Search for a Variation of the Fine Structure Constant around the Supermassive Black Hole in Our Galactic Center.

Searching for space-time variations of the constants of Nature is a promising way to search for new physics beyond general relativity and the standard model motivated by unification theories and models of dark matter and dark energy. We propose a new way to search for a variation of the fine-structure constant using measurements of late-type evolved giant stars from the S star cluster orbiting the supermassive black hole in our Galactic Center. A measurement of the difference between distinct absorption lines (with different sensitivity to the fine structure constant) from a star leads to a direct estimate of a variation of the fine structure constant between the star's location and Earth. Using spectroscopic measurements of five stars, we obtain a constraint on the relative variation of the fine structure constant below 10^{-5}. This is the first time a varying constant of nature is searched for around a black hole and in a high gravitational potential. This analysis shows new ways the monitoring of stars in the Galactic Center can be used to probe fundamental physics.

Nicotine and cigarette smoke modulate Nrf2-BDNF-dopaminergic signal and neurobehavioral disorders in adult rat cerebral cortex.

BACKGROUND: Nicotine and cigarette smoking (CS) are associated with addiction behavior, drug-seeking, and abuse. However, the mechanisms that mediate this association especially, the role of brain-derived neurotrophic factor (BDNF), dopamine (DA), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the cerebral cortex, are not fully known. Therefore, we hypothesized that overexpression of BDNF and DA, and suppression of Nrf2 contribute to several pathological and behavioral alterations in adult cerebral cortex. Methodology/Principal Observations: We treated Wistar rats with different doses of oral nicotine and passive CS for 4-week (short-term) and 12-week (long-term) duration, where doses closely mimic the human smoking scenario. Our result showed dose-dependent association of anxiogenic and depressive behavior, and cognitive interference with neurodegeneration and DNA damage in the cerebral cortex upon exposure to nicotine/CS as compared to the control. Further, the results are linked to upregulation of oxidative stress, overexpression of BDNF, DA, and DA marker, tyrosine hydroxylase (TH), with concomitant downregulation of ascorbate and Nrf2 expression in the exposed cerebral cortex when compared with the control. CONCLUSION/SIGNIFICANCE: Overall, our data strongly suggest that the intervention of DA and BDNF, and depletion of antioxidants are important factors during nicotine/CS-induced cerebral cortex pathological changes leading to neurobehavioral impairments, which could underpin the novel therapeutic approaches targeted at tobacco smoking/nicotine's neuropsychological disorders including cognition and drug addiction.

Determination of in vivo estrogenic potential of Di-isobutyl phthalate (DIBP) and Di-isononyl phthalate (DINP) in rats.

Estrogenic potential of Di-isobutyl phthalate (DIBP) and Di-isononyl phthalate (DINP) was studied using two different test systems. Two different doses of DIBP (250 and 1250 mg/kg) and DINP (276 and 1380 mg/kg) were administered to immature female rats (20 days old) orally once daily for 3 and 20 days in uterotrophic and pubertal assay, respectively. The animals were sacrificed on day 4 and day 41 in case of 3-day uterotrophic and 20-day pubertal assay, respectively. The results indicated that non-significant alterations in uterine and ovarian wet weight were observed in both the DIBP- and DINP-treated groups while the uterus weight increased significantly (i.e., 4-6 times) in the Diethylstilbesterol (DES)-treated group in both the assays. In the present study, precocious vaginal opening occurred at 26 days of age in the DES-treated group with a mean body weight of 30.39 ± 1.08 g. However, no precocious vaginal opening was found in any of the DIBP- and DINP-treated groups. The results indicated that both the phthalate compounds were unable to induce elevation in the uterine weight in both the assays and unable to cause vaginal opening indicating non-estrogenic potential of both the phthalate compounds, i.e., DIBP and DINP in vivo.

Effects of in utero di-butyl phthalate and butyl benzyl phthalate exposure on offspring development and male reproduction of rat.

