Genuine selective caspase-2 inhibition with new irreversible small peptidomimetics.

Caspase-2 (Casp2) is a promising therapeutic target in several human diseases, including nonalcoholic steatohepatitis (NASH) and Alzheimer's disease (AD). However, the design of an active-site-directed inhibitor selective to individual caspase family members is challenging because caspases have extremely similar active sites. Here we present new peptidomimetics derived from the VDVAD pentapeptide structure, harboring non-natural modifications at the P2 position and an irreversible warhead.

Evaluation of background radiation dose contributions in the United Arab Emirates.

The natural background radiation consists of three main components; cosmic, terrestrial, and skyshine. Although there are currently methods available to measure the total dose rate from background radiation, no established methods exist that allow for the measurement of each component the background radiation. This analysis consists of a unique methodology in which the dose rate contribution from each component of the natural background radiation is measured and calculated.

Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism.

The activity of kallikrein-related peptidase 6 (KLK6) is deregulated in various diseases such as cancer and neurodegenerative diseases. KLK6 is thus considered as an attractive therapeutical target. In this short report, we depict some novel findings on the regulation of the KLK6 activity.

Piperlongumine and some of its analogs inhibit selectively the human immunoproteasome over the constitutive proteasome.

The natural small molecule piperlongumine A is toxic selectively to cancer cells in vitro and in vivo. This toxicity has been correlated with cancer cell ROS, DNA damage and apoptotic cell death increases. We demonstrate here a new mechanistic property of piperlongumine: it inhibits selectively human immunoproteasome with no noticeable inhibition of human constitutive proteasome.

Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic β-Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet.

Intraperitoneal injection of arglabin (2.5 ng/g of body weight, twice daily, 13 weeks) into female human apolipoprotein E2 gene knock-in (ApoE2Ki) mice fed a high-fat Western-type diet (HFD) reduced plasma levels of glucose and insulin by ∼20.0% ± 3.

Pyrido-imidazodiazepinones as a new class of reversible inhibitors of human kallikrein 7.

The human tissue kallikrein-7 (KLK7) is a chymotryptic serine protease member of tissue kallikrein family. KLK7 is involved in skin homeostasis and inflammation. Excess of KLK7 activity is also associated with tumor metastasis processes, especially in ovarian carcinomas, prostatic and pancreatic cancers.

[Similarities and differences between pathological gambling and substance dependance: A clarification].

Unlabelled: Similarities and differences between pathological gambling and substance dependence: a clarification. A critical analysis of a French review of the international literature on gambling.

Introduction: The integration of pathological gambling in the spectrum of addictive disorders modeled by substance dependence is currently discussed.

Detectability of planetary characteristics in disk-averaged spectra II: synthetic spectra and light-curves of earth.

Spatially and spectrally resolved models were used to explore the observational sensitivity to changes in atmospheric and surface properties and the detectability of surface biosignatures in the globally averaged spectra and light-curves of the Earth. Compared with previous efforts to characterize the Earth using disk-averaged models, a more comprehensive and realistic treatment of the surface and atmosphere was taken into account here. Our results are presented as a function of viewing geometry and phases at both visible/near-infrared (0.

Synthesis of 5-aza-7-deazaguanine nucleoside derivatives as potential anti-flavivirus agents.

Coupling suitable sugars (D- or L-ribofuranose, 2' or 3-deoxysugar, branched sugars) with 2-aminoimidazo[1,2-a]-s-triazin-4-one was carried out using the different reaction conditions: 1) condensation in the presence of sodium hydride; or 2) condensation using Vorbrüggen's methods. The 5-aza- 7-deazaguanine nucleoside analogues obtained were evaluated in cell culture experiments for the inhibition of the replication of a number of RNA viruses, including BVDV, YFV, and WNV.

Synthesis of 2'-C-methyl-4'-thio ribonucleosides.

Starting from 2-C-methyl-ribonolactone, 1,2,3,5-tetra-O-acetyl-2-C-methyl-4-thioribofuranose was synthesized and condensed with heterocyclic bases to afford 2-C-methyl-4'-thioribonucleosides.

