Hex Me If You Can.

HexMe consists of 189 tetrahedral meshes with tagged features and a workflow to generate them. The primary purpose of HexMe meshes is to enable consistent and practically meaningful evaluation of hexahedral meshing algorithms and related techniques, specifically regarding the correct meshing of specified feature points, curves, and surfaces. The tetrahedral meshes have been generated with Gmsh, starting from 63 computer-aided design (CAD) models from various databases. To highlight and label the diverse and challenging aspects of hexahedral mesh generation, the CAD models are classified into three categories: simple, nasty, and industrial. For each CAD model, we provide three kinds of tetrahedral meshes (uniform, curvature-adapted, and box-embedded). The mesh generation pipeline is defined with the help of Snakemake, a modern workflow management system, which allows us to specify a fully automated, extensible, and sustainable workflow. It is possible to download the whole dataset or select individual meshes by browsing the online catalog. The HexMe dataset is built with evolution in mind and prepared for future developments. A public GitHub repository hosts the HexMe workflow, where external contributions and future releases are possible and encouraged. We demonstrate the value of HexMe by exploring the robustness limitations of state-of-the-art frame-field-based hexahedral meshing algorithm. Only for 19 of 189 tagged tetrahedral inputs all feature entities are meshed correctly, while the average success rates are 70.9% / 48.5% / 34.6% for feature points/curves/surfaces.

Changes in renal artery resistance after meal-induced splanchnic vasodilatation in cirrhotic patients.

PURPOSE: A relationship between vasomotor tone changes in mesenteric and renal vessels in cirrhotic patients has been suspected but remains controversial. The aim of this study was to assess by duplex Doppler sonography the changes in the circulatory resistance of the renal arteries and superior mesenteric artery (SMA) following meal-induced splanchnic vasodilatation. METHODS: Twenty-seven cirrhotic patients and 15 healthy volunteers with no hepatic or renal dysfunction were prospectively included in the study. The resistance index (RI) of the SMA and of the right and left renal arteries was measured by duplex Doppler sonography before and 30 minutes after ingestion of a standard 400-kcal balanced liquid meal. Values in controls and patients and values before and after the meal were compared, and correlations between RIs, Child-Pugh class (liver function), and creatinine clearance were assessed in cirrhotic patients. RESULTS: The fasting renal artery RI was greater in cirrhotic patients than in controls (p < 0.0001), but there was no difference in fasting SMA RIs. After the meal, there was a significant decrease in the SMA RI in controls (0.85 +/- 0.04 before versus 0.74 +/- 0.03 after meal, p = 0.0001) and in cirrhotic patients (0.85 +/- 0.04 before versus 0.77 +/- 0.04 after, p = 0.0001) and a significant increase in the renal artery RI (0.57 +/- 0.06 before versus 0.62 +/- 0.05 after in controls, p = 0.001; 0.68 +/- 0.07 before versus 0.70 +/- 0.07 after in cirrhotic patients, p = 0.001). No correlation was found in cirrhotic patients between the changes in renal artery RI and the postprandial SMA RI decrease, the Child-Pugh class, or the creatinine clearance. CONCLUSIONS: Meal-induced SMA vasodilatation (RI decrease) is associated with a marked increase in the renal artery RI, worsening the renal vasoconstriction in cirrhotic patients.

[Collagen gastroenterocolitis]. / Une gastroentérocolite collagène.

INTRODUCTION: Collagenous gastroenterocolitis is a recently known rare cause of chronic diarrhoea, that raises numerous nosological and diagnostic problems. OBSERVATION: A 41 year-old woman was hospitalised for severe diarrhoea, diagnosed as collagenous gastroenterocolitis. Gastroscopy and ileocolonoscopy were macroscopically normal, but a 20 to 40 microns thick sub-epithelial collagenous band was revealed in the gastric, duodenal and colic biopsies. Parenteral nutrition and treatment with salazopyrine and prednisolone progressively normalised the transit. Three months later, only a 30 microns colic mucosa collagenous band persisted. All the biopsies taken during control gastro-colonoscopy 2 years later were histologically normal. After 5 years follow-up and absence of treatment, the patient no longer presented diarrhoea or biological abnormality. COMMENTS: This exceptional observation is a reminder that sub-epithelial collagen deposits are not always limited to the colon and therefore justify, in patients with collagenous colitis, systematic gastro-duodenal and ileum biopsies.

