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Biomedical subjects

Vijay K Singh

Publications and source records attributed to Vijay K Singh.

12 recordsLinked to original sources
PubMed2006

Induction of cytokines by radioprotective tocopherol analogs.

Tocols are a family of eight isomers consisting of four tocopherols and four tocotrienols that exist in four isomeric forms: alpha (alpha), beta (beta), gamma (gamma), and delta (delta). Recently, tocols were found to have important and unique biological effects on nutrition and health other than antioxidant properties and are, therefore, now receiving increased attention. We have demonstrated the radioprotective efficacy of various tocol analogs and some of their esters. Three forms of tocols - alpha-tocopherol, alpha-tocopherol succinate, and gamma-tocotrienol - significantly protected mice against lethal gamma irradiation when administered subcutaneously 24 h before irradiation. The radioprotective effects of tocols on survival were associated with peripheral blood cell recovery after radiation induced cytopenia. Hematopoietic cytokines are known to promote the proliferation and differentiation of blood cell progenitors. Therefore, we hypothesized that peripheral blood cell recovery is preceded by hematopoietic cytokine induction. To test this hypothesis and compare the various radioprotective and non-radioprotective analogs, we measured serum cytokines using a sandwich ELISA, Luminex, and cytokine array in mice treated with various tocols (alpha-tocopherol succinate, alpha-tocopherol, delta-tocopherol, gamma- tocopherol, gamma-tocotrienol, and tocopherol acetate). Among the serum cytokines measured, ELISA and Luminex studies indicated that alpha-tocopherol, alpha-tocopherol succinate, and gamma-tocotrienol increased G-CSF levels in mice. Alpha-tocopherol succinate was most effective in stimulating G-CSF. IL-6 was detected by Luminex in sera samples from mice treated with the above three analogs. The results of the cytokine array suggest that other cytokines and chemokines in addition to G-CSF and IL-6 are induced. Since G-CSF, IL-6, and certain chemokines are important hematopoietic factors, these results support our hypothesis that the protection of mice from radiation-induced hematopoietic death is mediated by cytokines and chemokines. These studies may indicate that alpha-tocopherol succinate can be used as an adjunct in cancer chemotherapy, where neutropenia is a serious problem with threatening infectious complications.

Animals↗
PubMed2005

Role of cytokines and growth factors in radioprotection.

Cytokines and growth factors are growing groups of proteins that are responsible for the communication between cells of the immune system, hematopoietic cells, and other cell types. The cloning and large-scale production in a recombinant form of these agents in pharmacological quantities permitted investigations aimed at assessing the benefit they may provide in preserving and restoring functions of tissues compromised by irradiation. We have extensively examined past investigations which suggest that some cytokines and growth factors protect animals from radiation lethality when given prior to or after irradiation, and even in untreated animals, these cytokines serve in innate defenses against external stimuli. In contrast, some cytokines given before irradiation sensitize the animals to radiation lethality. Unfortunately, due to their adverse side effects, these cytokines were not found suitable as radioprotectors. Recent studies suggest that new approaches may bring cytokines and growth factors in clinic for radiation injury. The information and insight gained about therapeutic potential of cytokine manipulation will allow for more rational design of treatment protocols.

Animals↗
PubMed2005

Radioprotection by N-palmitoylated nonapeptide of human interleukin-1beta.

Interleukin-1beta (IL-1beta) is a cytokine involved in homeostatic processes of the immune system and specifically in inflammatory reactions. The nonapeptide of human IL-1beta (VQGEESNDK, position 163-171) has been shown to retain adjuvant and immunostimulatory activities of the native molecule without any inflammatory and pyrogenic properties. A lipophilic derivative of IL-1beta nonapeptide having a palmitoyl residue at the amino terminus was synthesized in order to determine the effects of such structural modification on its bioactivities. The structurally modified peptide derivative, palmitoylated peptide, significantly protected C3H/HeN mice against potentially lethal doses of ionizing radiation. The dose reduction factor was found to be 1.07. Hematological studies show improved recovery of red blood cells and platelets in irradiated and palmitoylated peptide treated mice as compared with the untreated and irradiated group. These results suggest the importance of the derivatization of small peptides of radioprotective, but toxic cytokines in order to enhance radioprotective activity while reducing unwanted toxic side effects.

Adjuvants, Immunologic↗
PubMed2005

Effects of whole-body gamma irradiation and 5-androstenediol administration on serum G-CSF.

