Changes in gene expression profile in human subcutaneous adipose tissue during significant weight loss.

Objective: To analyze the expression of peroxisome proliferator-activated receptor-γ1 and 2 (PPARγ1 and 2), 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), and leptin in adipose tissue (AT) of obese women during weight loss following Roux-en-Y gastric bypass (RYGB) and to compare these levels with those obtained in AT of nonobese subjects. Methods: Gene expression was determined by real-time RT-PCR prior to surgery and at 3, 6, and 12 months after RYGB. Results: All obese patients lost weight, reaching a mean BMI of 29.3 ± 1.0 kg/m(2) at 1 year after surgery (-33.9 ± 1.5% of their initial body weight). In obese subjects leptin and 11βHSD1 were over-expressed, whereas PPARγ1 was expressed at lower levels compared to controls. After surgery, leptin and 11βHSD1 gene expression decreased, whereas PPARγ1 expression increased. At 12 months after RYGB, these 3 genes had reached levels similar to the controls. In contrast, PPARγ2 gene expression was not different between groups and types of tissue and remained unchanged during weight loss. We found a positive correlation between BMI and levels of gene expression of leptin and 11βHSD1. Conclusion: Gene expression of leptin, PPARγ1, and 11βHSD1 in AT is modified in human obesity. This default is completely corrected by RYGB. Copyright © 2012 S. Karger GmbH, Freiburg.

Efectos de la suplementación con glutamina sobre el sistema antioxidante y la peroxidación lipídica en pacientes críticos con nutrición parenteral

INTRODUCTION In the critically ill patient, there is a continuous production of reactive oxygen species (ROS) that need to be neutralized to prevent oxidative stress (OS). Quantitatively speaking, the glutathione system (GSH) is the most important anti-oxidant endogenous defense. To increase it, glutamine supplementation has been shown to be effective by protecting against the oxidative damage and reducing the morbimortality. OBJECTIVE To assess the effect of adding an alanylglutamine dipeptide to PN on lipid peroxidation lipidica and glutathione metabolism, as well as its relationship with morbidity in critically ill patients. METHODS Determination through spectrophotometry techniques of glutathione peroxidase, glutathione reductase, total glutathione, and maloniladdehyde at admission adn after seven days of hospitalization at the Intensive Care Unit (ICU) in 20 patients older than 18 years on parenteral nutrition therapy. RESULTS The group of patients receiving parenteral nutrition with glutamine supplementation had significant increases in total glutathione (42.35+/-13 vs 55.29+/-12 micromol/l; p<0.05) and the enzymatic activity of glutathione peroxidasa (470+/-195 vs 705+/-214 micromol/l; p<0.05) within one week of nutritional therapy, whereas the group on conventional parenteral nutrition did not show significant changes of any of the parameters studied (p>0.05). However, both mortality and ICU stay were not different between the study group, whereas the severity (assessed by the SOFA score) was lower in the group of patients receiving glutamine (SOFA 5+/-2 vs 8+/-1.8; p<0.05). CONCLUSIONS Glutamine intake in critically ill patients improves the antioxidant defenses, which leads to lower lipid peroxidation and lower morbidity during admission at the ICU.

Efectos del consumo de aceites termo-oxidados sobre la peroxidación lipídica en animales de laboratorio.

INTRODUCTION The quality of fats and oils used for frying is as important as the quality of the final product since during the frying process oxidization by-products are formed and become part of the diet, being potentially harmful for the consumers' health. OBJECTIVE To determine the effects of thermo-oxidised fats and oils on the oxidization of plasma lipoproteins inexperimental rats. METHODS Determination by means of spectrophotometric techniques of those substances reacting with thiobarbituric acid and total cholesterol (enzymatic method) in the sera of 40 Wistar rats that consumed crude thermooxidised oils and fats with different levels of malonil aldehyde(MDA) for 30 days. RESULTS The group of rats receiving a diet with thermooxidised oils and fats experienced significant increases in MDA plasma levels throughout the study period, lipid peroxidation being higher with increasing MDA content (p < 0.05) regardless the type of fat compound consumed. However, those rats receiving crude oils and fats kept plasma levels of lipidic peroxides without significant changes throughout the experimental period (p > 0.05). By contrast, cholesterol levels increased towards the end of the experimental period in both the rats consuming crude fats and those consuming thermo-oxidised fats (p < 0.05). CONCLUSIONS Consumption of oils and fats submitted to repeat thermal heating has an influence on plasma lipidic peroxidation, which becomes higher with increasing number of heating processes applied, so that it would advisable not to abuse of reheating the oils used for frying foods.

