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Biomedical subjects

A Prasad

Publications and source records attributed to A Prasad.

At least 55 records · Page 3Linked to original sources
PubMed2000

Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis.

BACKGROUND: The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The present study was performed to determine whether angiotensin-1 (AT(1)) receptor inhibition improves endothelial dysfunction. METHODS AND RESULTS: In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects, we studied microvascular responses to reactive hyperemia, angiotensin II, acetylcholine, and sodium nitroprusside before and after the administration of intra-arterial losartan (10 mg). Femoral artery flow velocity was measured with a Doppler flow wire, and the femoral vascular resistance index (FVRI) was calculated as mean arterial pressure divided by flow velocity. Losartan induced a minor (5.9+/-2%, P=0. 02) reduction in FVRI and inhibited angiotensin II-mediated vasoconstriction in both patient groups (P<0.01). After the administration of losartan, acetylcholine-mediated vasodilation was augmented in patients (44+/-5% to 58+/-4% reduction in FVRI with infusion at a rate of 150 microgram/min, P<0.001) but not control subjects. Vasodilation during reactive hyperemia was also greater after AT(1) receptor inhibition (P=0.03) in patients, but the response to sodium nitroprusside remained unchanged. In a separate group of 31 patients with atherosclerosis, we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound. Oral losartan therapy improved flow-mediated brachial artery dilation (1.4+/-0.9% to 3.2+/-0.8%, P=0.03) but had no effect on the nitroglycerin response. Serum nitrogen oxide levels increased from 21.6+/-1.7 to 26.7+/-2.4 micromol/L (P=0.008). CONCLUSIONS: The results of the present study indicate that inhibition of the AT(1) receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits.

Acetylcholine↗
PubMed2000

Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis.

BACKGROUND: Chest physiotherapy is widely used in patients with cystic fibrosis in order to clear mucus from the airways. OBJECTIVES: To determine the effectiveness and acceptability of chest physiotherapy compared to no treatment or spontaneous cough alone to improve mucus clearance in cystic fibrosis. SEARCH STRATEGY: Relevant trials are identified in the Cochrane Cystic Fibrosis and Genetic Disorders Group Specialised Register of Controlled Trials. This register was compiled by conducting computerised searches of Medline from 1966 to present and from Embase from 1974 to 1995. The register of randomised controlled trials is updated every three months. Unpublished work has been identified by searching through the abstract books of the three major cystic fibrosis conferences; the International Cystic Fibrosis Conference: the European Cystic Fibrosis Conference and the North American Cystic Fibrosis Conference. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials in which a form of chest physiotherapy (airway clearance technique) were taken for consideration in patients with cystic fibrosis compared with either no physiotherapy treatment or spontaneous cough alone. DATA COLLECTION AND ANALYSIS: There were no randomised controlled trials or cross over trials eligible for inclusion in the review. MAIN RESULTS: There were no randomised controlled trials or cross over trials eligible for inclusion in the review. REVIEWER'S CONCLUSIONS: Short-term crossover trials, which had to be excluded from this review, suggest that airway clearance regimens could have beneficial effects in patients with cystic fibrosis. However based on this review there is currently no robust scientific evidence to support the hypothesis that chest physiotherapy for the purpose of clearing airway secretions has a beneficial effect in patients with cystic fibrosis.

Cystic Fibrosis↗
PubMed2000

Dehydroepiandrosterone-mediated decrease in caloric intake by obese Zucker rats is not due to changes in serum entrostatin-like immunoreactivity.

To understand the mechanism(s) of appetite modulation by DHEA, we have undertaken a series of studies to examine the effects of DHEA on neurotransmitters and neuropeptides known to affect appetitive behavior. Here, we report the effect of DHEA on serum enterostatin-VPDPR or E, a pentapeptide known to cause selective diminution in fat intake. Four-week-old lean (fa/+) and obese (fa/fa) Zucker rats were divided into control and treatment groups. DHEA-treated groups received powdered chow containing 0.6% DHEA ad lib for 16 weeks. Another group of obese rats was pair fed to match the intake of the obese DHEA-treated rats. At the end of this period, trunk blood was collected from fasted rats for assay of E-like immunoreactivity (E-LI) by ELISA. DHEA treatment caused a significant diminution in circulating E-LI in both lean (control: 2030 +/- 226; treated: 752 +/- 145 ng/mL; n = 10, p < 0.0001) and obese (control: 2489 +/- 391, n = 6; treated: 1123 +/- 185 ng/mL, n = 7; p = 0.0003) rats. Because DHEA treatment decreases caloric intake and body weight, we examined the effect of caloric intake and body weight on E-LI levels. Serum ELI levels were lower in the obese DHEA-treated group compared to that of obese pair fed (pair fed: 1589 +/- 313, n = 6; DHEA: 1123 +/- 185 ng/mL, n = 7), but the differences were statistically insignificant (p = 0.185). Also, both weight-matched lean and obese control rats had significantly (p < 0.008) higher E-LI than their DHEA-treated counterparts. To examine whether the decrease in serum E-LI following DHEA treatment could be due to increased peptide metabolism, the rate of disappearance of endogenous E-LI from serum (obese control and DHEA-treated) at 37 degrees C was evaluated. The results show an attenuation of peptide metabolism in serum from DHEA-treated rats, a finding contrary to our expectations. In summary, DHEA treatment lowers serum E-LI levels both in lean and obese Zucker rats. This decrement in peptide level is not secondary to changes in body weight or caloric intake due to DHEA, or due to altered serum peptide metabolism. Although DHEA appears to be a potent modulator of E-LI levels, the relationship between DHEA and E-LI in relation to appetitive behavior remains to be clarified.

