Search PubMed⌕ Search

Biomedical subjects

P Tripathi

Publications and source records attributed to P Tripathi.

At least 19 recordsLinked to original sources

Identification of Leishmania donovani antigens stimulating cellular immune responses in exposed immune individuals.

Human visceral leishmaniasis (VL), also known as kala azar (KA) in India, is a systemic progressive disease caused by Leishmania donovani. In VL, Th1 responses correlate with recovery from and resistance to disease and resolution of infection results in lifelong immunity against the disease. However, recent data suggest an important role for interleukin (IL)-10 in maintaining the resistant state. We evaluated whole cell extract (WE) and 11 antigenic fractions [F1-F11, molecular weight (MW) range of 139-24.2 kDa] from L. donovani (2001 strain, a fresh field isolate from Bihar), for their ability to induce in vitro T cell proliferation and production of interferon (IFN)-gamma, interleukin (IL)-12, IL-10 and IL-4 by peripheral blood mononuclear cells (PBMCs) of exposed immune individuals (14 patients with history of VL, 10 household endemic contacts) and 20 non-endemic healthy controls. Twenty-one of 24 exposed individuals and no healthy controls showed proliferative response to WE. Whole-extract activated IFN-gamma, IL-12, IL-10 levels were higher in the exposed group than in controls; IL-4 was not detectable in any of the samples. Among 21 responders to WE, frequent proliferative responses were seen to fractions F1-F4 (MW > 64.2 kDa) and none to fractions F5-F11; fractions F1-F11 stimulated comparable levels of IFN-gamma and IL-12 while IL-10 levels were higher in response to F5-F11 compared to F1-F4. These data demonstrate the presence of immunostimulatory antigens in the high MW fractions of whole L. donovani antigen. However, these fractions do not stimulate a Th1 response and produce variable amounts of IFN-gamma and the regulatory cytokine, IL-10. Hence, these high MW immunostimulatory fractions need to be evaluated in greater depth for their possible role as protective antigens.

Adolescent↗

HLA-E and immunobiology of pregnancy.

Recently, it has been suggested that non-classical antigens such as human leukocyte antigen (HLA)-G and HLA-E may interact with KIR receptors of NK cells which results into downregulation of immune response and helps in the maintenance of pregnancy. In the present study, we have investigated HLA-E polymorphism in normal fertile women and recurrent spontaneous aborters to assess the effect of HLA-E alleles on the success of pregnancy. Allele E*0101 was found to be significantly higher in patients with recurrent spontaneous abortion (chi(2) = 4.097 and P = 0.0430). Differential expression, peptide affinity, and stability of E*0101 may be one of the reasons.

Abortion, Habitual↗

Immunostimulatory cellular responses of cured Leishmania-infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of Leishmania donovani.

Development of an effective immunoprophylactic agent for visceral leishmaniasis (VL) has become imperative due to the increasing number of cases of drug resistance and relapse. Live and killed whole parasites as well as fractionated and recombinant preparations have been evaluated for vaccine potential. However, a successful vaccine against the disease has been elusive. Because protective immunity in human and experimental leishmaniasis is predominantly of the Th1 type, immunogens with Th1 stimulatory potential would make good vaccine candidates. In the present study, the integral membrane proteins (IMPs) and non-membranous soluble proteins (NSPs), purified from promastigotes of a recent field isolate, Leishmania donovani stain 2001, were evaluated for their ability to induce cellular responses in cured patients (n = 9), endemic controls (n = 5) of visceral leishmaniasis (VL) and treated hamsters (n = 10). IMPs and NSPs induced significant proliferative responses (SI 6.3 +/- 4.1 and 5.6 +/- 2.3, respectively; P < 0.01) and IFN-gamma production (356.3 +/- 213.4 and 294.29 +/- 107.6 pg/ml, respectively) in lymphocytes isolated from cured VL patients. Significant lymphoproliferative responses against IMPs and NSPs were also noticed in cured Leishmania animals (SI 7.2 +/- 4.7 & 6.4 +/- 4.1, respectively; P < 0.01). In addition, significant NO production in response both IMPs and NSPs was also noticed in macrophages of hamsters and different cell lines (J774A-1 and THP1). These results suggest that protective, immunostimulatory molecules are present in the IMP and NSP fractions, which may be exploited for development of a subunit vaccine for VL.