[Acute hepatitis due to ecstasy]. / Hépatite aiguë à l'ecstasy.

BACKGROUND: Ecstasy is a synthetic amphetamine which causes a wide variety of adverse effects. Hepatic toxicity was only recently demonstrated but can be quite severe. CASE REPORT: A 27-year-old male with no past medical or surgical history developed jaundice without fever. He was a regular user of ecstasy and had recently increased the number of doses consumed. No evidence of a viral, alcoholic, metabolic or autoimmune mechanism was found which could explain the hepatitis. Complete cure was obtained by discontinuing ecstasy. DISCUSSION: Few cases of ecstasy hepatic toxicity have been reported. Ecstasy was undoubtedly the causal agent in this case since other known causes of acute hepatitis were excluded, confirming the hepatotoxicity of ecstasy reported in the literature. The liver disease has been reported to range form acute regressive hepatitis to fatal liver failure. Iterative exposure can lead to fibrosis. The pathophysiological mechanism of this toxic effect is not well elucidated. Ischemia alone cannot explain all the clinical forms described, particularly cases without hyperpyrexia. Ecstasy must be added to the list of potential causes of acute hepatitis. Exposure must always be searched for in cases of acute hepatitis in young subjects.

[Hemostatic embolization of hepatocellular carcinoma with portal vein thrombosis complicated by hemoperitoneum]. / Embolisation hémostatique d'un carcinome hépatocellulaire avec thrombose de la veine porte compliqué d'un hémopéritoine.

A 59-year-old chronic drinker (120 g alcohol/day) was hospitalized for sudden increase in abdominal volume found to be caused by a hemoperitonoff resulting from ruptured hepatocellular carcinoma with thrombosis of the portal vein. Emergency arterial embolization with gelatin sponge successfully stopped intraperitoneal bleeding. No surgical treatment could be attempted due the severity of the cirrhosis. This patient survived for 4.5 month. Based on this observation and a review of the literature, it can be suggested that hemostatic embolization is an effective treatment for spontaneous hemorrhage of hepatocellular carcinoma even in cases with portal vein thrombosis.

[Post-traumatic thrombosis of the portal vein]. / Thrombose de la veine porte post-traumatique.

Blunt trauma to the abdomen is an exceptional cause of portal vein thrombosis. To our knowledge, 8 cases have been reported in the literature. When thrombosis of the portal vein occurs, a complete search for all the known main causes must be carried out before entertaining this diagnosis. Other causes may be cirrhosis, tumors and inflammation of the abdomen, coagulation disorders and hematologic diseases including latent myeloproliferative syndrome. We report a case in a 25-year-old man with an uneventful past history who presented with thrombosis of the portal vein after a violent blunt trauma which occurred during a rugby play. In this young man, none of the other potential causes was found, in particular bone marrow culture on medium with low growth-factor concentration allowed us to eliminate a latent myeloproliferative syndrome. The only triggering factor remaining was the recent abdominal trauma. After an 18-month follow-up, no other element has been observed which could have caused thrombosis of the portal vein.

Interaction of the antiarrhythmic agents SR 33589 and amiodarone with the beta-adrenoceptor and adenylate cyclase in rat heart.

