bluuebunny/crossref_metadata_2025 huggingface dataset:
Cigarette smoke induces growth differentiation factor 15 production in human lung epithelial cells: Implication in mucin over-expression
Authors: Wu Qun , Jiang Di , Chu Hong Wei
Published: December 2011

Excessive mucus is a hallmark of chronic obstructive pulmonary disease (COPD). There is an emerging interest in the role of TGF-β signaling in the initiation and progression of COPD. Growth differentiation factor 15 (GDF15) is a divergent member of TGF-β superfamily. However, whether cigarette smoke induces airway epithelial GDF15 production and its functions in the airways have not been revealed. Therefore, we first analyzed GDF15 protein expression in airway epithelium of human COPD smokers versus normal non-smokers. We then examined the regulation and function of GDF15 in human airway epithelial cells in response to cigarette smoke exposure. We found increased GDF15 protein expression in airway epithelium (mainly in ciliated cells) of human COPD smokers compared with normal non-smokers. Furthermore, cigarette smoke exposure consistently up-regulated GDF15 expression in human airway epithelial cells. Moreover, GDF15 was shown to play a critical role in cigarette smoke-induced airway epithelial MUC5AC expression. Lastly, activation of phosphoinositide 3-kinase (PI3K) pathway was largely responsible for GDF15-induced airway epithelial MUC5AC expression. Our findings indicate that human airway epithelial cells can produce GDF15 during cigarette smoke exposure, which subsequently activates PI3K pathway to promote mucin (e.g. MUC5AC) expression. This highlights a novel role of GDF15 in regulating airway mucosal immunity (e.g. mucin) in cigarette smoke-exposed lungs.
From injection therapies to natalizumab: views on the treatment of multiple sclerosis
Authors: Bomprezzi Roberto , Okuda Darin T. , Alderazi Yazan J. , Stüve Olaf , Frohman Elliot M.
Published: December 2011

Discoveries of the mechanisms that underlie the pathogenesis of multiple sclerosis have been acquired at an impressive rate over the last few decades and, as a consequence, a growing number of treatments are becoming available for this disease. This review first analyzes the experience from the early stages of the disease-modifying therapies, then, expanding on the concept of early treatment for improved outcomes, it focuses on natalizumab and its major complication, progressive multifocal leukoencephalopathy. We offer views on the risks associated with the use of natalizumab by underscoring the importance of the JC virus serology and by providing preliminary data on our experience with the extended interval dosing of natalizumab. This approach, which advocates individualized treatment plans, raises the question of the minimum effective natalizumab dose. Extended interval dosing suggests efficacy can be maintained while providing advantages of costs and convenience over regular monthly dosing. More data examining this strategy are necessary.
Health-related quality of life as an outcome variable in Parkinson’s disease
Authors: Martinez-Martin Pablo , Kurtis Mónica M.
Published: December 2011

In the past three decades, health-related quality of life (HRQoL) has become an outcome variable in Parkinson’s disease clinical trials. This review considers the measuring tools that have been developed, suitability of data reporting, complexity of outcome interpretation, and clinical application to provide evidence regarding available therapeutic interventions to date. In the introduction, different terms regarding quality of life are clearly defined. The methodology section offers an overview of generic, disease specific, and recommended HRQoL scales in Parkinson’s disease and the most important psychometric attributes a scale should meet. The interpretation of HRQoL outcomes is complex and not intuitive. Thus, appropriate reporting of data is crucial in order to calculate relative change, a result that facilitates understanding to what extent an intervention is beneficial. The concept of minimally important change/difference is explained as well as the different approaches to its calculation (anchor-based and distribution-based methods). In the results section, a brief overview of the impact on HRQoL of currently available treatments in Parkinson’s disease is provided. Special emphasis is given to data assessment, highlighting reports that helped understanding of the clinical significance of the intervention and therefore aided in making therapeutic decisions. The discussion section emphasizes the need for more clinical trials with HRQoL as a primary outcome and standardized reporting in order to further our understanding of the complexity of treatment effects and make evidence-based clinical decisions regarding HRQoL in patients with Parkinson’s disease.
Measuring the Effectiveness of Mutual Learning for Taiwan’s Tourist Hotels with the DEA Approach
Authors: Ting Chung-Te , Huang Chin-Wei
Published: December 2011

Taiwan’s international business and leisure hotels have created specific, divergent service operating systems to gain competitive advantage based on their distinctive target markets. For instance, the leisure properties focus on a hospitable, welcoming staff, while the business hotels aim for speedy service by employing relatively more workers. Given that hotel operators frequently benchmark direct competitors to improve on performance, researchers have suggested that hotel operators use a mutual learning strategy by benchmarking strategic techniques from hotels in disparate market segments. This study evaluates the effectiveness of the suggested mutual learning strategy between Taiwan’s business hotels and its leisure hotels, using the Different Systems model of data envelopment analysis (DEA) to examine potential improvements in efficiency. Empirical results show that few of Taiwan’s business hotels can gain efficiency through mutual learning from the leisure hotels—and some business hotels would actually lose efficiency if they adopted leisure properties’ operating practices. On the other hand, more than half of the leisure hotels in this sample would be able to achieve best practices from the mutual learning approach. On balance, both types of hotel can gain efficiency from the more common approach of benchmarking their direct competitors.
Motivational Effects of Empowerment on Employees’ Organizational Commitment
Authors: Kim BeomCheol (Peter) , Lee Gyumin , Murrmann Suzanne K. , George Thomas R.
Published: December 2011

