Effects of mitotane on gene expression in the adrenocortical cell line NCI-H295R: a microarray study.

Aim: The adrenolytic agent mitotane is widely used in the treatment of adrenocortical cancer; however, its mechanism of action is poorly elucidated. We have studied mitotane-induced mRNA expression changes in the NCI-H295R adrenocortical cancer cell line. Materials & methods: Cell viability and hormone assays were used to select the optimal mitotane concentration effectively inhibiting hormone secretion without affecting cell viability. RNA isolated from cultures treated for 48 and 72 h was subjected to Agilent 4×44K microarray platforms. Microarray results were validated by quantitative reverse-transcription PCR. Results: Altogether, 117 significantly differentially expressed genes were detected at 48 h and 72 h (p < 0.05) in mitotane-treated samples relative to controls. Three significantly underexpressed genes involved in steroid hormone biosynthesis (HSD3B1, HSD3B2 and CYP21A2) and four significantly overexpressed genes (GDF15, ALDH1L2, TRIB3 and SERPINE2) have been validated. Conclusion: Gene-expression changes might be involved in the adrenal action of mitotane and in the inhibition of hormone secretion. Original submitted 20 January 2012; Revision submitted 17 May 2012.

Fecundity of ant queens in relation to their age and the mode of colony founding

The change over time in the fecundity and weight of queens was investigated in three monogynous, independent colony founding species,Lasius niger, Camponotus ligniperda andC. herculaneus, and two polygynous dependent colony founding species,Plagiolepis pygmaea andIridomyrmex humilis. Queens of the three species founding independently exhibited a similar pattern with a significant loss of weight between mating and the emergence of the first workers. In contrast, weights of queens of the species employing dependent colony founding remained more stable. Fecundity of queens founding independently increased slowly with time whereas fecundity of queens founding dependently reached the maximum level some weeks after the beginning of the first reproductive season. These results are discussed in relation to some differences in the life history (e.g., life-span) between queens utilizing independent and dependent colony founding.

Effect of endotoxin on the angiotensin II receptor in cultured vascular smooth muscle cells.

1. In some tissues, a decrease in the number of cell surface receptors and alterations of the receptor coupling have been proposed as possible mechanisms mediating the deleterious effects of bacterial endotoxin in septic shock. 2. The effects of bacterial lipopolysaccharide (Escherichia coli 0111-B4; LPS) on vascular angiotensin II and vasopressin receptors have been examined in cultured aortic smooth muscle cells (SMC) of the rat by use of radioligand binding techniques. 3. In vascular SMC exposed to 1 micrograms ml-1 endotoxin for 24 h, a significant increase in angiotensin II binding was found. The change in [125I]-angiotensin II binding corresponded to an increase in the number of receptors whereas the affinity of the receptors was not affected by LPS. In contrast, no change in [3H]-vasopressin binding was observed. 4. The pharmacological characterization of angiotensin II binding sites in control and LPS-exposed cells demonstrated that LPS induced an increase in the AT1 subtype of the angiotensin II receptors. Receptor coupling as evaluated by measuring total inositol phosphates was not impaired by LPS. 5. The effect of LPS on the angiotensin II receptor was dose-, time- and protein-synthesis dependent and was associated with an increased expression of the receptor gene. 6. The ability of LPS to increase angiotensin II binding in cultured vascular SMC was independent of the endotoxin induction of NO-synthase. 7. These results suggest that, besides inducing factors such as cytokines and NO-synthase, endotoxin may enhance the expression of cell surface receptors. The surprising increase in angiotensin II binding in LPS exposed VSM cells may represent an attempt by the cells to compensate for the decreased vascular responsiveness. It may also result from a non-specific LPS-related induction of genes.

