Appropriateness and long-term discontinuation rate of biological therapies in ulcerative colitis.

BACKGROUND: Anti-TNFα agents are commonly used for ulcerative colitis (UC) therapy in the event of non-response to conventional strategies or as colon-salvaging therapy. The objectives were to assess the appropriateness of biological therapies for UC patients and to study treatment discontinuation over time, according to appropriateness of treatment, as a measure of outcome. METHODS: We selected adult ulcerative colitis patients from the Swiss IBD cohort who had been treated with anti-TNFα agents. Appropriateness of the first-line anti-TNFα treatment was assessed using detailed criteria developed during the European Panel on the Appropriateness of Therapy for UC. Treatment discontinuation as an outcome was assessed for categories of appropriateness. RESULTS: Appropriateness of the first-line biological treatment was determined in 186 UC patients. For 64% of them, this treatment was considered appropriate. During follow-up, 37% of all patients discontinued biological treatment, 17% specifically because of failure. Time-to-failure of treatment was significantly different among patients on an appropriate biological treatment compared to those for whom the treatment was considered not appropriate (p=0.0007). Discontinuation rate after 2years was 26% compared to 54% between those two groups. Patients on inappropriate biological treatment were more likely to have severe disease, concomitant steroids and/or immunomodulators. They were also consistently more likely to suffer a failure of efficacy and to stop therapy during follow-up. CONCLUSION: Appropriateness of first-line anti-TNFα therapy results in a greater likelihood of continuing with the therapy. In situations where biological treatment is uncertain or inappropriate, physicians should consider other options instead of prescribing anti-TNFα agents.

Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis.

BACKGROUND: The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. RESULTS: Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. CONCLUSIONS: The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.

Seroepidemiology of hepatitis B virus infection and high rate of response to hepatitis B virus Butang®vaccine in adolescents from low income families in Central Brazil

In order to evaluate the seroepidemiology and response to Butang® vaccine in adolescents from low income families in Central Brazil, blood samples of 664 adolescents were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs) markers, and multiple logistical regression analysis was carried out to determine variables associated with hepatitis B virus (HBV) infection markers. further, three 20 µg butang® vaccine doses were offered to all susceptible individuals (n = 304). Among those who accepted them (n = 182), the seroresponse was evaluated in 170 individuals by quantitative anti-HBs. an overall hbv prevalence of 5.9% was found: four adolescents were HBsAg positive, 24 were anti-HBc, anti-HBs-reactive, and 11 were anti-HBc only. The analyse of risk factors showed that age 16-19 years, place of birth outside Goiás, school B and body piercing were statistically associated with HBV infection markers (p < 0.05). All 170 adolescents responded to butang®, and a geometric mean titer (gmt) of 4344 mui/ml was obtained. these results reinforce the importance of hepatitis b vaccine in adolescents despite of the hbv regional endemicity, and suggest that three doses of 20 µg of the butang® should guarantee protective anti-hbs levels to individuals at a critical time for hepatitis b acquiring such as latter adolescence and adulthood.

(.)VO(2) and EMG activity kinetics during moderate and severe constant work rate exercise in trained cyclists.

The purpose of this study was to compare O(2) uptake ((.)VO(2)) and muscle electromyography activity kinetics during moderate and severe exercise to test the hypothesis of progressive recruitment of fast-twitch fibers in the explanation of the VO(2) slow component. After an incremental test to exhaustion, 7 trained cyclists (mean +/- SD, 61.4 +/- 4.2 ml x min(-1) x kg(- 1)) performed several square-wave transitions for 6 min at moderate and severe intensities on a bicycle ergometer. The (.)VO(2) response and the electrical activity (i.e., median power frequency, MDF) of the quadriceps vastus lateralis and vastus medialis of both lower limbs were measured continuously during exercise. After 2 to 3 min of exercise onset, MDF values increased similarly during moderate and severe exercise for almost all muscles whereas a (.)VO(2) slow component occurred during severe exercise. There was no relationship between the increase of MDF values and the magnitude of the (.)VO(2) slow component during the severe exercise. These results suggest that the origin of the slow component may not be due to the progressive recruitment of fast-twitch fibers.

Relation of heart rate to percent VO2 peak during submaximal exercise in the heat.

We tested the hypothesis that elevation in heart rate (HR) during submaximal exercise in the heat is related, in part, to increased percentage of maximal O(2) uptake (%Vo(2 max)) utilized due to reduced maximal O(2) uptake (Vo(2 max)) measured after exercise under the same thermal conditions. Peak O(2) uptake (Vo(2 peak)), O(2) uptake, and HR during submaximal exercise were measured in 22 male and female runners under four environmental conditions designed to manipulate HR during submaximal exercise and Vo(2 peak). The conditions involved walking for 20 min at approximately 33% of control Vo(2 max) in 25, 35, 40, and 45 degrees C followed immediately by measurement of Vo(2 peak) in the same thermal environment. Vo(2 peak) decreased progressively (3.77 +/- 0.19, 3.61 +/- 0.18, 3.44 +/- 0.17, and 3.13 +/- 0.16 l/min) and HR at the end of the submaximal exercise increased progressively (107 +/- 2, 112 +/- 2, 120 +/- 2, and 137 +/- 2 beats/min) with increasing ambient temperature (T(a)). HR and %Vo(2 peak) increased in an identical fashion with increasing T(a). We conclude that elevation in HR during submaximal exercise in the heat is related, in part, to the increase in %Vo(2 peak) utilized, which is caused by reduced Vo(2 peak) measured during exercise in the heat. At high T(a), the dissociation of HR from %Vo(2 peak) measured after sustained submaximal exercise is less than if Vo(2 max) is assumed to be unchanged during exercise in the heat.

Adenoviruses C in non-hospitalized Mexican children older than five years of age with acute respiratory infection

Adenoviruses (AdV) are commonly involved in acute respiratory infections (ARI), which cause high morbidity and mortality in children. AdV are grouped in six species (A-F), which are associated with a wide range of diseases. The aim of this study was to identify the AdV species infecting non-hospitalized Mexican children with ARI symptoms, attending to the same school. For that, a PCR/RFLP assay was designed for a region of the hexon gene, which was chosen, based on the bioinformatical analysis of AdV genomes obtained from GenBank. A total of 100 children's nasopharyngeal samples were collected from January to June, 2005, and used for viral isolation in A549 cells and PCR/RFLP analysis. Only 15 samples produced cytopathic effect, and in all of them AdV C was identified. AdV C was also identified in eight additional nasopharyngeal samples which were negative for viral isolation. In summary, this outpatient population showed a rate of AdV infection of 23%, and only AdV C was detected.

Prevalence of acute toxoplasmosis infection among 41,112 pregnant women and the mother-to-child transmission rate in a public hospital in South Brazil

Untreated acute toxoplasmosis among pregnant women can lead to serious sequelae among newborns, including neurological impairment and blindness. In Brazil, the risk of congenital toxoplasmosis (CTox) has not been fully evaluated. Our aim was to evaluate trends in acute toxoplasmosis prevalence from 1998-2005, the incidence of CTox and the rate of mother-to-child transmission (MTCT). A cross-sectional study was undertaken to dentify patients who fit the criteria for acute toxoplasmosis during pregnancy. Exposed newborns were included in a historical cohort, with a median follow-up time of 11 months, to establish definite diagnosis of CTox. Diagnoses for acute infection in pregnancy and CTox were based on European Research Network on Congenital Toxoplasmosis criteria. In 41,112 pregnant women, the prevalence of acute toxoplasmosis was 4.8/1,000 women. The birth prevalence of CTox was 0.6/1,000 newborns [95% confidence interval (CI): 0.4-0.9]. During the follow-up study, 12 additional cases were detected, increasing the CTox rate to 0.9/1,000 newborns (95% CI: 0.6-1.3). Among the 200 newborns exposed to Toxoplasma gondii,there were 37 babies presenting diagnostic criteria of CTox, leading to an MTCT rate of 18.5% (95% CI: 13.4-24.6%). The additional cases identified during follow-up reinforce the need for serological monitoring during the first year of life, even in the absence of evidence of congenital infection at birth.

Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients.

BACKGROUND Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients. METHODS AND FINDINGS Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype. CONCLUSIONS Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.

Rate and predictors of service disengagement in an epidemiological first-episode psychosis cohort.