Although studies have suggested that employee empowerment has a motivational effect on organizational commitment, the conceptual explanation and the factors that influence this relationship remain unexplored. To fill that gap, this study examines the mediating role of management trustworthiness in the relationship between empowerment and commitment, based on a survey of 330 employees in twenty-nine upscale hotel restaurants in Seoul, South Korea. A test of the model in this study finds that management trustworthiness fully mediates the relationship between influence, a dimension of empowerment, and organizational commitment while it partially mediates between attitude, another dimension of empowerment, and commitment. One implication is that managers can empower employees as a demonstration of the value the firm places its workers. Empowerment can support the notion of management trustworthiness, which is an essential element of organizational commitment.
Estimating the Impact of Free-Play Coupon Value on Players’ Slot Gaming Volumes
Authors: Suh Eunju
Published: December 2011

This study reports the results of a field experiment that assessed the relationship between free-play coupon value and a player’s slot gaming volume. Selected players in the customer database of a Las Vegas hotel casino received either a $50 or a $100 free-play incentive. Results indicated little effect of coupon value on a player’s slot volume. Indeed, the analysis found that complimentary rooms had a greater effect on coin-in, and complimentary food and beverage had the greatest effect of all. These findings imply that offering a relatively high incentive may not necessarily be more effective than providing a comparable lower incentive value in increasing a player’s slot gaming volume. Instead, casino managers should consider the overall profit picture from a given incentive and assess whether particular players are more responsive to complimentary amenities, such as room, food and beverage.
Posterior Knee Dislocation Following Septic Arthritis of the Knee
Authors: Bonnaig Nicolas S. , Casstevens E. Christopher , Freiberg Richard
Published: December 2011

This is a report of a case of nontraumatic posterior knee dislocation following septic arthritis in a 59-year-old male with leucopenia secondary to sarcoidosis. After confirmation of the diagnosis with synovial fluid analysis, the patient was taken emergently to the operating room for arthroscopic-assisted irrigation and debridement. Arthroscopy demonstrated intact cruciate ligaments but confirmed the diagnosis of septic arthritis demonstrating purulent synovial fluid. He was discharged after multiple repeat irrigation and debridement procedures and intravenous antibiotics improved his symptoms. The infection appeared to resolve as his laboratory values normalized following treatment. Three months later, however, x-rays revealed a nontraumatic posterior knee dislocation. We hypothesize that the soft tissues including the cruciate and collateral ligaments were made incompetent by enzymatic digestion and stretching with mobilization which allowed the knee to dislocate without a traumatic event.
Nonalcoholic Fatty Liver Disease
Authors: Leonard Barbara J.
Published: December 2011

Nonalcoholic fatty liver disease (NAFLD) is an accumulation of extra fat in the liver cells not caused by alcohol consumption. This disease is an increasingly common condition and the most common cause of abnormal liver function tests among adults. NAFLD is an array of liver diseases ranging from simple hepatic steatosis (fatty liver) to nonalcoholic steatohepatitis (NASH). A liver biopsy is the gold standard for determining hepatic fat content and staging fibrosis. However, the invasiveness of this approach can be a contraindication in certain patients. Noninvasive imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance (MR) can also detect hepatic fat content.
A Rare Multiple-Gestation Anomaly
Authors: Eastman Nicole
Published: December 2011

Conjoined twins are a rare anomaly. The classification of twinning that accounts for the majority of conjoined twins is thoraco-omphalopagus. This report discusses a case of female thoraco-omphalopagus twins who share a single cardiac system.
Intraductal Papilloma of the Extraglandular Segment of the Stensen Duct
Authors: Tandon Anupama , Wadhwa Neelam , Jain Bosky , Tandon Rajesh , Bhatt Shuchi
Published: December 2011

Intraductal papillary neoplasm of major salivary glands is exceedingly rare. Most reported cases have been diagnosed on histopathology; an extensive literature search found no case where a preoperative imaging diagnosis was suspected or established. This report depicts the sonographic diagnosis of intraductal papilloma of the extraglandular segment of the Stensen duct. The sonographic and histological appearances of this rare entity are illustrated.
Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa)
Authors: Couzi Lionel , Pitard Vincent , Sicard Xavier , Garrigue Isabelle , Hawchar Omar , Merville Pierre , Moreau Jean-François , Déchanet-Merville Julie
Published: December 2011

Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality in transplant recipients. Long-term protective immunity against HCMV requires both sustained specific T-cell response and neutralizing IgG production, but the interplay between these effector arms remains poorly defined. We previously demonstrated that γδ T cells play a substantial role as anti-HCMV T-cell effectors. The observation that CD16 (FcγRIIIA) was specifically expressed by the majority of HCMV-induced γδ T cells prompted us to investigate their cooperation with anti-HCMV IgG. We found that CD16 could stimulate γδ T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. Although CD16+γδ T cells did not mediate ADCC against HCMV-infected cells, in accordance with the low level of anti-HCMV IgGs recognizing infected cells, they produced IFNγ when incubated with IgG-opsonized virions. This CD16-induced IFNγ production was greatly enhanced by IL12 and IFNα, 2 cytokines produced during HCMV infection, and conferred to γδ T cells the ability to inhibit HCMV multiplication in vitro. Taken together, these data identify a new antiviral function for γδ T cells through cooperation with anti-HCMV IgG that could contribute to surveillance of HCMV reactivation in transplant recipients.
Morbidity and mortality in common variable immune deficiency over 4 decades
Authors: Resnick Elena S. , Moshier Erin L. , Godbold James H. , Cunningham-Rundles Charlotte
Published: December 2011

