[A descriptive epidemiological study on canine babesiosis in the Lake Geneva region]. / Etude épidémiologique descriptive de la Babésiose canine dans la Région Lémanique.

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. By blood smear and PCR, Babesia canis canis was found in 12 out of 21 cases with suspected babesiosis. In an additional 13th case, the parasite could only be detected by PCR. All autochthonous cases originated from the Western part of the Lake Geneva region. Clinical signs in affected dogs included inappetence, apathy, anemia, fever, hemoglobinuria and thrombocytopenia. There were no risk factors with regard to age, sex and breed. Most cases were diagnosed during the spring periods of 2005 and 2006 (11 cases) and two cases in autumn 2005, coinciding with the main activity period of Dermacentor reticulatus, the main vector of B. canis canis. A total of 495 ticks were collected on patients by the veterinarians, 473 were identified as Ixodes sp., 7 as Rhipicephalus sanguineus and 15 as Dermacentor reticulatus. While Ixodes sp. was found in the whole study area, D. reticulatus and R. sanguineus occurred only in the Western part till Lausanne. PCR and sequencing yielded B. canis canis positivity in 3 D. reticulatus specimen, these three ticks were collected from two different dogs both suffering from babesiosis. All R. sanguineus were negative by Babesia-PCR. Global warming, ecological changes in the potential habitat of ticks, increasing host- and vector-populations and increasing mobility of dog owners may be responsible for an emergence situation of infection risk for Babesia spp. by time. E.g., Dermacentor reticulatus has become autochtonously prevalent already till Lausanne in the Lake Geneva region, and further surveillance is suggested to tackle this problem.

Ambulatory blood pressure recordings. Reproducibility and unpredictability.

The accuracy of blood pressure readings taken by the portable semiautomatic blood pressure recorder Remler M 2000 was investigated in 101 unselected, untreated volunteers. On the average, pressures recorded during usual daily activities were lower by approximately 10 mm Hg than pressures measured in the office. However, individual ambulatory pressures could not be predicted from office readings, and the difference varied among the volunteers from +14 to -43 mm Hg. The reproducibility of office and ambulatory pressures was investigated in 84 subjects. There was a highly significant correlation between pressure levels determined at a 3- to 4-month interval with both the conventional auscultatory method in the office and the Remler ambulatory recorder. These data demonstrate that the Remler M 2000 ambulatory blood pressure recorder, when used properly, provides reproducible blood pressure profiles during customary daily activities. The ambulatory pressure recorder seems particularly useful for a baseline evaluation of the usual daily blood pressure, which in the individual subject differs in a highly unpredictable manner from the blood pressure measured at the physician's office.

Ambulatory blood pressure recordings. Reproducibility and unpredictability.

The accuracy of blood pressure readings taken by the portable semiautomatic blood pressure recorder Remler M 2000 was investigated in 101 unselected, untreated volunteers. On the average, pressures recorded during usual daily activities were lower by approximately 10 mm Hg than pressures measured in the office. However, individual ambulatory pressures could not be predicted from office readings, and the difference varied among the volunteers from +14 to -43 mm Hg. The reproducibility of office and ambulatory pressures was investigated in 84 subjects. There was a highly significant correlation between pressure levels determined at a 3- to 4-month interval with both the conventional auscultatory method in the office and the Remler ambulatory recorder. These data demonstrate that the Remler M 2000 ambulatory blood pressure recorder, when used properly, provides reproducible blood pressure profiles during customary daily activities. The ambulatory pressure recorder seems particularly useful for a baseline evaluation of the usual daily blood pressure, which in the individual subject differs in a highly unpredictable manner from the blood pressure measured at the physician's office.

Escape from mineralocorticoid excess: the role of angiotensin II.

