Introduction and Differential Diagnosis of Monkeypox in Argentina, 2022.

We report detection of cases of monkeypox virus infection in Argentina in the context of a marked increase in confounding cases of atypical hand-foot-and-mouth syndrome caused by enterovirus coxsackie A6. We recommend performing an accurate differential virological diagnosis for exanthematous disease in suspected monkeypox cases.

Vitamin D status during pregnancy and offspring outcomes: a systematic review and meta-analysis of observational studies.

BACKGROUND/OBJECTIVES: Vitamin D deficiency during pregnancy may influence adverse outcomes in offspring. The aim of this systematic review and meta-analysis of observational studies was to assess the association between low prenatal concentrations of 25(OH)D (by using three different cut-off levels), preterm birth (PTB) and anthropometric and neurodevelopmental outcomes in offspring. SUBJECTS/METHODS: Studies reporting data on the association between maternal vitamin D concentrations and offspring outcomes identified through a systematic review of scientific literature published in PubMed/MEDLINE, Scopus and the Cochrane Library databases up to April 2017. RESULTS: We included 54 eligible studies. Vitamin D-deficient mothers (<30 nmol/L) had offspring with lower birthweight (MD -87.82 g; 95% CI -119.73, -55.91 g), head circumference (MD -0.19 cm; 95% CI -0.32, -0.06 cm) and a higher risk of small for gestational age (SGA) infants and PTB (OR 1.59; 95% CI 1.24, 2.03) compared to mothers with concentrations ≥30 nmol/L. Vitamin D insufficiency (<50 nmol/L) was associated with a higher risk of SGA and PTB (OR 1.43; 95% CI 1.08, 1.91 and OR 1.28; 95% CI 1.08, 1.52, respectively). Concentrations of 25(OH)D ≥75 nmol/L were not found to be associated with birthweight, SGA or PTB. Offspring of vitamin D-insufficient mothers had lower scores in mental (MD -1.12 points; 95% CI -1.82, -0.42 cm) and language developmental tests (MD -0.35 points; 95% CI -1.00, 0.31 cm). CONCLUSION: Maternal vitamin D deficiency is associated with offspring adverse anthropometric outcomes and PTB; insufficiency with a higher risk of SGA, PTB and adverse neurodevelopmental outcomes.

Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study.

Early iron status plays an important role in prenatal neurodevelopment. Iron deficiency and high iron status have been related to alterations in child cognitive development; however, there are no data about iron intake during pregnancy with other environmental factors in relation to long term cognitive functioning of children. The aim of this study is to assess the relationship between maternal iron status and iron intake during pregnancy and child neuropsychological outcomes at 7 years of age. We used data from the INMA Cohort population-based study. Iron status during pregnancy was assessed according to serum ferritin levels, and iron intake was assessed with food frequency questionnaires. Working memory, attention, and executive function were assessed in children at 7 years old with the N-Back task, Attention Network Task, and the Trail Making Test, respectively. The results show that, after controlling for potential confounders, normal maternal serum ferritin levels (from 12 mg/L to 60 mg/L) and iron intake (from 14.5 mg/day to 30.0 mg/day), respectively, were related to better scores in working memory and executive functioning in offspring. Since these functions have been associated with better academic performance and adaptation to the environment, maintaining a good state of maternal iron from the beginning of pregnancy could be a valuable strategy for the community.

Vitamina D durante el embarazo y neurodesarrollo del niño: revisión sistemática / Vitamin D during pregnancy and neurodevelopment of the child: systematic review

