The metabolic syndrome--new and old data.

Initially called the "X Syndrome" by Reaven, then the "Killer Quartet" by Kaplan, the MS prevalence has dramatically increased in the past decades. The first criteria elaborated by WHO in 1998, and afterwards reformulated in 1999, were conceived by diabetologists as a working instrument for clinical practice and they shall consequently be updated in accordance with the new acquisitions in this field. MS expresses the complex disorder of the organism energetic metabolism, having as central element insulin resistance and compensatory hyperinsulinism, associated with the presence of some risk factors involved in the etiology and/or physiology of atherosclerosis.

Correlations between abdominal circumference and the breakage resistance of the fibrin clot in patients with diabetes mellitus type 2.

Unlabelled: Diabetes mellitus (DM) is considered a prothrombotic, proatherogenic state, characterized by chronic activation of platelets, exaggerated activation of coagulation factors and decreased fibrinolytic mechanisms. Haemostasis is additionally altered by increased plasmatic lipids and obesity. DM therefore represents a major risk factor for the onset and development of coronary disease or ischemic stroke.

Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.

The quantitative analysis of Plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. As a consequence, this important phase of the parasite's life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic P.

Phosphothioate oligodeoxynucleotides inhibit Plasmodium sporozoite gliding motility.

Plasmodium sporozoites, transmitted to the mammalian host through a mosquito bite, travel to the liver, where they invade hepatocytes, and develop into a form that is then able to infect red blood cells. In spite of the importance of innate immunity in controlling microbial infections, almost nothing is known about its role during the liver stage of a malaria infection. Here, we tested whether synthetic CpG phosphothioate (PS) oligodeoxynucleotides (ODNs), which bind to Toll-like receptor 9 (Tlr9), could have a protective effect on Plasmodium berghei infection in hepatocytes.

The implication of CNR1 gene's polymorphisms in the modulation of endocannabinoid system effects.

The endocannabinoid system (ECS) represents one of the most important physiologic systems involved in organism homeostasis, having various implications upon individual behavior and metabolic phenotype. It is composed of cannabinoid receptors CB1 and CB2, and their genes (CNR1 and CNR2), their endogenous ligands and the enzymes which mediate endogenous ligands' biosynthesis and degradation. Anandamide and 2-arachidonoylglycerol are two endogenous agonists of the cannabinoid receptors.

Imidazoquines as antimalarial and antipneumocystis agents.

Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria from mouse to mosquito and be highly stable toward hydrolysis at physiological conditions.

Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events.

Background: Plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step of malaria infection, the requirements of Plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.

Results: To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of P.

Plasmodium berghei-infection induces volume-regulated anion channel-like activity in human hepatoma cells.

Parasite infection can lead to alterations in the permeability of host plasma membranes. Presented here is the first demonstration that this phenomenon occurs in Plasmodium-infected liver cells. Using the whole-cell patch-clamp technique, volume-regulated anion channel (VRAC) activity was characterized in Huh-7 cells (a human hepatoma cell line) before and after infection with Plasmodium berghei.

A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.

The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes.

Behavioral and hormonal response of common marmosets, Callithrix jacchus, to two environmental conditions.

Captive animals of several species change their behavioral pattern and hormonal profile in response to physical (for example, cage size and temperature) and social (for example, group size and social isolation) modification of their environment. To evaluate the effect of environmental change in captivity, the affiliative (contact/proximity and allogrooming) and individual (approach, leaving, scent mark, locomotion, and autogrooming) behavior of five family groups of common marmosets, Callithrix jacchus, were recorded on weekdays (non-quiet) and at the weekend (quiet) for two months. In addition, fecal samples were collected for four of these groups to measure their cortisol levels under both conditions.

Risk factors for diabetic nephropathy: intrinsic or extrinsic renal?

Diabetic nephropathy (DN) is the result of numerous risk factors, such as hyperglycaemia, several genetic polymorphisms, offering susceptibility or individual resistance to DN. There are numerous, well-studied risk factors for DN, the majority being renal extrinsic, but there have been identified and studied renal intrinsic factors (the number of glomeruli, the volume of glomeruli) which can be structural determinants of the risk for the development of DN and may be precocious markers of DN. The clarification of the role of genetic factors in the pathogeny of DN may contribute to the evaluation of DN risk, allowing the selection of patients eligible to new precocious therapies (primary prevention) and the prevention of ESRD (secondary prevention).

The assessment of subclinic atherosclerosis objected through IMT in normal and dyslipidemic patients with various degrees of glucose tolerance.

Aim: The evaluation of atherosclerosis, by the measurement of intima media thickness (IMT) at the level of right common carotid arteries (CCA Right) and left (CCA Left), for normolipidemic patients (NL) and dislipidemic patients (DLP) with various degrees of alteration to glucose tolerance. DESIGN AND METHODS OF RESEARCH: We have analyzed a group of 120 NL patients and a group of 120 DLP patients. The test of orally provoked hyperglycemia was performed to assess the disturbance of tolerance to glucose.

