The expression of HSP27 is associated with poor clinical outcome in intrahepatic cholangiocarcinoma

<p>Abstract</p> <p>Background</p> <p>The heat shock proteins (HSPs) 27-kDa (HSP27) and 72-kDa (HSP72), are ubiquitous chaperone molecules inducible in cells exposed to different stress conditions. Increased level of HSPs are reported in several human cancers, and found to be associated with the resistance to some anticancer treatments and poor prognosis. However, there is no study of the relationship between HSPs expression and patient's prognosis in intrahepatic cholangiocarcinoma (IHCCA). In this exploratory retrospective study, we investigated the expressions of HSP27 and HSP72 as potential prognostic factors in IHCCA.</p> <p>Methods</p> <p>Thirty-one paraffin-embedded samples were analyzed by immunohistochemical methods using HSP27 and HSP72 monoclonal antibodies. Proliferation rate was assessed in the same specimens by using monoclonal antibody against phosphorylated histone H3 (pHH3). Fisher's exact test was used to assess the hypothesis of independence between categorical variables in 2 × 2 tables. The ANOVA procedure was used to evaluate the association between ordinal and categorical variables. Estimates of the survival probability were calculated using the Kaplan-Meier method, and the log rank test was employed to test the null hypothesis of equality in overall survival among groups. The hazard ratio associated with HSP27 and HSP72 expression was estimated by Cox hazard-proportional regression.</p> <p>Results</p> <p>The expression of HSP27 was related to mitotic index, tumor greatest dimension, capsular and vascular invasion while the expression of HSP72 was only related to the presence of necrosis and the lymphoid infiltration. Kaplan-Maier analysis suggested that the expression of HSP27 significantly worsened the patients' median overall survival (11 ± 3.18 vs 55 ± 4.1 months, P-value = 0.0003). Moreover HSP27-positive patients exhibited the worst mean survival (7.0 ± 3.2 months) in the absence of concomitant HSP72 expression.</p> <p>Conclusion</p> <p>The expression of HSP27, likely increasing cell proliferation, tumor mass, vascular and capsular invasion, might promote aggressive tumor behaviour in IHCCA and decrease patients' survival. Immunohistochemical detection of HSP27 on routine sections may provide a reliable prognostic marker for IHCCA able to influence the therapeutic strategies for this cancer.</p

TSPO ligand residence time influences human glioblastoma multiforme cell death/life balance

Abstract Ligands addressed to the mitochondrial Translocator Protein (TSPO) have been suggested as cell death/life and steroidogenesis modulators. Thus, TSPO ligands have been proposed as drug candidates in several diseases; nevertheless, a correlation between their binding affinity and in vitro efficacy has not been demonstrated yet, questioning the specificity of the observed effects. Since drug-target residence time is an emerging parameter able to influence drug pharmacological features, herein, the interaction between TSPO and irDE-MPIGA, a covalent TSPO ligand, was investigated in order to explore TSPO control on death/life processes in a standardized glioblastoma cell setting. After 90 min irDE-MPIGA cell treatment, 25 nM ligand concentration saturated irreversibly all TSPO binding sites; after 24 h, TSPO de-novo synthesis occurred and about 40 % TSPO binding sites resulted covalently bound to irDE-MPIGA. During cell culture treatments, several dynamic events were observed: (a) early apoptotic markers appeared, such as mitochondrial membrane potential collapse (at 3 h) and externalization of phosphatidylserine (at 6 h); (b) cell viability was reduced (at 6 h), without cell cycle arrest. After digitonin-permeabilized cell suspension treatment, a modulation of mitochondrial permeability transition pore was evidenced. Similar effects were elicited by the reversible TSPO ligand PIGA only when applied at micromolar dose. Interestingly, after 6 h, irDE-MPIGA cell exposure restored cell survival parameters. These results highlighted the ligand-target residence time and the cellular setting are crucial parameters that should be taken into account to understand the drug binding affinity and efficacy correlation and, above all, to translate efficiently cellular drug responses from bench to bedside

Maternal Mortality at the University of Nigeria Teaching Hospital, Enugu, Before and After Kenya

