Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancy

Obesity increases preeclampsia risk. Adipose tissue inflammation may contribute to the clinical syndrome of pre-eclampsia. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in pre-eclampsia and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and preeclampsia (n=13) mothers. Basal and lipopolysaccharide stimulated adipocyte TNFα, IL-6, CCL-2 and CRP release was measured. Adipose tissue cell densities of activated (cfms(+)) and total (CD68(+)) macrophages were determined. In pre-eclampsia only, visceral adipose tissue TNFα release was increased after lipopolysaccharide stimulation (57 [76] vs 81 [97] pg/mL/ug DNA, p=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r=-0.61, p=0.030) in pre-eclampsia. Visceral adipocyte IL-6 release was increased after lipopolysaccharide stimulation in pre-eclampsia only (566 [696] vs 852 [914] pg/mL/ugDNA, p=0.019). Visceral adipocyte CCL-2 basal (67 [61] vs 187 [219] pg/mL/ugDNA, p=0.049) and stimulated (46 [46] vs 224 [271] pg/mL/ugDNA, p=0.003) release was greater than in subcutaneous adipocytes in pre-eclampsia only. In pre-eclampsia, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13-4.14] vs 0.8 [0.00-1.27] TNF / PPIA ratio, p=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] vs 51.0[29.9] CSF1R/PPIA ratio, p=0.011) and activated (cfms+) macrophage count (6.7[2.6] vs 15.2[8.8] % cfms+/adipocyte, p=0.031) were higher in pre-eclampsia than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in pre-eclampsia. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with pre-eclampsia

Sirtuins 1–7 expression in human adipose-derived stem cells from subcutaneous and visceral fat depots: influence of obesity and hypoxia

The sirtuin family comprises seven NAD+-dependent deacetylases which control the overall health of organisms through the regulation of pleiotropic metabolic pathways. Sirtuins are important modulators of adipose tissue metabolism and their expression is higher in lean than obese subjects. At present, the role of sirtuins in adipose-derived stem cells has not been investigated yet. Therefore, in this study, we evaluated the expression of the complete panel of sirtuins in adipose-derived stem cells isolated from both subcutaneous and visceral fat of non-obese and obese subjects. We aimed at investigating the influence of obesity on sirtuins' levels, their role in obesity-associated inflammation, and the relationship with the peroxisome proliferator-activated receptor delta, which also plays functions in adipose tissue metabolism. The mRNA levels in the four types of adipose-derived stem cells were evaluated by quantitative polymerase chain reaction, in untreated cells and also after 8 h of hypoxia exposure. Correlations among sirtuins' expression and clinical and molecular parameters were also analyzed. We found that sirtuin1-6 exhibited significant higher mRNA expression in visceral adipose-derived stem cells compared to subcutaneous adipose-derived stem cells of non-obese subjects. Sirtuin1-6 levels were markedly reduced in visceral adipose-derived stem cells of obese patients. Sirtuins' expression in visceral adipose-derived stem cells correlated negatively with body mass index and C-reactive protein and positively with peroxisome proliferator-activated receptor delta. Finally, only in the visceral adipose-derived stem cells of obese patients hypoxia-induced mRNA expression of all of the sirtuins. Our results highlight that sirtuins' levels in adipose-derived stem cells are consistent with protective effects against visceral obesity and inflammation, and suggest a transcriptional mechanism through which acute hypoxia up-regulates sirtuins in the visceral adipose-derived stem cells of obese patients

The Sex and Race Specific Relationship between Anthropometry and Body Fat Composition Determined from Computed Tomography: Evidence from the Multi-Ethnic Study of Atherosclerosis.

BackgroundFew studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race.MethodsCT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity.ResultsParticipants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity.ConclusionThe relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used

Leishmaniasis: new approaches to disease control.

