A high-fat meal impairs muscle vasodilatation response to mental stress in humans with Glu27 beta(2)-adrenoceptor polymorphism

Background: Forearm blood flow responses during mental stress are greater in individuals homozygous for the Glu27 allele. A high-fat meal is associated with impaired endothelium-dependent dilatation. We investigated the impact of high-fat ingestion on the muscle vasodilatory responses during mental stress in individuals with the Glu27 allele and those with the Gln27 allele of the beta(2)-adrenoceptor gene. Methods: A total of 162 preselected individuals were genotyped for the Glu27Gln beta(2)-adrenoceptor polymorphism. Twenty-four individuals participated in the study. Fourteen were homozygous for the Gln27 allele (Gln27Gln, 40 +/- 2 years; 64 +/- 2 kg), and 10 were homozygous for the Glu27 allele (Glu27Glu, 40 +/- 3 years; 65 +/- 3 kg). Forearm blood flow was evaluated by venous occlusion plethysmography before and after ingestion of 62 g of fat. Results: The high-fat meal caused no changes in baseline forearm vascular conductance (FVC, 2.2 +/- 0.1 vs. 2.4 +/- 0.2; P = 0.27, respectively), but reduced FVC responses to mental stress (1.5 +/- 0.2 vs. 0.8 +/- 0.2 units; P = 0.04). When volunteers were divided according to their genotypes, baseline FVC was not different between groups (Glu27Glu = 2.4 +/- 0.1 vs. Gln27Gln = 2.1 +/- 0.1 units; P = 0.08), but it was significantly greater in Glu27Glu individuals during mental stress (1.9 +/- 0.4 vs. 1.0 +/- 0.3 units; P = 0.04). High-fat intake eliminated the difference in FVC responses between Glu27Glu and Gln27Gln individuals (FVC, 1.3 +/- 0.4 vs. 1.2 +/- 0.4; P = 0.66, respectively). Conclusion: These findings demonstrate that a high-fat meal impairs muscle vasodilatation responses to mental stress in humans. However, this reduction can be attributed to the presence of the homozygous Glu27 allele of the beta(2)-adrenoceptor gene.

Native LDL-Cholesterol Mediated Monocyte Adhesion Molecule Overexpression is Blocked by Simvastatin

Aim of the study This study sought to evaluate the effect of nLDL concentrations on monocyte adhesion molecule expression in hypercholesterolemic patients with stable corollary artery disease (CAD) and to determine whether lipid-lowering therapy with simvastatin Would change this effect. Methods Blood samples from patients with hypercholesterolemia (mean LDL 152 mg/dL) and CAD (HC, n = 23) were collected before and after a 12-week treatment with 40 mg of simvastatin. Healthy individuals (mean LDL 111 mg/dL) were used as controls (CT, n = 15). Isolated nLDL, at a fixed concentration of 100 mg/dL, was added to monocyte suspensions obtained before and after the simvastatin treatment. Monocyte activation was determined by changes in cellular adhesion molecule expression. Results In response to nLDL, CD11b and CD14 adhesion molecule expression was higher in HC patients than in CT patients before treatment (174.2+/-8.4 vs 102.2+/-6.3, P<0.03 and 140.4+/-5.0 vs 90.4+/-6.7, P<0.04). After simvastatin treatment, CD11b expression decreased to 116.9+/-12.5 (P< 0.03) and CD14 expression to 107.5+/-6.2 (P<0.04). Alternatively, L-selectin expression was lower in HC patients than in CT patients before therapy (46.0+/-3.5 vs 62.1+/-5.5, P<0.04), and it increased markedly after lipid reduction to 58.7+/-5.0 (P<0.04 vs baseline). After simvastatin treatment, LDL was reduced to mean 101.5 mg/dL. Conclusions These data demonstrate that monocytes from HC patients are more prone to marked nLDL-mediated changes of adhesion molecule expression than monocytes from controls. Simvastatin is capable of inhibiting such nLDL effects. This proinflammatory response to nLDL may have a role in the early onset of atherosclerosis.

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation

Dias RG, Alves MJ, Pereira AC, Rondon MU, dos Santos MR, Krieger JE, Krieger MH, Negrao CE. Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation. Physiol Genomics 37: 99-107, 2009. First published January 21, 2009; doi:10.1152/physiolgenomics.90368.2008.-The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). L-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not sympathetic vasoconstriction.

