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Biomedical subjects

S Srivastava

Publications and source records attributed to S Srivastava.

At least 91 records · Page 5Linked to original sources
PubMed2001

Identification of biochemical pathways for the metabolism of oxidized low-density lipoprotein derived aldehyde-4-hydroxy trans-2-nonenal in vascular smooth muscle cells.

Oxidation of low-density lipoproteins (LDL) generates high concentrations of unsaturated aldehydes, such as 4-hydroxy trans-2-nonenal (HNE). These aldehydes are mitogenic to vascular smooth muscle cells and sustain a vascular inflammation. Nevertheless, the processes that mediate and regulate the vascular metabolism of these aldehydes have not been examined. In this communication, we report the identification of the major metabolic pathways and products of [(3)H]-HNE in rat aortic smooth muscle cells in culture. High-performance liquid chromatography separation of the radioactivity recovered from these cells revealed that a large (60-65%) proportion of the metabolism was linked to glutathione (GSH). Electrospray mass spectrometry showed that glutathionyl-1,4 dihydroxynonene (GS-DHN) was the major metabolite of HNE in these cells. The formation of GS-DHN appears to be due aldose reductase (AR)-catalyzed reduction of glutathionyl 4-hydroxynonanal (GS-HNE), since inhibitors of AR (tolrestat or sorbinil) prevented GS-DHN formation, and increased the fraction of the glutathione conjugate remaining as GS-HNE. Gas chromatography-chemical ionization mass spectroscopy of the metabolites identified a subsidiary route of HNE metabolism leading to the formation of 4-hydroxynonanoic acid (HNA). Oxidation to HNA accounted for 25-30% of HNE metabolism. The formation of HNA was inhibited by cyanamide, indicating that the acid is derived from an aldehyde dehydrogenase (ALDH)-catalyzed pathway. The overall rate of HNE metabolism was insensitive to inhibition of AR or ALDH, although inhibition of HNA formation by cyanamide led to a corresponding increase in the fraction of HNE metabolized by the GSH-linked pathway, indicating that ALDH-catalyzed oxidation competes with glutathione conjugation. These metabolic pathways may be the key regulators of the vascular effects of HNE and oxidized LDL.

Aldehyde Reductase↗
PubMed2001

Changes in rodent-erythrocyte methemoglobin reductase system produced by two malaria parasites, viz. Plasmodium yoelii nigeriensis and Plasmodium berghei.

The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin and methemoglobin in blood. Exposure of red blood cells to oxidative stress (pathological/physiological) may cause impairment to this equilibrium. We studied the status of erythrocytic methemoglobin and the related reductase system during Plasmodium yoelii nigeriensis infection in mice and P. berghei infection in mastomys. Malaria infection was induced by intraperitoneal inoculation with 10(6) infected erythrocytes. The present investigation revealed a significant decrease in the activity of methemoglobin reductase, with a concomitant rise in methemoglobin content during P. yoelii nigeriensis infection in mice erythrocytes. This was accompanied with a significant increase in reduced glutathione and ascorbate levels. The activity of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase increased with a progressive rise in parasitemia. However, no methemoglobin or associated reductase activity was detected in normal and P. berghei-infected mastomys. P. berghei infection in mastomys resulted in an increase in the level of reduced glutathione and ascorbate in erythrocytes, and also in the activity of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase. These results suggest that antioxidants/antioxidant enzymes may prevent or reduce the formation of methemoglobin in the host and thereby protect the host from methemoglobinemia.

Animals↗
PubMed2001

Trends in biomarker research for cancer detection.

A key challenge in cancer control and prevention is detection of the disease as early as possible, enabling effective interventions and therapies to contribute to reduction in mortality and morbidity. Biomarkers are important as molecular signposts of the physiological state of a cell at a specific time. Active genes, their respective protein products, and other organic chemicals made by the cell create these signposts. As a normal cell progresses through the complex process of transformation to a cancerous state, biomarkers could prove vital for the identification of early cancer and people at risk of developing cancer. We discuss current research into the genetic and molecular signatures of cells, including microsatellite instability, hypermethylation and single-nucleotide polymorphisms. The use of genomic and proteomic high-throughput technology platforms to facilitate detection of early cancer by means of biomarkers, and issues on the analysis, validation, and predictive value of biomarkers based on these technologies are also discussed. We report on recent advances in identifying sources of biomarkers that can be accessed by noninvasive techniques, such as buccal-cell isolates, as well as traditional sources such as serum or plasma. We also focus on the work of the Early Detection Research Network at the National Cancer Institute, harnessing expertise from leading national and international institutions, to identify and validate biomarkers for the detection of precancerous and cancerous cells in assessing risk of cancer. The network also has a role in linking discovery to process development, resulting in early detection tests and clinical assessment.

