Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids.

Clozapine is an atypical antipsychotic drug used to treat treatment-resistant schizophrenia. Its side effects, including liver enzyme abnormalities, experienced by many patients preclude its more common use as a first-line therapy for schizophrenia. Toxicoproteomic approaches have been demonstrated to effectively guide the identification of toxicological mechanisms.

[A descriptive epidemiological study on canine babesiosis in the Lake Geneva region].

A descriptive study was carried out in the district of the Lake Geneva between March 1, 2005 and August 31,2006 to assess the incidence and prevalence of canine babesiosis, to genotype the Babesia species occurring, to assess the most frequently clinical signs found and to address the potential of autochthonous transmission. This included a data assessment on the different tick-populations occurring in the area and on the prevalence of Babesia-DNA in these ticks. A total of 56 veterinary practices participated in the study.

[Blood pressure recording in outpatient service: experience with the Sandoz Pressure System].

The Sandoz Pressure System (SPS) is a widely used device for ambulatory blood pressure recording. The accuracy of blood pressure profiles recorded in daily routine with this device has been demonstrated. In 34 untreated hypertensive patients the blood pressure values were in good agreement with measurements taken by auscultation.

Effects of SCH 34826, an orally active inhibitor of atrial natriuretic peptide degradation, in healthy volunteers.

Atrial natriuretic peptide is cleared from plasma by clearance receptors and by enzymatic degradation by way of a neutral metalloendopeptidase. Inhibition of neutral metalloendopeptidase activity appears to provide an interesting approach to interfere with metabolism of atrial natriuretic peptide to enhance the renal and haemodynamic effects of endogenous atrial natriuretic peptide. In this study, the effects of SCH 34826, a new orally active neutral metalloendopeptidase inhibitor, have been evaluated in a single-blind, placebo-controlled study involving eight healthy volunteers who had maintained a high sodium intake for 5 days.

Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers. Inhibition of pressor response to exogenous angiotensin I and II.

Background: The purpose of the present study was to assess the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy male volunteers.

Methods And Results: In the first study (single-dose study), eight volunteers were included in a 2-day protocol repeated four times at 1-week intervals. In each phase, a different dose of drug (2.

Precursors of neuropeptides in the marine worm Nereis diversicolor. In vitro translation of a precursor related to human prepro-cholecystokinin and immunolocalization of this precursor in the nervous system.

Total mRNA extracted from the brain of a marine worm, Nereis diversicolor, were in vitro translated using 2 cell-free systems: rabbit reticulocyte lysate and wheat germ extract. Among numerous products newly translated in both systems, only one class of 70 kDa polypeptides immunoprecipitated when we used a mixture of 3 well defined antibodies raised against known sequences of the human prepro-CCK. At the cellular level, using immunocytochemistry techniques, strong and moderate immunoreactivities were seen in perikarya located in various ganglionic nuclei of the worm brain.

Hemodynamic and humoral effects of the new renin inhibitor enalkiren in normal humans.

The effect of the renin inhibitor enalkiren (Abbott-64662) was evaluated in eight normal volunteer subjects on a standardized sodium diet (100 mmol/day) by measurement of various components of the renin-angiotensin system and drug levels in plasma. On day 1, vehicle and doses of 0.001, 0.

Effects of prolonged administration of the angiotensin converting enzyme inhibitor CGS 16617 in normotensive volunteers.

A new, orally active angiotensin converting enzyme (ACE) inhibitor, CGS 16617, has been evaluated in normotensive subjects during acute and prolonged administration. Single ascending doses of CGS 16617 20 to 100 mg were given to 9 normotensive volunteers at one week intervals and the changes in blood pressure, plasma ACE and renin activity were examined up to 72 h after drug intake. Also, CGS 16617 50 mg/day or placebo were given for 30 days to 8 and 6 normotensive subjects, respectively, maintained on an unrestricted salt diet.

Effects of intranasal administration of synthetic (4-28)human atrial natriuretic peptide to normal volunteers.

The effects of intranasal administration of increasing doses of synthetic human natriuretic peptide (4-28 hANP) were studied in six healthy volunteers. The peptide was administered as a nasal spray at doses of 50, 100, 200, and 500 micrograms in ascending order at 48-h intervals. Vehicle was administered by the same route randomly between any two of the doses.

Individual responses to converting enzyme inhibitors and calcium antagonists.

This study was designed to assess whether the acute blood pressure response of an individual hypertensive patient to a calcium antagonist or an angiotensin converting enzyme (ACE) inhibitor is a good predictor of the long-term efficacy of these drug classes in this particular patient. The concept that good responses to ACE inhibitors and calcium antagonists may be mutually exclusive was also tested. Sixteen patients were included in a randomized crossover trial of enalapril, 20 mg daily, and diltiazem, 120 mg daily, for 6 weeks each.

Hemodynamic, renal, and endocrine effects of 4-h infusions of human atrial natriuretic peptide in normal volunteers.

A synthetic human atrial natriuretic peptide of 26 aminoacids [human (3-28)ANP or hANP] was infused into normal male volunteers. Six subjects were infused for 4 h at 1-wk intervals with either hANP at the rate of 0.5 or 1.

Calcium entry blockade attenuates the acute blood pressure rise induced by cigarette smoking.

The purpose of this study was to assess whether the administration of a calcium entry blocker can prevent the acute blood pressure rise induced by cigarette smoking. Seven male habitual smokers were included. After 45 min of equilibration, they took in randomized single-blind fashion at a 1 week interval either a placebo or nifedipine, 10 mg p.

[Effect of atrial natriuretic factor on the hematocrit of patients in chronic hemodialysis].