Dyslipidemia and hypertension in patients with type 2 diabetes and retinopathy.

Aim: Type 2 diabetes is associated with dyslipidemia and higher cardiovascular risk and also generates multiple microvascular complications. Diabetic retinal changes, diabetic maculopathy and proliferative retinopathy are major causes of vision loss among the people of working age worldwide. We searched the association between diabetic retinopathy (as one of the most important long time microvascular complications in diabetes), lipids disorder and blood pressure in subjects with T2DM without known cardiovascular diseases.

The thyroid and autoimmunity.

Autoimmune thyroid diseases (Hashimoto thyroiditis, Graves' disease, postpartum thyroiditis, atrophic thyroiditis and drug induced thyroiditis) are prevalent disorders worldwide, especially in women (related to the millieu of sex steroids and X chromosome effects on the thyroid and the immune system). Disruption of thyroid self tolerance, usually induced by an infection, generates abnormal thyroid--immune interactions, implicating an array of cytokines and their receptors. Thyrocytes achieve antigen presenting cell properties which stimulate effector immune cells (Th1, Th2, Th17), in the context of defective immunomodulatory T regulatory cells, resulting in thyroid lymphocytic infiltration and activation of B cells, with production of antibodies against thyroid antigens, thyroid destruction or stimulation, depending on the Th1-Th2 balance.

Unlike the synchronous Plasmodium falciparum and P. chabaudi infection, the P. berghei and P. yoelii asynchronous infections are not affected by melatonin.

We have previously reported that Plasmodium chabaudi and P. falciparum sense the hormone melatonin and this could be responsible for the synchrony of malaria infection. In P.

Kinome-wide RNAi screen implicates at least 5 host hepatocyte kinases in Plasmodium sporozoite infection.

Plasmodium sporozoites, the causative agent of malaria, are injected into their vertebrate host through the bite of an infected Anopheles mosquito, homing to the liver where they invade hepatocytes to proliferate and develop into merozoites that, upon reaching the bloodstream, give rise to the clinical phase of infection. To investigate how host cell signal transduction pathways affect hepatocyte infection, we used RNAi to systematically test the entire kinome and associated genes in human Huh7 hepatoma cells for their potential roles during infection by P. berghei sporozoites.

Cerebral malaria and the hemolysis/methemoglobin/heme hypothesis: shedding new light on an old disease.

Malaria causes more than 1 million deaths every year with cerebral malaria (CM) being a major cause of death in Sub-Saharan African children. The nature of the malaria-associated pathogenesis is complex and multi-factorial. A unified hypothesis involving sequestration of infected red blood cells, systemic host inflammatory response and hemostasis dysfunction has been proposed to explain the genesis of CM.

Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection.

An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I scavenger receptor (SR-BI) is the strongest regulator of Plasmodium infection among these factors. Inhibition of SR-BI function reduced P.

Interactions of the malaria parasite and its mammalian host.

A hallmark of Plasmodium development inside its mammalian victim is the remarkable restriction to the host species. Adaptation to an intracellular life style in specific target cells is determined by multiple parasite-host interactions. The first line of crosstalk occurs during intradermal sporozoite injection by an Anopheles mosquito.

Genistein-supplemented diet decreases malaria liver infection in mice and constitutes a potential prophylactic strategy.

In tropical regions millions of people still live at risk of malaria infection. Indeed the emergence of resistance to chloroquine and other drugs in use in these areas reinforces the need to implement alternative prophylactic strategies. Genistein is a naturally occurring compound that is widely used as a food supplement and is thought to be effective in countering several pathologies.

Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection.

The clinically silent Plasmodium liver stage is an obligatory step in the establishment of malaria infection and disease. We report here that expression of heme oxygenase-1 (HO-1, encoded by Hmox1) is upregulated in the liver following infection by Plasmodium berghei and Plasmodium yoelii sporozoites. HO-1 overexpression in the liver leads to a proportional increase in parasite liver load, and treatment of mice with carbon monoxide and with biliverdin, each an enzymatic product of HO-1, also increases parasite liver load.

Adenylyl cyclase alpha and cAMP signaling mediate Plasmodium sporozoite apical regulated exocytosis and hepatocyte infection.

Malaria starts with the infection of the liver of the host by Plasmodium sporozoites, the parasite form transmitted by infected mosquitoes. Sporozoites migrate through several hepatocytes by breaching their plasma membranes before finally infecting one with the formation of an internalization vacuole. Migration through host cells induces apical regulated exocytosis in sporozoites.

Malaria liver stage susceptibility locus identified on mouse chromosome 17 by congenic mapping.

Host genetic variants are known to confer resistance to Plasmodium blood stage infection and to control malaria severity both in humans and mice. This work describes the genetic mapping of a locus for resistance to liver stage parasite in the mouse. First, we show that decreased susceptibility to the liver stage of Plasmodium berghei in the BALB/c mouse strain is attributable to intra-hepatic factors and impacts on the initial phase of blood stage infection.