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Biomedical subjects

M Perrin

Publications and source records attributed to M Perrin.

At least 91 records · Page 5Linked to original sources

[Significance of photoplethysmography in the diagnosis of deep venous insufficiency].

In chronic venous insufficiency, photoplethysmography, in addition to the clinical and Doppler examinations, offers important informations in the differential diagnosis between deep and superficial venous insufficiency. It is a simple, reproductible, non invasive test with data similar to venous pressure measurements. Photoplethysmography permits to set up quantitative criteria of venous insufficiency. It establishes the role of reflux in the dysfunction of the leg venous pump, and makes it possible to adjust for prescription of additional explorations, in particular popliteal or femoral dynamic phlebography. Furthermore, photoplethysmography offers a solid criterion to differentiate between various therapeutic surgeries: surgery of the superficial network, surgery of collateral veins, surgery to restore the deep venous network. Moreover, photoplethysmography is a useful tool to quantitatively appreciate the results of the venous insufficiency treatment. In conclusion, photoplethysmography appears as an additional examination necessary for functional exploration in chronic venous insufficiency. Its use in practical angiology is going to develop in view of its interesting results and its reasonable cost.

Chronic Disease↗

Gonadotropin releasing hormone antagonists: novel structures incorporating N omega-cyano modified guanidine moieties.

A series of GnRH antagonists with substitutions at positions 1, 2, 3, 5 and 6 that included the recently reported homoArg-N omega-cyano-N omega'-alkyl- or Lysine-N epsilon-5'-(3-amino-1H-1,2,4-triazole) [Lys(atz)] amino acid derivatives was synthesized, characterized and tested for antiovulatory and anaphylactoid activities and binding affinity. Overall, these analogs were found to be considerably more soluble at neutral pH than their homologs Nal-Glu or Antide. The decapeptides with these substitutions in positions 5 and/or 6 retained high in vivo potency while those with similar substitutions at positions 1, 2 and 3 were significantly less potent than Nal-Glu or Antide. Of the 16 new analogs reported here, Azaline (Ac-DNal1, DCpa2, DPal3, Lys5(atz),DLys6(atz), ILys8,DA1a10]-GnRH) showed the most promising physico-chemical and biological properties [Lys(atz) = N epsilon-5'-(3-amino-1H-1,2,4-triazole) lysine]. Azaline is readily soluble in dilute buffers at pH 7.0, completely inhibits ovulation at 2.0 to 3.0 micrograms per rat, is equipotent to GnRH in releasing histamine in the rat and has a weaker anaphylactoid response in the rat than other analogs such as Nal-Glu or even Antide.

Amino Acid Sequence↗

Novel gonadotropin-releasing hormone antagonists: peptides incorporating modified N omega-cyanoguanidino moieties.

In order to minimize the deleterious effects of histamine release resulting from the administration to rats and humans of some potent gonadotropin-releasing hormone (GnRH) antagonists, various arginine residues were replaced with the less basic N omega-cyano-N omega-alkyl- or -arylhomoarginine, -arginine, or -p-aminophenylalanine and N omega-triazolyllysine, -ornithine or -p-aminophenylalanine residues in active analogues. These novel analogues were synthesized on a solid-phase support via a two-step modification of the N omega-NH2 of lysine, ornithine, or p-aminophenylalanine residues in otherwise protected resin bound peptides. Most analogues were tested in the rat antiovulatory assay (AOA) and three in vitro assays; a pituitary cell culture assay, a binding assay to pituitary cell membranes, and a histamine release assay. Introduction of the cyanoguanidino and N omega-triazolyl moieties into GnRH analogues yielded several water-soluble antagonists which showed a desirable therapeutic ratio (low histamine release activity to high in vivo potency). Among them, "Azaline" (10, [Ac-DNal1,DCpa2,DPal3,Lys5(atz), DLys6(atz),ILys8,DAla10]GnRH), inhibited ovulation in the rat by 90% at 2 micrograms/rat with an ED50 in the in vitro histamine release assay comparable to that of GnRH itself.