The study was conducted to assess the effects of in utero di-butyl phthalate (DBP) and butyl benzyl phthalate (BBP) exposure during late gestation on offspring's development and reproductive system of male rats. Pregnant rats were treated orally with DBP (2, 10, 50 mg/kg), BBP (4, 20, 100 mg/kg), and diethylstilbestrol (DES) 6 µg/kg (positive control) from GD14 to parturition. A significant reduction in dams' body weight on GD21 in DBP-, BBP-, and DES-treated groups was observed. The gestation length was considerably elevated in the treated groups. Decline in male pups' body weight was significant at PND75 in DBP- (50 mg/kg), BBP- (20,100 mg/kg), and DES-treated groups. The weight of most of the reproductive organs and sperm quality parameters was impaired significantly in DBP- (50 mg/kg) and BBP- (100 mg/kg) treated groups. Further, a non-significant decline in testicular spermatid count and daily sperm production was also monitored in treated groups. A significant reduction in serum testosterone level in BBP (100 mg/kg), whereas the testicular activity of 17ß-HSD was declined non-significantly in the treated groups with respect to control. The data suggests that DBP and BBP exposure during late gestation period might have adverse effects on offspring's development, spermatogenesis, and steroidogenesis in adult rats.

Environmental & lifestyle factors in deterioration of male reproductive health.

BACKGROUND & OBJECTIVES: Male reproductive function in the general population has been receiving attention in recent years due to reports of various reproductive and developmental defects, which might be associated with various lifestyle and environmental factors. This study was carried out to determine the role of various lifestyle and environmental factors in male reproduction and their possible association with declining semen quality, increased oxidative stress as well as sperm DNA damage. METHODS: Semen samples were obtained from 240 male partners of the couples consulting for infertility problem. Semen analysis was carried out using WHO criteria and subjects were categorized on the basis of self reported history of lifestyle as well as environmental exposure. The oxidative and antioxidant markers; lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) as well as DNA damage by acridine orange test (AO) were determined. RESULTS: The presence of abnormal semen parameters was significantly higher among the lifestyle and/or environmental exposed subjects as compared to the non-exposed population. Further, the levels of antioxidants were reduced and sperm DNA damage was more among the lifestyle and/or environmental exposed subjects, though the changes were not significant. INTERPRETATION & CONCLUSIONS: These findings indicated that various lifestyle factors such as tobacco smoking, chewing and alcohol use as well as exposure to toxic agents might be attributed to the risk of declining semen quality and increase in oxidative stress and sperm DNA damage.

In utero and lactation exposure of mice to pan masala: effect on dams and pregnancy outcome.

Pan masala, a chewing mixture, is a popular alternate of areca nut/tobacco/betal quid in various parts of the world. In view of embryotoxic effects of areca nut and tobacco, it is hypothesized that in utero and lactational exposure to pan masala plain (PMP, containing areca nut as major ingredient), and pan masala with tobacco (PMT) can also have similar effects. To investigate this, pregnant female Swiss albino mice were treated with 3 and 6% of PMP and PMT from gestation day (GD) 0, 6, and 14 until lactation. They were weighed during pregnancy and lactation. At parturition, pups were counted, weighed, and measured. At weaning, dams were sacrificed for implantation count. Three percent and 6% PMT considerably reduced female fertility. Gestation length was lower in all the pan masala­treated mice, which was significant at 3 and 6% PMT treatment from GD 0. Pups born to pan masala­treated dams had significantly low birth weight at 3 and 6% PMT in GD 0 and GD 6, and 6% PMT in the GD 14 group. Sex ratio declined in the GD 0 pan masala­treated group. Neonatal death was observed in all the pan masala­treated groups from GD 0 and 6% of both PMP- and PMT-treated groups from GD 14 with respect to control. Weaning index was considerably altered in GD 0 and 14 pan masala­treated groups. Postimplantation loss was considerably high in all the pan masala­treated groups. The data points toward the in utero and lactational fetotoxic effects of pan masala treatment, mainly PMT.

A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone.

