Anti-Stress and Anti-Amnesic Effects of Coriandrum sativum Linn (Umbelliferae) Extract – an Experimental Study in Rats

Purpose: Coriandrum sativum Linn. (Umbelliferae, C. sativum) is cultivated throughout the world for its use as spice and as a folk medicine. This study deals with the anti-stress and anti-amnestic properties of C. sativum extract in rats.Methods: Urinary levels of vanillylmandelic acid (VMA) and ascorbic acid were used to evaluate antistress activity in rats, while conditioned avoidance response test in normal and scopolamine-induced amnesic rats was used to evaluate anti-amnesic effects. C. sativum extract was also evaluated for its antioxidant activities by inhibition of lipid peroxidation in brain and liver homogenates of the rats.Results: Daily administration of C. sativum extract (100, 200 and 300 mg/kg body weight) 1 h prior to induction of stress significantly decreased the stress-induced urinary levels of VMA from 382.79 ± 10.70 to 350.66 ± 15.15, 291.21 ± 16.53 and 248.86 ± 13.56 μg/kg/24 h and increased the ascorbic acid excretion levels from 66.73 ± 9.25 to 69.99 ± 7.37, 105.28 ± 13.74 and 135.32 ± 12.54 μg/kg/24 h at 100, 200 and 300 mg/kg, respectively, in a dose-dependent fashion without affecting the normal levels in control groups. The amnesic deficits (acquisition, retention and recovery) induced by scopolamine (1mg/kg, i.p.) in rats was reversed by C. sativum dose dependently. The extract also inhibited lipid peroxidation in both rat liver and brain to a greater extent than the standard antioxidant, ascorbic acid.Conclusion: C. sativum may be useful remedy in the management of stress and stress related disorders on account of its multiple actions such as anti-stress, anti-amnestic and antioxidant effects.Keywords: C. sativum, Stress, Lipid peroxidation, Vanillylmandelic acid, Memory

Magnetic Properties of Dilute Alloys: Equations for Magnetization and its Structural Fluctuations

The dilute Heisenberg ferromagnet is studied taking into account fluctuations of magnetization caused by disorder. A self-consistent system of equations for magnetization and its mean quadratic fluctuations is derived within the configurationally averaged two-time temperature Green's function method. This system of equations is analised at low concentration of non-magnetic impurities. Mean relative quadratic fluctuations of magnetization are revealed to be proportional to the square of concentration of impurities.Comment: 16 pages, LaTe

Identification of Novel Small Organic Compounds with Diverse Structures for the Induction of Epstein-Barr Virus (EBV) Lytic Cycle in EBV-Positive Epithelial Malignancies

Phorbol esters, which are protein kinase C (PKC) activators, and histone deacetylase (HDAC) inhibitors, which cause enhanced acetylation of cellular proteins, are the main classes of chemical inducers of Epstein-Barr virus (EBV) lytic cycle in latently EBV-infected cells acting through the PKC pathway. Chemical inducers which induce EBV lytic cycle through alternative cellular pathways may aid in defining the mechanisms leading to lytic cycle reactivation and improve cells’ responsiveness towards lytic induction. We performed a phenotypic screening on a chemical library of 50,240 novel small organic compounds to identify novel class(es) of strong inducer(s) of EBV lytic cycle in gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC) cells. Five hit compounds were selected after three successive rounds of increasingly stringent screening. All five compounds are structurally diverse from each other and distinct from phorbol esters or HDAC inhibitors. They neither cause hyperacetylation of histone proteins nor significant PKC activation at their working concentrations, suggesting that their biological mode of action are distinct from that of the known chemical inducers. Two of the five compounds with rapid lytic-inducing action were further studied for their mechanisms of induction of EBV lytic cycle. Unlike HDAC inhibitors, lytic induction by both compounds was not inhibited by rottlerin, a specific inhibitor of PKCδ. Interestingly, both compounds could cooperate with HDAC inhibitors to enhance EBV lytic cycle induction in EBV-positive epithelial cancer cells, paving way for the development of strategies to increase cells’ responsiveness towards lytic reactivation. One of the two compounds bears structural resemblance to iron chelators and the other strongly activates the MAPK pathways. These structurally diverse novel organic compounds may represent potential new classes of chemicals that can be used to investigate any alternative mechanism(s) leading to EBV lytic cycle reactivation from latency.published_or_final_versio

Inhibition of class I histone deacetylases by romidepsin potently induces Epstein-Barr virus lytic cycle and mediates enhanced cell death with ganciclovir