A synthetic atrial natriuretic peptide (ANF) has been administered to 7 patients with chronic renal failure to evaluate the role of ANF in the regulation of blood volume. ANF (2 micrograms/min) was infused for 60 minutes before hemodialysis and blood pressure, heart rate, plasma proteins and hematocrit were measured at regular intervals. Although a slight decrease in blood pressure occurred during ANF infusion, no significant changes in hematocrit and plasma proteins were observed.

Effect of eight-day converting enzyme inhibition on ambulatory blood pressure recordings in normotensive volunteers.

The three angiotensin converting enzyme (ACE) inhibitors cilazapril, perindopril and CGS 14824A were administered for 8 days to, respectively, 6, 5 and 5 normotensive healthy volunteers maintained on an unrestricted salt intake. Before starting treatment, as well as on the last day of therapy, an ambulatory blood pressure profile was obtained with a semi-automatic blood pressure recorder (Remler M2000). An additional blood pressure recording was performed 1 month after the end of the 8-day course of treatment with cilazapril and CGS 14824A.

Effect of prolonged angiotensin converting enzyme inhibition on ambulatory blood pressure of normotensive volunteers.

The blood pressure effect of 8-day angiotensin converting enzyme (ACE) inhibition was studied in normotensive healthy volunteers maintained on an unrestricted salt intake. Six volunteers received cilazapril (5 mg/day), 5 perindopril (8 mg/day) and 5 CGS14824A (10 mg/day). The 3 investigational inhibitors were found to have no consistent effect on blood pressure monitored during day-time outside the clinic using a semi-automatic blood pressure recorder (Remler M2000).

Angiotensin-converting enzyme inhibitor versus calcium antagonist in the treatment of hypertension.

Sixteen patients with essential hypertension were treated for 2 consecutive 6-week periods with either the angiotensin-converting enzyme (ACE) inhibitor enalapril (20 mg once daily) or the calcium antagonist diltiazem (120 mg twice daily). The sequence of the treatment phases was randomly allocated. Blood pressure decreased from 154/102 +/- 5/2 mm Hg (mean +/- SEM) to 135/96 +/- 4/2 and 140/98 +/- 3/2 mm Hg during treatment with enalapril and diltiazem, respectively.

Acute antihypertensive effect of angiotensin converting enzyme inhibition and calcium entry blockade.

The acute blood pressure response to an angiotensin converting enzyme inhibitor (enalaprilat) was compared in patients with uncomplicated essential hypertension with that obtained under similar conditions with a calcium entry blocker (nifedipine). The patients were studied after a 3 week washout period. At a 48 h interval, each patient received in randomized order either enalaprilat (5 mg i.

Repeated administration of the converting enzyme inhibitor cilazapril to normal volunteers.

Cilazapril 1.25 and 5.0 mg p.

[Effects of perfusion of human atrial natriuretic factor in normal volunteers].

The renal and systemic effects of a synthetic atrial natriuretic peptide (ANP) corresponding to the sequence of the human hormone was investigated in normal volunteers. Each subject was infused for 4 hours on 3 different days at a one week interval with either ANP (0.5 or 1 microgram/min) or its vehicle.

Four-hour infusions of synthetic atrial natriuretic peptide in normal volunteers.

Two doses of synthetic atrial natriuretic peptide (0.5 and 5.0 micrograms/min) and its vehicle were infused intravenously for 4 hours in eight salt-loaded normal volunteers, and the effect on blood pressure, heart rate, renal hemodynamics, solute excretion, and secretion of vasoactive hormones was studied.

Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects.

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril (S9490-3) was evaluated in 18 normotensive men. In three subjects the pressor response to exogenous angiotensin I was tested. A 8 mg oral dose reduced the pressor response by greater than 80%.

Unpredictability of blood pressures recorded outside the clinic in the treated hypertensive patient.

Ambulatory blood pressure profiles were obtained with the Remler M2000, a portable semiautomatic blood pressure recorder, in 38 chronically treated hypertensive patients who continued to have blood pressures measured by their physician greater than 140 mm Hg systolic and greater than 89 mm Hg diastolic. On the average, ambulatory recorded blood pressures were significantly lower (151/94 +/- 26/13 mm Hg; mean +/- SD) than those determined at the clinic not only by a physician (179/109 +/- 22/11 mm Hg), but by a nurse (163/101 +/- 24/10 mm Hg). Individual mean recorded ambulatory blood pressures could be predicted neither from office readings obtained by a physician nor from those measured by a nurse.

Atrial natriuretic peptides: reproducibility of renal effects and response of liver blood flow.

To assess the variability of the response to exogenous atrial natriuretic peptide (ANP), it was infused at the rate of 1 microgram/min for 2 h in 6 salt-loaded normal volunteers under controlled conditions on 2 occasions at an interval of 1 week. The effect on solute excretion and the haemodynamic and endocrine actions were highly reproducible. The constant ANP infusion caused a delayed and prolonged excretion of sodium, chloride and calcium, no change in potassium or phosphate excretion or in glomerular filtration rate but a marked decrease in renal plasma flow.

[Usefulness of ambulatory registration of arterial pressure in therapeutic trials of antihypertensive agents].

In the context of a controlled antihypertensive drug trial, blood pressure readings obtained by the physician in his office were compared with ambulatory blood pressures recorded with the semi-automatic Remler device. The beta-adrenoceptor blocking agent timolol or methyldopa were administered in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure of greater than 95 mm Hg at the end of a 4-week placebo period.

Blood pressure response to antihypertensive therapy: ambulatory versus office blood pressure readings.

Blood pressure readings obtained by the physician in his office and ambulatory blood pressures recorded with the semi-automatic Remler device, were compared during a controlled antihypertensive drug trial. Either timolol or methyldopa was administered in in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure greater than 95 mmHg at the end of a four-week placebo period.