Escape from the sodium-retaining action of mineralocorticoids coincides with the suppression of plasma renin and angiotensin II levels. The purpose of this study was to evaluate whether blockade of the renin system accelerates this escape. Eight male normotensive volunteers, aged 24--33 yr, were maintained during two subsequent periods of 12 days each, separated by 3--4 weeks, on a constant intake of sodium and potassium of 140 mmol/day. During both periods, fludrocortisone acetate (0.2 mg) was administered orally three times a day on days 4--12. In addition, on days 3--12, either a converting enzyme inhibitor (MK 421;20 mg orally, twice daily) or a placebo was added in double blind fashion and randomized sequence. During both periods, blood pressures were similar; they tended to increase slightly toward day 12. The weight increase did not differ between the two periods. With MK 421, angiotension II levels were significantly lower than with placebo on days 3--6 (P less than 0.001). On the same days, PRA was increased due to converting enzyme blockade. Despite the significantly different angiotensin II levels on days 3--6, daily urinary sodium excretion on all individual days as well as cumulative sodium balance were the same during both periods. Therefore, we could find no evidence in man that suppression of circulating angiotensin II levels is causally related to escape from mineralocorticoid excess.

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. Blood pressure was measured by ambulatory blood pressure recording. During the washout phase, the acute effect of nifedipine, 10 mg p.o., and enalaprilat, 5 mg i.v., was evaluated. Nifedipine and enalaprilat reduced blood pressure equally well. The long-term blood pressure reduction induced by enalapril and diltiazem was similar. The acute blood pressure response to a given drug was not a good predictor of the result obtained with long-term therapy. No age dependency of the antihypertensive effect of either drug class was apparent. There was no evidence that a good response to one drug excluded a similarly good response to the other.

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. The 0.5 micrograms/min infusion did not alter blood pressure or heart rate, whereas the 5.0 micrograms/min infusion significantly reduced the mean pressure by 20/9 mm Hg after 2.5 to 3 hours and increased the heart rate slightly. Inulin clearance was not significantly changed, but the mean p-aminohippurate clearance fell by 13 and 32% with the lower and higher doses, respectively. Urinary excretion of sodium and chloride increased slightly with the lower dose. With the higher dose, a marked increase in urinary excretion of sodium, chloride, and calcium was observed, reaching a peak during the second hour of the infusion. Potassium and phosphate excretion did not change significantly. A brisk increase in urine flow rate and fractional water excretion was seen only during the first hour of the high-dose infusion. Signs and symptoms of hypotension were observed in two subjects. No change in plasma renin activity, angiotensin II, or aldosterone was observed during either infusion, but a marked increase occurred after discontinuation of the high-dose infusion. In conclusion, the 5 micrograms/min infusion induced a transient diuretic effect, delayed maximal natriuretic activity, and a late fall in blood pressure, with no change in inulin clearance but a dose-related decrease in p-aminohippurate clearance. Despite large amounts of sodium excreted and blood pressure reduction, no counterregulatory changes were observed in the renin-angiotensin-aldosterone system or plasma vasopressin levels during the infusion.

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, 0.003, and 0.01 mg/kg i.v. were administered within 2 minutes at 90-minute intervals. On day 2, vehicle and doses of 0.01, 0.03, and 0.1 mg/kg i.v. were given. With the higher doses, blood pressure tended to decrease slightly with no change in heart rate. Plasma renin activity and plasma angiotensin-(1-8)octapeptide (angiotensin II) fell markedly in a dose-dependent manner. Inhibition of plasma renin activity was maximal 5 minutes after administration of the drug and persisted 90 minutes after the doses of 0.03 and 0.1 mg/kg. Not surprisingly, there was a close correlation between plasma renin activity and plasma angiotensin II levels (r = 0.81, n = 28, p less than 0.001). In contrast, active and total renin measured directly by monoclonal antibodies rose in dose-related fashion in response to renin inhibition. Pharmacokinetic parameters were calculated using the plasma drug concentrations obtained up to 6 hours after the 0.1 mg/kg dose. By means of a two-compartment model, plasma mean half-life of the drug was estimated at 1.60 +/- 0.43 hours.

