Lack of Galectin-3 Disturbs Mesenteric Lymph Node Homeostasis and B Cell Niches in the Course of Schistosoma mansoni Infection

Galectin-3 is a beta-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAc beta 1-4(Fuc alpha 1-3) GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine beta 1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in nonlymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S. mansoni.

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study

Background. Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. Method. Longitudinal regional grey matter volume and ventricle : brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. Results. While there was no longitudinal difference in ventricle : brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. Conclusions. Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.

Lack of Circadian Variation of Pulse Wave Velocity Measurements in Healthy Volunteers

Arterial stiffness is an independent marker of cardiovascular events. Pulse wave velocity (PWV) is a validated method to detect arterial stiffness that can be influenced by several factors including age and blood pressure. However, it is not clear whether PWV could be influenced by circadian variations. In the present study, the authors measured blood pressure and carotid-femoral PWV measurements in 15 young healthy volunteers in 4 distinct periods: 8 am, noon, 4 pm, and 8 pm. No significant variations of systolic (P=.92), mean (P=.77), and diastolic (P=.66) blood pressure among 8 am (113 +/- 15, 84 +/- 8, 69 +/- 6 mm Hg), noon (114 +/- 13, 83 +/- 8, 68 +/- 6 mm Hg), 4 pm (114 +/- 13, 85 +/- 8, 70 +/- 7 mm Hg), and 8 pm (113 +/- 7, 83 +/- 10, 68 +/- 7 mm Hg), respectively, were observed. Similarly, carotid-femoral PWV did not change among the periods (8 am: 7.6 +/- 1.4 m/s, noon: 7.4 +/- 1.1 m/s, 4 pm: 7.6 +/- 1.0 m/s, 8 pm, 7.6 +/- 1.3 m/s; P=.85). Considering all measurements, mean blood pressure significantly correlated with PWV (r=.31; P=.016). In young healthy volunteers, there is no significant circadian variation of carotid-femoral PWV. These findings support the concept that it does not appear mandatory to perform PWV measurements at exactly the same period of the day. J Clin Hypertens (Greenwich). 2011;13:19-22. (c) 2010 Wiley Periodicals, Inc.

Pharmacokinetics of ingested fluoride: Lack of effect of chemical compound

Fluoride in drinking water may be present from natural sources or added as sodium fluoride (NaF), sodium silicofluoride (Na2SiF6) or fluorosilicic acid (H2SiF6). Results from an early study with rats suggested that, when ingested as Na2SiF6, the absorption and excretion of fluoride were greater than when ingested as NaF. Objective: The present single-blind, crossover study with 10 adults was done to determine three key pharmacokinetic parameters: the maximum plasma fluoride concentrations (C-max), the elapsed time to reach the maximum concentrations (T-max) and the 6-h areas under the time-plasma concentration curves (AUCs) after ingestion of 500 ml, of water containing 0.67 or 5.45 mg F/L present naturally or added as NaF or H2SiF6. Design: Blood was collected prior to and at nine time points during 6 h after ingestion of the test solutions. Plasma was analysed by electrode after HMDS-facilitated diffusion and the data were analysed for statistically significant differences using repeated measures ANOVA. Results: The C-max, T-max and AUC values after ingestion of the solutions containing natural fluoride, NaF or H2SiF6 did not differ significantly at either dose level. Further, the Tmax values associated with the 0.67 and SAS mg/L solutions did not differ significantly indicating that the absorption, distribution and elimination rates were not affected by the dose size. Conclusions: Considered together with published reports, the present findings support the conclusion that the major features of fluoride metabolism are not affected differently by the chemical compounds commonly used to fluoridate water nor are they affected by whether the fluoride is present naturally or added artificially. (C) 2008 Elsevier Ltd. All rights reserved.

