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Biomedical subjects

B Saha

Publications and source records attributed to B Saha.

At least 37 records · Page 2Linked to original sources
PubMed2001

Oxidation of [Ru(NH3)5isn](BF4)2 by hyochlorous acid and chlorine in aqueous acidic media.

UV-vis stopped-flow studies of the reaction of [Ru(NH3)5isn](2+) (isn = isonicotinamide) with excess HOCl at 25 degrees C demonstrate that it proceeds in two time-resolved steps. In the first step [Ru(NH3)5isn](3+) is produced with the rate law -d[Ru(II)]/dt = 2(aK(h)[H(+)] + b[H(+)][Cl(-)] + c[Cl(-)])[HOCl](tot)[Ru(II)]/(K(h) + [H(+)][Cl(-)]). Here, K(h) is 1.3 x 10(-3) M(2) and corresponds to the equilibrium hydrolysis of Cl2, a is (8.34 +/- 0.19) x 10(3) M(-2) s(-1) and represents the acid-assisted reduction of HOCl, b is (4.04 +/- 0.13) x 10(4) M(-1) s(-1) and represents the reduction of Cl2, and c is (6.25 +/- 0.59) x 10(2) s(-1) and represents the Cl(-)-assisted reduction of HOCl. In the second step [Ru(NH3)5isn](3+) undergoes further oxidation to a mixture of products with the rate law -d[Ru(III)]/dt = e[Ru(III)][HOCl]/[H(+)] where e is (1.18 +/- 0.01) x 10(-2) s(-1). This step is assigned a mechanism with Cl(+) transfer from HOCl to [Ru(III)(NH3)4(NH2)isn](2+) occurring in the rate-limiting step. These results underline the resistance of HOCl to act as a simple outer-sphere one-electron oxidant.

Journal Article↗
PubMed2001

Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression.

CD28, described as a T cell costimulatory molecule so far, is expressed on human peripheral blood neutrophils, as shown by cell surface staining and immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of CD28 on these cells can be blocked by actinomycin D, an RNA transcription inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28 results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is down-regulated by receptor internalization 3 h after CD28 cross-linking with concurrent decrease in IL-8-induced chemotactic migration. Thus, our results demonstrate for the first time that CD28 is expressed on human peripheral blood neutrophils and that CD28 may play an important role in the regulation of IL-8RA expression and migration of neutrophils in response to IL-8.

Adult↗
PubMed2001

Circulating dopamine level, in lung carcinoma patients, inhibits proliferation and cytotoxicity of CD4+ and CD8+ T cells by D1 dopamine receptors: an in vitro analysis.

Besides cardiovascular and renal functions, the role of dopamine in periphery as an endogenous regulator of immune functions is in the limelight. In human malignancy, depression of T cell functions is known. Interestingly, recent evidences indicate significant elevation of plasma dopamine in malignancy due to stress of the disease process. Therefore, this study evaluates whether this increased plasma dopamine exerts any influence on the proliferation and cytotoxicity of CD4+ and CD8+ T cells. Patients with lung carcinoma were selected for this study due to the high prevalence rate of this kind of cancer in developing countries and also due to strong positive biochemical and psychological criteria of stress in most of the patients. Results showed significant elevation of plasma dopamine (48.6 +/- 5.1 pg/ml) in lung cancer patients than normal controls (10.2 +/- 0.9 pg/ml). In vitro dopamine concentration, simulating the plasma concentration of the patients, significantly inhibited the proliferation and cytotoxicity of T cells of these patients and also of the normal volunteers, in presence of their respective serum. The mechanism has been attributed to be D1 class of dopamine receptor mediated elevation of intracellular cAMP in these cell populations. The results may be of significance in understanding the role of peripheral dopamine as an immunomodulator in human health and diseases.

Adult↗
PubMed2001

Physiological concentrations of dopamine inhibit the proliferation and cytotoxicity of human CD4+ and CD8+ T cells in vitro: a receptor-mediated mechanism.

