HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma.

Medulloblastoma (MB) is the most prevalent brain cancer in children. Four subgroups of MB have been identified; of these, Group 3 is the most metastatic. Its genetics and biology remain less clear than the other groups, and it has a poor prognosis and few effective treatments available.

The marine-derived HIF-1α inhibitor, Yardenone 2, reduces prostate cancer cell proliferation by targeting HIF-1 target genes.

Background: Prostate cancer (PCa) ranks as the second most prevalent cancer in men, with advanced stages posing significant treatment challenges. Given its solid tumor nature, PCa is highly susceptible to hypoxia, a condition associated with resistance to radiation and chemotherapy, metastasis, and unfavorable patient outcomes. Hypoxia-inducible factors (HIFs) play a pivotal role in cancer cell adaptation to hypoxic environments, contributing to treatment resistance.

The mitochondrial NADH shuttle system is a targetable vulnerability for Group 3 medulloblastoma in a hypoxic microenvironment.

Medulloblastoma is a cancerous brain tumor that affects mostly children. Among the four groups defined by molecular characteristics, Group 3, the least well characterized, is also the least favorable, with a survival rate of 50%. Current treatments, based on surgery, radiotherapy, and chemotherapy, are not adequate and the lack of understanding of the different molecular features of Group 3 tumor cells makes the development of effective therapies challenging.

HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma.

Medulloblastoma (MB) is the most prevalent brain cancer in children. Four subgroups of MB have been identified; of these, Group 3 is the most metastatic. Its genetics and biology remain less clear than the other groups, and it has a poor prognosis and few effective treatments available.

A Cognitive Control-Inspired Approach to Object Tracking.

Under a tracking framework, the definition of the target state is the basic step for automatic understanding of dynamic scenes. More specifically, far object tracking raises challenges related to the potentially abrupt size changes of the targets as they approach the sensor. If not handled, size changes can introduce heavy issues in data association and position estimation.

Assessment of the effects of renal impairment on the pharmacokinetics of the soluble guanylate cyclase activator cinaciguat after a single intravenous dose.

This open-label, parallel-group, single-dose study assessed the safety and pharmacokinetics of cinaciguat, a novel soluble guanylate cyclase activator in clinical development for the treatment of acute decompensated heart failure, in individuals with mild, moderate, or severe renal impairment compared with individuals with normal renal function. Cinaciguat was administered as a 100 µg/h continuous infusion over 4 hours. Plasma concentrations were determined by high-performance liquid chromatography coupled with mass spectrometry.

A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer.

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer.

Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib.

Simultaneous administration of vardenafil and tamsulosin does not induce clinically significant hypotension in patients with benign prostatic hyperplasia.

Objectives: To assess the pharmacodynamic effects of coadministered vardenafil and tamsulosin in patients with benign prostatic hyperplasia (BPH) undergoing stable tamsulosin therapy.

Methods: In this Phase 1, placebo-controlled, two-stage, two-way, crossover study, 22 patients undergoing stable (longer than 4 weeks) tamsulosin therapy for BPH (18 using 0.4 mg and 4 using 0.

Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction.

The effects of food on the pharmacokinetics of vardenafil were examined in 25 healthy adult males. Single-dose vardenafil 20 mg was administered in a randomized four-way crossover design after an overnight fast (at 8 a.m.

The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease.

Objectives: The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD).

Background: Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED.

Influence of gender on the pharmacokinetics, safety, and tolerability of cerivastatin in healthy adults.

The pharmacokinetics, safety, and tolerability of cerivastatin, a synthetic HMG-CoA reductase inhibitor were studied in 49 healthy volunteers. In this double-blind, parallel group, multiple-dose study, volunteers were randomized as age-matched, male-female pairs and stratified into younger (18-65 years, premenopausal females) or older (65-85 years, postmenopausal females) groups. Thirty-two (16 female, 16 male) subjects received 0.

The CHORUS (Cerivastatin in Heart Outcomes in Renal Disease: Understanding Survival) protocol: a double-blind, placebo-controlled trial in patients with esrd.

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-mediated lowering of serum cholesterol has been associated with a significant reduction in cardiovascular morbidity and mortality. Recent studies suggest that additional non-lipid lowering effects (eg, endothelial stabilization, anti-inflammatory, antithrombogenic) may be important in modulating their effectiveness. Dyslipidemia is common in end-stage renal disease (ESRD), and hemodialysis patients have increased cardiovascular morbidity and mortality.

Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin.

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are metabolized by distinct pathways that may alter the extent of drug-drug interactions. Cerivastatin is metabolized by cytochrome P450 (CYP)3A4 and CYP2C8. Atorvastatin is metabolized solely by CYP3A4, and pravastatin metabolism is not well defined.

Influence of renal function on the pharmacokinetics of cerivastatin in normocholesterolemic adults.

Objective: The influence of impaired renal function on the pharmacokinetics of single and multiple doses of cerivastatin was evaluated in this nonrandomized, non-blinded, 7-day, multiple-dose study.

