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Biomedical subjects

A Chait

Publications and source records attributed to A Chait.

At least 19 recordsLinked to original sources

Study on the antinociceptive effects of Thymus broussonetii Boiss extracts in mice and rats.

In Morocco, Thymus broussonetii is widely used in folk medicine for the treatment of a variety of diseases including gastroenteric and bronchopulmonary disorders and to relieve dolorous process. The antinociceptive effect of the aqueous, butanolic and ethyl acetate extracts of this species was examined in rats and mice using chemical and thermal models. The results obtained showed that aqueous and butanolic extracts exerted an antinociceptive activity in the two phases of formalin (50-300 mg/kg), tail immersion and writhing tests. Whereas, the ethyl acetate extract reduced the nociceptive response only in the second phase of formalin (100-300 mg/kg) and writhing tests. The aqueous extract, which is the most effective, contains active analgesic principles acting both centrally and peripherally. Furthermore, this antinociceptive effect has been avoided by naloxone at a dose of 1mg/kg in the first phase of formalin and hot plate tests indicating that this extract acts partly through an opioid-mediated mechanism. The present results demonstrated that Thymus broussonetii contains active constituents which possess antinociceptive activity justifying its popular use to relieve some pains.

Acetic Acid↗

Seroprevalence of T. gondii in sheep from Marrakech, Morocco.

Toxoplasma gondii is a ubiquitous intracellular protozoan parasite transmitted by food. Concerning this parasite, there are few studies done in Morocco. In this study, 261 sera from sheep intended for consumption in Marrakech were subjected to the Toxoplasma ELISA based serology test for the detection of anti-T. gondii specific IgG confirming a past infection. Of the total tested 72 (27.6%) sera were positive for IgG. This result shows that the seroprevalence approaches the world average and is similar to what is found in other cities of Morocco. This has prompted us to investigate other animal species in the region in order to evaluate the degree of contamination by this parasite as well as the potential risk incurred on consumption of their meat.

Animals↗

Stochastic diffusion interactions and coarsening in a system of droplets growing from a supersaturated gas mixture.

In this work we study diffusion interactions among liquid droplets growing in stochastic population by condensation from supersaturated binary gas mixture. During the postnucleation transient regime collective growth of liquid droplets competing for the available water vapor decreases local supersaturation leading to the increase of critical radius and the onset of coarsening process. In coarsening regime the growth of larger droplets is prevailing noticeably broadening the droplet size-distribution function when the condensation process becomes more intensive than the supersaturation yield. Modifications in the kinetic equation are discussed and formulated for a stochastic population of liquid droplets when diffusional interactions among droplets become noteworthy. The kinetic equation for the droplet size-distribution function is solved together with field equations for the mass fraction of disperse liquid phase, mass fraction of water vapor component of moist air, and temperature during diffusion-dominated regime of droplet coarsening. The droplet size and mass distributions are found as functions of the liquid volume fraction, showing considerable broadening of droplet spectra. It is demonstrated that the effect of latent heat of condensation considerably changes coarsening process. The coarsening rate constant, the droplet density (number of droplets per unit volume), the screening length, the mean droplet size, and mass are determined as functions of the temperature, pressure, and liquid volume fraction.

Journal Article↗

Phase transition dynamics of liquid phase precipitation from a supersaturated gas mixture.

This work presents a self-consistent description of phase transition dynamics of disperse liquid phase precipitating from a supersaturated gas mixture. The unified approach integrates the macroscale transport phenomena of cloud dynamics with the essential microphysical kinetic processes of droplet condensation, evaporation, and droplet collisions simultaneously taking place in stochastic population of liquid droplets. A complete set of governing equations with well-defined dissipative fluxes and kinetic rates is derived for phase transition dynamics from nucleation to postnucleation to coarsening stages. The local thermodynamics of precipitating system, which is considered as ternary mixture of disperse liquid phase and water vapor with dry air, is redefined to explicitly include on equal basis both the vapor content and liquid content into the fundamental thermodynamic relations and equation of state. The molecular kinetic flux regularization method for growth of submicron droplets is reexamined to include, among others, significant contribution of vapor molecular energy flux into total heat flux, resulting in new expressions for the droplet temperature, growth rate, and effective diffusion coefficients. The local kinetic rates are determined on the basis of microscale kinetic equation for the droplet distribution function. This is in contrast to commonly used semiempirical parametrization schemes for kinetic rates with adjustable parameters, wherein the probabilistic aspects of microphysical processes are not rigorously addressed. Stochastic diffusion interactions among droplets competing for the available water vapor and modifications in the kinetic equation for droplets growing in stochastic population with direct long-range diffusion interactions amongst them are discussed and formulated as well.