Biomarkers, Tumor↗
PubMed2001

Three paths of adult development: conservers, seekers, and achievers.

This study examined the development of individuals whose motivations and skills led them to develop in different but equally positive ways. C. D. Ryff's (1989) scales for Environmental Mastery (EM) and Personal Growth (PG) were used to identify three configurations of positive mental health in 111 women of the Mills Longitudinal Study: Achievers, high on both scales; Conservers, high on EM, low on PG; and Seekers, high on PG, low on EM. Each pattern showed a distinctive profile of strengths on four criteria of maturity--competence, generativity, ego development, and wisdom--and each was predicted by distinctive features of positive and negative emotionality, identity processes, and change in self-control across 31 years of adulthood. Identity at age 43 mediated the influence of personality at age 21 in predicting positive mental health pattern at age 60.

Achievement↗
PubMed2001

Determinants of pancreaticoenteric anastomotic leak following pancreaticoduodenectomy.

BACKGROUND: The purpose of the present paper was to study the incidence, presentation and management of pancreaticoenteric anastomotic (PEA) leak following pancreaticoduodenectomy (PD) and to identify risk factors associated with PEA leak. METHODS: One hundred and twenty patients underwent PD for benign and malignant pancreatic and periampullary lesions from 1989 to 1998. Prospectively collected data were analysed for incidence and outcome of PEA leak. Four clinical, three laboratory parameters, preoperative biliary drainage (PBD), perioperative octreotide use, nine intraoperative parameters, site of tumour and stage of malignant tumours were analysed by univariate and multivariate logistic regression analysis to identify factors influencing PEA leak. RESULTS: Pancreatic leak developed in 15 (12.5%) patients. Nine patients (60%) had a PEA leak that manifested as controlled leak through the drain. All were managed conservatively and the leak stopped after a mean duration of 17 days (range: 6-32 days). Six (40%) patients had associated intra-abdominal complications, and three (50%) died in the postoperative period. Pancreatic fistula healed in the three remaining patients after a mean duration of 18 days (range: 15-25 days). Diabetes (P = 0.02; odds ratio (OR) = 4.60; 95% confidence interval (CI): 1.23-17.18), PBD (P = 0.03; OR = 4.82; 95% CI: 1.21-19.24), sequence of reconstruction (bilioenteric anastomosis as first anastomosis; P = 0.01; OR = 6.25; 95% CI: 1.45-26.83) and duration of surgery > 8 h (P = 0.01; OR: 5.61; 95% CI: 1.54-20.39) were associated with a significantly higher incidence of PEA leak. CONCLUSION: Pancreaticoenteric anastomotic leak occurred in 12% of patients undergoing PD for pancreatic and periampullary tumours. The majority of these were uncomplicated and healed with conservative treatment. Complicated leaks were associated with high mortality. Diabetes mellitus, PBD, prolonged surgery and the sequence of reconstruction were risk factors associated with an increased incidence of PEA leak.

Adult↗
PubMed2001

Recent advances in radionuclide therapy.

A variety of radionuclides continue to be investigated and/or clinically used for different therapeutic applications in nuclear medicine. The choice of a particular radionuclide with regard to appropriate emissions, linear energy transfer, and physical half-life is dictated to a large extent by the character of the disease (eg, solid tumor or metastatic disease) and by the carrier used to selectively transport the radionuclide to the desired site. An impressive body of information has appeared in the recent literature that addresses many of these considerations. This article summarizes and discusses the many recent advances and the progress in the clinical applications of therapeutic radionuclides in relatively new and developing areas, such as radioimmunotherapy, peptide therapy, intravascular therapy to prevent restenosis, radiation synovectomy, and bone malignancy therapy. Projections are made as to the future directions and progress in these areas. The crucial issue of a reliable, year-round supply of new and emerging therapeutic radionuclides in quantities sufficient initially for research, and then for routine clinical use, is a very worthy goal which, in the United States, remains to be achieved.

