Role of the caudal pressor area in the regulation of sympathetic vasomotor tone

It is well known that the ventrolateral medulla contains neurons involved in the tonic and reflex control of the cardiovascular system. Two regions within the ventrolateral medulla were initially identified: the rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM). Activation of the RVLM raises arterial blood pressure and sympathetic nerve activity, and activation of the CVLM causes opposite effects. The RVLM premotor neurons project directly to sympathetic preganglionic neurons and are involved in the maintenance of resting sympathetic vasomotor tone. A significant proportion of tonic activity in the RVLM sympathetic premotor neurons is driven by neurons located in a third region of the ventrolateral medulla denominated caudal pressor area (CPA). The CPA is a pressor region located at the extreme caudal part of the ventrolateral medulla that appears to have an important role controlling the activity of RVLM neurons. In this brief review, we will address the importance of the ventrolateral medulla neurons for the generation of resting sympathetic tone related to arterial blood pressure control focusing on two regions, the RVLM and the CPA.

Liver oxidative stress of the grey mullet Mugil cephalus presents seasonal variations in Ennore estuary

The objective of this study was to determine the liver oxidative stress status of grey mullets living in heavy-metal-rich polluted Ennore estuary compared with unpolluted Kovalam estuary. Fish were collected from both estuaries during the monsoon and summer seasons from October 2004 to September 2006. Fish liver homogenate (N = 20 per group) was prepared for evaluating oxidative stress parameters. Fish living in the polluted estuary had significantly higher lipid oxidation products, conjugated dienes (0.346 ± 0.017 vs 0.141 ± 0.012 DA233/mg protein), lipid hydroperoxides (0.752 ± 0.032 vs 0.443 ± 0.03 nmol/mg protein), and lipid peroxides (3.447 ± 0.14vs 1.456 ± 0.096 nmol MDA/mg protein) than those of the unpolluted estuary during the summer. In contrast, significantly lower levels of superoxide dismutase (20.39 ± 1.14 vs 53.63 ± 1.48 units/mg protein) and catalase (116 ± 6.87vs 153 ± 8.92 units/mg protein) were detected in the liver of fish from the polluted estuary (Ennore) compared to fish from the unpolluted estuary (Kovalam) during the summer. Variations in most of the oxidative stress parameters were observed between the summer and monsoon seasons, indicating the importance of seasonal variation for estuaries and their inhabitants.

The effect of a low dose of clenbuterol on rat soleus muscle submitted to joint immobilization

The aim of the present study was to evaluate the effect of joint immobilization on morphometric parameters and glycogen content of soleus muscle treated with clenbuterol. Male Wistar (3-4 months old) rats were divided into 4 groups (N = 6 for each group): control, clenbuterol, immobilized, and immobilized treated with clenbuterol. Immobilization was performed with acrylic resin orthoses and 10 µg/kg body weight clenbuterol was administered subcutaneously for 7 days. The following parameters were measured the next day on soleus muscle: weight, glycogen content, cross-sectional area, and connective tissue content. The clenbuterol group showed an increase in glycogen (81.6%, 0.38 ± 0.09 vs 0.69 ± 0.06 mg/100 g; P < 0.05) without alteration in weight, cross-sectional area or connective tissue compared with the control group. The immobilized group showed a reduction in muscle weight (34.2%, 123.5 ± 5.3 vs 81.3 ± 4.6 mg; P < 0.05), glycogen content (31.6%, 0.38 ± 0.09 vs 0.26 ± 0.05 mg/100 mg; P < 0.05) and cross-sectional area (44.1%, 2574.9 ± 560.2 vs 1438.1 ± 352.2 µm²; P < 0.05) and an increase in connective tissue (216.5%, 8.82 ± 3.55 vs 27.92 ± 5.36%; P < 0.05). However, the immobilized + clenbuterol group showed an increase in weight (15.9%; 81.3 ± 4.6 vs 94.2 ± 4.3 mg; P < 0.05), glycogen content (92.3%, 0.26 ± 0.05 vs 0.50 ± 0.17 mg/100 mg; P < 0.05), and cross-sectional area (19.9%, 1438.1 ± 352.2 vs 1724.8 ± 365.5 µm²; P < 0.05) and a reduction in connective tissue (52.2%, 27.92 ± 5.36 vs 13.34 ± 6.86%; P < 0.05). Statistical analysis was performed using Kolmogorov-Smirnov and homoscedasticity tests. For the muscle weight and muscle glycogen content, two-way ANOVA and the Tukey test were used. For the cross-sectional area and connective tissue content, Kruskal-Wallis and Tukey tests were used. This study emphasizes the importance of anabolic pharmacological protection during immobilization to minimize skeletal muscle alterations resulting from disuse.

