Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD.

Autonomous circadian clocks exist in nearly every mammalian cell type. These cellular clocks are subjected to a multilayered regulation sensitive to the mechanochemical cell microenvironment. Whereas the biochemical signaling that controls the cellular circadian clock is increasingly well understood, mechanisms underlying regulation by mechanical cues are largely unknown.

Probing molecular crowding in compressed tissues with Brillouin light scattering.

Volume regulation is key in maintaining important tissue functions, such as growth or healing. This is achieved by modulation of active contractility as well as water efflux that changes molecular crowding within individual cells. Local sensors have been developed to monitor stresses or forces in model tissues, but these approaches do not capture the contribution of liquid flows to volume regulation.

Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial.

Background: Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by CAG repeat expansion in the androgen receptor gene. Patients with this disease have low concentrations of insulin-like growth factor-1 (IGF-1), and studies of overexpression and administration of IGF-1 showed benefit in a transgenic model; thus the IGF-1 pathway presents as a potential treatment target. We assessed safety, tolerability, and preliminary efficacy of BVS857, an IGF-1 mimetic, in patients with spinal and bulbar muscular atrophy.

Monitoring of food spoilage by high resolution THz analysis.

High resolution rotational Terahertz (THz) spectroscopy has been widely applied to the studies of numerous polar gas phase molecules, in particular volatile organic compounds (VOCs). During the storage of foodstuffs packed under a protective atmosphere, microbial activity will lead to the generation of a complex mixture of trace gases that could be used as food spoilage indicators. Here we have demonstrated that the THz instrumentation presently available provides sufficient sensitivity and selectivity to monitor the generation of hydrogen sulfide (H2S) in the headspace of packed Atlantic salmon (Salmo salar) fillet portions.

Hexavalent Chromium Removal from Model Water and Car Shock Absorber Factory Effluent by Nanofiltration and Reverse Osmosis Membrane.

Nanofiltration and reverse osmosis are investigated as a possible alternative to the conventional methods of Cr(VI) removal from model water and industrial effluent. The influences of feed concentration, water recovery, pH, and the coexisting anions were studied. The results have shown that retention rates of hexavalent chromium can reach 99.

Competitive adsorption of fluoride and natural organic matter onto activated alumina.

Natural organic matter (NOM) is a major water constituent that affects the performance of water treatment processes. Several studies have shown that NOM can be adsorbed on the surface of oxides and may compete with other ions. The overall goal of this study was essentially to investigate the competitive adsorption between fluoride and NOM on activated alumina (AA).

Drug Development and Challenges for Neuromuscular Clinical Trials.

Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.

Electrophysiological characterization of isolated human atrial myocytes exposed to tegaserod.

Tegaserod (Teg), a 5-hydroxytryptamine type-4 (5-HT(4)) receptor partial agonist, represents a novel treatment for irritable bowel syndrome with constipation and chronic constipation. Cardiovascular safety data from pooled clinical studies showed a signal suggestive of increased occurrence of ischaemic cardiovascular events in patients exposed to Teg versus placebo. Thereafter, marketing of Teg was suspended in the USA and other countries.

Investigations on 5-HT₄ receptor expression and effects of tegaserod on human platelet aggregation in vitro.

A meta-analysis of 29 clinical studies on tegaserod revealed an imbalance of cardiovascular ischemic events in patients treated with drug versus placebo. Because increased platelet activity is known to attribute to cardiovascular events, we examined the presence of serotonin receptor type 4 (5-HT₄) receptors and the effects of tegaserod on in vitro aggregation of human platelets. Blood samples were obtained from 20 healthy volunteers and 20 subjects with irritable bowel syndrome with constipation.

Influence of ketoconazole on azimilide pharmacokinetics in healthy subjects.

Aim: To assess the influence of ketoconazole on azimilide pharmacokinetics.

Methods: A two-period randomized crossover study was conducted in healthy male and female subjects (19-45 years). Placebo or 200 mg ketoconazole were administered orally every 24 h for 29 days.

Influence of azimilide on CYP2C19-mediated metabolism.

The purpose of this study was to assess the influence of multiple-dose oral administration of azimilide dihydrochloride on CYP2C19-mediated metabolism. A two-period, randomized crossover study was conducted in 40 healthy male subjects who were phenotyped as extensive CYP2C19 metabolizers. Oral doses of placebo or 125 mg of azimilide dihydrochloride were administered every 12 hours for 3 days, followed by every 24 hours for 5 days; 20 mg omeprazole was coadministered on Day 8.

[Prognosis of retinoblastoma. Report of 50 cases].

Purpose: The aim of this study was to analyze the factors influencing the prognosis of retinoblastoma.

Materials And Methods: In 50 children with retinoblastoma, 69 eyes were reviewed. All patients had a full ophthalmic examination, a B-scan ultrasound, a computerized tomography scan and a pediatric examination.