Angioplasty, Balloon, Coronary↗
PubMed2001

A new alkaloid and other anti-implantation principles from Tabernaemontana heyneana.

A new alkaloid designated as ervatine, in addition to seven known alkaloids, viz. tabersonine, coronaridine, heyneanine, voacristine, voacristine hydroxyindolenine, hydroxyibogamine, and coronaridine hydroxyindolenine, were isolated from the fruit of Tabernaemontana heyneana Wall. Characterisation and structure elucidation of these compounds was made on the basis of their spectral analyses. The ethanolic extract and isolated alkaloids heyneanine and voacristine prevented pregnancy when administered during the preimplantation period in Sprague-Dawley rats. These were, however, found to possess significant uterotrophic activity.

Alkaloids↗
PubMed2001

Substance P (free acid) adopts different conformation than native peptide in DMSO, water and DPPC bilayers.

The conformation of substance P (free acid) (SPOH) has been investigated in dimethylsulfoxide (DMSO), water and dipalmitoylphosphotidylcholine (DPPC) bilayers by two-dimensional NMR and restraint molecular dynamics simulations. The observed NOE patterns for SPOH in these media are very much different from each other. Molecular modeling of the conformation of SPOH by incorporating NOEs as distance restraints shows wide differences in its conformation in three media. The main structural features for SPOH in DMSO are y-bends at Pro4 and Phe7 along with a non-specific bend around Lys3-Pro4-Gln5-Gln6, which are stabilized by Lys3CO-->Gln5NH, Gln6CO-->Phe8NH hydrogen bonding. The more flexible conformation of SPOH in water is transformed to an ordered structure after incorporation in DPPC bilayers. The conformation of SPOH in DPPC bilayers is characterized by gamma-bends at Pro4, Gln6 and Phe7, which are stabilized by hydrogen bonding between Lys3CO-->Gln5NH, Gln5CO-->Phe7NH and Gln6CO-->Phe8NH, respectively. The absence of biological activity in SPOH has been attributed to the absence of any helix like structure at the central residues and absence of any interresidue interaction with C-terminal OH group, in DPPC bilayers, a feature shown to be an important prerequisite for SP and SP agonists to bind to the NKI tachykinin receptor.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Effect of beta-arteether treatment on erythrocytic methemoglobin reductase system in Plasmodium yoelii nigeriensis infected mice.

BACKGROUND: The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin (Hb) and methemoglobin (MetHb) in blood. Exposure of red blood cells to an oxidative stress (pathological/physiological) may cause impairment in this equilibrium. OBJECTIVE: The status of MetHb and the related reductase system was studied during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and beta-arteether treatment in mice. METHODS: Mice were divided into four groups. Normal group, normal mice treated with beta-arteether, P. y. nigeriensis infected mice and P. y. nigeriensis infected mice treated with beta-arteether. RESULTS: The present investigation revealed a marked decrease in the activity of MetHb reductase, with concomitant rise in MetHb levels during P. y. nigeriensis infection in mice erythrocytes (P < 0.001) as compared to normal mice. However, the activities of the associated enzymes viz., lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase were found to be increased with progressive rise in parasitemia. beta-Arteether treatment (12.5 mg/kg body weight) of infected mice (parasitemia 20-25%) from day 5 of post infection resulted in complete clearance of parasitemia on day 7 of post infection, which was accompanied by restoration of all the altered above mentioned indices to near normal levels as compared to infected mice (P < 0.001). CONCLUSION: These results suggest that there is a marked impairment of methemoglobin and methemoglobin reductase system during P. y. nigeriensis infection in mice. beta-Arteether treatment of infected mice resulted in complete clearance of parasitemia which also caused the restoration of methemoglobin and methemoglobin reductase system to near normal levels.

Animals↗
PubMed2001

Blood lead and zinc in pregnant women and their offspring in intrauterine growth retardation cases.