Health, sleep and lack of time: relations to domestic and paid work in nurses

OBJECTIVE: To assess whether reported morbidity and complaints of lack of time and sleep are associated with the burden of professional work and housework among nurses. METHODS: A cross-sectional exploratory study was carried out among female nurses and nurse assistants (N=206) of a public hospital in Rio de Janeiro, Brazil. Data were collected by means of a questionnaire. The prevalence ratio and 95% confidence intervals were estimated. RESULTS: Mean duration of professional work and housework time was 40.4 and 31.6 hours/week, respectively. Long professional working time (over 44 hours/week) were associated with mild emotional disorders (PR=1.37; 95% CI: 1.05-1.80), complaints of lack of time for resting/leisure (PR=1.61; 95% CI: 1.31-1.97), housework (PR=1.48; 95% CI: 1.12-1.97), and childcare (PR=1.99; 95% CI: 1.51-2.63). Long housework time (over 28 hours/week) was associated with lower prevalence of lack of time for childcare (PR=0.62; 95% CI: 0.46-0.84). High housework load was associated with lack of personal time and complaints of varicose veins (PR=1.31; 95% CI: 1.14-1.50 and PR=1.31; 95% CI: 1.08-1.58, respectively). Complaints of varicose veins were also frequent among female nurses with a total work load above 84 hours (PR=1.30; 95% CI: 1.05-1.61), though this group has shown a lower prevalence of arterial hypertension and recurrent headaches (PR=0.35; 95% CI: 0.15-0.83 and PR=0.53; 95% CI: 0.32-0.89, respectively). CONCLUSIONS: Results suggest that both professional and home environments are relevant in the evaluation of work overload on nurses' health and their family and social life. It is stressed the need for instruments for analyzing total workload among female populations.

Lack of directed V alpha 14-J alpha 281 rearrangements in NK1+ T cells.

NK1.1+ T cells are an unusual subset of TCR alpha beta cells distinguished by their highly restricted V beta repertoire and predominant usage of an invariant V alpha 14-J alpha 281 chain. To assess whether a directed rearrangement mechanism could be responsible for this invariant alpha chain, we have analyzed V alpha 14 rearrangements by polymerase chain reaction and Southern blot in a panel of cloned T-T hybrids derived from thymic NK1.1+ T cells. As expected a high proportion (17/20) of the hybrids had rearranged V alpha 14 to J alpha 281. However, V alpha 14-J alpha 281 rearrangements always occurred on only one chromosome and were accompanied by other V alpha-J alpha rearrangements (not involving V alpha 14) on the homologous chromosome. These data argue that rigorous ligand selection rather than directed rearrangement is responsible for the high frequency of V alpha 14-J alpha 281 rearrangements in NK1.1+ T cells.

Lack of Correlation between Seminal and Plasma HIV-1 Viral Loads is Associated with CD4T Cell Depletion in Therapy-naïve HIV-1+ Patients

The present study was conducted to investigate a possible correlation between plasma (PVL) and seminal viral load (SVL) on treatment-naïve HIV-1-infected patients in Vitória, ES, Brazil. We also evaluated whether the progressive immunosuppression associated with HIV disease (as evidenced by declining CD4 T cell counts) has any impact on the correlation between PVL and SVL HIV-1. Viral load on paired blood and semen samples from 56 consecutive treatment-naïve patients were evaluated and compared to CD4 cell counts. Viral load and T cell counts (cells/µl) were determined by NASBA and by flow cytometry, respectively. Overall, a strong positive correlation between PVL and SVL (rho = 0.438, p = 0.001) was observed. However, when patients were grouped according to their CD4 counts, this correlation was only significant among patients with CD4 counts > 200 cells/µl. Results presented here demonstrate the existence of a strong correlation between PVL and SVL on patients with CD4 cell counts > 200 cells/µl, suggesting that this association may correlate with disease progression.

Is confidence in decisions related to feedback? Evidence-and lack of evidence-from random samples of real-world managerial behavior?

Confidence in decision making is an important dimension of managerialbehavior. However, what is the relation between confidence, on the onehand, and the fact of receiving or expecting to receive feedback ondecisions taken, on the other hand? To explore this and related issuesin the context of everyday decision making, use was made of the ESM(Experience Sampling Method) to sample decisions taken by undergraduatesand business executives. For several days, participants received 4 or 5SMS messages daily (on their mobile telephones) at random moments at whichpoint they completed brief questionnaires about their current decisionmaking activities. Issues considered here include differences between thetypes of decisions faced by the two groups, their structure, feedback(received and expected), and confidence in decisions taken as well as inthe validity of feedback. No relation was found between confidence indecisions and whether participants received or expected to receivefeedback on those decisions. In addition, although participants areclearly aware that feedback can provide both confirming and disconfirming evidence, their ability to specify appropriatefeedback is imperfect. Finally, difficulties experienced inusing the ESM are discussed as are possibilities for further researchusing this methodology.