Postpartum changes in plasma viral load and CD4 percentage among HIV-infected women from Latin American and Caribbean countries: the NISDI Perinatal Study

The goal of this study was to evaluate changes in plasma human immunodeficiency virus (HIV) RNA concentration [viral load (VL)] and CD4+ percentage (CD4%) during 6-12 weeks postpartum (PP) among HIV-infected women and to assess differences according to the reason for receipt of antiretrovirals (ARVs) during pregnancy [prophylaxis (PR) vs. treatment (TR)]. Data from a prospective cohort of HIV-infected pregnant women (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. Women experiencing their first pregnancy who received ARVs for PR (started during pregnancy, stopped PP) or for TR (initiated prior to pregnancy and/or continued PP) were included and were followed PP. Increases in plasma VL (> 0.5 log10) and decreases in CD4% (> 20% relative decrease in CD4%) between hospital discharge (HD) and PP were assessed. Of the 1,229 women enrolled, 1,119 met the inclusion criteria (PR: 601; TR: 518). At enrollment, 87% were asymptomatic. The median CD4% values were: HD [34% (PR); 25% (TR)] and PP [29% (PR); 24% (TR)]. The VL increases were 60% (PR) and 19% (TR) (p < 0.0001). The CD4% decreases were 36% (PR) and 18% (TR) (p < 0.0001). Women receiving PR were more likely to exhibit an increase in VL [adjusted odds ratio (AOR) 7.7 (95% CI: 5.5-10.9) and a CD4% decrease (AOR 2.3; 95% CI: 1.6-3.2). Women receiving PR are more likely to have VL increases and CD4% decreases compared to those receiving TR. The clinical implications of these VL and CD4% changes remain to be explored.

Vitaminas B y homocisteína en la insuficiencia renal crónica

Metabolic, biochemical, and hormonal changes occur in chronic renal failure usually associated with hyponutrition states. In predialysis patients, knowing the nutritional state about water-soluble vitamins such as thiamine, riboflavin, pyridoxine, cianocobalamine, and folic acid is becoming more and more important since some of the manifestations of chronic renal failure may be due to the deficiency of some of these water-soluble vitamins. The metabolic pathways in which most of these vitamins participate are interrelated and it is difficult to understand how the individual deficits of each vitamin affect renal pathology. This work aims at reviewing not only this issue but also the status of these water-soluble vitamins that different authors have found in groups of predialysis patients. On the other hand, the issue on the high prevalence of hyperhomocysteinemia in chronic renal failure as the main mortality risk factor due to cardiovascular pathologies as well as the implication of these vitamins in the metabolism of homocysteine, and consequently in plasma levels of this metabolite in predialysis patients is reviewed.

