Resurgence of chikungunya virus in India: an emerging threat.
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Alphavirus Infections↗
Biomedical subjects
S K Saxena
Publications and source records attributed to S K Saxena.
Total direct cost, length of hospital stay, institutional discharges and their determinants from rehabilitation settings in stroke patients.
BACKGROUND: Length of hospital stay (LOHS) is the largest determinant of direct cost for stroke care. Institutional discharges (acute care and nursing homes) from rehabilitation settings add to the direct cost. It is important to identify potentially preventable medical and non-medical reasons determining LOHS and institutional discharges to reduce the direct cost of stroke care. AIM: The aim of the study was to ascertain the total direct cost, LOHS, frequency of institutional discharges and their determinants from rehabilitation settings. METHODOLOGY: Observational study was conducted on 200 stroke patients in two rehabilitation settings. The patients were examined for various socio-demographic, neurological and clinical variables upon admission to the rehabilitation hospitals. Information on total direct cost and medical complications during hospitalization were also recorded. The outcome variables measured were total direct cost, LOHS and discharges to institutions (acute care and nursing home facility) and their determinants. RESULTS: The mean and median LOHS in our study were 34 days (SD = 18) and 32 days respectively. LOHS and the cost of hospital stay were significantly correlated. The significant variables associated with LOHS on multiple linear regression analysis were: (i) severe functional impairment/functional dependence Barthel Index < or = 50, (ii) medical complications, (iii) first time stroke, (iv) unplanned discharges and (v) discharges to nursing homes. Of the stroke patients 19.5% had institutional discharges (22 to acute care and 17 to nursing homes). On multivariate analysis the significant predictors of discharges to institutions from rehabilitation hospitals were medical complications (OR = 4.37; 95% CI 1.01-12.53) and severe functional impairment/functional dependence. (OR = 5.90, 95% CI 2.32-14.98). CONCLUSION: Length of hospital stay and discharges to institutions from rehabilitation settings are significantly determined by medical complications. Importance of adhering to clinical pathway/protocol for stroke care is further discussed.
Adult↗
Studies on the production and quality assurance of miniature (125)I radioactive sources suitable for treatment of ocular and prostate cancers.
(125)I sources were prepared by adsorption of (125)I on palladium-coated silver wires. The effect of reducing agent on percentage adsorption of (125)I was studied and the amount of adsorbed activity on source core was studied by repeated adsorption cycles. The activity per source in the sources produced from the same batch varied with coefficient of variation (i.e. the ratio of standard deviation to mean multiplied by 100) less than 10%. The unencapsulated source exhibited low leachability (< 0.01%). The laser parameters were optimized to obtain quality welds with negligible leak rate. The sources were laser-encapsulated in titanium capsules of 0.8 mm (OD) x 4.5mm (l). The release of radioactivity from encapsulated sources in an immersion test at 50 degrees C for 5 h was <5 nCi (185 Bq). The surface contamination on the sealed capsules was found to be<0.05 nCi or 1.85 Bq per source. The sources were used in the treatment of a child having retinoblastoma.
Adsorption↗
Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial.
OBJECTIVES: The authors evaluated the effect of zinc treatment as an adjunct to oral rehydration therapy on stool output and diarrheal duration in children with acute noncholera diarrhea with dehydration. METHODS: This double-blind, randomized, controlled trial was conducted at two urban hospitals in New Delhi. A total of 287 dehydrated male patients, ages 3 to 36 months, with diarrhea for 12 months) and weight for height (65%-80% or >80% National Centre for Health Statistics median). Participants in the zinc group received 15 mg ( 12 months) elemental zinc daily in three divided doses for 14 days. The main outcome measures were stool output and diarrheal duration. RESULTS: Zinc treatment reduced total stool output (ratio of geometric means, 0.69; 95% confidence interval [CI]: 0.48, 0.99) and stool output per day of diarrhea (ratio of geometric means, 0.76; 95% CI: 0.59, 0.98). The risk of continued diarrhea was lower (relative hazards, 0.76; 95% CI: 0.59, 0.97) and the proportion of diarrheal episodes lasting >or= 5 days (odds ratio, 0.49; 95% CI: 0.25, 0.97) or >or= 7 days was less (odds ratio, 0.09; 95% CI: 0.01, 0.73) in the zinc group. CONCLUSIONS: This study demonstrates a beneficial effect of zinc administered during acute diarrhea on stool output, diarrheal duration, and proportion of episodes lasting more than 7 days. The effects are large enough to merit routine use of zinc during acute diarrhea in developing countries.
