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Biomedical subjects

A Fournier

Publications and source records attributed to A Fournier.

At least 379 records · Page 21Linked to original sources
PubMed1991

Contribution of hGH20K variant to blood hGH response in sauna and exercise.

Exercise-induced increases in blood somatotropin (hGH) have always been considered in terms of quantity of the circulating molecules. Knowing that the hypophysis can release several GH species, we investigated the differential release in blood of total hGH (hGHT) and the main hGH variant (hGH20K) molecules in six trained male swimmers exposed to three different conditions known to favor GH release in blood: 45 min--70% maximum oxygen uptake (VO2max) bicycling and swimming, and 20 min of sauna bathing. Based on the binding specificity of hGH antibodies, hGH20K was isolated then assayed using the Nichols immunoradiometric assay system. All three experimental conditions produced significant (P less than 0.001) elevations in blood hGHT and hGH20K. In all three cases, mean blood hGH20K contribution to blood hGHT was relatively constant (11.9, SE 0.7%). Rises in rectal temperature were not statistically related to the changes in blood hGHT. This demonstration of a relatively constant elevation in hGH20K during bicycling, swimming, and sauna bathing can hardly explain the large differences in blood hGHT responses reported in literature under similar conditions.

Adult↗
PubMed1991

Myxoedema coma: response of thyroid hormones with oral and intravenous high-dose L-thyroxine treatment.

Myxoedema coma is a medical emergency with high mortality. In this study, clinical response and plasma variations of thyroid hormones were analysed in 7 patients, 6 presenting with myxoedema coma and one with myxoedema ileus. These patients were treated with intravenous or oral l-thyroxine (l-T4). 1000 mu l-T4 iv were administered in two patients. Within 3 h, plasma T4 and triiodothyronine (T3) reached a peak upper normal range, then diminished slowly during 5-9 days. The 5 remaining patients were treated with 500 micrograms l-T4 po on the first day, then 100 micrograms l-T4 daily by mouth. Plasma T4 and T3 increased slowly, remaining in hypothyroid range but clinical response (assessed on mental status, pulse rate and body temperature) occurred within 24-72 h. Cortisone therapy was used in 3 patients. Two patients died of myocardial infarction, or septicemia, one while receiving cortisone therapy and i.v. l-T4, another one treated only by oral l-T4. This study suggests: 1) oral absorption of l-T4 is variable, but clinical response occurs quickly even in myxoedema ileus; 2) the intravenous route involves high peaks of plasma T4 and T3; 3) peripheral conversion of T4 to T3 allows gradually T3 delivery to organ systems, even if only l-T4 is used and 4) initial and daily dosage determinations need further studies.

Administration, Oral↗
PubMed1991

Pancreatitis related to severe acute hypertriglyceridemia during pregnancy: treatment with lipoprotein apheresis.

We report a clinical observation of acute pancreatitis due to severe hypertriglyceridemia in a pregnant woman. In order to decrease the serum triglyceride level rapidly, two lipaphereses were undertaken using the double-filtration technique. This lipoprotein apheresis technique is briefly described and the efficacy in reducing rapidly hypertriglyceridemia is outlined. Like in 3 previously published reports, the patient had a rapid recovery, confirming that lipoprotein apheresis should be an adequate and a well-tolerated treatment in such a condition.

Adult↗
PubMed1991

Structure-function analysis of stimulation of food intake by neuropeptide Y: effects of receptor agonists.