Animals↗

[Epidemiologic aspects of viral hepatitis at a Parisian university hospital. Apropos of 130 cases].

One hundred and thirty adults with viral hepatitis were hospitalized in the Department of Hepatology-Gastroenterology at the Hospital Salpètrière between October 1984 and October 1986. Eighty had acute hepatitis and 50 suffered from chronic hepatitis. Among the former, 15 had hepatitis A, 40 had hepatitis B and/or delta and 25 had non A-non B hepatitis. The latter group was divided into 32 hepatitis B and/or delta and 18 non A-non B. The results of clinical, biological, serological and histological analyses were comparable to those reported in the literature for hepatitis A and B. Hepatitis non A-non B was more prevalent in males (72%). This predominance seems to be associated with the high number of heart transplant patients (12, 11 of them were men) in our study population. A liver biopsy was performed on 19 out of the 25 acute and on 32 of the chronic non A-non B hepatitis patients. Persistent chronic hepatitis was the most commonly found lesion. Transfusion was implicated in 53.8% of the patients, drug addiction in 18.6% of the cases and intramuscular injection or acupuncture in 5% of them. No risk factor was found in 23.2% of the patients. Seventy-two percent of the acute non A-non B hepatitis cases evolved towards a chronic form. We have attempted to find the factors involved in progression to chronicity. No correlation was found for age or the means of contamination. In contrast, immunodepression was significantly correlated. This study reflects the prevalence of non A-non B hepatitis infection post-transfusion in a hospitalized population including many transplant recipients.

Acute Disease↗

[Experimental reproduction and the course of contagious bovine pleuropneumonia in a group of cattle and goats: anatomoclinical aspects].

Five cows were inoculated with 3.10(9) CFU Mycoplasma mycoides subsp. mycoides. Five other cows and five goats were placed in close contact with inoculated cows. Clinical observations, serological survey and microbial excretion by culture for mycoplasma from tracheobronchial washes liquid were carried out during 4 months. Mycoplasmas excretion is detected before antibodies responses on all 10 infected cows. The cows never presented clinical respiratory signs and showed no or light lesions but one animal having typical lesions of acute form of contagious bovine pleuropneumonia. Goats do not seem to be susceptible and play no part in the spreading of the infection.

Animals↗

[Correlation of the excretion of mycoplasma and kinetics of antibodies detected by complement fixation, passive hemagglutination and rapid seroagglutination in Mycoplasma mycoides subsp. mycoides SC experimental infection in cattle].

During an experimental reproduction of CBPP, 5 inoculated cows and 5 contacts cows were bled twice a week and antibodies research was performed using complement fixation test (CFT), passive haemagglutination test (PHAT) and slide agglutination test (SAT). In the same period, trachobronchial washings were performed weekly to detect and to count Mycoplasma mycoides subsp. mycoides SC. For four months these tests were used to compare antibodies kinetics with kinetics of mycoplasmas excretion. With titer over 40 as threshold of positivity, PHAT detects antibodies earlier than CFT and SAT at the beginning of infection, but fails to detect chronic carriers. In contacts cows no failure has been observed with CFT and SAT except during prodromic phase of infection. These results are valid for natural infections. However, for inoculated animals, most serious failures to detect infected cows occur.

Animals↗

[Studies of the origin of false positive reactions in the serodiagnosis of contagious bovine pleuropneumonia].

Four groups of cattle were experimentally immunised by four mycoplasma species of "mycoides-like" group, Mycoplasma (M) capricolum, M. mycoides subsp. mycoides (LC), M. mycoides subsp. capri and M. species group 7 of LEACH (PG50). They were then bled weekly during 2 months to establish antibodies kinetics against homologous and heterologous antigens. The standard method of complement fixation test (CFT) used in Europe and a new ELISA test for diagnosis of contagious bovine pleuropneumonia were performed in comparison with passive haemagglutination test (PHA) against antigens used for experimental immunisation. Cross reactions obtained are rather equal to the degree of similitude between these mycoplasma species. With CFT-cross reactions are transitory and occur only while homologous titers are very high, particularly with "PG50" and the two caprine mycoides strains. ELISA results using a threshold of positivity of optical density of 0.20, were similar to that obtained with CFT except ELISA specificity is not so different from CFT one. This experimental model could explain some natural situations.