Chloroquine resistant Plasmodium falciparum malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment

Chloroquine (CQ) resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1%) of the patients were cured and 44 (37.9%) failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP) and 20 received chlorpheniramine + chloroquine (CH+CQ) combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05). There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92% while those of CH+CQ was 85%. There was a significant difference in parasite clearance time (p = 0.01) between the two groups. The 38% treatment failure for CQ reported in this study is higher than the 10% recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.

Routine use of self-expanding venous cannulas for cardiopulmonary bypass: benefits and pitfalls in 100 consecutive cases.

OBJECTIVE: Assess the performance of self-expanding venous cannulas for routine use in open-heart surgery. METHODS: Prospective study in 100 unselected consecutive patients undergoing open-heart surgery with either remote or central smart venous cannulation. RESULTS: The study focuses on the 76 consecutive adult patients (mean age 59.2+/-17.3 years; 60 males, 16 females) undergoing surgical procedures with total cardiopulmonary bypass for either valve procedures (42/76 patients=55.3%), ascending aorta and arch repair (20/76 patients=26.3%), coronary artery revascularization (13/76 patients=17.1%) or other procedures (11/76 patients=14.5%) with 14/76 patients (18.4%) undergoing redo surgery and 6/76 patients (7.9%) undergoing small access surgery. The mean pump flow achieved by gravity drainage alone accounted for 5.0+/-0.6l/min (=114% of target) in the entire study population (n=76) as compared to the calculated, theoretical pump flow of 4.4+/-0.5l/min (p<0.0001). For the femoral cannulation sub-group (n=35) pump flow achieved by gravity drainage alone accounted for 4.9+/-0.6l/min (=114% of target) as compared to the calculated theoretical pump flow of 4.3+/-0.4l/min (p<0.0001). The corresponding numbers for trans-subclavian cannulation (n=7) are 5.2+/-0.5l/min (111%) for the pump flow achieved by gravity drainage as compared to the theoretical target flow of 4.7+/-0.4l/min. For the central cannulation sub-group (n=34) mean flow achieved by gravity drainage with a self-expanding venous cannula accounted for 5.1+/-0.7l/min (=116% of target) as compared to the calculated theoretical flow of 4.4+/-0.6l/min (p<0.0001). CONCLUSION: Full or more than target flow was achieved in 97% of the patients studied undergoing CPB with self-expanding venous cannulas and gravity drainage. Remote venous cannulation with self-expanding cannulas provides similar flows as central cannulation. Augmentation of venous return is no longer necessary.

Prevalence of antiretroviral drug resistance among treatment-naive and treated HIV-infected patients in Venezuela

An in-house, low-cost method was developed to determine the genotypic resistance of immunodeficiency virus type 1 (HIV-1) isolates. All 179 Venezuelan isolates analysed belonged to subtype B. Primary drug resistance mutations were found in 11% of 63 treatment-naïve patients. The prevalence of resistance in isolates from 116 HIV-positive patients under antiretroviral treatment was 47% to protease inhibitors, 65% to nucleoside inhibitors and 38% to non-nucleoside inhibitors, respectively. Around 50% of patients in the study harboured viruses with highly reduced susceptibility to the three classical types of drugs after only five years from their initial diagnoses.

Microbiological activities in moonmilk monitored using isothermal microcalorimetry (cave of Vers Chez le Brandt, Neuchatel, Switzerland)

Studies of the influence of microbial communities on calcium carbonate deposits mostly rely on classical or molecular microbiology, isotopic analyses, and microscopy. Using these techniques, it is difficult to infer microbial activities in such deposits. In this context, we used isothermal microcalorimetry, a sensitive and nondestructive tool, to measure microbial activities associated with moonmilk ex-situ. Upon the addition of diluted LB medium and other carbon sources to fresh moonmilk samples, we estimated the number of colony forming units per gram of moonmilk to be 4.8 3 105 6 0.2 3 105. This number was close to the classical plate counts, but one cannot assume that all active cells producing metabolic heat were culturable. Using a similar approach, we estimated the overall growth rate and generation time of the microbial community associated with the moonmilk upon addition of various carbon sources. The range of apparent growth rates of the chemoheterotrophic microbial community observed was between 0.025 and 0.067 h21 and generation times were between 10 and 27 hours. The highest growth rates were observed for citrate and diluted LB medium, while the highest carbon-source consumption rates were observed for low molecular weight organic acids (oxalate and acetate) and glycerol. Considering the rapid degradation of organic acids, glucose, and other carbon sources observed in the moonmilk, it is obvious that upon addition of nutrients during snow melting or rainfall these communities can have high overall activities comparable to those observed in some soils. Such communities can influence the physico-chemical conditions and participate directly or indirectly to the formation of moonmilk.