A comparative retrospective analysis of maternal deaths at the University of Nigeria Teaching Hospital, Enugu, Nigeria, was carried out for two ten-year periods ? 1976-1985 and 1991-2000 ? in order to evaluate the effect of Safe Motherhood Initiative on maternal mortality in the hospital. Variables for the two periods were compared by means of the t-test at 95% confidence level. Maternal mortality ratio was significantly higher in Period II than in Period I (1406 versus 270 per 100,000; p = 0.00). The leading causes of maternal death were uterine rupture for Period I and septicaemia for Period II. Although from the first to the second ten-year period there was a significant decrease in the number of midwives, physicians and nurse anaesthetists, there was more than a proportionate decrease in the number of deliveries. There was also increase in the incidence of anaemia due to diminished standards of living and in the mean decision-intervention interval (1.5 ± 0.5 versus 5.8 ± 1.2 hours; p = 0.000) as a result of worker dissatisfaction and changes in hospital policies. We conclude that since the launching of the Safe Motherhood Initiative, MMR at the University of Nigeria Teaching Hospital, Enugu, Nigeria, has increased five-fold as a result of institutional delays and a deterioration in the living standards of Nigerians, both consequences of a depressed economy. To halt this trend, we recommend that the living standard of all Nigerians should be improved. Furthermore, healthcare personnel should be motivated through enhanced salaries and provision of working materials including efficient mobile telephone services. (Afr J Reprod Health 2001; 5[2]: 90-97) RÉSUMÉ Mortalité matrenelle au Centre Hospitalier Universitaire à Enugu, Nigéria: Avant et après le Kenya. Une analyse retrospective comparée des décès maternels au Centre Hospitalier Universitaire à Enugu au Nigeria a été faite au cours de deux périodes de dix ans chacune, 1976-1985 et 1991-2000. Le but de l'analyse était d'évaluer l'effet de la Safe Motherhood Initiative sur la mortalité maternelle dans l'hôpital. Des variables pour les deux périodes ont été comprarés à l'aide du test de t à un niveau de confiance de 95%. Le rapport de mortalité maternelle était, de manière significative, plus élevé dans la période II que dans la Période I (1406 par opposition à 270 par 100,000, p = 0,00). Les causes principales du décès maternel étaient la rupture de l'utérine pour la Période I et la septicémie pour la Période II. Bien que depuis la première jusqu'à la deuxième période de dix ans il y ait une baisse significative dans le nombre de sages-femmes, de médecins et d'infirmières anesthésistes, il y avait plus qu'une baisse proportionnelle dans le nombre d'accouchements. Il y avait également une augmentation de l'incidence d'anémie à cause du niveau de vie baissé et dans l'espace de la moyenne décision-intervention (1,5 ± 0,5 par opposition à 5,8 ± 1,2 heures; p = 0,000) à cause du mécontentement chez les salariés et des changements dans la politique de l'hôpital. Nous concluons que depuis qu'on a lancé la Safe Motherhood Initiative, le taux de mortalité maternelle a augmenté cinq fois au Centre Hospitalier Universitaire à Enugu, Nigéria, a cause des délais institutionnels et à cause de la déterioration du niveau de vie des Nigérians, deux conséquences d'une économie en déclin. Pour mettre fin à cette tendance, nous recommandons que le niveau de vie de tous les Nigérians soit amélioré. En plus, les membres du personnel du service de santé doivent être motivés à travers les salaires augmenté et en mettant à la disposition des membres du personnel tous les matériels du travail y compris les services du téléphone portable. (Rev Afr Santé Reprod 2001; 5[2]: 90-97 ) KEY WORDS: Increasing, maternal mortality ratio, Enugu, Nigeria, Keny

Constraints to utilization of maternal health services at the primary health care level in Nnewi, Nigeria

Background: Ensuring universal access to quality maternal health services brings to the fore the need to determine and tackle factors that deter women from utilizing these services.Objective: To determine the constraints to utilization of maternal health services in the primary health centres in Nnewi, Nigeria.Methodology: This was a cross-sectional survey. Using the multi-stage sampling technique, 280 women utilizing maternal health services from four randomly selected public primary health centres in Nnewi, Nigeria, were chosen for the study. Data collection employed a mix of quantitative and qualitative methods. Quantitative data was analyzed using the Statistical Package for Social Sciences (SPSS) version 16 (2007).Results: The mean age of the 280 respondents studied was 29.2±5.9 years; 168 (60%), 70 (25%) and 26 (9.3%) of the respondents accessed ante-natal care, post-natal care and delivery services, respectively. Eighty-four (30%) mothers were not vaccinated against tetanus for such reasons as non-availability of vaccines (28.6%), fear of side effects (25%), and lack of belief in vaccination efficacy (20.3%). Difficulties experienced before accessing the facilities were: bad state of roads (60.7%), lack of transportation (34.6%) and high transportation cost (25%). Whereas, difficulties experienced at the facilities were: lack of equipment and supplies (27.5%), lack of transportation (13.2%) and unavailability of drugs (11.1%).Conclusion: This study found that apart from ante-natal care, other maternal health services were underutilized. Funding, good access roads, affordable transportation and appropriately integrated services would boost utilization.Keywords: Accessibility, drugs, education, equipment, funds, transportatio

Rigid-flexible coupling virtual prototyping-based approach to the failure mode, effects, and criticality analysis

International audienc