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Biomedical subjects

J J Serrano

Publications and source records attributed to J J Serrano.

At least 19 recordsLinked to original sources
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

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↗
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↗
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↗
PubMed1997

Characterization of vanadyl sulfate effect on vascular contraction: roles of calcium and tyrosine phosphorylation.

In order to explore the mechanism of action of vanadyl sulfate (VOSO4), previously described as an antidiabetic and antihypertensive agent, we have investigated the role of calcium and tyrosine phosphorylation in the contractile responses of rat aorta or skinned rabbit mesenteric artery rings. VOSO4 induced a concentration-dependent contraction of aorta (pD2 = 3.2), which was potentiated by endothelium removal (pD2 = 4.2). After a first exposure to VOSO4, no change in responsiveness was observed even though high vanadium concentrations had accumulated in the aortic tissue (approximately 4 x 10(-3) M). VOSO4 induced, in calcium-free medium, a significant response that, relative to contractions measured in Krebs-Henseleit buffer, was higher (36%) than norepinephrine (16%)-, arginine-vasopressin (8%)- or KCI (5%)-induced responses. 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an intracellular calcium release inhibitor, did not modify VOSO4-induced response either in the presence or in the absence of ambient calcium. On skinned preparations, VOSO4 antagonized Ca++-induced contraction. The tyrosine kinase inhibitors tyrphostin 23 (T23) and tyrphostin 47 (T47) potentiated by 4- and 14-fold, respectively, the activity of VOSO4, in contrast to the lack of effect of T47 on pervanadate-induced contraction. When phosphotyrosine content was revealed by Western blotting, VOSO4 had no effect alone, but in the presence of T47, it dramatically increased the phosphotyrosine content. This result contrasts again with PV-induced tyrosine phosphorylation, which was blocked by T47. These data suggest that the signaling events involved in vascular effects of VOSO4, although they depend little on calcium mobilization, are related to tyrosine phosphorylation, likewise through a pathway different from that of pervanadate.

Animals↗
PubMed1996

Vanadyl sulphate differently influences insulin response to glucose in isolated pancreas of normal rats after in vivo or in vitro exposure.

The effect of the antidiabetic agent vanadyl sulphate (VOSO4) on the endocrine pancreas function of normal rats was studied using the isolated pancreas preparation. A short-term (8 days) i.p. treatment (15 mg/kg per day) resulted in attenuation of high glucose-stimulated insulin release, at day 9 but also at days 19, i.e., after full recovery of appetite and weight, while blood and pancreas vanadium concentrations were still elevated. Six months of oral VOSO4 treatment (0.75 mg/ml in drinking water) resulted in elevated vanadium concentrations while glucose-stimulated insulin release was attenuated as compared to pair-fed animals. Conversely, when directly perfused in pancreas, VOSO4 potentiated glucose-stimulated insulin release. These apparently opposite effects may be related to the ability of VOSO4 to exert both peripheral insulinomimetic effects-leading to chronic reduction in insulin demand-, and a direct pancreatic insulinotropic activity.

Administration, Oral↗
PubMed1996

Entamoeba histolytica: proteinase secretion induced by collagen type I is dependent on cytoskeleton integrity.

Proteolytic activities of the protozoan parasite Entamoeba histolytica strain HM1:IMSS and the cytochalasin D-resistant mutant BG-3 were analyzed following stimulation with collagen type I and Ca2+, which induces electron-dense associated collagenase secretion. The mutant BG-3 had a protease activity of 73 kDa and secretion of total protease activity was not stimulated by collagen type I and Ca2+, which produced, in contrast, a 2-fold increase in protease secretion by the parental strain. This collagen-stimulated protease secretion was inhibited by cytochalasin D at a concentration of 1 microgram/ml. Cytochalasin D did not have any effect on the protease activity released by the mutant BG-3. These findings suggest that cytoskeleton integrity is necessary for collagen-induced protease secretion.

Animals↗
PubMed1994

Entamoeba histolytica: electron-dense granule secretion, collagenase activity and virulence are altered in the cytoskeleton mutant BG-3.

HM-1:IMSS, a pathogenic strain of Entamoeba histolytica, and its mutant BG-3, identified by resistance to cytochalasin D, were tested for their capacity to: (i) secrete electron-dense granules; (ii) adhere and digest native type I collagen gels; and (iii) produce liver abscesses in new-born hamsters. The results demonstrate that the mutant has low adherence to collagen, low electron-dense granule secretion and collagenolytic activity, and low capacity to produce liver lesions in vivo, compared with the parental strain HM1:IMSS.

Animals↗
PubMed1994

Actinobacillus pleuropneumoniae: virulence and gene cloning.

