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Biomedical subjects

S Agarwal

Publications and source records attributed to S Agarwal.

At least 217 records · Page 12Linked to original sources
PubMed1995

Hepatoprotective studies on Phyllanthus emblica Linn. and quercetin.

Phyllanthus emblica is a constituent of many hepatoprotective formulations available in market. 50% alcoholic extract of P. emblica and quercetin isolated from it were studied for hepatoprotective effect against country made liquor (CML) and paracetamol challenge in albino rats and mice respectively. The extract at the dose of 100 mg/100 g [corrected], po and quercetin at the dose of 15 mg/100 g, po, produced significant hepatoprotection.

Animals↗
PubMed1995

Leukemoid reaction in amoebic liver abscess.

A case of amoebic liver abscess with leukemoid reaction is described. This patient also had jaundice as the presenting feature. Therapy with metronidazole resulted in improved general condition and both blood picture and liver function tests also became normal.

Adult↗
PubMed1995

Up-regulation of cytokine mRNA in human monocytes and myeloid cell lines by the differentiation/activation factor p48.

Polypeptide 48 is a 48,000 MW protein, originally isolated from conditioned media of some human leukaemic cell lines, that induces differentiation and cytolytic activity in HL-60 promyelocytic leukaemia cells and activates human peripheral blood monocytes to secrete interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha). In the present study we examined the effects of p48 on the accumulation of a series of monokine transcripts, including TNF-alpha, IL-1 alpha, IL-1 beta and IL-6, in human peripheral blood monocytes and the myeloid/monocyte cell lines HL-60 and U937. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis, p48 was found to induce accumulation of TNF-alpha, IL-1 alpha and IL-1 beta mRNA in peripheral blood monocytes, HL-60 and U937 cells. IL-6 mRNA was found to be increased in p48-stimulated peripheral blood monocytes but not HL-60 or U937. Thus, the secretion of IL-1 and TNF-alpha by p48-stimulated monocytic cells was associated with up-regulation of cytokine mRNA, suggesting that p48 leads to increased transcription or mRNA stability in these cells. As U937 and HL-60 are likely to represent premonocyte stages of haemopoietic differentiation, it is possible that the effect of p48 on IL-6 mRNA, in contrast to its effect on TNF and IL-1, requires cells to be at a later differentiation step.

Blotting, Northern↗
PubMed1995

Role of cytokines in periodontal diseases.

The known actions of cytokines suggest that these molecules hold a great potential for modulating the host immune response and enhancing tissue regeneration. These molecules would be useful in controlling the adverse effects of the host immune response and/or augmenting the regenerative potential of cytokines. Once the technology is optimized, it may be possible for dentists to apply cytokine therapy to resolve periodontal infections. Such therapeutic measures hold promise not only in the resolution of periodontal infections, but also in the treatment of other diseases of the oral cavity.

Cytokines↗
PubMed1994

DNA oxidative damage and life expectancy in houseflies.

The objective of this study was to explore the relationship between oxidative molecular damage and the aging process by determining whether such damage is associated with the rate of aging, using the adult housefly as the experimental organism. Because the somatic tissues in the housefly consist of long-lived postmitotic cells, it provides an excellent model system for studying cumulative age-related cellular alterations. Rate of aging in the housefly was manipulated by varying the rate of metabolism (physical activity). The concentration of 8-hydroxydeoxyguanosine (80HdG) was used as an indicator of DNA oxidation. Exposure of live flies to x-rays and hyperoxia elevated the level of 8OHdG. The level of 8OHdG in mitochondrial as well as total DNA increased with the age of flies. Mitochondrial DNA was 3 times more susceptible to age-related oxidative damage than nuclear DNA. A decrease in the level of physical activity of the flies was found to prolong the life-span and corresponding reduce the level of 8OHdG in both mitochondrial and total DNA. Under all conditions examined, mitochondrial DNA exhibited a higher level of oxidative damage than total DNA. The 8OHdG levels were found to be inversely associated with the life expectancy of houseflies. The pattern of age-associated accrural of 8OHdG was virtually identical to that of protein carbonyl content. Altoghether, results of this study support the hypothesis that oxidative molecular damage is a causal factor in senescence.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice.