UNLABELLED: The effect of quercetin C-glucoside (QCG) on osteoblast function in vitro and bone formation in vivo was investigated. QCG supplementation promoted peak bone mass achievement in growing rats and new bone formation in osteopenic rats. QCG has substantial oral bioavailability. Findings suggest a significant bone anabolic effect of QCG. INTRODUCTION: Recently, we showed that extracts of Ulmus wallichiana promoted peak bone mass achievement in growing rats and preserved trabecular bone mass and cortical bone strength in ovariectomized (OVx) rats. 3,3',4',5,7-Pentahydroxyflavone-6-C-ß-D-glucopyranoside, a QCG, is the most abundant bioactive compound of U. wallichiana extract. We hypothesize that QCG exerts bone anabolic effects by stimulating osteoblast function. METHODS: Osteoblast cultures were harvested from rat calvaria and bone marrow (BM) to study differentiation and mineralization. In vivo, growing female Sprague Dawley rats and OVx rats with osteopenia were administered QCG (5.0 or 10.0 mg kg(-1) day(-1)) orally for 12 weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by determination of new bone formation by fluorescent labeling of bone. Plasma and BM levels of QCG were determined by high-performance liquid chromatography. RESULTS: QCG was much more potent than quercetin (Q) in stimulating osteoblast differentiation, and the effect of QCG was not mediated by estrogen receptors. In growing rats, QCG increased BM osteoprogenitors, bone mineral density, bone formation rate, and cortical deposition. In osteopenic rats, QCG treatment increased bone formation rate and improved trabecular microarchitecture. Comparison with the sham group (ovary intact) revealed significant restoration of trabecular bone in osteopenic rats treated with QCG. QCG levels in the BM were ~50% of that of the plasma levels. CONCLUSION: QCG stimulated modeling-directed bone accrual and exerted anabolic effects on osteopenic rats by direct stimulatory effect on osteoprogenitors likely due to substantial QCG delivery at tissue level following oral administration.

Cytogenetic alterations in buccal mucosa cells of chewers of areca nut and tobacco.

OBJECTIVE: the rationale of the study was to evaluate the cytological alterations especially micronucleus (MN) and other nuclear anomalies in buccal mucosa cells of chewers to understand the genotoxic and clastogenic potential of chewing mixture (containing areca nut and tobacco as main ingredients). METHODS: the buccal cytome assay involves the examination of epithelial smear to determine micronucleated cell and other nuclear anomalies after the Feulgen plus light green staining. The assay was applied to exfoliated buccal mucosa cells of 262 subjects [non-chewers - 161 and chewers - 101 (includes 20 subjects with OSMF)] and 1000 cells per individual were examined microscopically. Nuclear anomalies were compared among chewers, non-chewers and OSMF subjects and correlated with consumption of quids per day and duration of chewing in years. RESULTS: MN cells were found significantly (p<0.0001) higher among chewers and OSMF subjects as compared to non-chewers. Further analysis indicated that MN was significantly higher in OSMF subjects with respect to even chewers. Nuclear buds were significantly higher (p<0.0001) in OSMF subjects as compared to chewers as well as non-chewers. Nuclear anomalies viz. binucleated, karyorrhexis and karyolysis were also considerably higher in OSMF subjects as compared to non-chewers. CONCLUSION: the MN and other nuclear anomalies reflected genetic damage and cytotoxicity, associated with tobacco and areca nut consumption. Further, these data reveal a risk for development of OSMF among chewers of mixture containing areca nut and/or tobacco, as all the OSMF subjects were chewers.

Evaluation of genotoxicity of pan masala employing chromosomal aberration and micronucleus assay in bone marrow cells of the mice.

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.

Demonstration of sperm head shape abnormality and clastogenic potential of cypermethrin.