Influence of Sensory Cues on the Stimulability for Liquid Sounds in Brazilian Portuguese-Speaking Children

Objective: Stimulability is the ability to produce an adequate sound under specific conditions. This study aimed to describe the stimulability of Brazilian Portuguese-speaking children with and without phonological disorders for the production of liquid sounds with the aid of visual and tactile cues. Patients and Methods: The study sample included 36 children between 5; 0 and 11; 6 years of age, 18 with phonological disorder and 18 without any speech-language disorders. Stimulability was measured for syllable imitation. The stimulability test employed includes 63 syllables with the sounds [1], [(sic)], and [(sic)], as well as seven oral vowels. If the subject was unable to imitate a sound, a visual cue was given. When necessary, a tactile cue was also given. Results: The sound [(sic)] required greater use of sensory cues. Children with phonological disorder needed a greater number of cues. Conclusion: The use of sensory cues seemed to facilitate sound stimulability, making it possible for the children with phonological disorder to accurately produce the sounds modeled. Copyright (C) 2009 S. Karger AG, Basel

Safety of oral glutamine in the abbreviation of preoperative fasting; a double-blind, controlled, randomized clinical trial

Introduction: No study so far has tested a beverage containing glutamine 2 h before anesthesia in patients undergoing surgery. Objectives: The aim of the study was to investigate: 1) the safety of the abbreviation of preoperative fasting to 2 h with a carbohydrate-L-glutamine-rich drink; and 2) the residual gastric volume (RGV) measured after the induction of anesthesia for laparoscopic cholecystectomies. Methods: Randomized controlled trial with 56 women (42 (17-65) years-old) submitted to elective laparoscopic cholecystectomy. Patients were randomized to receive either conventional preoperative fasting of 8 hours (fasted group, n = 12) or one of three different beverages drunk in the evening before surgery (400 mL) and 2 hours before the initiation of anesthesia (200 mL). The beverages were water (placebo group, n = 12), 12.5% (240 mOsm/L) maltodextrine (carbohydrate group, n = 12) or the latter in addition to 50 g (40 g in the evening drink and 10g in the morning drink) of L-glutamine (glutamine group, n = 14). A 20 F nasogastric tube was inserted immediately after the induction of general anesthesia to aspirate and measure the RGV. Results: Fifty patients completed the study. None of the patients had either regurgitation during the induction of anesthesia or postoperative complications. The median (range) of RGV was 6 (0-80) mL. The RGV was similar (p = 0.29) between glutamine group (4.5 [0-15] mL), carbohydrate group (7.0 [0-80] mL), placebo group (8.5 [0-50] mL), and fasted group (5.0 [0-50] mL). Conclusion: The abbreviation of preoperative fasting to 2 h with carbohydrate and L-glutamine is safe and does not increase the RGV during induction of anesthesia. (Nutr Hosp. 2011;26:86-90) DOI:10.3305/nh.2011.26.1.4993

Lymph Node Size in Rectal Cancer Following Neoadjuvant Chemoradiation-Can We Rely on Radiologic Nodal Staging After Chemoradiation?

OBJECTIVES: Local excision is currently being considered as an alternative strategy for ypT0-2 rectal cancer. However, patient selection is crucial to rule out nodal disease and is performed by radiologic studies that consider size as a surrogate marker for positive nodes. The purpose of this study was to determine the difference in size between metastatic and nonmetastatic nodes and the critical lymph node size after neoadjuvant chemoradiation therapy. METHODS: The 201 lymph nodes available from 31 patients with ypT0-2 rectal cancer were reviewed and measured. Lymph nodes were compared according to the presence of metastases and size. RESULTS: There was a mean of 6.5 lymph nodes per patient and 12 positive nodes of the 201 recovered (6%). Ninety-five percent of all lymph nodes were <5 mm, whereas 50% of positive lymph nodes were <3 mm. Metastatic lymph nodes were significantly greater in size (5.0 vs. 2.5mm; P = 0.02). Lymph nodes >4.5 mm had a greater risk of harboring metastases (P = 0.009). CONCLUSIONS: Patients with ypT0-2 rectal cancer following neoadjuvant chemoradiation have very small perirectal nodes. Individual metastatic lymph nodes are significantly larger. However, a significant number of lymph nodes after neoadjuvant chemoradiation (negative and positive) are <3 mm. Individual lymph node size is not a good predictor of nodal metastases and may lead to inaccurate radiologic staging.

