Accumulation of filamentous tau in the cerebral cortex of human tau R406W transgenic mice

Missense mutations of the tau gene cause autosomal dominant frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an illness characterized by progressive personality changes, dementia, and parkinsonism. There is prominent frontotemporal lobe atrophy of the brain accompanied by abundant tau accumulation with neurofibrillary tangles and neuronal cell loss. Using a hamster prion protein gene expression vector, we generated several independent lines of transgenic (Tg) mice expressing the longest form of the human four-repeat tau with the R406W mutation associated with FTDP-17. The TgTauR406W 21807 line showed tau accumulation beginning in the hippocampus and amygdala at 6 months of age, which subsequently spread to the cortices and subcortical areas. The accumulated tau was phosphorylated, ubiquitinated, conformationally changed, argyrophilic, and sarcosyl-insoluble. Activation of GSK-3beta and astrocytic induction of mouse tau were observed. Astrogliosis and microgliosis correlated with prominent tau accumulation. Electron microscopic examination revealed the presence of straight filaments. Behavioral tests showed motor disturbances and progressive acquired memory loss between 10 to 12 months of age. These findings suggested that TgTauR406W mice would be a useful model in the study of frontotemporal dementia and other tauopathies such as Alzheimer's disease (AD).     

Characteristics of Unscheduled and Scheduled Outpatient Palliative Care Clinic Patients at a Comprehensive Cancer Center

Context

There is limited literature regarding outpatient palliative care and factors associated with unscheduled clinic visits.

Public knowledge and attitudes towards epilepsy in Jordan.

BACKGROUND: Social acceptances of people with epilepsy very often constitute a considerable problem for patients and their family. Nationwide opinion polls on the public knowledge and attitudes towards epilepsy have been reported from several countries. The purpose of this study is to assess the knowledge and attitudes of the Jordanian public towards epilepsy, which have not been verified before. METHODS: A total of 16,044 people (8158 males and 7886 females) living in different areas of Jordan were interviewed by invitation using standard four set questionnaire constructed from previous similar studies (Caveness and Gallup) that tested public knowledge and attitudes toward epilepsy. Two hundred and thirty senior students of the faculty of pharmacy at Jordan University of Science and Technology are involved in this study. Each student interviewed at least 50 individuals, aged 18 years or older, from their immediate community including family members, relatives, neighbors and friends by invitation. The interviews took place during the period from February to June of 2005. RESULTS: Eighty-eight percent had read or knew about epilepsy, and 52.4% had witnessed an epileptic attack at least once in their life. From the people interviewed, 84.7% believed that the cause of epilepsy is a neurological disease, and 80.6% believe that the main symptom is brief loss of consciousness. The response of the younger participants and those with higher education were statistically significant more positive regarding the knowledge on causes and symptoms of epilepsy. More than 70% accepts shaking hands with people with epilepsy; they also believe that people with epilepsy are able to have children and to get high academic degrees. Less than 50% accepts letting their children play with children with epilepsy or employ people with epilepsy. Nine percent had negative attitudes, and believed that patients with epilepsy are insane and 88.5% objects the marriage of people with epilepsy to their sons or daughters. Approximately one third of the respondents believed that epilepsy is more dangerous than diabetes mellitus and hypertension. CONCLUSIONS: The overall knowledge and attitudes of Jordanians towards epilepsy is relatively comparable with the results from Asian countries but more negative when compared with reports from the Western countries. Consequently, well-organized educational campaigns are needed to improve public perception about epilepsy.     

Lupus nephritis. Clinicopathological correlation

OBJECTIVE: To classify all renal biopsies of lupus nephritis patients presenting in the last 10 years, according to the modified World Health Organization (WHO) classification using the facilities of light, fluorescent, and electron microscopy. To assess the activity and chronicity indices of renal biopsies according to the National Institute of Health protocol, and to correlate the histological findings with the clinical features of the patients presented up to the time of biopsy. METHODS: Seventy-eight patients with lupus nephritis, biopsied over 10 years between January 1995 to December 2005 in King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia were reviewed by 2 histopathologists with the assistance of a nephrologist. RESULTS: The predominant histological type was WHO class IV. Patients of this class were more commonly associated with microhematuria, elevated proteinuria, and renal insufficiency. Active and chronic lesions were more likely to occur in patients of class III/IV. These patients were also more likely to have evidence of clinical renal disease than patients in class II. There was a significant association between nephrotic syndrome and class V lupus nephritis. CONCLUSION: Although the clinical and pathological correlation demonstrated a significant relationship between underlying histopathology and the clinical course of the patient, however, the biopsy findings did not uniformly correlate with the clinical features. Moreover, the status prediction of lupus nephritis patients based on clinical information alone was significantly enhanced by information obtained from renal biopsy.     