As part of our program to investigate the possible role of environmental pollutants in the incidence of intrauterine-growth retardation (IUGR) in India, we determined the lead and zinc levels in mothers and neonatal blood, collected at parturition, in cases with normal and IUGR babies. Both maternal and cord blood lead levels were significantly higher in IUGR cases than in normal cases (p < 0.05). The mean level of zinc was also higher in maternal blood of IUGR cases. Significantly, the mean cord blood lead level was > 10 microg/dL, which is greater than Centers for Disease Control's intervention level, in 54% of newborns. A good correlation (r = 0.53, p < 0.01) between maternal and cord blood lead levels confirmed the transfer of lead from mother to the fetus. There was a weak but significant relationhsip between cord blood lead levels and birth weight of newborns (r = -0.22, p < 0.05). The study may serve as a pointer to the perils of in utero exposure to chemical contaminants and a call for measures by the public health authorities for a continuous bio-monitoring program to evaluate impact of environmental pollutants on women and children's health.

Adult↗
PubMed2001

Proteomic approaches within the NCI early detection research network for the discovery and identification of cancer biomarkers.

In the postgenome era, proteomics provides a powerful approach for the analysis of normal and transformed cell functions, for the identification of disease-specific targets, and for uncovering novel endpoints for the evaluation of chemoprevention agents and drug toxicity. Unfortunately, the genomic information that has greatly expounded the genetic basis of cancer does not allow an accurate prediction of what is actually occurring at the protein level within a given cell type at any given time. The gene expression program of a given cell is affected by numerous factors in the in vivo environment resulting from tissue complexity and organ system orchestration, with cells acting in concert with each other and responding to changes in their microenvironment. Repositories of genomic information can be considered master "inventory lists" of genes and their maps, which need to be supplemented with protein-derived information. The National Cancer Institute's Early Detection Research Network is employing proteomics, or "protein walking", in the discovery and evaluation of biomarkers for cancer detection and for the identification of high-risk subjects. Armed with microdissection techniques, including the use of Laser Capture Microdissection (LCM) to procure pure populations of cells directly from human tissue, the Network is facilitating the development of technologies that can overcome the problem of tissue heterogeneity and address the need to identify markers in easily accessible biological fluids. Proteomic approaches complement plasma-based assays of circulating DNA for cancer detection and risk assessment. LCM, coupled with downstream proteomics applications, such as two-dimensional polyacrylamide gel electrophoresis and SELDI (surface enhanced laser desorption ionization) separation followed by mass spectrometry (MS) analysis, may greatly facilitate the characterization and identification of protein expression changes that track normal and disease phenotypes. We highlight recent work from Network investigators to demonstrate the potential of proteomics to identify proteins present in cancer tissues and body fluids that are relevant for cancer screening.

Biomarkers, Tumor↗
PubMed2001

ANX7 as a bio-marker in prostate and breast cancer progression.

The ANX7 gene codes for a Ca2+-activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro-arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 expression has prognostic value for predicting survival of breast cancer patients.

Animals↗
PubMed2001

Outcome following pancreaticoduodenectomy in patients undergoing preoperative biliary drainage.

OBJECTIVE: To assess the role of preoperative biliary drainage (PBD) in the early outcome following pancreaticoduodenectomy (PD) for periampullary tumors. DESIGN: Retrospective analysis of prospective database. PATIENTS AND METHODS: 121 PDs were performed for periampullary tumors between 1989 and 1998. 54 patients were operated following a PBD (group A) while 67 patients were operated without PBD. 50 patients underwent internal biliary drainage while 4 patients underwent external biliary drainage. Of the 67 patients without PBD, serum bilirubin was >10 mg% in 41 patients (group B) while 26 patients had bilirubin level of <10 mg% (group C). RESULT: Patients were well matched for age, sex distribution, presence of medical risk factors, duration of surgery, operative blood loss and stage of disease. Group A patients had a higher incidence of wound infection (43 vs. 24%; p = 0.03), intra-abdominal abscess (28 vs. 15%; p = 0.06), pancreaticojejunal anastomotic leak (20 vs. 5%; p = 0.01) and overall infective complications (52 vs. 29%; p = 0.01) compared to group B patients, and a higher overall infective complication rate than group C patients (52 vs. 27%; p = 0.02). Group B patients had a higher incidence of intra-abdominal bleeding compared to group A (20 vs. 6%; p = 0.01) and group C patients (20 vs. 4%; p = 0.03). Reoperation rate was significantly higher in group B compared to group A patients (27 vs. 13%; p = 0.04). The mortality rates were not significantly different in the three groups. CONCLUSION: Patients with jaundice (>10 mg%) have a higher risk of bleeding complications while those with PBD have more infective complications. PBD should be judicially employed in selected patients.

