Cognitive training increases platelet PLA(2) activity in healthy elderly subjects

Phospholipases A(2) (PLA(2)) are ubiquitous enzymes involved in membrane fatty acid metabolism and intracellular signalling. Recent studies have shown that PLA(2) subtypes are implicated in the modulation of pathways related to memory acquisition and retrieval. We investigated the effects of cognitive training on platelet PLA(2) activity in healthy elderly individuals. Twenty-three cognitively unimpaired older adults were randomly assigned to receive memory training or standard outpatient care only. Both groups were cognitively assessed by the same protocol, and the experimental group (EG) underwent a four-session memory training intervention. Pre- and post-test measures included prose and list recall, WAIS-III digit symbol, strategy use measures and platelet PLA(2) group activity. After cognitive training, patients in the EG group had significant increase in cytosolic, calcium-dependent PLA(2) (cPLA(2)), extracellular (or secreted), calcium-dependent PLA(2) (sPLA(2)), total platelet PLA(2) activity, and significant decrease in platelet calcium-independent PLA(2) (iPLA(2)) activity. Our results suggest that memory training may have a modulating effect in PLA(2)-mediated biological systems associated with cognitive functions and neurodegenerative diseases. (c) 2008 Elsevier Ltd. All rights reserved.

Autoimmunity in Hyper-IgM syndrome

Introduction Immunodeficiency with hyper-IgM (HIGM) results from genetic defects in the CD40-CD40 ligand (CD40L) pathway or in the enzymes required for immunoglobulin class switch recombination and somatic hypermutation. HIGM can thus be associated with an impairment of both B-cell and T-cell activation. Results and discussions There are seven main subtypes of HIGM and the most frequent is X-linked HIGM, resulting from CD40L mutations. In addition to the susceptibility to recurrent and opportunistic infections, these patients are prone to autoimmune manifestations, especially hemato-logic abnormalities, arthritis, and inflammatory bowel disease. Furthermore, organ-specific autoantibodies are commonly found in HIGM patients. Conclusions The mechanisms by which HIGM associates to autoimmunity are not completely elucidated but a defective development of regulatory T cells, the presence of IgM autoantibodies and an impaired peripheral B-cell tolerance checkpoint have been implicated. This article reviews the main subtypes of HIGM syndrome, the clinical autoinumme manifestations found in these patients, and the possible mechanisms that would explain this association.

In utero exposure to air pollution lowers erythrocyte antioxidant defense and decreases weight in adult mice

In this study, we tested the influence of ambient air pollution on different phases of development of adult mice. With respect to adult weight, the animals that had spent their in utero period exposed to pollution showed less weight gain over their lifetime, as well as lower activity levels of the antioxidant enzymes catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). Our study suggests that contact with atmospheric pollutants during the foetal period produces important changes on enzymatic erythrocyte antioxidant defense and weight in adult mice. (C) 2011 Elsevier B.V. All rights reserved.

Deregulated expression of superoxide dismutase-2 correlates with different stages of cervical neoplasia

Objective: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme may be involved in carcinogenesis, particularly in lung, gastric, colorectal and breast cancer. Methods: In the present study, we have evaluated SOD2 protein levels by immunohistochemistry (IHC) in 331 cervical histological samples including 31 low-grade cervical intraepithelial neoplasia (LSIL), 51 high-grade cervical intraepithelial neoplasia (HSIL), 197 squamous cervical carcinomas (SCC) and 52 cervical adenocarcinomas (ADENO). Results: We observed that SOD2 staining increases with cervical disease severity. Intense SOD2 staining was found in 13% of LSIL, 25.5% of HSIL and 40% of SCC. Moreover, 65.4% of ADENO exhibited intense SOD2 staining. Conclusions: Differences in the expression of SOD2 could potentially be used as a biomarker for the characterization of different stages of cervical disease.

Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome?

