Effects of bilateral adrenalectomy on systemic kainate-induced activation of the nucleus of the solitary tract. Regulation of blood pressure and local neurotransmitters

Glutamatergic transmission through metabotropic and ionotropic receptors, including kainate receptors, plays an important role in the nucleus of the solitary tract (NTS) functions. Glutamate system may interact with several other neurotransmitter systems which might also be influenced by steroid hormones. In the present study we analyzed the ability of systemic kainate to stimulate rat NTS neurons, which was evaluated by c-Fos as a marker of neuronal activation, and also to change the levels of NTS neurotransmitters such as GABA, NPY, CGRP, GAL, NT and NO by means of quantitative immunohistichemistry combined with image analysis. The analysis was also performed in adrenalectomized and kainate stimulated rats in order to evaluate a possible role of adrenal hormones on NTS neurotransmission. Male Wistar rats (3 month-old) were used in the present study. A group of 15 rats was submitted either to bilateral adrenalectomy or sham operation. Forty-eight hours after the surgeries, adrenalectomized rats received a single intraperitoneal injection of kainate (12 mg/kg) and the sham-operated rats were injected either with saline or kainate and sacrificed 8 hours later. The same experimental design was applied in a group of rats in order to register the arterial blood pressure. Systemic kainate decreased the basal values of mean arterial blood pressure (35%) and heart rate (22%) of sham-operated rats, reduction that were maintained in adrenalectomized rats. Kainate triggered a marked elevation of c-Fos positive neurons in the NTS which was 54% counteracted by adrenalectomy. The kainate activated NTS showed changes in the immunoreactive levels of GABA (143% of elevation) and NPY (36% of decrease), which were not modified by previous ablation of adrenal glands. Modulation in the levels of CGRP, GAL and NT immunoreactivities were only observed after kainate in the adrenalectomized rats. Treatments did not alter NOS labeling. It is possible that modulatory function among neurotransmitter systems in the NTS might be influenced by steroid hormones and the implications for central regulation of blood pressure or other visceral regulatory mechanisms control should be further investigated.

Histologic Study of Perifascial Areolar Tissue Implanted in Rabbit Vocal Folds: An Experimental Study

Objectives: Perifascial areolar tissue (PAT) consists of loose areolar tissue with viscoelastic properties that are similar to those found in tissues in the superficial layer of the vocal fold. The aim of this study was to quantify the inflammatory process and the collagen content of the graft, as well as that of the host tissue, after placement of a strip of PAT into the rabbit vocal fold. Methods: Surgeries were performed on 30 rabbits. The grafts were implanted in pockets that were surgically created in the right vocal fold. The left vocal fold (control group) was subjected only to surgical manipulation. The animals were divided into 3 groups for evaluations at 15 days, 3 months, and 6 months, and their larynx tissues were subsequently reviewed by histology. Results: The grafts were characterized by disorganized and thick collagen bundles and were identified in all study groups. The collagen density stayed constant over time. There was an acute inflammatory response induced by the graft at 15 clays that did not exist in the specimens taken at 3 and 6 months. Deposition of collagen fibers in the lamina propria was observed starting at 15 days after the operation and was more intense in the experimental vocal fold than in the control vocal fold. Conclusions: Our findings indicated that PAT has a low tendency for promoting an inflammatory response. However, there was a loss of the original architecture of the graft tissue and a greater deposition of collagen in the implanted vocal folds than in the control group.

Resistance exercise and glycemic control in women with gestational diabetes mellitus

OBJECTIVE: The objective of the study was to evaluate the effect of a resistance exercise program with an elastic band on insulin requirement and glycemic control in patients with gestational diabetes mellitus (GDM). STUDY DESIGN: Sixty-four patients with gestational diabetes mellitus were randomly assigned into 2 groups: an exercise group (EG; n = 32) and a control group not submitted to the exercise program (CG; n = 32). RESULTS: A significant reduction in the number of patients who required insulin was observed in the EG (7/32) compared with the CG group (18/32) (P = .005). The percentage of time spent within the proposed target glucose range (of at least 80% of weekly measurements below the limits preestablished for the disease) was significantly higher in EG compared with the CG group (EG = 0.63 +/- 0.30; CG = 0.41 +/- 0.31; P = .006). CONCLUSION: The resistance exercise program was effective in reducing the number of patients with GDM who required insulin and in improving capillary glycemic control in this population.