Adult↗
PubMed2001

Androgens suppress osteoclast formation induced by RANKL and macrophage-colony stimulating factor.

Androgen deficiency in males leads to an increase in osteoclastic bone resorption and a progressive decrease in bone mineral density. In the current studies, we examined the ability of 5 alpha-dihydrotestosterone to suppress osteoclast formation induced by receptor activator of NF-kB ligand (RANKL) and macrophage-colony stimulating factor in vitro. 5 alpha-Dihydrotestosterone suppressed the differentiation of bone marrow monocytes into osteoclasts from both sham-operated and orchidectomized mice. Androgen deficiency also led to an increase in the number of hematopoietic precursors capable of forming osteoclasts and increased the relative responsiveness of these cells to androgens in vitro. Interestingly, E2 was as effective as 5 alpha-dihydrotestosterone in suppressing osteoclast formation in bone marrow monocytes from both sham and orchidectomized mice. As with bone marrow monocytes, 5 alpha-dihydrotestosterone also suppressed RANKL-induced osteoclast formation in the monocyte-macrophagic cell line RAW264.7. In RAW264.7 cells, androgens appear to block RANKL-induced osteoclast formation through selective regulation of c-JUN: Accordingly, 5 alpha-dihydrotestosterone suppressed RANKL-induced c-Jun N-terminal kinase activation and reduced c-Jun expression levels. These effects resulted in a reduction in RANKL-induced activator protein-1 DNA binding activity and a corresponding suppression in activator protein-1-mediated transcriptional activation. These studies indicate that both E and androgens can suppress osteoclast formation via a direct, stromal cell-independent action on osteoclast precursors to block key transcription factors such as c-Jun essential for osteoclast differentiation.

Androgens↗
PubMed2001

Identification of inhibitors of DNA topoisomerase II from a synthetic library of glycoconjugates.

A library of 24 glycoconjugates related to glycosylated beta-amino acid derivative (I) was been prepared and screened against DNA topoisomerase-II of the filarial parasite S. cervi. Among these, compound 6 was found to be a potent inhibitor of DNA topoisomerase-II with 95% inhibition at 1.09 microM. Furthermore, compound 6 was at least three times more potent than the lead compound, glycosylated beta-amino acid derivative I.

Enzyme Inhibitors↗
PubMed2001

Mitral valve replacement with chordal preservation in a rheumatic population.

BACKGROUND AND AIM OF THE STUDY: Mitral valve replacement (MVR) with preservation of the subvalvular apparatus may maintain postoperative left ventricular (LV) function better than conventional MVR. A prospective study was undertaken to assess the advantages of chordal preservation in rheumatic patients undergoing isolated MVR. METHODS: Between January 1996 and January 1999, 240 patients with rheumatic etiology and normal LV ejection fraction (>50%) underwent isolated MVR using a St. Jude Medical prosthesis. Patients were allocated to two groups: in group I (n = 168), both the anterior and posterior chordae were preserved; in group II (n = 72), the entire native mitral valve apparatus was excised. Patients from both groups were evaluated postoperatively (mean 12.5 months) by echocardiography and treadmill testing. RESULTS: Demographic and clinical profiles were comparable in both groups. There were three early deaths in group I, and one in group II. There were no late deaths. One patient in group I required reoperation for a stuck mitral prosthesis. LV function (ejection fraction >50%) was better in group I (94%) than in group II (82%) (p <0.05). No patient in either group had LV outflow tract obstruction on echocardiography. Patients in group I showed better exercise performance on treadmill (Bruce protocol): 92% of group I patients versus 88% of group II patients (p >0.05) completed stage I; 16% of group I patients, but no group II patients, were able to complete stage IV (p <0.05). CONCLUSION: Mitral valve replacement with preservation of the subvalvular apparatus maintains LV function, and does not cause LV outflow tract obstruction.

Adult↗