Acute pancreatitis (AP) is a rare and life-threatening manifestation of juvenile systemic lupus erythematosus (JSLE). The objective of this study was to evaluate the prevalence and clinical features of AP in our JSLE population. AP was defined according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Of note, in the last 26 years, 5367 patients were followed up at our Pediatric Rheumatology Unit and 263 (4.9%) of them had JSLE diagnosis (ACR criteria). AP was observed in 4.2% (11/263) of JSLE patients. The median of age of the JSLE patients at AP diagnosis was 12.4 years (8.8-17.9). All of them had lupus disease activity at AP onset. Three patients were receiving corticosteroids before AP diagnosis. Interestingly, 10/11 JSLE patients fulfilled preliminary guidelines for macrophage activation syndrome, three of them with macrophage hemophagocytosis in bone marrow aspirate and hyperferritinemia. The hallmark of this syndrome is excessive activation and proliferation of T lymphocytes and macrophages with massive hypersecretion of proinflammatory cytokines and clinically it is characterized by the occurrence of unexplained fever, cytopenia and hyperferritinemia. AP treatment was mainly based on intravenous methylprednisolone. Four JSLE patients with AP died and two developed diabetes mellitus. In conclusion, AP was a rare and severe manifestation in active pediatric lupus. The association between AP and macrophage activation syndrome suggests that the pancreas could be a target organ of this syndrome and that pancreatic enzyme evaluation should also be carried out in all patients. Lupus (2010) 19, 1654 1658.

Inhibition of phospholipase A(2) in rat brain decreases the levels of total Tau protein

The microtubule-associated protein Tau promotes the assembly and stability of microtubules in neuronal cells. Six Tau isoforms are expressed in adult human brain. All six isoforms become abnormally hyperphosphorylated and form neurofibrillary tangles in Alzheimer disease (AD) brains. In AD, reduced activity of phospholipase A(2) (PLA(2)), specifically of calcium-dependent cytosolic PLA(2) (cPLA(2)) and calcium-independent intracellular PLA(2) (iPLA(2)), was reported in the cerebral cortex and hippocampus, which positively correlated with the density of neurofibrillary tangles. We previously demonstrated that treatment of cultured neurons with a dual cPLA(2) and iPLA(2) inhibitor, methyl arachidonyl fluorophosphonate (MAFP), decreased total Tau levels and increased Tau phosphorylation at Ser(214) site. The aim of this study was to conduct a preliminary investigation into the effects of in vivo infusion of MAFP into rat brain on PLA(2) activity and total Tau levels in the postmortem frontal cortex and dorsal hippocampus. PLA(2) activity was measured by radioenzymatic assay and Tau levels were determined by Western blotting using the anti-Tau 6 isoforms antibody. MAFP significantly inhibited PLA(2) activity in the frontal cortex and hippocampus. The reactivity to the antibody revealed three Tau protein bands with apparent molecular weight of close to 40, 43 and 46 kDa in both brain areas. MAFP decreased the 46 kDa band intensity in the frontal cortex, and the 43 and 46 kDa band intensities in the hippocampus. The results indicate that in vivo PLA(2) inhibition in rat brain decreases the levels of total (nonphosphorylated plus phosphorylated) Tau protein and corroborate our previous in vitro findings.

Salt-Induced Cardiac Hypertrophy and Interstitial Fibrosis Are Due to a Blood Pressure-Independent Mechanism in Wistar Rats

High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg.kg(-1).d(-1) hydralazine in the drinking water), and HSD8+LOS (20 mg.kg(-1).d(-1) losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT(1)) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT(1) conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT(1) antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT(1) receptor internalization is probably due to angiotensin II binding. J. Nutr. 140: 1742-1751, 2010.

Synthesis of Fructooligosaccharides in Banana `Prata` and Its Relation to Invertase Activity and Sucrose Accumulation

Levels of sucrose and total fructool igosaccha rides (FOS) were quantified in different phases of banana `Prata` ripening during storage at ambient (similar to 19 degrees C) and low (similar to 10 degrees C) temperature. Total FOS levels were detected in the first days after harvest, whereas 1-kestose remained undetectable until the sucrose levels reached approximately 200 mg/g (dry weight) in both groups. Sucrose levels increased slowly but constantly at low temperature, but they elevated rapidly when the temperature was raised to 19 degrees C. Total FOS and sucrose levels were higher in bananas stored at low temperature than in the control group. In both samples, total FOS levels were higher than those of 1-kestose. The carbohydrate profiles obtained by HPLC and TLC suggest the presence of neokestose, 6-kestose, and bifurcose. The enzymes putatively involved in banana fructosyltransferase activity were also evaluated. Results obtained indicate that the banana enzyme responsible for the synthesis of FOS by transfructosylation is an invertase rather than a sucrose-sucrosyl transferase-like enzyme.