Adult male Swiss albino mice were administered ip. suspension solution of cypermethrin in 0.15% DMSO at the doses of 30 mg, 60 mg and 90 mg/kg b. wt. daily for 5 days. Another group of animals was injected cyclophosphamide ip. (60 mg/kg b. wt.) in similar manner which served as positive control. Effect of cypermethrin on body and testes weight and sperm head morphology was studied. Clastogenic potential of cypermethrin was studied by using modified Allium test. The cytological changes were studied in the root tip cells of Allium cepa after 3 days treatment with three different concentration of cypermethrin (0.1, 1.0 and 10.0 microg/ml). The results revealed that body weight gain was considerably reduced in higher dose groups, but the testicular weight did not change significantly in any of the cypermethrin treated groups. However, a significant elevation in the number of abnormal shape of sperm head was noticed in higher dose groups as compared to control. It was observed that the abnormality in the shape of sperm head was dose-dependent. The cytological changes in the root tip cells of Allium cepa indicated that cypermethrin is having toxic effects on the root tip cells in the form of stickiness of chromosomes and also affect the mitotic activity. This study suggest that cypermethrin may have the potential to induce adverse effects on sperm head shape morphology of mouse as well as clastogenic effects on root tip cells of Allium cepa.

Semen quality and reproductive hormones among welders -A preliminary study.

OBJECTIVES: Welders are exposed to intense heat, toxic metals and their oxides and toxic gases during welding, and some of these substances reported to have adverse effects on reproductive organs. Thus, the present study was planned to investigate the sperm quality as well as reproductive hormones among welders exposed to a complex mixture of pollutants. METHODS: Seventeen welders aged 43.8±12.0 (mean±SD) years with welding exposure of 1 to 10 years or more participated in this study. They were performing are and gas welding in a workshop. Blood (5-6 ml) and semen samples by masturbation were collected from them. Serum was separated and analyzed for reproductive hormones by RIA techniques. Semen was processed for microscopic examination. RESULTS: The results of this study indicated that sperm concentration was in the normal range (≥20 million/ml) in all seventeen welders, however, motility, morphology as well as Hypo Osmotic Swelling test (HOS) demonstrated impairment in few welders, indicating deterioration in sperm quality compared to the reported normal reference value. Compared with the normal value of hormones provided in diagnostic kits brochure, follicle stimulating hormone (FSH), leutinizing hormone (LH) and testosterone levels were in the normal range, except in two subjects who showed higher FSH and LH levels and one who showed a lower value of testosterone. CONCLUSIONS: This study suggests that welding might have had some adverse effects on sperm motility, morphology and physiologic function even though sperm concentration was in the normal range. Hormonal changes did not show any definite pattern, indicating a need for further study.

Lead induced spermatoxicity in mouse and MPG treatment.

Protective efficacy of MPG (2-mercaptopropionyl glycine) was studied against the toxic effects of lead acetate in Swiss albino mice. The animals were treated with single dose of lead acetate @ 180, 200 and 250 mg/kg b.wt. in presence and absence of MPG. The results indicated that the body weight was slightly higher in MPG treated groups on day 10 as compared to only respective lead treated groups in all the three dose level. However, significantly lower body weight was observed in both lead treated and lead along with MPG treated groups as compared to control. Patten of mortality is similar in both lead treated and lead plus MPG treated groups. Conspicuous degenerative changes in testicular tissues and elevation in sperm head shape abnormality were observed in both lead treated and lead along with MPG treated groups but the sperm head shape abnormality and damage were more in lead treated groups as compared to lead plus MPG treated groups. But this difference was non-significant between the two groups. These observations suggest that MPG may not be significantly effective against lead induced damage in testicular tissues at cellular level. However, MPG is able to maintain slightly lower level of sperm abnormality in all the three dose level as compared to their respective lead treated groups. Further, studies are needed to find out the optimum dose of MPG for protection against the lower doses of lead induced lethality as MPG is not significantly effective against the higher doses of lead.

Detection of germ cell genotoxic potential of carbon disulphide using sperm head shape abnormality test.

1. Adult male albino rats (CF Strain) were administered i.p. CS2 dissolved in cotton seed oil at doses of 25, 50, 100 and 200 mg/kg b. wt. for a period of 60 days. Effect of CS2 on epididymis, adrenal weight, sperm count and sperm head shape abnormality was studied. 2. Epididymal weight remained unaltered in 25, 50 and 100 mg/kg CS2 treated groups, whereas in highest dose of CS2 treated (200 mg/kg) group a non-significant reduction in epididymis weight was observed. A slight increase in adrenal weight was observed in lower doses groups (25 and 50 mg/kg) while a considerable decrease in adrenal weight was noted in highest dose (200 mg/kg) of CS2 treated group in the present study. 3. An increase in sperm head shape abnormality and decrease in sperm count was observed in all the CS2 treated groups. However, the changes were statistically significant only after higher dose of CS2 treatment as compared to control. 4. This study suggests that CS2 may have the potential to induce adverse effects on male reproductive system of rats. Sperm head shape abnormality assay used in this study also elicits germ cell genotoxic potential of carbon disulphide.