Estudio longitudinal del Índice de masa corporal (IMC) en pacientes en diálisis

Chronic renal failure is commonly related to hyponutrition, affecting approximately on third of patients with advanced renal failure. We carried out a longitudinal study to assess nutritional evolution of 73 patients on a regular hemodialysis program, assessing changes in the anthropometrical parameter body mass index (BMI) and its correspondence to biochemical nutritional parameters such as total protein (TP) levels and serum albumin (Alb). Every three months plasma TP and albumin levels were collected and BMI was calculated by the standard formula: post-dialysis weight in kg/height in m2. For classifying by BMI categories, overweight and low weight were defined according to the WHO Expert Committee. Studied patients had a mean age of 53 years, 43 were male and 30 were female patients. BMI in women was lower than that in men (p < 0.001), as well as TP (p < 0.001) and Alb (p < 0.001) levels. Mean BMI was 29.3 kg/m2. Three point two percent of the determinations showed low weight, 12.16% overweight, and 83.97% normal BMI. TP were normal in 90.76% and decreased in 9.24%. Alb was normal in 82.2% and low in 17.78%. After the follow-up time (21.6 months, minimum 18 months, maximum 53 months), the Kruskal-Wallis test did not show a statistically significant change for BMI but it did show a change for the biochemical parameters albumin and total proteins (p < 0.05): nutritional impairment in CRF patients is manifested on biochemical parameters (TP and Alb) with no reflection on anthropometrical data.

Differential phosphorylation of some proteins of the neuronal cytoskeleton during brain development.

The cytoskeleton is important for neuronal morphogenesis. During the postnatal development of cat brain, the molecular composition of the neuronal cytoskeleton changes with maturation. Several of its proteins change in their rate of expression, in their degree of phosphorylation, in their subcellular distribution, or in their biochemical properties. It is proposed that phosphorylation is an essential mechanism to regulate the plasticity of the early, juvenile-type cytoskeleton. Among such proteins are several microtubule-associated proteins (MAPs), such as MAP5a, MAP2c or the juvenile tau proteins. Phosphorylation may also act on neurofilaments, postulated to be involved in the adult-type stabilization of axons. These observations imply that phosphorylation may affect cytoskeleton function in axons and dendrites at various developmental stages. Yet, the mechanisms of phosphorylation and its regulation cascades are largely unknown. In view of the topic of this issue on CD15, the potential role of matrix molecules being involved in the modulation of phosphorylation activity and of cytoskeletal properties is addressed.

Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir (1500/100 mg) together with 2 nucleos(t)ide reverse transcriptase inhibitors in real life: a multicentre prospective study.

BACKGROUND. Ritonavir-boosted saquinavir (SQVr) is nowadays regarded as an alternative antiretroviral drug probably due to several drawbacks, such as its high pill burden, twice daily dosing and the requirement of 200 mg ritonavir when given at the current standard 1000/100 mg bid dosing. Several once-daily SQVr dosing schemes have been studied with the 200 mg SQV old formulations, trying to overcome some of these disadvantages. SQV 500 mg strength tablets became available at the end of 2005, thus facilitating a once-daily regimen with fewer pills, although there is very limited experience with this formulation yet. METHODS. Prospective, multicentre study in which efficacy, safety and pharmacokinetics of a regimen of once-daily SQVr 1500/100 mg plus 2 NRTIs were evaluated under routine clinical care conditions in either antiretroviral-naïve patients or in those with no previous history of antiretroviral treatments and/or genotypic resistance tests suggesting SQV resistance. Plasma SQV trough levels were measured by HPLV-UV. RESULTS. Five hundred and fourteen caucasian patients were included (47.2% coinfected with hepatitis C and/or B virus; 7.8% with cirrhosis). Efficacy at 52 weeks (plasma RNA-HIV <50 copies/ml) was 67.7% (CI95: 63.6 - 71.7%) by intention-to-treat, and 92.2% (CI95: 89.8 - 94.6%) by on-treatment analysis. The reasons for failure were: dropout or loss to follow-up (18.4%), virological failure (7.8%), adverse events (3.1%), and other reasons (4.6%). The high rate of dropout may be explained by an enrollment and follow-up under routine clinical care condition, and a population with a significant number of drug users. The median SQV Cmin (n = 49) was 295 ng/ml (range, 53-2172). The only variable associated with virological failure in the multivariate analysis was adherence (OR: 3.36; CI95, 1.51-7.46, p = 0.003). CONCLUSIONS. Our results suggests that SQVr (1500/100 mg) once-daily plus 2 NRTIs is an effective regimen, without severe clinical adverse events or hepatotoxicity, scarce lipid changes, and no interactions with methadone. All these factors and its once-daily administration suggest this regimen as an appropriate option in patients with no SQV resistance-associated mutations.