The demographics, immunologic parameters, medical complications, and mortality statistics from 473 subjects with common variable immune deficiency followed over 4 decades in New York were analyzed. Median immunoglobulin levels were IgG, 246 mg/dL; IgA, 8 mg/dL; and IgM, 21 mg/dL; 22.6% had an IgG less than 100 mg/dL. Males were diagnosed earlier (median age, 30 years) than females (median age, 33.5 years; P = .004). Ninety-four percent of patients had a history of infections; 68% also had noninfectious complications: hematologic or organ-specific autoimmunity, 28.6%; chronic lung disease, 28.5%; bronchiectasis, 11.2%; gastrointestinal inflammatory disease, 15.4%; malabsorption, 5.9%; granulomatous disease, 9.7%; liver diseases and hepatitis, 9.1%; lymphoma, 8.2%; or other cancers, 7.0%. Females had higher baseline serum IgM (P = .009) and were more likely to develop lymphoma (P = .04); 19.6% of patients died, a significantly shorter survival than age- and sex-matched population controls (P < .0001). Reduced survival was associated with age at diagnosis, lower baseline IgG, higher IgM, and fewer peripheral B cells. The risk of death was 11 times higher for patients with noninfectious complications (hazard ratio = 10.95; P < .0001). Mortality was associated with lymphoma, any form of hepatitis, functional or structural lung impairment, and gastrointestinal disease with or without malabsorption, but not with bronchiectasis, autoimmunity, other cancers, granulomatous disease, or previous splenectomy.
Model systems of genetically modified platelets
Authors: Thijs Tim , Deckmyn Hans , Broos Katleen
Published: December 2011

Although platelets are the smallest cells in the blood, they are implied in various processes ranging from immunology and oncology to thrombosis and hemostasis. Many large-scale screening programs, genome-wide association, and “omics” studies have generated lists of genes and loci that are probably involved in the formation or physiology of platelets under normal and pathologic conditions. This creates an increasing demand for new and improved model systems that allow functional assessment of the corresponding gene products in vivo. Such animal models not only render invaluable insight in the platelet biology, but in addition, provide improved test systems for the validation of newly developed anti-thrombotics. This review summarizes the most important models to generate transgenic platelets and to study their influence on platelet physiology in vivo. Here we focus on the zebrafish morpholino oligonucleotide technology, the (platelet-specific) knockout mouse, and the transplantation of genetically modified human or murine platelet progenitor cells in myelo-conditioned mice. The various strengths and pitfalls of these animal models are illustrated by recent examples from the platelet field. Finally, we highlight the latest developments in genetic engineering techniques and their possible application in platelet research.
The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo
Authors: Ponader Sabine , Chen Shih-Shih , Buggy Joseph J. , Balakrishnan Kumudha , Gandhi Varsha , Wierda William G. , Keating Michael J. , O'Brien Susan , Chiorazzi Nicholas , Burger Jan A.
Published: December 2011

B-cell receptor (BCR) signaling is a critical pathway in the pathogenesis of several B-cell malignancies, including chronic lymphocytic leukemia (CLL), and can be targeted by inhibitors of BCR-associated kinases, such as Bruton tyrosine kinase (Btk). PCI-32765, a selective, irreversible Btk inhibitor, is a novel, molecularly targeted agent for patients with B-cell malignancies, and is particularly active in patients with CLL. In this study, we analyzed the mechanism of action of PCI-32765 in CLL, using in vitro and in vivo models, and performed correlative studies on specimens from patients receiving therapy with PCI-32765. PCI-32765 significantly inhibited CLL cell survival, DNA synthesis, and migration in response to tissue homing chemokines (CXCL12, CXCL13). PCI-32765 also down-regulated secretion of BCR-dependent chemokines (CCL3, CCL4) by the CLL cells, both in vitro and in vivo. In an adoptive transfer TCL1 mouse model of CLL, PCI-32765 affected disease progression. In this model, PCI-32765 caused a transient early lymphocytosis, and profoundly inhibited CLL progression, as assessed by weight, development, and extent of hepatospenomegaly, and survival. Our data demonstrate that PCI-32765 effectively inhibits CLL cell migration and survival, possibly explaining some of the characteristic clinical activity of this new targeted agent.
Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis
Authors: Zhang Jing , Summah Hanssa , Zhu Ying-gang , Qu Jie-Ming
Published: December 2011

Background

Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease. Recent studies suggested an association between COPD and polymorphisms in CHRNA coding subunits of nicotinic acetylcholine receptor. Herein, we performed a meta-analysis to clarify the impact of CHRNA variants on COPD.

Methods

We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on CHRNA. Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.

Results

Among seven reported variants in CHRNA, rs1051730 was finally analyzed with sufficient studies. Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed. A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10-5). At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10-5). Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).