Neuropeptide Y (NPY) is a potent natural orexigenic signal in the rat. In this study, we have compared the effects of several COOH-terminal fragments of NPY and NPY receptor agonists on cumulative food intake in male rats. Rats were implanted with permanent cannulae either into the third cerebroventricle or paraventricular nucleus (PVN). NPY1-36 and various COOH-terminal fragments of NPY, two agonist analogues [Leu31, Pro34]NPY and NPY 1-4-Aca (epsilon-amino-caproic acid)-25-36, were administered intracerebroventricularly (ICV) or directly into the PVN, and the cumulative 2-h food intake response was compared. We observed that peptides that were effective by ICV were also effective when administered into the PVN, but smaller amounts of the peptides were required after PVN injection to evoke an equivalent food intake response. Injection of NPY1-36 induced a dose-dependent increment in food intake. Surprisingly, deletion of NH2-terminal tyrosine residue did not adversely affect feeding behavior. In fact, NPY2-36 was consistently more effective than NPY1-36; the enhancement in feeding by NPY2-36 was dose-related and was higher than evoked by NPY1-36 at each dose tested. Further serial deletion of aminoacids at NH2-terminal resulted in complete loss of activity. In addition, NPY agonist analogue, NPY 1-4-Aca-25-36, failed to stimulate feeding. However, NPY Y1 receptor agonist, [Leu31, Pro34]NPY, but not Y2 receptor agonist, NPY13-36, stimulated feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neurobehavioral profile of neuropeptide Y.

In order to better delineate the profile of central actions of neuropeptide Y (NPY), the effects of intracerebroventricular administration of several doses (2.5-20 micrograms) of the peptide on spontaneous activity, muscular tone, body temperature, food intake, nociception and cataleptic manifestations were examined in rats. Results indicate that, starting at 5 micrograms. NPY significantly decreased motor activity of animals in a dose-related fashion. NPY also significantly lowered body temperature of animals. The hypothermic effect was obtained following injections of 10.0 and 20.0 micrograms of the peptide. Administration of the same two doses of NPY resulted in significant increases in food intake, muscular tone and induced a significant catalepsy in animals. On the other hand, nociceptive response times of animals in the hot plate test were not affected by any of the NPY doses tested. Together, these results indicate that the profile of NPY's neurobehavioral actions is more complex than previously reported and suggest that the peptide might be implicated functionally in a variety of neurophysiological processes.

Animals↗
PubMed1991

In vivo structure activity study supports the existence of heterogeneous neuropeptide Y receptors.

The purpose of the present study was to examine relationships between structure and activity of the peptide for stimulating food intake and decreasing body temperature in rats. Various NPY fragments and structural analogs were administered intracerebroventricularly in several doses (2.5-160 micrograms) and their effects on feeding and body temperature evaluated and compared. Globally, results indicate that the C-terminal portion of the peptide is responsible for both central effects of NPY. However, the distributions of potencies of the various fragments and analogs for increasing food intake and decreasing body temperature were clearly different. The most salient difference was that deletion of the N-terminal residue Tyr1 of NPY resulted in a five-fold loss in the potency for decreasing rectal temperature, whereas NPY2-36 was relatively more potent than the native peptide to increase food intake in animals. These results suggest that the purported receptors mediating the effect of NPY on food intake are different than those responsible for the influence of the peptide on body temperature. The results of the present in vivo work are discussed in relation to those obtained in previous in vitro studies.

Animals↗
PubMed1991

Diet, vitamin D and vertebral mineral density in hypercalciuric calcium stone formers.

To elucidate the pathophysiology of dietary calcium independent hypercalciuria, 42 calcium stone formers (Ca SF) were selected because they had on free diet a calciuria greater than 0.1 mmol/kg/day. For four days they were put on a diet restricted in calcium (Ca RD) by exclusion of the dairy products. They collected 24 hour urines on free diet and on day 4 of Ca RD as well as the two-hour fasting urines on the morning of the day 5 and the four-hour urines passed after an oral calcium load of 1 g, for measurement of creatinine, Ca, PO4, urea and total hydroxyprolinuria (THP). On day 5 fasting plasma concentrations of Ca, PO4, intact PTH, Gla protein, calcidiol and calcitriol were measured. The patients were firstly classified into dietary hypercalciuria (DH, 18 patients) and dietary calcium-independent hypercalciuria (IH, 24 patients) on the basis of the disappearance or not of hypercalciuria on Ca RD. Then the patients with IH were subclassified into absorptive hypercalciuria (AH) because of normal fasting calciuria (8 patients) and into fasting hypercalciuria (16 patients). Fasting hypercalciuric patients were subsequently divided according to the PTH levels into renal hypercalciuria (RH, 1 patient) with elevated fasting PTH becoming normal after the Ca load and undetermined hypercalciuria (UH, 15 patients) with normal PTH levels. Furthermore, their vertebral mineral density (VMD) was measured by quantitative computerized tomography which was normal in DH (91 +/- 6% of the normal mean for age and sex) but was decreased in IH to 69 +/- 4%. No difference in VMD was observed between AH and UH. Urinary excretions of urea, phosphate and THP was higher in IH than in DH and comparable in AH and UH. Sodium excretion Ca RD was the same in all groups and subgroups as well as the plasma parameters. Plasma calcitriol was increased in IH and DH comparatively to normal in spite of normal plasma calcidiol. Calciuria increase after oral calcium load, an index of Ca absorption, was higher in IH than in controls and comparable in IH and DH as well as in the three subgroups of IH. From these data and correlation studies in IH it is concluded: (1.) VMD is decreased in Ca stone formers with IH but not in those with DH, making the distinction of these two groups of hypercalciuria patients clinically relevant.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Stable multicopy vectors for high-level secretion of recombinant human serum albumin by Kluyveromyces yeasts.