Cognitive performance of young and elderly subjects on the free word recall memory test: effect of presentation order on recall order

The influence of aging on memory has been extensively studied, but the importance of short-term memory and recall sequence has not. The objective of the current study was to examine the recall order of words presented on lists and to determine if age affects recall sequence. Physically and psychologically healthy male subjects were divided into two groups according to age, i.e., 23 young subjects (20 to 30 years) and 50 elderly subjects (60 to 70 years) submitted to the Wechsler Adult Intelligence Scale-Revised and the free word recall test. The order of word presentation significantly affected the 3rd and 4th words recalled (P < 0.01; F = 14.6). In addition, there was interaction between the presentation order and the type of list presented (P < 0.05; F = 9.7). Also, both groups recalled the last words presented from each list (words 13-15) significantly more times 3rd and 4th than words presented in all remaining positions (P < 0.01). The order of word presentation also significantly affected the 5th and 6th words recalled (P = 0.05; F = 7.5) and there was a significant interaction between the order of presentation and the type of list presented (P < 0.01; F = 20.8). The more developed the cognitive functions, resulting mainly from formal education, the greater the cognitive reserve, helping to minimize the effects of aging on the long-term memory (episodic declarative).

Differential gene expression profiles of hepatocellular carcinomas associated or not with viral infection

Chronic hepatitis B (HBV) and C (HCV) virus infections are the most important factors associated with hepatocellular carcinoma (HCC), but tumor prognosis remains poor due to the lack of diagnostic biomarkers. In order to identify novel diagnostic markers and therapeutic targets, the gene expression profile associated with viral and non-viral HCC was assessed in 9 tumor samples by oligo-microarrays. The differentially expressed genes were examined using a z-score and KEGG pathway for the search of ontological biological processes. We selected a non-redundant set of 15 genes with the lowest P value for clustering samples into three groups using the non-supervised algorithm k-means. Fisher’s linear discriminant analysis was then applied in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Different transcriptional levels of genes were identified in HCC of different etiologies and from different HCC samples. When comparing HBV-HCC vs HCV-HCC, HBV-HCC/HCV-HCC vs non-viral (NV)-HCC, HBC-HCC vs NV-HCC, and HCV-HCC vs NV-HCC of the 58 non-redundant differentially expressed genes, only 6 genes (IKBKβ, CREBBP, WNT10B, PRDX6, ITGAV, and IFNAR1) were found to be associated with hepatic carcinogenesis. By combining trios, classifiers could be generated, which correctly classified 100% of the samples. This expression profiling may provide a useful tool for research into the pathophysiology of HCC. A detailed understanding of how these distinct genes are involved in molecular pathways is of fundamental importance to the development of effective HCC chemoprevention and treatment.

Genetic variability of vascular endothelial growth factor and prognosis of head and neck cancer in a Brazilian population

Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis. Polymorphisms in this gene have been evaluated in patients with several types of cancer. The objectives of this study were to determine if there was an association of the -1154G/A polymorphism of the VEGF gene with head and neck cancer and the interaction of this polymorphism with lifestyle and demographic factors. Additionally, the distribution of the VEGF genotype was investigated with respect to the clinicopathological features of head and neck cancer patients. The study included 100 patients with histopathological diagnosis of head and neck squamous cell carcinoma. Patients with treated tumors were excluded. A total of 176 individuals 40 years or older were included in the control group and individuals with a family history of neoplasias were excluded. Analysis was performed after extraction of genomic DNA using the real-time PCR technique. No statistically significant differences between allelic and genotype frequencies of -1154G/A VEGF polymorphism were identified between healthy individuals and patients. The real-time PCR analyses showed a G allele frequency of 0.72 and 0.74 for patients and the control group, respectively. The A allele showed a frequency of 0.28 for head and neck cancer patients and 0.26 for the control group. However, analysis of the clinicopathological features showed a decreased frequency of the A allele polymorphism in patients with advanced (T3 and T4) tumors (OR = 0.36; 95%CI = 0.14-0.93; P = 0.0345). The -1154A allele of the VEGF gene may decrease the risk of tumor growth and be a possible biomarker for head and neck cancer. This polymorphism is associated with increased VEGF production and may have a prognostic importance.

