Search PubMed⌕ Search

Biomedical subjects

C Prakash

Publications and source records attributed to C Prakash.

At least 55 records · Page 3Linked to original sources

Prevalence of transfusion associated infections in multitransfused children in relation to mandatory screening of HIV in donated blood.

Any change in risk behavior related to acquisition of human immunodeficiency virus (HIV) infection is likely to reduce simultaneously the risk for other agents transmitted through identical routes. A study carried out in the city of Delhi, India on the load of transfusion associated infections among multitransfused (MT) children in relation to mandatory screening of HIV infection in donated blood indicated unchanged prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among the group of MT children transfused after the implementation of mandatory screening of HIV infections in blood banks, i.e. post-implementation period (prevalence of HBV, HCV and HDV being 32.8%, 31.3% and 1.6% respectively) compared to a group of MT children transfused over a similar duration before the implementation of mandatory screening i.e. pre-implementation period (prevalence of HBV, HCV and HDV being 28.1%, 26.6% and 1.6% respectively). However, reduction could be recorded in the prevalence of IgM and IgG classes of antibodies to both CMV and HSV-2 infections among MT children receiving transfusion during the post-implementation period (prevalence of 3.1% and 37.1% for CMV IgM and CMV IgG respectively; prevalence of 3.1% and 25% for HSV-2 IgM and HSV-2 IgG, respectively) compared to the group of MT children transfused in the pre-implementation period (prevalence of 15.6% and 56.3% for CMV IgM and CMV IgG respectively; prevalence of 18.8% and 45.2% for HSV-2 IgM and HSV-2 IgG, respectively). These reductions were statistically significant (p values < 0.02 and < 0.05 for CMV IgM and CMV IgG; p values < 0.01 and < 0.02 for HSV-2 IgM and HSV-2 IgG respectively). These observations were in accordance with the recorded reduction in the prevalence of CMV and HSV-2 infections and unaltered prevalence of HBV, HCV and HDV infections in the group of donors donating blood during the post-implementation period compared to those donating in the pre-implementation period. Study of epidemiological risk factors among blood donors showed a change in behavior towards safer sex practice with only 13.0% of donors in the post-implementation period having history of sex with one or more female commercial sex workers during their donation periods compared to 41.5% of donors in the pre-implementation period having similar history (p < 0.001). However no change could be recorded in the proportion of donors donating at frequency higher than the permissible guidelines among the two groups. The present study points out nosocomial transmission as well as limitations in the existing guidelines for screening of infectious agents in blood banks as possible incriminating factors towards acquisition of hepatitis virus infections in blood donors as well as in MT children.

Adult↗

Non Hepatitis viruses in causation of acute sporadic non-A, non-B viral hepatitis.

Viruses other than Hepatitis viruses i.e. Cytomegalovirus, Epstein-Barr Rubella etc., can cause a clinical picture resembling that of viral hepatitis. Consequently, these viruses can falsely contribute to the diagnosis of Non-A, Non-B hepatitis amongst of sporadic jaundice. This study attempts to find out the possibility of occurrence of such an event.

Acute Disease↗

Mechanism of block of a human cardiac potassium channel by terfenadine racemate and enantiomers.

1. The cardiac toxicity of racemic terfenadine (marked QT prolongation and polymorphic ventricular arrhythmias) is probably due to potassium channel blockade. To test whether one of its enantiomers would be a less efficient potassium channel blocker, we compared the mechanism of action of the racemate with that of the individual enantiomers. 2. We synthesized the individual enantiomers of terfenadine and examined under whole cell voltage-clamp conditions the mechanism of action of the racemate, both enantiomers and a major metabolite on a cloned human cardiac potassium channel, hKv1.5. This delayed rectifier is sensitive to quinidine, clofilium and other 'class III' antiarrhythmic drugs at clinically relevant concentrations. 3. Upon depolarization, racemic terfenadine and its enantiomers induced a fast decline of hKv1.5 current towards a reduced steady state current level. During subsequent repolarization the tail currents deactivated more slowly than the control, resulting in a 'crossover' phenomenon. 4. The voltage-dependence of block was biphasic with a steep increase in block over the voltage range of channel opening (-30 to 0 mV), and a more shallow phase positive to 0 mV (where the channel is fully open). The latter was consistent with a binding reaction sensing 21% of the transmembrane electrical field (with reference to the cell interior). 5. The EC50 for hKv1.5 block by racemic terfenadine was 0.88 microM, while the values for R- and S-terfenadine were 1.19 microM and 1.16 microM, respectively. In contrast, the acid metabolite reduced hKv1.5 current by only 5% at a concentration of 50 microM. 6. These findings suggest that terfenadine blocks the hKvl.5 channel after it opens by entering into the internal mouth of the channel. We have previously shown that quinidine blocks hKvl.5 in a similar manner but with an apparent affinity of ~6 micro M. Thus, terfenadine and its enantiomers are approximately equipotent open state blockers of this human K+ channel and about 6 times more potent than quinidine. The similar state-, time-, and voltage-dependence of hKvl.5 block by both enantiomers also indicates that the chiral centre does not significantly constrain the orientation of critical binding determinants of terfenadine with respect to the receptor site.