El déficit de vitamina D durante el embarazo tiene un impacto negativo en la salud materno-infantil. OBJETIVO: Evaluar el efecto del estado de vitamina D durante el embarazo sobre el neurodesarrollo del niño. Selección de estudios: Se realizó una búsqueda de la literatura científica publicada en PubMed/MEDLINE, Scopus y Cochrane hasta enero del 2018. Se seleccionaron los estudios que relacionaban el estado de la vitamina D durante el embarazo con algún dominio del neurodesarrollo del niño (mental, motor, lenguaje, cociente intelectual y comportamiento). La calidad de los estudios incluidos se evaluó a través de la escala Newcastle-Ottawa. RESULTADOS: De los 164 estudios encontrados en la búsqueda, once estudios cumplieron los criterios y fueron considerados diez de alta calidad metodológica y uno de moderada. La revisión sistemática mostró que niveles prenatales de vitamina D <50 nmol/L se asocian frecuentemente a un peor desarrollo mental, motor y del lenguaje de sus hijos en comparación con las madres con concentraciones ≥ 50 nmol/L. CONCLUSIÓN: Aunque existe poca evidencia científica que corrobore la relación entre la deficiencia de vitamina D prenatal y su impacto en el neurodesarrollo de los hijos, los datos actuales sugieren un perjuicio sobre el desarrollo mental, motor y del lenguaje del niño

BACKGROUND: A deficiency of vitamin D during pregnancy has a negative impact on the health of the mother and the child. OBJECTIVE: To evaluate the effect of vitamin D status during pregnancy on the neurodevelopment of children. Selection of studies: We explored studies that linked the maternal status of vitamin D with neurodevelopment in the infant. The selected studies were identified through a systematic review of the scientific literature published in PubMed/MEDLINE, Scopus and Cochrane until January 2018. The quality of the included studies was carried out through the Newcastle-Ottawa scale. RESULTS: 164 studies were identified and reviewed for selection. At the end of this review, 11 studies were included, all of high methodological quality. This systematic review shows that prenatal vitamin D levels <50 nmol/L are associated with worse mental, motor and language development of their children compared with pregnant women with good vitamin D status. CONCLUSION: There is still little scientific evidence to corroborate the relationship between prenatal vitamin D deficiency and its impact on the neurodevelopment of children, although current data suggest a detrimental effect on the child's mental, motor and language development

Prevalence of Anemia in Children from Latin America and the Caribbean and Effectiveness of Nutritional Interventions: Systematic Review and Meta⁻Analysis.

Anemia affects 1.62 billion people worldwide. Latin America and the Caribbean (LAC) comprise several developing countries where children are a population at risk. This systematic review and meta-analysis aimed to estimate the prevalence of anemia in this population. Electronic databases, reference lists, and websites of health ministries were searched until December 2018. Stratified analyses were performed using RevMan5.3 to estimate the overall prevalence of anemia in preschool and school-age children. The effectiveness of nutritional interventions was also evaluated. We included 61 studies from the 917 reviewed, which included 128,311 preschool- and 38,028 school-age children from 21 LAC countries. The number of anemic children was 32.93% and 17.49%, respectively, demonstrating a significant difference according to age (p < 0.01). No difference was observed by gender and only school-age children from low/very low socioeconomic status (SES) (25.75%) were more prone to anemia than those from middle SES (7.90%). It was not a concern in the Southern Cone but constituted a serious public health problem in the Latin Caribbean. Nutritional interventions reduced the prevalence from 45% to 25% (p < 0.01). Anemia is still a public health problem for children in LAC countries. National surveys should include school-age children. Further nutritional interventions are required to control anemia.

Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants.

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7 ± 1.5 to 52.0 ± 1.5 ng/mL; p < 0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8 ± 1.5 vs 37.9 ± 1.3 ng/mL, p < 0.018, and 54.3 ± 1.5 vs 44.0 ± 1.4 ng/mL, p < 0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p = 0.046 and p = 0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.

Diversity of human herpesvirus 8 genotypes in patients with AIDS and non-AIDS associated Kaposi's sarcoma, Castleman's disease and primary effusion lymphoma in Argentina.

HHV-8 genotypes are distributed heterogeneously worldwide. The variable K1 gene and the conserved ORF26E region serve to genotype. The aim of the study was to characterize HHV-8 isolates from patients with AIDS, classical, and iatrogenic KS, primary effusion lymphoma and Castleman's disease and one organ donor from Argentina by analysis of ORFK1 and ORF26E regions. DNA was extracted from fresh or paraffin embedded biopsies, blood, and saliva samples and submitted to HHV-8 PCR. Phylogenetic analyses of ORFK1 showed that subtypes C (C1, C2, and C3), B1 and A (A1, A2, and A3) were present in 70.8%, 16.7%, and 12.5% of cases, respectively. Analyses of ORF26E fragment revealed that most strains (45.8%) were subtype A/C while the remaining fall into K, J, B2, R, and D subtypes. Linkage between ORFK1-ORF26E subtypes corresponded to reported relationships, except for one strain that clustered with B1 (K1 African) and D (ORF26E Asian-Pacific) subtypes. This research reveals predominance of subtype C, a broad spectrum of HHV-8 genotypes and reports the first isolation of the African B genotype in Argentina.