Prevalence and genotyping of hepatitis C virus in blood donors in the state of Pará, Northern Brazil

Given the scarcity of epidemiological information on hepatitis C virus (HCV) infection in Northern Brazil, we determined the prevalence and genotypic frequency in blood donors in the state of Pará (PA). Blood samples from all of the blood donors at the Fundação HEMOPA (blood bank of PA) from 2004-2006 were screened for the presence of antibodies to anti-HCV and samples seroreactive to anti-HCV were further tested for HCV RNA using real-time PCR. In total, 116 HCV-RNA samples were genotyped, based on maximum likelihood phylogenetic analyses, using BioEdit, Modelgenerator, PHYML and FigTree software. The population consisted of 242,726 volunteers who donated blood from 2004-2006; the most common subgroup was males between the ages of 18-29 years old (37.30%). Within the whole group, 1,112 blood donors (0.46%) had indeterminate or positive serology; among these, 28.78% were males whose ages ranged from 18-29 years. A diagnosis of chronic HCV infection was confirmed for 304 donors (60.20% males; 66.45% were 30-49 years old), resulting in a prevalence of HCV RNA in 0.13% of the samples (304 of 242,726). HCV genotyping revealed a high frequency of genotype 1 (108/116) followed by genotype 3 (8/116). This study found HCV infection to be relatively infrequent in PA; genotype 1 was most commonly isolated. This information can help guide prevention and control policies aimed at efficient diagnosis and control measures.

Physiques sonores

Ce livre, publié grâce aux soutiens logistiques et financiers du Lausanne Underground Film and Music Festival et du Groupe de la Riponne, est le premier de la collection Rip on / off. Textes édités et traduits (de l'anglais) par Christian Indermuhle et Thibault Walter dans le cadre des activités éditoriales du Groupe de la Riponne à l'occasion du Lausanne Underground Film and Music Festival 2008. Avec des collaborations de Nikola Mounoud, Boris Wlassof, Fernando Sixto, Guy-Marc Hinant, Naut Humon pour les textes ; de Julien Notter et Sébastien Vigne pour le graphisme. Un CD original, Form & Disposition, composé et masterisé par Zbigniew Karkowski, joué aux percussions par Daniel Buess et enregistré par Alex Buess en septembre 2008 aux studios 2.8.1 à Bâle, est offert avec ce livre. "Ces textes ne sont pas des compléments à l'oeuvre musicale de Zbigniew Karkowski, ils n'en sont ni une théorie, ni une explication. La musique se suffit à elle-même, elle déploie ses propres régimes d'intelligence et de conceptualités. Il s'agit donc ici de dire autre chose. Et de permettre à zk de rendre compte de sa pratique et de sa longue expérimentation de la matérialité des sons et de leur puissance. Quand nous avons choisi d'éditer, de traduire ces textes et de les enrichir de matériaux nouveaux, nous savions que nous ne pouvions nous dispenser des réseaux souterrains multipliés qu'un tel projet suppose. Ainsi, et suite à plusieurs rencontres, notamment dans le cadre de concerts donnés depuis 2005 sur la scène du luff, nous avons demandé à zk d'écrire ce livre, de rassembler ses textes d'il y a vingt ans ceux-là mêmes qui flottaient à la dérive du web, et de les compléter en enrichissant les entretiens qu'il avait eus en 2002 avec Boris Wlassof, dont les textes avaient initialement été publiés dans le numéro 59 de Revue et Corrigée. Nous avons choisi par ailleurs d'aider ou de perdre le lecteur en lui proposant, pour se guider un peu, en fin de parcours, deux glossaires reprenant quelques uns des termes musicaux et des personnages évoqués dans ce livre, et aussi d'inviter Fernando Sixto et Naut Humon à nous donner l'écho de deux oreilles ayant entendu l'oeuvre de zk, afin que ce livre multipliât les accès à ses univers musicaux, et qu'il ne soit pas le marbre qui refermât leur tombeau. Le bruit est vivant, c'est cette vitalité qu'il s'agit ici d'écouter."