Acute Disease↗
Free glutamic acid content of milk in Indian mothers.
Free amino acids levels in the milk of 11 healthy Indian mothers were determined using automatic precolumn derivatization procedure. The aim of the study was to find out the relative concentration of glutamic acid and glutamine in the milk. Glutamic acid is the dominant free amino acid found in the milk of Indian mothers. Glutamic acid and glutamine together formed the major nonessential amino acids present in the human milk. Although glutamic acid has been shown to be the major amino acid in human milk in many studies, to the best our knowledge, this is the first report to confirm that glutamic acid is the most abundant amino acid in milk in Indian mothers.
Adult↗
Preparation and evaluation of [166Ho] holmium-dimethyl diethylenetriaminepentaaceticacid (DMDTPA) as potential radiopharmaceutical for endovascular radiation therapy (EVRT).
Holmium-166 with its favorable radiation characteristics could be used in endovascular radionuclide therapy (EVRT) technique in liquid filled low-pressure balloon angioplasty. 166Ho-dimethyl di ethylene triamine penta acetic acid (DMDTPA) was prepared and its biodistribution carried out to evaluate its suitability as an EVRT formulation. DMDTPA was synthesized, characterized and was complexed with 166Ho. The complex was stable at 37 degrees C in human serum environment and at room temperature for 48 h. Biodistribution studies in mice revealed rapid renal clearance (approximately 90% of the injected dose in 30 min p.i.) with insignificant retention in any of the major organs including bone. The studies show that 166Ho-DMDTPA is a good formulation which can be explored as an EVRT source.
Animals↗
Alteration in plasma glucose levels in Japanese encephalitis patients.
A unique factor, human T cell hypoglycaemic factor (hTCHF), has been shown to produce hypoglycaemia during the convalescent stage in the plasma of patients with Japanese encephalitis virus (JEV) infection. The present study was undertaken to investigate the ability of T cells from fresh peripheral blood mononuclear cells (PBMC) of such patients to produce hTCHF. The PBMC, as well as the individual subpopulations, were cultured for 24 h and the culture supernatants (CS) were assayed for hypoglycaemic activity. The activity was observed in the CD8+ T cells. The hypoglycaemia in JE-confirmed patients coincided with the gradual rise in circulating glucagon level, with no significant alterations in insulin, growth hormone and cortisol levels. The hTCHF was purified by ion exchange chromatography and the purified protein was observed as a approximately 25 kDa band on SDS-PAGE. Secretory hTCHF in the sera of patients and T cell CS was present in 88% of convalescent serum samples. We conclude that during the convalescent stage of JEV infection, a unique factor, hTCHF, is secreted by activated CD8+ T cells from patients and that this is responsible for the development of hypoglycaemia.
Adolescent↗
Induction of nitric oxide synthase during Japanese encephalitis virus infection: evidence of protective role.
