Cancer mortality in the meat and delicatessen departments of supermarkets (1950-2006).

Meat cutters and meat wrappers in the meat department of supermarkets are exposed to oncogenic viruses present in raw meat from cattle, pigs, sheep, and poultry, and their products (unpasteurized milk and raw eggs). Up to the mid 1970s, meat wrappers were also exposed to carcinogens present in fumes emitted from the machine used to wrap meat. Because of this we studied cancer mortality in a cohort of 10,701 workers in the meat and delicatessen departments of supermarkets, and we report here the findings after the third follow-up. Standardized mortality ratios (SMR) were estimated in the cohort as a whole and in race/sex subgroups, using the US population for comparison. Study subjects were followed up from January 1950 to December 2006. Significantly increased SMRs of 1.3 (95% CI, 1.2-1.5), and 2.7 (95% CI, 1.2-5.3) were recorded for cancers of the lung, and tonsils/oropharynx, respectively, in the entire cohort, affecting nearly all race/sex subgroups. SMRs of 4.6 (95% CI, 1.0-13.6) for cancer of the floor of the mouth, and 2.8 (95% CI, 1.3-5.3) for cancer of the gall bladder and biliary tract were recorded only in White male meatcutters. Significantly decreased SMRs were observed for a few cancers. It is not known if the observed excess of cancers is a result of occupational exposures. However, substantial evidence points to fumes from the wrapping machine as a possible candidate for explaining the excess in female meat wrappers. Nested case-control studies that can examine risks from occupational exposures in greater detail, and adequately control for confounding factors are now needed, to permit specifically investigate the role of the oncogenic viruses, fumes and non-occupational risk factors in the occurrence of these cancers. The findings are important, not only occupationally but also because the general population may also experience these exposures, albeit to a lesser degree.

Chemical sympathectomy restores baroreceptor-heart rate reflex and heart rate variability in rats with chronic nitric oxide deficiency.

Nitric oxide (NO) plays a crucial role not only in regulation of blood pressure but also in maintenance of cardiac autonomic tone and its deficiency induced hypertension is accompanied by cardiac autonomic dysfunction. However, underlying mechanisms are not clearly defined. We hypothesized that sympathetic activation mediates hemodynamic and cardiac autonomic changes consequent to deficient NO synthesis. We used chemical sympathectomy by 6-hydroxydopamine to examine the influence of sympathetic innervation on baroreflex sensitivity (BRS) and heart rate variability (HRV) of chronic N(G)-nitro-L-arginine methyl ester (L-NAME) treated adult Wistar rats. BRS was determined from heart rate responses to changes in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. Time and frequency domain measures of HRV were calculated from 5-min electrocardiogram recordings. Chronic L-NAME administration (50 mg/kg per day for 7 days orally through gavage) in control rats produced significant elevation of blood pressure, tachycardia, attenuation of BRS for bradycardia and tachycardia reflex and fall in time as well as frequency domain parameters of HRV. Sympathectomy completely abolished the pressor as well as tachycardic effect of chronic L-NAME. In addition, BRS and HRV improved after removal of sympathetic influence in chronic L-NAME treated rats. These results support the concept that an exaggerated sympathetic activity is the principal mechanism of chronic L-NAME hypertension and associated autonomic dysfunction.

Cholinergic receptor blockade by scopolamine and mecamylamine exacerbates global cerebral ischemia induced memory dysfunction in C57BL/6J mice.

Global cerebral ischemia/reperfusion (GCI/R) injury encompasses complex pathophysiological sequalae, inducing loss of hippocampal neurons and behavioural deficits. Progressive neuronal death and memory dysfunctions culminate from several different mechanisms like oxidative stress, excitotoxicity, neuroinflammation and cholinergic hypofunction. Experimental evidences point to the beneficial effects of cholinomimetic agents such as rivastigmine and galantamine in improving memory outcomes following GCI/R injury. However, the direct implications of muscarinic and nicotinic receptor blockade during global cerebral ischemia/reperfusion injury have not been investigated. Therefore, we evaluated the relative involvement of muscarinic and nicotinic receptors in spatial/associative memory functions and neuronal damage during global cerebral ischemia reperfusion injury. The outcomes of present study support the idea that preservation of both muscarinic and nicotinic receptor functions is essential to alleviate hippocampal neuronal death in CA1 region following global cerebral ischemia/reperfusion injury.

Effect of losartan, an angiotensin II type 1 receptor antagonist on cardiac autonomic functions of rats during acute and chronic inhibition of nitric oxide synthesis.

We studied the effect of losartan on baroreflex sensitivity (BRS) and heart rate variability (HRV) of adult Wistar rats during acute and chronic inhibition of nitric oxide synthesis by N(G)-nitro-L-arginine methyl ester (L-NAME). Chronic L-NAME administration (50 mg/kg per day for 7 days, orally through gavage) increased mean arterial pressure (MAP), heart rate but significantly decreased BRS. In addition, a significant fall of standard deviation of normal RR intervals, total spectral power, high frequency spectral power and a rise of low frequency to high frequency (LF: HF) ratio was seen. Acute L-NAME administration (30 mg/kg, i.v. bolus dose) also raised MAP and impaired HRV but it was associated with augmented BRS for bradycardia reflex. Losartan treatment (10 mg/kg, i.v.) in both acute and chronic L-NAME treated rats, decreased MAP but the difference was not significant. On the other hand, losartan administration normalized depressed BRS for bradycardia reflex and significantly reduced LF to HF ratio in chronic L-NAME treated rats. But this improvement was not observed in acute L-NAME group. These results indicate importance of mechanisms other than renin-angiotensin system in the pressor response of both acute as well as chronic L-NAME. However, autonomic dysregulation especially following chronic L-NAME appears to be partly angiotensin dependent.

Free chelatable zinc modulates the cholinergic function during hypobaric hypoxia-induced neuronal damage: an in vivo study.

The deregulation of cholinergic system and associated neuronal damage is thought to be a major contributor to the pathophysiologic sequelae of hypobaric hypoxia-induced memory impairment. Uniquely, the muscarinic receptors also play a role in zinc uptake. Despite the potential role of muscarinic receptors in the development of post hypoxia cognitive deficits, no studies to date have evaluated the mechanistic relationship between memory dysfunction and zinc homeostasis in brain. In the present study, we evaluated the effect of Ca(2)EDTA, a specific zinc chelator in the spatial working and associative memory deficits following hypobaric hypoxia. Our results demonstrate that accumulation of intracellular free chelatable zinc in the hippocampal CA3 pyramidal neurons is accompanied with neuronal loss and memory impairment in hypobaric hypoxic condition. Chelation of this free zinc with Ca(2)EDTA (1.25 mM/kg) ameliorated the hippocampus-dependent spatial as well as associative memory dysfunction and neuronal damage observed on exposure to hypobaric hypoxia. The zinc chelator significantly alleviated the downregulation in expression of choline acetyltransferase, muscarinic receptor 1 and 4, and acetylcholinesterase activity due to hypobaric hypoxia. Our data suggest that the free chelatable zinc released during hypobaric hypoxia might play a critical role in the neuronal damage and the alteration in cholinergic function associated with hypobaric hypoxia-induced memory impairment. We speculate that zinc chelation might be a potential therapy for hypobaric hypoxia-induced cognitive impairment.

Peroxisome proliferator activating receptor (PPAR) in cerebral malaria (CM): a novel target for an additional therapy.

Cerebral malaria (CM) is a global life-threatening complication of Plasmodium infection and represents a major cause of morbidity and mortality among severe forms of malaria. Despite developing knowledge in understanding mechanisms of pathogenesis, the current anti-malarial agents are not sufficient due to drug resistance and various adverse effects. Therefore, there is an urgent need for the novel target and additional therapy. Recently, peroxisome proliferator-activated receptor (PPAR) a nuclear receptors (NR) and agonists of its isoforms (PPARγ, PPARα and PPARß/δ) have been demonstrated to exhibit anti-inflammatory and immunomodulatory properties, which are driven to a new approach of research on inflammatory diseases. Although many studies on PPARs have confirmed their diverse biological role, there is a lack of knowledge of its therapeutic use in CM. The major objective of this review is to explore the possible experimental studies to link these two areas of research. We focus on the data describing the beneficial effects of this receptor in inflammation, which is observed as a basic pathology in CM. In conclusion, PPARs could be a novel target in treating inflammatory diseases, and continued work with the available and additional agonists screened from various sources may result in a potential new treatment for CM.

Involvement of angiotensin converting enzyme in cerebral hypoperfusion induced anterograde memory impairment and cholinergic dysfunction in rats.

