Intact myocardial preparations reveal intrinsic transmural heterogeneity in cardiac mechanics

Determining transmural mechanical properties in the heart provides a foundation to understand physiological and pathophysiological cardiac mechanics. Although work on mechanical characterisation has begun in isolated cells and permeabilised samples, the mechanical profile of living individual cardiac layers has not been examined. Myocardial slices are 300 μm-thin sections of heart tissue with preserved cellular stoichiometry, extracellular matrix, and structural architecture. This allows for cardiac mechanics assays in the context of an intact in vitro organotypic preparation. In slices obtained from the subendocardium, midmyocardium and subepicardium of rats, a distinct pattern in transmural contractility is found that is different from that observed in other models. Slices from the epicardium and midmyocardium had a higher active tension and passive tension than the endocardium upon stretch. Differences in total myocyte area coverage, and aspect ratio between layers underlined the functional readouts, while no differences were found in total sarcomeric protein and phosphoprotein between layers. Such intrinsic heterogeneity may orchestrate the normal pumping of the heart in the presence of transmural strain and sarcomere length gradients in the in vivo heart

Prévention de la peroxydation radio-induite de LDL par des dérivés de vitamine E

La prévention de la peroxydation de LDL humaines par un analogue de vitamine E a été étudiée par radiolyse continue. Les conséquences de l'action de doses croissantes d'irradiation ont été évaluées à l'aide de plusieurs paramètres : formation de substances réagissant avec l'acide thiobarbiturique (SRTBA), disparition de la vitamine E endogène et de l'analogue vitaminique (MOH). Les résultats obtenus permettent de conclure à l'action protectrice de MOH vis-à-vis de la peroxydation des LDL initiée par les radicaux libres OH°/O2°- en présence d'oxygène

Valeur prédictive des variations de l'activité sérique de la DNAse alcaline dans le pronostic des cancers des voies aérodigestives supérieures traités par chimiothérapie.

Variations in serum alkaline DNase activity before and repeatedly after standardized chemotherapy were examined in patients with head and neck carcinomas. The enzyme activity was measured by way of a modified spectrophotometric method. No variations of such activity observed in patients without therapeutic response or with minor response could be considered as a marker of primary or acquired resistance to chemotherapy. Distinct variations in serum alkaline DNase activity (a steep decrease after therapy followed a few weeks later by a regain of values higher than the initial value) correspond to complete or partial positive responses. Such observations of the variations in enzyme activity in relation to individual initial values measured before therapy could be considered as a reliable prognostic test for the therapy of many head and neck carcinomas

4521TUBIANA

Abstract. The purpose of this work was to determine the response rate and toxicity of a combination of Carmustine and The prognosis for primary brain tumors is very poor. Surgery and radiotherapy are currently the standard therapies to treat anaplastic astrocytoma (grade III) and glioblastoma multiforme (grade IV). No effective treatment is available, in spite of very active fundamental research on these tumors. Although major advances have been made in therapeutic methods such as surgery, radiotherapy, chemotherapy and various combinations, the overall prognosis for glioblastomas remains unfavorable (1,2) and the median survival time ranges from 6 to 12 months. Few patients are still alive 2 years after diagnosis. The initial therapeutic approach consists of surgical resection. It is rarely curative due to infiltration of tumor cells into the surrounding brain parenchyma and migration inside the brain. Resection represents a prognostic factor since there is a good correlation between patient survival and complete resection (3). However, resection is frequently impossible because of the volume or location of the tumor at a vital brain site. Post-operative radiotherapy produces only a minor prolongation in survival with median survival, increasing from 4.5 -6 months in the case of surgery alone to 9-10 months for a combination of surgery and post-operative radiotherapy (4). Chemotherapy has a limited impact on the survival, despite meta analyses of randomized cases which suggested a survival benefit of 5% to 10% at two years by adjuvant chemotherapy for high grade astrocytoma (5,6). Median survival increased from 9.4 to 12 months. The most commonly used chemotherapy consisted of nitrosoureas such as Carmustine (7). The timing of chemotherapy and radiotherapy is the subject of much debate. It is believed that the blood-brain barrier is more permeable to the penetration of cytotoxic drugs before radiotherapy rather than after, and that tumors are intrinsically less resistant prior to radiotherapy. However, some patients have chemoresistant tumors and therefore require early radiotherapy. We report the results of a pre-irradiation chemotherapy protocol, described first by Grossman et al. (8), used in 37 adults with a glioblastoma for whom complete resection was impossible. Planning of the protocol was based on Grossman's published results. Chemotherapy relied on a combination of 2 effective drugs: BCNU and Cisplatin. BCNU administered as single-drug therapy for postradiotherapy recurrent or progressive glioblastomas yielded a 29% response rate in glioblastomas and 64% in anaplastic astrocytomas, while the corresponding rates achieved with Cisplatin were, respectively, 73% and 83% (9). 1249 Correspondence to: N