OBJECTIVE: Dopamine, a catecholamine neurotransmitter, influences growth and proliferation of lymphocytes. Pharmacological doses of dopamine have been shown to modulate T cell functions significantly, but no information is available on the effect of physiological concentrations of circulating dopamine on CD4+ and CD8+ T cell functions. This information may be of importance since significantly elevated plasma dopamine levels were observed in humans during uncoping stress, and suppression of T cell functions during stress is a well-known phenomenon. However, the mechanism inducing the suppression of T cell functions during stress is not yet clear. In the present investigation, we evaluated the effect of the dopamine level attained in the plasma of individuals with uncoping stress on the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. METHODS: T cell subpopulations were separated by panning. The effect of dopamine on IL-2-induced cell proliferation in vitro was evaluated by [3H]thymidine incorporation and cytotoxicity by 51Cr release, receptors by radioligand binding, cAMP by an assay kit and apoptosis by DNA fragmentation. RESULTS: At these elevated physiological concentrations, dopamine was found to inhibit significantly the proliferation and cytotoxicity of CD4+ and CD8+ T cells in vitro. This dopamine-mediated inhibition of proliferation was more marked on CD8+ T cells than on CD4+ T cells. The underlying mechanism was found to be D1 class of dopamine-receptor-mediated stimulation of intracellular cAMP. CONCLUSION: Results may be of significance to understand the role of peripheral dopamine in human neuroimmune communication in terms of physiological homeostasis in health and disease.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Antinociceptive effects of tetrahydrocannabinol side chain analogs: dependence upon route of administration.

The role of flexibility of the alkyl side chain in the tetrahydrocannabinols to cannabinoid activity has been delineated in previous studies with side chain analogs of Delta(8)-tetrahydrocannabinol with double or triple bonds. This study investigated the site of antinociceptive action for these analogs through analysis of structure-activity relationships following different routes of administration. In analogs without terminal substitutions, potency was greater following intrathecal (i. t.) injection than with intracerebroventricular (i.c.v.). Further, optimal structural features differed for each route of administration. Absolute position of the double or triple bond best predicted i.t. potency. In contrast, i.c.v. potency was best predicted by the size of the alkyl substituent beyond the point of unsaturation. Terminal substitutions tended to increase i.c.v. potency while decreasing or not affecting i.t. These results suggest that receptor mechanisms for cannabinoid antinociceptive effects differ in brain and spinal cord, although potential pharmacokinetic differences in rate of local distribution cannot be eliminated.

Analgesics, Non-Narcotic↗
PubMed2000

Thermal and photochemical reduction of aqueous chlorine by ruthenium(II) polypyridyl complexes.

Studies are reported on the reactions of aqueous chlorine with a series of substitution-inert, one-electron metal-complex reductants, which includes [Ru(bpy)3]2+, [Ru(4,4'-Me2bpy)3]2+, [Ru(4,7-Me2phen)3]2+, [Ru(terpy)2]2+, and [Fe(3,4,7,8-Me4phen)3]2+. The reactions were studied by spectrophotometry at 25 degrees C in acidic chloride media at mu = 0.3 M. In general the reactions have the stoichiometry 2[ML3]2+ + Cl2-->2[ML3]3+ + 2Cl-. In the case of [Ru(bpy)3]2+, the reaction is quite photosensitive; the thermal reaction is so slow as to be practically immeasurable. The reactions of [Ru(4,4'-Me2bpy)3]2+ and [Ru(4,7-Me2phen)3]2+ are also highly photosensitive, giving pseudo-first-order rate constants that depend on the monochromator slit width in a stopped-flow instrument; however, the thermal rates are fast enough that they can be obtained by extrapolation of kobs to zero slit width. The reactions of [Ru(terpy)2]2+ and [Fe(3,4,7,8-Me4phen)3]2+ show no appreciable photosensitivity, allowing direct determination of their thermal rate laws. From the kinetic effects of pH, [Cl2]tot, and [Cl-] it is evident that all of the thermal rate laws have a first-order dependence on [ML3]2+ and on [Cl2]. The second-order rate constants decrease as Eo for the complex increases, consistent with the predictions of Marcus theory for an outer-sphere electron-transfer mechanism. Quantum yields at 460 nm for the reactions of [Ru(4,4'-Me2bpy)3]2+ and [Ru(4,7-Me2phen)3]2+ exceed 0.1 and show a dependence on [Cl2] indicative of competition among spontaneous decay of *Ru, nonreactive quenching by Cl2, and reactive quenching by Cl2.