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

We studied the effects of adverse conditions such as constant light (LL) on the circadian rhythm of malate (MDH, EC 1.1.1.37) and lactate (LDH, EC 1.1.1.27) dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28), anxiety-like behavior (elevated plus-maze test) at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark), LL (light from day 10 to 21 of pregnancy), and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy). LL offspring did not show circadian rhythms of MDH (N = 62) and LDH (N = 63) activities (cosinor and ANOVA-LSD Fisher). They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test), an increase in mounting (94.4%), intromission (94.5%) and ejaculation (56.6%) latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test) and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12) compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher), anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.

Regulation of protein synthesis and the role of eIF3 in cancer

Maintenance of cell homeostasis and regulation of cell proliferation depend importantly on regulating the process of protein synthesis. Many disease states arise when disregulation of protein synthesis occurs. This review focuses on mechanisms of translational control and how disregulation results in cell malignancy. Most translational controls occur during the initiation phase of protein synthesis, with the initiation factors being the major target of regulation through their phosphorylation. In particular, the recruitment of mRNAs through the m7G-cap structure and the binding of the initiator methionyl-tRNAi are frequent targets. However, translation, especially of specific mRNAs, may also be regulated by sequestration into processing bodies or stress granules, by trans-acting proteins or by microRNAs. When the process of protein synthesis is hyper-activated, weak mRNAs are translated relatively more efficiently, leading to an imbalance of cellular proteins that promotes cell proliferation and malignant transformation. This occurs, for example, when the cap-binding protein, eIF4E, is overexpressed, or when the methionyl-tRNAi-binding factor, eIF2, is too active. In addition, enhanced activity of eIF3 contributes to oncogenesis. The importance of the translation initiation factors as regulators of protein synthesis and cell proliferation makes them potential therapeutic targets for the treatment of cancer.

Increased expression of keratinase and other peptidases by Candida parapsilosis mutants

Keratinases are enzymes of great importance involved in pathogenic processes of some fungi. They also have a widespread ecological role since they are responsible for the degradation and recycling of keratin. On the one hand, studying them furthers our knowledge of pathogenicity mechanisms, which has important implications for human health, and on the other hand, understanding their ecological role in keratin recycling has biotechnological potential. Here, a wild-type keratinolytic Candida parapsilosis strain isolated from a poultry farm was treated with ethyl methanesulfonate in order to generate mutants with increased keratinase activity. Mutants were then cultured on media with keratin extracted from chicken feathers as the sole source of nitrogen and carbon. Approximately 500 mutants were screened and compared with the described keratinolytic wild type. Three strains, H36, I7 and J5, showed enhanced keratinase activity. The wild-type strain produced 80 U/mL of keratinolytic activity, strain H36 produced 110 U/mL, strain I7, 130 U/mL, and strain J5, 140 U/mL. A 70% increase in enzyme activity was recorded for strain J5. Enzymatic activity was evaluated by zymograms with proteic substrates. A peptidase migrating at 100 kDa was detected with keratin, bovine serum albumin and casein. In addition, a peptidase with a molecular mass of 50 kDa was observed with casein in the wild-type strain and in mutants H36 and J5. Gelatinase activity was detected at 60 kDa. A single band of 35 kDa was found in wild-type C. parapsilosis and in mutants with hemoglobin substrate.

Prevalence of the STK15 F31I polymorphism and its relationship with mammographic density

Several studies have identified the single nucleotide polymorphism STK15 F31I as a low-penetrance risk allele for breast cancer, but its prevalence and risk association in the Brazilian population have not been determined. The goal of this study was to identify the frequency of this polymorphism in the Brazilian setting. Considering the high degree of admixture of our population, it is of fundamental importance to validate the results already reported in the literature and also to verify the relationship between this variant and breast cancer risk. A total of 750 women without breast cancer were genotyped using the TaqMan PCR assay for STK15 F31I polymorphism. Clinical information was obtained from review of the medical records and mammographic density from the images obtained using the BI-RADS System. The estimated risk of developing cancer was calculated according to the Gail model. The genotypic frequencies observed in this study were 4.5, 38.7, and 56.6%, respectively, for the STK15 F31I AA, AT and TT genotypes. The AT and AA genotypes were encountered significantly more often in premenopausal women with moderately dense, dense and heterogeneously dense breast tissue (P = 0.023). In addition, the presence of the TT genotype was significantly associated with age at menarche ≥12 years (P = 0.023). High mammographic density, associated with increased breast cancer risk, was encountered more frequently in premenopausal women with the risk genotypes STK15 F31I AA and AT. The genotypic frequencies observed in our Brazilian sample were similar to those described in other predominantly European populations.

Functional and morphological effects of resistance exercise on disuse-induced skeletal muscle atrophy

Abstract The reduction of skeletal muscle loss in pathological states, such as muscle disuse, has considerable effects in terms of rehabilitation and quality of life. Since there is no currently effective and safe treatment available for skeletal muscle atrophy, the search for new alternatives is necessary. Resistance exercise (RE) seems to be an important tool in the treatment of disuse-induced skeletal muscle atrophy by promoting positive functional (strength and power) and structural (hypertrophy and phenotypic changes) adaptive responses. Human and animal studies using different types of resistance exercise (flywheel, vascular occlusion, dynamic, isometric, and eccentric) have obtained results of great importance. However, since RE is a complex phenomenon, lack of strict control of its variables (volume, frequency, intensity, muscle action, rest intervals) limits the interpretation of the impact of the manipulation on skeletal muscle remodeling and function under disuse. The aim of this review is to critically describe the functional and morphological role of resistance exercise in disuse-induced skeletal muscle atrophy with emphasis on the principles of training.

Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

Simultaneous allergen inactivation and detoxification of castor bean cake by treatment with calcium compounds

Ricinus communis L. is of great economic importance due to the oil extracted from its seeds. Castor oil has been used for pharmaceutical and industrial applications, as a lubricant or coating agent, as a component of plastic products, as a fungicide or in the synthesis of biodiesel fuels. After oil extraction, a castor cake with a large amount of protein is obtained. However, this by-product cannot be used as animal feed due to the presence of toxic (ricin) and allergenic (2S albumin) proteins. Here, we propose two processes for detoxification and allergen inactivation of the castor cake. In addition, we establish a biological test to detect ricin and validate these detoxification processes. In this test, Vero cells were treated with ricin, and cell death was assessed by cell counting and measurement of lactate dehydrogenase activity. The limit of detection of the Vero cell assay was 10 ng/mL using a concentration of 1.6 x 10(5) cells/well. Solid-state fermentation (SSF) and treatment with calcium compounds were used as cake detoxification processes. For SSF, Aspergillus niger was grown using a castor cake as a substrate, and this cake was analyzed after 24, 48, 72, and 96 h of SSF. Ricin was eliminated after 24 h of SSF treatment. The cake was treated with 4 or 8% Ca(OH)2 or CaO, and both the toxicity and the allergenic properties were entirely abolished. A by-product free of toxicity and allergens was obtained.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Serum 25-hydroxyvitamin D and biochemical markers of bone metabolism in patients with juvenile idiopathic arthritis

Our objective was to evaluate the concentrations of serum 25-hydroxyvitamin D [25(OH)D], serum calcium, serum phosphorus, alkaline phosphatase, and parathormone (PTH) in patients with polyarticular juvenile idiopathic arthritis (JIA) and to associate them with disease duration and activity, bone mineral density and use of medications. In a cross-sectional and controlled study, 30 patients with polyarticular JIA were evaluated and compared to 30 healthy individuals matched for age and gender. Clinical status, anthropometry, laboratory markers in both patients and controls, and bone mineral density, only in the patients, were measured. Of the 30 patients included in the study, 23 (76.7%) were female and 16 (53.3%) non-Caucasian; mean age was 14 years (range = 4 to 20 years). Mean disease duration was 5 years (range = 1 to 12 years). The mean concentrations of serum albumin-corrected calcium (9.04 ± 0.41 mg/dL) and alkaline phosphatase (153.3 ± 100.1 IU) were significantly lower in patients with JIA than in controls (P < 0.0001 and P = 0.001, respectively). No differences in 25(OH)D, PTH or serum phosphorus were observed between JIA and control subjects. Regarding 25(OH)D concentration, 8 patients (26.7%) and 5 controls (16.7%) had 25(OH)D concentrations compatible with deficiency (lower than 20 ng/mL) and 14 patients (46.7%) and 18 controls (60%) had concentrations compatible with insufficiency (20-32 ng/mL). These values were not associated with disease activity, use of medications or bone mineral density. We observed a high frequency of 25(OH)D insufficiency and deficiency in the study sample. The compromised bone metabolism emphasizes the importance of follow-up of JIA patients.