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Biomedical subjects

M Z Hussain

Publications and source records attributed to M Z Hussain.

At least 19 recordsLinked to original sources

Lactate down-regulates cellular poly(ADP-ribose) formation in cultured human skin fibroblasts.

BACKGROUND: Polyadenosine diphosphate-ribose (poly(ADP-ribose)) is a nuclear polymer which is derived from nicotinamide adenine dinucleotide (NAD(+)) catalysed by poly(ADP-ribose) polymerase 1 (PARP-1). Aside from the well known role of poly(ADP-ribosyl)ation (pADPR) in DNA repair, pADPR is also involved in other cellular processes such as apoptosis and gene expression. However, the factors that regulate the level of pADPR are not fully elucidated. In view of the fact that healing wounds contain high concentrations of lactate (10-15 mM) and exogenous lactate reduce the NAD(+) pool in cultured fibroblasts, we propose that high lactate lowers the level of nuclear pADPR. MATERIALS AND METHODS: Neonatal human dermal fibroblasts (NHDF) were plated to subconfluence and allowed to adhere. Cells were treated with 15 mM l-lactate and pADPR production was assessed by immunofluorescence analysis using 10H antibody. Difference in pADPR production was determined by calculation of positively stained cells compared to total cell numbers. Inhibition of PARP activity was tested by treatment with 100 microM 3-aminobenzamide (3-AB). Specificity of the lactate effect on pADPR synthesis was verified by using the analogue d-lactate. The contents of nicotinamide adenine dinucleotide (NAD(+)) and its reduced form (NADH) in lactated and non-lactated cell cultures were quantified by the enzymatic cyclic assay. RESULTS: We found that exogenous l-lactate (15 mM) can significantly depress pADPR content in cultured fibroblasts. PARP-1 activity was inhibited by 3-AB and analogue d-lactate showed no effect on pADPR synthesis. NAD(+)/NADH ratio was significantly lowered in lactated compared to non-lactated cell culture. CONCLUSIONS: Exogenous l-lactate (15 mM) can depress pADPR content in cultured fibroblasts. In view of the fact that healing wounds contain such high concentrations of lactate, we propose that down regulation of pADPR is associated with elevated tissue repair via pADPR dependent gene expression. This observation is important in understanding the stimulation of lactate-mediated protein expression during wound healing.

Cells, Cultured↗

Soil properties and crop productivity as influenced by flyash incorporation in soil.

Field experiments were carried out during 1996-97 at Gulawathi, Muthiani and Salarpur Villages, IARI Farm, New Delhi and NCPP Campus, Dadri to evaluate changes in soil characteristics and growth of wheat (Triticum aestivum L.), mustard (Brassica juncea L.), lentil (Lence esculenta Moench.), rice (Oryza sativa L.) and maize (Zea mays L.) by varying amounts of flyash addition (up to 50t ha(-1)) in soils at sowing/transplanting time of crops. Flyash addition in areas adjoining NCPP Thermal Power Plant, Dadri, Ghaziabad, U.P. ranged from 5-12 t ha(-1)] yr(-1) in 1995-96. Shoot and root growth and yield of test crops at different locations after flyash incorporation resulted in beneficial effects of flyash addition in most cases. The silt dominant texture of flyash improved loamy sand to sandy loam textures of the surface soils at the farmers' fields. The increased growth in yield of crops with flyash incorporation was possibly due to modifications in soil moisture retention and transmission characteristics, bulk density, physico-chemical characters such as pH and EC and organic carbon content. The response of flyash addition in the soil on soil health and crop productivity needs to be evaluated on long-term sustainable aspects.

Agriculture↗

Hydrogen peroxide stimulates macrophage vascular endothelial growth factor release.

Neutrophils gather at the wound site shortly after trauma and release bactericidal reactive oxygen species (ROS) and H2O2 to kill bacteria and prevent infection. Macrophages arrive at the wound in response to environmental stimuli, phagocytose foreign particles, and release vascular endothelial growth factor (VEGF), an angiogenic factor crucial for wound healing. Because oxidants are released early in inflammation and have been found to regulate transcription factors, we investigated a possible role of H2O2 in VEGF stimulation. Human U937 macrophages exposed to H2O2 and allowed to recover in H2O2-free medium rapidly showed an increase in VEGF mRNA. The H2O2-mediated mRNA increase was dose dependent, blocked by catalase, and associated with elevated VEGF in conditioned media. The increase in VEGF was also found in primary rat peritoneal macrophages and the RAW 264.7 murine macrophage cell line. Transcriptional inhibition with actinomycin D revealed no significant difference in mRNA half-life. Transient transfections with a 1.6-kb VEGF promoter-luciferase construct (Shima DT, Kuroki M, Deutsch U, Ng YS, Adamis AP, and D'Amore PA. J Biol Chem 271: 3877-3883, 1996) showed a ninefold stimulation of VEGF gene promoter activity. We concluded that H2O2 increases macrophage VEGF through an oxidant induction of VEGF promoter. This oxidant stimulation can be mediated by activated neutrophils.