Steroidogenic impairment after lindane treatment in male rats.

The effect on testicular steroidogenesis after lindane (delta-isomer of hexachlorocyclohexane) administration of 4 and 8 mg/kg, i.p. daily for 45 days to male mature rats was investigated. A significant decline in testicular weight of both test groups was observed. Cellular degeneration in Leydig cells of the 8 mg/kg treated group was conspicuous. A sharp decline in the Leydig cell's population and morphological deformation were supported by the decreased activities of testicular hyaluronidase and 3 beta delta 5-hydroxysteroid dehydrogenase. A high level of testicular cholesterol and depletion of ascorbic acid were also responsible for steroidogenic impairment in the treated groups. These impairments also led to a significant diminution in serum testosterone.

Steroidogenic inhibition in testicular tissue of formaldehyde exposed rats.

Three groups of rats (n = 10) were subjected to intraperitoneal treatment of formaldehyde daily at doses of 5, 10 and 15 mg/kg body weight over a period of 30 days. Gradual diminution in body and testicular weight was observed in all treated groups. Leyding cell impairement was conspicuous in those given doses of 10 and 15 mg/kg. Inhibition of 3 beta-delta 5-hydroxy steroid dehydrogenase and accumulation of sudanophillic materials in testicular tissue of formaldehyde treated rats was recorded histochemically. Significant decline of serum testosterone was also observed in the same groups. Structural and functional impairement of Leydig cells after formaldehyde treatment caused steroidogenic inhibition.

BHC induced testicular impairments in rats.

Benzene hexachloride (BHC) was fed to mature male rats weighing 160 g at dosages of 3 and 6 mg/kg body weight over a period of 180 days. Significant decrease in testicular weight and degeneration of seminiferous tubules with deformed spermatogenic cells were noted at a dose of 6 mg/kg BHC. Marked increase in BHC residue in testis revealed that the drug was able to cross blood-testis barrier.

Lindane induced changes in morphology and lipids profile of testes in rats.

Intraperitoneal treatment of adult male rats with lindane at dosages of 4 and 8 mg/kg over a period of 45 days caused retardation in body and testicular growth. Testicular degeneration was conspicuous over a period of 45 days in both dosages of lindane. After treatment with lindane, histochemical and biochemical studies revealed the accumulation of testicular lipid components, i.e. total lipids, triglycerides and cholesterol along with fatty degeneration in testicular tissues. Moreover, the loss of male accessory organ weight indicated androgen deficiency in treated rats.

Methylmercury- and mercuric-chloride-induced alterations in rat epididymal sperm.

Four-week-old male albino rats weighing 70 +/- 5 g were treated intraperitoneally daily with 0, 5 and 10 micrograms methylmercuric chloride (MMC)/kg or 0, 50 and 100 micrograms mercuric chloride (MC)/kg body weight, respectively, over a period of 90 days. Studies were carried out a intermittent intervals, i.e. on days 0, 15, 30, 60 and 90 of the experiment. Gradual decrements in body and epididymal weights were observed from day 30 onwards in both the MMC- and MC-treated groups. Morphological deformations of epididymal epithelium were noted from day 30 onwards in the mercurial-treated groups. MMC treatment caused severe degeneration of the epididymal epithelium on days 60 and 90 in comparison to MC treatment. Total sperm count was significantly less in the MC-treated groups, while motile sperm count was affected most in the MMC-administered groups. The frequency of sperm abnormality increased consistently at both doses of mercurial treatment over a period of 90 days. Maximum sperm abnormality among the treated groups was noted in the groups given 10 micrograms MMC/kg. The observations revealed that MMC and MC have variable potency to alter epididymal structure and the sperm.