Hepcidin levels and gastric cancer risk in the EPIC-EurGast study.

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93-0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: -69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

Elevated iron status and risk of gestational diabetes mellitus: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis of observational studies was to assess the relationship between elevated iron status, measured as hemoglobin and ferritin levels, and the risk of gestational diabetes mellitus (GDM). The present study was recorded in PROSPERO (2013:CRD42013005717). The selected studies were identified through a systematic review of scientific literature published in The Cochrane Library and PubMed/MEDLINE databases from their inception until March 10, 2016, in addition to citation tracking and hand-searches. The search strategy of original articles combined several terms for hemoglobin, ferritin, pregnancy, and GDM. OR and 95% CI of the selected studies were used to identify associations between hemoglobin and/or ferritin levels with the risk of GDM. Summary estimates were calculated by combining inverse-variance using fixed-effects model. 2468 abstracts were initially found during the search. Of these, 11 with hemoglobin and/or ferritin data were selected for the meta-analyses. We observed that high hemoglobin (OR = 1.52; 95% CI: 1.23-1.88), as well as ferritin (OR = 2.09; 95% CI: 1.48-2.96) levels were linked to an increased risk of GDM. Low heterogeneity was observed in hemoglobin (I2  = 33.3%, P = 0.151) and ferritin (I2  = 0.7%, P = 0.418) meta-analyses, respectively. Publication bias was not appreciated. High hemoglobin or ferritin levels increase the risk of GDM by more than 50% and more than double, respectively, in the first and third trimester. Therefore, determining of hemoglobin or ferritin concentration in early pregnancy might be a useful tool for recognizing pregnant women at risk of GDM.

Increased iron levels and lipid peroxidation in a Mediterranean population of Spain.

BACKGROUND: Many chronic diseases are adversely affected by elevated iron levels. It has been speculated that this relationship is mediated by increased oxidative stress, due to the ability of iron to generate reactive oxygen species. The aim of this study was to assess the relationship between elevated iron levels and lipid peroxidation in Caucasian adults residing in the north-eastern Mediterranean region of Spain. MATERIALS AND METHODS: This cross-sectional case-control study included 300 subjects: 150 adults displaying elevated iron levels (cases) selected from a representative sample of our general population and 150 age- and sex-matched adults exhibiting normal iron levels (controls). Dietary assessment (3-day food records), iron biomarkers (serum iron, ferritin and transferrin saturation) and lipid profile were determined. Elevated iron levels were defined by high serum ferritin (SF>110 µg/L in women and>200 µg/L in men) and/or transferrin saturation (TS)>45%. Oxidized low-density lipoprotein (oxLDL) plasma levels were measured, and oxLDL/LDL-cholesterol ratio was calculated to estimate lipid peroxidation. Multiple linear regression (MLR) models were applied. RESULTS: Individuals with elevated serum iron levels showed increased oxLDL/LDL ratio, but not oxLDL levels, compared to control subjects (20·92 ± 4·89 U/mmol vs. 19·72 ± 3·573 U/mmol, P = 0·028). These results were further confirmed by the regression models adjusted for demographic characteristics, diet, lipid profile and inflammation. Importantly, higher serum levels of triglycerides, LDL-cholesterol and lower intake of Vitamin E increased lipid peroxidation. CONCLUSIONS: In our general population, we have observed that higher circulating levels of iron, measured by serum ferritin and/or TS, increased lipid peroxidation (measured by oxLDL/LDL ratio).

Selective inhibition of sphingosine kinase-1 protects adipose tissue against LPS-induced inflammatory response in Zucker diabetic fatty rats.