Journal Article↗
PubMed2000

O-1057, a potent water-soluble cannabinoid receptor agonist with antinociceptive properties.

Cannabinoids have low water solubility, necessitating the use of a solubilizing agent. In this paper we investigated whether a novel water-soluble cannabinoid, 3-(5'-cyano-1', 1'-dimethylpentyl)-1-(4-N-morpholinobutyryloxy)-Delta(8)- tetrahydroca nnabinol hydrochloride (O-1057), would interact with cannabinoid receptors when water or saline were used as the only vehicle. O-1057 displaced [(3)H]-CP55940 from specific binding sites on Chinese hamster ovary (CHO) cell membranes expressing CB(1) or CB(2) cannabinoid receptors, with pK(i) values of 8.36 and 7.95 respectively. It also displaced [(3)H]-CP55940 from specific binding sites on rat brain membranes (pK(i) = 7.86). O-1057 inhibited forskolin-stimulated cyclic AMP production by both CB(1)- and CB(2)-transfected CHO cells (pEC(50) = 9.16 and 9.72 respectively), its potency matching that of CP55940 and exceeding that of Delta(9)-tetrahydrocannabinol. In the mouse isolated vas deferens, O-1057 inhibited electrically-evoked contractions with pEC(50) and E(max) values of 9.73 and 76.84% respectively. It was antagonized by 100 nM SR141716A, the pK(B) of SR141716A against O-1057 (8.90) approximating to that against CP55940 (8.97). O-1057 also behaved as a CB(1) receptor agonist in vivo, reducing mouse spontaneous activity and rectal temperature when injected intravenously and inducing antinociception in the mouse tail flick test when given intravenously (ED(50) = 0.02 mg kg(-1)), intrathecally, intracerebroventricularly or by gavage. In all these assays, O-1057 was more potent than Delta(9)-tetrahydrocannabinol and, at 0.1 mg kg(-1) i.v., was antagonized by SR141716A (3 mg kg(-1) i.v.). These data demonstrate the ability of the water-soluble cannabinoid, O-1057, to act as a potent agonist at CB(1) and CB(2) receptors and warrant investigation of the clinical potential of O-1057 as an analgesic.

Analgesics↗
PubMed2000

Th1-specific bystander costimulation imparts resistance against Mycobacterium tuberculosis infection.

The protection against Mycobacterium tuberculosis infection is mediated by T helper type-1 (Th1) cells. Infection of BALB/c mice with M. tuberculosis downregulates expression of a Th1-specific costimulatory molecule, M150, on the surface of infected macrophages. The proliferation of Th cells and Th1-cytokine production by these cells are higher in case of M. tuberculosis antigen presentation by uninfected macrophages than by infected macrophages. The difference in inducing interleukin(IL)-2 and interferon (IFN)-gamma secretion is abolished by providing bystander costimulation through M150 on liposomes.

Animals↗
PubMed2000

Material equations for electromagnetism with toroidal polarizations.

With regard to the toroid contributions, a modified system of equations of electrodynamics moving continuous media has been obtained. Alternative formalisms to introduce the toroid moment contributions in the equations of electromagnetism has been worked out. The two four-potential formalism has been developed. Lorentz transformation laws for the toroid polarizations has been given. Covariant form of equations of electrodynamics of continuous media with toroid polarizations has been written.