Conclusions

Our findings suggest that rs1051730 in CHRNA is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction.
NanoStriDE: normalization and differential expression analysis of NanoString nCounter data
Authors: Brumbaugh Christopher D , Kim Hyunsung J , Giovacchini Mario , Pourmand Nader
Published: December 2011

Background

The nCounter analysis system (NanoString Technologies, Seattle, WA) is a technology that enables the digital quantification of multiplexed target RNA molecules using color-coded molecular barcodes and single-molecule imaging. This system gives discrete counts of RNA transcripts and is capable of providing a high level of precision and sensitivity at less than one transcript copy per cell.

Results

We have designed a web application compatible with any modern web browser that accepts the raw count data produced by the NanoString nCounter analysis system, normalizes it according to guidelines provided by NanoString Technologies, performs differential expression analysis on the normalized data, and provides a heatmap of the results from the differential expression analysis.

Conclusion

NanoStriDE allows biologists to take raw data produced by a NanoString nCounter analysis system and easily interpret differential expression analysis of this data represented through a heatmap. NanoStriDE is freely accessible to use on the NanoStriDE website and is available to use under the GPL v2 license.
Genetic analysis of the merozoite surface protein-1 block 2 allelic types in Plasmodium falciparum clinical isolates from Lao PDR
Authors: Khaminsou Naly , Kritpetcharat Onanong , Daduang Jureerut , Charerntanyarak Lertchai , Kritpetcharat Panutas
Published: December 2011

Background

MSP-1 is one of the potential malarial vaccine candidate antigens. However, extensive genetic polymorphism of this antigen in the field isolates of Plasmodium falciparum represents a major hindrance for the development of an effective vaccine. Therefore, this study aimed to establish the prevalence and genetic polymorphisms of K1, MAD20 and RO33 allelic types of msp-1 block 2 among P. falciparum clinical isolates from Lao PDR.

Methods

Plasmodium falciparum isolates were collected from 230 P. falciparum-infected blood samples from three regions of Lao PDR. K1, MAD20 and RO33 were detected by nested PCR; SSCP was used for polymorphism screening. The nested PCR products of each K1, MAD20 and RO33 allelic types that had different banding patterns by SSCP, were sequenced.

Results

The overall prevalence of K1, MAD20 and RO33 allelic types in P. falciparum isolates from Lao PDR were 66.95%, 46.52% and 31.30%, respectively, of samples under study. Single infections with K1, MAD20 and RO33 allelic types were 27.83%, 11.74% and 5.22%, respectively; the remainders were multiple clonal infections. Neither parasite density nor age was related to MOI. Sequence analysis revealed that there were 11 different types of K1, eight different types of MAD20, and 7 different types of RO33. Most of them were regional specific, except type 1 of each allelic type was common found in 3 regions under study.

Conclusions

Genetic polymorphism with diverse allele types was identified in msp-1 block 2 among P. falciparum clinical isolates in Lao PDR. A rather high level of multiple clonal infections was also observed but the multiplicity of infection was rather low as not exceed 2.0. This basic data are useful for treatment and malaria control program in Lao PDR.
Using WHO-FRAX to Describe Fracture Risk: Experience in Primary Care
Authors: Maclean F R , Thomson S A , Gallacher S J
Published: December 2011

Ideally those at highest risk of fracture should be identified prior to fracture occurrence to reduce mortality, morbidity and costs. Case-finding strategies for those at high risk of first fracture or systematic case-finding strategies following fracture are recommended in the UK, rather than population-based screening to identify individuals at high fracture risk. General practices in the UK hold relevant data on individuals beyond fracture history that could allow identification of a wider group of patients at highest risk of fracture. The aim of the paper is to evaluate the feasibility of applying the WHO-FRAX fracture risk calculator to general practice populations using existing recorded data. A cross-sectional study of 2467 women aged 50 years and older (mean 66.2 years, standard deviation = 11.3) registered with two Scottish General Practices with low deprivation (one semi-rural, one urban) was undertaken. Patient data were extracted from the two general practices’ patient information databases and the WHO-FRAX calculator was applied to these data. WHO-FRAX calculation was possible on 1872 patients. Of these, 687 patients were found to have a high fracture risk (risk of major facture ≥15% and or risk of hip fracture ≥3% – 37% of the WHO-FRAX assessed cohort) and should be considered for follow-up. In conclusion, use of the WHO-FRAX calculator using general practice-held data is feasible and can help to identify a patient group at higher fracture risk. Further evaluation and treatments can then be targeted at this group.
Circulating Soluble Intercellular Adhesion Molecule 1 and Subclinical Atherosclerosis: the Coronary Artery Risk Development in Young Adults Study
Authors: Gross Myron D , Bielinski Suzette J , Suarez-Lopez Jose R , Reiner Alex P , Bailey Kent , Thyagarajan Bharat , Carr J Jeffrey , Duprez Daniel A , Jacobs David R
Published: December 2011

BACKGROUND

Soluble intercellular adhesion molecule 1 (sICAM-1) is associated with endothelial dysfunction and clinical cardiovascular disease. We investigated the relationship of subclinical atherosclerosis with sICAM-1 concentration.

METHODS

sICAM-1 concentration was assayed at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (black and white men and women, average age 40 years). We assessed progression of coronary artery calcification (CAC) through year 20 (n = 2378), and both carotid artery stenosis (n = 2432) and intima-media thickness (IMT) at year 20 (n = 2240).