OBJECTIVES: To assess the prevalence and predictors of service disengagement in a treated epidemiological cohort of first-episode psychosis (FEP) patients. METHODS: The Early Psychosis Prevention and Intervention Centre (EPPIC) in Australia admitted 786 FEP patients from January 1998 to December 2000. Treatment at EPPIC is scheduled for 18 months. Data were collected from patients' files using a standardized questionnaire. Seven hundred four files were available; 44 were excluded, because of a non-psychotic diagnosis at endpoint (n=43) or missing data on service disengagement (n=1). Rate of service disengagement was the outcome of interest, as well as pre-treatment, baseline, and treatment predictors of service disengagement, which were examined via Cox proportional hazards models. RESULTS: 154 patients (23.3%) disengaged from service. A past forensic history (Hazard ratio [HR]=1.69; 95%CI 1.17-2.45), lower severity of illness at baseline (HR=0.59; 95%CI 0.48-0.72), living without family at discharge (HR=1.75; 95%CI 1.22-2.50) and persistence of substance use disorder during treatment (HR=2.30; 95%CI 1.45-3.66) were significant predictors of disengagement from service. CONCLUSIONS: While engagement strategies are a core element in the treatment of first-episode psychosis, particular attention should be paid to these factors associated with disengagement. Involvement of the family in the treatment process, and focusing on reduction of substance use, need to be pursued in early intervention services.

Co-infections associated with human immunodeficiency virus type 1 in pregnant women from southern Brazil: high rate of intraepithelial cervical lesions

Human immunodeficiency virus type 1 (HIV-positive) pregnant women require specific prophylactic and therapeutic approaches. The efficacy of established approaches is further challenged by co-infection with other sexually transmitted diseases (STDs). The objective of this study was to determine the prevalence of co-infections in pregnant women infected with different HIV-1 subtypes and to relate these findings, together with additional demographic and clinical parameters, to maternal and infant outcomes. Blood samples from pregnant women were collected and tested for syphilis, hepatitis B virus (HBV) and hepatitis C virus (HCV). Human papillomavirus (HPV) diagnosis was evaluated by the presence of alterations in the cervical epithelium detected through a cytopathological exam. Medical charts provided patient data for the mothers and children. Statistical analyses were conducted with STATA 9.0. We found a prevalence of 10.8% for HCV, 2.3% for chronic HBV, 3.1% for syphilis and 40.8% for HPV. Of those co-infected with HPV, 52.9% presented high-grade intraepithelial lesions or in situ carcinoma. Prematurity, birth weight, Apgar 1' and 5' and Capurro scores were similar between co-infected and non-co-infected women. The presence of other STDs did not impact maternal and concept outcomes. More than half of the patients presenting cervical cytology abnormalities suggestive of HPV had high-grade squamous intraepithelial lesions or cervical cancer, evidencing an alarming rate of these lesions.

Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil

In Brazil, the treatment of hepatitis C virus (HCV) infection is funded by the national public health system (SUS). To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4%) had cirrhosis and HCV genotype 1 predominated (64.3%). Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6% of cases). Twenty-six of these 175 were retreatments and the sustained virological response (SVR) rate among them was 30.8%; the SVR rate was 32.9% among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8%, whereas it was 37.5% in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR): 7.7; confidence interval (CI) 95%: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95%: 1.5, 21.4), non-1 genotype (OR: 5.3; CI 95%: 1.7, 16.7) and uninterrupted treatment (OR: 9.0; CI 95%: 3.3, 45.4). The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.

Response to treatment in Brazilian patients with chronic hepatitis C is associated with a single-nucleotide polymorphism near the interleukin-28B gene