Narrowed lumen of the right coronary artery in chronic chagasic patients is associated with ischemic lesions of segmental thinnings of ventricles

Thinning of myocardial segments, mainly at the apex and basal posterior region of left ventricle, are frequent lesions in chronic chagasic cardiopathy (CCC), but still without a well determined etiology. Previously we found severe myocardial microvascular dilatation that could cause ischemia in watershed regions. In this study we analyzed whether narrowness in epicardial coronary arteries in CCC might explain these thinned ventricular lesions. Two groups of dilated hearts with similar weights were compared: eleven hearts from patients with CCC versus four hearts from patients with dilated cardiomyopathy (IDCM). As normal controls we studied three non dilated normal weight hearts. There were no atherosclerotic plaques in the main branches of epicardial coronary arteries and cross-sectional luminal areas of proximal and distal segments were histologically measured. It was found that CCC hearts presented a lower mean luminal area in the right coronary artery (RCA) branch than IDCM, in proximal (4.3 +/- 1.4 vs 6.6 +/- 2.0 mm(2); p = 0.02) and in distal (1.6 +/- 1.0 vs 3.4 +/- 0.9 mm(2); p = 0.01) segments, with no statistical differences with normal hearts (2.7 +/- 1.3 and 1.5 +/- 0.3 mm(2)) in proximal (p = 0.2) and distal (p = 0.11) sections. In conclusion thinning of ventricular wall in CCC patients seems to be ischemic lesions in the peripheral territory irrigated by the right coronary artery, possibly due to a steal phenomenon by the left coronary, induced by micro vessels dilatation.

Bowel dilation as a predictor of adverse outcome in isolated fetal gastroschisis

Objectives This study was designed to evaluate bowel diameter as a predictor of adverse outcome in isolated fetal gastroschisis Methods Retrospective study involving 94 singleton pregnancies Ultrasound measurements of herniated bowel transverse diameter (BTD) were performed up to 3 weeks before delivery Adverse outcome was intrauterine/neonatal death and/or bowel complications Results Last BTD was recorded at 35 6 +/- 1 6 weeks and mean interval to delivery was 6 2 +/- 5 0 days Intrauterine/neonatal death occurred in 10 (10 6%) cases, bowel complications were observed in 8 (8 5%) BTD >= 15, >= 20, >= 25, and >= 30 mm were found in 87, 46, 13, and 4% of pregnancies with a favorable outcome. respectively BTD >= 25 mm sensitivity was 38%. and positive and negative predictive values were 38 and 87% For BTD >= 30 mm. the values were 19, 50, and 85% Observed/expected BTD ROC curve showed an area of 0 67, best cut-off value at 1 39, prediction values were similar to those for BTD >= 25 mm Bowel dilatation was also significantly associated with lower rate of primary surgical closure. longer period to full oral feeding, and prolonged hospital stay Conclusions Bowel dilatation demonstrated up to 3 weeks before delivery is a predictor of intestinal complications and is associated with lower late of primary surgical closure, longer period to achieve full oral feeding. and hospital stay Copyright (C) 2010 John Wiley & Sons, Ltd

HDL concentration, lipid transfer to HDL, and HDL size in normolipidemic nonobese menopausal women

Objective: To determine the impact of menopause on lipid transfer from donor lipoproteins to high-density lipoproteins (HDLs)-a process that is related to the protective function of HDL-and the size of HDL particles. Method: Plasma from 22 prernenopausal and 18 postmenopausal nonobese, normolipidemic women paired for age (40-50 years) was incubated in an artificial nanoemulsion labeled with radioactive lipids. Then the HDL fraction was assessed for radioactivity; the percentage of radioactive lipids transferred from the nanoemulsion to HDL was determined; and the size of HDL particles was measured by laser light scattering. Results: There were no differences between the 2 groups in serum concentration of HDL cholesterol (61 12 mg/dL vs 61 +/- 14 mg/dL) or apolipoprotein A(1) (1.5 +/- 0.3 g/L vs 1.5 +/- 0.2 g/L); lipid transfer to HDL; or size of HDL particles (8.8 +/- 0.8 vs 9.0 +/- 0.5 nm). Conclusion: Menopause was not found to affect HDL cholesterol plasma concentration, lipid transfer to HDL, or size of HDL particles in normolipidemic nonobese women. (C) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.All rights reserved.