The Heartfile Lodhran CVD prevention project--end of project evaluation

Mainstream preventive interventions often fail to reach poor populations with a high risk of cardiovascular diseases (CVDs) in Pakistan. A community-based CVD primary prevention project aimed at developing approaches to reduce risk factors in such populations was established by Heartfile in collaboration with the National Rural Support Program in the district of Lodhran. The project implemented a range of activities integrated with existing social and health service mechanisms during a three year intervention period 2000/01-03/04. These were targeted in 4 key settings: community health education, mass media interventions, training of health professionals and health education through Lady Health Workers. The project received support from the Department for International Development, U.K. At the community level, a pre-test-post-test quasi-experimental design was used for examining project outcomes related to the community component of the intervention. Pre and post-intervention (training) evaluations were conducted involving all health care providers in randomly selected workshops in order to determine baseline levels of knowledge and the impact of training on knowledge level. In order to assess practices of physician and non-physician health care providers patient interviews, with control comparisons were conducted at each health care facility. Significant positive changes were observed in knowledge levels at a community level in the district of intervention compared with baseline knowledge levels particularly in relation to a heart healthy diet, beneficial level of physical activity, the causes of high blood pressure and heart attack and the effects of high blood pressure and active and passive smoking on health. Significant changes in behaviors at a practice level were not shown in the district of intervention. However the project played a critical role in spurring national action for the prevention and control of non-communicable diseases and introducing sustainable public health interventions for poor communities in Pakistan.     

Inactivation of endothelial derived relaxing factor by oxidized lipoproteins.

Endothelial cell derived relaxing factor (EDRF) mediated relaxation of blood vessels is impaired in vessels exposed to lipoproteins in vitro and in arteries of hyperlipidemic humans and animals. To investigate the mechanism by which lipoproteins impair the effects of EDRF, which is likely nitric oxide (NO) or a related molecule, we have bioassayed EDRF/NO activity by measuring its ability to increase cGMP accumulation in rat fetal lung cultured fibroblasts (RFL-6 cells). Low density lipoprotein modified by oxidation (ox-LDL) induced a concentration-dependent inhibition of EDRF activity that had been released from bovine aortic endothelial cells (BAEC) stimulated with bradykinin or the calcium ionophore A23187. In addition, lipoproteins directly impaired authentic NO-induced stimulation of cGMP accumulation in the detector cells; stimulation by sodium nitroprusside was unaffected. Ox-LDL or oxidized HDL3 were highly potent in blocking NO-stimulated cGMP accumulation with EC50's of approximately 1 microgram/ml. Lipid extracted from ox-LDL blocked NO-stimulated cGMP accumulation to about the same extent as intact ox-LDL, while the protein component of ox-LDL did not inhibit the cGMP response. These results suggest that the lipid component of oxidized lipoproteins inactivate EDRF after its release from endothelial cells.     

High dietary fructose induces a hepatic stress response resulting in cholesterol and lipid dysregulation

High-fructose feeding causes diet-induced alterations of lipid metabolism and decreased insulin sensitivity with alterations of hepatic pyruvate dehydrogenase and hepatic very low-density lipoprotein secretion. Inflammatory cytokines also induce dramatic changes in lipid metabolism, particularly in serum triglycerides via increased hepatic secretion and/or delayed clearance of very low-density lipoprotein. The aim of this study was to determine whether the mechanism of lipid dysregulation in the high-fructose diet is induced by stress response pathways. Animals were fed a high-fructose diet for 14 d to establish hypertriglyceridemia and then were treated with lipoxygenase inhibitors for 4 d concurrent with the diet. At the end of drug treatment, the animals were divided into two groups and treated with lipopolysaccharide or a vehicle. Serum samples were taken pretreatment and posttreatment, and liver tissue was harvested at the end of study. Serum samples were tested for metabolic parameters, and the tissue samples were tested for metabolic and stress pathway responses. Our results show that fructose-fed rats have changes in the c-Jun N-terminal kinase pathway with correspondingly elevated activator protein-1 activity, consistent with an inflammatory response. Treatment with lipoxygenase inhibitors reversed the hypertriglyceridemia and also reduced activator protein-1 activation, suggesting that the basis for lipid dysregulation in this model is due to activation of inflammatory pathways in the liver.     

Gonadal effects on plasma ACE activity in mice

Angiotensin-converting enzyme (ACE) regulates blood pressure and is an important target in the management of hypertension. Hypertension is a gender biased disease. Plasma ACE activity is significantly higher in male mice (309 U/l) than female mice (237 U/l) and is reduced significantly upon gonadectomy to 224 and 209 U/l, respectively. Although, the gonads influence plasma ACE activity in both male and female mice, the effect is more pronounced in male mice. Plasma ACE is derived from the cleavage of tissue ACE and lung has the highest concentration of tissue ACE. However, lung ACE activity is not gender dimorphic but increases significantly upon gonadectomy in both male and female. ACE mRNA level in the lung is not influenced by gender or gondaectomy. Therefore, the gonads affect plasma ACE activity by influencing cleavage of tissue ACE to plasma ACE and/or decrease stability of plasma ACE in gonadectomized mice is mediated.