The objective of this study was to explore the role of molecular oxidative damage and caloric intake in the aging process. The concentration of 8-hydroxydeoxyguanosine (8-OHdG), a product of DNA oxidation, was compared in five different tissues of mice (skeletal muscle, brain, heart, liver and kidney) as a function of age and in response to dietary restriction. A comparison of 8- and 27-month-old mice indicated that the age-related increase in 8-OHdG concentration was greater in skeletal muscle, brain and heart, which are primarily composed of long-lived, post-mitotic cells, than in liver and kidney, which consist of slow-dividing cells. Dietary restricted (DR) mice kept on 60% caloric intake as compared to the ad libitum-fed (AL) mice showed a lower concentration in 8-OHdG content in all the tissues compared to AL mice. The DR-related amelioration of DNA oxidative damage was greater in the post-mitotic tissues compared to those undergoing slow mitoses. Results support the hypothesis that oxidative damage to long-lived post-mitotic cells may be a key factor in the aging process.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Poly ADP-ribosylation of a 90-kDa protein is involved in TNF-alpha-mediated cytotoxicity.

Nicotinamide and 3-aminobenzamide prevent TNF-alpha-mediated cytotoxicity, indicating that ADP-ribosylation plays a crucial role in this reaction. We have studied the role of ADP-ribosylation during TNF-alpha action in TNF-alpha-sensitive and TNF-alpha-resistant cells. Treatment of 3T3 cells with TNF-alpha, in the presence of [adenylate-32P]NAD followed by SDS-PAGE, revealed the involvement of specific ADP-ribosylation of a 90-kDa protein in TNF-alpha-mediated cytotoxicity. The stability of the ADP-ribosyl linkage on the 90 kDa protein in 100 mM 2-(N-cyclohexylamino)ethanesulfonic acid at pH 9.0 confirmed that ADP-ribosylation of the 90 kDa protein was mediated by an enzymatic reaction. Analysis of ADP-ribose residues by phosphodiesterase hydrolysis showed that the 90-kDa protein was modified by poly ADP-ribosylation. Poly ADP-ribosylation of the 90-kDa protein concomitant with cytotoxicity was observed in all TNF-alpha-sensitive but not TNF-alpha-resistant cells. Inhibition of ADP-ribosylation of the 90-kDa protein by benzamide but not by benzoic acid abrogated cytotoxicity, which further suggested that the poly-ADP-ribosylation of the 90-kDa protein is causally related to TNF-alpha-induced cell death. Our results demonstrate that TNF-alpha modifies a specific protein by poly-ADP-ribosylation during its action. Furthermore, ADP-ribosylation of specific proteins may be yet another mechanism regulating protein function during cellular metabolism.

3T3 Cells↗
PubMed1994

Aging and proteolysis of oxidized proteins.

The main objective of this study was to investigate the possible cause(s) of the age-related augmentation of oxidatively damaged proteins in animal tissues. The hypothesis that activity of alkaline proteases, involved in the proteolysis of oxidized proteins, declines during aging was tested in the adult male housefly and further explored in the rat. Alkaline protease activity was measured fluorometrically by the release of trichloroacetic acid-soluble fluorescamine-reactive material from X ray-oxidized bovine serum albumin (BSA). Alkaline protease activity in the housefly was linearly related to the number of protein carbonyl groups. Possible involvement of serine or serine and thiol proteases was deduced from a 70% proteolytic inhibition by aprotinin and a 50% inhibition by leupeptin. Protease activity of houseflies for oxidized or native BSA did not alter with age. In contrast, a varied age-related pattern of protease activity was observed in the tissues of the rat. A comparison of 3-, 13-, and 23-month-old Sprague-Dawley rats indicated no age-related decline in alkaline protease activity in the brain, a 50% decline in the liver, and a 20% decline in the heart during 13 to 22 months. Results of this study suggest that in some species or tissues an age-related increase in the oxidized protein content is primarily due to a corresponding increase in the rate of protein oxidation, while in some other tissues a decline in proteolysis may be a contributory factor.

Aging↗
PubMed1994

Identification of a deoxyguanosine-malondialdehyde adduct in rat and human urine.

In an ongoing study, rat and human urine have been examined for the presence of malondialdehyde (MDA) derivatives as indicators of the nature of lipid peroxidative damage caused by this compound in vivo. MDA in urine was found to be present mainly in the form of two lysine adducts, one acetylated and the other unacetylated, reflecting in vivo reactions with tissue proteins. Two minor metabolites were identified as adducts with the phospholipid bases serine and ethanolamine and a third one as an adduct with the nucleic acid base guanine. The identification of an MDA adduct with deoxyguanosine (dG-MDA) among the products of hydrolysis of rat liver DNA suggested the possible occurrence of this compound in urine. In the present study dG-MDA was identified in rat and in human urine, and a high-performance liquid chromatographic method utilizing fluorescence detection was developed for its estimation. The method is sensitive to 1 pmol of dG-MDA and requires a minimum of 1 mL of rat urine or 5 mL of human urine. Its rate of excretion by five-week-old rats (28.54 +/- 2.28 nmol/kg/24 h) (mean +/- SEM) was higher than that for nine-week-old rats (6.29 +/- 1.02) and much higher than that for adult humans (0.40 +/- 0.05). The results indicate that, as reported for 8-hydroxy-deoxyguanosine, dG-MDA excretion is related to metabolic rate. Excretion of dG-MDA by the rat, like the excretion of total MDA, declines during growth on a body weight basis at a rate similar to the decrease in resting energy metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1994