Osteoporotic Fractures in the Brazilian Community-Dwelling Elderly: Prevalence and Risk Factors

The risk of osteoporotic fractures is known to vary among populations. There are no studies analyzing concomitantly clinical, densitometric, and lab risk factors in miscigenated community-dwelling population of Brazil. A total of 1007 elderly subjects (600 women and 407 men) from Sao Paulo, were evaluated using a questionnaire that included risk factors for osteoporotic fractures. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the hip and lumbar spine. Laboratory blood tests were also obtained. The prevalence of osteoporotic fractures was 13.2% (133 subjects), and the main fracture sites were distal forearm (6.0%), humerus (2.3%), femur (1.3%), and ribs (1.1%). Women had a higher prevalence (17.5%; 95% confidence interval [CI]: 14.6-20.6) than men (6.9%; 95% CI: 4.4-9.3) (p < 0.001). After adjusting for significant variables, logistic regression revealed that female gender (odds ratio [OR] = 2.7; 95% CI; 1.6-4.5; p < 0.001), current smoking (OR = 1.9; 95% CI: 1.2-3.3; p = 0.013), and the femoral neck T-score (OR = 0.7; 95% CI: 0.5-0.9; p = 0.001) remain significant risk factors for osteoporotic fractures in the community-dwelling elderly. Our findings identified that female gender, current smoking, and low hip BMD are independent risk factors for osteoporotic fractures.

Comparing topiramate with naltrexone in the treatment of alcohol dependence

To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence. The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of Sao Paulo, Brazil. A total of 155 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, patients were assigned randomly to receive topiramate (induction to 300 mg/day), naltrexone (50 mg/day) or placebo. Time to first relapse (consumption of > 60 g ethyl alcohol), cumulative abstinence duration and weeks of heavy drinking. In intention-to-treat analyses, topiramate was statistically superior to placebo on a number of measures including time to first relapse (7.8 versus 5.0 weeks), cumulative abstinence duration (8.2 versus 5.6 weeks), weeks of heavy drinking (3.4 versus 5.9) and percentage of subjects abstinent at 4 weeks (67.3 versus 42.6) and 8 weeks (61.5 versus 31.5), but not 12 weeks (46.2 versus 27.8). Results remained significant after controlling for Alcoholics Anonymous attendance, which was higher in topiramate than in other groups. There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups, but naltrexone showed trends toward inferior outcomes when compared to topiramate. The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism. Suggestive evidence was also obtained for superiority of topiramate versus naltrexone, but this needs to be verified in future research with larger sample sizes.

Oral lesions in 166 patients with cutaneous psoriasis: A controlled study

Objectives. This study was aimed to test if the frequency of oral lesions bears statistical correlation or not with the condition of cutaneous psoriasis. Study design. Two groups were examined, one made up of 166 patients with skin psoriasis and the other with the same number of individuals with a negative history of skin diseases (control group), matched by age, race, and sex. Patients with psoriasis were grouped according to their having localized or generalized forms of the disease. The oral mucosa was thoroughly examined in both groups. Data were analyzed using chi-square test, Fisher`s test, the odds ratio (OR) with a 95% confidence interval (CI), and the Ryan-Holm step-down Bonferroni procedure. The overall significance was set at P <= 0.05. Results. The oral lesions significantly associated with psoriasis were fissured tongue (FT, OR=2.7; 95% CI: 1.3-5.6), and geographic tongue (GT, OR=5.0; 95% CI: 1.5-16.8). Other factors analyzed, such as topical and/or systemic medication for treatment of psoriasis versus nontreated patients, and localized versus generalized forms of psoriasis presented no statistical association with the frequency of FT or GT lesions (P > 0.05). Conclusions. Patients with psoriasis presented no specific oral lesion different from those seen in the control group. Although further investigation is warranted to establish whether or not either FT or GT can be characterized as an oral expression of psoriasis, the present investigation did find for both these types of lesions that the frequency of each bore a statistically significant relation with the presence of cutaneous psoriasis.