Journal Article↗

Postnucleation droplet growth in supersaturated gas with arbitrary vapor concentration.

This work concerns the reexamination and extension of the current theory of phase transition dynamics for liquid droplets growing on soluble aerosols from a supersaturated gas mixture for the general case of arbitrary value of vapor concentration. We found that the inconsistency in the common treatment of the vapor diffusion, due to an implicit assumption of the constancy of gas density in the vicinity of a droplet by neglecting its dependency on temperature and vapor concentration, leads to the obvious discrepancy in the Maxwell expression for the growth rate regarding droplets of near critical size. Restoring the correct treatment of the vapor diffusion in terms of the mass concentration of water vapor and taking into the consideration variations of gas density in the vicinity of a droplet in compliance with the equation of state of moist air, we have obtained a new expression for the droplet growth rate valid for an arbitrary value of vapor concentration. The limitations imposed by the molecular kinetic fluxes to postnucleation diffusional growth of small droplets with a large Knudsen number are also reevaluated to include previously neglected physical effects. In particular, the essential contribution of the vapor molecular energy flux into the total kinetic molecular heat flux as well as the temperature variations of mean thermal velocities of air and vapor molecules in the vicinity of the droplet interface have been taken into consideration. Surprisingly significant differences have been found in new expressions derived for the droplet growth rate and droplet temperature, even in the limit of small vapor concentration, if comparing with commonly used results. These findings could help with better interpretation of experimental measurements to infer more reliable data for the mass and thermal accommodations coefficients.

Journal Article↗

Thiazolidinediones reduce the LDL binding affinity of non-human primate vascular cell proteoglycans.

AIMS/HYPOTHESIS: Retention of atherogenic lipoproteins in the artery wall by proteoglycans is a key step in the development of atherosclerosis. Thiazolidinediones have been shown to reduce atherosclerosis in mouse models. The aim of this study was to determine whether thiazolidinediones modify vascular proteoglycan synthesis in a way that decreases LDL binding. METHODS: Primate aortic smooth muscle cells were exposed to troglitazone or rosiglitazone, or no stimulus at all for a 24-hour steady-state labelling period. Sulphate incorporation, size and LDL binding affinity of proteoglycans were determined. Proteoglycans secreted by cells in the presence or absence of troglitazone were separated into large and small classes by size exclusion chromatography, and LDL binding affinity was determined. RESULTS: Proteoglycans synthesised by cells exposed to troglitazone or rosiglitazone were smaller, with decreased sulphate incorporation and decreased LDL binding affinity. However, troglitazone had a greater effect than rosiglitazone. Troglitazone reduced the LDL binding affinities of both the large and small proteoglycans compared with control. The binding differences persisted when glycosaminoglycan chains released from proteoglycans were incubated with LDL, indicating that troglitazone affects the glycosaminoglycan synthetic machinery of these cells. CONCLUSIONS/INTERPRETATION: Thiazolidinediones decrease the LDL binding affinity of the proteoglycans synthesised by primate aortic smooth muscle cells. This could, in part, account for the reduced atherosclerosis observed in animal models.

Animals↗

Impact of nitrate intake in drinking water on the thyroid gland activity in male rat.

