Alterations in cholinergic and non-cholinergic neurotransmitter receptor densities in transgenic Tg2576 mouse brain with beta-amyloid plaque pathology.

Cholinergic deficits in Alzheimer's disease are accompanied by a number of alterations in other transmitter systems including glutamate, noradrenaline and serotonin, suggesting the involvement also of other neurotransmitter systems in the pathogenesis of the disease. To address the question whether beta-amyloid may contribute to these deficits, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages of 5 (still no significant plaque load) and 17 months (moderate to high cortical beta-amyloid plaque load) were examined for a number of cholinergic and non-cholinergic markers. Transgenic mice with no significant plaque load demonstrated reduced hemicholinium-3 (HCh-3) binding to choline uptake sites in anterior brain regions as compared to non-transgenic littermates, while in aged transgenic mice with high number of plaque deposits decreased HCh-3 binding levels were accompanied by increased vesicular acetylcholine transporter binding in selected cortical brain regions. In aged transgenic mice GABA(A), NMDA, AMPA, kainate, and beta-adrenergic as well 5-HT(1A)- and 5-HT(2A)-receptor binding levels were hardly affected, whereas alpha(1)- and alpha(2)-adrenoceptor binding was increased in selected cerebral cortical regions as compared to non-transgenic littermates. The development of changes in both cholinergic and non-cholinergic markers in transgenic Tg2576 mouse brain already before the onset of progressive plaque deposition provides in vivo evidence of a modulatory role of soluble beta-amyloid on cortical neurotransmission and may be referred to the deficits in learning and memory observed in these mice also before significant plaque load.     

Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake

Low brain uptake is a generally accepted problem in developing technetium-99m brain receptor imaging agents. For a class of potential 5-HT_2A receptorbinding agents we tried to improve the original low brain uptake of 0.4% injected dose (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules. Because of the presence of a protonable nitrogen, which according to the pK _a value leads to ionization of the molecule at blood pH, the pK _a value was considered to be the parameter most suitable for adjustment of lipophilicity. Insertion of ether-oxygen in the molecule of five candidates lowers the apparent pK _a value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID at 5 min. The direct relationship between brain uptake and apparent pK _a cannot be simply explained by the increase in the pK _a-governed proportion of the neutral species.     

Klatskin tumors and Klatskin mimicking lesions of the biliary tree.

AIM: We report on the preoperative capability of imaging modalities and clinical assessment to differentiate between Klatskin tumors and Klatskin mimicking lesions of the biliary tree. Adenocarcinomas of the hepatic ducts (Klatskin tumors) mimic benign fibrosing cholangitis. Extensive resections carry a substantial risk but offer the only chance for cure in patients with a Klatskin tumor. METHODS: Thirty-three consecutive patients who underwent resection for suspicion of a malignant tumor of the hepatic hilum were reviewed. All patients underwent preoperative ultrasonography, computed tomography, ERCP and angiography. The patients were divided into a group of true Klatskin tumors and a group of benign Klatskin mimicking lesions. RESULTS: Twenty-seven of the resected specimens were malignant tumors, and six lesions showed only fibrosing cholangitis. Preoperative clinical presentation and imaging modalities were very similar between Klatskin tumors and fibrosing cholangitis. CONCLUSIONS: Management of obstruction of the liver hilum is dictated by the suspicion of malignancy. Complete removal of the tumor remains the therapeutic aim but clinical presentation and imaging modalities cannot help to differentiate between Klatskin tumors and Klatskin mimicking lesions prior to surgery.     

Development of Scheelite Tailings-Based Ceramic Formulations with the Potential to Manufacture Porcelain Tiles,Semi-Stoneware and Stoneware

New ceramic formulations based on scheelite tailing were developed, and their potential in the ceramic industry was evaluated. Green bodies with different contents of scheelite tailing (0–8 wt%) were sintered (1150 °C, 1200 °C, and 1250 °C) and characterized in terms of the main mineralogical phases, microstructure, and physico-mechanical properties. The mullite was the main phase identified in all sintered temperatures. This result was also ratified with the aid of scanning electron microscope (SEM) images, in which small needles of the mullite were detected. The presence of mullite is required because it contributes to increasing the mechanical resistance of the material. The physico-mechanical properties measured (water absorption, linear shrinkage, apparent porosity, and flexural strength) were compared to the ISO 13006, and the samples sintered at 1150 °C presented potential to be used as semi-stoneware, while those sintered at 1200 °C and 1250 °C can be employed stoneware and porcelain tiles, respectively.     

