Najmul Islam

Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males

OBJECTIVE To investigate the impact of Withania somnifera roots on semen profile, oxidative biomarkers, and reproductive hormone levels of infertile men. DESIGN Prospective study. SETTING Departments of Biochemistry and Urology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India. PATIENT(S) Seventy-five normal healthy fertile men (control subjects) and 75 men undergoing infertility screening. INTERVENTION(S) High-performance liquid chromatography assay procedure for quantization of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma were estimated by standard spectrophotometric procedures. Estimation of T, LH, FSH, and PRL in blood serum by RIA methods. MAIN OUTCOME MEASURES(S) Before and after the treatment, seminal plasma biochemical parameters, antioxidant vitamins, and serum T, LH, FSH, and PRL levels were measured. RESULT(S) Withania somnifera inhibited lipid peroxidation and protein carbonyl content and improved sperm count and motility. Treatment of infertile men recovered the seminal plasma levels of antioxidant enzymes and vitamins A, C, and E and corrected fructose. Moreover, treatment also significantly increased serum T and LH and reduced the levels of FSH and PRL. CONCLUSION(S) The treatment with W. somnifera effectively reduced oxidative stress, as assessed by decreased levels of various oxidants and improved level of diverse antioxidants. Moreover, the levels of T, LH, FSH and PRL, good indicators of semen quality, were also reversed in infertile subjects after treatment with the herbal preparation.

Crossreactivity of SLE Autoantibodies with 70 kDa Heat Shock Proteins of Mycobacterium tuberculosis

Heat shock proteins (hsp) may be involved in the initiation and perpetuation of autoimmune diseases. In order to investigate the possible role of hsp and other intracellular proteins of Mycobacterium tuberculosis in the autoantibody production in SLE, the immuno‐crossreactivity of SLE autoantibodies with Mycobacterium tuberculosis sonic extract and hsp‐70 kDa was investigated. These proteins showed significant binding with Protein A‐Sepharose isolated SLE IgG. Western blotting of hsp‐70 with SLE IgG showed strong recognition, suggesting possible involvement of hsp and other intracellular proteins of Mycobacterium tuberculosis in the autoantibody induction in SLE.

Elevated blood lead levels and cytogenetic markers in buccal epithelial cells of painters in India: genotoxicity in painters exposed to lead containing paints.

Background, aim, and scopeLead, a major contaminant, is highly used in paint manufacturing due to its anticorrosive properties. Recent reports indicated high lead content among Indian paints used for commercial purposes. Painters are continuously exposed to these lead containing paints during painting of both commercial as well as residential buildings. Lead is well-known for its genotoxicty in occupational workers; however, in Indian painters the genotoxic effects of lead have not been reported to date. Therefore we aimed to study the genotoxic end points in painters due to their long-term exposure to these high lead-containing Indian paints.Materials and methodsStudy group selection was made after a questionnaire administration, which included questions about lifestyle and medical history to exclude exposure to the other potential sources of genotoxics. Blood and buccal cell samples were obtained from 30 male painters and from a similar number of age-matched controls of same location with no occupational exposure to lead. Blood lead levels (Pb-B) were measured in painters and controls. Micronucleus (MN) frequencies and nuclear changes, i.e., karyorrhexis, karyolysis, broken egg, and binucleated, were investigated in buccal epithelial cells.ResultsPainters had significantly (P < 0.01) greater lead levels in blood than the control group. MN frequencies and nuclear changes in buccal epithelial cells were also significantly (P < 0.01) elevated in painters as compared with control subjects. Regression analysis also revealed significant (P < 0.01) association of Pb-B with all the genotoxic endpoints in painters. Cytogenetic damage was significantly associated with Pb-B as no other co-founding factors (smoking, alcohols) showed significant difference between both groups.DiscussionLead is widely used in paints which may serve as potential source of exposure among painters due to their long-term engagement with paints. Our results clearly demonstrated genotoxicity among the exposed population as evident from increase micronucleus frequencies, frequent nuclear changes, and apoptosis. Many studies had previously related nuclear change events in buccal epithelial cells with the progression of different carcinomas. Furthermore in-depth investigations with larger sample size are needed to provide evidence to this effect.ConclusionsHere, we report cytogenetic toxicity to the exposed population by the high lead containing paints from India for the first time. Frequent, high and unregulated use of lead in paints may cause genetic mutation and may accelerate cytogenetic damage which may further lead to different carcinomas in painters. These findings need to be considered and necessary steps should be taken to protect the occupational workers engaged with these high lead-containing paints.RecommendationsThe use of lead in paints is completely unregulated in India and routine surveillance of paints for lead content is still lacking. These paints are readily available in markets and are also used in other products (jewelry, miniblinds) which could be exported to other countries including United States and Europe. Serious consideration should be given to the inclusion of regulations and bans on the use of lead in paints. Moreover, attention should also be paid towards the use of various protective measures (face-masks, hand gloves, and separate clothes) by the workers as safe work practices during working periods.