Animals↗

[Does Q fever hepatitis mimic acute alcoholic hepatitis?].

The authors report the case of a chronic alcoholic woman, hospitalized for chest pain accompanied with fever. The laboratory test mimic an acute alcoholic hepatitis; the presence of a clinical and radiological pulmonary affection led to the discovery of Q fever, the diagnosis of which was confirmed by serology and the discovery of a granuloma on histological examination of the liver.

Acute Disease↗

Design of potent cyclic gonadotropin releasing hormone antagonists.

In order to improve the biological potency of cyclic gonadotropin releasing hormone (GnRH) antagonists, we have synthesized analogues, the conformations of which were restrained through internal side chain/side chain amide bridges linking aspartic acid or glutamic acid and L-2,3-diaminopropionic acid or L-ornithine. A disulfide bridge linking L-cysteine residues was also introduced. Residues belonging to the bridge spanned from position 4 to positions 9 or 10. Two series of analogues were synthesized and are characterized by residues at positions 1 [Ac-D-3-(2'-naphthyl)alanine], 2 [D-(4-chlorophenyl)alanine or D-(4-fluorophenyl)alanine], 3 [D-3-(3'-pyridyl)alanine or D-tryptophan], 5 (arginine or tyrosine), and 6 [D-3-(3'-pyridyl)alanine or D-arginine], respectively. These substitutions were selected in an effort to optimize high biopotency for inhibition of luteinizing hormone secretion, minimization of histamine release activity, and high (relative) hydrophilicity. The most potent analogues in the antiovulatory assay were cyclo(4-10) [Ac-DNal1,DCpa2,DPal3,(Asp4 or Glu4),Arg5,DPal]6,Dpr10]GnRH (compounds 5 and 7), which were fully active at ca. 12.5 micrograms/rat in the first series, and cyclo(4-10)[Ac-DNal1,DFpa2,DTrp3,Asp4,DArg6++ +,Dpr10]GnRH (compound 12), which was fully active at 2.5 micrograms/rat in the second.

Amino Acid Sequence↗

Identification and characterization of a pituitary corticotropin-releasing factor binding protein by chemical cross-linking.

A corticotropin-releasing factor (CRF) binding protein has been identified based on the chemical cross-linking of ovine [Nle21,m-125I-Tyr32]CRF (125I-oCRF) to bovine anterior pituitary membranes using disuccinimidyl suberate (DSS). The apparent molecular weight of the cross-linked complex determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography was approximately 75,000 and was slightly decreased in its nonreduced state, suggesting the presence of intramolecular disulfide bonds. Subtracting the molecular weight of 125I-oCRF, the binding protein appeared to have a molecular weight of approximately 70,000. The cross-linking was specific since an excess (1 microM) of an unrelated peptide (insulin) did not affect the appearance of the Mr 75,000 band. The concentration of CRF required to inhibit cross-linking by 50% was found to be similar to that determined for bovine pituitary CRF receptors by radioreceptor assay. The nonhydrolyzable GTP analogue 5'-guanylylimidodiphosphate dose dependently inhibited the cross-linking of 125I-oCRF to the Mr 70,000 protein. 50 nM of the inactive CRF analogue, [Ala14]oCRF, had no effect on the cross-linking, an observation which is consistent with this compound's low potencies in bioassays and radioreceptor assays. These results strongly suggest that this Mr 70,000 protein is the biological bovine anterior pituitary CRF receptor.

Adrenocorticotropic Hormone↗

New effective gonadotropin releasing hormone antagonists with minimal potency for histamine release in vitro.