The ability of Japanese encephalitis virus (JEV) and JEV-induced macrophage-derived factor (MDF) to modulate nitric oxide synthase (NOS) activity in brain and tumor necrosis factor-alpha (TNF-alpha) and the possible antiviral role of NOS during JEV infection were investigated. NOS activity and particularly that of the inducible form of NOS (iNOS) was significantly enhanced in JEV or JEV-induced MDF-treated mice. Following JEV infection, total NOS activity in brain was gradually increased from Day 3 and reached a peak on Day 6. MDF-induced NOS activity and iNOS activity were dose dependent and maximum activity was observed at 1 h after treatment. The response was sensitive to anti-MDF antibody treatment and N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NOS. Pretreatment of JEV-infected mice with L-NMMA increased the mortality as evident from reduced mean survival time (MST, 11.8 days) compared to placebo treated JEV-infected mice (MST, 17 days). The enhanced level of TNF-alpha observed in the early phase of JEV infection correlated well with the enhanced activity of iNOS. These observations thus provide evidence of the protective role of iNOS during JEV infection and indicate that iNOS may be a key mediator in host innate immune response to infection.
Animals↗
Potential 166Ho radiopharmaceuticals for endovascular radionuclide therapy. II. Preparation and evaluation of 166Ho-DTPA.
166Ho, with its favourable radiation characteristics of t(1/2) 26.8 h and Ebeta 1.85 and 1.75 MeV, is proposed as a suitable choice for the endovascular radionuclide therapy (EVRT) technique of liquid filled, low pressure balloon angioplasty. 166Ho was produced by the (n,gamma) reaction on a natural Ho2O3 target. The specific activity obtained was approximately 100 mCi x mg(-1) when irradiated at a flux of 2 x 10(13) n x cm(-2) s(-1) for approximately 7 days, and the possible contaminant 166Ho(m) was not detected. 166Ho was easily complexed with diethylenetriaminepentaacetic acid (DTPA) at a ligand to metal molar ratio ([L]:[M]) of 1:1 at room temperature (22-23 degrees C) and a reaction time of a few minutes. The radiochemical purity was >99%, as determined by paper chromatography using a mixture of pyridine, ethanol and water (1:2:4) as solvent. The complex had good stability up to 72 h at 37 degrees C in a serum environment. In a study using Swiss mice > 85% of the injected dose was cleared into the urine within 30 min post-injection, with insignificant retention in any major tissues. The studies show that the 166Ho-DTPA complex could be an alternative to the more expensive and difficult to access 188Re based products for EVRT, and provide adequate uniform radiation dose for the arterial vessel wall under treatment.
Angioplasty, Balloon, Coronary↗
Effect of trypanosomes infection on blood ascorbic acid and serum aldolase levels on the fresh water fishes, Clarias batrachus and Heteropneustus fossilis.
The trypanosomes presence has been found to decrease blood ascorbic acid levels in fishes, Clarias batrachus and Heteropneustus fossilis by 55.7% and 54.70% respectively. The infection also showed significant increase in serum aldolase level of three fishes by 50.19% and 48.06% respectively.
Animals↗
Regulation of intestinal regeneration: new insights.
Intestinal regeneration is the process by which intestinal injury penetrating deep to the lamina propria heals. The regenerative process involves epithelial cell migration and proliferation, changes in cellular function, adaptation of subepithelial tissues, and contraction of the injured area. This requires interaction of multiple cell types. While many observations have been made about the process of regeneration, its regulation is not well understood. Previous studies, performed primarily in a serosal patch model, have identified many potential regulatory factors. These include location and size of the injury, other associated injury, e.g., resection, and a variety of agents that influence one or more of the primary processes involved. Epidermal growth factor (EGF), in particular, appears to play a role in many aspects of regeneration. Recent advances in the understanding of intestinal growth regulation have provided new insights into the regulation of intestinal regeneration. Developmental studies in genetically manipulated mice suggest a role for gene products not previously implicated in regeneration. The importance of apoptosis in growth regulation has recently been emphasized. Mesenchymal-epithelial interactions have gained greater appreciation. Finally, it has become clear that immune cells and cytokines are important factors in this process. Transforming growth factor-beta (TGFbeta) has been implicated as another important regulator of several of the processes involved in intestinal regulation. Improved understanding of the regulation of intestinal regeneration will lead to new therapeutic approaches to stimulate intestinal healing in the clinical setting.
