes on the pharmacokinetics of sodium tungstate in rat was investigated. The compound was administered intravenously (9 mg/kg) and orally in the form of solution (36 mg/kg). An empirical Bayes methodology was used to compute individual pharmacokinetic parameters. Sodium tungstate followed first-order kinetics, and plasma concentration versus time data were described by a two-compartment model. A significant relationship was found between the bioavailability and the status of the animals. Total plasma clearance and elimination half-life averaged 3.1 ml/min/kg and 1.6 h, respectively. Food had some effects on the extent of sodium tungstate absorption. After oral administration, the bioavailability (0.67 versus 0.85), C(max) (6.10 versus 15.2 microg/ml) and AUC (70.7 versus 105 mgh/l) were 20, 60 and 32% lower in fed than in fasted rats, respectively. The presence of cellulose and sulphate anions in rat chow could partially explain the fed state-associated reduction of tungstate bioavailability. In streptozotocin-induced diabetic fed rats, a 25% decrease occurred in AUC and F, and a 14% increase occurred in the elimination rate constant compared with healthy fed rats. These changes could be explain on the one hand, by the increase of liquid consumption and food intake, and on the other hand, by a gastroparesis in the early diabetic rats.

Animals↗
PubMed2001

Effects of the aqueous and methylene chloride extracts of Bidens pilosa leaf on fructose-hypertensive rats.

We investigated the effects of the aqueous (150-350 mg/kg) and methylene chloride (150-300 mg/kg) extracts of Bidens pilosa on fructose-induced hypertension in rats. Food and liquid intake were measured as well as systolic blood pressure and plasma levels of glucose, insulin, cholesterol, triglycerides and creatinine. Fructose feeding for 6 weeks induced hypertension, hyperinsulinemia and increased plasma triglyceride levels in male Wistar rats. The aqueous and methylene chloride extracts of B. pilosa reversed the high blood pressure and hypertriglyceridemia developed due to fructose feeding but did not have any effects on plasma levels of insulin and glucose. High doses of the extracts reduced plasma creatinine levels and tended to increase plasma cholesterol. These results suggest that the extracts of B. pilosa possess hypotensive effects whose mechanism of action is not related to insulin sensitivity.

Animals↗
PubMed2001

Estimation of pharmacokinetic parameters of sodium tungstate after multiple-dose during preclinical studies in beagle dogs.

In this paper, an empirical Bayes methodology was used to determine the pharmacokinetic profile of sodium tungstate in beagle dogs after multiple oral dosing using the P-PHARM computer program. The population estimation algorithm used in P-PHARM is an EM-type procedure. Sodium tungstate was administered orally, three times a day, (i) for 11 days (21 and 42 mg/kg per day) to 18 dogs (nine males and nine females) and (ii) for 13 weeks (15, 30 and 60 mg/kg per day) to 28 dogs (14 males, 14 females). Six other dogs received the compound intravenously (25 and 50 mg/kg). Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. After oral administration, F (0.61+/-0.086 vs. 0.48+/-0.093), and normalized (to a 7-mg/kg dose of sodium tungstate) AUC (54+/-8.4 vs. 41.2+/-8.5 mg/l x h), C(max) (10.6+/-0.49 vs. 8.5+/-0.57 microg/ml) and C(min) (3.04+/-0.23 vs. 2.04+/-0.22 microg/ml), were higher in male than in female dogs. However, the introduction of the gender in the final model did not contribute statistically to an improvement of the fit of the population pharmacokinetic model. In males, t(1/2) elimination averaged 3.1+/-0.56 vs. 2.6+/-0.18 h in females. The duration of treatment did not modify statistically the pharmacokinetic parameters. After repeated multiple oral administration of 15-60 mg/kg per day of sodium tungstate, tungsten plasma concentrations increased in proportion to dose. No dose-dependent changes in pharmacokinetic parameters occurred.

Administration, Oral↗
PubMed2001

Antioxidant capacities and phenolics levels of French wines from different varieties and vintages.