Aging and protein oxidative damage.

The hypothesis that aging is associated with the accumulation of oxidative damage was tested in the adult male housefly by monitoring the loss of membrane protein -SH groups, and activities of glucose-6-phosphate dehydrogenase and alcohol dehydrogenase, the cytosolic enzymes that are particularly susceptible to oxidative damage. Membrane protein -SH content and activities of these enzymes decreased with age and were correlated with the life expectancy or physiological age rather than the chronological age of the flies. Because the experimentally-induced loss of membrane protein -SH groups has a demonstrable deleterious effect on a variety of cellular functions, such damage during aging can be hypothesized to contribute to the physiological attrition associated with senescence.

Aging↗
PubMed1994

Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse.

This study was conducted in order to test the concept that oxidative damage is associated with aging and may be a factor in the modulation of life span in response to variations in caloric intake. Mice fed a diet that was 40% lower in calories (DR) than the ad libitum fed (AL) animals exhibited a 43% extension in average life span and a 61% prolongation in mortality rate doubling time. A comparison of AL and DR mice at 9, 17 and 23 months of age indicated that the protein carbonyl content in the brain, heart and kidney increased with age and was significantly greater in the AL than DR group in each organ at each of the three ages. Mitochondrial state 4 or resting respiratory rate increased with age in the AL, but not the DR group, and was also relatively higher in the former. The rates of mitochondrial superoxide and hydrogen peroxide generation increased with age and were higher in the AL than DR mice in all the three organs at each age. In contrast, there was no clear-cut overall pattern of age-related or dietary-related changes in antioxidant defenses provided by superoxide dismutase, catalase and glutathione peroxidase. Results suggest that mechanisms of aging and life span shortening by enhanced caloric intake are associated with oxidative damage arising from corresponding changes in mitochondrial oxidant production. Protein carbonyl content, and mitochondrial O2.- and H2O2 generation may act as indices of aging.

Aging↗
PubMed1994

Neutrophil function in juvenile periodontitis: induction of adherence.

Polymorphonuclear leukocytes (neutrophils) in patients with localized juvenile periodontitis with decreased chemotaxis exhibit increased adherence. The molecular basis of increased adherence of neutrophils in localized juvenile periodontitis is not clear. We show that the neutrophils from localized juvenile periodontitis patients with decreased neutrophil chemotaxis and increased adherence exhibit increased expression of the CD11/CD18 family of adherence molecules, Mac-1, leukocyte function-associated antigen (LFA-1) and p150,95, as compared with neutrophils obtained from systemically and periodontally healthy controls. Treatment of neutrophils obtained from healthy subjects with sera from localized juvenile periodontitis patients resulted in an increased expression of Mac-1, leukocyte function-associated antigen and p150,95 molecules. Sera obtained from health subjects, patients with adult periodontitis or localized juvenile periodontitis patients with normal chemotaxis did not increase the expression of CD11/CD18 molecules on the neutrophils obtained from healthy subjects. The ability of localized juvenile periodontitis sera to induce expression of adherence molecules was at least partially inhibited by pretreatment of localized juvenile periodontitis sera with anti-tumor necrosis factor and anti-interleukin-1 antibodies. Furthermore, increasing concentrations of rh-tumor necrosis factor-alpha and interleukin-1 beta also induced increased expression of the Mac-1 molecule on neutrophils from localized juvenile periodontitis patients and healthy subjects. The increased expression of adherence molecules on neutrophils from localized juvenile periodontitis patients was sustained and could not be reversed by treatment of localized juvenile periodontitis neutrophils with sera obtained from healthy subjects. The upregulation of adherence molecules on neutrophils by localized juvenile periodontitis sera in these experiments emphasizes the physiologic importance of quantitatively small but biologically significant levels of cytokines in the modulation of neutrophil functions in localized juvenile periodontitis.

