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.     

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.     

Differential secretion of proteins and glycoproteins by livers of immature and adult rats. Effect of antimicrotubule drugs

This study was initiated to re-examine reported differences in the action of antimicrotubule agents on plasma protein secretion from livers of immature versus adult rats. The aim was (1) to determine the composition and to monitor the secretion of various plasma proteins and glycoproteins from liver slices labeled in vitro with specific amino acids and sugar residues, and (2) to correlate observed differences in secretion of these proteins with structural changes in the hepatocytes of the different aged animals. For the most part, slices of liver from fetal (term), neonatal (4- to 5 days old), and adult rats (70 days old) were incubated with radioactive amino acids or various tritiated sugars specific for N-linked core oligosaccharide and/or N-linked terminal oligosaccharide chains. Our findings indicate that liver slices of fetal and neonatal rats are efficient in synthesizing plasma proteins including fully glycosylated glycoproteins. The secretion of glycosylated and nonglycosylated proteins believed to be processed through Golgi complexes was inhibited to the same extent (approximately 70-80%) by antimicrotubule agents, regardless of the age of the host animal. However, other proteins and glycoproteins secreted by livers of immature rats were found to be relatively insensitive (i.e. inhibited to only 30-40%) to the action of various antimicrotubule drugs. The glycoproteins were found to lack N-linked terminal sugars (although the glycoproteins did contain N-linked core sugars), and it is likely that the drug-insensitive proteins bypassed critical glycosylating sites in the Golgi compartment prior to release. Overall, these findings support earlier data showing that antimicrotubule drugs have a special impact on Golgi-associated events in liver cells. To what extent these findings are related to the action of microtubules remains to be seen.     

Nutrition and cardiac cachexia

PURPOSE OF REVIEW: Congestive heart failure is a leading cause of morbidity and mortality, especially in older persons. In advanced stages of the disease, congestive heart failure can be associated with serious complications such as cardiac cachexia (defined here as weight loss of more than 6% in 6 months). This review will discuss recent insights into the pathophysiology, anthropometric predictors and potential management of cardiac cachexia. RECENT FINDINGS: Cardiac cachexia and the associated progressive weight loss are sometimes overlooked by care providers. A delay in diagnosis often results in further loss of vital tissues, progressive weakness, fall-related injuries and potentially long-term care institutionalization and/or death. Emerging data suggest that congestive heart failure is a dynamic disorder of many organ systems, including the myocardial, neurohormonal, immune, vascular, gastrointestinal, renal and musculoskeletal systems. It is becoming more widely appreciated that it is the deterioration of this interactive multisystem complex that results in the systemic inflammation and progressive wasting and atrophy of muscle and other organ tissues, which is the hallmark of cardiac cachexia. SUMMARY: Cardiac cachexia in congestive heart failure patients may be associated with a low level of physical activity. A high systemic inflammatory state is another marker of cardiac cachexia. Prudent anti-inflammatory nutrition, dietary supplements and exercise can serve to ameliorate and/or potentially prevent progressive wasting. A better understanding of factors contributing to the development of cardiac cachexia will enable us to design preventive strategies and provide improved care for individuals with this debilitating condition.     

Process, rationale, and interventions of Pakistan's National Action Plan on Chronic Diseases

Most developing countries do not comprehensively address chronic diseases as part of their health agendas because of lack of resources, limited capacity within the health system, and the threat that the institution of national-level programs will weaken local health systems and compete with other health issues. An integrated partnership-based approach, however, could obviate some of these obstacles. In Pakistan, a tripartite public-private partnership was developed among the Ministry of Health, the nongovernmental organization (NGO) Heartfile, and World Health Organization. This was the first time an NGO participated in a national health program; NGOs typically assume a contractual role. The partnership developed a national integrated plan for health promotion and the prevention and control of noncommunicable diseases (NCDs), which as of January 2006 is in the first stage of implementation. This plan, called the National Action Plan on NCD Prevention, Control, and Health Promotion (NAP-NCD), was released on May 12, 2004, and attempts to obviate the challenges associated with addressing chronic diseases in countries with limited resources. By developing an integrated approach to chronic diseases at several levels, capitalizing on the strengths of partnerships, building on existing efforts, and focusing primary health care on chronic disease prevention, the NAP-NCD aims to mitigate the effects of national-level programs on local resources. The impact of the NAP-NCD on population outcomes can only be assessed over time. However, this article details the plan's process, its perceived merits, and its limitations in addition to discussing challenges with its implementation, highlighting the value of such partnerships in facilitating the missions and mandates of participating agencies, and suggesting options for generalizability.     

Multiple emulsions: an overview

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.