We have designed stable pKD1 derivatives for efficient secretion of recombinant human serum albumin (rHSA) by industrial strains of Kluyveromyces yeasts. A comparison of this multi-copy expression system with isogenic cassettes integrated at chromosomal loci demonstrated that high level secretion of rHSA is a function of gene dosage in K. lactis. Various signal sequences could be used, and the secretion levels were independent of the presence of the native pro peptide. The mitotic stability of the pKD1-based expression vectors was found to be species and strain dependent and was influenced by promoter strength and culture conditions. Vector stability was drastically enhanced when the HSA gene was expressed from an inducible promoter: 90% of the transformed cells still harbored the vector after 100 generations of non-selective growth in uninduced culture conditions. Secretion levels in the range of several grams per liter of correctly folded and processed rHSA were obtained at the pilot scale, thus making the industrial production of pharmaceutical-grade, Kluyveromyces-derived rHSA economically feasible.

Base Sequence↗
PubMed1991

HGH20k species and variability of GH responses to long-duration exercise in male cyclists fed different food supplements.

Exercise studies dealing with hGH have always considered this hormone as a unique molecular entity. We postulated that the well-known variability in blood total hGH response could possibly be explained, at least in part, by concomitant changes in blood hGH20k levels, variant form possibly expressing some of the hGH anti-insulinic properties. Six male trained cyclists were imposed a 2-hr long ergocycle exercise. Food supplements were given prior to and/or during exertion to exacerbate a possible contribution from hGH20k to total hGH variability by modification of substrate availability. Both blood total hGH and hGH20k levels increased with exercise, the largest increases being observed in absence of supplementation. Large variability of responses were observed in both blood total hGH and hGH20k levels, the latter variant contributing minimally to total blood hGH response (4.3 +/- 0.8%), and being closely associated with the main species (r = 0.90; p less than 0.001). It was concluded that variations associated with hGH20k increases observed in response to prolonged exercise cannot explain the large intra-and inter-individual variability measured in blood total hGH response.

Adult↗
PubMed1991

Neuropeptide Y inhibits Ca2+ influx into cultured dorsal root ganglion neurones of the rat via a Y2 receptor.

1. The identity of the neuropeptide Y (NPY) receptor associated with the observed inhibition of neuronal Ca2+ currents (ICa) in rat dorsal root ganglion (DRG) cells has been established on the basis of agonist responses to analogues and carboxy terminal (C-terminal) fragments of the NPY molecule. 2. Whole cell barium currents (IBa) in DRG cells were reversibly inhibited by 100 nM NPY, 100 nM PYY and C-terminal fragments of NPY in a manner that correlated with the length of the NPY fragments (for inhibition of the IBa NPY = PYY greater than NPY2-36 greater than NPY13-36 greater than NPY16-36 greater than NPY18-36 much greater than NPY25-36). 3. C-terminal fragments of NPY were also effective in reversibly reducing the ICa, the associated increase in the intracellular Ca2+ concentration [( Ca2+]i) and the increased [Ca2+]i produced by evoked action potentials in the DRG cells. In addition, a Ca(2+)-activated Cl- conductance was also reversibly reduced by NPY fragments only when accompanied by a reduction in Ca2+ entry. 4. We conclude that the Y2 receptor for neuropeptide Y is coupled to inhibition of Ca2+ influx via voltage-sensitive calcium channels in DRG cells.