In order to minimize the adverse effect of histamine release in the rat of some gonadotropin releasing hormone (GnRH) antagonists, such as [Ac-D2Nal1,D4FPhe2,DTrp3,DArg6]-GnRH, new structures with modifications at positions 1, 2, 3, 5, 6, 7, and 10 were synthesized and tested in several biological systems. In vitro: the affinity for the pituitary GnRH receptor was measured as was the ability of the analogues to inhibit GnRH-stimulated release of luteinizing hormone (LH) by dispersed anterior pituitary cells in culture and to release histamine from rat mast cells. In vivo: inhibition of ovulation in the cycling rat was determined after subcutaneous (sc) injection of the peptides at noon on the day of proestrus; the duration of action of the peptides was evaluated by measuring LH levels in the castrated male rat after sc injection of some selected analogues. [Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,D-4-p-methoxy benzoyl-2-aminobutyric acid6,DAla10]-GnRH was found to be one of the most potent analogues of this series, causing a 100% inhibition of ovulation at 5 micrograms/kg or less. Release of histamine was observed at doses 10-25 times that required for [Ac-D2Nal1,D4FPhe2,DTrp3,DArg6]-GnRH. Thus, introduction of arginine in position 5 with a hydrophobic amino acid in position 6 is compatible with high potency in several biological systems and results in compounds with lowered potency to release histamine compared to homologous peptides with tyrosine in position 5 and D-arginine in position 6.

Animals↗

Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus.

The neonatal rat shows a period of decreased responsiveness to noxious stimuli during the first 3 weeks of life, but the nature of this impairment is still controversial. To test the functionality of the hypothalamus-pituitary-adrenal axis during this period, we studied pituitary and adrenal responsiveness to exogenous ovine CRF and the ability of various stressors (ether vapors, electroshocks, and hypoxia) to elicit ACTH and corticosterone secretion. We also measured hypothalamic CRF content and pituitary ACTH content as well as CRF-binding sites in the anterior pituitary. From days 3-10, small elevations in plasma ACTH and corticosterone levels were observed after a 3-min exposure to ether vapors or electroshocks. In contrast, during this period, a 20-min exposure to hypoxia (5% O2 in N2) was unable to trigger measurable ACTH secretion, while corticosterone was significantly elevated. From days 14-21, plasma ACTH and corticosterone levels increased significantly after exposure to ether stress, hypoxia, and, to a lesser extent, electroshocks. By contrast, administration of urethane (1.2 g/kg BW) caused a significant increase in ACTH secretion on days 3, 5, and 10, an effect that was partially suppressed by pretreatment with an anti-CRF serum. This suggests that endogenous CRF can be released by at least some stimuli as early as day 3. Direct stimulation of the pituitary with synthetic oCRF (10 micrograms/kg BW) caused significant elevations in plasma ACTH levels at all ages tested (days 3 through 21), though these increases were significantly (P less than or equal to 0.01) smaller on day 3 (2.7-fold) than on day 21 (4.3-fold). Hypothalamic CRF content as well as ACTH content increased gradually with age, but the values reached by the third week of life were still low compared to the values on day 45. Finally, anterior pituitary CRF-binding sites averaged 317 +/- 48 fmol/mg protein on day 5 and 158 +/- 22 fmol/mg protein on day 17. The affinity (Kd) of the receptor for CRF was not significantly different on day 5, 17, or 45. These results show that although pituitary corticotrophs appear to be functional at birth, exposure to stress does not elicit marked increases in plasma ACTH until day 14 of age.

Adrenal Glands↗

Identification of corticotropin-releasing factor (CRF) target cells and effects of dexamethasone on binding in anterior pituitary using a fluorescent analog of CRF.

A fluorescein-conjugated bioactive analog of corticotropin-releasing factor (CRF) was synthesized and used to label cells that have high affinity CRF-binding sites. Of cultured bovine anterior pituitary cells, 6.1 +/- 0.6% were visible by fluorescence microscopy after incubation with the analog. Fluorescence was eliminated by coincubation with a 200-fold excess of unlabeled CRF. Treatment with dexamethasone (10(-9)-10(-7) M) decreased visible fluorescence in a dose-dependent manner. These results demonstrate the utility of a fluorescent CRF analog for identification of cells with specific CRF-binding sites and suggest that binding of CRF to anterior pituitary cells is altered by glucocorticoids.

Adrenocorticotropic Hormone↗