The leishmaniases afflict the world's poorest populations. Among the two million new cases each year in the 88 countries where the disease is endemic (fig 1), it is estimated that 80% earn less than $2 a day. Human infections with Leishmania protozoan parasites, transmitted via the bite of a sandfly, cause visceral, cutaneous, or mucocutaneous leishmaniasis. The global burden of leishmaniasis has remained stable for some years, causing 2.4 million disability adjusted life years (DALYs) lost and 59 000 deaths in 2001. Neglected by researchers and funding agencies, leishmaniasis control strategies have varied little for decades, but in recent years there have been exciting advances in diagnosis, treatment, and prevention. These include an immunochromatographic dipstick for diagnosing visceral leishmaniasis; the licensing of miltefosine, the first oral drug for visceral leishmaniasis; and evidence that the incidence of zoonotic visceral leishmaniasis in children can be reduced by providing dogs with deltamethrin collars. There is also hope that the first leishmaniasis vaccine will become available within a decade. Here we review these developments and identify priorities for research

Seroepidemiology of Visceral Leishmaniasis In Ardabil Province During 2002-2011

Background & Objectives: Visceral leishmaniasis is caused by a protozoan called Leishmania, that is a fatal disease for human. In Iran, this disease is caused by Leishmania infantum and occurres in early ages. Ardabil province is a known endemic region for Visceral leishmaniasis in the world. Methods: This retrospective study has been done based on information of 8306 suspected cases available on the health center from 2002 to 2011. Results: A total of 278 (3.35%) direct agglutination tests were positive in Ardabil, Meshkinshahr and Germi districts. The most infections were seen in Meshkinshahr and the least obtained in Ardabil district. Data analysis showed almost regular decrease in prevalence of human visceral leishmaniasis in the last decade in Meshkinshahr district where is considered as the main focus of the disease. In 2011, the incidence of human visceral leishmaniasis in Germi was completely similar to Meshkinshahr district. Conclusion: The health proceedings for visceral leishmaniasis control showed to be successful in Ardabil province especially in Meshkinshahr district during past 10 years. Regarding to the susceptibility of neighboring regions of endemic foci and also the possibility of disease transmission from asymptomatic dogs, it is necessary to educate people to avoid displacement of ownership dogs and continue diagnosis and control proceedings on dogs. Keywords: Visceral Leishmaniasis; Seroepidemiology; Ardabi

Advances in leishmaniasis.

Governed by parasite and host factors and immunoinflammatory responses, the clinical spectrum of leishmaniasis encompasses subclinical (inapparent), localised (skin lesions), and disseminated infection (cutaneous, mucosal, or visceral). Symptomatic disease is subacute or chronic and diverse in presentation and outcome. Clinical characteristics vary further by endemic region. Despite T-cell-dependent immune responses, which produce asymptomatic and self-healing infection, or appropriate treatment, intracellular infection is probably life-long since targeted cells (tissue macrophages) allow residual parasites to persist. There is an epidemic of cutaneous leishmaniasis in Afghanistan and Pakistan and of visceral infection in India and Sudan. Diagnosis relies on visualising parasites in tissue or serology; culture and detection of parasite DNA are useful in the laboratory. Pentavalent antimony is the conventional treatment; however, resistance of visceral infection in India has spawned new treatment approaches--amphotericin B and its lipid formulations, injectable paromomycin, and oral miltefosine. Despite tangible advances in diagnosis, treatment, and basic scientific research, leishmaniasis is embedded in poverty and neglected. Current obstacles to realistic prevention and proper management include inadequate vector (sandfly) control, no vaccine, and insufficient access to or impetus for developing affordable new drugs

Declining Visceral Leishmaniasis in Malta

Aims: To study visceral leishmaniasis (VL) trends in Malta. Methods: Analysis of epidemiological and clinical trends, a veterinary questionnaire and questioning a canine laboratory testing facility. Results: A decline in VL in the past 25 years (1980-2005) was noted for both paediatric (p<0.001) and adult (p=0.002) populations. No seasonal variation in infection rates was found. Serological testing was reliable and a useful adjunct to bone marrow diagnosis. Treatment with sodium stibogluconate was highly effective and there were no permanent sequelae associated with disease or treatment. Vets are encountering less canine VL with no differences in localities Discussion: The decline in VL was paralleled by a decline in the stray canine reservoir population and by better management of canine infection in both sanctuaries and in domestic settings.peer-reviewe

Purinergic mechanosensory transduction and visceral pain

In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X(3) and P2X(2/3) receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown