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Biomedical subjects

A Fournier

Publications and source records attributed to A Fournier.

At least 19 recordsLinked to original sources
PubMed2006

Pituitary adenylate cyclase-activating polypeptide directly modulates the activity of proopiomelanocortin neurons in the rat arcuate nucleus.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and the proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) both regulate multiple neuroendocrine functions and feeding behavior. Two subtypes of PACAP receptor mRNAs, pituitary adenylate cyclase-activating polypeptide-specific receptor (PAC1-R) and pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide mutual receptor (VPAC2-R), are actively expressed in the arcuate nucleus of the hypothalamus, where POMC cell bodies are located. This observation led us to investigate the possible regulatory action of PACAP on rat POMC neurons. Double-labeling in situ hybridization histochemistry revealed that approximately 50% of POMC-producing neurons express PAC1-R and/or VPAC2-R mRNAs. The proportion of POMC neurons that also contain PAC1-R mRNA was homogeneous along the rostro-caudal axis of the arcuate nucleus while POMC-positive cell bodies expressing the VPAC2-R subtype were more abundant in the rostral region. Incubation of mediobasal hypothalamic explants with PACAP (10(-7) M; 30 min) increased POMC mRNA expression, and this effect was blocked by PACAP6-38 (10(-6) M). In contrast, incubation with vasoactive intestinal polypeptide (10(-7) M) did not affect POMC mRNA level. Incubation of hypothalamic fragments with PACAP (10(-7) M) caused a significant increase in alpha-MSH content in the tissue and in the incubation medium. Altogether, the present results reveal that exogenous PACAP, acting probably through PAC1-R, regulates the activity of POMC neurons in the rat hypothalamus. These data suggest that the effects of PACAP on the gonadotropin-releasing hormone neuroendocrine axis and the regulation of feeding behavior may be mediated, at least in part, through modulation of POMC neurons.

Animals↗
PubMed2005

Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition.

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids - notably androgens and oestrogens - promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Delta4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids -the androgens as well as the oestrogens - elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23-2.33), androstenedione 1.94 (1.40-2.69), testosterone 1.85 (1.33-2.57) and free testosterone 2.50 (1.76-3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42-3.02), oestradiol 2.28 (1.61-3.23) and free oestradiol (odds ratios 2.13 (1.52-2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

Aged↗
PubMed2004

[Inaugural unilateral adrenal hematoma of an antiphospholipid syndrome].

INTRODUCTION: A primary antiphospholipid syndrome is a very rare cause of adrenal haemorrhage. OBSERVATION: A 51 year-old man presented with a unilateral adrenal haemorrhage, enhanced by the prescription of Synacthène during the 4 days that preceded. There was no adrenal deficiency but the immunological control revealed the presence of anti-phospholipid antibodies. After 2 years of follow-up, adrenal controls have not shown any underlying tumour or endocrine insufficiency. COMMENTS: Adrenal involvement is described in the anti-phospholipid syndrome and may present in the form of adrenal deficiency in the case of occasionally only microscopic bilateral haemorrhages. Furthermore, Synacthène is known to induce adrenal haemorrhages although this complication remains rare. Moreover, any unilateral adrenal haemorrhage requires subsequent follow-up for several months or even years in order to eliminate any underlying tumour and to control the absence of any adrenal deficiency if the involvement is bilateral.

Adrenal Gland Diseases↗
PubMed2004

[Muscular haematoma in Henoch-Schönlein purpura].

INTRODUCTION: Henoch-Schonlein purpura is one of the most frequent systemic vasculitis in children. In adults, muscle involvement is extremely rare and not very well characterized. We report a case of Henoch-Schonlein purpura with severe skin and renal involvement in witch multiple intramuscular haematoma leaded to severe anaemia. Histological examination confirms the muscle localization of the disease. EXEGESIS: A 68 years old man treated by oral anticoagulation for multiple venous thrombosis, was admitted with necrotic vasculitis of the skin, abdominal pain and segmental IgA glomerulopathy. The diagnosis of Henoch-Schonlein purpura was rapidly made and intensive steroid therapy started. After rapid improvement, a haemorrhagic shock due to voluminous intramuscular haematoma was diagnosed by MRI. Histological examination of the muscle, confirms the localization of the disease. CONCLUSION: Intramuscular haematomas are very uncommon in Henoch-Schonlein purpura. There are usually a consequence of muscular immune complex vasculitis. In our patient, high dose corticosteroid was not unable to control the disease.

Aged↗
PubMed2004

PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of I k in the anti-apoptotic action of PACAP.