Correlation between bone mineral density and oxidative stress in postmenopausal women.

Background: Postmenopausal osteoporosis affects large fraction of elderly women. Oxidative stress (OS) appears to be involved in its pathogenesis. The scarcity of human studies focusing on the correlation between bone mineral density (BMD) and OS in postmenopausal women has prompted us to study on this issue. Materials and Methods: We conducted a cross sectional study in 95 subjects, between 21–65 years of age, including postmenopausal osteoporotic females (n = 35), healthy postmenopausal females (n = 30) and healthy females in reproductive age group (n = 30). We measured serum antioxidant activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and total antioxidant power (TAP). BMD was obtained at lumbar spine and femur neck by dual-energy X-ray absorptiometry scan. Osteoporosis was considered when subjects had a BMD of 2.5 standard deviations or more below the mean value for young adults. Results: Serum GPx, SOD, catalase and TAP level were found significantly lower in osteoporotic postmenopausal group as compared to healthy postmenopausal women and women in healthy reproductive age group healthy reproductive women (P < 0.005). but correlation between BMD and serum antioxidants were not found to be statistically significant (P > 0.005). Conclusion: These findings support that oxidative stress plays an important role in pathogenesis of postmenopausal osteoporosis. We did not find any significant association between BMD and serum level of antioxidants (P > 0.05). The failure to detect this association does not preclude the role of OS in osteoporosis because OS is complex and dynamic process.

Correlation between serum neuron specific enolase and functional neurological outcome in patients of acute ischemic stroke

Context: The use of biomarkers to predict stroke prognosis is gaining particular attention nowadays. Neuron specific enolase (NSE), which is a dimeric isoenzyme of the glycolytic enzyme enolase and is found mainly in the neurons is one such biomarker. Aims: This study was carried out on patients of acute ischemic stroke with the aims to determine the correlation between NSE levels on the day of admission with infarct volume, stroke severity, and functional neurological outcome on day 30. Materials and Methods: Seventy five patients of acute ischemic stroke admitted in the Department of Medicine were included in the study. Levels of NSE were determined on day 1 using the human NSE ELISA kit (Alpha Diagnostic International Texas 78244, USA). Volume of infarct was measured by computed tomography (CT) scan using the preinstalled software Syngo (version A40A) of Siemens medical solutions (Forchheim, Germany). Stroke severity at admission was assessed using Glasgow coma scale (GCS) and functional neurological outcome was assessed using modified Rankin scale (mRS) on day 30. Statistical Analysis Used: Statistical analysis was performed using the SPSS software for windows version 15.0 (SPSS). Results: A positive correlation was found between concentration of NSE on day 1 and infarct volume determined by CT scan (r = 0.955, P < 0.001). A strong negative correlation was found between GCS at presentation and concentration of NSE on day 1 (r = −0.806, P < 0.001). There was a positive correlation between NSE levels at day 1 and functional neurological outcome assessed by mRS at day 30 (r = 0.744, P < 0.001). Conclusions: Serum levels of NSE in first few days of ischemic stroke can serve as a useful marker to predict stroke severity and early functional outcome. However, larger studies with serial estimation of NSE are needed to establish these observations more firmly.