Animals↗
Antiviral effect of nitric oxide during Japanese encephalitis virus infection.
The ability of Japanese encephalitis virus (JEV) and JEV-induced macrophage derived neutrophil chemotactic factor (MDF) to produce nitric oxide (NO), and the possible antiviral effect of NO during JEV infection, was investigated. Splenic macrophages of JEV infected mice produced maximum NO in vivo at day 7 post infection, and in vitro at 24 h after JEV stimulation. MDF-induced NO production was dose dependent and maximal at 60 min after MDF treatment. The response was sensitive to anti-MDF antibody treatment and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Pretreatment of mice with L-NMMA increased the mortality to 100% in JEV infected mice in vivo and inhibited NO production in vitro, while MDF stimulated macrophages inhibited virus replication with high levels of NO production. MDF treatment increased the survival rate of JEV infected mice. The findings thus demonstrate that MDF induces production of NO during JEV infection, which has an antiviral effect. This may be one of the important mechanisms of natural immunity in controlling the initial stages of JEV infection.
Animals↗
Development of a computer software for analysis of SDS-PAGE protein fingerprints of bacterial isolates.
Protein fingerprinting is a widely used technique in epidemiological studies for typing bacterial strains. This study reports the development of a computer based gel analysis system. The system has the capability to analyse SDS-PAGE whole-cell protein profiles using digital image processing techniques. The software incorporates spatial and frequency domain operators for image enhancement, support for geometric correction of images and new algorithms for identification of strain tracks and protein bands. The system also provides facilities for correcting imaging defects for inter-gel comparison, similarity analysis, clustering and pictorial representation of results as a dendrogram. The software is highly interactive, user-friendly and can produce accurate results for differentiation of bacterial strains with minimal overhead of time.
Algorithms↗
Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction.
Several nonmammalian members of the RNase A superfamily exhibit anticancer activity that appears to correlate with resistance to the cytosolic ribonuclease inhibitor (RI). We mutated two human ribonucleases-pancreatic RNase (hRNAse) and eosinophil-derived neurotoxin (EDN)-to incorporate cysteine residues at putative sites of close contact to RI, but distant from the catalytic sites. Coupling of Cys89 of RNase and Cys87 of EDN to proteins at these sites via a thioether bond produced enzymatically active conjugates that were resistant to RI. To elicit cellular targeting as well as to block RI binding, transferrin was conjugated to a mutant human RNase, rhRNase(Gly89)-->Cys) and a mutant EDN (Thr87-->Cys). The transferrin-rhRNase(Gly89-->Cys) thioether conjugate was 5000-fold more toxic to U251 cells than recombinant wild-type hRNase. In addition, transferrin-targeted EDN exhibited tumor cell toxicities similar to those of hRNase. Thus, we endowed two human RI-sensitive RNases with greater cytotoxicity by increasing their resistance to RI. This strategy has the potential to generate a novel set of recombinant human proteins useful for targeted therapy of cancer.
Animals↗
Degradation of Japanese encephalitis virus by neutrophils.
The ability of neutrophils to degrade the phagocytosed Japanese encephalitis (JE) virion, via triggering of the respiratory burst and generation of toxic radicals has been investigated. JEV or JEV-induced macrophage derived factor (MDF) induces increase in intracellular oxidative signals with generation of superoxide anion (O2-), via activation of cytosolic NADPH and subsequent formation of hydrogen peroxide, with maximum activity on day 7 post infection. The response was sensitive to anti-MDF antibody treatment. Further, the study revealed rapid degradation of phagocytosed JE viral protein and nucleic acid. The viral protein degradation was partially dependent on the generation of toxic oxygen species as it could be abrogated by pretreatment of the cells with staurosporine.
Animals↗
Efficacy of milk versus yogurt offered as part of a mixed diet in acute noncholera diarrhea among malnourished children.