Abstract Activation of potassium (K(+)) currents plays a critical role in the control of programmed cell death. Because pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to inhibit the apoptotic cascade in the cerebellar cortex during development, we have investigated the effect of PACAP on K(+) currents in cultured cerebellar granule cells using the patch-clamp technique in the whole-cell configuration. Two types of outward K(+) currents, a transient K(+) current (I(A)) and a delayed rectifier K(+) current (I(K)) were characterized using two different voltage protocols and specific inhibitors of K(+) channels. Application of PACAP induced a reversible reduction of the I(K) amplitude, but did not affect I(A), while the PACAP-related peptide vasoactive intestinal polypeptide had no effect on either types of K(+) currents. Repeated applications of PACAP induced gradual attenuation of the electrophysiological response. In the presence of guanosine 5'-[gammathio]triphosphate (GTPgammaS), PACAP provoked a marked and irreversible I(K) depression, whereas cell dialysis with guanosine 5'-[betathio]diphosphate GDPbetaS totally abolished the effect of PACAP. Pre-treatment of the cells with pertussis toxin did not modify the effect of PACAP on I(K). In contrast, cholera toxin suppressed the PACAP-induced inhibition of I(K). Exposure of granule cells to dibutyryl cyclic adenosine monophosphate (dbcAMP) mimicked the inhibitory effect of PACAP on I(K). Addition of the specific protein kinase A inhibitor H89 in the patch pipette solution prevented the reduction of I(K) induced by both PACAP and dbcAMP. PACAP provoked a sustained increase of the resting membrane potential in cerebellar granule cells cultured either in high or low KCl-containing medium, and this long-term depolarizing effect of PACAP was mimicked by the I(K) specific blocker tetraethylammonium chloride (TEA). In addition, pre-incubation of granule cells with TEA suppressed the effect of PACAP on resting membrane potential. TEA mimicked the neuroprotective effect of PACAP against ethanol-induced apoptotic cell death, and the increase of caspase-3 activity observed after exposure of granule cells to ethanol was also significantly inhibited by TEA. Taken together, the present results demonstrate that, in rat cerebellar granule cells, PACAP reduces the delayed outward rectifier K(+) current by activating a type 1 PACAP (PAC1) receptor coupled to the adenylyl cyclase/protein kinase A pathway through a cholera toxin-sensitive Gs protein. Our data also show that PACAP and TEA induce long-term depolarization of the resting membrane potential, promote cell survival and inhibit caspase-3 activity, suggesting that PACAP-evoked inhibition of I(K) contributes to the anti-apoptotic effect of the peptide on cerebellar granule cells.

4-Aminopyridine↗
PubMed2004

Endothelins as local activators of adrenocortical cells.

Besides the classical corticotropic hormones, ACTH and angiotensin II, various regulatory peptides produced by the adrenal gland are thought to participate in the control of corticosteroid secretion. Here, we review the evidence that endothelins (ETs) synthesized within the adrenal cortex may act as autocrine and/or paracrine factors to regulate adrenocortical cell activity. The expression of ETs has been detected in normal, hyperplastic and neoplastic adrenocortical cells. The occurrence of ET receptors has been described in the different zones of the cortex. ETs stimulate the secretion of both glucocorticoids and mineralocorticoids, and modulate the proliferation of adrenocortical cells. The effects of ETs on steroidogenic cells are mediated through the activation of various signaling mechanisms including stimulation of phospholipase C, phospholipase A2 and adenylyl cyclase activity, as well as calcium influx through plasma channels. These observations suggest that locally produced ETs may play an important role in the regulation of corticosteroid secretion and in the control of mitogenesis in normal and tumoral adrenocortical cells.

Adenylyl Cyclases↗
PubMed2003

Management of fetal tachyarrhythmia based on superior vena cava/aorta Doppler flow recordings.

OBJECTIVE: To evaluate a management protocol of fetal supraventricular tachycardia (SVT) based on prior identification of the underlying mechanism. DESIGN AND SETTING: Prospective study in a mother-child tertiary university centre. PATIENTS: During a consecutive 36 month period, 18 fetuses with sustained SVT underwent a superior vena cava/ascending aorta (SVC/AA) Doppler investigation in an attempt to determine the atrioventricular (AV) relation and to treat the arrhythmia according to a pre-established management protocol. MAIN OUTCOME MEASURE: Rate of conversion to sinus rhythm. RESULTS: Seven fetuses had short ventriculoatrial tachycardia, five of these with a 1:1 AV conduction suggesting re-entrant tachycardia. The first choice drug was digoxin and all were converted. One fetus had AV dissociation leading to the diagnosis of junctional ectopic tachycardia, which was resistant to digoxin and sotalol; amiodarone achieved postnatal conversion. One fetus had SVT and first or second AV block; the diagnosis was atrial ectopic tachycardia (AET), which responded to sotalol given as a drug of first choice. Seven fetuses had long ventriculoatrial tachycardia: one with sinus tachycardia (no treatment), one with permanent junctional reciprocating tachycardia (PJRT), and three with AET. The first choice drug was sotalol and all were converted. One AET was classified postnatally as PJRT. Six fetuses had intra-atrial re-entrant tachycardia: five with 2:1 AV conduction and one with variable block. The first choice drug was digoxin. Conversion was achieved in all but one, who died after birth from advanced cardiomyopathy. CONCLUSION: The electrophysiological mechanisms of fetal SVT can be clarified with SVC/AA Doppler. The proposed management protocol has so far yielded a good rate of conversion to sinus rhythm.