The purpose of this study was to determine the effects of nitrate on both the activity of the thyroid gland and other biological parameters. After 5-month treatment, nitrate 150 and 500 mg/l induced a significant decrease in the serum level of thyroid hormone T3. For T4, the 500 mg/l dose only reduced its plasma level. On the other hand, nitrate induced a dose-dependent increase in the weight of the thyroid gland. The histological study of the thyroid gland shows vacuolisation and an increase in the size of the follicles accompanied by a flatness of follicular epithelium with nitrate 150 and 500 mg/l. We concluded that the presence of high concentrations of nitrate in drinking water influence the growth, induce morpho-functional modifications of the thyroid gland and might be considered as a goitrigenic factor.

Administration, Oral↗

[Toxoplasma gondii: level of carriage in sheep of Marrakech region (Mnabha)].

Toxoplasma gondii is an ubiquitous parasite with a prevalence variable from country to country. In Morocco very few studies were devoted to this prevalence. To fill this gap we were interested to study the epidemiology of this parasite and to know the level of carriage by the different vectors which are the sources of contamination in humans. The study was done by directly detecting the cysts in the cerebral tissue of the 50 sheep killed and destined for consumption. The results of this preliminary study show that 30% of the cases carry the cysts of T. gondii. To confirm this result and verify the virulence, cerebral specimens were inoculated into mice. These findings are encouraging to complete this study with serological tests and to look for the parasite in cows and goats of this region.

Animals↗

The effect of apolipoprotein E deficiency on islet amyloid deposition in human islet amyloid polypeptide transgenic mice.

AIMS/HYPOTHESIS: Islet amyloid deposits are present in over 85% of Type 2 diabetic patients and have been suggested to be pathogenic. The mechanism that converts islet amyloid polypeptide (IAPP), the unique component of these deposits, into amyloid fibrils in vivo is not known. The amino acid sequence of IAPP is critical but insufficient for beta-pleated sheet formation. As apolipoprotein E (apoE), another component of islet amyloid deposits, plays a critical role in amyloid formation in Alzheimer's disease, we hypothesised that apoE could play an important role in islet amyloid formation. METHODS: Transgenic mice expressing the human form of IAPP ( hIAPP (+/0)) were crossbred with apoE deficient ( apoE (-/-)) mice and followed for 12 months, at which time the prevalence and severity of islet amyloid, as well as plasma glucose, hIAPP, immunoreactive insulin (IRI) and lipid concentrations were measured. RESULTS: The prevalence and severity of islet amyloid after one year of follow up were comparable among hIAPP (+/0) mice that were apoE (+/+), apoE (+/-) or apoE (-/-). Differences in glucose tolerance, lipid abnormalities or changes in pancreatic content or plasma concentrations of hIAPP and/or IRI did not account for these findings. CONCLUSION/INTERPRETATION: Our data shows that, unlike in the localized amyloidosis in the brain characteristic of Alzheimer's disease, apoE is not critical for islet amyloid formation in a transgenic mouse model of Type 2 diabetes mellitus. These results indicate that the mechanisms of localised amyloid formation probably vary among different amyloid-associated disorders. Therefore, therapeutic strategies targeting apoE might not apply equally to patients with different amyloid associated diseases.

Amyloid↗

pH dependence of the relative hydrophobicity and lipophilicity of amino acids and peptides measured by aqueous two-phase and octanol-buffer partitioning.

Partitioning of a series of free amino acids, their derivatives, and homo-oligopeptides in aqueous dextran-PEG two-phase systems and octanol buffer systems was examined at pH values from 2.0 up to 12.5. The pH-dependent partition behavior of free amino acids and peptides in the two-phase systems was compared with that of monofunctional drug-like compounds and found to be clearly different. The differences observed indicate that the information provided by the techniques of partitioning in octanol buffer (log(D)(pH)) and in aqueous two-phase systems, N(CH2), is different. It is suggested that the combination of the two descriptors, log(D) (lipophilicity) and N(CH2) (relative hydrophobicity), may be useful for QSAR analysis of the biological activities involving distribution and/or transport of chemical compounds in biological systems.

Amino Acids↗

Relative hydrophobicity of di- to hexapeptides as measured by aqueous two-phase partitioning.

