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71.
Strategy, Management and Health Policy
Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Postmarketing Phase IV
Heliopsis longipes is a popular medicinal plant in Mexico. One of the main constituents that can be extracted from H. longipes is affinin (N‐isobutylamide). However, available information regarding this compound is scarce, and there is only a single report related to the effect of affinin on the central nervous system. Affinin extracted from H. longipes was evaluated for its psychopharmacological activity in several models and for its safety. H. longipes extract and affinin demonstrated antinociceptive effect, modified anxiety behavior and prolonged the time of sodium pentobarbital‐induced hypnosis. Affinin elicited these activities at high doses. Both the extract and affinin decreased the time of clonic and tonic PTZ‐induced seizures. In the Ames test, neither the extract nor affinin induced mutations in the Salmonella typhimurium strains TA98 and TA100 or TA102 with or without the S9 microsomal fraction. Lethal dose 50 values in mice suggest that the H. longipes extract may contain sedative principles with potential anxiolytic activity; however, it may also increase convulsive activity.  相似文献   
72.
A 16-year-old with left-sided pneumothorax   总被引:1,自引:0,他引:1  
Mendonca C  Lynch L 《Chest》1999,115(3):881-882
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73.
OBJECTIVE: To explore perceptions of well-being, family support, and economic resources in relation to level of contact with migration to the U.S. among a sample of elderly males from rural Mexico. METHOD: The snowballing technique was used to obtain a sample of 372 participants. Four groups were created according to the level of contact with migration among older adults and their children. RESULTS: Greater level of contact with migration was associated with a higher likelihood that an older adult was literate, married or living with someone, self-employed, and retired or pensioned. In addition, greater level of contact with migration to the U.S. was associated with a higher level of perceived well-being, family support, and economic security. DISCUSSION: Elderly, rural Mexican men with a greater degree of contact with migration to the U.S. seem to have more security and well-being in their old age.  相似文献   
74.
75.
Heliopsis longipes (Compositae) is a Mexican plant used as analgesic in pain toothache. A solution of 10mug/ml of dichloromethane extract from this plant showed analgesic activity determined by means of GABA release in mice brain slices. Through a bioassay-directed separation, fractions G-1, G-2, G-4 and G-6 at the same concentration were active. Affinin was the unique and common active compound, and evoke the GABA release 0.5min after administration at 1x10(-4)M concentration. Inactive compound were undeca-2E-en-8,10-dyinoic acid isobutylamide, hinokinin, 2'-hydroxyhinokinin, 3beta-sn-glyceroyl-(1'-palmitoxy)urs-12-ene, 13(18)-ursen-3beta-ol, 13(18)-ursen-3beta-acetate, beta-sitosterol and stigmasterol. The analgesic activity of Heliopsis longipes could be associated to affinin.  相似文献   
76.
Exposure to ionizing radiation (IR) is a risk factor for carcinogenesis because it is a mutagen. However, a single 4-Gy whole body X-ray exposure only induced a modest increase of mutations at the Aprt reporter gene locus in mouse T cells. Intriguingly, when the same dose of IR was given in a fractionated protocol (1 Gy x 4 at weekly intervals), there was a strong induction of Aprt mutations in T cells. Many of these were mutations that arose via interstitial deletions inclusive of Aprt or by intragenic deletions. We hypothesized that the weekly fractionated X-ray exposures select for somatic cells with reduced p53 expression and/or reduced apoptosis, which, in turn, may have facilitated the accumulation of interstitial deletions, as in p53-deficient mice. We indeed found that splenocytes of mice with three previous exposures (1 Gy x 4 in total) were more resistant to X-ray-induced apoptosis than those of mice exposed to X-rays for the first time (1 Gy total). Thus, repeated X-ray radiation selects for reduced apoptosis in vivo. However, this reduced apoptosis is p53-independent, because p53 induction and the up-regulation of genes downstream of p53, such as Bax and p21, were similar between the 1-Gy and 1 Gy x 4 groups. Reduced apoptosis probably allows the generation of more mutations, particularly deletion mutations. Because both reduced apoptosis and increased somatic mutation are risk factors for carcinogenesis, they may contribute to the paradigm in which different radiation exposure schemes are varied in their efficiency in inducing lymphomagenesis.  相似文献   
77.