Journal Article↗
PubMed2000

Recent trends in leprosy in a large district of West Bengal, India, revealed by a modified leprosy elimination campaign (MLEC), 1998.

A Modified Leprosy Elimination Campaign (MLEC) in September 1998 in the District of Midnapore, West Bengal, covered a population of 8.1 million people and detected 8181 new cases. Available data from 7328 cases were studied to observe the trend for leprosy in this area. Data are presented on sex and age distribution, classification and the proportions of multibacillary (MB), paucibacillary (PB) and single skin lesion (SSL) cases discovered in a period of only 8 days. The large numbers of people examined in this district and the high total of new cases revealed are in keeping with experience in other parts of the State and in other parts of India. However, many cases were found in endemic areas and these will receive special attention in a second MLEC, planned for January 2000.

Adolescent↗
PubMed2000

Efficacy of single-dose ROM therapy plus low-dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion.

The recent World Health Organization multicentric field study on the treatment of paucibacillary (PB) leprosy patients with single skin lesion (SSL) and a single dose of rifampin-ofloxacin-minocycline (ROM) brought new hope to those who are engaged in the eradication of leprosy from India. Being encouraged by the WHO report, we undertook the present hospital-based study and found that PB leprosy patients with SSL were morphologically and histopathologically heterogeneous. The histological spectrum of SSL ranged from indeterminate through tuberculoid (TT) to borderline tuberculoid (BT) leprosy, and most patients had active BT leprosy. Ninety new, untreated PB leprosy patients with SSL were included in the present study for comparative assessment of the efficacies of ROM and ROM plus Convit vaccine therapies. Children, pregnant women, lactating mothers and patients with any thickening of nerves were excluded. All patients were bacteriologically negative (skin-smear test) but lepromin reactive. The patients were divided into two groups after proper matching for morphological and histological status of SSL: a) The test group included 60 patients and the control group included 30 patients. The test group was given a single dose of ROM initially and two injections of low-dose Convit vaccine, one initially and the other at the end of 3 months. b) The control group was given only a single dose of ROM initially. Both groups were followed clinically every 2 weeks for 6 months and retested for histological, bacteriological and lepromin status at the end of 6 months. Thereafter, they were followed clinically every month for another 6 months. In the test group, the SSL resolved in 33.3%, regressed in 48.3%, and remained active in 18.3% of the patients, while the granuloma disappeared in 70% of the cases. Only one patient developed neuritis, and in another patient the disease relapsed on the eighth month. On the other hand, the SSL in the control patients resolved, regressed and remained active in 13.3%, 63.3% and 23.3% of the cases, respectively, while the granuloma disappeared in 53.3% of the cases. In the seven patients who remained active, the disease course was progressive, and two of them developed neuritis. The clinical outcome of the patients treated with ROM plus low-dose Convit vaccine was statistically superior to those treated with single-dose ROM therapy alone.

Adjuvants, Immunologic↗
PubMed1999

Susceptibility or resistance to Leishmania infection is dictated by the macrophages evolved under the influence of IL-3 or GM-CSF.