Adolescent↗

Sensitization of T cells to apoptosis--a role for ROS?

T cell homeostasis is achieved by balancing the production and proliferation of T cells with their apoptotic cell death. Activation of naïve T cells by antigen in the context of MHC results in the massive expansion of antigen-specific T cells and the production of reactive oxygen species (ROS). Following expansion, the majority of the T cells die via apoptosis, while a small number of them survive and differentiate into memory T cells. This cell fate decision is crucial to our understanding of how autoimmunity is avoided and how immunity is maintained. It has become increasingly clear that ROS can affect this cell fate decision by sensitizing T cells to apoptosis. Interestingly, ROS have effects on both intrinsic and extrinsic apoptosis pathways through modulation of expression of the major molecules in these pathways, Bcl-2 and FasL. In this review, we will focus on the pro-apoptotic effects of ROS and mechanisms by which they regulate the death of T cells.

Animals↗

Analysis of human leukocyte antigen (HLA)-G polymorphism in normal women and in women with recurrent spontaneous abortions.

Human leukocyte antigen (HLA)-G is a non-classical class I antigen. It has limited expression, but is high at the foetomaternal interface. This unique expression pattern of HLA-G suggests that it might be important for survival of the foetus during pregnancy. In the present study, 120 women with recurrent spontaneous abortions (RSA) and 120 fertile control women were genotyped for the HLA-G locus. This is the first report describing HLA-G polymorphism in normal fertile and RSA women from India. The allele HLA-G*010103 was higher in women with recurrent foetal losses. Interestingly, the HLA-G*010105 and G*010108 alleles were totally absent in normal fertile women but present in RSA women with frequencies of 1.7% and 0.4%, respectively. Allele G*010107 was absent in both the groups. The frequency of the null allele G*0105N was high (13.8%) in our population as compared to other world populations. Our data support the hypothesis that HLA-G polymorphism may contribute to recurrent foetal loss.

Abortion, Habitual↗

Role of 14-bp deletion in the HLA-G gene in the maintenance of pregnancy.

Differential expression of human leukocyte antigens (HLAs) on trophoblast has been the focus of many studies, specially on extravillous cytotrophoblast cells, which migrates into the maternal uterine tissues. These invading cells do not express classical major histocompatibility complex class I (-A and -B) and class II molecules, along with low expression of HLA-C. HLA-G is the predominantly expressed antigen along with HLA-E. Hence, it is believed that expressed antigens may be involved in materno-fetal tolerance. In the present study, we have studied 14-bp deletion polymorphism in the exon-8 of the non-classical HLA-G antigen. There was no difference in the frequency of deletion/insertion polymorphism in fertile normal women and recurrent spontaneous abortion (RSA) women. However, the number of heterozygotes (-14b/+14b) were increased in RSA women. The probable mechanism for the increase of heterozygotes in recurrent fetal loss is discussed in light of soluble HLA-G.

Abortion, Habitual↗

Evaluation of chemical constituents and free-radical scavenging activity of Swarnabhasma (gold ash), an ayurvedic drug.

From ancient times, Swarnabhasma (gold ash) has been used in several clinical manifestations including loss of memory, defective eyesight, infertility, overall body weakness and incidence of early aging. Swarnabhasma has been used by Ayurvedic physicians to treat different diseases like bronchial asthma, rheumatoid arthritis, diabetes mellitus, nervous disorders, etc. In the present investigation, Swarnabhasma was prepared after proper purification and calcination as per Ayurvedic pharmacy which consisted of Realger (As(2)S(2)), Lead oxide (Pb(3)O(4)), Pure gold (Au) and Latex of Calotropis gigantea. Qualitative analyses indicated that Swarnabhasma contained not only gold but also several microelements (Fe, Al, Cu, Zn, Co, Mg, Ca, As, Pb, etc.). Infrared spectroscopy showed that the material was free from any organic compound. The metal content in the bhasma was determined by atomic absorption spectrometry. Acute oral administration of Swarnabhasma showed no mortality in mice (up to 1 ml /20 g b.w. of Swarnabhasma suspension containing 1mg of drug). Chronic administration of Swarnabhasma also showed no toxicity as judged by SGPT, SGOT, serum creatinine and serum urea level and histological studies. In an experimental animal model, chronic Swarnabhasma-treated animals showed significantly increased superoxide dismutase and catalase activity, two enzymes that reduce free radical concentrations in the body.