A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

Role of c-Myc in homeostasis of memory CD8 T cells

RESUME La mémoire immunologique est essentielle durant la vie et permet aux lymphocytes de répondre plus rapidement et efficacement lors d'une deuxième rencontre avec un antigène connu. Les facteurs contrôlant l'homéostasie des cellules T CD8 mémoires in vivo ne sont pas encore bien définis. Cependant, la prolifération homéostatique de ces cellules dans un hôte déplété en cellules hématopoietiques nécessite l'intéraction du TCR avec les molecules du MHC de class I du soi. De plus, le rôle de cytokines, telles que 1'IL-15 et l'IL-7, est essentiel dans ce mécanisme, aussi bien que dans la maintenance des cellules T CD8 mémoires. Puisque la protéine c-Myc - impliquée dans des mécanismes tells que la division, la prolifération, l'apoptose et la differentiation - a été définie comme étant impliquée dans la réponse à différentes cytokines, nous nous sommes intéressés à l'analyse de l'homéostasie des lymphocytes T CD8 mémoires dans des souris déficientes en c-Myc (c_rnycΔORF/+), qui expriment un niveau réduit de cette protéine. Bien que le développement des cellules T dans le thymus soit normal dans les souris c_rnycΔORF/+, nous avons observé une réduction de 2 à 3 fois dans la population des cellules T CD8 de phenotype mémoire (CD44+) dans les organes lymphoïdes de la périphérie de ces souris. Cette différence ne correspond pas à une réduction de prolifération ou d'expression de protéines de survie telles que Bel-2. Cependant, la prolifération homéostatique de cellules T CD8 c_rnycΔORF/+, mais pas T CD4 c_rnycΔORF/+, est reduite de manière dramatique lorsqu'elles sont transférées dans un hôte irradié. De plus, le transfert adoptif de lymphocytes T dans des souris irradiées déficientes en l'IL-15 nous a permis de montrer que la prolifération homéostatique dépendante de l'IL-15 des cellules T CD8 nécessite l'expression de c-Myc. De plus, contrairement aux cellules T CD8 CD44+ de type sauvage, nous avons observé que l'expansion induite par l'IL-15 des cellules T CD8 CD44+ c_rnycΔORF/+ est altérée aussi bien in vivo (en réponse à une injection de polyI:C) et in vitro. Par conséquent, nos résultats identifient c-Myc comme une nouvelle protéine régulatrice de la signalisation par l'IL-15 impliquée dans l'homéostasie des cellules T CD8 CD44+. SUMMARY Immunological memory is essential throughout life and allows memory lymphocytes to respond faster and more efficiently upon re-encounter of a known antigen. Factors controlling homeostasis of memory CD8 T cells under steady-state conditions in vivo are currently not well defined. However, the homeostatic proliferation of memory CD8 T cells in lymphopenic hosts requires the interaction of the TCR with self MHC class I molecules. In addition, cytokines, such as IL-15 and to a lesser extent IL-7, are essential for both homeostatic proliferation and maintenance of memory CD8 T cells. Since c-Myc, a proto-oncogene involved in cell division, proliferation, apoptosis and differentiation, has been widely implicated in responsiveness to cytokines, we were interested in analyzing homeostasis of memory CD8 T cells in c-myc hypomorph (c_rnycΔORF/+) mice, which express reduced levels of c-Myc. Although T cell development in the thymus was normal in c_rnycΔORF/+ mice, we found a selective 2- to 3-fold reduction in the memory-phenotype CD44high CD8 T cell population in the periphery. Reduced numbers of CD44high CD8 T cells did not correlate with decreased steady-state turnover rate or low expression of survival factors such as Bcl- 2. However, homeostatic proliferation of c_rnycΔORF/+ CD8 T cells, but not c_rnycΔORF/+ CD4 T cells, was dramatically reduced upon transfer into sublethally irradiated wild-type recipients. In addition, upon transfer of c_rnycΔORF/+ and c-myc WT cells into IL-15-/- mice, we observed that IL-15-induced homeostatic proliferation of CD8 T cells requires c-Myc. Moreover, in contrast to c-myc WT CD44high CD8 T cells, IL-15-induced expansion of c_rnycΔORF/+ CD44high CD8 T cells was strongly impaired both in vivo (in response to polyI:C injection) and in vitro. Collectively, our data identify c-Myc as a novel downstream regulator of IL-15 signaling involved in homeostasis of memory CD8 T cells.