Diabétologie : nouveautés en médecine 2007 [Trends in diabetes]

Une méta-analyse concernant l'utilisation de la rosiglitazone chez les diabétiques de type 2 a révélé une augmentation significative du risque d'infarctus du myocarde et une tendance à la surmortalité cardiovasculaire. La méthodologie de cette étude ainsi que ses conclusions ont été beaucoup critiquées. Cette étude montre les limites des méta-analyses auxquelles on prête un rang manifestement trop élevé dans la hiérarchie des niveaux de preuve. L'étude 4T a évalué trois schémas d'insuline dans le traitement du diabète de type 2. Les résultats à un an montrent que seule une minorité des patients atteignent les objectifs. Post-Steno 2 a été présenté au congrès européen du diabète. Ces nouvelles données confirment que le traitement intensifié de tous les facteurs de risque cardiovasculaire permet une réduction majeure de la mortalité cardiovasculaire après 13,3 ans. A recent meta-analysis on the rosiglitazone in the treatment of type 2 diabetes revealed a significant increased risk of myocardial infarction and a trend to a higher cardiovascular mortality. In the following month after this publication, the methodology as its conclusions were criticized. This study shows the limits of the meta-analyses to which one lends a row obviously too high in the hierarchy of the levels of evidence. The study 4T evaluated 3 insulin strategies in the treatment of the type 2 diabetes. The results at one year show that only a minority of the patients achieve the goals. Post-Steno 2 was presented at the European congress diabetes. These new data confirm that the intensified treatment of all cardiovascular factors risk allows a major reduction of cardiovascular mortality after 13.3 years

Human polyomaviruses JC and BK in the urine of Brazilian children and adolescents vertically infected by HIV

The aim of this study was to characterize the urinary excretion of the BK (BKV) and JC (JCV) human polyomaviruses in a cohort of human immunodeficiency virus (HIV)-infected children and adolescents. One hundred and fifty-six patients were enrolled: Group I included 116 HIV-infected children and adolescents [median age = 11.4 years (y); range 1-22 y]; Group II included 40 non-HIV-infected healthy controls (median age = 11.37 y; range 7-16 y). Single urine samples from both groups were screened for the presence of JCV and BKV DNA by polymerase chain reaction at enrolment. The overall rate of JCV and BKV urinary excretion was found to be 24.4% and 40.4%, respectively (n = 156). Group I had urinary excretion of JCV and BKV in 27.6% and 54.3% of subjects, respectively. In contrast, Group II showed positive results for JCV in 17.5% of subjects and for BKV in 12.5% of subjects (p Pearson JCV = 0.20; p Pearson BKV < 0.0001). In Group I, there was no association between JCV/BKV shedding and age, gender or CD4 values. Patients with an HIV viral load < 50 copies/mL had a lower excretion of BKV (p < 0.001) and a trend of lower JCV excretion (p = 0.07). One patient in Group I (1/116, 0.9%) showed clinical and radiological features consistent with progressive multifocal leukoencephalopathy, suggesting that children with HIV/polyomavirus coinfection should be kept under surveillance.