Atypical forms of Guillain-Barré syndrome and H1N1-influenza vaccination

Recent epidemiological studies established extremely rare incidence of Guillain-Barre syndrome (GBS) after contemporary H1N1-influenza vaccine. We saw five patients with 'atypical' GBS variants that started within four weeks of 2010/2011 H1N1-influenza vaccine. There was no evidence for other etiologies of GBS. The patients presented with sensory ataxia, areflexia, extremity and oropharyngeal paresthesias, numbness, pain, weakness, sphincteric disturbances, and dysautonomia. One patient had Miller Fisher syndrome. All had elevated cerebrospinal fluid protein, and classic electrodiagnostic finding suggestive of GBS. All received the treatment with intravenous immunoglobulin with variable response. These pilot observations suggest that H1N1-influenza vaccine may be associated with rare and atypical variants of GBS. However, epidemiological studies with large cohorts are necessary to confirm excess cases of atypical GBS after H1N1-influenza vaccination.     

Synthesis and α1-adrenoceptor antagonist activity of tamsulosin analogues

Tamsulosin (-)-1 is the most utilized α(1)-adrenoceptor antagonist in the benign prostatic hyperplasia therapy owing to its uroselective antagonism and capability in relieving both obstructive and irritative lower urinary tract symptoms. Here we report the synthesis and pharmacological study of the homochiral (-)-1 analogues (-)-2-(-)-5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for α(1)-adrenoceptor subtypes. The benzyl analogue (-)-3, displaying a preferential antagonist profile for α1A-than α1D-and α1B-adrenoceptors, and a 12-fold higher potency at α1A-adrenoceptors with respect to the α1B subtype, may have improved uroselectivity compared to (-)-1.     

The impact of environmental and biological factors on paraoxonase 1 and γ-glutamyltranspeptydase activities in the blood of smelters

Disorders of paraoxonase and γ-glutamyltranspeptydase activities can induce development of the atherosclerotic process. The aim of the study was to examine the effect of occupational exposure to heavy metals, tobacco smoke and alcohol consumption on the activities of paraoxonase and γ-glutamyltranspeptydase as well as glutathione concentration. We have observed reduced paraoxonase activity and higher γ-glutamyltranspeptydase activity in serum of smelters when compared to control groups. In the blood of smoking smelters was demonstrated a negative correlation between paraoxonase activity and BMI value as well as between paraoxonase activity and tobacco smoke and consumption of 40 % alcohol. Also, negative correlation was found for the activity of paraoxonase and glutathione concentration as well as γ-glutamyltranspeptydase activity. Higher γ-glutamyltranspeptydase activity and lower paraoxonase activity in the serum of smelters exposed to heavy metals and tobacco smoke can cause disorders in functioning of the body.     

One year duration of immunity of the modified live bovine viral diarrhea virus type 1 and type 2 and bovine herpesvirus-1 fractions of Vista® Once SQ vaccine

Three studies were performed to determine the duration of immunity of the bovine viral diarrhea virus type 1 and type 2 (BVDV-1 and BVDV-2) and bovine herpesvirus-1 (BHV-1) fractions of a commercially prepared modified-live vaccine. Vista^® Once SQ (Vista^®) vaccine contains five modified-live viruses, BVDV-1, BVDV-2, BHV-1, bovine respiratory syncytial virus, and bovine parainfluenza 3 virus, and two modified-live bacteria, Pasteurella multocida and Mannheimia haemolytica. For all three studies, calves were administered a single dose of vaccine or placebo vaccine subcutaneously, and were challenged with one of the three virulent viruses at least one year following vaccination. Calves were evaluated daily following challenge for clinical signs of disease associated with viral infection, nasal swab samples were evaluated for virus shedding, and serum was tested for neutralizing antibodies. Following the BVDV-1 and BVDV-2 challenges, whole blood was evaluated for white blood cell counts, and for the BVDV-2 study, whole blood was also evaluated for platelet counts. Calves vaccinated with BVDV type 1a, were protected from challenge with BVDV type 1b, and had significant reductions in clinical disease, fever, leukopenia, and virus shedding compared to control calves. Vaccinated calves in the BVDV-2 study were protected from clinical disease, mortality, fever, leukopenia, thrombocytopenia, and virus shedding compared to controls. Vaccinated calves in the BHV-1 study were protected from clinical disease and fever, and had significantly reduced duration of nasal virus shedding. These three studies demonstrated that a single administration of the Vista^® vaccine to healthy calves induces protective immunity against BVDV-1, BVDV-2 and BHV-1 that lasts at least one year following vaccination.     

HIF-1α inhibitors: synthesis and biological evaluation of novel moracin O and P analogues

The natural products moracins O and P exhibited potent in vitro inhibitory activity against hypoxia-inducible factor (HIF-1), which is a key mediator during adaptation of cancer cells to tumour hypoxia. Systematic variations of the structures of benzofuran type moracins were made and structure-activity relationship analysis showed the importance of the 2-arylbenzofuran ring and the (R)-configuration of the core scaffold. Further evaluation of the representative compound 5 showed its inhibitory effect on HIF-1α protein accumulation and target gene expression under hypoxia.     

Effect of a Glyphosate-Based Herbicide on Gene Expressions of the Cytokines Interleukin-1β and Interleukin-10 and of Heme Oxygenase-1 in European Sea Bass,Dicentrarchus labrax L.

Glyphosate-based herbicides are the most frequently used herbicides in the world. We evaluated the effect of Roundup 360 SL on the expression of interleukin-1β (il-1β), interleukin-10 (il-10) and heme-oxygenase-1 (ho-1) in the gills, intestines and spleen of young European sea bass (Dicentrachus labrax L.), aged 8 mo. A group of fish was exposed to 647 mg/L of Roundup for 96 h. This treatment did not alter gene expression levels of il-1β and il-10 cytokine in the intestines, but significantly lowered both levels in the gills (p = 0.02 and p = 0.04 respectively). Expression levels of ho-1 were increased significantly in the three organs of fish from the treated group (the gills p = 0.04, the intestines p = 0.004 and the spleen p < 0.001). These changes may in turn negatively impact the immune system of European sea bass exposed to Roundup.     

Oral administration of docosahexaenoic acid attenuates interleukin-1β response and clinical course of septic neonates

ObjectiveTo analyze cytokine responses and the clinical course of septic neonates orally supplemented with docosahexaenoic acid as well as to evaluate fatty acid incorporation into leukocytes.MethodsA quasiexperimental study was conducted in neonates who developed sepsis following a surgical procedure. Selected neonates were randomly assigned to receive 100 mg docosahexaenoic acid (G-DHA) daily or olive oil (G-OO) as placebo for 14 d throughout a sepsis episode. At selection (baseline), blood samples were obtained to determine interleukin-1 (IL-1)β, interleukin-6 (IL-6), and tumor necrosis factor-α as well as the leucocyte fatty acid profile. Measurements were repeated at 7 (D7) and 14 d (D14) of follow-up. Within- and between-group comparisons were conducted with parametric statistics after logarithmic transformation. Repeated measurement analyses with a general linear model procedure were used, adjusting according to human milk intake, use of anti-inflammatory drugs, and nutritional status.ResultsSixty-three neonates were included: 29 in G-DHA group and 34 in G-OO group. Although decreases of cytokines during hospitalization were similar in both groups, there was a greater decrease of IL-1β in the G-DHA group than in the G-OO group after adjusting by confounders (P = 0.028). Leukocyte docosahexaenoic acid increased from 4.96 ± 2.96 at baseline to 5.52 ± 3.05 and 5.92 ± 2.8 at D7 and D14, respectively, in the G-DHA group (P = 0.044). Illness severity was inversely associated with the proportion of docosahexaenoic acid in leukocytes throughout follow-up (P = 0.034).ConclusionsOral supplementation with docosahexaenoic acid to neonates attenuates IL-1β response and the clinical course of sepsis. This may be an additional strategy to further benefit ill neonates even if they are not candidates for parenteral nutrition.     

Safety, tolerability, and immunogenicity after 1 and 2 doses of zoster vaccine in healthy adults ≥60 years of age

Background

Incidence and severity of herpes zoster (HZ) and postherpetic neuralgia increase with age, associated with age-related decrease in immunity to varicella-zoster virus (VZV). One dose of zoster vaccine (ZV) has demonstrated substantial protection against HZ; this study examined impact of a second dose of ZV.

