Role of testosterone in prevention of Alzheimer\u27s Disease

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Presence of atrial natriuretic factor prohormone in enterochromaffin cells of the human large intestine

Atrial natriuretic factor is a hormone intimately involved in water and salt homeostasis. The heart constitutes the major but not exclusive site of synthesis of this hormone. Among other functions, the gastrointestinal tract has endocrine functions, plays an important role in volume regulation of the body, and seems to be a target organ for atrial natriuretic factor. Therefore, the presence of atrial natriuretic factor was investigated in the human gut. Immunoreactive atrial natriuretic factor was found in intraoperatively obtained samples of normal human colon. Acidic extracts of human large intestine contained about 0.4 pmol/g wet wt of atrial natriuretic factor. Analysis of atrial natriuretic factor immunoreactivity by gel-filtration and reverse-phase high-performance liquid chromatography showed that about 65% of the immunoreactivity corresponded to the atrial natriuretic factor phohormone and about 35% corresponded to the C-terminal ANF99-126. Immunohistochemistry showed atrial natriuretic factor prohormone location in enterochromaffin cells of the colon mucosa. Altogether, these findings show the presence of atrial natriuretic factor prohormone in enterochromaffin cells of the human large intestine and may suggest this organ as a site of atrial natriuretic factor synthesis in humans

Kinetics of the disappearance of lipoprotein cholesteryl esters in pigs as affected by dietary fat

Forty crossbred, castrated male pigs were fed diets containing primarily beef tallow (T) or soy oil (S) at 20% or 40% of energy as fat in a 2 x 2 factorial design. During week 6, pigs were fitted with femoral arterial, common bile duct, and duodenal catheters. After week 8, pigs were injected with autologous low-density lipoprotein (LDL) containing [superscript]3H-cholesteryl esters and high-density lipoprotein (HDL) containing [superscript]14C-cholesteryl esters. Blood and bile were collected for 48 hours. Disappearance of the labeled cholesteryl esters fit a biexponential function, and the parameters of the function were described by compartmental analysis. Pigs fed T diets had greater concentrations of cholesterol in Longissimus dorsi and a greater percentage of total lipid in liver than did pigs fed S diets. Pigs fed T diets had greater percentages of palmitic, palmitoleic, and oleic acids and lesser percentages of stearic, linoleic, and linolenic acids in bile. Pigs fed S diets had a greater retention of cholesterol derived from LDL-cholesteryl esters (LDL-CE) in L. dorsi and a greater appearance of cholesterol from HDL-cholesteryl esters (HDL-CE) as biliary cholesterol. Twelve hour fasted HDL-CE concentrations were greater in pigs fed T diets. After a meal, the HDL-Ce concentrations in pigs fed T diets decreased to concentrations similar to those in pigs fed S diets. Pigs fed diets containing 40% of energy as fat (40%) had greater LDL-CE production rates and fractional catabolic rates than did pigs fed diets containing 20% of energy as fat (20%). In the L. dorsi the percentage of cholesterol derived from LDL-CE was greater in pigs fed the 40% diets. The percentage of cholesterol derived from HDL-CE was greater in livers of pigs fed 20% diets, whereas pigs fed 40% diets secreted more HDL- and LDL-CE as biliary cholesterol, had greater bile flows, and secreted more biliary cholesterol. In summary, dietary fats affected LDL- but not HDL-lipoprotein kinetics. Clearance of cholesterol into bile and storage of cholesterol in tissues were increased by polyunsaturated fat and high fat diets, which is consistent with current theories on mechanisms of dietary fatty acid effects on cholesterol metabolism

Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect?