Animals↗
PubMed2000

Dealloying and electroformation in high-Pd dental alloys.

OBJECTIVE: The corrosion of high-Pd dental alloys, depending on their composition, is postulated to be associated with dealloying and electroformation. The aim of this study was to obtain additional information to support these postulations. METHODS: The corrosion characteristics of two commercial high-Pd alloys, Naturelle (79Pd-10Cu-2Au-9Ga wt%) and Rx 91 (54Pd-37Ag-9Sn), and their elemental components were evaluated in a phosphated buffer saline (PBS) solution. Indium, a common element in high-Pd alloys, was also included. The corrosion characteristics measured for each material were the 24 h open circuit potential (OCP) and the potentiodynamic anodic polarization curve. Additionally, the surface composition of the two alloys, before and after immersion corrosion in PBS for 2 months, was analyzed by X-ray photo electron spectroscopy (XPS). RESULTS: Of the pure metals, Ga had the most electroactive OCP followed in order by In, Sn, Cu, Ag, Au, and Pd. The anodic polarization data showed all base metals to be unstable in PBS. The electroformation of AgCl was evidenced in the polarization curve of pure Ag. Both electrochemical characteristics of the PdCu-based alloy were very similar to that of pure Pd. The PdAg-based alloy displayed corrosion behavior resembling that of Ag. XPS data showed that the corrosion of the PdCu-based alloy was associated with a decrease in surface content of Cu and Ga but an increase in Pd and Au. The PdAg-based alloy surface during corrosion showed a decrease in Sn, an increase in Ag, and an unaltered Pd content. The behavior of the PdCu-based alloy is attributed to the operation of a galvanic interaction that causes dissolution of base metals and surface enrichment with primarily Pd. Dealloying, Ag-enrichment, and AgCl formation are thought to have contributed to the observed behavior of the PdAg-based alloy. These mechanisms are consistent with data from published ion release studies. SIGNIFICANCE: The allergenic potential of any Pd alloy is dependent on its propensity to develop a Pd-rich surface and thus release Pd+2 ions. The present study, though limited, has shown that electrochemical characteristics, namely OCP and polarization curves, can be used to identify such alloys. Further studies are warranted to evaluate the widespread applicability of these characteristics in distinguishing between Pd alloys that are biologically safe and those that are not.

Copper↗
PubMed2000

Regional and developmental expression of the Npc1 mRNA in the mouse brain.

Niemann-Pick type C (NP-C) disease is a fatal, autosomal recessive disorder of cholesterol metabolism that results in progressive central nervous system deterioration and premature death. Recently, a gene mutated in NP-C disease (NPC1) was identified in both human patients and in the npc(nih) mouse model. Although the function of the NPC1 gene is at present unknown, determining the pattern of its expression in the brain may facilitate identification of the mechanisms underlying the neuropathology of this disease and in identifying relevant targets for any potential therapeutic intervention. We have used in situ hybridization techniques to characterize the pattern of Npc1 mRNA expression in both the wild-type and the npc(nih) mutant mouse brain. In adult animals of both genotypes, the Npc1 mRNA was detected in the majority of neurons in nearly all regions, but at significantly higher levels in the cerebellum and in specific pontine nuclei. Analysis of Npc1 mRNA levels during development in the wild-type mouse indicated that this transcript was expressed in neurons as early as embryonic day 15 and that a significant region-specific pattern of expression was established by postnatal day 7. Our data suggest that whereas the NPC1 gene is widely expressed in neurons of the brain, the higher levels of expression in the cerebellum and pontine structures established by early postnatal ages may make these regions more susceptible to neuronal dysfunction in NP-C disease.

Aging↗
PubMed2000

Assessment of different methods for staining Helicobacter pylori in endoscopic gastric biopsies.