Methods

Randomized, double-blind, multicenter study with 210 subjects ≥60 years old compared immunity and safety profiles after one and two doses of ZV, separated by 6 weeks, vs. placebo. Immunogenicity was evaluated using VZV interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay and VZV glycoprotein enzyme-linked immunosorbent antibody (gpELISA) assay. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card.

Results

No serious vaccine-related AEs occurred. VZV IFN-γ ELISPOT geometric mean count (GMC) of spot-forming cells per 10⁶ peripheral blood mononuclear cells increased in the ZV group from 16.9 prevaccination to 49.5 and 32.8 at 2 and 6 weeks postdose 1, respectively. Two weeks, 6 weeks and 6 months postdose 2, GMC was 44.3, 42.9, and 36.5, respectively. GMC in the placebo group did not change during the study. The peak ELISPOT response occurred ∼2 weeks after each ZV dose. The gpELISA geometric mean titers (GMTs) in the ZV group were higher than in the placebo group at 6 weeks after each dose. Correlation between the IFN-γ ELISPOT and gpELISA assays was poor.

Conclusions

ZV was generally well-tolerated and immunogenic in adults ≥60 years old. A second dose of ZV was generally safe, but did not boost VZV-specific immunity beyond levels achieved postdose 1.     

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Length of maternity leave and health of mother and child – a review

Summary Objectives: Assessment of the literature on the length of maternity leaves and health of mothers and children; evaluation of the Swiss situation in view of the maternity leave policy implemented in 2005. Methods: Review of thirteen original studies identified by PubMed using topic-related terms. Results: A positive association was shown between the length of maternity leave and mother’s mental health and duration of breastfeeding. Extended maternity leaves were also associated with lower perinatal, neonatal and post-neonatal mortality rates as well as lower child mortality; however, results are obtained in ecological studies. There is less evidence regarding other health outcomes. The new policy in Switzerland extends maternity leave for a considerable number of women to 14 weeks. With this prolongation, fewer depressive symptoms and longer breastfeeding duration can be expected, while benefits regarding other health outcomes would warrant longer leaves. Conclusions: Longer maternity leaves are likely to produce health benefits. The new policy in Switzerland will probably improve the situation of those women, who previously were granted only minimal leave and/or mothers with additional social risk factors. Submitted: 21 October 2005; Revised: 10 October 2006; Accepted: 5 December 2006     

Molecular modeling study and synthesis of quinazolinone-arylpiperazine derivatives as α1-adrenoreceptor antagonists

Three series of new 2-[(4-substituted piperazin-1-yl) methyl]quinazolin-4(3H)-ones 4a-c, Ethyl 6,7-dimethoxy-4-oxo-3-[2-(4-substituted piperazin-1-yl)acetamido/propanamido]-3,4-dihydroquinazoline-2-carboxylates 9a-f and their 2-methyl analogues 13a-l were designed and synthesized as promising α₁-adrenoceptor antagonists. The final compounds were evaluated for their in vivo hypotensive activity in normotensive cats. The most potent hypotensive quinazolinone derivatives 4b, 9e, 13i, 13j were further tested on isolated thoracic aortic rings of male Wister rats. All the tested compounds displayed α₁-blocking activity with IC₅₀ ranging from 0.2 to 0.4 mM less than prazosin. Furthermore, in the present work, molecular modeling study using Accelrys Discovery Studio 2.1 software was performed by mapping the synthesized compounds to the α₁-adrenoceptor antagonist hypothesis in order to predict their mechanism of action. Compound 13j which has the best-fitting score displayed the highest in vivo and in vitro activity among the tested compounds.     

The Impact of 1 Year of Healthier School Food Policies on Students’ Diets During and Outside of the School Day

Background

In 2012, Massachusetts implemented both the updated national school meal standards and comprehensive competitive food/beverage standards that closely align with current national requirements for school snacks.