Although enhanced monocytopoiesis is a hallmark of leishmaniasis, its significance in determining the course of the disease has not been addressed. While the number of granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cells increases in the draining lymph nodes in a resistant mouse strain (C57BL/6) during disease, in a susceptible strain (BALB/c) the number of interleukin-3 (IL-3)-secreting cells increases. Treatment of BALB/c mice with anti-IL-3 antibody significantly reduces the disease score. Bone marrow macrophages derived under stimulation with IL-3 (IL-3-Mphi) or GM-CSF (GM-Mphi) differ functionally. GM-Mphi are significantly more responsive to IFN-gamma-induced augmentation and more refractory to IL-4-mediated suppression of anti-leishmanial activity than IL-3-Mphi. LPS-induced IL-12 and TNF-alpha secretion by both the susceptible and resistant strain-derived macrophage subsets are down-regulated. Despite down-regulation of IL-12 secretion, GM-Mphi favor expansion of IFN-gamma-secreting cells and IL-3-Mphi favor IL-6-dependent expansion of the IL-4-secreting Th subset. Adoptive transfer of leishmanial antigen-pulsed IL-3-Mphi and GM-Mphi prior to infection either aggravated or reduced the disease score, respectively, in BALB/c mice. Anti-IL-6 treatment reverted the Th subset profile not only in vitro but also in vivo, resulting in a reduced disease score in both infected BALB/c mice and IL-3-Mphi recipients. The disease score in IL-3-Mphi recipients is also reduced significantly after anti-IL-4 treatment.

Adoptive Transfer↗
PubMed1999

An investigation into the structural determinants of cannabinoid receptor ligand efficacy.

1. A number of side-chain analogues of delta8-THC were tested in GTPgammaS binding assay in rat cerebellar membranes. O-1125, a saturated side-chain compound stimulated GTPgammaS binding with an Emax of 165.0%, and an EC50 of 17.4 nM. 2. O-1236, O-1237 and O-1238, three-enyl derivatives containing a cis carbon-carbon double bond in the side-chain, stimulated GTPgammaS binding, acting as partial agonists with Emax values ranging from 51.3-87.5% and EC50 values between 4.4 and 29.7 nM. 3. The stimulatory effects of O-1125, O-1236, O-1237 and O-1238 on GTPgammaS binding were antagonized by the CB1 receptor antagonist SR 141716A. The K(B) values obtained ranged from 0.11-0.21 mM, suggesting an action at CB1 receptors. 4. Five-ynyl derivatives (O-584, O-806, O-823, O-1176 and O-1184), each containing a carbon-carbon triple bond in the side-chain, did not stimulate GTPgammaS binding and were tested as potential cannabinoid receptor antagonists. 5. Each -ynyl compound antagonized the stimulatory effects of four cannabinoid receptor agonists on GTPgammaS binding. The K(B) values obtained, all found to be in the nanomolar range, did not differ between agonists or from cerebellar binding affinity. 6. In conclusion, alterations of the side-chain of the classical cannabinoid structure may exert a large influence on affinity and efficacy at the CB1 receptor. 7. Furthermore, this study confirms the ability of the GTPgammaS binding assay to assess discrete differences in ligand efficacies which potentially may not be observed using alternative functional assays, thus providing a unique tool for the assessment of the molecular mechanisms underlying ligand efficacies.

Animals↗
PubMed1999

Structural determinants of the partial agonist-inverse agonist properties of 6'-azidohex-2'-yne-delta8-tetrahydrocannabinol at cannabinoid receptors.