Lipoprotein lipase (LPL) is a key enzyme in lipid metabolismand is associatedwith obesity, dyslipidemias, hypertension (HTN) and type 2 diabetes mellitus (T2DM). LPL gene polymorphisms can be related with the development of cardiovascular risk factors. The present study was conducted to analyze the relationship of the HindIII and S447X polymorphisms in LPL gene with cardiovascular risk factors in Mexican families. The study population comprised ninety members of 30 Mexican families, in which an index case had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical parameters. Screening for both polymorphisms was made by PCR-RFLPs. In the parents, both polymorphisms were in Hardy-Weinberg’s equilibrium. We found that the genotype T/T of HindIII was associated with diastolic blood pressure ≧ 85 mmHg (OR = 1.1; p = 0.011), whereas the genotype C/C of S447X was associated with systolic blood pressure ≧ 130 mmHg (OR = 1.2; p < 0.001), diastolic blood pressure ≧ 85 mmHg (OR = 1.3; p < 0.001), T2DM (OR = 1.3; p < 0.001) and with increase of total cholesterol (β = 23.6 mg/mL; p = 0.03). These data suggest that the HindIII and S447X LPL gene polymorphisms can confer susceptibility for the development of hypertension and T2DM in Mexican families.  相似文献   
78.
Background/AimsThe development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association.MethodsThe SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies (n = 39,448).ResultsVariability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89–1.04) or in the meta-analysis (OR = 1.01; 0.98–1.05).ConclusionOur data exclude a role for the SH2B1 obesity locus in the modulation of AGH.  相似文献   
79.
Until recently, conversion of arginine to agmatine by arginine decarboxylase (ADC) was considered important only in plants and bacteria. In the following, we demonstrate ADC activity in the membrane-enriched fraction of brain, liver, and kidney cortex and medulla by radiochemical assay. Diamine oxidase, an enzyme shown here to metabolize agmatine, was localized by immunohistochemistry in kidney glomeruli and other nonrenal cells. Production of labeled agmatine, citrulline, and ornithine from [3H]arginine was demonstrated and endogenous agmatine levels (10(-6)M) in plasma ultrafiltrate and kidney were measured by HPLC. Microperfusion of agmatine into renal interstitium and into the urinary space of surface glomeruli of Wistar-Frömter rats produced reversible increases in nephron filtration rate (SNGFR) and absolute proximal reabsorption (APR). Renal denervation did not alter SNGFR effects but prevented APR changes. Yohimbine (an alpha 2 antagonist) microperfusion into the urinary space produced opposite effects to that of agmatine. Microperfusion of urinary space with BU-224 (microM), a synthetic imidazoline2 (I2) agonist, duplicated agmatine effects on SNGFR but not APR whereas an I1 agonist had no effect. Agmatine effects on SNGFR and APR are not only dissociable but appear to be mediated by different mechanisms. The production and degradation of this biologically active substance derived from arginine constitutes a novel endogenous regulatory system in the kidney.  相似文献   
80.
A 27-month prospective study was conducted of patient assaults on nurses in a Canadian psychiatric hospital. Rates were low (4% of the patients committing an assault) and the injuries mostly trivial. Schizophrenics accounted for 43% of attacks, but when allowance was made for the disproportionate number of patients in the hospital with this diagnosis, individuals with mental retardation or dementia were approximately twice as likely to be assaultive as schizophrenics. Repeat assaulters (greater than 4 attacks) were more likely to be suffering from paranoid schizophrenia.  相似文献   
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