Pan-histone deacetylase (HDAC) inhibitors, which inhibit 11 HDAC isoforms, are widely used to induce Epstein-Barr virus (EBV) lytic cycle in EBV-associated cancers in vitro and in clinical trials. Here, we hypothesized that inhibition of one or several specific HDAC isoforms by selective HDAC inhibitors could potently induce EBV lytic cycle in EBV-associated malignancies such as nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). We found that inhibition of class I HDACs, particularly HDAC-1, -2 and -3, was sufficient to induce EBV lytic cycle in NPC and GC cells in vitro and in vivo. Among a panel of selective HDAC inhibitors, the FDA-approved HDAC inhibitor romidepsin was found to be the most potent lytic inducer, which could activate EBV lytic cycle at ∼0.5 to 5 nM (versus ∼800 nM achievable concentration in patients' plasma) in more than 75% of cells. Upregulation of p21WAF1 , which is negatively regulated by class I HDACs, was observed before the induction of EBV lytic cycle. The upregulation of p21WAF1 and induction of lytic cycle were abrogated by a specific inhibitor of PKC-δ but not the inhibitors of PI3K, MEK, p38 MAPK, JNK or ATM pathways. Interestingly, inhibition of HDAC-1, -2 and -3 by romidepsin or shRNA knockdown could confer susceptibility of EBV-positive epithelial cells to the treatment with ganciclovir (GCV). In conclusion, we demonstrated that inhibition of class I HDACs by romidepsin could potently induce EBV lytic cycle and mediate enhanced cell death with GCV, suggesting potential application of romidepsin for the treatment of EBV-associated cancers.postprin

Excitatory Amino Acids Contribute to the Pathogenesis of Perinatal Hypoxic-Ischemic Brain Injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75512/1/j.1750-3639.1992.tb00697.x.pd

Smoking and non-neoplastic lung disease in Canadian men and women

MAIN OBJECTIVE: To document and assess the current health impact of non-neoplastic lung disease (NNLD) in Canadian men and women that is attributable to smoking. DESIGN: Comparison of three recent studies providing estimates of smoking-attributable deaths, potential years of life lost, hospital separations and hospital days due to NNLD in Canada. Review of recent epidemiological studies providing relative risk estimates of smoking-attributable mortality and morbidity for chronic obstructive pulmonary disease and pneumonia, including a meta-analysis. MAIN RESULTS: Each year at least 6700 Canadian men and women die from NNLD attributable to smoking. Smoking-attributable NNLD deaths in men outnumber those in women by about 2 to 1. The majority of these deaths are due to chronic obstructive pulmonary disease, which is exceeded in importance as a smoking-attributable cause of death only by lung cancer and ischemic heart disease. NNLD accounts for about 20% of all smokingattributable deaths in Canada, 14% of the potential years of life lost due to smoking, and 22% and 25% of all smokingattributable hospital separations and hospital days, respectively. Long term follow-up assessments of large cohorts suggest that the impact of smoking on health has been underestimated. Recent studies also suggest that women may be more susceptible than men to the adverse effects of smoking on lung function. CONCLUSION: NNLD caused by smoking has an important health impact in Canada. Tobacco control strategies must be enhanced. Key Words: Lung diseases, Morbidity, Mortality, Smoking Le tabagisme et la maladie pulmonaire non cancéreuse chez les Canadiens et Canadiennes OBJECTIF PRINCIPAL : Documenter et évaluer les influences actuelles sur la santé de la maladie pulmonaire non cancéreuse chez des Canadiens et Canadiennes, et qui sont imputables au tabagisme. MODÈLE : Comparaison de trois études récentes fournissant des estimés des décès attribuables au tabagisme, des années potentielles de vie perdues, des congés donnés aux patients hospitalisés et des journées d'hospitalisation dus à la maladie pulmonaire non cancéreuse au Canada. Revue des études épidémiologiques récen-tes fournissant des estimés du risque relatif de la mortalité attribuable au tabagisme et de la morbidité liée à la maladie pulmonaire obstructive chronique et à la pneumonie, incluant une méta-analyse. voir page suivante I t is now well established that smoking is the most important preventable cause of premature mortality and morbidity in Canadian men and women (1,2), as it is in the populations of other developed countries (3,4). At least 33,000 Canadians die each year as a result of tobacco use, which also accounts for more than 200,000 hospital separations, three million hospital days and some $9.5 billion in costs from lost productivity and direct health care expenditures (2). Despite this enormous health toll, smoking remains prevalent. Estimates from the National Population Health Survey conducted in 1994 indicate that 6.9 million Canadians, 31% of the population aged 15 years and over, smoke (5). Further, rates of smoking among young Canadians, after some years of decline, have now plateaued (6) and may actually be increasing in some provinces, notably in Ontario The primary purpose of this paper is to document and assess current estimates of the health impact of smoking in Canada with regard to non-neoplastic lung disease (NNLD) and to point out some limitations of these data. As well, recent reports concerning long term epidemiological studies of the relationship of smoking to NNLD are reviewed, including a meta-analysis of relative risk estimates. Attention is drawn to recent studies that indicate the possibility that the lungs of women may be particularly susceptible to the adverse effects of tobacco smoke. HEALTH IMPACT OF SMOKING DUE TO NNLD Smoking-attributable mortality: Three studies provide estimates of the current mortality impact of tobacco use in Canadian men and women Makomaski Illing and Kaiserman (1), using risk estimates from the same source, concluded that in 1991 there were more than 8100 NNLD deaths among Canadians attributable to smoking, out of a total of 41,408 smoking-attributable deaths. Most recently, Single et al (2) used mortality estimates derived from a meta-analysis of epidemiological studies conducted by English et al (10), discussed further below. They concluded that in 1992 NNLD deaths in Canadians attributable to smoking exceeded 6700, out of a total estimate of more than 33,000 smoking-attributable deaths. In all three estimates shown in Comparability of the mortality estimates: Because the RISKS OF NNLD MORTALITY AND MORBIDITY ASSOCIATED WITH SMOKING Mortality: A study by Canadian investigators was among the first to document the excess risk of mortality from NNLD in smokers compared with nonsmokers (11,12). In the final six-year follow-up study of some 78,000 male veterans, initiated in 1955 by the Department of National Health and Welfare (12), it was found that veterans with a lifetime history of smoking cigarettes had about 11 and eight times the risk of mortality from chronic bronchitis and emphysema, respectively, compared with nonsmokers. A dose-response relationship between the amount smoked daily and the risk of mortality was also observed. For pneumonia and influenza there was a small increase in relative risk (1.4). Since then, a host of epidemiological studies from many countries have confirmed the causal relationship between smoking and COPD in both men and women, as well as a small increase in the risk of mortality from pneumonia (13-17). Doll et al Doll et al Recently, Gold et al (27), in a study of the effects of cigarette smoking on the level and rate of growth of pulmonary function in large cohorts of adolescent boys and girls, demonstrated that the growth of lung function in association with smoking was more severely affected in the girls. This finding is particularly worrisome in the context of the ages at which adolescent girls and boys begin to smoke. In the 1994 Canadian Youth Smoking Survey (6) it was found that although the rates of beginning to smoke were similar in boys and girls ages 10 to 12 years (4% in each), by ages 13 to 14 years this rate was significantly higher than girls (15%) compared with boys (9%). Girls may not only be more susceptible to the adverse effects of smoking, but they appear to be getting a 'head start' on this addiction. While sex differences in susceptibility to the smokinginduced changes in lung function require more study, particularly with regard to underlying biological mechanisms, the primal importance of smoking cessation in reducing the age-related decline in FEV 1 in smokers with mild obstructive pulmonary disease is beyond disput