Anti-Arrhythmia Agents↗
PubMed2003

[Acute renal insufficiency secondary to interferon].

Alpha interferon is increasingly used in the treatment of malignancies and viral hepatitis. Renal involvement after its use consist in more cases on proteinuria. We report one case of acute renal failure without nephrotic syndrome but with tubulointerstitiel infiltration by mononuclear cells in 65 old man who had before interferon therapy 151 mumol/l of serum creatinine. Interferon was administrated for digestive carcinoid neoplasia and bone and liver metastasis. Outcome was improvement of renal function after withdrawn of interferon, dialysis and steroid treatment.

Acute Kidney Injury↗
PubMed2003

[Randomized trials in the prevention of recurrent calcium oxalate stones].

Kidney stone, with or without lumbar pain, is a major health care problem because of its prevalence and cost for both the patient and the society. Although, surgical procedures are well known, medical treatment and recurrences prophylaxis are uncodified. Fifteen stone recurrence prevention studies have been reviewed, evaluating dietary intake and drugs. The most important factor is a daily diuresis of at least 2 liters. Calcium intake shouldn't be restricted, whereas oxalate, sodium, and protein intakes have to be limited. Hyper and normocalciuretic kidney stone formers improve their outcome with thiazide or indapamide treatment. Hyperuricosuria justifies allopurinol. Potassium citrate (without sodium) may decrease recurrence risk, even in patients without hypocitraturia.

Calcium Oxalate↗
PubMed2002

PACAP protects cerebellar granule neurons against oxidative stress-induced apoptosis.

Oxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in neuronal cell death associated with neurodegenerative diseases and stroke. In the present study, we have investigated the potential neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on oxidative stress-induced apoptosis. Incubation of cerebellar granule cells with PACAP inhibited hydrogen peroxide-evoked cell death in a concentration-dependent manner. The effect of PACAP on granule cell survival was not mimicked by vasoactive intestinal polypeptide and was blocked by the antagonist PACAP6-38. The protective action of PACAP upon hydrogen peroxide-induced neuronal cell death was abolished by the MAP-kinase kinase (MEK) inhibitor U0126 and mimicked by the caspase-3 inhibitor Z-DEVD-FMK. PACAP markedly inhibited hydrogen peroxide-evoked caspase-3 activation and DNA fragmentation. Taken together, these data indicate that PACAP, acting through PACAP receptor type 1, exerts a potent protective effect against neuronal degeneration induced by hydrogen peroxide. The anti-apoptotic effect of PACAP is mediated through the MAP-kinase pathway and can be accounted for by inhibition of caspase-3 activation resulting from oxidative stress.

Animals↗
PubMed2002

[Chronic interstitial nephritis induced by 5-aminosalicylic acid: a new case report].

5-aminosalicylic acid (5-ASA) used for the treatment of inflammatory bowel disease is known to induce chronic interstitial nephritis (CIN). However, the frequency of occurrence and the spectrum of severity of 5-ASA-induced CIN are not known. In this paper, we report a new case of CIN induced by 5-ASA in a patient treated for about 7 years for a Crohn disease. After that 5-ASA was discontinued and prednisone therapy started, renal function improved partially. About 30 observations of CIN induced by the use of 5-ASA in patients treated for inflammatory bowel disease have already been published. None were published in patients treated for other diseases such as arthritis rheumatism. The review of the literature suggests that the prognosis is poor and correlates with the duration of treatment, the cumulative dose and the level of renal impairment at diagnostic. We believe that the control of the renal function in patients treated by 5-ASA must be regular and prolonged.

Adult↗
PubMed2001

Molecular characterization of human and bovine ceruloplasmin using MALDI-TOF mass spectrometry.

Using SDS-PAGE and MALDI-TOF mass spectrometry, we investigated the difference in the molecular structure between human and bovine ceruloplasmin. In both cases, we found that the protein is present in two majors forms of different molecular mass. The difference between human and bovine ceruloplasmin was more obvious when characterized by MALDI-TOF than with the SDS-PAGE analysis. Furthermore, we established that the N-glycoside content of both enzymes is dissimilar and that the N-glycosyl moieties are distributed in a distinctive fashion in two glycoproteins. Finally, it appeared that both proteins exhibited different cleavage patterns after treatment with trypsin. This study indicates that human and bovine ceruloplasmin differ not only in sugar composition but also in primary structure.

Amidohydrolases↗