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Methods We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < 18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI > 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >= 30 kg/m(2) (0.43, 0.33-0.57), compared with BMI > 18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < 18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies

Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors. We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models. ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (a parts per thousand yen25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers. The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.

Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

A randomized controlled trial comparing a computer-assisted insulin infusion protocol with a strict and a conventional protocol for glucose control in critically ill patients

Purpose: The objective of this study is to evaluate blood glucose (BG) control efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU) patients. Methods: This was a multicenter randomized controlled trial involving 167 MICU patients with at least one BG measurement +/- 150 mg/dL and one or more of the following: mechanical ventilation, systemic inflammatory response syndrome, trauma, or burns. The interventions were computer-assisted insulin protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL; Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or conventional treatment-subcutaneous insulin if glucose > 150 mg/dL. The main efficacy outcome was the mean of patients` median BG, and the safety outcome was the incidence of hypoglycemia (<= 40 mg/dL). Results: The mean of patients` median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs conventional). In CAIP, 12 patients (21.4%) had at least one episode of hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P = .02, CAIP vs Leuven; P = .006, CAIP vs conventional). Conclusions: The CAIP is safer than and as effective as the standard strict protocol for controlling glucose in MICU patients. Hypoglycemia was rare under conventional treatment. However, BG levels were higher than with IV insulin protocols. (C) 2009 Elsevier Inc. All rights reserved.

Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case-control study

Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited. We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37-30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72-16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use. In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.

Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions

Background Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Methods Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). Results HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). Conclusions A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

The Alzheimer`s Association external quality control program for cerebrospinal fluid biomarkers

Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta (A beta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer`s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer`s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for A beta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A beta-(1-42), P-tau(181P), and T-tau), and 5 used Mesa Scale Discovery with the A beta triplex (A beta N-42, A beta N-40, and A beta N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers. (C) 2011 The Alzheimer`s Association. All rights reserved.

Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders

Objective: Although bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly prevalent, few controlled studies have assessed this comorbidity. The objective of this study was to investigate the clinical characteristics and expression of comorbid disorders in female BD patients with OCD. Method: We assessed clinically stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15 without (BD/no-OCD group). All were submitted to the Structured Clinical Interview for DSM-IV, with additional modules for the diagnosis of kleptomania, trichotillomania, pathological gambling, onychophagia and skin picking. Results: The BD+OCD patients presented more chronic episodes, residual symptoms and previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients, 86% had a history of treatment-emergent mania, compared with only 40% of the BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control disorders; eating disorders; and tic disorders. Conclusion: Female BD patients with OCD may represent a more severe form of disorder than those without OCD, having more depressive episodes and residual symptoms, and being at a higher risk for treatment-emergent mania, as well as presenting a greater anxiety and impulse control disorder burden.

Quality control of Toxoplasma gondii in meat packages: Standardization of an ELISA test and its use for detection in rabbit meat cuts

Toxoplasma gondii causes severe disease both to man and livestock and its detection in meat after slaughtering requires PCR or biological tests. Meat packages contain retained exudate that could be used for serology due to its blood content. Similar studies reported false negative assays in those tests. We standardized an anti-T. gondii IgG ELISA in muscle juices from experimentally infected rabbits, with blood content determination by cyanhemoglobin spectrophotometry. IgG titers and immunoblotting profiles were similar in blood, serum or meat juice, after blood content correction. These assays were adequate regardless of the storage time up to 120 days or freeze-thaw cycles, without false negative results. We also found 1.35% (1/74) positive sample in commercial Brazilian rabbit meat cuts, by this assay. The blood content determination shows ELISA of meat juice may be useful for quality control for toxoplasmosis monitoring. (C) 2011 Elsevier Ltd. All rights reserved.