Phenolics from grapes and wines can play a role against oxidation and development of atherosclerosis. Levels of phenolics, major catechins [(+)-catechin, (-)-epicatechin, procyanidin dimers B1, B2, B3, and B4], phenolic acids (gallic acid and caffeic acid), caftaric acid, malvidin-3-glucoside, peonidin-3-glucoside, and cyanidin-3-glucoside were quantified by HPLC with UV detection for 54 French varietal commercial wines taken from southern France to study the antioxidant capacity and the daily dietary intake of these compounds for the French population. The highest antioxidant capacity was obtained with red wines and ranged from 12.8 mmol/L (Grenache) to 25.2 mmol/L (Pinot Noir). For white wines, Chardonnay enriched in phenolics by special wine-making was found to have an antioxidant capacity of 13.8 mmol/L, comparable to red wine values. For red wines classified by vintages (1996-1999) antioxidant capacities were approximately 20 mmol/L and then decreased to 13.4 mmol/L for vintages 1995-1991. Sweet white wines have 1.7 times more antioxidant capacity (3.2 mmol/L) than dry white wines (1.91 mmol/L). On the basis of a still significant French wine consumption of 180 mL/day/person, the current daily intake of catechins (monomers and dimers B1, B2, B3, and B4) averaged 5 (dry white wine), 4.36 (sweet white wines), 7.70 (rosé wines), 31.98 (red wines), and 66.94 (dry white wine enriched in phenolic) mg/day/resident for the French population. Red wine, and particularly Pinot Noir, Egiodola, Syrah, Cabernet Sauvignon, and Merlot varieties, or Chardonnay enriched in phenolics during wine-making for white varieties contribute to a very significant catechin dietary intake.

Anthocyanins↗
PubMed2001

Vanadium pharmacokinetics and oral bioavailability upon single-dose administration of vanadyl sulfate to rats.

Vanadium pharmacokinetic parameters and oral bioavailability were determined after administration of vanadyl sulfate, an antidiabetic agent, to male Wistar rats. An optimal sampling design was used over a 21-day period; vanadium was measured in blood by atomic absorption spectrophotometry (AAS). After i.v. bolus injection (3.025 mg V/kg body weight), a three-compartment model was fitted to the data. Mean (+/- SD) half-lives were 0.90 +/- 0.56 hours, 24.8 +/- 14.5 h and 201 +/- 74 h, respectively, for the three phases observed. Vanadium clearance averaged 37.6 +/- 15.8 mL/h. Initial volume of distribution was 2.43 +/- 1.22 L/kg whereas total volume of distribution was 25.4 +/- 3.9 L/kg; these values largely exceeded body weight (i.e. 300 g), in agreement with a great uptake and retention of vanadium in tissues. After oral gavage administration (15.12 and 7.56 mg V/kg body weight), vanadium disposition was best described by a three-compartment model, with absorption appearing to occur by a zero-order rate. This process lasted 10.3 +/- 1.3 h and 10.9 +/- 1.1 h for the two dosage levels, respectively. Half-lives corresponding to the terminal log-linear part of the curve were 173.5 +/- 1.6 h and 172 +/- 6 h (Bayesian estimates). No dose-dependency was observed for any of the parameters determined. Absolute bioavailabilities, with reference to the i.v. administration, were 12.5% and 16.8% when determined from AUCmod. Bioavailability appeared to be higher than generally stated in the literature.

Administration, Oral↗
PubMed2001

Antihypertensive effects of Dorstenia psilurus extract in fructose-fed hyperinsulinemic, hypertensive rats.

We examined the effect of methanol/methylene chloride extract of Dorstenia psilurus given by gastric intubation on systolic blood pressure, plasma glucose, insulin, cholesterol, triglycerides and creatinine in rats with fructose-induced hypertension. Male Wistar rats in groups of 6 animals each were fed fructose-rich diets or standard chow for 3 weeks and treated with 100 mg/kg/day or 200 mg/kg/day of plant extract or vehicle for 3 subsequent weeks. Systolic blood pressure was measured every three days using the indirect tail cuff method. Systolic blood pressure was higher in fructose-fed rats (142+/-2 mm Hg, p < 0.01) compared with the controls (112+/-2 mm Hg), and was lower in Dorstenia psilurus-treated groups (127+/-2 and 119+/-1 mm Hg for the dose of 100 and 200 mg/kg, respectively) compared with the fructose-fed rats. Plasma insulin, cholesterol and triglycerides were higher on the fructose-rich diet compared with the controls. Plasma insulin and cholesterol were lower in the Dorstenia psilurus-treated groups. These results suggest that, Dorstenia psilurus treatment could prevent and reverse high blood pressure induced by a diet rich in fructose probably by improvement of plasma insulin levels. The plant extract might prove useful in the treatment and/or prevention of hypertension.