Endothelial Growth Factors↗

Detection of interleukin-6 in human dental pulp and periapical lesions.

Pulpal and periapical diseases are characterized by inflammation. The cytokine IL-6 is a major mediator of the host response to tissue injury and infection. This study examined the level of interleukin-6 (IL-6) in six inflamed human pulps and six human periapical lesions of endodontic origin using ELISA. Pulp samples from eight clinically impacted teeth were used as controls. The periapical samples exhibited significant levels of IL-6 (mean = 78.1 +/- 9 pg/mg protein) as did inflamed pulpal tissues mean = 36 +/- 3.9 pg/mg protein) compared to healthy pulp mean = 0.01 +/- 0.02 pg/mg protein). These data indicated that IL-6 was produced and released locally in the inflamed pulpal and periapical lesions.

Adult↗

Prevalence of diabetes in a suburban population of Bangladesh.

To determine the prevalence of diabetes and hypertension, 6847 subjects of age 15 years or older, were investigated in a suburban population in Bangladesh. Fasting and post-prandial (capillary) blood glucose (2-hPG) was estimated. According to WHO criteria the crude prevalence of impaired glucose tolerance (IGT) was 7.5% and non-insulin-dependent diabetes mellitus (NIDDM) was 4.1%. The age standardized (30-64 years) prevalence of IGT was 7.7% with 95% confidence interval (CI) 6.96-8.44 and NIDDM was 4.5%, CI 3.94-5.12. Compared with the younger subjects the older subjects (< 40 vs. > or = 40 years) showed significant association with IGT (chi2, 65.9; P < 0.001) and NIDDM (chi2, 92.0; P < 0.001). Higher BMI (< or = 22.0 vs. > 22.1) was also significantly associated with IGT (chi2, 16.6; P < 0.001) and NIDDM (chi2, 83.9; P < 0.001). The higher BMI had stronger association with NIDDM than with IGT. Lower height showed significant association only with NIDDM. The logistic regression analyses also showed that increased age, higher BMI and short stature were independent risks for NIDDM. The study showed an increased prevalence of IGT and NIDDM among the suburban population of Bangladesh and the excess risk was observed with increased age, higher BMI and short stature.

Adolescent↗

Removal of intracanal smear by doxycycline in vitro.

UNLABELLED: Cleansing and shaping result in a smear layer on the instrumented canal wall surfaces. The smear layer may inhibit close contact between sealers and dentin, and inhibits diffusion of medicaments. OBJECTIVE: This study assessed the effect of doxycycline hydrochloride (DH) on smear layer on intracanal walls. STUDY DESIGN: Scanning electron microscopy was used to evaluate the remaining smear layer using different concentrations of DH. Single-canal palatal roots of extracted maxillary molars were irrigated with saline-15% EDTA; saline-25 mg/ml DH; saline-50 mg/ml DH; saline-100 mg/ml DH; NaOCl-15% EDTA; NaOCl-25 mg/ml DH; NaOCl-50 mg/ml DH; and NaOCl-100 mg/ml DH. The roots were fractured into halves and the amount of smear layer assessed in the middle and apical third. RESULTS: Doxycycline-HCl of 100 mg/ml was the most effective in removing smear layer. In the saline group, 100 mg/ml of DH was more effective than EDTA. In the hypochlorite group, 50 mg/ml and 100 mg/ml of DH were more effective than EDTA (p < 0.05). CONCLUSION: Doxycycline solution may be an effective irrigant.

Anti-Bacterial Agents↗

Effect of socioeconomic risk factors on the difference in prevalence of diabetes between rural and urban populations in Bangladesh.