Data from basic science experiments is overwhelmingly supportive of the causal role of immune-inflammatory response(s) at the core of atherosclerosis, and therefore the theoretical potential to manipulate the inflammatory response to prevent cardiovascular events. However, extrapolation to humans requires care and we still lack definitive evidence to show that interfering in immune-inflammatory processes may safely lessen clinical atherosclerosis. In this review, we discuss key therapeutic targets in the treatment of vascular inflammation, placing basic research in to a wider clinical perspective, as well as identifying outstanding questions

Apolipoprotein D

Apolipoprotein D (ApoD) is an extracellular glycoprotein of the lipocalin protein family, involved in different functions such as immune response, cell proliferation regulation, chemoreception, retinoid metabolism, axon growth, and proteolysis regulation. This lipocalin is expressed predominantly in the nervous system (NS), both prenatally (vascular pericytes) and postnatally (glia and neurons) and in adulthood. It is also expressed in other tissues and is carried by high-density lipoprotein (HDL) in plasma, so it could interfere in cholesterol and other lipids regulation. ApoD increases considerably in systemic apocrine gland tumors and also in some primary brain tumors. Although the specific biological role of ApoD is unknown, the presence of ApoD in tumors appears to be a prognostic factor in their evolution. Regarding the NS, increased ApoD expression observed in many neurodegenerative diseases could be used to make an early diagnosis thereof

Models to study atherosclerosis: a mechanistic insight

The recent failure of candidate drugs like cholesterol ester transfer protein (CETP) and acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors calls for a revised approach for screening anti-atherosclerotic drugs and development of new models of atherosclerosis. For this it is important to understand the mechanism of the disease in a particular model. Models simultaneously showing hyperlipidemia, inflammation and associated complications of diabetes and hypertension will serve the purpose better as they mimic the actual clinical condition. Besides this, analyzing candidate molecules in vivo, in vitro and at various levels of atherosclerosis progression is important. Models based on various cells and process involved in atherosclerosis should be used for screening candidate molecules. The challenge lies in bridging the gap between genetically friendly small animal and human-like bigger animal models. Sequencing of the mouse and human genome, development of a single nucleotide polymorphism (SNP) database and in silico quantitative trait loci (QTL) linkage analysis may enhance the understanding of atherosclerosis and help develop new therapeutic targets

Identification of novel subgroup a variants with enhanced receptor binding and replicative capacity in primary isolates of anaemogenic strains of feline leukaemia virus

<b>BACKGROUND:</b> The development of anaemia in feline leukaemia virus (FeLV)-infected cats is associated with the emergence of a novel viral subgroup, FeLV-C. FeLV-C arises from the subgroup that is transmitted, FeLV-A, through alterations in the amino acid sequence of the receptor binding domain (RBD) of the envelope glycoprotein that result in a shift in the receptor usage and the cell tropism of the virus. The factors that influence the transition from subgroup A to subgroup C remain unclear, one possibility is that a selective pressure in the host drives the acquisition of mutations in the RBD, creating A/C intermediates with enhanced abilities to interact with the FeLV-C receptor, FLVCR. In order to understand further the emergence of FeLV-C in the infected cat, we examined primary isolates of FeLV-C for evidence of FeLV-A variants that bore mutations consistent with a gradual evolution from FeLV-A to FeLV-C.<p></p> <b>RESULTS:</b> Within each isolate of FeLV-C, we identified variants that were ostensibly subgroup A by nucleic acid sequence comparisons, but which bore mutations in the RBD. One such mutation, N91D, was present in multiple isolates and when engineered into a molecular clone of the prototypic FeLV-A (Glasgow-1), enhanced replication was noted in feline cells. Expression of the N91D Env on murine leukaemia virus (MLV) pseudotypes enhanced viral entry mediated by the FeLV-A receptor THTR1 while soluble FeLV-A Env bearing the N91D mutation bound more efficiently to mouse or guinea pig cells bearing the FeLV-A and -C receptors. Long-term in vitro culture of variants bearing the N91D substitution in the presence of anti-FeLV gp70 antibodies did not result in the emergence of FeLV-C variants, suggesting that additional selective pressures in the infected cat may drive the subsequent evolution from subgroup A to subgroup C.<p></p> <b>CONCLUSIONS:</b> Our data support a model in which variants of FeLV-A, bearing subtle differences in the RBD of Env, may be predisposed towards enhanced replication in vivo and subsequent conversion to FeLV-C. The selection pressures in vivo that drive the emergence of FeLV-C in a proportion of infected cats remain to be established