The recent implication of Helicobacter pylori in the pathogenesis of gastritis-peptic ulcer syndrome and its relevance for the development of upper gastrointestinal malignancy warrant efficient methods for the detection and demonstration of the organism in biopsy specimens. We have compared 5 staining methods, namely, haematoxylin and eosin (H & E), immunohistochemistry (IHC), the silver staining HpSS, the alcian yellow-toluidine blue (Leung) method (A-Y) and Genta staining, for the demonstration of the organism in gastric biopsies taken from antrum, body and fundus of 118 patients who presented to our hospital with upper gastrointestinal symptoms. We found no significant differences in the efficacy of H & E, IHC, HpSS and A-Y in the demonstration of H. pylori in all 3 gastric sites. The least reproducible stain in our hands was the Genta stain. We conclude that H & E is adequate for the initial assessment of gastric biopsies in symptomatic upper gastrointestinal patients. This is because it is a well-tested, cheap and easy staining method, requiring a relatively short period of time to perform, with highly reproducible results. It has an added advantage of enabling simultaneous assessment of morphological changes accompanying H. pylori infection. When the density of the organism is expected to be low, we recommend addition of HpSS staining because of its high sensitivity and low cost. The disadvantages of the other staining methods (IHC, A-Y and Genta) are discussed.

Adolescent↗
PubMed2000

Intermittency transitions to strange nonchaotic attractors in a quasiperiodically driven duffing oscillator

Different mechanisms for the creation of strange nonchaotic attractors (SNAs) are studied in a two-frequency parametrically driven Duffing oscillator. We focus on intermittency transitions in particular, and show that SNAs in this system are created through quasiperiodic saddle-node bifurcations (type-I intermittency) as well as through a quasiperiodic subharmonic bifurcation (type-III intermittency). The intermittent attractors are characterized via a number of Lyapunov measures including the behavior of the largest nontrivial Lyapunov exponent and its variance, as well as through distributions of finite-time Lyapunov exponents. These attractors are ubiquitous in quasiperiodically driven systems; the regions of occurrence of various SNAs are identified in a phase diagram of the Duffing system.

Journal Article↗
PubMed2000

Modern adjunctive pharmacotherapy of myocardial infarction.

During acute myocardial infarction (MI), aspirin, beta-adrenergic antagonists and oral angiotensin converting enzyme (ACE) inhibitors should be used as an adjunct to reperfusion therapy. Medications upon discharge from the hospital should include aspirin and a beta-blocker. An ACE inhibitor should also be prescribed unless the ejection fraction is > 45%. Particular indications for an ACE inhibitor are an anterior MI, congestive heart failure, ejection fraction < 45% and mitral regurgitation. beta-blockers, when given to patients treated with ACE inhibitors, appear to produce an additional benefit compared with an ACE inhibitor alone. Based on the Scandinavian Simvastatin Survival Study (4S), Cholesterol and Recurrent Events (CARE) and Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trials, a statin should also be given to subjects with low density lipoprotein (LDL)-cholesterol levels above 125 mg/dl, independent of total cholesterol levels. Therapy should be administered in an attempt to reduce the LDL-cholesterol level to 90-100 mg/dl (2.3-2.6 mM/l). In patients with normal or low levels on initial evaluation, screening for lipid abnormalities should be deferred for 2 months since acute phase responses and passive hepatic congestion can cause spuriously normal levels. Calcium channel blockers, nitrates, lidocaine, anti-arrhythmic drugs and i.v. magnesium should not be administered routinely after acute MI and their use should be restricted to selected settings.

Adrenergic beta-Antagonists↗
PubMed1999

Induction of Purkinje fiber differentiation by coronary arterialization.

A synchronized heart beat is controlled by pacemaking impulses conducted through Purkinje fibers. In chicks, these impulse-conducting cells are recruited during embryogenesis from myocytes in direct association with developing coronary arteries. In culture, the vascular cytokine endothelin converts embryonic myocytes to Purkinje cells, implying that selection of conduction phenotype may be mediated by an instructive cue from arteries. To investigate this hypothesis, coronary arterial development in the chicken embryo was either inhibited by neural crest ablation or activated by ectopic expression of fibroblast growth factor (FGF). Ablation of cardiac neural crest resulted in approximately 70% reductions (P < 0.01) in the density of intramural coronary arteries and associated Purkinje fibers. Activation of coronary arterial branching was induced by retrovirus-mediated overexpression of FGF. At sites of FGF-induced hypervascularization, ectopic Purkinje fibers differentiated adjacent to newly induced coronary arteries. Our data indicate the necessity and sufficiency of developing arterial bed for converting a juxtaposed myocyte into a Purkinje fiber cell and provide evidence for an inductive function for arteriogenesis in heart development distinct from its role in establishing coronary blood circulation.

Animals↗
PubMed1999

Relationship of the C242T p22phox gene polymorphism to angiographic coronary artery disease and endothelial function.