OBJECTIVE: To compare the prevalence of diabetes between the poor and rich of rural and urban populations in Bangladesh. RESEARCH DESIGN AND METHODS: A total of 1,052 subjects from urban and 1,319 from rural communities (age > or = 20 years) of different socioeconomic classes were investigated. Capillary blood glucose levels, fasting and 2 h after a 75-g glucose drink (2-h blood glucose [BG]), were measured. Height, weight, waist, hips, and blood pressure were also measured. RESULTS: Age-adjusted (30-64 years) prevalence of NIDDM was higher in urban (7.97% with 95% CI 6.17-9.77) than in rural subjects (3.84%, CI 2.61-5.07), whereas impaired glucose tolerance (IGT) prevalence was higher in rural subjects. In either urban or rural areas, the highest prevalence of NIDDM was observed among the rich, and the lowest prevalence was observed among the poor socioeconomic classes. The rural rich had much higher prevalence of IGT than their urban counterpart (16.5 vs. 4.4%, CI 6.8-17.4). Increased age was an important risk factor for IGT and NIDDM in both rural and urban subjects, whereas the risk related to higher BMI and waist-to-hip ratio (WHR) was less significant in rural than urban subjects. Using logistic regression and adjusting for age, sex, and social class, the urban subjects had no excess risk for NIDDM. In contrast, an excess risk for glucose intolerance (2-h BG > or = 7.8 mmol/l) was observed in the rural subjects. CONCLUSIONS: Adjusting for age, sex, and social class, the prevalence of NIDDM among urban subjects did not differ significantly from that among rural subjects. Increased age, higher socioeconomic class, and higher WHR were proven to be independent risk factors for glucose intolerance in either area.

Adult↗

Biochemical alterations in inflammatory periodontal diseases I. Poly (ADP-ribose) synthetase activity in gingiva and gingival fibroblasts from humans with periodontitis.

Periodontal diseases are characterized in part by generation of oxygen free radicals, which can cause breaks in cellular DNA strands. Repair of damaged DNA is dependent upon the synthesis of poly (ADP-ribose)(PADPR) catalyzed by PADPR synthetase, an enzyme known to be activated by the broken ends of DNA strands. We measured the activities of PADPR synthetase and of PADPR glycohydrolase, which degrades PADPRS, in gingival biopsy specimens from 16 sites with adult periodontitis and 12 clinically healthy control sites. The results indicated that sites with periodontitis displayed markedly reduced PADPR synthetase activity compared with healthy control sites, whereas PADPR glycohydrolase activity was not changed. The mean specific activity of PADPR synthetase for the diseased specimens was one-sixth of that of the healthy specimens (p < 0.001). The PADPR synthetase activity was negatively correlated with the Gingival Index (rs = -0.60), pocket depth (rs = -0.70) and bleeding upon probing (rs = -0.72). Cultured fibroblasts derived from clinically characterized healthy and diseased gingival sites reflected similar patterns of enzyme activity. The mean specific activity of PADPR synthetase for the diseased-site cultures (n = 9) was 56 +/- 7% (p < 0.001) of the cultures from healthy control sites (n = 6). These results suggest that a reduced level of PADPR synthetase activity is associated with increased inflammation and periodontal destruction, and that the ability to synthesize PADPR is compromised in adult periodontitis.

Adult↗

Lactate stimulation of macrophage-derived angiogenic activity is associated with inhibition of Poly(ADP-ribose) synthesis.

Injury and inflammation lead to hypoxia and elevated lactate in wounds. This redox environment establishes cells in a reparative phenotype and leads macrophages to release angiogenic substances by unclear mechanisms. We investigated compounds known to modulate polyadenosine diphophoribose (pADP-R) levels in their effect on macrophage-derived angiogenic activity. Macrophages cultured from rabbit bone marrow were exposed to lactate, nicotinamide, and/or beta-nicotinamide adenine dinucleotide (NAD+). Supernatants were assayed for angiogenesis, and macrophages were analyzed for NAD+ content, poly(ADP-ribose) synthetase activity, and total (ADP-ribose)n synthesis. Lactate-, nicotinamide-, and lactate and nicotinamide-treated macrophages elicited significantly increased angiogenic activity compared with control or NAD+-treated cells. Lactate treatment decreased NAD+ content by 42 +/- 4% and (ADP-ribose)n synthesis by 37 +/- 5%. Nicotinamide reduced poly(ADP-ribose) synthetase activity and poly(ADP-ribose) synthesis. Thus, macrophage-derived angiogenic activity may be mediated by the redox environment involving NAD+ metabolites.

Animals↗

MRI of white matter changes in the Sjögren-Larsson syndrome.

We report a case of Sjögren-Larsson syndrome with spastic diplegia and conduction aphasia. MRI demonstrated the white matter changes deep in the cerebral hemispheres. We analyse the MRI findings and compare the results with neuropsychological signs.