Animals↗

An outbreak of viral hepatitis E: role of community practices.

A small localised outbreak of viral hepatitis due to HEV occurred in an educated and well placed community. The overall attack rate was found to be 1.9%; the children and adults were equally affected. No fatality was observed. Five blood samples collected from the cases of jaundice were found negative for Anti HAV IgM, HBsAg and Anti HBc IgM, but positive for Anti HEV. The infection spread by contamination of piped water by sewage system resulting from scarcity of water, intermittent water supply and installation of on-line private booster pumps by the residents. Community action, especially the boiling of drinking water till the quality of piped water improved, restricted jaundice cases to only one incubation period. The outbreak highlights the importance of community behaviour in first precipitating the crisis and then limitating the damage.

Adolescent↗

An institutional outbreak of hepatitis E--reported first time from Calcutta city.

A sudden outbreak of hepatitis occurred in a micro-epidemic form, amongst the staff members of the School of Tropical Medicine, Calcutta, during May-June, 1995. A total of 21 persons developed jaundice, out of whom 11 members who attended the Virology Department and were tested for detection of different serological markers of hepatitis by ELISA. All the sera (N = 11) showed evidence of non-A, non-B infection by process of exclusion and 9 of the above sera showed evidence of anti-HEV when tested specifically. This is the first documented outbreak of viral hepatitis in respect of Calcutta.

Adult↗

An outbreak of viral hepatitis in Jodhpur city of Rajasthan.

An outbreak of Viral hepatitis occurred in Jodhpur city of Rajasthan during April to June, 1994. The attack rate was 3.04 per cent among 0-14 years age group and 5.49% among the age group above 15 years, the overall attack rate being 4.5 per cent. Males were more affected than females. Epidemiological and serological findings suggest that the outbreak was due to enterically transmitted Non A Non B virus. The source of infection was drinking water contaminated with sewage.

Adolescent↗

Decreased systemic thromboxane A2 biosynthesis in normal human subjects fed a salmon-rich diet.

Nine normal male subjects were fed a reference diet typical of that consumed in the United States and a diet containing approximately 450 g salmon (salmon-rich diet). The salmon diet contained approximately 6 g omega 3 fatty acids that comprised 2.0% energy intake/d for each individual. The percent energy contribution of protein, carbohydrate, and fat (19%, 56%, and 25%, respectively) was identical for the two diets. Urinary excretion of 2,3-dinor-thromboxane B2 was significantly lower (0.74 +/- 0.26 ng/24 h) with the salmon diet compared with the reference diet (0.95 +/- 0.31 ng/24 h). In addition, in vitro generation of thromboxane B2 in response to collagen-stimulated aggregation of platelet-rich plasma from subjects consuming the salmon diet was reduced (1.87 +/- 0.79 ng/mL) compared with subjects consuming the reference diet (3.10 +/- 1.81 ng/mL). Urinary 2,3-dinor-6-oxo-prostaglandin F1 alpha excretion in subjects was not significantly different between the salmon diet (0.69 +/- 0.33 ng/24 h) and the reference diet (0.81 +/- 0.44 ng/24 h).

Adult↗

Hepatic manifestations in typhoid fever.

Thirty one children with typhoid fever aged 2 months to 12 years and blood culture positive for multidrug resistant S. typhi were prospectively studied for their hepatic functions at the time of hospitalization and 2-3 weeks after completion of antibiotic therapy. Hepatic manifestations included hepatomegaly (51.6%); jaundice (16.1%); raised levels of serum glutamic oxaloacetic transaminase (SGOT) (61.3%), serum glutamic pyruvic transaminase (SGPT) (48.4%), alkaline phosphatase (AP) (22.6%) and serum bilirubin (SB) (6.1%); reduced levels of serum albumin (SA) (41.9%); prolonged prothrombin time (PT) (9.7%) and abnormal ultrasound abdomen (19.3%). Hepatic dysfunction was a notable feature even in those cases without hepatomegaly, with raised levels of SGOT (60%), SGPT (40%), AP (20%), SB (6.7%), decreased SA (53.3%) and prolonged PT (6.7%). There was no correlation between the degree of hepatic enlargement or hyperbilirubinemia with abnormalities in liver functions. Hepatic dysfunction was noticed to be transient, as all these parameters returned to normal within 2-3 weeks after successful antibiotic therapy.