Formation of thymine-lysine and cytosine-lysine adducts in DNA-lysine photoconjugate.

Lysine was covalently conjugated to calf thymus DNA by irradiation with UV light (wavelength, 253.7 nm). The results showed monofunctional covalent photobinding of lysine molecules with bases in DNA. Only the epsilon-amino group of lysine participated in the photoconjugation reaction. Thymine and cytosine were modified by 60% and 25% respectively. The kinetics of the DNA-lysine photoreaction showed that one lysine molecule was in the photobound state per 10, 6, 5 and 4 nucleotide base pairs of DNA on irradiation for 20, 30 40 and 60 min respectively.

Immunological studies on DNA‐lysine photoadduct

Calf thymus native DNA was covalently linked with lysine by irradiation with 254 nm light. Thermal melting studies indicated a decrease of 16°C in the Tm of DNA‐lysine photoadduct over native DNA. The decrease in Tm was dependent of irradiation dose. The photoadduct was found to be a potent immunogen in experimental animal. Thymine‐lysine photoconjugate in DNA‐lysine photo‐monoadduct appears to be the major immunodominant portion. A strong recognition of DNA‐lysine photoadduct was observed with anti‐DNA autoantibodies found in the sera of patients with SLE. Thymine‐lysine conjugate in DNA‐lysine photo‐monoadduct appears to provide an immunodominant epitope(s) for SLE autoantibody recognition. The results suggests for the possible involvement of DNA‐lysine photoadduct or similar modified structure(s) as a potential trigger for anti‐DNA autoantibody production.

Naturally occurring SLE anti-DNA antibodies recognize unique conformation on DNA-lysine photoadduct

Native calf thymus DNA has been covalently modified with lysine under UV‐A light. Human autoantibodies on purification through affinity column of native DNA linked to polylysyl‐Sepharose 4B showed almost equal recognition of DNA and photoadduct. The recognition of DNA‐lysine photoadduct by the affinity‐purified autoantibodies might be helpful in understanding their origin in SLE vis‐à‐vis the role of positively charged amino acids in the pathogenesis of autoimmune diseases.

Ubiquitous hazardous metal lead induces TNF-α in human phagocytic THP-1 cells: primary role of ERK 1/2.

Induction of tumor necrosis factor-α (TNF-α) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-α is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-α induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-α m-RNA and protein secretion. Moreover, the stability of TNF-α m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-α m-RNA. However, SB 203580 partially inhibited production and stability of TNF-α m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-α m-RNA. Data tends to suggest that expression and stability of TNF-α induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.

Erythrocyte Markers of Oxidative Stress in Higher Age-Group Preeclamptic and Normal Pregnant Mothers

Preeclampsia can have significant impact on health of both mother and fetus. It had been proposed that maternal endothelial cell dysfunction is the key event resulting in the diverse clinical manifestations of preeclampsia and evidence has since accumulated. Research in recent times is indicative of the role of oxidative stress in the endothelial cell dysfunction. Preeclampsia is more common in first pregnancy and studies have further shown an increase in risk of preeclampsia with maternal age. The aim of this study was to explore the status of oxidative stress in higher age-group preeclamptic and normal pregnant mother. The study included 20 normal pregnant women and 60 preeclamptic women. They were allocated into 4 subgroups between ages 20–25, 26–30, 31–35, and 36–40. Erythrocytes were analyzed for the following antioxidant enzymes, i.e., glutathione peroxidase, superoxide dismutase and catalase.Lipid peroxidation product, malondialdehyde, was analyzed to determine oxidative stress. The results showed an increase in oxidative stress, and high magnitude suppression/decrease in antioxidant enzymes activities in erythrocytes with increase in age groups in both preeclamptic and normal pregnant women. This indicates that an increase in the risk of preeclampsia with maternal age could be due to an increase in oxidative stress with age. This further attests to the role of oxidative stress in preeclampsia.