Patients with coronary artery disease (CAD) have impaired endothelial function in part due to an increase in vascular oxidant stress. p22phox, an essential component of the NADPH oxidase, is thought to play a critical role in the generation of superoxide anions in the vessel wall. The C242T polymorphism, located in the potential heme-binding site of the p22phox gene, has recently been reported to confer a protective effect on CAD risk in a Japanese study population. In a U.S. population of 252 patients (83% Caucasian) undergoing angiography for diagnosis of CAD, we investigated whether the C242T polymorphism was associated with the presence of CAD. In a subset of 142 patients, we studied whether the polymorphism manifests its potential protective effects through alteration of vascular endothelial function by measuring coronary epicardial and microvascular responses to intracoronary acetylcholine and sodium nitroprusside. Prevalence of the C242T allele was not different in 149 patients with CAD compared to 103 patients with angiographically normal coronary arteries (65.1% vs. 54.4%, P = 0.11). The C242T allele frequency in our population was nearly fourfold higher than reported previously in a Japanese population. There were also no significant differences in coronary epicardial or microvascular responses to acetylcholine or sodium nitroprusside between groups of patients with or without the C242T allele. In a U.S. population, the C242T polymorphism does not appear to confer protection from endothelial dysfunction or CAD. Am. J. Med. Genet. 86:57-61, 1999. Published 1999 Wiley-Liss, Inc.

Acetylcholine↗
PubMed1999

Effect of enalaprilat on nitric oxide activity in coronary artery disease.

Atherosclerosis is associated with vascular endothelial dysfunction and reduced nitric oxide (NO) activity. Enhancement of NO activity may have an antiatherogenic action. This study was performed to determine whether angiotensin-converting enzyme (ACE) inhibition improves peripheral vascular NO activity in patients with atherosclerosis. In the femoral circulation of 43 patients with atherosclerosis and 10 controls, we studied endothelium-dependent vasodilation with bradykinin and acetylcholine, and endothelium-independent vasodilation with sodium nitroprusside before and after enalaprilat. In 22 patients, we repeated these infusions in the presence of L-N(G) monomethyl arginine (L-NMMA). Doppler-femoral artery flow velocity was measured. Before ACE inhibition, acetylcholine responses were depressed in patients with atherosclerosis compared with controls (p = 0.03). Enalaprilat did not alter femoral vascular tone at rest or vasodilation with sodium nitroprusside, but potentiated bradykinin-mediated vasodilation in patients (p<0.001) and controls (p = 0.02). Acetylcholine-mediated vasodilation was augmented only in patients (p<0.001), but not in control subjects. L-NMMA inhibited the potentiation by enalaprilat of acetylcholine and bradykinin responses. This study demonstrates that ACE inhibition selectively improves endothelial dysfunction in human atherosclerosis by enhancing NO activity. The antithrombotic and antiproliferative effects of NO may reduce adverse manifestations related to atherosclerosis during long-term therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Isolation, characterization, and distribution of a 24-kDa proteoglycan in the urine of cachectic cancer and AIDS patients.

Substantial weight loss in individuals with AIDS or cancer is associated with a poor prognosis and increased mortality. We have isolated and partially characterized a proteoglycan (named azaftig) from the urine of a cancer patient experiencing weight loss. Furthermore, we have raised a polyclonal antibody to azaftig in rabbits and developed a procedure to measure the level of this proteoglycan in urine by Western blot. We report the presence of azaftig in the urine of cancer and AIDS patients experiencing weight loss, but not in the control or weight-stable subjects. The azaftig-like immunoreactivity was present in 69.2% (9/13) of patients with weight loss, but only in 27.0% (3/11) of weight-stable cancer or AIDS patients and none of the control subjects (n = 8).

Adult↗
PubMed1999

Bioactive fragment of human interleukin-1beta (163-171) modulates the immune response to synthetic peptides of RESA of Plasmodium falciparum.

In this study a bioactive fragment, residues 163-171 of human interleukin-1beta (hu IL-1beta), that mimics the functions of the whole IL-1 molecule was chemically linked to two peptide sequences of the ring erythrocyte surface antigen (RESA), an asexual blood stage antigen of Plasmodium falciparum. The immunogenicity of different formulations was studied in different haplotypes of inbred mice. The peptide-IL-1beta conjugates delivered in liposomes showed the maximal antibody production. Antigen entrapped in liposomes at a dose of 5 microg showed antibody levels comparable to that of peptide conjugate in alum. The IgG subclass profile with different RESA peptides and its conjugates at various doses in liposomes induced predominantly IgG2a/2b isotypes while alum-delivered formulations showed both IgG1 and IgG2a/2b isotypes. In vitro studies of merozoite reinvasion showed varying degree (50-85%) of inhibition, maximum being with the peptide conjugates in liposomes (80-87%). Thus, this approach suggests that linking of hu IL-1beta is instrumental in augmenting the immune response against otherwise poorly immunogenic synthetic peptides.

Animals↗