Action Potentials↗
PubMed1991

Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor.

1. The action of analogues and C-terminal fragments of neuropeptide Y (NPY) was examined on excitatory synaptic transmission in area CA1 of the rat hippocampal slice in vitro, by use of intracellular and extracellular recordings, to determine by agonist profile the NPY receptor subtype mediating presynaptic inhibition. 2. Neither NPY, analogues nor fragments of NPY affected the passive or active properties of the post-synaptic CA1 pyramidal neurones, indicating their action is at a presynaptic site. 3. The full-sequence analogues, peptide YY (PYY) and human NPY (hNPY), were equipotent with NPY at the presynaptic receptor, while desamido hNPY was without activity. 4. NPY2-36 was equipotent with NPY. Fragments as short as NPY 13-36 were active, but gradually lost activity with decreasing length. NPY 16-36 had no effect on extracellular field potentials, but still significantly inhibited excitatory postsynaptic potential amplitudes. Fragments shorter than NPY 16-36 had no measurable effect on synaptic transmission. 5. The presynaptic NPY receptor in hippocampal CA1 therefore shares an identical agonist profile with the presynaptic Y2 receptor at the peripheral sympathetic neuroeffector junction.

Action Potentials↗
PubMed1991

Effects of endothelin-1 on vascular permeability in the conscious rat: interactions with platelet-activating factor.

1. The objectives of the present experiments were to assess the effects of endothelin-1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet-activating factor (PAF) in vascular responses to endothelin-1 and to examine the vascular effects of combined administration of endothelin-1 and PAF in conscious rats. 2. Intravenous bolus injection of endothelin-1 (0.1-2 nmol kg-1) resulted in a dose-dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose-dependent increase in haematocrit values. 3. Endothelin-1 (0.1 and 1 nmol kg-1) increased dose-dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin-1 treatment. 4. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1, i.v.) or BN 52021 (10 mg kg-1, i.v.) reduced the endothelin-1 (1 nmol kg-1)-induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin-1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin-1.5. When low doses of endothelin-1 (0.1 nmolkg-')and PAF (0.19nmolkg-')were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin-1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP.6. Combined administration of higher doses of endothelin-1 (1nmolkg-') and PAF (1.9nmolkg-') resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin-1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin-1 and PAF resulted in a slight, but significant increase in MABP.7. The present findings show that endothelin-1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin-1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.

Animals↗
PubMed1991

Pharmacokinetics of single-dose intravenous, oral, and intraperitoneal pefloxacin in patients on chronic ambulatory peritoneal dialysis.

Comparison of plasma and dialysate concentrations of pefloxacin after intravenous, oral, or intraperitoneal administration shows excellent bidirectional diffusion of the quinolone through the peritoneal membrane, demonstrating that therapeutical concentrations can be achieved in the dialysate after intravenous or oral administration. In this study, the half-life of the drug was 18.8 +/- 1.4 h, i.e., apparently longer than that reported for normal controls or uremic patients on hemodialysis.

Administration, Oral↗
PubMed1991

Atrial natriuretic factor in pregnancy and pregnancy-induced hypertension.