Structural alterations in adult rat carotid bodies exposed to hyperbaric oxygenation

Inhibition of carotid body (CB) function is the main mechanism involved in the attenuation of respiratory drive observed during hyperoxia However, only a few studies at 5 0 atmospheres absolutes (ATA) have analyzed carotid body structure or function in hyperbaric oxygenation (HBO(2)) situations We hypothesized that rats will present CB structural alterations when exposed to different lower hyperbaric oxygen doses enough to alter their chemosensory response to hypoxia Methods - Twenty-one adult male Wistar rats, divided into three groups, were maintained in room air or exposed to O(2) at 2 4 or 3 0 ATA for six hours Histological, ultrastructural and immunohistochemical analyses for neuronal nitric oxide synthase (nNOS) and F2-isoprostane were performed in the excised CBs Results - Histological analyses revealed signs of intracellular edema in animals exposed to both conditions, but this was more marked in the 3 0 ATA group, which showed ultrastructural alterations at the mitochondrial level There was a significant increase in the volume density of intraglomic-congested capillaries in the 3 0 ATA group associated with an arteriolar vasoconstriction In the 2 4 ATA group, there was a relative increase of glomic light cells and a decrease of glomic progenitor cells Additionally, there was a stronger immunoreactivity for F2-isoprostane in the 3 0 ATA O(2)-exposed carotid bodies The glomic cells stained positive for nNOS, but no difference was observed between the groups Our results show that high 02 exposures may induce structural alterations in glomic cells with signs of lipid peroxidation We further suggest that deviation of blood flow toward intraglomic capillaries occurs in hyperbaric hyperoxia

High-Resolution Genomic Mapping Reveals Consistent Amplification of the Fibroblast Growth Factor Receptor Substrate 2 Gene in Well-Differentiated and Dedifferentiated Liposarcoma

Well-differentiated liposarcoma (WDLS) is one of the most common malignant mesenchymal tumors and dedifferentiated liposarcoma (DDLS) is a malignant tumor consisting of both WDLS and a transformed nonlipogenic sarcomatous component. Cytogenetically, WDLS is characterized by the presence of ring or giant rod chromosomes containing several amplified genes, including MDM2, TSPAN31 CDK4, and others mainly derived from chromosome bands 12q13-15. However, the 12q13-15 amplicon is large and discontinuous. The focus of this study was to identify novel critical genes that are consistently amplified in primary (nonrecurrent) WDLS and with potential relevance for future targeted therapy. Using a high-resolution (5.0 kb) ""single nucleotide polymorphism""/copy number variation microarray to screen the whole genome in a series of primary WDLS, two consistently amplified areas were found on chromosome 12: one region containing the MDM2 and CPM genes, and another region containing the FRS2 gene. Based on these findings, we further validated FRS2 amplification in both WDLS and DDLS. Fluorescence in situ hybridization confirmed FRS2 amplification in all WDLS and DDLS tested (n = 57). Real time PCR showed FRS2 mRNA transcriptional upregulation in WDLS (n = 19) and DDLS (n = 13) but not in lipoma (n = 5) and normal fat (n = 9). Immunoblotting revealed high expression levels of phospho-FRS2 at 1436 and slightly overexpression of total FRS2 protein in liposarcoma but not in normal fat or preadipocytes. Considering the critical role of FRS2 in mediating fibroblast growth factor receptor signaling, our findings indicate that FRS2 signaling should be further investigated as a potential therapeutic target for liposarcoma. (C) 2011 Wiley-Liss, Inc.

Associations of serious mental illness with earnings: results from the WHO World Mental Health surveys

Background Burden-of-illness data, which are often used in setting healthcare policy-spending priorities, are unavailable for mental disorders in most countries. Aims To examine one central aspect of illness burden, the association of serious mental illness with earnings, in the World Health Organization (WHO) World Mental Health (WMH) Surveys. Method The WMH Surveys were carried out in 10 high-income and 9 low- and middle-income countries. The associations of personal earnings with serious mental illness were estimated. Results Respondents with serious mental illness earned on average a third less than median earnings, with no significant between-country differences (chi(2)(9)=5.5-8.1, P=0.5-0.79). These losses are equivalent to 0.3-0.8% of total national earnings. Reduced earnings among those with earnings and the increased probability of not earning are both important components of these associations: Conclusions These results add to a growing body of evidence that mental disorders have high societal costs. Decisions about healthcare resource allocation should take these costs into consideration.