Child↗

Stereoselective disposition of hexobarbital and its metabolites: relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects.

In vitro studies with human liver preparations suggest that the metabolism of hexobarbital involves CYP2CMP--the determinant of the S-mephenytoin 4'-hydroxylation polymorphism, but no in vivo evidence of interphenotypic differences exist. The pharmacokinetics and urinary excretion of hexobarbital and its metabolites were, therefore, investigated following oral administration of a differentially labelled pseudoracemate that allowed determination of the fate of the individual enantiomers. Studies were undertaken in 10 Caucasian and nine Chinese healthy subjects known to be either extensive (EM) or poor (PM), metabolizers of mephenytoin. No inter-racial differences were observed in any of the measured parameters within a given phenotype. However, pronounced stereoselectivity in disposition was noted in EMs with R-(-)-hexobarbital's oral clearance being five- to six-fold greater than that for the S-(+)-enantiomer. By contrast, the S-(+)-isomer was eliminated twice as fast as R-(-) hexobarbital in PMs and, in addition, the oral clearances of both enantiomers were significantly reduced compared with their values in EMs. Formation of 3'-hydroxy- and 3'-ketohexobarbital and 1,5-dimethylbarbituric acid were the major identified routes of metabolism for each enantiomer in both phenotypes. Furthermore, these pathways were found to co-segregate with the mephenytoin polymorphism and in EMs they were primarily responsible for the observed stereoselectivity in disposition. These findings, therefore, confirm the stereoselectivity in hexobarbital's disposition in humans and identify the major pathways of metabolism involved. Additionally, the results indicate that CYP2CMP is a major determinant of the in vivo metabolism of both of hexobarbital's enantiomers but especially that of the R-(-)-enantiomer.

Administration, Oral↗

Prostaglandin E2 limits arachidonic acid availability and inhibits leukotriene B4 synthesis in rat alveolar macrophages by a nonphospholipase A2 mechanism.

Prostaglandin E2 (PGE2), a potent mediator of inflammation released in large amounts by endotoxin-stimulated alveolar macrophages (AM), has been shown to inhibit leukotriene B4 (LTB4) release by activated neutrophils. We investigated the hypothesis that LTB4 synthesis by AM can be regulated by PGE2 and performed experiments to determine the biochemical site of regulation. AM obtained from Sprague-Dawley rats were preincubated with PGE2 before stimulation with the calcium ionophore A23187. LTB4, platelet-activating factor (PAF), lysoPAF, (AA), and 5-hydroxyeicosatetraenoic acid were isolated from AM cells and supernatants, then quantified by gas chromatography/electron capture negative ion mass spectrometry. Stimulated AM released 30.50 +/- 4.52 ng LTB4/10(6) cells and were inhibited by PGE2 in a dose dependent manner. PGE2 (1 microM) inhibited LTB4 synthesis by 37% and decreased release of both 5-hydroxyeicosatetraenoic acid and arachidonic acid by stimulated AM, but did not alter synthesis of PAF or lysoPAF. These mass measurements suggest that PGE2 does not affect the activity of phospholipase A2, PAF acetyltransferase, leukotriene A4 hydrolase. We conclude that PGE2 attenuates LTB4 production in alveolar macrophages by altering the activity of lipases other than phospholipase A2. PGE2-mediated inhibition of LTB4 synthesis by AM may regulate the initiation of lung inflammation.

Animals↗

Cyclooxygenase-derived metabolites of 8,9-epoxyeicosatrienoic acid are potent mitogens for cultured rat glomerular mesangial cells.

The mitogenic effects of 11(R)-hydroxy-8,9-epoxyeicosatrienoic acid (EET) enantiomers were investigated in cultured rat glomerular mesangial cells. Both 11(R)-hydroxylated 8(R),9(S)- and 8(S),9(R)-EET at 1 microM stimulated [3H]-thymidine incorporation to 300% and 280%, with 50% maximal effect occurring at 8 x 10(-9) M and 1 x 10(-8) M, respectively. Similar concentration-dependent effects were observed in stimulating induction of the immediate early gene, c-fos. Mitogenic activity of the 11(R)-hydroxylated enantiomers was not affected by prior downregulation of protein kinase C, suggesting involvement of protein kinase C-independent mechanisms. These findings suggest that either trans- or intracellular metabolism of 8,9-EET by cyclooxygenase occurs during inflammatory glomerular diseases and that the resulting metabolites are involved in mesangial cell proliferation.