In normal pregnancy, cross-sectional clinical data do not consistently show plasma ANF concentration differences between early pregnancy and the nonpregnant state. Sequential data in the baboon (but not in rat) show a significant decrease in plasma ANF concentration and in cardiac filling pressures in early pregnancy. The latter data support the view that pregnancy is an underfill state secondary to a primary vasodilatation. Cross-sectional and longitudinal studies in normal pregnancy in humans show that plasma ANF levels tend rise to values that are, in the third trimester, higher than in the nonpregnant state. However, late postpartum sequential data (1.5-3 months) in humans do now show a significant drop in plasma ANF concentrations, suggesting that plasma ANF is not actually increased in normal pregnancy. In the baboon (but not in the rat) there is a steady rise in plasma ANF levels to values that are significantly higher in third trimester than before pregnancy. These data suggest that in human pregnancy, in contrast with the baboon, the plasma volume expansion induced by normal pregnancy is not sensed as such by the atria probably because of an isopressive adaptation of plasma volume to an enlarged vascular bed. However, acute decrease or increase of venous return induced by low sodium diet, changing position or infusion of isotonic saline are sensed as such by the atria in normal pregnancy as in the nonpregnant state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Destructive spondyloarthropathy with beta 2-microglobulin amyloid deposits in a uremic patient before chronic hemodialysis.

We report a case of erosive arthropathies discovered radiologically before dialysis in a uremic patient with Alport syndrome. This patient had no hereditary amyloidosis or causes of acquired generalized amyloidosis (no chronic infections or inflammatory disease, neoplasia, lymphoma or monoclonal gammapathy). Erosive spondyloarthropathies of the cervical spine at the C5-C6 and C6-C7 levels, erosive arthropathy of the right acromioclavicular joint, metacarpal lacuna of the right hand, and lacuna of the left femoral neck were discovered 24 months before starting dialysis in this patient with chronic renal insufficiency of 17 years duration. Puncture of the vertebral disc before starting dialysis took a fragment showing amyloid deposits with permanganate-sensitive Congo red staining and positive staining with anti-beta 2-microglobulin antibodies. This observation suggests that beta 2-microglobulin amyloidosis in uremia may not be exclusively related to chronic kidney replacement therapy, but to uremia per se, especially when the latter is of long duration.

Amyloid↗
PubMed1991

Neuropeptide-Y in the trout brain and pituitary: localization, characterization, and action on gonadotropin release.

Using a specific antiserum raised against synthetic neuropeptide-Y (NPY), the distribution of NPY-like immunoreactivity in the brain and pituitary of the trout Oncorhynchus mykiss has been examined with the indirect immunofluorescence and peroxidase-antiperoxidase methods. The highest density of NPY-immunoreactive elements was found in the basal telencephalon and hypothalamus. In particular, NPY-immunoreactive neurons were located in the nucleus entopeduncularis and the preoptic nucleus. NPY-immunoreactive fibers were observed throughout the trout brain. The preoptic nucleus, the suprachiasmatic nucleus, and the nucleus entopeduncularis were densely innervated. In addition, NPY-positive fibers were detected in the nucleus lateralis tuberis and in the distal and intermediate lobes of the pituitary. The NPY-like peptide of the trout brain was characterized by combining HPLC analysis and radioimmunological detection. Serial dilutions of trout hypothalamus and pituitary extracts produced displacement curves that were parallel to the standard curve. HPLC analysis resolved a major peak which was slightly less hydrophobic than porcine NPY. The possible effect of NPY, either alone or in combination with a GnRH antagonist, on gonadotropin (GtH) release from trout pituitaries was investigated using a perifusion system technique. Graded concentrations of synthetic NPY induced a dose-dependent stimulation of GtH release. The stimulatory activities of NPY and various short chain analogs on GtH release were compared: the order of potency was NPY greater than NPY-(2-36) greater than NPY-(16-36) greater than NPY-(25-36). This result suggests that the biological determinant of NPY is located in the C-terminal part of the molecule. Administration of a short pulse of NPY or GnRH (10(-7) M each) induced a marked stimulation of GtH release. Prolonged infusion of the GnRH antagonist D-Phe2-6,Pro3-GnRH induced a significant reduction of GnRH-evoked GtH secretion. In addition, the GnRH antagonist blocked NPY-induced GtH release. The widespread distribution of NPY in the trout brain suggests the involvement of this neuropeptide in a variety of physiological functions. The present data support the view that NPY, released by nerve terminals in the distal lobe of the pituitary, may act presynaptically on GnRH fibers to modulate GtH release.

Animals↗