Nasopharyngeal carcinoma: time lapse before diagnosis and treatment

This is a descriptive study of 168 patients with nasopharyngeal carcinoma who were referred to public oncology departments for primary treatment between July and September 1996. The mean duration from the onset of the symptoms to histological diagnosis was 5.0 months; the duration ranged from 6.1 months (for patients presenting with nasal symptoms) to 1.8 months (for those with cranial nerve dysfunction). The mean period between the onset of symptoms and the seeking of medical advice was 2.9months. For 54% of the patients, there was a further delay of up to 2.4 months between the initial medical consultation and referral to the appropriate specialist. The majority (84%) of patients attended public institutions for histological confirmation. The mean total time taken from the onset of symptoms to the commencement of radiotherapy was 6.5 months (range, 1.3-74.0 months)---45% of the delay was attributed to the patient, 20% to initial consultations, 14% to diagnostic arrangement, and 21% to preparation for radiotherapy. Concerted efforts are needed to minimise further the time between the onset of symptoms and treatment. A substantial reduction in this delay can be achieved if both public and primary care doctors were made more aware of the significance of relevant symptoms.published_or_final_versio

Opportunities for improving pLDH-based malaria diagnostic tests

<p>Abstract</p> <p>Background</p> <p>Monoclonal antibodies to <it>Plasmodium </it>lactate dehydrogenase (pLDH) have been previously used to format immunochromatographic tests for the diagnosis of malaria. Using pLDH as an antigen has several advantages as a sensitive measure of the presence of parasites within patient blood samples. However, variable results in terms of specificity and sensitivity among different commercially available diagnostic kits have been reported and it has not been clear from these studies whether the performance of an individual test is due simply to how it is engineered or whether it is due to the biochemical nature of the pLDH-antibody reaction itself.</p> <p>Methods</p> <p>A series of systematic studies to determine how various pLDH monoclonal antibodies work in combination was undertaken. Different combinations of anti-pLDH monoclonal antibodies were used in a rapid-test immunochromatographic assay format to determine parameters of sensitivity and specificity with regard to individual <it>Plasmodium </it>species.</p> <p>Results</p> <p>Dramatic differences were found in both species specificity and overall sensitivity depending on which antibody is used on the immunochromatographic strip and which is used on the colorimetric colloidal-gold used for visual detection.</p> <p>Discussion</p> <p>The results demonstrate the feasibility of different test formats for the detection and speciation of malarial infections. In addition, the data will enable the development of a universal rapid test algorithm that may potentially provide a cost-effective strategy to diagnose and manage patients in a wide range of clinical settings.</p> <p>Conclusion</p> <p>These data emphasize that using different anti-pLDH antibody combinations offers a tractable way to optimize immunochromatographic pLDH tests.</p