Partitioning of 153 di- to hexapeptides in an aqueous dextran-PEG two-phase system containing 0.15 m NaCl in 0.01 m sodium phosphate buffer, pH 7.4 was examined. The relative hydrophobicity of the peptides was estimated and expressed in equivalent numbers of methylene units. Analysis of the data shows that the additivity principle applies for the relative hydrophobicity of up to hexapeptides. The relative hydrophobicities of Trp, Glu, and Asp residues in heterooligopeptides are noticeably different from those in corresponding homooligopeptides. The relative hydrophobicity of peptides can be calculated and used as a structural descriptor in quantitative structure-activity relationship analysis. The peptide bitterness threshold is shown to be quantitatively related to the peptide structure described as a combination of the relative hydrophobicity and lipophilicity (logD) of peptides.

Chemistry↗

Relative hydrophobicity of amino acid residues in homooligopeptides as measured by aqueous two-phase partitioning.

Partitioning of 17 amino acids and their homooligopeptides of different lengths in an aqueous dextran-PEG two-phase system containing 0.15 m NaCl in 0.01 M sodium phosphate buffer, pH 7.4 and 0.11 m sodium phosphate buffer, pH 7.4 was examined. The relative hydrophobicity of the amino acid residues was estimated and expressed in equivalent numbers of methylene units. Analysis of the data shows that the additivity principle does hold for the hydrophobicity of homooligopeptides. The relative hydrophobicity of essentially all amino acid residues is noticeably affected by the ionic composition of aqueous media.

Amino Acid Sequence↗

Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease.

BACKGROUND: Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL. METHODS: In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). RESULTS: The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group. CONCLUSIONS: Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.

Antioxidants↗

A new method for analysis of components in a mixture without preseparation: evaluation of the concentration ratio and protein-protein interaction.

A new method for evaluating the ratio of two structurally different proteins or other compounds in a mixture that does not require any preseparation steps and is based on using the aqueous two-phase partition technique is described. Mathematical analysis of the partitioning of a mixture of two solutes demonstrates its ability to quantitatively evaluate the ratio of the concentrations of the solutes in the initial mixture. It also provides the means for detecting interactions between the two solutes. Experimental results confirm the analysis to be correct for mixtures of low-molecular-weight compounds as well as for mixtures of structurally different proteins. An example of analysis of a clinically relevant mixture of two proteins-transferrin and carbohydrate-deficient transferrin-is provided. An analysis of interactions between two proteins and/or peptides is also illustrated using two examples.

Animals↗

Enhanced oxidative susceptibility and reduced antioxidant content of metabolic precursors of small, dense low-density lipoproteins.

PURPOSE: Elevated plasma concentrations of low-density lipoproteins (LDL) increase risk for coronary heart disease. However, lipoprotein profiles rich in small, dense LDL particles confer greater risk than those that mainly consist of large, buoyant LDL. This may be due, in part, to the greater oxidative susceptibility of small, dense LDL. In the current studies, we tested whether differences in the oxidative behavior of buoyant and dense LDL arise from differences in their immediate metabolic precursors, intermediate-density lipoproteins. SUBJECTS AND METHODS: We compared the properties of intermediate-density lipoproteins and buoyant and dense LDL subfractions in 9 subjects with the large, buoyant LDL phenotype versus 6 with the small, dense LDL phenotype. Oxidative susceptibility was evaluated based on conjugated diene formation and parinaric acid oxidation induced by copper. Antioxidants (ubiquinol-10 and alpha-tocopherol) were measured by high-performance liquid chromatography. RESULTS: Oxidative susceptibility was increased and antioxidant concentrations were decreased with increasing lipoprotein density (intermediate intermediate-density lipoproteins to buoyant LDL to dense LDL). Intermediate-density lipoproteins from subjects with the small, dense LDL phenotype had a greater oxidative susceptibility (by the parinaric acid test) and lower antioxidant concentrations than corresponding particles from subjects with the large, buoyant LDL phenotype. CONCLUSIONS: Differences in oxidative susceptibility between large, buoyant and small, dense LDL particles are apparent in their lipoprotein precursors. These results suggest that lipoprotein oxidative susceptibility may be metabolically programmed and that intermediate-density lipoproteins may contribute to the increased risk associated with the small, dense LDL phenotype.