Adolescent↗

Prevalence of diabetes and hypertension in a rural population of Bangladesh.

OBJECTIVE--To determine the prevalence of non-insulin-dependent diabetes mellitus (NIDDM), impaired glucose tolerance (IGT), and hypertension in a rural community of Bangladesh. RESEARCH DESIGN AND METHODS--A cluster sampling of 1,005 subjects > 15 years of age in the rural community of Dohar was investigated. Capillary blood glucose of fasting and 2 h after 75 g oral glucose (2hBG) were estimated. World Health Organization criteria were used for diagnosis of NIDDM and IGT. Blood pressure, height, and weight were also measured. RESULTS--The crude prevalence of NIDDM was 2.1% (men 3.1, women 1.3%) and IGT was 13.3% (men 14.4, women 12.4%). Age-adjusted (30-64 years of age) prevalence was 2.23% (95% confidence interval [CI] 1.01-3.45) for NIDDM and 15.67% (95% CI 12.59-18.75) for IGT. Prevalence of hypertension with systolic blood pressure (sBP) > or = 140 mmHg was 10.5% and with diastolic blood pressure (dBP) > 90 mmHg was 9.0%. Increased age was the risk factor for NIDDM, IGT, and hypertension; whereas increased BMI showed inconsistent association with them. Relative risk for sBP with higher BMI ( < 22.0 vs. > or = 22.1) was 1.94 with CI 1.55-2.43 and for dBP it was 2.2 with CI 1.40-3.46. Correlation of sBP was significant with age, BMI, and 2hBG. Similar correlation was also observed with dBP. CONCLUSIONS--High prevalences of NIDDM, IGT, and hypertension were observed among rural subjects. Increased age was shown to be an important risk factor for all these disorders, whereas BMI-associated risk was significant with NIDDM and hypertension but not with IGT.

Adolescent↗

Can wound healing be a paradigm for tissue repair?

This paper is written in the hope, if not the conviction, that it will be helpful to investigators of muscle physiology and development. Its thesis is that cell growth, connective tissue matrix deposition, and angiogenesis are stimulated in wounds in response to NAD+ depletion caused by a burst in lactate generation. We surmise that muscle development may also involve this metabolic control.

Adenosine Diphosphate Ribose↗

Alterations of fibroblast metabolism in early ligature-induced periodontitis in the cynomolgus monkey.

Cellular and biochemical observations were made of fibroblasts harvested from ligature-induced periodontitis and treated gingivitis areas in four adult female cynomolgus monkeys (Macaca fascicularis) to define the changes that occur in the early periodontitis lesion. Compared with fibroblasts from the treated sites, fibroblasts from the diseased areas had a significantly higher rate of proliferation, produced about two-thirds the amount of total protein and collagen, and failed to respond to TGF-beta, which normally stimulates extracellular matrix formation in mesenchymal cells. The diseased cells were also deficient in the activity of poly(ADP-ribose) synthetase, an enzyme involved in the repair of DNA breaks such as occur from the insults of superoxide and other active radicals present in inflamed areas. Although the precise nature of these biochemical defects is not fully elucidated, they may have an important bearing on chronic periodontitis cases with a "downhill" course.

Animals↗

Blood pressure and glycemic status in relation to body mass index in a rural population of Bangladesh.

A cluster sampling of five villages in Dohar thana were selected for screening of hypertension and diabetes in relation to age structure and body habitus. All the subjects over 15 years of age were enlisted for investigation. The response rate was more than 70%. Height, weight, blood pressure (BP) and capillary blood glucose (fasting and 2-hPG) were measured. Diagnostic criteria of international standard were used for hypertension and diabetes. Out of 1005 participants 106 subjects (10.5%) had systolic blood pressure (sBP) more than 140 mmHg and 9% of them had diastolic blood pressure (dBP) more than 90 mmHg. The prevalence of non-insulin-dependent diabetes mellitus (NIDDM) was 2.1% and impaired glucose tolerance (IGT) was 13.3%. The mean body mass index (BMI) of men was 20.39 (SD = 2.91) and that of women was 20.11 (SD = 2.92), having no significant difference between them. Increased age (> or = 50 yr), high BMI (> or = 23.0) and hyperglycemia (2-hPG > 7.8 mmol/L) were the risk factors for both systolic (sBP > 140 mmHg) and diastolic (dBP > 90 mmHg) hypertension. Likewise, increased age, high BMI and hypertension showed significant association with glucose intolerance. Moreover, significant correlations were observed between age and BP (sBP, r = 0.328 p < 0.001; dBP, r = 0.187 p < 0.001) BMI and BP (sBP, r = 0.193 p < 0.001; dBP, r = 0.192 p < 0.001) and 2-hPG and BP (sBP, r = 0.188 p < 0.001; dBP, r = 0.134 p < 0.001).