[Post-radiation coronary diseases. Presentation of 7 cases and review of the literature].

Coronary lesions are one of the complications of mediastinal radiotherapy; they are more uncommon, at least in their clinical expression, than the involvement of the pericardium, but they are interesting by their gravity and occurrence in young patients (35 years old, in an average). We are reporting 7 cases in addition to the 53 already recorded in the literature. The neoplasm which led to the radiation treatment is, in 85 p.

[Malignant pheochromocytoma. Apropos of a case report].

Pheochromocytoma was diagnosed in a male of 38 on the basis of severe and progressive hypertension associated with marked increases in urinary catecholamines and vanilmandelic acid. Left extra-adrenal topography was examined by tomography and confirmed by surgical treatment involving exeresis of the primary tumor and the metastatic latero-aortic lymph nodes, thus corroborating the diagnosis of malignancy. Complementary post-operative radiotherapy was performed on the abdomen.

[Multiple congenital coronaro-left ventricular fistulas. Apropos of 7 cases].

Multiple congenital coronary-left ventricular fistulae (CLVF) are rare (4.5% of all coronaro-cardiac fistulae, the same incidence as isolated CLVF); data obtained from 7 personal and 25 previously reported cases, showed that this anomaly, is diagnosed at coronary angiography performed for anginal chest pains in 2 out of 3 cases; cardiac auscultation was usually normal but the basal ECG was pathological in 3 out of 4 cases; the electrical changes suggested myocardial ischaemia in 20 out of 24 cases. However, exercise stress testing was negative in 47% of cases.

[Proximal and peripheral coronaro-pulmonary fistulae. Apropos of 10 cases].

Coronaro-pulmonary fistula (CPF) is a rare congenital malformation comprising about 17 p. 100 of coronaro-cardiac fistulae. The authors report a series of 10 cases of CPF diagnosed in over 6 000 coronary angiographic studies.

[Effects of lidocaine at the plasma concentrations obtained by peridural injection on atrioventricular conduction disorders].

The aim of this study was to measure plasma concentrations obtained during lidocaine extradural blocks, and to determine whether these concentrations were able to induce high degree AV blocks in patients with impaired AV conduction. In a preliminary study, 12 patients were given an extradural block with an initial bolus of 3.4 mg .

[Subacute ischemia of the lower leg caused by a popliteal synovial cyst. Apropos of a case].

Based on the observation of a cyst compressing the popiteal artery, the authors discuss the characteristic clinical picture and radiology of this benign neoformation. They emphasize two possible causes: cystic degeneration of the arterial median or a cyst of articular derivation. Histological data from this observation supports the second hypothesis.

[Topographic diagnosis of pheochromocytoma. Value of computerized axial tomography].

The localisation of a pheochromocytoma is difficult and sometimes hazardous. There are many radiological techniques of varying sensitivity and the risks of hypertensive crises or of cardiovascular collapse are not negligeable (especially during arteriography and venography). Abdominal computerised axial tomography (CAT) would appear to be of considerable value.

[Automatic activity of the pre-excitation pathways].

The possibility of preexcitation pathways exhibiting automatic activity was demonstrated in 3 cases: in two cases electrophysiological studies supported this diagnosis which was confirmed in the third case by histological examination of the preexcitation pathway. During sinus node dysfunction, spontaneous or induced (by rapid right atrial pacing or by a reciprocating tachycardia), the substitute rhythm arose from the Kent Bundle either transiently or for a longer period: rhythms arising from the Kent Bundle can only be diagnosed after eliminating the possibility of an atrioventricular junctional rhythm conducted to the ventricles by Mahaïm fibres.

[Congenital arteriopathies and Leo Buerger's disease].

A homogenous series of 7 consecutive cases of Buerger's disease were investigated and the congenital malformations of the upper and lower limb arterial trunks were classified. These malformations constitute the anatomical basis of Buerger's disease and define an autonomous disease entity. Total supra-malleolar interruption of the main lower limb arteries either by triple vessel agenesis or, more rarely, by femoro-popliteal or popliteal and tibio-peronal agenesis was observed.