Genetic analysis of c-Myc in mouse bone marrow and liver

1. Summary The transcription factor and proto-oncogene c-myc plays an important role in integrating many mitogenic signals within the cell. The consequences are both broad and varied and include the regulation of apoptosis, cellular differentiation, cellular growth and cell cycle progression. It is found to be mis-regulated in over 70% of all cancers, however, our knowledge about c-Myc remains limited and very little is known about its physiological role in mammalian development and in adulthood. We have addressed the physiological role of c-Myc in both the bone marrow and the liver of mice by generating adult c-myc flox/flox mice that lacked c-myc in either the bone marrow or the liver after conversion of the c-myc flox alleles into null alleles by the inducible Mx¬Cre transgene with polyI-polyC. In investigating the role of c-Myc in the haematopoietic system, we concentrated on the aspects of cellular proliferation, cellular differentiation and apoptosis. Mice lacking c-Myc develop anaemia between 3-8 weeks and all more differentiated cell types are severely depleted leading to death. However in addition to its role in driving proliferation in transient amplifying cells, we unexpectedly discovered a new role for c-Myc in controlling haematopoietic stem cell (HSC) differentiation. c-Myc deficient HSCs are able to proliferate normally in vivo. In addition, their differentiation into more committed progenitors is blocked. These cells expressed increased adhesion molecules, which possibly prevent HSCs from being released from the special stem cell supporting stromal niche cells with which they closely associate. Secondly we used the liver as a model system to address the role of c-Myc in cellular growth, meaning the increase in cell size, and also cellular proliferation. Our results revealed c-Myc to play no role in metabolic cellular growth following a period of fasting. Following treatment with the xenobiotic TCPOBOP, c-Myc deficient hepatocytes increased in cell size as control hepatocytes and could surprisingly proliferate albeit at a reduced rate demonstrating a c-Myc independent proliferation pathway to exist in parenchymal cells. However, following partial hepatectomy, in which two-thirds of the liver was removed, mutant livers were severely restricted in their regeneration capacity compared to control livers demonstrating that c-Myc is essential for liver regeneration. Résumé Le facteur de transcription et proto-oncogène c-myc joue un rôle important dans l'intégration de nombreux signaux mitogéniques dans la cellule. Les conséquences de son activation sont étendues et variées et incluent la régulation de l'apoptose, de la différenciation, de la croissance et de la progression du cycle cellulaire. Même si plus de 20% des cancers montrent une dérégulation de c-myc, les connaissances sur ce facteur de transcription restent limitées et ses rôles physiologiques au cours du développement et chez l'adulte sont très peu connus. Nous avons étudié le rôle physiologique de c-Myc dans la molle osseuse et le foie murin en générant des souris adultes c-myc flox/flox. Dans ces souris, les allèles c-myc flox sont convertis en allèles nuls par le transgène Mx-Cre après induction avec du Poly-I.C. Pour notre étude du rôle de c-Myc dans le système hématopoiétique, nous nous sommes concentrés sur les aspects de la prolifération et de la différenciation cellulaire, ainsi que sur l'apoptose. Les souris déficientes pour c-Myc développent une anémie 3 à 8 semaines après la délétion du gène; tous les différents types cellulaires matures sont progressivement épuisés ce qui entraîne la mort des animaux. Néanmoins, outre sa capacité à induire la prolifération des cellules transitoires de la molle osseuse, nous avons inopinément découvert un nouveau rôle pour c-Myc dans le contrôle de la différenciation des cellules souches hématopoiétiques (HSC). Les HSC déficientes pour c-Myc prolifèrent normalement in vivo mais leur différenciation en progéniteurs plus engagés dans une voie de différenciation est bloquée. Ces cellules surexpriment certaines molécules d'adhésion ce qui empêcherait les HSC d'être relachées du stroma spécialisé, ou niche, auquel elles sont étroitement associées. D'autre part, nous avons utilisé le foie comme système modèle pour étudier le rôle de c-Myc dans la prolifération et dans la croissance cellulaire, c'est à dire l'augmentation de taille des cellules. Nos résultats ont révélé que c-Myc ne joue pas de rôle dans le métabolisme cellulaire qui suit une période de jeûne. L'augmentation de la taille cellulaire des hépatocytes déficients pour c-Myc suite au traitement avec l'agent xénobiotique TCPOBOP est identique à celle observée pour les cellules de contrôle. Le taux de prolifération des hépatocytes mutants est par contre réduit, indiquant qu'une voie de différenciation indépendante de c-Myc existe dans les cellules parenchymales. Néanmoins, après hépatectomie partielle, où deux-tiers du foie sont éliminés chirurgicalement, les foies mutants sont sévèrement limités dans leur capacité de régénération par rapport aux foies de contrôle, montrant ainsi que c-Myc est essentiel pour la régénération hépatique.

Prevalence of hepatitis C virus infection among recyclable waste collectors in Central-West Brazil

The prevalence of hepatitis C virus (HCV) in a population of recyclable waste collectors (n = 431) was assessed using a cross-sectional survey in all 15 cooperatives in the city of Goiânia, Central-West Brazil. The HCV prevalence was 1.6% (95% confidence interval: 0.6-3.6) and a history of sexually transmitted infections was independently associated with this infection. HCV RNA (corresponding to genotype 1; subtypes 1a and 1b) was detected in five/seven anti-HCV-positive samples. Although the study population reported a high rate (47.3%) of sharps and needle accidents, HCV infection was not more frequent in recyclable waste collectors than in the general Brazilian population.