Africa↗
PubMed2001

Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome.

To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and IRS-2 genes in insulin resistance, we explored the genomic DNA in women with polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)] 3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct sequencing. Whereas no novel mutations were found in these genes, gene-dosage effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h plasma glucose for the Gly1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was more prevalent in insulin-resistant patients compared with non-insulin-resistant individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031, respectively). A multivariate model that included BMI as a variable revealed significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P < 0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of both IRS variants than in those with IRS-2 mutations only or those with wild-type variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS.

Adult↗
PubMed2000

Pharmacokinetics of sodium tungstate in rat and dog: a population approach.

Sodium tungstate has been found to correct hyperglycemia in insulin- and noninsulin-dependent models of diabetes when administered in drinking fluid with a low degree of toxicity; thus, it provides a potential treatment for diabetes. In the present report, pharmacokinetic studies with sodium tungstate were carried out in the Sprague-Dawley rat and beagle dog. This drug was administered either i.v. (8.97 mg/kg in rat; 25 and 50 mg/kg in dog) or orally in the form of solution (35.9 and 107.7 mg/kg in rat; 25 and 50 mg/kg in dog). Tungsten was quantified using an inductively coupled plasma method. Pharmacokinetic parameters were estimated using a population approach. Sodium tungstate followed first order kinetics, and plasma concentration-versus-time data were adequately described by a two-compartment model. In rat, bioavailability was high (92%), whereas it was lower in dog (approximately 65%). The total volume of distribution expressed by unit of body weight was much higher when the animal was smaller (0.46 l/kg in rat versus 0.23 l/kg in dog). The total body clearance normalized by weight, 0.19 l/h/kg in rat versus 0.043 l/h/kg in dog, changed as for the volume of distribution. The elimination half-life was two times higher in dog (approximately 4 h) than in rat (approximately 1.7 h). In the range of 35.9 to 107.7 mg/kg after oral administration in rat and 25 to 50 mg/kg after oral and i.v. administration in dog, tungsten plasma concentrations increased in proportion to dose.

Administration, Oral↗
PubMed1999

Vasopressin V2 (SR121463A) and V1a (SR49059) receptor antagonists both inhibit desmopressin vasorelaxing activity.

Although [Arg(8)]vasopressin is a potent vasoconstrictor, it possesses vasorelaxant properties manifested either after vasopressin V1 receptor blockade or directly in some vascular beds. The nature of the receptor involved in the vasorelaxant effect of [deamino-Cys(1) D-Arg(8)]vasopressin (desmopressin), a vasopressin V2 receptor agonist, was studied on rat precontracted aortic rings by the use of highly selective new non-peptide vasopressin receptor antagonists. The present study demonstrates for the first time that desmopressin relaxant effect is antagonized by the vasopressin V2 receptor antagonist SR121463A, but also by the vasopressin V1A receptor antagonist SR49059, suggesting that desmopressin-induced relaxation is mediated by a receptor subtype sharing both V1A and V2 pharmacological profiles.

Animals↗
PubMed1999

Contrasting effects of streptozotocin-induced diabetes on the in vitro relaxant properties of adenosine in rat pancreatic vascular bed and thoracic aorta.