Animals↗

Outcome from poor grade aneurysmal subarachnoid haemorrhage--which poor grade subarachnoid haemorrhage patients benefit from aneurysm clipping?

Patients with poor grade aneurysmal subarachnoid haemorrhage (SAH) are associated with high mortality and morbidity, and hence are often treated conservatively. This study has set out to determine the outcome for all poor grade subarachnoid haemorrhage patients, and attempts to identify a subgroup with a more favourable prognosis. During a prospective audit of patients with aneurysmal SAH, patients of poor grade [World Federation of Neurological Surgeons (WFNS) IV (and not obeying commands) and V] were sedated, paralysed and ventilated for transfer to the Regional Neurosurgical Unit. Any intraventricular blood and/or hydrocephalus was treated by external ventricular drainage. Following a 24-h period for active blood gas, fluid and electrolyte resuscitation, patients were assessed after reversal of sedation. Selection for angiography and potential aneurysm surgery was restricted to those who showed a purposeful response to painful stimulation. Patients who could readily obey commands were not considered 'true' poor grade and were excluded from analysis. In 102 patients with 'true' poor grade SAH admitted between 1991 and 1997, the overall management outcome at 6 months was poor (favourable outcome 25%, mortality 67%). Following reversal of sedation, 55 patients demonstrated a purposeful response and proceeded to angiography, of whom 37 underwent clipping and three coiling of aneurysm. The outcome in this aneurysm treated subgroup was favourable in 53% (mortality 28%). If patients over the age of 65 years are excluded, the management outcome was favourable in 35% (mortality 58%), with those patients proceeding to clipping or coiling of aneurysms having a favourable outcome in 57% (mortality 27%). Patients over the age of 65 years with poor grade SAH had a favourable outcome in only 6% (mortality 85%). The mortality for poor grade SAH patients remains high. However, following resuscitation and correction of any acute hydrocephalus, a patient subgroup identified on simple clinical criteria can be identified who can expect a better outcome.

Adolescent↗

Immune response in rabbits against Rhipicephalus sanguineus.

Rabbits immunised with homogenates of unfed larvae and nymphs of the tick R. sanguineus developed significant level of protective immunity to infestation with all the stages of the species. The acquisition of resistance was based on feeding and developmental performance parameters (rejection, moulting percentages and feeding period) of larvae and nymphs. The acquisition of resistance against adults was also measured by feeding and reproductive performance of female ticks viz., rejection percent, engorged female and egg mass weights, engorgement, preoviposition and oviposition periods and efficiency of female ticks in converting their food reserve to eggs and larvae. Sera from larval extract (RLAg) immunised rabbits were strongly positive for anti-RLAg antibodies after 3 weeks of immunisation while nymphal extract (RNAg) immunised rabbits were positive for anti-RNAg antibodies after 2 weeks of immunisation in enzyme linked immunosorbent assay. The immunised rabbits were also positive for immediate type hypersensitivity (ITH) reaction on Intradermal inoculation of RLAg and RNAg.

Animals↗

Identification of a cyclic peptide inhibitor of platelet-derived growth factor-BB receptor-binding and mitogen-induced DNA synthesis in human fibroblasts.