Isoforms of hyaluronidases can be a predictor of a prostate cancer of good prognosis

Introduction: Hyaluronidases (HAases) are enzymes related to cancer progression. Isoforms of HAases have been described as products of alternative splicing responsible for differences in enzyme activity. The heterogeneity of HAase expression has been identified in tumors and could be related to the differences in their biological behavior. Methods: Thirty-seven patients subjected to radical prostatectomy for prostate cancer were divided into 2 groups for the analyses: Low (<= 6-18) and high (>= 7-19) Gleason score and tumor behavior; recurrence 15 and nonrecurrence 22, mean follow-up 52.6 months. Conclusion: A profile of HAase related to low Gleason score and non-tumor recurrence was characterized by expression of HYAL3-v1, HYAL1-v3, and HYAL3-v2. More studies should be made in order to confirm with larger series. (C) 2009 Elsevier Inc. All rights reserved.

Autoimmune hepatitis and juvenile systemic lupus erythematosus

Juvenile systemic lupus erythematosus (JSLE) and autoimmune hepatitis (AIH) are both autoimmune disorders that are rare in children and have a widespread clinical manifestation. A few case reports have shown a JSLE-AIH associated disorder. To our knowledge, this is the first study that simultaneously evaluated the prevalence of JSLE-AIH in a large JLSE and AIH population in groups of Hepatology and Rheumatology of a tertiary Paediatric University Hospital. In a 24-year period, 228 patients were diagnosed with JSLE (ACR criteria). In the same period, 252 patients were diagnosed with AIH according to the International Autoimmune Hepatitis Group. In this article, we present the demographic data, clinical features, laboratory exams and treatment of four children with both the diseases. The prevalence was 1.8% in JSLE population and was 1.6% in AIH population. The current median age was 15.5 years and three were females. In three of them, the diagnosis of AIH preceded JSLE. All of them had increased liver enzymes with a characteristic liver biopsy of AIH and responded to the combination of prednisone, azathioprine and antimalarial drugs. In conclusion, the presence of AIH-JSLE associated disorder was rarely observed. The liver biopsy could be necessary in patients with JLSE with a persistent increase of liver enzymes. Lupus (2009) 18, 747-751.

Plantain and Banana Starches: Granule Structural Characteristics Explain the Differences in Their Starch Degradation Patterns

Different banana cultivars were used to investigate the influences of starch granule structure and hydrolases on degradation. The highest degrees of starch degradation were observed in dessert bananas during ripening. Scanning electron microscopy images revealed smooth granule surface in the green stage in all cultivars, except for Mysore. The small and round granules were preferentially degraded in all of the cultivars. Terra demonstrated a higher degree of crystallinity and a short amylopectin chain length distribution, resulting in high starch content in the ripe stage. Amylose content and the crystallinity index were more strongly correlated than the distribution of amylopectin branch chain lengths in banana starches. alpha- and beta-amylase activities were found in both forms, soluble in the pulp and associated with the starch granule. Starch-phosphorylase was not found in Mysore. On the basis of the profile of alpha-amylase in vitro digestion and the structural characteristics, it could be concluded that the starch of plantains has an arrangement of granules more resistant to enzymes than the starch of dessert bananas.

Exercise Training Reduces Sympathetic Modulation on Cardiovascular System and Cardiac Oxidative Stress in Spontaneously Hypertensive Rats

BACKGROUND Spontaneously hypertensive rats (SHRs) show increased cardiac sympathetic activity, which could stimulate cardiomyocyte hypertrophy, cardiac damage, and apoptosis. Norepinephrine (NE)induced cardiac oxidative stress seems to be involved in SHR cardiac hypertrophy development. Because exercise training (ET) decreases sympathetic activation and oxidative stress, it may alter cardiac hypertrophy in SHR. The aim of this study was to determine, in vivo, whether ET alters cardiac sympathetic modulation on cardiovascular system and whether a correlation exists between cardiac oxidative stress and hypertrophy. METHODS Male SHRs (15-weeks old) were divided into sedentary hypertensive (SHR, n = 7) and exercise-trained hypertensive rats (SHR-T, n = 7). Moderate ET was performed on a treadmill (5 days/week, 60 min, 10 weeks). After ET, cardiopulmonary reflex responses were assessed by bolus injections of 5-HT. Autoregressive spectral estimation was performed for systolic arterial pressure (SAP) with oscillatory components quantified as low (LF: 0.2-0.75 Hz) and high (HF:0.75-4.0 Hz) frequency ranges. Cardiac NE concentration, lipid peroxidation, antioxidant enzymes activities, and total nitrates/nitrites were determined. RESULTS ET reduced mean arterial pressure, SAP variability (SAP var), LIF of SAP, and cardiac hypertrophy and increased cardiopulmonary reflex responses. Cardiac lipid peroxidation was decreased in trained SHRs and positively correlated with NE concentrations (r= 0.89, P < 0.01) and heart weight/body weight ratio (r= 0.72, P < 0.01), and inversely correlated with total nitrates/nitrites (r= -0.79, P < 0.01). Moreover, in trained SHR, cardiac total nitrates/nitrites were inversely correlated with NE concentrations (r= -0.82, P < 0.01). CONCLUSIONS ET attenuates cardiac sympathetic modulation and cardiac hypertrophy, which were associated with reduced oxidative stress and increased nitric oxide (NO) bioavailability. Am J Hypertens 2008;21:1138-1193 (C) 2008 American Journal of Hypertension, Ltd.