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. SCH 34826 had no effect on blood pressure or heart rate in these normotensive subjects. SCH 34826 promoted significant increases in excretion of urinary sodium, phosphate, and calcium. The cumulative 5-hour urinary sodium excretion was 15.7 +/- 7.3 mmol for the placebo and 22.9 +/- 5, 26.7 +/- 6 (p less than 0.05), and 30.9 +/- 6.8 mmol (p less than 0.01) for the 400, 800, and 1600 mg SCH 34826 doses, respectively. During the same time interval, the cumulative urinary phosphate excretion increased by 0.3 +/- 0.4 mmol after placebo and by 1.5 +/- 0.3 (p less than 0.01), 1.95 +/- 0.3 (p less than 0.01), and 2.4 +/- 0.4 mmol (p less than 0.001) after 400, 800, and 1600 mg SCH 34826, respectively. There was no change in diuresis or excretion of urinary potassium and uric acid. The natriuretic response to SCH 34826 occurred in the absence of any change in plasma atrial natriuretic peptide levels but was associated with a dose-dependent elevation of urinary atrial natriuretic peptide and cyclic guanosine monophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

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%. Single oral perindopril doses of 2, 4, 8, and 16 mg were given to groups of five subjects each. Eight and 16 mg decreased plasma ACE activity within 4 hours to less than 10% of control; 72 hours later, plasma ACE activity was still reduced by at least 40%. Doses of 4 and 8 mg po once a day were then given for 8 days to two groups of six subjects. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone, and plasma ACE activity fell significantly, whereas blood angiotensin I and plasma renin activity rose. There was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed. Thus in normotensive subjects, perindopril seems an effective, orally active, long-lasting ACE inhibitor.

Three new long-acting converting-enzyme inhibitors: relationship between plasma converting-enzyme activity and response to angiotensin I.

Three new angiotensin converting-enzyme inhibitors were given orally to 20 men in single doses ranging from 1.25 to 40 mg. Two of them induced comparable marked inhibition of both the blood pressure response to exogenous angiotensin I and plasma converting-enzyme activity. Onset of action was relatively slow, but 21 to 24 hr after drug plasma converting-enzyme activity was still clearly reduced. The third was less active. There was a close correlation between blood pressure response on administration of angiotensin I and plasma converting-enzyme activity. There were no adverse effects. These new drugs are interesting because of their long duration of action. The measurement of plasma converting-enzyme activity seems useful for monitoring efficacy of converting-enzyme blockade and compliance to therapy.

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. All patients then received a combination of hydrochlorothiazide (25 mg/day) and amiloride (2.5 mg/day). After four weeks of diuretic therapy, timolol (10 mg/day, n = 14) or methyldopa (250 mg/day, n = 16) were added randomly for six weeks. The dose of all antihypertensive agents was doubled after two weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels greater than 90 mmHg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower in the patients given timolol (P less than 0.05 for the diastolic). With both regimens, the blood pressure response measured outside the clinic during usual daily activities could not be predicted from that observed with office blood pressure readings. Furthermore the magnitude of the drug induced blood pressure decrease was more reproducible in time when determined outside the clinic. These data suggest that ambulatory blood pressure monitoring is more precise in evaluating the efficacy of antihypertensive therapy than office blood pressure measurement.

The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers.

The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.

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 1.0 microgram/min or its vehicle in a single-blind randomized order. Human (3-28)ANP at the dose of 0.5 microgram/min raised immunoreactive plasma ANP levels from 104 +/- 17 to 221 +/- 24 pg/ml (mean +/- SEM), but it induced no significant change in blood pressure, heart rate, effective renal plasma flow, glomerular filtration rate, or renal electrolyte excretion. At the rate of 1.0 microgram/min, human (3-28)ANP increased immunoreactive plasma ANP levels from 89 +/- 12 to 454 +/- 30 pg/ml. It reduced effective renal plasma flow from 523 +/- 40 to 453 +/- 38 ml/min (P less than 0.05 vs. vehicle), but left glomerular filtration rate unchanged. Natriuresis rose from 207 +/- 52 to 501 +/- 69 mumol/min (P less than 0.05 vs. vehicle) and urinary magnesium excretion from 3.6 +/- 0.5 to 5.6 +/- 0.5 mumol/min (P less than 0.01 vs. vehicle). The excretion rate of the other electrolytes, blood pressure, and heart rate were not significantly modified. At both doses, human (3-28)ANP tended to suppress the activity of the renin-angiotensin-aldosterone system. In 3 additional volunteers, the skin blood flow response to human (3-28)ANP, infused for 4 h at the rate of 1.0 microgram/min, was studied by means of a laser-doppler flowmeter. The skin blood flow rose during the first 2 h of peptide administration, then fell progressively to values below baseline. After the infusion was discontinued, it remained depressed for more than 2 h. Thus, in normal volunteers, human (3-28)ANP at the dose of 1.0 microgram/min produced results similar to those obtained previously with rat (3-28)ANP. It enhanced natriuresis without changing the glomerular filtration rate while effective renal plasma flow fell. It also induced a transient vasodilation of the skin vascular bed.