In the present work, we have studied adenosine-induced vasodilation in streptozotocin-induced diabetic rats and compared it to that observed in normal age-matched or weight-matched animals. Experiments were performed on a vascular bed, the isolated perfused pancreas, and a large vessel, the thoracic aorta, provided from the same animal. Vasodilator activity was assessed, for isolated pancreas, as the increase in flow induced by the infusion of 2 microM adenosine for 30 min, or for noradrenaline-contracted aortae, as the relaxant response to adenosine (1 microM-1 mM). In both preparations the results obtained with selective adenosine receptors ligands (CPA, CGS 21680 and NECA) agreed with the presence of adenosine receptor of A2a subtype. In normal animals, adenosine vasodilator activity on both preparations diminished with advancing age in the rat, while diabetes was associated with a decreased or increased responsiveness to adenosine in pancreatic vascular bed or aorta, respectively. Further, the involvement of nitric oxide (NO), in relaxant responses, was evaluated by the use of the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). In all groups of animals, the flow rate of isolated pancreas dropped in the presence of 200 microM L-NAME, but was restored by adenosine to the level observed without L-NAME. L-NAME (10 microM) significantly reduced the dilator response to adenosine in aortic rings from diabetic animals, but not in those from normal rats. These results showed that adenosine vasorelaxant activity is significantly but differentially altered by diabetes according to the origin of the vascular preparation, and suggest that NO is involved in the vasorelaxant activity of adenosine in large vessels of diabetic animals. The potential pathophysiological role of adenosine in the vascular complications of diabetes remains to be determined.

Adenosine↗
PubMed1999

Identification by RT-PCR and immunolocalization of arginine vasopressin in rat pancreas.

Arginine vasopressin (AVP), a hormone of the hypothalamic pituitary axis, has been described in several peripheral tissues, including pancreas. To demonstrate the ectopic synthesis of AVP at the pancreatic level, we explored the expression of the AVP-neurophysin-II (AVP-NP-II) precursor gene by reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing and attempted to localise the peptide by immunocytochemistry in normal rat pancreas. Primers designed at the 3' and 5' ends of the AVP-NP-II gene, RT-PCR, and automatic sequencing of PCR products from rat pancreas revealed transcripts of the predicted size with an identical sequence to those from the hypothalamus. In addition, AVP antiserum revealed immunoreactive material of perivascular localisation. These data provide the first direct evidence for the presence of AVP transcripts in rat pancreatic tissue, whereas concurrent immunodetection of this hormone offers further support for the potential role of ectopic AVP in local regulation of the secretory activity of the pancreas.

Animals↗
PubMed1999

[Insulin resistance: from clinical diagnosis to molecular genetics. Implications in diabetes mellitus].

Insulin resistance is observed in several diseases such as non insulin dependent diabetes mellitus (NIDDM) or polycystic ovarian syndrome (PCOS). To understand genetic determinism of this abnormality we have developed a multidisciplinary approach including selection of phenotypes with insulin resistance confirmed in vivo by minimal model of Bergman and characterization of cellular defects in insulin action on circulating erythrocytes and monocytes. Exploration of variability in candidate genes by direct sequencing in some genetic syndromes of severe insulin resistance and acanthosis nigricans (mainly the Type A syndrome) revealed mutations of the insulin receptor gene associated with major defects in insulin binding or kinase activity. In other rare genetic syndromes or patients affected by NIDDM or PCOS defects appear to be located at post-receptor level, where IRS (insulin receptor substrate) genes are the most attractive candidates. Prevalence of some allelic variants suggested a potential role of IRS genes in insulin resistance, although their involvement in the pathogenesis of NIDDM remains controversial. Genotype-phenotype correlations in first degree relatives of an index case caring the Type A syndrome, suggested that association of allelic variants of IRS-1 and IRS-2 with insulin receptor mutations contribute, by synergistic effects, to phenotypic expression of defects in signal transduction. These mechanisms through genetic epistasis, involving several genes in insulin action, fit better with the polygenic nature of current forms of NIDDM and represent a good model in the study of pathogenesis of insulin resistance.

Acanthosis Nigricans↗
PubMed1998

Synthesis and biodistribution of new oxo and nitrido 99mTc complexes with asymmetrical potentially dianionic or trianionic tetradentate SNNO ligands derived from methyl-2-aminocyclopentene-1-dithiocarboxylic acid.