RESULTS

Median sICAM-1 was 145.9 μg/L. Among a subgroup with advanced atherosclerotic plaque (either CAC or stenosis), IMT was 0.010 (95% CI 0.003–0.017 mm) higher per SD of sICAM-1 (44 μg/L) in a model adjusted for age, race, sex, clinic, smoking, exercise, body size, education, blood pressure, antihypertensive medication, plasma lipids, and cholesterol-lowering medication. With the same adjustment, the odds ratio (OR) for the presence of year-20 carotid artery stenosis per SD of sICAM-1 was 1.12 (95% CI 1.01–1.25, P < 0.04), whereas for occurrence of CAC progression the OR was 1.16 (1.04–1.31, P < 0.01). The associations with CAC and carotid stenosis were strongest in the top 20th of the sICAM-1 distribution.

CONCLUSIONS

sICAM-1 concentration may be an early biomarker that indicates changes in the artery wall that accompany atherosclerosis, as well as the presence of advanced plaque in the coronary and carotid arteries. This finding holds in people with low total burden of atherosclerosis, decades before the development of clinical CVD.
Should diabetic women with breast cancer have their own intervention studies?
Authors: Potter David A , Yee Douglas , Guo Zhijun , Rodriguez Mariangellys
Published: December 2011

This commentary on ‘Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity’ by Nogueiraet al., published in this issue ofEndocrine-Related Cancer, addresses the challenges of translating diet, exercise, and pharmacologic trials in diabetic mouse mammary tumor models to human studies. We propose that trials specifically designed to test such interventions in diabetic women with breast cancer would be valuable and informative.
The renin–angiotensin system in the breast and breast cancer
Authors: Vinson Gavin P , Barker Stewart , Puddefoot John R
Published: December 2011

Much evidence now suggests that angiotensin II has roles in normal functions of the breast that may be altered or attenuated in cancer. Both angiotensin type 1 (AT1) and type 2 (AT2) receptors are present particularly in the secretory epithelium. Additionally, all the elements of a tissue renin–angiotensin system, angiotensinogen, prorenin and angiotensin-converting enzyme (ACE), are also present and distributed in different cell types in a manner suggesting a close relationship with sites of angiotensin II activity. These findings are consistent with the concept that stromal elements and myoepithelium are instrumental in maintaining normal epithelial structure and function. In disease, this system becomes disrupted, particularly in invasive carcinoma. Both AT1 and AT2 receptors are present in tumours and may be up-regulated in some. Experimentally, angiotensin II, acting via the AT1 receptor, increases tumour cell proliferation and angiogenesis, both these are inhibited by blocking its production or function. Epidemiological evidence on the effect of expression levels of ACE or the distribution of ACE or AT1 receptor variants in many types of cancer gives indirect support to these concepts. It is possible that there is a case for the therapeutic use of high doses of ACE inhibitors and AT1 receptor blockers in breast cancer, as there may be for AT2 receptor agonists, though this awaits full investigation. Attention is drawn to the possibility of blocking specific AT1-mediated intracellular signalling pathways, for example by AT1-directed antibodies, which exploit the possibility that the extracellular N-terminus of the AT1 receptor may have previously unsuspected signalling roles.
13-cis-Retinoic acid specific down-regulation of angiotensin type 1 receptor in rat liver epithelial and aortic smooth muscle cells
Authors: Snyder Russell , Thekkumkara Thomas
Published: December 2011

Transcriptional repression throughcis- andtrans-acting factors enabling an alternate approach to control angiotensin type 1 receptor (AT1 or AGTR1 as listed in the MGI database) expression has not been studied. In previous investigations, treatment with retinoic acid was found to be associated with enhanced insulin sensitivity. In our previous study, expression of AT1 was found to be inversely correlated with intracellular glucose concentrations. Therefore, we hypothesized that 13-cis-retinoic acid (13cRA), an antioxidant, enhances insulin-sensitive glucose-mediated down-regulation of the AT1. In this study, we used continuously passaged rat liver epithelial cells. Our study shows that cells exposed to 13cRA specifically down-regulated the AT1 protein in a dose- and time-dependent manner, independently of any change in receptor affinity. Down-regulation of the AT1 expression leads to reduced AngII-mediated intracellular calcium release, a hallmark of receptor-mediated intracellular signaling. Similarly with receptor down-regulation, we observed a significant reduction inAT1mRNA; however, the AT1 down-regulation was independent of insulin-sensitive glucose uptake and retinoic acid receptor activation (RAR/RXR). Treatment with 13cRA resulted in phosphorylation of p42/p44 MAP kinases in these cells. Subsequent studies using MEK inhibitor PD98059 prevented 13cRA-mediated AT1 down-regulation and restored AngII-mediated intracellular calcium response. Furthermore, 13cRA-mediated inhibitory effects on AT1 were validated in primary rat aortic smooth muscle cells. In summary, our results demonstrate for the first time that 13cRA has a glucose- and RAR/RXR-independent mechanism for transcriptional inhibition of AT1, suggesting its therapeutic potential in systems in which AT1 expression is deregulated in insulin-sensitive and -insensitive tissues.
17β-Estradiol regulates cyclin A1 and cyclin B1 gene expression in adult rat seminiferous tubules
Authors: Bois Camille , Delalande Christelle , Bouraïma-Lelong Hélène , Durand Philippe , Carreau Serge
Published: December 2011