[Blood pressure recording in outpatient service: experience with the Sandoz Pressure System]. / Enregistrement tensionnel en ambulatoire: expérience avec le 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. The variability of recordings was less or equal to 5 mmHg in 10% of patients for the systolic and in 94% of patients for the diastolic value. During daily activity 100 +/- 6% (mean +/- standard deviation) of the values expected by programming were available for analysis. These results confirm that arterial pressure under ambulatory conditions cannot be reliably predicted based on blood pressure measurements in the doctor's office.

[Neuroendocrine control of reproduction in worms]. / Contrôle neuroendocrine de la reproduction chez les vers.

In "worms", up to now only neurohormones produced by neurosecretory cells are known; no endocrine organ has been demonstrated. These neurohormones can be involved in the regulation of asexual reproduction (planarians). But their actions have been essentially studied in annelids (oligochaetes, polychaetes, hirudinae) where it is possible to give evidence of several types of functional regulations: endocrine control of sexual differentiation, gonadotropic action, conditioning of gametes development. The isolation of different neurohormones will allow to study and understand their differential action at the level of target cells and to better perceive the evolution of endocrine functions in the animal kingdom.

[Purification of the brain hormone of Nereis diversicolor and Perinereis cultrifera (Annelida:Polichaeta) by high-pressure liquid chromatography (HPLC)]. / Purification par chromatographie liquide de haute pression (HPLC) de l'hormone cérébrale chez Nereis diversicolor et Perinereis cultrifera (Annélides Polychètes).

Five thousand brains inhibiting gametogenesis in Nereis diversicolor and Perinereis cultrifera were extracted with cold methanol, giving a micromolecular fraction containing the whole of the inhibitory activity of the brains. This micromolecular fraction, fractionated (i) on Sephadex G 25 fine and (ii) on Sephadex G 25 superfine, gave an inhibitory peak (P 5) in organ culture. Fraction P 5, purified by high-pressure liquid chromatography, showed an area with the same biological inhibitory activity as the blank brains.

Purification and characterization of oocyte vitellin from Perinereis cultrifera (polychaete annelid).

Vitellin was identified and purified from submature oocytes of Perinereis cultrifera by concanavalin-A - Sepharose and Ultrogel AcA 34 column chromatography. The yolk protein was defined as a glycolipoprotein with a relative molecular mass of 380000. Upon dissociation by sodium dodecyl sulphate, vitellin was shown to release five polypeptide subunits which ranged in relative molecular mass from 98000-16000. The purified vitellin was further characterized by amino acid analysis and its lipid and carbohydrate contents. The molecule contained about 5% carbohydrate and 16% lipid. Antiserum prepared against vitellin was shown to react with a component from the coelomic fluid of maturing females. Thus, it was suggested that in nereid annelids, considered phylogenetically and morphologically primitive, oocyte differentiation might depend upon the incorporation of a vitellogenin as in insects and many oviparous vertebrates.

Study of the conversion of GDP-mannose into GDP-fucose in Nereids: a biochemical marker of oocyte maturation.

Homogenates of Perinereis cultrifera oocytes were found to transform GDP-D-mannose into another sugar nucleotide. Ultraviolet absorption spectra, chromatographic behaviour, gas-liquid chromatography coupled to mass spectrometry analysis revealed that GDP-D-mannose had been converted into GDP-L-fucose. This conversion is a multi-step reaction as proved by the involvement of two intermediates identified as GDP-4-oxo-6-deoxy-D-mannose and GDP-4-oxo-6-deoxy-L-galactose, this latter being reduced by NADPH to give GDP-L-fucose. It is shown that the enzymatic activities responsible for the conversion of GDP-D-mannose into GDP-L-fucose is recovered only in oocytes and is not present in the other coelomic cells (i.e. coelomocytes). More interesting is the fact that maximum activity is recovered at a well defined stage of the hormone-controlled oogenesis. Thus, this enzymatic system appears as a biochemical marker of the oocyte maturation in P. cultrifera.