In this work, 10 new asymmetrical tetradentate SNNO ligands were prepared by reaction of the amine function of methyl 2-[(beta-aminoethyl)amino]cyclopentene-1-dithiocarboxylate with various bifunctional substituents bearing hydroxyl/ketone and hydroxyl/aldehyde functional groups and with diethyl oxalate. 99mTc labeling efficiency was optimized by adjusting temperature and pH conditions. Seven nitrido and two oxo 99mTc complexes were isolated. Six of them proved to be stable near physiological conditions. Biodistribution studies in the rat showed a significant heart uptake for four of them and strong kidney and liver uptake for the other two.

Animals↗
PubMed1998

Vanadyl treatment normalizes submandibular salivary gland insulin-like immunoreactivity in streptozotocin-diabetic rats.

Rat submandibular salivary glands (SSG) contain a compound displaying insulin-like immunoreactivity (ILI) and various biological activities of insulin. As SSG ILI levels were reported to be increased in streptozotocin (STZ)-induced diabetes but not normalized by a two-week insulin treatment, we decided to check whether another antidiabetic treatment, vanadyl sulphate (VOSO4), was able to regulate SSG ILI concentration. A short term (8 days) i.p. VOSO4 treatment (total dose = 1.3 mmol/kg) of rats made diabetic 8 days earlier by a single i.v. injection of STZ (60 mg/kg BW) was able to induce a long-term (4 weeks) correction of hyperglycemia while weight gain was re-established. In untreated diabetic animals (approximately -25%) and increased (approximately +175%) as compared to normal rats. Both parameters were normalized in VOSO4-treated diabetic rats.

Animals↗
PubMed1998

Vanadium levels in French and Californian wines: influence on vanadium dietary intake.

An accurate and reproducible method for direct determination of vanadium (V) in wine using graphite furnace atomic absorption spectrometry (GFAAS) is described. This method gave results insignificantly different from those obtained using dry mineralization of wine samples, with a detection limit of 42 pg. A total of 68 wine samples from different regions of France and California were analysed. Vanadium levels ranged from 7.0 to 90.0 micrograms/l in red and from 6.6 to 43.9 micrograms/l in white wines. The method was also adapted to the determination of vanadium levels in 12 grape samples from different varieties after acid mineralization. Vanadium content varied from 2 to 17 micrograms/kg for white and from 5 to 11 micrograms/kg for red varieties. Our data indicate that wine storage conditions may increase vanadium content. The contribution of wine consumption to daily vanadium dietary intake of the French population was estimated to be 11 micrograms/day per individual.

Canada↗
PubMed1998

Identification and sequence analysis of arginine vasopressin mRNA in normal and Brattleboro rat aortic tissue.

Arginine vasopressin (AVP), a hormone of the hypothalamic-pituitary axis, was also localized in peripheral tissues. To explore AVP precursor gene expression at the vascular level, we have investigated gene transcripts by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing in aortic tissue of normal rat and in the particular genetic condition of the homozygous (di/di) Brattleboro rat strain suffering from diabetes insipidus. In these rats, a gene deletion induces an unprocessed AVP precursor in the hypothalamus with undetectable immunoreactive AVP, in contrast to the detection of immunoreactive material at the vascular level. In normal rats, using primers complementary to exon 1 and 3 of the AVP neurophysin precursor gene, RT-PCR and sequencing revealed transcripts of the expected size from aorta, mesenteric artery and hypothalamus with normal, authentic sequences. Removal of aortic endothelium severely reduced the amounts of transcripts, suggesting their main endothelial origin. In Brattleboro rats, transcripts of similar size were obtained from aorta and hypothalamus and sequencing revealed the homozygous deletion (deltaG316) in both tissues, identical to that found in genomic DNA (deltaG1864). While sequence data from normal rats provide the first direct evidence for the presence of AVP precursor transcripts in rat aortic tissue, identification of the deleted sequence of transcripts in Brattleboro rat aorta suggests that tissue-specific mechanisms are operating for the expression of vasopressin neurophysin precursor in peripheral vascular tissue compared with the hypothalamus.

Animals↗