Spermatogenesis, which is the fundamental mechanism allowing male gamete production, is controlled by several factors, and among them, estrogens are likely concerned. In order to enlighten the potential role of estrogen in rat spermatogenesis, seminiferous tubules (ST) from two groups of seminiferous epithelium stages (II–VIII and IX–I) were treated with either 17β-estradiol (E2) agonists or antagonists for estrogen receptors (ESRs). In this study, we show that cyclin A1 and cyclin B1 gene expression is controlled by E2at a concentration of 10−9 M only in stages IX–I. This effect is mimicked by a treatment with the G-protein coupled estrogen receptor (GPER) agonist G1 and is abolished by treatment with the ESR antagonist ICI 182 780. Moreover, using letrozole, a drug that blocks estrogen synthesis, we demonstrate that these genes are under the control of E2within rat ST. Thus, germ cell differentiation may be regulated by E2which acts through ESRs and GPER, expressed in adult rat ST.
Política de Saúde Mental no Brasil: evolução do gasto federal entre 2001 e 2009
Authors: Gonçalves Renata Weber , Vieira Fabíola Sulpino , Delgado Pedro Gabriel Godinho
Published: December 2011

OBJETIVO: Analisar a evolução de estimativas do gasto federal com o Programa de Saúde Mental desde a promulgação da lei nacional de saúde mental. MÉTODOS: O gasto federal total do Programa de Saúde Mental e seus componentes de gastos hospitalares e extra-hospitalares foi estimado a partir de 21 categorias de gastos de 2001 a 2009. Os valores dos gastos foram atualizados para valores em reais de 2009 por meio da aplicação do Índice de Preços ao Consumidor Amplo. Foi calculado o valor per capita/ano do gasto federal em saúde mental. RESULTADOS: Observou-se o crescimento real de 51,3% do gasto em saúde mental no período. A desagregação do gasto revelou aumento expressivo do valor extra-hospitalar (404,2%) e decréscimo do hospitalar (-39,5%). O gasto per capita teve crescimento real menor, embora expressivo (36,2%). A série histórica do gasto per capita desagregado mostrou que em 2006, pela primeira vez, o gasto extra-hospitalar foi maior que o hospitalar. O valor per capita extra-hospitalar teve o crescimento real de 354,0%; o valor per capita hospitalar decresceu 45,5%. CONCLUSÕES: Houve crescimento real dos recursos federais investidos em saúde mental entre 2001 e 2009 e investimento expressivo nas ações extra-hospitalares. Houve inversão no direcionamento dos recursos, a partir de 2006, na direção dos serviços comunitários. O componente do financiamento teve papel crucial como indutor da mudança de modelo de atenção em saúde mental. O desafio para os próximos anos é sustentar e aumentar os recursos para a saúde mental num contexto de desfinanciamento do Sistema Único de Saúde.
Spatial analysis of leprosy incidence and associated socioeconomic factors
Authors: Cury Maria Rita de Cassia Oliveira , Paschoal Vania Del´Arco , Nardi Susilene Maria Tonelli , Chierotti Ana Patrícia , Rodrigues Júnior Antonio Luiz , Chiaravalloti-Neto Francisco
Published: December 2011

OBJECTIVE: To identify clusters of the major occurrences of leprosy and their associated socioeconomic and demographic factors. METHODS: Cases of leprosy that occurred between 1998 and 2007 in São José do Rio Preto (southeastern Brazil) were geocodified and the incidence rates were calculated by census tract. A socioeconomic classification score was obtained using principal component analysis of socioeconomic variables. Thematic maps to visualize the spatial distribution of the incidence of leprosy with respect to socioeconomic levels and demographic density were constructed using geostatistics. RESULTS: While the incidence rate for the entire city was 10.4 cases per 100,000 inhabitants annually between 1998 and 2007, the incidence rates of individual census tracts were heterogeneous, with values that ranged from 0 to 26.9 cases per 100,000 inhabitants per year. Areas with a high leprosy incidence were associated with lower socioeconomic levels. There were identified clusters of leprosy cases, however there was no association between disease incidence and demographic density. There was a disparity between the places where the majority of ill people lived and the location of healthcare services. CONCLUSIONS: The spatial analysis techniques utilized identified the poorer neighborhoods of the city as the areas with the highest risk for the disease. These data show that health departments must prioritize politico-administrative policies to minimize the effects of social inequality and improve the standards of living, hygiene, and education of the population in order to reduce the incidence of leprosy.
Prevalência de quedas e fatores associados em idosos
Authors: Cruz Danielle Teles da , Ribeiro Luiz Cláudio , Vieira Marcel de Toledo , Teixeira Maria Teresa Bustamante , Bastos Ronaldo Rocha , Leite Isabel Cristina Gonçalves
Published: December 2011