1. We have extended previous investigations of four analogues of Delta8-tetrahydrocannabinol (Delta8-THC): 6'-azidohex-2'-yne-Delta8-THC (O-1184), 6'-azidohex-cis-2'-ene-Delta8-THC (O-1238) and octyl-2'-yne-Delta8-THC (O-584) and its 1-deoxy-analogue (O-1315). 2. O-1184, O-1238 and O-584 displaced [3H]-CP55940 from specific binding sites on Chinese hamster ovary (CHO) cell membranes expressing CB1 or CB2 cannabinoid receptors, with pKi values of 8.28 to 8.45 (CB1) and 8.03 to 8.13 (CB2). The pKi values of O-1315 were significantly less, 7.63 (CB1) and 7.01 (CB2). 3. All the analogues inhibited forskolin-stimulated cyclic AMP production by CB1-transfected CHO cells (pEC50=9.16 to 9.72). Only O-1238 behaved as a full agonist in this cell line. 4. In mouse vasa deferentia, O-1238 inhibited electrically-evoked contractions (pEC50=10.18 and Emax=70.5%). Corresponding values for O-1184 were 9.08 and 21.1% respectively. At 1 nM, O-1184 produced surmountable antagonism of the cannabinoid receptor agonist, CP55940. However, at 0.1 nM, O-1184 did not attenuate CP55940-induced inhibition of cyclic AMP production by CB1-transfected CHO cells. 5. In CB2-transfected CHO cells, cyclic AMP production was inhibited by CP55940 (pEC50=8.59), enhanced by O-1184 and O-584 (pEC50=8.20 and 6.86 respectively) and not significantly affected by O-1238 or O-1315. 6. At 100 nM, O-1184 and O-1238 produced surmountable antagonism of CP55940 in CB2 cells, decreasing the pEC50 of CP55940 from 8.61 to 7.42 (O-1184) or from 8. 54 to 7.44 (O-1238). 7. These data support the hypothesis that increasing the degree of unsaturation of the aliphatic side-chain of Delta8-THC analogues has little effect on CB1 or CB2 receptor affinity but can reduce CB1 receptor efficacy and reverse the direction of responses elicited at CB2 receptors.

Animals↗
PubMed1999

Production of xylitol by Candida peltata.

The ability of Candida peltata NRRL Y-6888 to ferment xylose to xylitol was evaluated under different fermentation conditions such as pH, temperature, aeration, substrate concentration and in the presence of glucose, arabinose, ethanol, methanol and organic acids. Maximum xylitol yield of 0.56 g g-1 xylose was obtained when the yeast was cultivated at pH 6.0, 28 degrees C and 200 rpm on 50 g L-1 xylose. The yeast produced ethanol (0.41 g g-1 in 40 h) from glucose (50 g L-1) and arabitol (0.55 g g-1 in 87 h) from arabinose (50 g L-1). It preferentially utilized glucose > xylose > arabinose from mixed substrates. Glucose (10 g L-1), ethanol (7.5 g L-1) and acetate (5 g L-1) inhibited xylitol production by 61, 84 and 68%, respectively. Arabinose (10 g L-1) had no inhibitory effect on xylitol production.

Journal Article↗
PubMed1999

Apoptosis of Th1-like cells in experimental tuberculosis (TB).

Th1 cell-induced anti-mycobacterial immunity is lost during a progressive Mycobacterium tuberculosis infection in a susceptible host. This study was designed to test the mechanism of the loss of anti-mycobacterial cell-mediated immune response. We demonstrate that M. tuberculosis infection results in increased Fas expression and decreased Bcl-2 expression in CD4+ T cells. When CD4+ T cells are stimulated in vitro, they show increased apoptosis and decreased production of IL-2 and interferon-gamma (IFN-gamma) but not of IL-4. These changes may result in selective apoptosis of Th1-like cells, leading to the loss of cell-mediated immune response against M. tuberculosis.

Animals↗
PubMed1999

Leishmania donovani infection of a susceptible host results in CD4+ T-cell apoptosis and decreased Th1 cytokine production.

The disease visceral leishmaniasis is caused by a protozoan parasite, Leishmania donovani and is characterized by depressed cell-mediated immunity (CMI) and unhindered parasite growth in a susceptible host. The opposite trend is observed in a resistant host. However, the mechanism of this loss of CMI during the progressive disease is unknown as yet. In this report, we demonstrate that more than 40% of CD4+ T cells from a susceptible host undergo apoptosis resulting in a significant decrease in interleukin (IL)-2 and interferon (IFN)-gamma secretion, leaving IL-4 secretion unaffected. These changes are not apparent in the case of CD4+ T cells derived from a resistant host. The data reported here suggest that experimental Leishmania donovani infection leads to selective deletion of the IL-2 and IFN-gamma-secreting cells but not Th2-like cells in a susceptible but not a resistant host.

Animals↗