We compared the clinical outcome of acute diarrhea in 96 malnourished boys (aged 4 to 47 months) receiving full-strength milk compared with yogurt offered as part of a mixed diet. All had weight for height less than or equal to 80% of the National Centre for Health Statistics median. They were randomly assigned to receive milk formula (MF; 67 cal/100 ml) or yogurt formula (YF; prepared from the same milk formula) at the rate of 120 ml/kg body weight in seven divided feedings. Stool-reducing substances (> 1%) were detected more frequently in the MF group, and the differences were significant for day 3 of the study (p = 0.04). However, the geometric mean (95% confidence interval) of the total stool weights (gm/kg) during 0 to 72 hours (MF 128.8 [103, 161.4]; YF 110.9 [87, 142.2]) was comparable (p = 0.37) as was the median (range) duration of diarrhea (hours) (MF 45 [4, 183]; YF 52 [7, 173] p = 0.94). The treatment failure rates in the MF (8.2%) and YF (6.3%) groups were also similar (p = 0.67). The children consuming milk had higher median percent weight gain at the end of 72 hours of the study (p = 0.04) and at recovery (p = 0.02). Routine substitution of yogurt as small frequent feedings as an addition for semisolid food to malnourished children with acute diarrhea does not achieve any significant clinical benefit versus milk.
Acute Disease↗
Inhibition of HIV-1 production and selective degradation of viral RNA by an amphibian ribonuclease.
Ribonucleases appear to have physiologic roles in host defense against cancer, viruses, and other parasites. Previously it was shown that select ribonucleases added to cells concurrently with virions blocked human immunodeficiency virus, type I (HIV-1) infection of H9 cells. We now report that a ribonuclease homologous to RNase A, named onconase, inhibits virus replication in chronically HIV-1-infected human cells without killing the virally infected cell. Examining the mechanism of this inhibition shows that onconase enters the infected cells and degrades HIV-1 RNA without degrading ribosomal RNA or the three different cellular messenger RNAs analyzed. The homologous human pancreatic RNase lacks anti-viral activity. Comparing recombinant forms of onconase and a onconase-human RNase chimera shows that the N-terminal 9 amino acids and the pyroglutamyl residue of onconase are required for full anti-viral activity. Thus extracellular ribonucleases can enter cells, metabolize select RNAs, and inhibit HIV virion production within viable replicating cells.
Antiviral Agents↗
Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity.
A number of biochemical properties differ dramatically among homologues within the pancreatic ribonuclease superfamily. Human pancreatic ribonuclease (hRNase) has high enzyme activity, extreme sensitivity to ribonuclease inhibitor (RI) and is non-toxic, whereas a homologous RNase from frog eggs, called onconase, has much lower enzyme activity, is not sensitive to RI and is cytotoxic to cancer cell lines and animals. To explore the structural basis of these differences among members in the RNAse family we synthesized genes for onconase, hRNase, a mutant onconase (K9Q) and onconase-hRNase N-terminal hybrids and expressed the proteins in Escherichia coli with final yields of 10 to 50 mg per liter of culture after purification. A recombinant version of onconase with an N-terminal methionine instead of the native pyroglutamyl residue had decreased cytotoxicity and enzyme activity. Cleavage of the recombinant onconase Met-1 residue, and cyclization of the Gln1 residue to reform the pyroglutamyl N terminus, reconstituted cytotoxicity and enzyme activity. Thus a unique role of the pyroglutamyl residue in the active site of amphibian RNases is indicated. Replacement of one to nine residues of onconase with the homologous residues of hRNase increased the enzymatic activity against most of the substrates tested with a simultaneous shift in the enzyme specificity from high preference for poly(U) to slight preference for poly(C). Cytotoxicity of the chimera decreased, dissociating cytotoxicity from enzymatic activity. The molecular basis for the low binding affinity of onconase for RI has been examined experimentally with the recombinant RNases and by fitting onconase and RNase A structures to the coordinates from the recently published RNase A-RI complex.
Amino Acid Sequence↗