Obesity is associated with a state of chronic inflammation. The chemokine (C-C motif) ligand 5 (CCL5) has been proposed to modulate the inflammatory response in adipose tissue (AT). However, the mechanisms underlying CCL5 upregulation in AT remain undefined. The objective of the present study was to evaluate whether the enzyme sphingosine kinase-1 (SK1) would modulate the expression of CCL5 and other inflammatory biomarkers in primary adipocytes and its potential role in lipopolysaccharide (LPS)-induced AT inflammation in a rat model of diabetes. To address this, LPS-stimulated primary adipocytes and 3T3-L1 cells were treated with a SK inhibitor, and the expression of Ccl5 and other CC chemokines were studied. Moreover, the effect of SK1 knockdown on cytokine production was analyzed in 3T3-L1 cells by transfection of SK1-specific small-interfering RNA (siRNA). The anti-inflammatory effects of SK inhibitor in AT were also investigated in vivo using the Zucker lean normoglycemic control (ZLC) rats. LPS treatment stimulated Ccl5, IL-6, pentraxin 3 (Ptx3), and Tnfα mRNA expression in primary adipocytes and 3T3-L1 cells, whereas pharmacologically and siRNA-mediated SK1 inhibition strongly reduced mRNA levels of proinflammatory cytokines in these cells. Similarly, administration of SK inhibitor to ZLC rats prevented the LPS-induced inflammatory response in AT. Our data demonstrate a role for SK1 in endotoxin-induced cytokine expression in adipocytes and suggest that inhibition of SK1 may be a potential therapeutic tool in the prevention and treatment of chronic and common metabolic disorders, including obesity, insulin-resistance, and type 2 diabetes.

Systems biology approach to identify alterations in the stem cell reservoir of subcutaneous adipose tissue in a rat model of diabetes: effects on differentiation potential and function.

AIMS/HYPOTHESIS: Autologous progenitor cells represent a promising option for regenerative cell-based therapies. Nevertheless, it has been shown that ageing and cardiovascular risk factors such as diabetes affect circulating endothelial and bone marrow-derived progenitor cells, limiting their therapeutic potential. However, their impact on other stem cell populations remains unclear. We therefore investigated the effects of diabetes on adipose-derived stem cells (ASCs) and whether these effects might limit the therapeutic potential of autologous ASCs. METHODS: A systems biology approach was used to analyse the expression of genes related to stem cell identification in subcutaneous adipose tissue (SAT), the stromal vascular fraction and isolated ASCs from Zucker diabetic fatty rats and their non-diabetic controls. An additional model of type 2 diabetes without obesity was also investigated. Bioinformatic approaches were used to investigate the biological significance of these changes. In addition, functional studies on cell viability and differentiation potential were performed. RESULTS: Widespread downregulation of mesenchymal stem cell markers was observed in SAT of diabetic rats. Gene expression and in silico analysis revealed a significant effect on molecules involved in the maintenance of pluripotency and self-renewal, and on the alteration of main signalling pathways important for stem cell maintenance. The viability and differentiation potential of ASCs from diabetic rats was impaired in in vitro models and in in vivo angiogenesis. CONCLUSIONS/INTERPRETATION: The impact of type 2 diabetes on ASCs might compromise the efficiency of spontaneous self-repair and direct autologous stem cell therapy.

Hepatic lipase- and endothelial lipase-deficiency in mice promotes macrophage-to-feces RCT and HDL antioxidant properties.

Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol (HDLc) levels and presumably could affect two main HDL atheroprotective functions, macrophage-to-feces reverse cholesterol transport (RCT) and HDL antioxidant properties. In this study, we assessed the effects of both HL and EL deficiency on macrophage-specific RCT process and HDL ability to protect against LDL oxidation. HL- and EL-deficient and wild-type mice were injected intraperitoneally with [(3)H]cholesterol-labeled mouse macrophages, after which the appearance of [(3)H]cholesterol in plasma, liver, and feces was determined. The degree of HDL oxidation and the protection of oxidative modification of LDL co-incubated with HDL were evaluated by measuring conjugated diene kinetics. Plasma levels of HDLc, HDL phospholipids, apoA-I, and platelet-activated factor acetyl-hydrolase were increased in both HL- and EL-deficient mice. These genetically modified mice displayed increased levels of radiolabeled, HDL-bound [(3)H]cholesterol 48h after the label injection. The magnitude of macrophage-derived [(3)H]cholesterol in feces was also increased in both the HL- and EL-deficient mice. HDL from the HL- and EL-deficient mice was less prone to oxidation and had a higher ability to protect LDL from oxidation, compared with the HDL derived from the wild-type mice. These changes were correlated with plasma apoA-I and apoA-I/HDL total protein levels. In conclusion, targeted inactivation of both HL and EL in mice promoted macrophage-to-feces RCT and enhanced HDL antioxidant properties.

Effects of two commonly found strains of influenza A virus on developing dopaminergic neurons, in relation to the pathophysiology of schizophrenia.

Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.

La grasa saturada en la dieta disminuye la expresión hepática de APOA5 en ratones deficientes en apo E / Saturated fat from diet downregulates APOA5 hepatic expression in apo E-deficient mice

Introducción. En el desarrollo de la arteriosclerosis intervienen numerosos factores; en especial la edad, la dieta y la hiperlipidemia. La apolipoproteína (apo) A-V desempeña un papel destacado en el control del metabolismo lipídico. Nuestro objetivo es estudiar en ratones hiperlipémicos el efecto que la grasa de la dieta tiene en la expresión hepática del gen de la apo A-V (APOA5) y su relación con el desarrollo de la arteriosclerosis y sus factores de riesgo. Material y métodos. Utilizamos 72 ratones knock-out para el gen de la apo E (KO-APOE) separados en 3 grupos (n = 24): los que recibían dieta convencional de ratón o dieta rica en grasa saturada (20% aceite de palma) sola o suplementada con 0,25% de colesterol. Las muestras se tomaron a las 16, 24 y 32 semanas de edad. Las determinaciones analíticas incluyeron parámetros lipídicos e inflamatorios, la superficie de lesión arteriosclerótica en la aorta y la expresión de APOA5 en hígado. Resultados. La ingesta de dieta rica en grasa saturada disminuye un 48% (p = 0,001) de media la expresión hepática de APOA5 y la suplementación con colesterol revierte este efecto. Estos efectos se observaron a las diferentes edades de los ratones. La expresión hepática de APOA5 aumenta significativamente (p < 0,0001) en función de la edad, el número de lesiones arterioscleróticas en la aorta y el grado de inflamación en los ratones. Conclusiones. La grasa saturada de la dieta disminuye significativamente la expresión hepática de APOA5, que a su vez aumenta con la edad a todas las dietas suministradas y se correlaciona con el área ateromatosa y el estado inflamatorio (AU)

Introduction. Many factors are involved in atherosclerosis development, especially age, diet and hyperlipidemia. Apolipoprotein (apo) A-V plays a key role in the control of lipid metabolism. The aim of this study was to determine the effect of dietary fat intake on hepatic expression of the apo A-V gene (APOA5) in hyperlipidemic mice and its association with risk factors for atherosclerosis and atherosclerosis development. Material and methods. We used 72 knock-out mice for the apo E gene (KO-APOE) divided in three groups (n=24) that received a chow diet, a diet rich in saturated fat (20% palm oil) alone, or a diet supplemented with 0.25% of cholesterol. Samples were obtained at 16, 24, and 32 weeks. Laboratory determinations included lipid and inflammatory parameters, area of atherosclerotic lesions in the aorta, and APOA5 expression in the liver. Results. Intake of a saturated fat-rich diet reduced mean hepatic expression of APOA5 by 48% (P=0.001), while cholesterol supplementation reversed this effect. These effects were found at the different ages of mice. Hepatic APOA5 expression significantly increased (P=0.001), depending on age, the number of atherosclerotic lesions in the aorta, and the degree of inflammation in these mice. Conclusions. Saturated dietary fat significantly downregulates hepatic APOA5 expression, which also increases with age, in all the diets administered and correlates with atheromatous area and inflammatory status (AU)

Manipulation of inflammation modulates hyperlipidemia in apolipoprotein E-deficient mice: a possible role for interleukin-6.