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

Human pregnane X receptor is expressed in breast carcinomas, potential heterodimers formation between hPXR and RXR-alpha.

BACKGROUND The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P-450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to determine whether their expression profile in localized infiltrative breast cancer is associated with an increased risk of recurrent disease. METHODS Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis. RESULTS Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha. CONCLUSION Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator.

Impact of dietary betaine and conjugated linoleic acid on insulin sensitivity, protein and fat metabolism of obese pigs.

To determine possible mechanisms of action that might explain the nutrient partitioning effect of betaine and conjugated linoleic acid (CLA) in Iberian pigs and to address potential adverse effects, twenty gilts were restrictively fed from 20 to 50 kg BW Control, 0.5% betaine, 1% CLA or 0.5% betaine + 1% CLA diets. Serum hormones and metabolites profile were determined at 30 kg BW and an oral glucose test was performed before slaughter. Pigs were slaughtered at 50 kg BW and livers were obtained for chemical and histological analysis. Decreased serum urea in pigs fed betaine and betaine + CLA diets (11%; P = 0.0001) indicated a more efficient N utilization. The increase in serum triacylglycerol (58% and 28%, respectively; P = 0.0098) indicated that CLA and betaine + CLA could have reduced adipose tissue triacylglycerol synthesis from preformed fatty acids. Serum glucose, low-density lipoprotein (LDL) cholesterol and non-esterified fatty acids were unaffected. CLA and betaine + CLA altered serum lipids profile, although liver of pigs fed CLA diet presented no histopathological changes and triglyceride content was not different from Control pigs. Compared with controls, serum growth hormone decreased (20% to 23%; P = 0.0209) for all treatments. Although serum insulin increased in CLA, and especially in betaine + CLA pigs (28% and 83%; P = 0.0001), indices of insulin resistance were unaffected. In conclusion, CLA, and especially betaine + CLA, induced changes in biochemical parameters and hormones that may partially explain a nutrient partitioning effect in young pigs. Nevertheless, they exhibited weak, although detrimental, effects on blood lipids. Moreover, although livers were chemically and histologically normal, pigs fed CLA diet challenged with a glucose load had higher serum glucose than controls.

Schistosomal glomerulopathy and changes in the distribution of histological patterns of glomerular diseases in Bahia, Brazil

Distinct patterns of glomerular lesions, including membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis, are associated with infection by Schistosoma mansoni or Schistosoma japonicum. Evidence suggests that immune complex deposition is the main mechanism underlying the different forms of schistosomal glomerulonephritis and that immune complex deposition may be intensified by portal hypertension. The relationship between focal segmental glomerulosclerosis and schistosomiasis remains poorly understood. A clinicopathologic classification of schistosomal glomerulopathies was proposed in 1992 by the African Association of Nephrology. In Brazil, mass treatment with oral medications has led to a decrease in the occurrence of schistosomal glomerulopathy. In a survey of renal biopsies performed in Salvador, Brazil, from 2003-2009, only 24 (4%) patients were identified as positive for S. mansoni infection. Among these patients, only one had the hepatosplenic form of the disease. Focal segmental glomerulosclerosis was found in seven patients and membranoproliferative glomerulonephritis was found in four patients. Although retrospective studies on the prevalence of renal diseases based on kidney biopsies may be influenced by many patient selection biases, a change in the distribution of glomerulopathies associated with nephrotic syndrome was observed along with a decline in the occurrence of severe forms of schistosomiasis.