Peptides corresponding to residues from Loops I and III of platelet-derived growth factor-BB (PDGF-BB) were examined for their potential to act as PDGF antagonists. We have identified two peptides which directly stimulated DNA synthesis in human dermal fibroblasts and a cyclic peptide which inhibited PDGF-induced DNA synthesis. The inhibitory action of cyclic PDGF-BB(73-81), on DNA synthesis was shown to be restricted to cells which express PDGF receptors. Also cyclic PDGF-BB(73-81) specifically competed for 125I-labelled PDGF-BB but not for 125I-labelled EGF binding to their respective cellular receptors. The cyclic peptide therefore provides a minimum structure to investigate PDGF/receptor interactions and our findings confirm the importance of the loop configuration of PDGF-BB(73-81) in the native molecule. The cyclic peptide may constitute a basis for developing more potent inhibitors of PDGF action.

Amino Acid Sequence↗

Antioxidant and anti-inflammatory property of Sandhika: a compound herbal drug.

The present study was envisaged to assess the rationality for the use of "Sandhika", a popular Ayurvedic drug in rheumatoid arthritis. This drug, when tested against carrageenan induced paw oedema and cotton pellet granuloma, showed significant anti-inflammatory activity at the dose of 0.25 g/kg body weight. The antioxidant property was assessed by determining cumene hydroperoxide (CHP) induced lipid peroxidation and reduced glutathione content in rat liver homogenate (in vitro). Experiments show the significant protection against lipid peroxidation at the dose of 80 micrograms/ml, measured as reduction in the level of malondialdehyde (MDA) induced by 1.5 mM cumene hydroperoxide (CHP). This effect was accompanied by the maintained reduced glutathione (GSH) content in drug treated rats. Oral treatment of drug up to 2 g/kg body weight for 15 days did not show any rise in serum transaminases (SGOT and SGPT). The results suggest that "Sandhika" which is an indigenous drug for inflammation with no detectable adverse effect, might be acting through scavenging the free radicals.

Animals↗

Hepatoprotective and toxicological evaluation of hepatomed, an ayurvedic drug.

Hepatoprotective effect of Hepatomed (an ayurvedic drug containing water extract of 6 medicinal plants) has been studied on cumene hydroperoxide (CHP) induced lipid peroxidation and reduced glutathione content in rat liver homogenate. In vitro experiments show significant reduction in the level of malondialdehyde (MDA) induced by 1.5 mM cumene hydroperoxide(CHP). Glutathione content was almost maintained to normal in drug treated rats. Oral treatment of drug up to 3 ml/100 g body weight for 15 days did not show any rise in serum GOT and GPT. On similar doses, significant choleratic effect was observed without any adverse histological changes after 4 days treatment. The results suggest that 'Hepatomed' is a strong hepatoprotective ayurvedic medicine with no detectable adverse effects.

Alanine Transaminase↗

Reassessing the status of antiphospholipid syndrome in systemic lupus erythematosus.

The antiphospholipid syndrome was initially described in 1986. To reassess the validity of antiphospholipid antibodies in systemic lupus erythematosus (SLE), 95 patients with SLE were studied. Their antiphospholipid antibody profile was analysed and correlated with clinical findings such as thrombosis, abortions, or thrombocytopenia. A low prevalence of these antibodies was found (13 patients; 14%) with a high specificity for thrombosis (92%) and abortions (92%). The importance of anticardiolipin antibodies as a risk factor for thrombosis or abortions, or both, in patients with SLE is reaffirmed by this work.

Abortion, Spontaneous↗

The effect of the chewing side on parotid amylase secretion in conscious rabbits.

This study was conducted to investigate whether changes in amylase output accompany changes in salivary flow which occur during feeding. New Zealand White rabbits were trained to eat food offered to them in the laboratory. After chronic parotid duct cannulation, saliva was collected and flow rates recorded bilaterally while the animals fed on fresh carrots or pelleted food. The amylase concentration (U/ml) obtained with carrots was greater than with pellets, but because of the differences in flow rate, the overall amylase output (U/min) for both foods did not differ. There was no difference in the amylase concentration in saliva collected either ipsilateral to or contralateral to the chewing side. However, amylase output was significantly greater ipsilateral than contralateral to chewing with both pellets (p less than 0.01) and carrots (p less than 0.05).

Amylases↗