Adolescent↗
PubMed1994

Preliminary report--combined surgical and radiological penile vein occlusion for the management of impotence caused by venous-sinusoidal incompetence.

OBJECTIVES: To combine surgical and radiological penile vein occlusion therapy in the treatment of patients with venogenic impotence, to try to improve on the results of either treatment used separately. PATIENTS AND METHODS: Fourteen patients, with a mean age of 46 years (range 25-71), with pure venous-sinusoidal impotence were treated by surgical ligation of accessible veins and embolization of surgically inaccessible veins. The preliminary results over a follow-up period of at least 8 months are reported for each patient. RESULTS: Venous embolization was considered complete in 11 patients. Overall, 13 had improved erectile function. Post-operatively, eight patients developed spontaneous erections and four (aged < 40 years) have maintained this for 8-24 months. CONCLUSION: Combined surgery and radiology treats the end result of the failure of the sinusoidal smooth muscle to relax. Although some patients, the majority of whom are young (aged < 40 years), will achieve short-term benefit, all individuals need to be fully counselled with regard to the likelihood of long-term benefit before undergoing this invasive method of treatment.

Adult↗
PubMed1994

Role of cytokines in the modulation of neutrophil chemotaxis in localized juvenile periodontitis.

Decreased neutrophil chemotaxis has been implicated in the pathophysiology of the disease, localized juvenile periodontitis (LJP). The biological basis for the altered neutrophil function in LJP has been suggested to be an intrinsic cellular defect, involving a decrease in the number of N-formyl-methionyl-leucyl-phenylalanine (FMLP) receptors on the cell surface. We have investigated the relative contribution of serum-borne factors in the modulation of neutrophil functions in LJP, in a large population of LJP patients and healthy control subjects (HS). Treatment of HS-neutrophils with LJP-sera, resulted in a decreased neutrophil chemotactic response, and down regulation of FMLP receptors on the cell surface. Pretreatment of LJP-sera with anti-TNF and anti-IL-1 antibodies effectively, although incompletely, neutralized the ability of LJP-sera to modulate chemotaxis and FMLP receptor levels in HS-neutrophils. The changes induced by LJP sera were specific and sustained and could not be reversed by placing LJP-serum treated neutrophils in HS-serum. Sera obtained from HS and patients with adult periodontitis (AP), both of which exhibit normal chemotaxis, and patients with clinically diagnosed LJP with normal neutrophil chemotaxis (LJP-nctx) did not modulate HS neutrophil chemotaxis or FMLP receptors. Furthermore, recombinant human TNF-alpha, rhIL-1 alpha and rhIL-1 beta, at very low concentrations (15 pg/ml to 150 pg/ml), modulated the chemotactic response as well as FMLP receptor numbers on HS-neutrophils, in a manner similar to those observed in LJP. The present findings demonstrate that the biologic basis for the altered neutrophil function may not be an intrinsic cellular defect in neutrophils, but at least in part due to quantitatively small but biologically significant elevations in the levels of TNF-alpha and IL-1 in the serum.

Adolescent↗
PubMed1994

Characterization of beta-thalassaemia mutations in 57 beta-thalassaemia families seen at Lucknow.

As an initial step towards establishing prenatal diagnostic service for beta-thalassaemia in the state of Uttar Pradesh, we have investigated the prevalence of five common mutations reported from India in 57 families, each with an index patient of thalassaemia major, by amplification refractory mutation system (ARMS). Thirtyone of the 57 families (54.3%) hailed from Uttar Pradesh; 11 (19.3%) from Sindh in Pakistan, 6 (10.5%) from Punjab, 6 (10.5%) from North-West Pakistan and one each (1.8%) from Bengal, Madhya Pradesh and Bihar. In the 31 families from Uttar Pradesh, 29 were of beta-thalassaemia and 2 of HbE/beta-thalassaemia. IVS-1 nt 5 (G-C) mutation was the most common mutation in families native to Uttar Pradesh. This mutation was identified in 60 per cent (33 out of 55) of the obligate heterozygotes. Amongst the 43 obligate heterozygote carriers originating from Western India, the prevalence of IVS-1 nt 5 (G-C) mutation was 46.5 per cent; 619 bp deletion 23.3 per cent; Co 8/9 (+G) mutation 11.6 per cent and Co 41/42 (-CTTT) mutation 4.6 per cent. In 23.6 per cent of carriers from Uttar Pradesh and 7.0 per cent of carriers from Western India, none of the 5 mutations tested were detected. IVS-1 nt 1 (G-T) mutation was found in one family native to Sindh.

Base Sequence↗