Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

BACKGROUND AND OBJECTIVE: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242). DESIGN AND METHODS: The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. RESULTS: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations). CONCLUSION: In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.

The Road from Marja: Wounded in Afghanistan, Capt. Erik Quist '99, USMC, sees another side of combat

Marine Corps Capt. Erik Quist ’99 had fought in two wars. Now he fights again as he recovers from severe wounds suffered in Afghanistan.

Maternal cholestasis during pregnancy programs metabolic disease in offspring

The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.

A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window

The only treatment of patients with acute ischemic stroke is thrombolytic therapy, which benefits only a fraction of stroke patients. Both human and experimental studies indicate that ischemic stroke involves secondary inflammation that significantly contributes to the outcome after ischemic insult. Minocycline is a semisynthetic second-generation tetracycline that exerts antiinflammatory effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against focal brain ischemia with a wide therapeutic window. Using a rat model of transient middle cerebral artery occlusion, we show that daily treatment with minocycline reduces cortical infarction volume by 76 ± 22% when the treatment is started 12 h before ischemia and by 63 ± 35% when started even 4 h after the onset of ischemia. The treatment inhibits morphological activation of microglia in the area adjacent to the infarction, inhibits induction of IL-1β-converting enzyme, and reduces cyclooxygenase-2 expression and prostaglandin E2 production. Minocycline had no effect on astrogliosis or spreading depression, a wave of ionic transients thought to contribute to enlargement of cortical infarction. Treatment with minocycline may act directly on brain cells, because cultured primary neurons were also salvaged from glutamate toxicity. Minocycline may represent a prototype of an antiinflammatory compound that provides protection against ischemic stroke and has a clinically relevant therapeutic window.

The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains

Mouse Tabby (Ta) and X chromosome-linked human EDA share the features of hypoplastic hair, teeth, and eccrine sweat glands. We have cloned the Ta gene and find it to be homologous to the EDA gene. The gene is altered in two Ta alleles with a point mutation or a deletion. The gene is expressed in developing teeth and epidermis; no expression is seen in corresponding tissues from Ta mice. Ta and EDA genes both encode alternatively spliced forms; novel exons now extend the 3′ end of the EDA gene. All transcripts recovered have the same 5′ exon. The longest Ta cDNA encodes a 391-residue transmembrane protein, ectodysplasin-A, containing 19 Gly-Xaa-Yaa repeats. The isoforms of ectodysplasin-A may correlate with differential roles during embryonic development.

Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia

Ischemic stroke is the most common life-threatening neurological disease and has limited therapeutic options. One component of ischemic neuronal death is inflammation. Here we show that doxycycline and minocycline, which are broad-spectrum antibiotics and have antiinflammatory effects independent of their antimicrobial activity, protect hippocampal neurons against global ischemia in gerbils. Minocycline increased the survival of CA1 pyramidal neurons from 10.5% to 77% when the treatment was started 12 h before ischemia and to 71% when the treatment was started 30 min after ischemia. The survival with corresponding pre- and posttreatment with doxycycline was 57% and 47%, respectively. Minocycline prevented completely the ischemia-induced activation of microglia and the appearance of NADPH-diaphorase reactive cells, but did not affect induction of glial acidic fibrillary protein, a marker of astrogliosis. Minocycline treatment for 4 days resulted in a 70% reduction in mRNA induction of interleukin-1β-converting enzyme, a caspase that is induced in microglia after ischemia. Likewise, expression of inducible nitric oxide synthase mRNA was attenuated by 30% in minocycline-treated animals. Our results suggest that lipid-soluble tetracyclines, doxycycline and minocycline, inhibit inflammation and are neuroprotective against ischemic stroke, even when administered after the insult. Tetracycline derivatives may have a potential use also as antiischemic compounds in humans.

Síndrome da boca ardente: etiologia

A Síndrome da Boca Ardente (SBA) é caracterizada por dor na cavidade oral, com ou sem sinais inflamatórios, mas sem lesões específicas. Acomete geralmente mulheres na faixa etária entre 40 a 60 anos. A dor é do tipo queimação, de intensidade moderada a severa, sendo a língua o local mais acometido, podendo haver sensação dolorosa também em gengivas, lábios e mucosa jugal. Pode haver piora da intensidade dolorosa no decorrer do dia, nos estados de tensão, fadiga, ao falar muito, à ingestão de alimentos picantes e/ou quentes e melhora com alimentos frios, trabalho e distração. O objetivo desta revisão é contemplar as possíveis etiologias da SBA, agrupando-as em 4 grandes grupos para que melhor possam ser estudados: dor oral de causa local, sistêmica, emocional e idiopática. Sabendo dos diagnósticos diferenciais da síndrome, estabelecemos um protocolo para o manejo destes pacientes. Dentre as etiologias de dor bucal local, deve-se pesquisar as de causa dentária, alérgicas e infecciosas. Para as causas sistêmicas, pesquisar doenças do tecido conectivo, doenças endócrinas, neurológicas, deficiências nutricionais e as alterações das glândulas salivares que levam à xerostomia. A etiologia da SBA pode ser de difícil diagnóstico, muitas vezes com mais de um fator causando dor na boca. A realização de anamnese detalhada, exame físico geral, inspeção minuciosa da cavidade oral e orofaringe, além de exames laboratoriais são de fundamental importância, para evitar que o tratamento dos pacientes com esta síndrome, seja baseado em tentativa e erro.