1. The effects of SR 33589 and amiodarone on the cardiac beta-adrenoceptor were studied in vitro and after chronic treatment by means of [125I]-(-)-iodocyanopindolol ([125I]-(-)-CYP) binding and measurement of adenylate cyclase activity. 2. Binding of [125I]-(-)-CYP was inhibited in a dose-dependent manner by SR 33589 (IC50=1.8 +/- 0.4 microM, nH=0.93 +/- 0.06) and amiodarone (IC50=8.7 +/- 2.0 microM, nH=9.2 +/- 0.03). Saturation binding experiments indicated a non-competitive interaction such that SR 33589 (1 and 3 microM) and amiodarone (5 and 10 microM) reduced the Bmax of [125I]-(-)-CYP binding without any effect on the KD. Kinetic studies showed that the rate of association of [125I]-(-)-CYP was unchanged while the rate of dissociation was increased both in the presence of SR 33589 (10 microM) and amiodarone (30 microM).3. Under the same conditions, the receptor stimulated adenylate cyclase activity was inhibited in a dose-dependent, but non-competitive manner, by SR 33589 (isoprenaline-, glucagon- and secretin-stimulated enzyme inhibited 50% at 6.8 +/- 0.6 microM, 31 +/- 10 microM and 12 +/- 3 microM, respectively) while the basal, GTP- and GPP(NH)p-stimulated enzyme was inhibited by 5-10% and the NaF and forskolin-stimulated enzyme by 50% at 500 microM. Amiodarone exhibited a similar pattern of inhibition. 4. After chronic oral treatment (50, 100, 150 mg kg(-1) per day, 14 days), both SR 33589 and amiodarone produced a dose-dependent decrease in Bmax without any effect on KD as determined from [125I]-(-)-CYP saturation experiments and a decrease of the isoprenaline- and glucagon-stimulated adenylate cyclase activity without any effect on basal enzyme activity or activity when stimulated by agents acting directly on regulatory catalytic units. 5. Unlike amiodarone, SR 33589 does not contain iodine substituents. Plasma levels of T3, T4, and rT3 were changed after SR 33589 treatment except a decrease in T4 level at the highest dose whilst the T4 T3 ratio and the level of rT3 were dose-dependently increased by amiodarone treatment. 6. In vitro, SR 33589 and amiodarone were characterized as non-competitive beta-adrenoceptor antagonists. Chronic treatment led to a down-regulation of the beta-adrenoceptor; the down-regulation cannot be attributed to an indirect effect mediated by the thyroid hormones. To reconcile these opposing observations, we propose that SR 33589 and amiodarone interact with the beta-adrenoceptor at a site close to the intracellular loops which are involved in the coupling with Gs and contain the phosphorylable sites.

Characterization of the binding of [3H]SR 33805 to the slow Ca2+ channel in rat heart sarcolemmal membrane.

SR 33805 is a representative of a new class of compounds (indole sulfone) that inhibits L-type Ca2+ channels. [3H]SR 33805 has been shown to bind with a high affinity (Kd approximately 20 pM calculated from saturation isotherms and association/dissociation kinetics) to a single site in a purified preparation of rat cardiac sarcolemmal membranes. The binding was found to be saturable and reversible. The maximal binding capacity was in approximately 1:1 stoichiometry with that of other Ca2+ channel antagonists. Various cations (Na+, Ca2+, Cd2+, and La3+) were shown to inhibit specific [3H]SR 33805 binding, with La3+ being the most potent. Using a range of receptor or channel ligands (including omega-conotoxin and Na+ and K+ channel modulators), only the L-type Ca2+ channel antagonists were found to displace [3H]SR 33805. However, dihydropyridines, phenylalkylamines, benzothiazepines, and diphenyl-butylpiperidines were found to inhibit [3H]SR 33805 in a non-competitive manner as demonstrated by displacement experiments in addition to dissociation kinetics. In contrast, the interaction of SR 33805 with fantofarone has been found to be competitive. Binding of [3H]SR 33805 (and [3H]fantofarone) is entropy driven as opposed to that of the [3H]nitrendipine which is enthalpy driven. From these results we suggest that SR 33805 binds with a high affinity to a unique site on the L-type Ca2+ channel found in rat cardiac sarcolemmal membranes. This site is equivalent to that of fantofarone and in allosteric interaction with that of the dihydropyridines, phenylalkylamines and benzothiazepines.