There are increasing evidences showing that inflammation participates in atherosclerosis. Therefore, the therapeutic use of anti-inflammatory agents should be considered. We have induced chronic, aseptic inflammation upon the injection of turpentine and tested the effect of dexamethasone on lipoprotein metabolism and, consequently, atherosclerosis in apolipoprotein E-deficient mice. Aseptic inflammation caused a significant decrease in hyperlipidemia. Treatment with dexamethasone elicited the opposite effect increasing hyperlipidemia through mechanisms related to the increase in the synthesis of triglyceride-rich lipoproteins. Changes in plasma lipids correlated with those observed in the size of atherosclerotic lesions. Our data suggest the presence of a common mechanism present in both observations and which is probably related to the cytokine secretion. Among the candidates, we chose to test the effect of interleukin-6 because it is involved in both processes, atherosclerosis and inflammation, and its expression is efficiently repressed by corticosteroids. The injection of recombinant interleukin-6 in our mice elicited the same effects observed in our model of inflammation. We conclude that manipulation of inflammation-related mechanisms modulates lipid homeostasis and development of atherosclerotic plaque in rodents.

Effects of rosiglitazone and metformin on postprandial paraoxonase-1 and monocyte chemoattractant protein-1 in human immunodeficiency virus-infected patients with lipodystrophy.

Highly active antiretroviral therapy in Human Immunodeficiency Virus (HIV) has been associated with lipodystrophy, insulin resistance and atherosclerosis. We investigated the effects of rosiglitazone or metformin on fasting and postprandial inflammatory and antioxidant variables in HIV-infected males with lipodystrophy. Thirty-one patients were randomly assigned to receive either rosiglitazone (4 mg twice daily) or metformin (1 g twice daily) for 26 weeks. At baseline and after treatment, standardized 10-h oral fat loading tests were performed. Before treatment, inflammatory variables remained unchanged but there was a postprandial decrease in high density lipoprotein (HDL)-cholesterol and paraoxonase (PON1) activity. Rosiglitazone and metformin reduced homeostasis model assessment index (HOMA) similarly (-34% and -37%, respectively, P<0.05 for each). Both treatments increased fasting and postprandial PON1 activity and decreased postprandial monocyte chemoattractant protein 1 (MCP-1) concentrations. However, plasma C-reactive protein (CRP) and Interleukin-6 (IL-6) concentration did not change throughout the study. To decrease insulin resistance results in a higher anti-oxidant and consequent lower pro-inflammatory action of HDL. This may confer protection against accelerated atherosclerosis in these patients.

Experimentos con ratones susceptibles a arteriosclerosis. Ventajas, inconvenientes y aspectos que considerar / Experimentation with arteriosclerosis-susceptible mice. Advantages, disadvantages and aspects to be considered

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HIV-infected patients with lipodystrophy have higher rates of carotid atherosclerosis: the role of monocyte chemoattractant protein-1.

Individuals with HIV-1 infection are at increased risk for cardiovascular events, and lipodystrophy is generally associated with pro-atherogenic metabolic disturbances. We conducted a case-control study to assess the presence of sub-clinical atherosclerosis in HIV-1-infected patients with or without lipodystrophy (LD) and to evaluate the influence of monocyte chemoattractant protein-1 (MCP-1) on the development of both carotid atherosclerosis and LD. The study population consisted of 43 patients with LD and 86 patients without LD. We determined carotid intima-media thickness (IMT), MCP-1 concentrations in plasma, and MCP-1 genotype (presence or absence of the -2518G allele). HIV-1-infected patients with LD showed increased risk (OR=3.71, 95% CI=1.10-12.47, p=0.03) for sub-clinical atherosclerosis, and MCP-1 plasma concentration was significantly correlated with IMT in these patients (Pearson=0.31, p=0.03). Furthermore, presence of LD was a determinant for MCP-1 plasma concentration (beta=0.18, p=0.05). In summary, HIV-1-infected patients with clinically manifest LD are at higher risk for atherosclerosis and our observations support the relationship between inflammation and atherosclerotic disease.