Biological, biochemical and molecular features of Trypanosoma cruzi strains isolated from patients infected through oral transmission during a 2005 outbreak in the state of Santa Catarina, Brazil: its correspondence with the new T. cruzi Taxonomy Consensus (2009)

We examined strains of Trypanosoma cruzi isolated from patients with acute Chagas disease that had been acquired by oral transmission in the state of Santa Catarina, Brazil (2005) and two isolates that had been obtained from a marsupial (Didelphis aurita) and a vector (Triatoma tibiamaculata). These strains were characterised through their biological behaviour and isoenzymic profiles and genotyped according to the new Taxonomy Consensus (2009) based on the discrete typing unities, that is, T. cruzi genotypes I-VI. All strains exhibited the biological behaviour of biodeme type II. In six isolates, late peaks of parasitaemia, beyond the 20th day, suggested a double infection with biodemes II + III. Isoenzymes revealed Z2 or mixed Z1 and Z2 profiles. Genotyping was performed using three polymorphic genes (cytochrome oxidase II, spliced leader intergenic region and 24Sα rRNA) and the restriction fragment length polymorphism of the kDNA minicircles. Based on these markers, all but four isolates were characterised as T. cruzi II genotypes. Four mixed populations were identified: SC90, SC93 and SC97 (T. cruzi I + T. cruzi II) and SC95 (T. cruzi I + T. cruzi VI). Comparison of the results obtained by different methods was essential for the correct identification of the mixed populations and major lineages involved indicating that characterisation by different methods can provide new insights into the relationship between phenotypic and genotypic aspects of parasite behaviour.

Longitudinal analysis of patterns and predictors of changes in self-reported adherence to antiretroviral therapy: Swiss HIV Cohort Study.

BACKGROUND: Adherence to combination antiretroviral therapy (cART) is a dynamic process, however, changes in adherence behavior over time are insufficiently understood. METHODS: Data on self-reported missed doses of cART was collected every 6 months in Swiss HIV Cohort Study participants. We identified behavioral groups associated with specific cART adherence patterns using trajectory analyses. Repeated measures logistic regression identified predictors of changes in adherence between consecutive visits. RESULTS: Six thousand seven hundred nine individuals completed 49,071 adherence questionnaires [median 8 (interquartile range: 5-10)] during a median follow-up time of 4.5 years (interquartile range: 2.4-5.1). Individuals were clustered into 4 adherence groups: good (51.8%), worsening (17.4%), improving (17.6%), and poor adherence (13.2%). Independent predictors of worsening adherence were younger age, basic education, loss of a roommate, starting intravenous drug use, increasing alcohol intake, depression, longer time with HIV, onset of lipodystrophy, and changing care provider. Independent predictors of improvements in adherence were regimen simplification, changing class of cART, less time on cART, and starting comedications. CONCLUSIONS: Treatment, behavioral changes, and life events influence patterns of drug intake in HIV patients. Clinical care providers should routinely monitor factors related to worsening adherence and intervene early to reduce the risk of treatment failure and drug resistance.

Exploring the association between Trypanosoma cruzi infection in rural communities and environmental changes in the southern Gran Chaco

The association between land use and land cover changes between 1979-2004 in a 2.26-million-hectare area south of the Gran Chaco region and Trypanosoma cruzi infection in rural communities was analysed. The extent of cultural land, open and closed forests and shrubland up to 3,000 m around rural communities in the north, northwest and west of the province of Córdoba was estimated using Landsat satellite imagery. The T. cruzi prevalence was estimated with a cross-sectional serological survey conducted in the rural communities. The land cover showed the same patterns in the 1979, 1999 and 2004 satellite imagery in both the northwest and west regions, with shrinking regions of cultured land and expanding closed forests away from the community. The closed forests and agricultural land coverage in the north region showed the same trend as in the northwest and west regions in 1979 but not in 1999 or 2004. In the latter two years, the coverage remote from the communities was either constant or changed in opposite ways from that of the northwest and west regions. The changes in closed forests and cultured vegetation alone did not have a significant, direct relationship with the occurrence of rural communities with at least one person infected by T. cruzi. This study suggests that the overall decrease in the prevalence of T. cruzi is a consequence of a combined effect of vector control activities and changes in land use and land cover.