Older Adults’ Use of Online and Offline Sources of Health Information and Constructs of Reliance and Self-Efficacy for Medical Decision Making

We know little about older adults' use of online and offline health information sources for medical decision making despite increasing numbers of older adults who report using the Internet for health information to aid in patient–provider communication and medical decision making. Therefore we investigated older adult users and nonusers of online and offline sources of health information and factors related to medical decision making. Survey research was conducted using random digit dialing of Florida residents' landline telephones. The Decision Self-Efficacy Scale and the Reliance Scale were used to measure relationships between users and nonusers of online health information. Study respondents were 225 older adults (age range = 50?92 years, M = 68.9, SD = 10.4), which included users (n = 105) and nonusers (n = 119) of online health information. Users and nonusers differed in frequency and types of health sources sought. Users of online health information preferred a self-reliant approach and nonusers of online health information preferred a physician-reliant approach to involvement in medical decisions on the Reliance Scale. This study found significant differences between older adult users and nonusers of online and offline sources of health information and examined factors related to online health information engagement for medical decision making.     

The anti-metastatic efficacy of β-ionone and the possible mechanisms of action in human hepatocarcinoma SK-Hep-1 cells

β-Ionone (BI), a precursor for carotenoids, is widely distributed in fruit and vegetables. Recent in vitro studies have demonstrated the potential anti-metastatic effects of BI, but the mechanisms underlying such actions are not clear. Because liver cancer is the most endemic cancer in Taiwan and in a large region of the world, we hereby investigate the anti-metastatic effects of BI and its mechanisms of actions in a highly metastatic human hepatocarcinoma SK-Hep-1 cells. We show that incubation of cells with BI (1-50?μm) for 24 and 48?h significantly inhibited cell invasion, migration and adhesion. Mechanistically, incubation of cells with BI (1-50?μm) for 24?h resulted in the following: (1) significant inhibition of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator activities, (2) up-regulation of protein expression of the tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and plasminogen activator inhibitor-1, (3) down-regulation of the expression of migration-related proteins, including focal adhesion kinase (FAK), phosphorylated form of FAK, Rho, Rac1 and Cdc42 and (4) up-regulation of the expression of nm23-H1 protein (P?相似文献   

Oat β-glucan and dietary calcium and phosphorus differentially modify intestinal expression of proinflammatory cytokines and monocarboxylate transporter 1 and cecal morphology in weaned pigs

Physiologic effects of dietary oat β-glucan and low and high dietary calcium-phosphorus (CaP) on intestinal morphology and gene expression related to SCFA absorption, mucus production, inflammation, and peptide digestion have not been established in weaned mammals. We therefore randomized 32 weaned pigs into 4 equal groups that received a cornstarch-casein-based diet with low (65% of the Ca and P requirement) and high (125 and 115% of the Ca and P requirement, respectively) CaP levels and low- and high-CaP diets supplemented with 8.95% oat β-glucan concentrate for 14 d. High-CaP diets downregulated duodenal expression of IL-1β (P < 0.05) by 30% compared with low-CaP diets. Furthermore, high-CaP diets reduced (P < 0.05) cecal crypt depth by 14% compared with low-CaP diets. Dietary β-glucan upregulated the expression of cecal MCT1 (P < 0.05) by 40% and that of colonic IL-6 (P < 0.05) by 142% compared with the control diet. Correlation analysis indicated that cecal MCT1 (r = 0.99, P < 0.001) and colonic IL-6 (r = 0.84, P < 0.05) expression was positively related to luminal butyrate and total SCFA, respectively, indicating that β-glucan may partly modify gene expression via increased SCFA generation. In conclusion, β-glucan and CaP levels modulated the expression of selected genes and morphology in the postweaning period, but effects were specific to intestinal segment. The present results further indicate that, in addition to being essential nutrients for bone accretion, dietary CaP level may modify the intestinal tissue response in young pigs.     

STRATOS guidance document on measurement error and misclassification of variables in observational epidemiology: Part 1—Basic theory and simple methods of adjustment

Measurement error and misclassification of variables frequently occur in epidemiology and involve variables important to public health. Their presence can impact strongly on results of statistical analyses involving such variables. However, investigators commonly fail to pay attention to biases resulting from such mismeasurement. We provide, in two parts, an overview of the types of error that occur, their impacts on analytic results, and statistical methods to mitigate the biases that they cause. In this first part, we review different types of measurement error and misclassification, emphasizing the classical, linear, and Berkson models, and on the concepts of nondifferential and differential error. We describe the impacts of these types of error in covariates and in outcome variables on various analyses, including estimation and testing in regression models and estimating distributions. We outline types of ancillary studies required to provide information about such errors and discuss the implications of covariate measurement error for study design. Methods for ascertaining sample size requirements are outlined, both for ancillary studies designed to provide information about measurement error and for main studies where the exposure of interest is measured with error. We describe two of the simpler methods, regression calibration and simulation extrapolation (SIMEX), that adjust for bias in regression coefficients caused by measurement error in continuous covariates, and illustrate their use through examples drawn from the Observing Protein and Energy (OPEN) dietary validation study. Finally, we review software available for implementing these methods. The second part of the article deals with more advanced topics.     