8,11,14-Eicosatrienoic Acid↗

Dietary modification of omega 6 fatty acid intake and its effect on urinary eicosanoid excretion.

A group of women were fed two separate diets in a crossover study and urinary eicosanoids were quantified. One diet contained 3.1% of total energy (en%) as polyunsaturated fatty acids (3.0 en% linoleic acid) and the other contained 8.4 en% polyunsaturated fatty acids (8.3 en% linoleic acid). Carbohydrate replaced fat in the low-polyunsaturated-fat diet. No changes were observed in the urinary excretion of 6-oxo-prostaglandin F1 alpha, its 2,3-dinor metabolite or thromboxane B2 by subjects on either of the diets. Urinary 2,3-dinor-thromboxane B2 excretion was lower (206.5 ng/24 h) when subjects were fed the high-omega 6 polyunsaturated fatty acid diet when compared with the lower-omega 6 polyunsaturated fatty acid diet (275.3 ng/24 h). Conversely, urinary prostaglandin E2 was higher (139.2 ng/g creatinine) during the higher-omega 6 polyunsaturated fatty acid diet when compared with the lower-omega 6 polyunsaturated fatty acid diet (94.4 ng/g creatinine).

6-Ketoprostaglandin F1 alpha↗

Role of transfusion-mediated viral infections on the lymphocyte subset profile in multi-transfused children.

A total of 74 multitransfused (MT) children of beta thalassaemia major were analysed for prevalent viral markers transmitted through transfusion. A higher incidence of serological markers for Hepatitis B virus (HBV), cytomegalovirus (CMV) could be observed in the group of MT children compared to control group. There was a significant trend (chi 2 = 33.4; P < 0.001) in the increase in prevalence of viral markers along with the increase in the number of transfusions. MT children receiving more than 50 transfusions were found to have evidence for at least one or multiple viral infections transmitted through blood. Children receiving more than 50 transfusions were characterized by marked alteration of T3, T8, and B cells while T4/T8 ratio was found to be significantly decreased (P < 0.001) only in the group of children receiving more than 100 transfusions. Relative assessment of the alteration of lymphocyte subsets in various groups of viral infection showed that cases with CMV IgM to have more marked influence on the alteration of T8 cells, T4/T8 ratio, and B cells compared to other groups of viral infections. Reassessment of the lymphocyte subset profile in MT children in the light of CMV IgM positive cases revealed that in children receiving more than 50 transfusions significant alterations of lymphocyte subjects were influenced by the presence of CMV IgM positive cases in these groups. Our study points out that the correlation between the alteration of lymphocyte subset profile and number of transfusion in MT children need to be reassessed in the light of acute CMV infection in the form of CMV IgM.

Acquired Immunodeficiency Syndrome↗

Studies on the peptides encoded by rat and human angiotensin II complementary RNA.

Some evidence suggests that RNA complementary to the messenger RNA encoding a peptide hormone encodes a complementary peptide that binds the original peptide hormone. The objective of this investigation was to assess in vivo the ability of complementary angiotensin II (II Ang) peptides to block the biological effects of angiotensin II (Ang II). Increasing concentrations of rat or human II Ang were preincubated with Ang II for 2 hours, and this solution was then infused intra-arterially into the superior mesenteric artery. Human, but not rat, II Ang dose-dependently inhibited Ang II-induced mesenteric vasoconstriction. The in vivo inhibitory potencies of human II Ang and [Sar1,Ile8]Ang II, with respect to inhibition of the pressor response to Ang II, were compared by infusing intravenously increasing doses of each blocker and determining their effects on a fixed intravenous dose of Ang II. Although human II Ang could abolish the pressor response to Ang II, [Sar1,Ile8]Ang II was approximately 100 times more potent in this regard. A fixed dose of human II Ang (150 micrograms/min i.v.) inhibited the effects of increasing doses of Ang II on mesenteric vascular resistance, arterial blood pressure, and aldosterone secretion. The 1H nuclear magnetic resonance spectra of human II Ang and Ang II were determined both separately and when combined in the same cuvette. The spectrum obtained by overlaying the separate spectra for these two peptides was the same as the spectrum obtained from the mixture of these two peptides in the same cuvette.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Epidemiology of a jaundice outbreak in Rairangpur town in Orissa.

A jaundice epidemic broke out in Rairangpur town of Orissa during December 1989 to January 1990. The attack rate was 1.2 per cent with 89.8 per cent cases among 11-40 years age group. Male-female ratio of cases was 2.3:1. The source of infection was traced to contamination of drinking water from leakage in the pipe line which was confirmed by a subsequent case control study. The outbreak was due to enterically transmitted Non A Non B hepatitis virus.

Adolescent↗