Starch mobilization and sucrose accumulation in the pulp of Keitt mangoes during postharvest ripening

Sugar is a determinant for the quality of mangoes, but information about its accumulation is scarce. Although starch can contribute to sugar production during ripening, not much is known about the enzymes involved. This work presents the changes in carbohydrate and enzymes during the development and ripening of Keitt mangoes. Starch disappearance was concomitant to a fivefold increase of sucrose, the most abundant sugar of the ripe fruits. The activities of alpha-amylase, beta-amylase, phosphorylase and isoamylase were detected in the pulp, and while alpha-amylase increased parallel to the starch content, beta-amylase presented a 20-fold increase during ripening. On the other hand, high phosphorylase activity was observed when fruits were still accumulating starch, and lowered during ripening. Isoamylase was detected during development and increased slightly during ripening, which would be in agreement to the expected role for isoamylases as acting on both subproduct of starch synthesis and degradation.

HDL atheroprotection by aerobic exercise training in type 2 diabetes mellitus

Purpose: In this study we analyzed the role played by aerobic exercise training in the plasma lipoprotein profile, prebeta 1-HDL concentration, and in the in vitro HDL3 ability to remove cholesterol from macrophages and inhibit LDL oxidation in type 2 diabetes mellitus (DM) patients and control subjects, in the fasting and postprandial states. Methods: Healthy controls (HTC, N = 11; 1 M/10 F) and subjects with type 2 diabetes mellitus (DMT, N = 11; 3M/ 8F) were engaged in a 4-month aerobic training program, and compared with a group of sedentary subjects with type 2 diabetes mellitus (DMS, N = 10; 4 M/6 F). All groups were submitted to an oral fat load test to analyze all parameters, both at the beginning of the investigation protocol (basal) and at the end of the study period (final). Results: Exercising did not modify body weight, BMI, plasma concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (TG), glucose, insulin, or HOMA-IR, but it reduced the waist circumference. The HDL3 Composition did not change, and its ability to remove cell cholesterol was unaltered by aerobic training. In DMT but not in HTC, aerobic training improved 15% the HDL3 protective effect against LDL maximal oxidation rate in the fasting state, and reduced 24% the plasma prebeta 1-HDL concentration in the postprandial state, suggesting an enhanced prebeta 1-HDL conversion into larger, more mature HDL particles. In this regard, regular aerobic exercise enriched HDL2 with TG in the fasting and postprandial states in HTC and in the fasting phase in DMT. Conclusion: Our results show that aerobic exercise training in diabetes mellitus improves the HDL efficiency against LDL oxidation and favors HDL maturation. These findings were independent of changes in insulin resistance and of the rise of plasma HDL cholesterol concentration.

Preliminary analysis of miRNA pathway in Schistosoma mansoni

RNA silencing refers to a series of nuclear and cytoplasmatic processes involved in the post-transcriptional regulation of gene expression or post-transcriptional gene silencing (PTGS), either by sequence-specific mRNA degradation or by translational at-rest. The best characterized small RNAs are microRNAs (miRNAs), which predominantly perform gene silencing through post-transcriptional mechanisms. in this work we used bioinformatic approaches to identify the parasitic trematode Schistosoma Mansoni sequences that are similar to enzymes involved in the post-transcriptional gene silencing mediated by miRNA pathway. We used amino acid sequences of well-known proteins involved in the miRNA pathway against S. mansoni genome and transcriptome databases identifying a total of 13 Putative proteins in the parasite. In addition, the transcript levels of SinDicer1 and SmAgo2/3/4 were identified by qRT-PCR using cercariae, adult worms, eggs and in vitro Cultivated schistosomula. Our results showed that the SmDicer1 and SmAgo2/3/4 are differentially expressed during schistosomula development, suggesting that the miRNA pathway is regulated at the transcript level and therefore may control gene expression during the life cycle of S. mansoni. (C) 2008 Published by Elsevier Ireland Ltd.