Prevention of calcium overload and down-regulation of calcium channels in rat heart by SR 33557, a novel calcium entry blocker.

The effect of SR 33557, a novel calcium entry blocker, on calcium overload, and regulation of calcium channels and beta-adrenergic receptors was investigated in the rat heart. Calcium overload and infarct-like lesions were produced by a large dose of isoproterenol (40 mg/kg, subcutaneously) to rats. Calcium overload was maximal 8 hours after administration of isoproterenol (control: 5.7 mmol Ca2+/kg dry weight, isoproterenol: 34.9 mmol Ca2+/kg dry weight). At that time, a decrease in the total number of beta-adrenergic receptors (-27%) and calcium channels (-20% and -23%) was observed. Intravenous injection of SR 33557 (0.5-10 mg/kg), 30 minutes before administration of isoproterenol, attenuated the increase in calcium content in a dose-related manner, such that 5 mg/kg SR 33557 reduced calcium overload by 50%. At this dose, SR 33557 had no effect on the number of beta-adrenergic receptors but prevented the decrease in the number of calcium channels. The total number of binding sites and the dissociation constants of each radioligand were estimated from saturation isotherms. The dissociation constants were unchanged when animals given isoproterenol or SR 33557 and isoproterenol were compared to the control group. The results indicate that SR 33557 is able to protect against the calcium overload induced by sympathetic over-stimulation. This over-stimulation of the sympathetic system causes a down-regulation of the number of active beta-adrenergic receptors and calcium channels. The down-regulation of calcium channels is selectively reduced by earlier administration of SR 33557.

Characterization of the slow calcium channel binding sites for [3H]SR 33557 in rat heart sarcolemmal membranes.

SR 33557 represents a new class of compounds (indolizine sulfone) that inhibit L-type Ca2+ channels. [3H]SR 33557 has been shown to bind with high affinity (Kd congruent to 0.36 nM, calculated from saturation isotherms and association/dissociation kinetics) to a single class of sites in a purified preparation of rat cardiac sarcolemmal membranes. The binding was found to be saturable and reversible. The maximal binding capacity was in approximately 1:1 stoichiometry with that of other Ca2+ channel antagonists. Various divalent cations (Mg2+, Mn2+, Ca2+, Ba2+, and Cd2+) were shown to inhibit specific [3H]SR 33557 binding, with Cd2+ being the most potent. Among several receptor or channel ligands (including omega-conotoxin and Na+ and K+ channel modulators), only the L-type Ca2+ channel antagonists were found to displace [3H]SR 33557. However, dihydropyridines, phenylalkylamines, benzothiazepines, and diphenylbutylpiperidines were found to inhibit [3H]SR 33557 in a noncompetitive manner as demonstrated by displacement and saturation experiments in addition to dissociation kinetics. From these results, we suggest that SR 33557 binds with high affinity to a unique site on the L-type Ca2+ channel found in rat cardiac sarcolemmal membranes.

SR 33557, a novel calcium entry blocker. II. Interactions with 1,4-dihydropyridine, phenylalkylamine and benzothiazepine binding sites in rat heart sarcolemmal membranes.