Lack of association between central adiposity and lipaemia in UK Sikh men

OBJECTIVE: To determine whether the positive statistical associations between measures of total and regional adiposity and measures of glucose, insulin and triacylglycerol ( TAG) metabolism reported in Caucasian men, are also observed in UK Sikhs. DESIGN: A matched cross-sectional study in which each volunteer provided a blood sample after a 12-h overnight fast and had anthropometric measurements taken. SUBJECTS: A total of 55 healthy Caucasian and 55 healthy UK Sikh men were recruited. The Caucasian and Sikh men were matched for age ( 48.7 +/- 10.9 and 48.3 +/- 10.0 y, respectively) and body mass index (BMI) ( 26.1 +/- 2.8 and 26.3 +/- 3.2 kg/m(2), respectively). MEASUREMENTS: Anthropometric measurements were performed to assess total and regional fat depots. The concentrations of plasma total cholesterol, high-density cholesterol (HDL- C), low-density cholesterol (LDL-C) and small dense LDL (LDL3), TAG, glucose, fasting insulin (ins) and nonesterified fatty acids (NEFA) were analysed in fasted plasma. Surrogate measures of insulin resistance (HOMA-IR) and insulin sensitivity (RQUICKI) were calculated from insulin and glucose (HOMA-IR) and insulin, glucose and NEFA ( RQUICKI) measurements. RESULTS: The Sikh men had significantly higher body fat, with the sum of the four skinfold measurements (Ssk) ( P = 0.0001) and subscapular skinfold value (P = 0.009) higher compared with the Caucasian men. The Sikh volunteers also had characteristics of the metabolic syndrome: lower HDL-C (P = 0.07), higher TAG (P = 0.004), higher % LDL3 (P = 0.0001) and insulin resistance (P = 0.05). Both ethnic groups demonstrated positive correlations between insulin and waist circumference (Caucasian: r = 0.661, P = 0.0001; Sikh: r = 0.477, P = 0.0001). The Caucasian men also demonstrated significant positive correlations between central adiposity (r = 0.275, P = 0.04), other measures of adiposity (BMI and suprailiac skinfold) and plasma TAG, whereas the Sikh men showed no correlation for central adiposity (r = 0.019, ns) and TAG with a trend to a negative relationship between other measures ( Ssk and suprailiac) which reached near significance for subscapular skinfold and TAG (r = - 0.246, P = 0.007). The expected positive association between insulin and TAG was observed in the Caucasian men (r = 0.318, P = 0.04) but not in the Sikh men (r = 0.011, ns). CONCLUSIONS: In the Caucasian men, the expected positive association between plasma TAG and centralized body fat was observed. However, a lack of association between centralized, or any other measure of adiposity, and plasma TAG was observed in the matched Sikh men, although both ethnic groups showed the positive association between centralized body fat and insulin resistance, which was less strong for Sikhs. These findings in the Sikh men were not consistent with the hypothesis that there is a clear causal relationship between body fat and its distribution, insulin resistance, and lipid abnormalities associated with the metabolic syndrome, in this ethnic group.

Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function

Background: Greatly increasing dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALA)] or fish oil [rich in the long-chain n-3 PUFAs eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids] can reduce markers of immune cell function. The effects of more modest doses are unclear, and it is not known whether ALA has the same effects as its long-chain derivatives. Objective: The objective was to determine the effects of enriching the diet with ALA or EPA+DHA on immune outcomes representing key functions of human neutrophils, monocytes, and lymphocytes. Design: In a placebo-controlled, double-blind, parallel study, 150 healthy men and women aged 25-72 y were randomly assigned to I of 5 interventions: placebo (no additional n-3 PUFAs), 4.5 or 9.5 g ALA/d, and 0.77 or 1.7 g EPA+DHA/d for 6 mo. The n-3 PUFAs were provided in 25 g fat spread plus 3 oil capsules. Blood samples were taken at 0, 3, and 6 mo. Results: The fatty acid composition of peripheral blood mononuclear cell phospholipids was significantly different in the groups with higher intakes of ALA or EPA+DHA. The interventions did not alter the percentages of neutrophils or monocytes engaged in phagocytosis of Escherichia coli or in phagocytic activity, the percentages of neutrophils or monocytes undergoing oxidative burst in response to E. coli or phorbol ester, the proliferation of lymphocytes in response to a T cell mitogen, the production of numerous cytokines by monocytes and lymphocytes, or the in vivo delayed-type hypersensitivity response. Conclusion: An intake of f less than or equal to9.5 g ALA/d or less than or equal to1.7 g EPA+DHA/d does not alter the functional activity of neutrophils, monocytes, or lymphocytes, but it changes the fatty acid composition of mononuclear cells.

Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS)

Phosphoenolpyruvate carboxykinase-1 (PCK1) is the rate-limiting enzyme in the hepatic gluconeogenic pathway. Studies have shown that overexpression of Pck1 in mice results in obesity-related traits and higher levels of physical activity (PA). Therefore, our aims were to investigate whether common genetic variation in the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age-group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum of four skinfolds, PA, and fitness, and also with the risk of being overweight or obese (P > 0.05). The interactions between the polymorphisms and age-group, gender, PA, and fitness were not statistically significant. This is the first study to comprehensively examine the association of PCK1 polymorphisms with obesity, PA, and fitness. Despite strong evidence from animal studies, our study in the EYHS cohort failed to identify an association of PCK1 polymorphisms with obesity, PA, and fitness.

Lack of photoreceptor signaling alters the expression of specific synaptic proteins in the retina

Synaptic modulation by activity-dependent changes constitutes a cellular mechanism for neuronal plasticity. However, it is not clear how the complete lack of neuronal signaling specifically affects elements involved in the communication between neurons. In the retina, it is now well established that both chemical and electrical synapses are essential to mediate the transmission of visual signaling triggered by the photoreceptors. In this study, we compared the expression of synaptic proteins in the retinas of wild-type (WT) vs. rd/rd mice, an animal model that displays inherited and specific ablation of photoreceptors caused by a mutation in the gene encoding the beta-subunit of rod cGMP-phosphodiesterase (Pde6b(rd1)). We specifically examined the expression of connexins (Cx), the proteins that form the gap junction channels of electrical synapses, in addition to synaptophysin and synapsin 1, which are involved in the release of neurotransmitters at chemical synapses. Our results revealed that Cx36 gene expression levels are lower in the retinas of rd/rd when compared with WT. Confocal analysis indicated that Cx36 immunolabeling almost disappeared in the outer plexiform layer without significant changes in protein distribution within the inner plexiform layer of rd/rd retinas. Likewise, synaptophysin expression remarkably decreased in the outer plexiform layer of rd/rd retinas, and this down-regulation was also associated with diminished transcript levels. Furthermore, we observed down-regulation of Cx57 gene expression in rd/rd retinas when compared with WT and also changes in protein distribution. Interestingly, Cx45 and synapsin I expression in rd/rd retinas showed no noticeable changes when compared with WT. Taken together, our results revealed that the loss of photoreceptors leads to decreased expression of some synaptic proteins. More importantly, this study provides evidence that neuronal activity regulates, but is not essential to maintain, the expression of synaptic elements. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Cocaine-induced behavioral sensitization in adolescent rats endures until adulthood: Lack of association with GluR1 and NR1 glutamate receptor subunits and tyrosine hydroxylase

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lack of papillomavirus (HPV) in pterygia of a Brazilian sample

OBJETIVO: Existem controvérsias a respeito da influência do papilomavirus (HPV) no desenvolvimento do pterígio. Assim, este estudo foi elaborado com o objetivo de verificar se o papilomavirus está presente na lesão. MÉTODOS: Trinta e seis portadores de pterígio unilateral foram operados, preparando-se o tecido removido e uma amostra de conjuntiva normal para exame de reação em cadeia da polimerase (PCR) para detecção de DNA. RESULTADOS: em todas as amostras do pterígio e da conjuntiva normal a pesquisa do DNA-papilomavirus por PCR resultou negativa. CONCLUSÃO: Segundo nossos resultados, o papilomavirus não é importante para o desenvolvimento do pterígio.

Lack of Epstein-Barr virus infection in cervical carcinomas

Context.-The Epstein-Barr virus (EBV) is a ubiquitous microorganism strongly associated with lymphoproliferative disorders and a large number of human neoplasms, mainly undifferentiated nasopharyngeal carcinoma and Burkitt lymphoma. The viral DNA has been detected in other tumors, such as carcinomas from tonsil, salivary glands, and thymus, and malignancies of the female genital tract. Some authors have proposed that EBV could play a role in the carcinogenesis of cervical tumors; however, other studies do not support this hypothesis.Objective.-To assess whether EBV is associated with female genital tract neoplasms.Design.-Sixty-five biopsy specimens (5 in situ carcinomas, 24 invasive squamous cell carcinomas, 6 lymphoepithelioma-like carcinomas, and 30 endocervical adenocarcinomas) were used to perform EBV detection through RNA in situ hybridization.Results.-None of the cervical carcinoma cases studied was positive for EBV infection.Conclusions.-The results suggest that it is still premature to incriminate EBV in the carcinogenesis of cervical carcinoma.