OBJETIVO: Estimar a prevalência de quedas em idosos e analisar fatores associados. MÉTODOS: Estudo transversal com 420 idosos (60 anos ou mais) residentes em Juiz de Fora, MG, em 2010. Foi realizado inquérito domiciliar e descrita a ocorrência de queda nos últimos 12 meses. Para a análise dos fatores associados ao desfecho, foi construído um modelo teórico de determinação com três blocos hierarquizados. As variáveis foram ajustadas entre si dentro de cada bloco; aquelas com nível de significância < 0,20 foram incluídas no modelo de regressão de Poisson e ajustadas ao nível superior ao seu, com o nível de 5% de significância. RESULTADOS: A prevalência de quedas entre os idosos foi de 32,1% (IC95% 27,7;36,9). Entre aqueles que sofreram queda, 53% tiveram uma única queda e 19% tiveram fratura como conseqüência. Maior parte das quedas (59%) ocorreu no domicílio do idoso. A ocorrência de quedas associou-se com idade avançada, sexo feminino, necessidade de auxílio para locomoção e diagnóstico auto-referido de osteoporose. CONCLUSÕES: As quedas são freqüentes entre idosos. O conhecimento dos fatores associados à ocorrência desse evento pode auxiliar na elaboração de estratégias de prevenção e serviços de saúde adequados.
Distribuição regional e socioeconômica da disponibilidade domiciliar de alimentos no Brasil em 2008-2009
Authors: Levy Renata Bertazzi , Claro Rafael Moreira , Mondini Lenise , Sichieri Rosely , Monteiro Carlos Augusto
Published: December 2011

OBJETIVO: Descrever a distribuição regional e socioeconômica da disponibilidade domiciliar de alimentos no Brasil. MÉTODOS: Estudo com dados secundários da Pesquisa de Orçamentos Familiares 2008-2009, realizada pelo Instituto Brasileiro de Geografia e Estatística sobre aquisições de alimentos e bebidas para consumo domiciliar. As quantidades de alimentos, registradas durante sete dias consecutivos nos 55.970 domicílios brasileiros amostrados, foram transformadas em calorias e nutrientes. Indicadores de qualidade da dieta foram construídos e analisados segundo estratos socioeconômicos e regionais da população brasileira. RESULTADOS: O teor protéico da disponibilidade alimentar mostrou-se adequado em todos os estratos regionais e econômicos. Em contrapartida, observou-se excesso de açúcares livres e de gorduras em todas as regiões, especialmente nas regiões Sul e Sudeste. A proporção de gorduras saturadas foi elevada no meio urbano e consistente com a maior participação de produtos de origem animal. A presença insuficiente de frutas, legumes e verduras foi comum em todas as regiões. Intensificação do teor de gorduras e diminuição do teor de carboidratos da dieta foram observadas com o aumento da renda. CONCLUSÕES: As características negativas da qualidade da dieta da população brasileira observadas ao final da primeira década do século XXI conferem alta prioridade para políticas públicas de promoção da alimentação saudável.
Prevalence of pediculosis capitis in children from a rural school in Yucatan, Mexico
Authors: Manrique-Saide Pablo , Pavía-Ruz Norma , Rodríguez-Buenfil Jorge C. , Herrera Herrera Roodeth , Gómez-Ruiz Pilar , Pilger Daniel
Published: December 2011

We conducted an analytical cross-sectional survey to estimate the prevalence of and factors associated with active head lice infestation. In total 140 children, aged 6 to 16-years, from a public school in rural Yucatan, Mexico, were examined by wet-combing. A structured questionnaire was used to collect information on individuals and the conditions in the surrounding environment. Head lice infestation was found in 19 out of the 140 children tested (13.6%) and this was associated with both lower income (OR 9.9, 95% CI 2.15-45.79, p = 0.003) and a higher frequency of hair washing (OR 8, 95% CI 1.58-50, p = 0.012). Intersectoral control programs that take into account the socioeconomic differences of children should be implemented.
Potential utility of hyperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime
Authors: Ayres Diana Copi , Fedele Thiago Antonio , Marcucci Maria Cristina , Giorgio Selma
Published: December 2011

In this study we investigated the efficacy of hyperbaric oxygen (HBO) therapy, alone or combined with the pentavalent antimonial glucantime on Leishmania amazonensis infection. In parallel, the effect of Brazilian red propolis gel (propain) alone or combined with glucantime on L. amazonensis infection was evaluated. The inhibition of the infection in macrophages treated with glucantime in combination with HBO exposition was greater than that of macrophages treated with glucantime alone or HBO alone. The susceptible mouse strain BALB/c infected in the shaved rump with L. amazonensis treated with glucantime and exposed to HBO showed: time points in the course of the disease in which lesions were smaller than those of mice treated with glucantime alone and revascularization of the skin in the lesion site; interferon-gamma (IFN-g) levels were not elevated in lymph node cells from these animals. Propain alone was not efficient against lesions, although less exudative lesions were observed in animals treated with propain alone or combined with glucantime. These results reveal the potential value of HBO and red propolis in combination with glucantime for treating cutaneous leishmaniasis and encourage further studies on the effect of more aggressive HBO, propolis and glucantime therapies on different mouse models of leishmaniasis.
Municipalities of higher vulnerability to Sylvatic Yellow Fever occurrence in the São Paulo State, Brazil
Authors: Moreno Eduardo Stramandinoli , Barata Rita de Cássia Barradas
Published: December 2011