We have assessed the binding characteristics of a structurally novel calcium entry blocker, SR 33557, to purified rat heart sarcolemma. SR 33557 prevented completely the binding of (+)-[3H]PN200-110, (-)-[3H]D888 and cis-(+)-[3H]diltiazem to their specific binding sites in an apparently competitive manner (nH congruent to 1.0) and with a high affinity (Ki = 0.5-2.0 nM). Equilibrium and kinetic studies suggest that SR 33557 does not act as a simple competitive antagonist at the 1,4-dihydropyridine, the phenylalkylamine or the benzothiazepine-selective sites associated with the L-type calcium channel: 1) inhibition of (-)-[3H]D888 and cis-(+)-[3H]diltiazem binding by SR 33557 resulted in a decrease in maximum binding, 2) cis-(+)-diltiazem and (+)-PN200-110 allosterically increased the inhibition of (+)-[3H]PN200-110 binding and of (-)-[3H]D888 and cis-(+)-[3H]diltiazem binding by SR 33557, respectively and 3) dissociation kinetics of the three radioligands were accelerated by SR 33557. Calcium (in millimolar concentrations) decreased the apparent affinity of SR 33557 for its high-affinity binding sites. This observation was similar to that seen with the phenylalkylamines and cis-(+)-diltiazem, but contrasted from that seen with the 1,4-dihydropyridines. These results indicate that SR 33557 interacts with a high affinity to a novel binding site associated with the L-type calcium channel and has a strong negative allosteric interaction with the well-characterized binding sites for 1,4-dihydropyridines, phenylalkylamines and benzothiazepines.

SR 33557, a novel calcium-antagonist: interaction with [3H]-(+/-)-nitrendipine and [3H]-(-)-desmethoxy-verapamil binding sites in cerebral membranes.

We investigated the pharmacological properties of SR 33557, a novel compound with calcium-antagonist properties, in both functional tests in vitro and radioligand binding studies. SR 33557 potently antagonized calcium-induced contraction of potassium-depolarized rat aorta in vitro with an IC50 value of 5.6 +/- 0.9 nM, but was a much weaker inhibitor of noradrenaline-induced contraction of the same tissue (IC50 = 96 +/- 22 nM). SR 33557 totally inhibited [3H]-(+/-)-nitrendipine binding to rat brain membranes with a Ki value of 0.19 +/- 0.03 nM. Diltiazem, which used alone increases [3H]-(+/-)-nitrendipine binding, reversed this inhibition indicating that SR 33557 allosterically regulates [3H]-(+/-)-nitrendipine binding. SR 33557 also fully inhibited [3H]-(-)-desmethoxyverapamil binding to cerebral membranes, but inhibition curves were biphasic. IC50 value calculated for that part of the curve which reflects the high affinity binding site of SR 33557 (IC50 = 0.20 +/- 0.02 nM) was very similar to the Ki value determined for inhibition of [3H]-(+/-)-nitrendipine binding. Kinetic evidences indicate that SR 33557 binds to a site which is distinct from the 1,4-dihydropyridine or the phenylalkylamine binding sites associated with the calcium channel. To test the pharmacological specificity of these interactions, the ability of SR 33557 to interact with eight other receptors in cerebral or heart membranes was assessed by binding assays. No high-affinity interaction was observed between SR 33557 and any of the receptors investigated. We conclude that SR 33557 binds specifically and with a high affinity to a site closely associated with the voltage-operated calcium channel in cerebral membranes.

Uncoupling between beta-adrenoceptors and adenylate cyclase in dog ischemic myocardium.

We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior descending coronary in 5 anesthetized dogs. Crude cardiac membrane preparations were isolated from control and ischemic areas of ventricular myocardium and tested for: 1. L-(125I)iodocyanopindolol binding, in the absence and presence of +/- -isoprenaline and GTP, and 2. adenylate cyclase activity. The density of beta-adrenoceptors increased by 35% in membranes from ischemic areas while the proportion of receptors in a high affinity state for +/- -isoprenaline decreased from 43% to 20%. Adenylate cyclase activities in the basal state and under stimulation with NaF, forskolin, Gpp(NH)p, +/- -isoprenaline and VIP were all markedly and similarly reduced, being only about 30% of comparable activities in membranes from control areas. The +/- -isoprenaline subsensitivity of cardiac adenylate cyclase can, thus, be attributed to a defective enzymatic system and not to a reduction in the number of beta-adrenoceptors implying that the internal components of the system were more sensitive to acute ischemia than the outward oriented hormone receptors. It is tempting to ascribe this uncoupling to a functional depletion in the guanine nucleotide-binding regulatory protein Ns that might reflect a loss of high energy phosphate stores including GTP.