Forebrain cholinergic dysfunction is the hallmark of vascular dementia (VaD) and Alzheimer's dementia (AD) induced by cerebral hypoperfusion during aging. The aim of the present study is to evaluate the role of angiotensin converting enzyme (ACE) in cerebral hypoperfusion-induced dementia and cholinergic dysfunction. Chronic cerebral hypoperfusion (CHP) was induced by permanent bilateral common carotid artery (2VO) occlusion in rats. Chronic cerebral hypoperfusion resulted in anterograde memory impairment revealed from Morris water maze (MWM) and passive avoidance step through tasks (PA), which was significantly attenuated by ACE inhibitor, captopril. Cerebral hypoperfusion down-regulated the relative expression of cholinergic muscarinic receptor (ChM-1r) and choline acetyltransferase (ChAT) as well as up-regulated the angiotensin II type-1 receptor (AT-1) expression in hippocampus of vehicle treated CHP group on the 54th day post-hypoperfusion. The diminished number of presynaptic cholinergic neurons and the pyramidal neurons were evident from ChAT-immunofluorescence and the hematoxylin and eosin (H&E) staining studies respectively in hippocampal Cornu ammonis1 (CA1); region of vehicle-treated hypoperfused animals. Further the lipid peroxidation level was also found to be elevated in the hippocampus of the vehicle-treated group. Our results demonstrated that continuous captopril treatment (50 mg/kg, i.p. twice daily) for 15 days mitigated the hypoperfusion-induced cholinergic hypofunction and neurodegeneration in hippocampus. The present study robustly reveals that the angiotensinergic system plays a pivotal role in progression of neuronal death and memory dysfunctions during cerebral hypoperfusion.

An antifungal protein from Escherichia coli.

A cytosolic protein was purified from Escherichia coli BL21 that demonstrated potent antifungal activity against pathogenic strains of Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger and Candida albicans. The MIC of purified protein from E. coli BL21 (PPEBL21) against Aspergillus species and C. albicans was 1.95-3.98 and 15.62 microg ml(-1), respectively. In vitro toxicity tests demonstrated no cytotoxicity of PPEBL21 to human erythrocytes up to the tested concentrations of 1250 microg ml(-1). Amphotericin B was lethal to 100 % of human erythrocytes at a concentration of 37.5 microg ml(-1). The N-terminal amino acid sequence of PPEBL21 was found to be DLAEVASR, which showed 75 % sequence similarity with alcohol dehydrogenase of yeast. Mass fingerprinting by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry also substantiated these observations. The results suggested that E. coli BL21 might be an important bioresource of lead molecules for developing new peptide-based therapies for treating fungal infections.

The treatment of skin carcinoma, induced by UV B radiation, using 1-oxo-5beta, 6beta-epoxy-witha-2-enolide, isolated from the roots of Withania somnifera, in a rat model.

Histopathological studies of the cutaneous tissues of Wistar rats exposed to UV B radiation (294 nm) for 20 days and rats exposed to UV B radiation for 20 days, followed by topical treatment with benzoyl peroxide, a tumor promoter (20 mg/animal/0.2 ml acetone) twice a week for 1 month, and kept under observation for 12 weeks, demonstrate the development of malignancy. Pretreatment of the animals with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide (20 mg/kg bwt.), isolated from the roots of Withania somnifera, prior to exposing the animals to UV B radiation, prevents the incidence of skin carcinoma. The administration of 1-oxo-5beta, 6beta-epoxy-witha-2-enolide, to the animals after exposing them to UV B radiation/UV B radiation and benzoyl peroxide also prevents the occurrence of malignancy in the cutaneous tissue. Immunohistochemical staining of the cutaneous tissues of rats exposed to UV B radiation show the presence of p53 + foci (clusters of cells containing the mutated p53 protein), whereas an absence of p53 + foci is observed in animals pretreated with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide. These results prove that 1-oxo-5beta, 6beta-epoxy-witha-2-enolide has the potential for acting as an effective agent to prevent the incidence of skin carcinoma induced by UV B radiation.

How to be a good woman: the playway method.

PIP: This analysis considers the "history of [mothers'] voices" embodied in traditional Bengali "chhada" (nursery rhymes, cradle songs, and lullabies). The analysis is confined to the chhadas whose content socializes female children to accept their gender roles in the patriarchal culture and recognizes that the seemingly innocent nature of the material increases and masks its power. The introduction reinforces the accuracy of the assumption that these chhadas were composed by women for use as maternal texts and applies Pierre Bourdieu's analysis of the process of indoctrination from infancy to the use of chhadas to generate "second nature" attitudes and resulting behaviors in daughters. The next section of the analysis synthesizes common themes and motifs from over 500 popular chhadas that prepare girls to accept the sorrows of separation upon marriage, warn them about the necessity of pleasing mothers-in-law, and acknowledge norms of female beauty (pale skin and sharp features). This section also notes that chhadas used to coax children to eat are overwhelmingly addressed to sons. An attempt to subvert the power structure is found in chhadas that ridicule or insult sons-in-law. The third section of the paper identifies the process by which the chhada has functioned as a patriarchal tool and addresses the paradox arising from the impulse to retain the valuable communicative and bonding aspect of the medium. After referring to Anne Kaplan's insight that motherhood is a patriarchal construct, the analysis call for identification of ways women negotiated the patriarchy and acknowledges that the use of chhadas is diminishing in the age of television.^ieng