Until 1999 the endemic cases of Sylvatic Yellow Fever were located in the states of northern, midwestern and pre-Amazon regions. Since then, the disease progressively expanded its territory of occurrence, cases being registered beyond the traditional boundaries of endemism. The São Paulo State is considered to be part of this context, since after decades without registration of autochthonous cases of the disease, it reported, in 2000 and 2008-2009, epizootic occurrence in non-human primates and 30 cases in humans. Facts like these, added to the increase in incidences of serious adverse effects resulting from the Yellow Fever vaccination, have highlighted the importance of defining priority municipalities for vaccination against the disease in the state. Two groups of municipalities, some affected and some non-affected by YF, were compared for environmental variables related to the eco-epidemiology of the disease according to literature. The Multiple Correspondence Analysis (MCA) was used to pinpoint the factor able to differentiate the two groups of municipalities and define the levels of risk. The southeast region of the São Paulo State was considered to be the area with a higher number of municipalities classified as high risk and should be considered a priority for the application of prevention measures against Yellow Fever.
Cardiomiotomia com fundoplicatura videolaparoscópica no tratamento do megaesôfago não avançado
Authors: Silva Carolina de Melo , Souza Fábio Augusto Albanez , Cruz Carlos Augusto Teixeira da , Torres Ana Verusca , Barbosa Camila Oliveira , Magalhães Vanessa Solé Ferreira , Ribeiro Paulo Roberto Faria , Silva Jordana de Melo
Published: December 2011

RACIONAL: O megaesôfago chagásico é disfunção da motilidade esofágica de caráter progressivo. Seus principais sintomas são disfagia, regurgitação e perda de peso. A cardiomiotomia associada à fundoplicatura é usada como tratamento para o megaesôfago não avançado há algumas décadas. OBJETIVO: Avaliar os resultados obtidos com a cardiomiotomia associada à fundoplicatura por videolaparoscopia para o tratamento do megaesôfago não avançado. MÉTODO: Estudo retrospectivo com análise dos resultados obtidos com essa operação para tratamento do megaesôfago graus I e II. Avaliou-se perda ponderal, tempo e intensidade dos sintomas, tempo operatório, taxa de conversão, índice de complicações, tempo de internação. RESULTADOS: Foram operados 68 pacientes, sendo 34 homens. A maioria (42%) apresentava sintomas intensos. O tempo médio de sintomas foi de 9,27 anos. A perda ponderal média foi de 5,1 kg. Sorologia para Chagas foi positiva em 88,13%. O tempo médio de operação foi de 190 minutos. Houve uma conversão para laparotomia. A mediana do tempo de internação foi de três dias. A taxa de complicações foi de 4,4%. A melhora dos sintomas foi observada em 92% dos pacientes. CONCLUSÃO: O tratamento videolaparoscópico do megaesôfago não-avançado pela cadiomiotomia associada à fundoplicatura mostrou-se método seguro e eficaz. Apresenta baixo índice de complicações e bons resultados no seguimento a curto prazo.
Perfil dos pacientes ambulatoriais com doenças inflamatórias intestinais
Authors: Kleinubing-Júnior Harry , Pinho Mauro de S. L , Ferreira Luis Carlos , Bachtold Guilherme Augusto , Merki Amanda
Published: December 2011

INTRODUÇÃO: As doenças inflamatórias intestinais são enfermidades crônicas, que afetam significativamente a qualidade e expectativa de vida dos pacientes. Existe polimorfismo clínico e a abordagem terapêutica tem sido modificada nos últimos anos. OBJETIVO: Reavaliar o perfil dos pacientes em acompanhamento ambulatorial analisando o comportamento das doenças, sua prevalência e conduta terapêutica. MÉTODOS: Foi realizado um estudo transversal da última atualização da base de dados dos pacientes de ambulatório de doença inflamatória intestinal em 2010. Os itens analisados foram sexo e idade dos pacientes, tipo da doença (retocolite ulcerativa ou doença de Crohn), localização da doença, tipo de medicação em uso, e se os pacientes estavam sintomáticos ou assintomáticos na última consulta. RESULTADOS: Foram estudados 171 pacientes. O sexo feminino mostrou-se predominante (60,8%) e a média de idade dos pacientes foi de 42,3, variando de 16 a 84 anos. Em relação ao tipo de doença inflamatória, a retocolite ulcerativa mostrou-se mais prevalente (58,5%). As localizações mais frequentes na retocolite ulcerativa foram pancolite e retite, ambas com 26% (n=26). Na doença de Crohn a localização ileocolônica foi a mais prevalente, com 47,9% (n=34), sendo seguida pela colônica com 25,4% (n=18). A monoterapia foi a mais utilizada, correspondendo a 54,4% dos pacientes, sendo que os imunossupressores foram as drogas de uso mais frequente (35,5%). A associação de medicamentos foi necessária em 36,3% dos casos, sendo a combinação mais frequente salicilato local com sistêmico em 33,9%. Nos portadores de retocolite ulcerativa 82% estavam em uso de salicilatos, seja local ou sistêmico. Na doença de Crohn 57,7% faziam uso de imunossupressores. Em relação à atividade da doença na última consulta, 71,3% dos pacientes apresentavam-se assintomáticos. CONCLUSÃO: A retocolite ulcerativa foi pouco mais prevalente que a doença de Crohn, sendo pancolite e retite as localizações mais frequentes. Na doença de Crohn a localização ileocolônica foi a mais encontrada seguida pela colônica. A monoterapia com imunossupressores foi o esquema terapêutico mais utilizado. A maioria dos pacientes apresentava-se assintomático na última consulta.