[Emphysematous pyelonephritis: report of 3 cases].

Emphysematous pyelonephritis is a rare and life-endangering suppurative infection characterized by the production of gas in the renal parenchyma and perirenal space. It affects mainly patients with diabetes mellitus. Authors report three cases of emphysematous pyelonephritis and insist on the role of radiological investigations in diagnosis.

Stereoselective glucuronidation of (R)- and (S)-naproxen by recombinant rat phenol UDP-glucuronosyltransferase (UGT1A1) and its human orthologue.

Recombinant rat phenol UDP-glucuronosyltransferase (UGT1A1) conjugates (R)-naproxen at a much higher rate (> 17-fold) than its (S)-enantiomer, substantiating previous findings on stereoselective glucuronidation of racemic naproxen. In contrast, the recombinant human orthologue conjugated both enantiomers at equal rates. In line with high constitutive expression of UGT1A1 in extrahepatic tissues, a high R/S ratio of naproxen glucuronidation was found in rat testes, intestine, lung and kidney.

[Pulmonary emphysema: quantification using computed tomography and correlations with respiratory function tests].

Pulmonary emphysema can be defined in precise anatomical terms. Only histological examination of an entire lung will enable the extension and the severity of the emphysema to be fully assessed. The authors propose a visual score, using computed tomography to quantify emphysema in 61 subjects.

Drug metabolizing enzyme activities in rat liver epithelial cell lines, hepatocytes and bile duct cells.

P450-dependent mono-oxygenase and conjugating enzyme activities were studied in rat liver epithelial cells (RLEs) and compared to those in hepatocytes and bile duct cells. Various RLE cell lines were investigated since (a) they are suspected to be derived from cells in the lineage from putative pluripotent stem cells to either hepatocytes or bile duct cells, and (b) they may represent targets of chemical carcinogens. Despite considerable variation between lines, common features were recognized.

[Recurrent multifocal periostosis in children. Report of a familial form].

Recurrent multifocal periostosis of childhood is an infrequent disease. All cases reported to date have been sporadic. A familial form affecting three siblings is reported herein.

Stereoselective (S)- and (R)-naproxen glucuronosyl transferases of rat liver.

Stereoselective glucuronidation of naproxen, one of the 2-arylpropionic acids that are widely used as anti-inflammatory drugs, was investigated in chromatofocusing fractions of solubilized liver microsomes from 3-methylcholanthrene- (MC) and phenobarbital- (PB) treated rats. On chromatofocusing of solubilized microsomes of PB-treated rats, two naproxen glucuronosyltransferase (GT) fractions were separated. The fraction eluting at pH 8.

Hepatic drug conjugation/deconjugation systems in hepatosplenic schistosomiasis.

The biotransformation capacity of the liver is altered in hepatosplenic schistosomiasis being more in favor of deconjugation pathways. These alterations should be considered when xenobiotics are administered and in studies of hepatic toxicity and carcinogenicity.

Application of solid-phase extraction to the isolation and determination of paracetamol and its metabolites.

A series of clean-up columns for solid-phase extraction (SPE) were packed with various C18 phases of different physico-chemical surface properties. These SPE columns were used for the isolation and determination of paracetamol and its metabolites from biological samples. The packing with a monomeric structure of chemically bonded phase showed the best recovery of tested substances in urine.

Pulmonary histiocytosis X: evaluation with high-resolution CT.

Eighteen patients with pulmonary lesions of histiocytosis X were studied with high-resolution computed tomography (CT). Thin-walled cysts were found in all but one patient. The other abnormalities included nodules (n = 14), cavitated nodules (n = 3), thick-walled cysts (n = 7), reticulation (n = 4), ground-glass opacities (n = 4), and irregular interfaces (n = 4).

[Hepatic puncture-biopsy with embolization of the tract].

Recently reported by Shuang, percutaneous liver biopsy with embolisation of the tract (PLBET), involves the use of a coaxial needle system permitting embolisation of the tract while avoiding the haemorrhage complications of conventional biopsy. We conceived a system similar to shuang's 14G, 16G. We report the description of this system and the results obtained on 50 patients.

Species-dependent enantioselective glucuronidation of three 2-arylpropionic acids. Naproxen, ibuprofen, and benoxaprofen.

The enantioselective glucuronidation of several racemic 2-arylproprionic acids (naproxen, ibuprofen, and benoxaprofen) was investigated in vitro with immobilized microsomal protein from human, rhesus monkey, and rabbit liver as the source of UDP-glucuronyl-transferases. Human microsomes, solubilized microsomal protein, and immobilized protein all gave comparable enantioselectivity. The diastereomeric glucuronides were separated and quantitated by HPLC and characterized stereochemically by co-elution with glucuronides formed from authentic resolved enantiomers.