5-Androstenediol (5-AED) is a natural circulating adrenocortical steroid hormone that interconverts in vivo with other members of the 5-androstene family of steroids: dehydroepiandrosterone and 5-androstenetriol. These steroids stimulate immune responses and resistance to infection. 5-AED has been identified as a systemic radiation countermeasure that enhances survival in mice exposed to gamma irradiation and ameliorates radiation-induced neutropenia in mice and nonhuman primates. 5-AED mitigates radiation-induced decreases in platelets, natural killer (NK) cells, red blood cells, and monocytes. Administration of 5-AED causes functional activation of circulating granulocytes (phagocytic ability), monocytes (oxidative burst), and NK cells (surface CD11b expression). The effects of 5-AED on survival and hematological parameters are consistent with induction of hematopoietic cytokines. To test this hypothesis, we measured serum cytokines by ELISA, Luminex, and a cytokine array. A cytokine array was used for 62 different cytokines, chemokines, growth factors, and soluble receptors. 5-AED caused significant increases in circulating granulocyte colony-stimulating factor (G-CSF) in irradiated and unirradiated animals as observed with ELISA and Luminex. The cytokine array results suggest induction of G-CSF and additional cytokines, and related molecules. Since G-CSF is an important hematopoietic cytokine, the results support our hypothesis that the previously observed increases in numbers of hematopoietic progenitors, circulating innate immune cells and platelets, and functional activation of granulocytes, monocytes, and NK cells result from a cytokine cascade induced by 5-AED.

Androstenediol↗
PubMed2005

Ghrelin and leptin levels of sojourners and acclimatized lowlanders at high altitude.

The circulatory levels of two appetite regulatory hormones i.e. leptin and ghrelin were estimated in sojourners and acclimatized subjects to investigate their possible role in high altitude (HA) induced anorexia. A group of 30 lowlanders who had never visited HA were inducted to a height of 3600 m by air and after 48 h they were further taken to an altitude of 4300 m by road. Blood samples were collected after 48 h stay at 3600 m and again after 48 h and 7 days of stay at 4300 m during 0700-0730 h. There was a decrease in energy intake (850 kcal/day) of sojourners, which resulted in loss of body weight by 2.12 kg at HA. At an altitude of 4300 m there was a significant increase in leptin over basal levels (54.9%, p < 0.001) at 48 h that persisted even after 7 days of stay at this altitude. Ghrelin levels of sojourners decreased by more than 30% in comparison to basal values at 48 h of ascent to HA. Leptin levels of acclimatized lowlanders were also higher in comparison with control group (acclimatized group 7.6 + 0.6 ng/ml vs. control 5.6 + 0.5 ng/ml, p < 0.01, n = 50).

Acclimatization↗
PubMed2004

Human S-antigen: peptide determinant recognition in uveitis patients.

Uveitis is an inflammation of the uveal tract and is one of the major causes of visual impairment. Several lines of evidence suggest an important role for activated T lymphocytes in the perpetuation of posterior uveitis. In sequel to our preliminary observations with human S-antigen, we have further investigated the proliferative response of peripheral blood lymphocytes of posterior uveitis patients against 20 linear and 9 overlapping peptides of retinal S-antigen. The expression of surface markers CD4, CD8, CD29, CD45RA in peripheral blood was detected by flow cytometry. We have also assessed the pattern of cytokines present in peripheral blood mononuclear cells (PBMCs) using ribonuclease protection assay (RPA). Nineteen out of 32 patients' lymphocytes showed proliferative response to S-antigen, one or more of its 20 linear and nine overlapping synthetic peptides. Six patients showed significant lymphoproliferative response against various peptides. The maximum response was found to peptides from the 231-270 amino acid region of human S-antigen sequence. The percentage of CD29(+) (memory cells) and CD45RA(+) (naive cells) T-lymphocytes was higher in patients compared to healthy volunteers. There was a demonstrable difference in the percentage of CD4(+) and CD8(+) lymphocytes in the patients (P <== 0.05) as compared to controls. Higher message for interleukin (IL)-5, IL-10, IL-15, IL-9, IL-2, IL-13, and interferon (IFN)-gamma was observed in uveitis patients than in healthy individuals. In brief, our study suggests that a particular region of S-antigen plays an important role in idiopathic uveitis.

Adolescent↗
PubMed2003

Inhibition of LPS-induced nitric oxide production in RAW cells by radioprotective thiols.