Actinobacillus pleuropneumoniae is the causal agent of porcine contagious pleuropneumonia (PCP). The infection produces important economic losses in porciculture due to its high morbidity and mortality. Survivors are asymptomatic carriers infectious to other pigs and have low alimentary conversion. The causative agent possesses several virulence factors: adhesion fimbriae, lipopolysaccharide of the outer membrane, capsule, and cytolysins. In addition, our group has reported secretion proteases of a wide pH range of activity. These proteases degrade different substrates such as porcine gelatin, hemoglobin and IgA, and bovine or human hemoglobin. To control PCP dissemination, farmers require serodiagnostic tests which detect carriers and discriminate between vaccinated and infected animals. Bacterines used as immunogens are serotype specific and do not prevent the infection. Genes have been cloned that codify a cohemolysin, cytolysins, and an iron-binding protein. We have cloned A. pleuropneumoniae genes using the expression plasmids pUC19 and Bluescript, in Escherichia coli Q358 and DH5 alpha; the screening for antigen production was made in four groups of pigs (vaccinated, experimentally infected, naturally infected, and from slaughterhouses); two E. coli clones expressed polypeptides recognized by sera from all the groups.

Actinobacillus Infections↗
PubMed1994

Secreted proteases from Actinobacillus pleuropneumoniae serotype 1 degrade porcine gelatin, hemoglobin and immunoglobulin A.

It was found that 48 hour cultures of Actinobacillus pleuropneumoniae secreted proteases into the medium. Electrophoresis in polyacrylamide gels (10%) copolymerized with porcine gelatin (0.1%), of the 70% (NH4)2SO4 precipitate from the culture supernatants, displayed protease activities of different molecular weights: > 200, 200, 90, 80, 70 and 50 kDa. They had activity over a broad range of pHs (4-8), with an optimal pH of 6-7. All were inhibited by 10 mM EDTA, and reactivated by 10 mM calcium. They were stable at -20 degrees C for more than a month. The proteases also degraded porcine IgA and porcine, human, and bovine hemoglobin, although they appeared to be less active against the hemoglobins. The IgA was totally cleaved in 48 h, using supernatants concentrated with polyvinyl pyrrolidone or the 70% (NH4)2SO4. Extracellular proteases could play a role in virulence.

Actinobacillus Infections↗
PubMed1993

In vivo antidiabetic actions of naglivan, an organic vanadyl compound in streptozotocin-induced diabetes.

The vanadyl (+IV) form of vanadium has been demonstrated to have insulin-mimetic activity in vivo. In an effort to improve the poor gastrointestinal absorption of the ion, an organic complex of vanadyl (naglivan) was synthesized. We tested the antidiabetic effects of naglivan in rats made diabetic with streptozotocin (55 mg/kg, i.v.). Four days after the streptozotocin injection, one diabetic group (DVI) and a control group (CV) were treated with naglivan (50 mg/kg/day, equivalent to 0.06 mmol vanadium/kg/day) by oral gavage. Treatment in the DVI group was supplemented with daily insulin while a second diabetic group (DI) was administered daily titrated doses of insulin alone (Protamine Zinc, s.c.) to achieve stable euglycemia. The dose of exogenous insulin required to maintain normal glucose was significantly lower in the DVI group compared to the DI throughout the treatment period. At the end of week 3, exogenous insulin was withdrawn from both the DVI and DI groups, while naglivan treatment was continued in the CV and DVI groups for an additional 5 weeks. At termination, hearts were isolated and cardiac function (+dP/dt, -dP/dt and left ventricular developed pressure) was assessed in all the animals. After insulin was withdrawn, 4/8 DVI animals which continued to receive naglivan had consistent normoglycemia (as determined by % glycosylated hemoglobin) and an improved cardiac function. All the DI animals and 4/8 DVI rats were hyperglycemic and had depressed heart function despite having similar plasma insulin levels to the euglycemic DVI animals. As with vanadyl sulfate, there were no signs of long-term toxicity with regards to renal or liver function after 8 weeks of treatment. Thus, naglivan is an orally effective form of vanadyl with an oral potency 7.6 times greater than that of vanadyl sulfate (minimum effective dose: 0.06 mmol vanadium.kg-1.day-1) as compared to vanadyl sulfate (0.46 mmol vanadium.kg-1.day-1). The lack of incidence of diarrhea in either control or diabetic animals demonstrates that naglivan could be a more therapeutically desirable form of vanadyl.

Animals↗
PubMed1992

Impairment of contractility associated with muscarinic supersensitivity in trachea isolated from diabetic rats: lack of correlation with ultrastructural changes or quinuclidinyl benzylate binding to lung membranes.

Evolution of cholinergic response of rat isolated trachea was determined after various durations of diabetes (17, 40, 90, 150 and 210 days). Long-term diabetes was associated with both impairment of contractility and supersensitivity to cholinergic stimulation. However, the mechanism of these alterations remains to be determined, as response to field stimulation was not specifically altered while electron microscopy studies could not detect any significant change in the aspect of nerves, smooth muscle or epithelium. As well, binding studies of lung cholinergic receptors using the antagonist ligand [3H]-quinuclidinyl benzylate and the agonist carbachol did not detect any change in diabetic animals.

Animals↗