Methods: Thirty-five adults between the ages of 21 years and 75 years with normal renal function (CL(CR) >90 ml/min/1.73 m2, n = 9), or patients with either mild (CL(CR) 61 ml/min/1.

Lack of mutual pharmacokinetic interaction between cerivastatin, a new HMG-CoA reductase inhibitor, and digoxin in healthy normocholesterolemic volunteers.

The potential mutual interaction between cerivastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, and digoxin was assessed in this nonmasked, nonrandomized, multiple-dose study. The effect of cerivastatin 0.2 mg on mean plasma digoxin levels and the effect of digoxin on the single-dose pharmacokinetics of cerivastatin were assessed in 20 healthy normocholesterolemic men between 18 and 45 years of age weighing 140 to 200 lbs (63.

Biopharmaceutical profile of cerivastatin: a novel HMG-CoA reductase inhibitor.

The biopharmaceutical properties of cerivastatin were evaluated in a series of worldwide clinico-pharmacological studies. Young healthy males aged 18-45 years were randomized to receive 0.05-0.

Pharmacodynamics, safety, tolerability, and pharmacokinetics of the 0.8-mg dose of cerivastatin in patients with primary hypercholesterolemia.

Cerivastatin is a third generation hydroxy-methyl-glutaryl-Co-enzyme A (HMG-CoA) reductase inhibitor proven to lower low-density lipoprotein (LDL) cholesterol 28% to 31% in patients with primary hypercholesterolemia when given at 0.3 mg/day. This study evaluates the safety, tolerability, pharmacodynamics, and pharmacokinetics of cerivastatin 0.

Influence of age on the safety, tolerability, and pharmacokinetics of the novel HMG-CoA reductase inhibitor cerivastatin in healthy male volunteers.

The safety, tolerability, and pharmacokinetics of cerivastatin, a novel, synthetic, potent, and highly selective HMG-CoA reductase inhibitor, were studied in 48 young and elderly male volunteers in a randomized, double-blind, placebo-controlled study. Eight men ranging from 18 to 38 years of age (young) and 15 men ranging from 65 to 78 years of age (elderly) received 0.1-mg cerivastatin tablets daily for 7 days.

Thrombolytic therapy with urokinase reduces increased circulating endothelial adhesion molecules in acute myocardial infarction.

The aim was to investigate circulating E-selectin and Intercellular Adhesion Molecule-1 (ICAM-1) in acute myocardial infarction. Our study was carried out in 80 patients, 40 hospitalized for acute myocardial infarction (AMI), 20 suffering from chronic stable angina and 20 healthy control subjects. Samples of venous blood were taken from all patients at the moment of hospitalization and after 2, 4, 6, 8, 10, 12 and 24 hours from the thrombolytic treatment (AMI + urokinase) or conventional therapy (AMI + nitroglycerin), for the dosage of creatinine kinase (CK) and adhesion molecules.

Early reactivation of ischaemia after abrupt discontinuation of heparin in acute myocardial infarction.

Intravenous heparin after thrombolytic therapy for acute myocardial infarction is an effective, widely used treatment. Six cases of acute myocardial infarction are reported with early disease reactivation following the abrupt discontinuation of heparin infusion three days after alteplase thrombolysis and concomitant aspirin therapy. Immediate reinfusion of heparin resulted in regression of symptomatic ischaemia in all six patients.

Myocardial bridging involving more than one site of the left anterior descending coronary artery: an uncommon cause of acute ischemic syndrome.

An infrequent angiographic finding is reported of myocardial bridging involving more than one site of the left anterior descending coronary artery in a symptomatic patient with ischemia exacerbated by nitroglycerin administration. Beta-blocker therapy alone was followed by a favorable long-term outcome.

Comparative effects of nitrendipine and hydrochlorothiazide on calciotropic hormones and bone density in hypertensive patients.

The effects of the calcium antagonist nitrendipine and the diuretic hydrochlorothiazide on plasma calciotropic hormone concentrations and lumbar bone density were compared during the treatment of hypertension in a randomized, double-blind, 8 week parallel study, followed by a 52 week open label study. There were 32 subjects with stable essential hypertension (sitting diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg without medication) without evidence of renal insufficiency or active heart disease. They were randomly assigned to receive either 10 mg nitrendipine twice daily or 50 mg hydrochlorothiazide daily.

Multiple dose pharmacokinetics of four different doses of nisoldipine in hypertensive patients.

This randomized double-blind parallel group study characterized the pharmacokinetics of the calcium channel antagonist, nisoldipine (core-coat tablets), administered once daily for 7 days in doses of 5 mg (n = 12), 10 mg (n = 13), 20 mg (n = 12), and 30 mg (n = 11) to patients with mild to moderate hypertension. Serial blood samples were obtained from 0 to 24 hours and from 0 to 48 hours after nisoldipine administration on days 1 and 7, respectively. Nisoldipine plasma concentrations were determined by gas chromatography with electron capture detection.