Nitric oxide (NO) is involved in producing damage after exposure to radiation and also in the toxicity associated with bacterial endotoxin (lipopolysaccharide, LPS). We have evaluated different radioprotective thiols for their effects on LPS-stimulated NO production in mouse macrophage cells, RAW 264.7. Our results indicate that although thiols inhibited NO production in general, the degree of inhibition depended upon the thiol compound. Long-chain aminothiols like WR-1065 [N-(2-mercaptoethyl)-1,3-diaminopropane] exerted a strong inhibition; but its parent drug, amifostine, which protects mice against radiation lethality, was not as effective as WR-1065. Diethyl dithiocarbamate, which is less effective than amifostine as a radioprotector, strongly inhibited NO production from macrophages. These results indicate that the radioprotective potential of sulfhydryl compounds is not related to its ability to inhibit NO production by macrophages and suggest that some of the thiol radioprotectors may effectively ameliorate the fatal symptoms of hypotensive shock, associated with endotoxin (LPS)-induced NO production.

Acetylcysteine↗
PubMed2003

Immunomodulation by peptide analogs of retroviral envelope protein.

The mechanism by which retroviral proteins exert their immunosuppressive influence has remained enigmatic. Early studies have demonstrated that retroviral infection suppresses cellular and humoral immune responses. A hydrophilic 26 amino acid region of the otherwise hydrophobic transmembrane envelope protein of murine and feline leukemia viruses, p15E, is conserved among the transmembrane envelope proteins of numerous animal retroviruses (e.g. murine, feline, bovine and simian) as well as in human T-cell leukemia virus, and to a lesser extent, in human immunodeficiency virus (HIV). We evaluated the immunomodulatory properties of various synthetic retroviral envelope peptides synthesized as overlapping fragments to this conserved sequence. We report that two small peptides inhibit human mixed lymphocyte reaction (MLR), interleukin-2 (IL-2) and tumor necrosis factor (TNF-alpha) production. These peptides did not affect human natural killer (NK) cell cytotoxicity in vitro, and nitric oxide (NO) production in mouse macrophage cells, RAW264.7. Our observations suggests immunomodulatory potential of two retroviral peptide analogs.

Amino Acid Sequence↗
PubMed2003

Immunomodulation by lead.

Lead, a potential human carcinogen, is a ubiquitous environmental pollutant in the industrial environment that poses a serious threat to human health. This toxic lead can modulate the immune response of animals as well as humans. In some instances, the immune system appears to be exquisitely sensitive to lead as compared with other toxicological parameters. Both stimulation and suppression of immune response have been demonstrated in lead exposed animals and humans depending on the T helper (Th)1 vs Th2 response. Although the majority of data accumulated to date pertains to the effects of lead in small laboratory rodents, there is little reason to believe that similar quantifiable effects do not occur in domestic and food-producing animals owing to basic functional similarities of the immune system of mammals. In this review, we have discussed the immunomodulatory role of the toxic heavy metal, lead, on cellular and humoral components of the immune system with particular reference to effector cells such as B cells, T cells, natural killer (NK) cells, and soluble mediators such as cytokines, chemokines, and nitric oxide (NO).

Animals↗
PubMed2002

Gene therapy in ocular diseases.

Gene therapy is a novel form of drug delivery that enlists the synthetic machinery of the patient's cells to produce a therapeutic agent. Genes may be delivered into cells in vitro or in vivo utilising viral or non-viral vectors. Recent technical advances have led to the demonstration of the molecular basis of various ocular diseases. Ocular disorders with the greatest potential for benefit of gene therapy include hereditary diseases such as retinitis pigmentosa, tumours such as retinoblastoma or melanoma, and acquired proliferative and neovascular retinal disorders. Gene transfer into ocular tissues has been demonstrated with growing functional success and may develop into a new therapeutic tool for clinical ophthalmology in future.

Animals↗
PubMed2002

Kala-azar in Uttar Pradesh--a study of 66 patients.

Sixty-six laboratory confirmed cases of Kala-azar from Uttar Pradesh attending various hospitals of Delhi over a period of 10 years (1989-1999) have been analysed. The geographical distribution showed that the disease involved widespread areas varying from a height of 10,000 ft. extending up-to the plains. Male, female ratio was 2:1 and maximum patients were in the age group of 5-15 years. L.D. bodies could be demonstrated in 59 patients in bone marrow aspirate smears while in 7 in splenic aspirate smears. One patient was co-infected with HIV. Indirect immuno fluorescent test was positive in 65 patients in titres ranging from 1:100 to 1:25,600 except in one HIV co-infected patient where no antibodies could be detected. Sixty-two (93.9%) patients responded completely to sodium stibogluoconate.

AIDS-Related Opportunistic Infections↗