Anxiety does not affect the antinociceptive effect of Delta 9-THC in mice: participation of cannabinoid and opioid receptors

Cannabinoid receptor agonists significantly inhibit nociceptive responses in a large number of animal models. The present study examined whether mice displaying different basal levels of anxiety in the plus-maze test of anxiety might differ in terms of responsiveness to the antinociceptive effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Further, the involvement of the cannabinoid and/or opioid receptors in Delta(9)-THC-induced antinociception was investigated by using SR 141716A and naloxone, respectively, cannabinoid and opioid receptor antagonists. Delta(9)-THC-induced antinociception was evaluated in the formalin test that involves a biphasic response with an early and a late phase of high paw-licking activity. This characteristic biphasic response was observed in all control animals selected as "anxious" and "nonanxious." Delta(9)-THC (0.5-5 mg/kg i.p.) caused a dose-dependent antinociceptive effect in both groups of mice during the early and late phases. This response was fully reversed by SR 141716A (1 mg/kg i.p.) and partially reversed by naloxone (2 mg/kg i.p.). These findings suggest that mice selected for differences in anxiety-related behavior show similar responses to the antinociceptive action of Delta(9)-THC and that this action involves predominantly cannabinoid mechanisms.     

Hearing impairment and socioeconomic factors: a population-based survey of an urban locality in southern Brazil.

OBJECTIVE: To provide the first population-based data on deafness and hearing impairment in Brazil. METHODS: In 2003, a cross-sectional household survey was conducted of 2,427 persons 4 years old and over. The study population was composed of 1,040 systematically chosen households in 40 randomly selected census tracts (dwelling clusters) in the city of Canoas, which is in the state of Rio Grande do Sul, in southern Brazil. Hearing function was evaluated in all subjects by both pure-tone audiometry and physical examination, using the World Health Organization Ear and Hearing Disorders Survey Protocol and definitions of hearing levels. The socioeconomic data that were gathered included the amount of schooling of all individuals tested and the income of the head of the household. RESULTS: It was found that 26.1% of the population studied showed some level of hearing impairment, and 6.8% (95% confidence interval (CI) = 5.5%-8.1%) were classified in the disabling hearing impairment group. The prevalence of moderate hearing loss was 5.4% (95% CI = 4.4%-6.4%); for severe hearing loss, 1.2% (95% CI = 0.7%-1.7%); and for profound hearing loss, 0.2% (95% CI = 0.03%-0.33%). The groups at higher risk for hearing loss were men (odds ratio (OR) = 1.54; 95% CI = 1.06-2.23); participants 60 years of age and over (OR = 12.55; 95% CI = 8.38-18.79); those with fewer years of formal schooling (OR = 3.92; 95% CI = 2.14-7.16); and those with lower income (OR = 1.56; 95% CI = 1.06-2.27). CONCLUSIONS: These results support advocacy by health policy planners and care providers for the prevention of deafness and hearing impairment. The findings could help build awareness in the community, in universities, and in government agencies of the health care needs that hearing problems create.     

Hypertension and salt intake in an urban population

OBJECTIVE: To evaluate the salt intake and urinary Na+/K+ ratio in a randomized sample from an ethnically mixed urban population. METHODS: A randomized residential sample of 2,268 individuals aged 25-64 in Vit ria, ES, was selected, of whom 1,663 (73.3%) reported to the hospital for standardized tests. Salt, Na+ and K+ intake was estimated from 12-hour urine excretion (7 p.m. to 7 a.m.) and from the monthly salt consumption at home reported in the interview. Clinic arterial pressure was measured twice under standard conditions by two trained investigators, using mercury sphygmomanometry. The Student t and Tukey tests were utilized for statistical analysis. RESULTS: Urinary Na+ excretion was higher in men and individuals of lower socioeconomic level (P<0.000). No difference between ethnic groups was observed. K+ excretion was unrelated to socioeconomic level and ethnicity, but was significantly higher among men (25 18 vs. 22 18 mEq/12h; P=0.002). Positive linear correlation was observed between urinary Na+ excretion and systolic (r=0.15) and diastolic (r=0.19) arterial pressure. Hypertensive individuals showed higher urinary Na+ excretion and Na+/K+ ratio than normotensive individuals. Reported salt intake was around 50% of the intake estimated from 12-hour urine collection (around 45% of 24-hour urinary excretion). CONCLUSIONS: Salt intake is strongly influenced by socioeconomic level and may partially explain the higher prevalence of hypertension in lower socioeconomic classes.     

Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation

OBJECTIVES: We hypothesized that exercise-related periodic breathing (EPB) would be associated with poor prognosis in advanced chronic heart failure (CHF). BACKGROUND: Patients with CHF might present instability of the ventilatory control system characterized by cyclic waxing and waning of tidal volume (periodic breathing [PB]). This condition is associated with several deleterious circulatory and neuro-endocrine responses; in fact, PB in awake and asleep patients has been identified as an independent risk factor for cardiac death. During exercise, however, the prognostic value of PB is still unknown in CHF patients awaiting heart transplantation. METHODS: Eighty-four patients with established CHF (65 male, 19 female) were submitted to clinical evaluation, echocardiogram, ventricular scintigraphy, determination of resting serum norepinephrine levels, and an incremental cardiopulmonary exercise test on cycle ergometer. Patients were followed for up to 49.7 months (median = 15.3), and 26 patients (30.9%) died during this period. RESULTS: Twenty-five of 84 patients presented EPB (29.7%). The following variables were related to mortality according to Kaplan-Meier and univariate Cox regression analysis: EPB (p = 0.004), New York Heart Association class (p = 0.04), serum norepinephrine (p = 0.06), peak oxygen uptake (ml.min(-1).kg(-1) and % predicted; p = 0.085 and p = 0.10, respectively), slope of the ratio of change in minute ventilation to change in carbon dioxide output during exercise (p = 0.10), and scintigraphic left ventricular ejection fraction (p = 0.10). Cox multivariate analysis identified EPB as the only independent variable for cardiac death prediction (p = 0.007). Therefore, EPB alone was associated with a 2.97-fold increase in risk of death in this population (95% confidence interval = 1.34 to 6.54). CONCLUSIONS: Exercise-related periodic breathing independently predicts cardiac mortality in CHF patients considered for heart transplantation.     

Monocarboxylate Transporters 1 and 4 Are Associated with CD147 in Cervical Carcinoma

Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression.     

Evaluation of IGF-2/ApaI polymorphism in pregnant women infected with human immunodeficiency virus type 1 taking antiretroviral drugs

ObjectiveStudies carried out to assess the effects of antiretroviral drugs (ARV) in HIV-1 infected pregnant women have demonstrated carbohydrate intolerance. Some reports also refer to the effect of disturbances in the expression of the insulin-like growth factor (IGF) system on pancreas beta-cell function in humans and IGF-2/ApaI polymorphisms have been associated with obesity and features of the metabolic syndromes. In the present study, we tested the association between IGF-2/ApaI genotype and hyperglycemia in HIV-1 infected pregnant women receiving ARV.DesignWe studied IGF-2/ApaI polymorphism in 87 healthy pregnant women, 43 HIV-1 infected pregnant women taking ARV with hyperglycemia during pregnancy, and 43 HIV-1-negative pregnant women with gestational diabetes. Blood samples were obtained for DNA extraction, PCR and genotyping. Data were analyzed statistically by the Kolmogorov–Smirnov normality, ANOVA and chi-square tests.ResultsThere were no significant differences in genotype frequency among the three groups analyzed. Considering the HIV-1-infected pregnant women, there were no significant differences in genotype frequency between the zidovudine group and the triple antiretroviral treatment group. There were no significant differences in allele frequencies among the groups evaluated. Non-white pregnant women tended to present the GG genotypes compared to white pregnant women.ConclusionThese results contribute to a better understanding of metabolic glycemic disorders in HIV-1-infected pregnant women using ARV, showing that IGF-2/ApaI polymorphisms are not responsible as a single causative factor of glycemic alterations. These data indicate that other variables should be studied in order to explain these glycemic abnormalities.