Adult↗

Measurement of the relative hydrophobicity of organic compounds without organic solvent. Effects of salt composition and pH on organic acids and nonionic compounds.

Partitioning of a variety of nonionic and acidic organic compounds was examined in aqueous dextran-poly(ethylene glycol) (PEG) two-phase systems of different ionic composition at pH 2.00 and 7.40. Relative hydrophobicity of the compounds was estimated in terms of equivalent numbers of methylene units. Effect of the ionic composition and pH of aqueous media on the relative hydrophobicity of organic compounds was established and described quantitatively. The results obtained indicate that the ionic composition affects the relative hydrophobicity of ionized compounds and has no effect on that of nonionic compounds and ionizable compounds in the undissociated state. Ionization of a given ionic group seems to bring about a constant change in the relative hydrophobicity of a compound. This result supports the applicability of the additivity principle to the relative hydrophobicity estimates obtained with the aqueous two-phase partitioning technique.

Benzoic Acid↗

MMP9 production by human monocyte-derived macrophages is decreased on polymerized type I collagen.

The production of matrix metalloproteinases (MMPs), such as MMP9, by macrophages may be a critical factor in the rupture of unstable atherosclerotic plaques and aortic aneurysms. Therefore, we studied the role of matrix and soluble cytokines in the regulation of monocyte/macrophage expression of MMP9. Although freshly isolated monocytes synthesize little MMP9, cells cultured on tissue-culture plastic differentiate into macrophages and synthesize maximal amounts of MMP9. Differentiated macrophages cultured on plastic are unresponsive to further stimulation by interleukin 1beta, tumor necrosis factor alpha, or platelet-derived growth factor BB. In contrast, monocytes cultured on polymerized collagen synthesize much less MMP9 than cells cultured on plastic and demonstrate a more than three-fold increase in MMP9 synthesis in response to interleukin 1beta, tumor necrosis factor alpha, and platelet-derived growth factor BB. To determine whether the physical state of the collagen was critical for the decrease in basal synthesis of MMP9, monocytes were cultured in suspension for 5 days to allow differentiation and then seeded onto monomer or polymerized collagen. Synthesis of MMP9 was significantly decreased in cells on polymerized collagen and modestly increased in macrophages seeded on monomer collagen. These results suggest that MMP9 synthesis by macrophages in the vessel wall may be under negative control by native, polymerized collagen and that disruption of this native conformation could increase MMP9 production. In addition, cells in contact with the collagen matrix are potentially more responsive to soluble mediators such as platelet-derived growth factor, interleukin 1beta, and tumor necrosis factor alpha.

Aortic Aneurysm↗

Biglycan, a vascular proteoglycan, binds differently to HDL2 and HDL3: role of apoE.

Lipoprotein retention by vascular extracellular matrix proteoglycans is important in atherogenesis. Proteoglycans bind apolipoprotein (apo)B- and apoE-containing lipoproteins. However, the colocalization of apoA-I and apoE with biglycan in atherosclerotic lesions suggests that vascular proteoglycans also may trap high density lipoproteins (HDLs). Because the major HDL subclasses may be atheroprotective to different degrees, we investigated the role of apoE in mediating HDL(2) and HDL(3) binding to the extracellular vascular proteoglycan, biglycan. ApoE-free HDL(2) and HDL(3) did not bind to purified [(35)S]SO(4)-biglycan, whereas apoE-containing HDL(2) and HDL(3) (HDL+E) did. The extent of binding correlated positively with the apoE content for both HDL(2) and HDL(3), although HDL(2)+E had a 3.5-fold higher affinity than did HDL(3)+E. ApoE on HDL(3) was cleaved into 22- and 12-kDa fragments, whereas apoE on HDL(2) remained intact. These results suggest that the cleaved apoE on HDL(3) results in diminished biglycan binding of HDL(3)+E relative to HDL(2)+E. Reducing positive charges on lysine and arginine residues on HDL+E eliminated biglycan binding, suggesting an ionic interaction. Thus, apoE is an important determinant of HDL binding to extracellular vascular proteoglycans and may play a role in HDL retention in the artery wall.

Apolipoprotein A-I↗