CAT correlates positively with respiratory rate and is a significant predictor of the impact of COPD on daily life of patients: a cross sectional study

Background

The pathophysiological changes of COPD tend to worsen with progression, triggering limiting symptoms and implying the decrease in the activities of daily living and quality of life. The COPD Assessment Test (CAT) is a questionnaire designed to measure the impact of COPD on the health status. The aim of this study was to evaluate the impact of the disease through the CAT in a Brazilian sample of COPD patients and to correlate symptoms at rest with the CAT score in these patients.

Methods

Study of cases with COPD patients was conducted by pulmonary rehabilitation program (RP). Respiratory rate (RR) and symptoms (dyspnea by Modified Borg Scale Dyspnea Index; symptoms by CAT) were analyzed at the beginning of the RP.

Results

The study analyzed 28 COPD patients, both genders, age 65.93?±?7.84 years and many patients ranging from severe and very severe disease. The majority of patients were rated by CAT with low impact-disease (n?=?13/46, 4%);medium (n?=?11/39, 3%) and the high impact-diseases were observed in a few subjects (n?=?4/14.3%). The difference between all CAT scores was significant, p?=?0.000. There was a positive correlation between respiratory rate and CAT scores impact-level (r?=?0.585, p?=?0.001). The results obtained by the Borg Scale revealed a high presence of symptoms in these COPD patients but no association with CAT.

Conclusion

The CAT is a sensitive tool to assess the current health status of COPD patients, and in Southern Brazil it is positively correlated with respiratory rate.

     

Quality of life of older adults in Canada and Brazil

In this study, we examined the factors contributing to quality of life (QOL) of older adults in regions of Canada and Brazil. The WHOQOL-BREF and a demographic data sheet were administered to random samples of 202 older adults from Canada and 288 from Brazil. Ratings on overall QOL and on the physical, psychological, and environmental domains were higher in the Canadian sample. Social domain scores were not significantly different. The authors found the same pattern of factors (health satisfaction, enough money, meaning in life, and opportunities for leisure activities) contributed to the variance of QOL in both countries, except for physical environment, which was significant in Brazil and not in Canada. Health satisfaction was the strongest contributor to QOL in both samples, and satisfaction with personal relationships was not significant in either country.     

Diphenyl diselenide protects rat hippocampal slices submitted to oxygen-glucose deprivation and diminishes inducible nitric oxide synthase immunocontent

Diphenyl diselenide (PhSe)2 is an organic selenium compound that has been little studied. In this study we investigated the effects of (PhSe)2 (0.1-3 microM) in a classical model of in vitro brain ischemia, which consists of exposing rat hippocampal slices to oxygen-glucose deprivation (OGD). Hippocampal slices were exposed for 60 min to OGD and the cellular viability (performed by MTT assay) as well as the immunocontent of nitric oxide synthase inducible (iNOS) were evaluated after 180 min of a recovery period. OGD decreased cellular viability by 50% and increased more than twice the immunocontent of iNOS of hippocampal slices. (PhSe)2 (1 and 3 microM) added during OGD and the recovery period abolished both effects. These results demonstrate for the first time the neuroprotective effects of (PhSe)2. Although the selenium analog--ebselen--has been widely used in ischemia models, our results suggest that other selenoorganic compounds could be investigated as pharmacological tools against brain disorders.     

Predictive factors of mortality due to polymicrobial peritonitis with Candida isolation in peritoneal fluid in critically ill patients

BACKGROUND: Candida peritonitis (CP) is generally considered to be a severe disease, but its impact on outcome in critically ill patients remains unknown. HYPOTHESIS: The predictive factors of mortality due to CP can be determined by study of a population of patients with CP. DESIGN: A retrospective review of a prospective surgical intensive care unit (ICU) database of patients (January 1, 1994, through December 31, 2000). SETTING: University hospital in Paris, France. PATIENTS: Eighty-three patients with generalized CP. MAIN OUTCOME MEASURES: Demographic and microbiologic data and outcome were collected, and nonsurvivors were compared with survivors. RESULTS: Overall ICU mortality due to CP was 43 (52%) of 83 patients. In a stepwise multivariate logistic regression, the following 4 variables were independently associated with mortality: APACHE II (Acute Physiology and Chronic Health Evaluation II) score on admission of at least 17 (odds ratio [OR], 28.4; 95% confidence interval [CI], 5.7-142.5; P<.001), respiratory failure on admission (OR, 10.6; 95% CI, 2.2-51.2; P =.003), upper gastrointestinal tract site of peritonitis (OR, 7.7; 95% CI, 1.7-34.7; P =.007), and results of direct examination of peritoneal fluid that were positive for Candida (OR, 4.7; 95% CI, 1.2-19.7; P =.002). CONCLUSIONS: These results confirm the severity of CP in ICU patients and emphasize the prognostic value of direct examination of peritoneal fluid for Candida in this context.