Adolescent↗

Detection of interleukin-1 beta in human periapical lesions.

Interleukins are involved in modulating bone cell activity. Interleukin-1 (IL-1) has been shown to be potent stimuli of bone resorption in organ culture. This hormone-peptide is produced primarily by monocytes and macrophages. Diverse inflammatory cell types are clearly present in periapical lesions. The purpose of this study was to detect IL-1 beta activity in human periapical lesions. Eight human periapical lesions were examined for the presence of IL-1 beta. Pulp tissue of clinically impacted teeth were used as controls. Each specimen was quick-frozen and stored in liquid nitrogen. IL-1 beta activity was measured with, an IL-1 beta enzyme-linked immunosorbent assay that used monoclonal antibodies specific for IL-1 beta. Periapical samples exhibited significant activity of IL-1 beta (mean 604.4 +/- 563.0 pg/mg protein), whereas normal pulp had no activity. These results demonstrate that IL-1 beta is produced and released locally in inflammatory periapical lesions to mediate bone resorption.

Adult↗

Clinical and light microscopic observations of gingivitis and early ligature-induced periodontitis in the cynomolgus monkey.

Clinical and histological observations were made on gingivitis and ligature-induced periodontitis in 4 adult female cynomolgus monkeys (Macaca fascicularis) to define the changes occurring in the early periodontitis lesion. Silk ligatures were tied around selected posterior teeth and replaced weekly for 4 weeks. The changes from gingivitis to periodontitis induced by ligation, and back to a state of clinical health after ligature removal, scaling and polishing, were characterized by Plaque Index, Gingival Index, probing pocket depth, attachment loss, and histologic evaluation. A mild, chronic marginal gingivitis was the normal finding in the gingiva of posterior teeth. The inflammatory infiltrate in the connective tissue contained primarily lymphocytes. Hygienic measures once a week reduced the amount of infiltrate and the epithelial proliferation, but did not eliminate it. Placement of silk ligatures rapidly changed the clinical picture to a moderate or severe gingivitis, which presented an almost bizarre response of sulcular and oral epithelium, with an increase in polymorphonuclear neutrophil infiltration. Within 2 weeks there was significant probing attachment loss. The clinical response on removal of ligatures and plaque was almost as rapid as the onset. The animal model is useful for manipulating variables in ways not possible in the study of human periodontitis.

Animals↗

Inhibition of prolyl hydroxylase by poly(ADP-ribose) and phosphoribosyl-AMP. Possible role of ADP-ribosylation in intracellular prolyl hydroxylase regulation.

Poly(ADP-ribose) prepared by incubating NAD+ with rat liver nuclei inhibited the hydroxylation reaction catalyzed by purified prolyl hydroxylase (proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) in vitro. Near complete inhibition of the enzyme was seen in the presence of 6 nM (ADP-Rib)18 with a Ki(app) of 1.5 nM. The monomer unit of poly(ADP-ribose), adenosine diphosphoribose (ADP-Rib), was found to be a weak inhibitor. On the other hand, poly(ADP-ribose)-derived phosphoribosyl-AMP (PRib-AMP) and its dephosphorylated product, ribosyl-ribosyl-adenine (Rib-RibA), inhibited the enzyme in nanomolar concentrations (Ki(app) 16.25 nM). The order of inhibition was (ADP-Rib)18 greater than PRib-AMP, Rib-RibA much greater than ADP-Rib. These results suggested that the 1"----2' ribosyl-ribosyl moiety in these compounds was involved in the inhibition of the enzyme. The possibility that intracellular prolyl hydroxylase is regulated by the involvement of ADP-ribosylation reactions was examined in confluent cultures of skin fibroblast treated with 20 mM lactate. The activity of prolyl hydroxylase was stimulated by 145% over that of untreated cultures. In the lactate-treated cells, the level of NAD+ was lowered and the total ADP-ribosylation of cellular proteins reduced by 40%. These observations imply that the lactate-induced activation of cellular prolyl hydroxylase is mediated by a reduction in ADP-ribosylation and that the synthesis and degradation of ADP-ribose moiety(ies) may possibly regulate prolyl hydroxylase activity in vivo.

Adenosine↗