Comparative effect of genistein and daidzein on the expression of MCP-1, eNOS, and cell adhesion molecules in TNF-��-stimulated HUVECs

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-1 production. The effects of genistein and daidzein on MCP-1 secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-α exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)κB activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-1 and eNOS expression than that of daidzein. Additionally, NFκB transactivation might be partially related to the down-regulation of these mRNAs in TNF-α-stimulated HUVECs.     

Apolipoprotein D and α1-microglobulin in human urine: effect of cadmium exposure

Summary Apolipoprotein D is a previously unrecognized urinary protein of unknown function which we have tested as a potential marker for kidney malfunction. This protein and ₁-microglobulin have been quantified by zone immunoelectrophoresis assay in urine samples from a group of eight men occupationally exposed to cadmium-containing welding fumes for many years. All these workers had highly elevated concentrations of urinary cadmium and indications of tubular proteinuria, as compared to a group of 50 apparently healthy normal men analyzed in parallel. The cadmium-exposed workers demonstrated three- and 15-fold average increases in apolipoprotein D and ₁-microglobulin, respectively, over normal values in urine, estimated both as excretion rates and as milligrams of protein per mmol of creatinine. All these increments were highly significantly different (P < 0.001) from the corresponding values of the reference group. Essentially the same results were obtained for each of the proteins from two independent consecutive samplings of the workers' urine. There were good linear (R = 0.70, 0.80) and logarithmic (R = 0.84, 0.81) correlations between the urinary concentrations of ₁-microglobulin and apolipoprotein D for both the reference and the study group. Although not as sensitive an indicator for tubular proteinuria as ₁-microglobulin, apolipoprotein D, being a storage-stable urinary protein, seems a valuable complement for the diagnosis of tubular malfunction.     

Differential effects of 1α,25-dihydroxycholecalciferol on MCP-1 and adiponectin production in human white adipocytes

Background/aim

Obesity is characterized by a low-grade inflammation in white adipose tissue (WAT), which promotes insulin resistance. Low serum levels of 1α,25-dihydroxycholecalciferol (DHCC) associate with insulin resistance and higher body mass index although it is unclear whether vitamin D supplementation improves insulin sensitivity. We investigated the effects of DHCC on adipokine gene expression and secretion in adipocytes focusing on two key factors with pro-inflammatory [monocyte chemoattractant protein-1 (MCP-1/CCL2)] and anti-inflammatory [adiponectin (ADIPOQ)] effects.

Methods

Pre-adipocytes were isolated from human subcutaneous WAT and cultured until full differentiation. Differentiated adipocytes were either pre-treated with DHCC (10^?7 M) and subsequently incubated with tumor necrosis factor-α (TNFα, 100 ng/mL) or concomitantly incubated with TNFα/DHCC. MCP1 and adiponectin mRNA expression was measured by RT–PCR and protein release by ELISA.

Results

DHCC was not toxic and did not affect adipocyte morphology or the mRNA levels of adipocyte-specific genes. TNFα induced a significant increase in CCL2 mRNA and protein secretion, while DHCC alone reduced CCL2 mRNA expression (~25%, p < 0.05). DHCC attenuated TNFα-induced CCL2 mRNA expression in both pre-incubation (~15%, p < 0.05) and concomitant (~60%, p < 0.01) treatments. TNFα reduced ADIPOQ mRNA (~80%) and secretion (~35%). DHCC alone decreased adiponectin secretion to a similar degree (~35%, p < 0.05). Concomitant treatment with DHCC/TNFα for 48 h had an additive effect, resulting in a pronounced reduction in adiponectin secretion (~70%).

Conclusions

DHCC attenuates MCP-1 and adiponectin production in human adipocytes, thereby reducing the expression of both pro- and anti-inflammatory factors. These effects may explain the difficulties so far in determining the role of DHCC in insulin sensitivity and obesity in humans.