Avaliação da antibioticoterapia na morbidade pós-adenotonsilectomia: estudo prospectivo randomizado

A tonsilectomia, associada ou não à adenoidectomia, continua a ser um dos procedimentos cirúrgicos mais realizados mundialmente, incidindo principalmente sobre a população pediátrica. OBJETIVO: Investigar o impacto do uso da amoxacilina por 7 dias na recuperação pós adenoamigdalectomia, comparando os resultados com um grupo controle. Tipo de Estudo: Estudo prospectivo randomizado controlado com 120 pacientes. PACIENTES E MÉTODO: Os pacientes foram randomizados ao tempo da cirurgia para receber um curso de 7 dias de amoxacilina associada a analgésicos ou apenas analgésicos. Durante a primeira semana de pós-operatório foram avaliados o grau de dor, aceitação da via oral, náuseas e vômitos, febre e retorno às atividades. RESULTADOS: Somente no 4º pós-operatório o grupo recebendo antibiótico teve uma diferença estatística significante no grau de dor. Não houve diferença entre os dois grupos para outros dados analisados. CONCLUSÃO: Considerando os resultados do nosso estudo e revisando a literatura sobre o uso de antibióticos, nós concordamos que não há nenhuma melhora na recuperação dos pacientes submetidos à adenoamigdalectomia após o uso de amoxicilina por 7 dias.

Teamwork and Gendered Work Cultures: The Case of Finland

In this article I focus on women workers’ experiences of transformation from line work to teamworking in Finnish clothing companies in the 1990s and also show what happened after this transformation in the clothing branch. The undertone of it is rather melancholic. Following an initial period of intensive and successful development, clothing work was moved from Finland to countries of cheap labour, such as Estonia, Latvia, Lithuania and Russia, and even China. In this type of network manufacturing, the development of modern information and communication technologies played a central role. My aim is to present the standpoint of women clothing workers in this process. The main body of the empirical data of my study consists of dialogues with clothing workers, union representatives, supervisors and managers. I also make use of my fieldwork notes, memos and research diaries from three companies over a period of five years. Furthermore, in the background lie the action research material from Scandinavian type work conferences and the survey material of an extensive mail inquiry that covered the whole branch in Finland. My own research started in 1991 as a mail inquiry and then continued as a case study in companies from 1992 to 2000, by employing action research and ethnographic methodologies.

TEA: Timing and Energy Aware compression architecture for Efficient Configuration in CGRAs

Coarse Grained Reconfigurable Architectures (CGRAs) are emerging as enabling platforms to meet the high performance demanded by modern applications (e.g. 4G, CDMA, etc.). Recently proposed CGRAs offer time-multiplexing and dynamic applications parallelism to enhance device utilization and reduce energy consumption at the cost of additional memory (up to 50% area of the overall platform). To reduce the memory overheads, novel CGRAs employ either statistical compression, intermediate compact representation, or multicasting. Each compaction technique has different properties (i.e. compression ratio, decompression time and decompression energy) and is best suited for a particular class of applications. However, existing research only deals with these methods separately. Moreover, they only analyze the compaction ratio and do not evaluate the associated energy overheads. To tackle these issues, we propose a polymorphic compression architecture that interleaves these techniques in a unique platform. The proposed architecture allows each application to take advantage of a separate compression/decompression hierarchy (consisting of various types and implementations of hardware/software decoders) tailored to its needs. Simulation results, using different applications (FFT, Matrix multiplication, and WLAN), reveal that the choice of compression hierarchy has a significant impact on compression ratio (up to 52%), decompression energy (up to 4 orders of magnitude), and configuration time (from 33 n to 1.5 s) for the tested applications. Synthesis results reveal that introducing adaptivity incurs negligible additional overheads (1%) compared to the overall platform area.

Mycobacteria other than tubercle bacilli in sputum specimens from patients in Manaus (Amazonia, Brasil)

SUMMARYMycobacteria which are most commonly isolated in pulmonary secretions of patients with respiratory symptoms living in the State of Amazonas are given. The high percentage of isolates (25,4) and the species obtained indicate a strong relationship of contamination of man by the environment. Among the species isolated, seven of them are considered potentially pathogenic mycobacteria. Since some of these species may interfere with present and further vaccination programs against Tuberculosis and Leprosy, these investigations indicate a necessity of carrying out studies of population awareness against specific PPD's prepared from the same species.

Tinea pedis na cidade de Manaus - AM, Brasil

De 1981 a 1985, foram atendidos 96 acientes nas unidades de saúde: Instituto de Dermatologia Troppical e Venereologia "Alfredo da Matta" IDTV-AM e Serviço Médico do Instituto nacional de Pesquisas da Amazônia (INPA), Manaus-AM.Os portadores de diagnóstico clínico de Tiena pedis (pé-de-atleta), foram submetidos ao exame micológico, os quais revelaram que dos segmentos podais mais afetados foram os da Região plantar (42,0%) e interdigital (26,0%). Das 99 espécies fúngicas, 74% eram dermatófitos e 26% de leveduras. Dentre as espécies observadas, verificou-se que as mais frequentes por número de ocorrência foram: Trichophyton rubrum (335,5%), Trichopthyton mentagrophytes (25,00% e Candida sp. (25,0%).

Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer.

Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (±6 months) and date of sampling (±3 months) were selected. Estradiol, estrone and progesterone in first-trimester serum were measured by high-performance liquid chromatography tandem mass spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08-3.06), but inversely associated with risk in women who were diagnosed ≥age 40 (upper quartile OR, 0.64; CI, 0.40-1.04), p(interaction) 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.

Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case-control study.

BACKGROUND: Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC). METHODS: A case-control study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case. RESULTS: Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58-1.62) or GCT (OR 1.13, 95% CI 0.51-2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85-1.43) or GCT (OR 0.93, 95% CI 0.68-1.28). CONCLUSIONS: Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC.