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Biomedical subjects

A Simon

Publications and source records attributed to A Simon.

At least 271 records · Page 15Linked to original sources
PubMed1994

Continuing development of acid pump inhibitors: site of action of pantoprazole.

Both receptor antagonists and acid pump inhibitors are clinically useful suppressants of acid secretion. The latter class of drugs, the substituted benzimidazoles, inhibit acid secretion more effectively and, therefore, provide superior symptom relief and healing in all acid-related diseases. The H2-receptor antagonists competitively block the action of histamine on the H2-receptors of parietal cells. This histamine is released from enterochromaffin-like cells (ECL cells) due to gastrin, acetylcholine or epinephrine stimulation. In addition, parietal cells have M3-receptors which can function independently of H2-receptors. Hence, there is no single common pathway for parietal cell stimulation. Stimulation of acid secretion by parietal cells requires activation of the acid pump, the gastric H+,K(+)-ATPase. The target site for the benzimidazoles is the activated gastric H+,K(+)-ATPase, and, in particular, the cysteines of the pump that are exposed to the acid space of the secretory canaliculus of the parietal cells. Pantoprazole in its protonated form selectively reacts with cysteines present in both the fifth and sixth membrane segments of the ATPase, explaining its mechanism of inhibiting proton transport by this enzyme.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

A relationship between aortic stiffness and serum HDL3 cholesterol concentrations in hypercholesterolaemic, symptom-free men. The PCVMETRA Group (Groupe de Prévention Cardiovasculaire en Médecine du Travail).

OBJECTIVE: We set out to evaluate the relationship between aortic stiffness and serum lipids and lipoprotein fractions, including high-density-lipoprotein (HDL) cholesterol subfractions. METHODS: One hundred and five asymptomatic, normotensive, untreated, hypercholesterolaemic men underwent measurement of aortic pulse-wave velocity (PWV) by mecanography and assay of total cholesterol, triglycerides, HDL cholesterol and its subfractions (HDL2 cholesterol and HDL3 cholesterol), determined by electrophoresis. RESULTS: PWV was related to HDL cholesterol (r = 0.21, p = 0.05) and more specifically to HDL3 cholesterol subfraction (r = 0.29, p < 0.01). The latter association remained significant after adjustment for systolic blood pressure and age. Multivariate analysis demonstrated an independent association of PWV (r2 = 0.27, P < 0.001) with age, systolic blood pressure and HDL3 cholesterol. CONCLUSION: Although hypercholesterolaemia was not accompanied by increased aortic rigidity, there was a positive relationship between PWV and HDL cholesterol and between PWV and HDL3 cholesterol independently of the influence of age and systolic blood pressure on PWV. These results suggest that, in hypercholesterolaemic men, HDL3 could, in addition to its anti-atherogenic property, have a prosclerotic stiffening effect. This duality could explain why, in clinical studies, although the level of the HDL2 subfraction is frequently associated with a lower incidence of coronary artery disease, results for the HDL3 subfraction are less convincing and remain equivocal.

Adult↗
PubMed1994

[Detection and significance of coronary calcinosis].

Coronary calcifications (CC) are the witness of atheromatous disease because they lies in intima. This is a best stamp of coronary atheromatosis than all the well know risk factors. CC scores is perfectly estimated by EBT. The reproductibility expressed in logarithm data is 7.2% in inter-examination, 1.3% in inter-observers, 2% in intra-observers [4]. CC detection is more specific in young population than in old population because CC appear and increase with age in asymptomatic patients [12]. But the score curve raised higher in symptomatic than in asymptomatic subjects. A patient with an abnormal score for his age will have 5 to 10% of ischemic cardiac disease during the following 6 months [11].

Adult↗
PubMed1994

Platelet aggregation and in vivo shear forces.

Haemodynamic shear forces have been reported to exert direct and indirect effects on platelet reactivity. In vitro, they activate platelets leading to spontaneous or facilitated aggregation. In vivo, they stimulate the production of endothelium-derived anti-aggregatory agents. This study was designed to evaluate in hypertensive patients, before and after antihypertensive treatment, the possible role of these haemodynamic forces, determined at the brachial artery level on the ex vivo platelet aggregatory response to ADP and collagen. Platelet reactivity, evaluated by EC50 for ADP and collagen, was found to be related to blood velocity, shear rate and shear stress (p < 0.01 for each). These inverse correlations of platelet aggregation with stress levels did not depend on age, body mass index, mean blood pressure, serum cholesterol and triglycerides or haematocrit. They were also independent of platelet cytosolic Ca2+ and cyclic AMP. The changes in shear forces and in aggregatory responses to ADP and collagen induced by nitrendipine treatment for 6 months remained negatively correlated, confirming the relationships existing between haemodynamic shear forces and platelet reactivity. These results indicate that the shear antiaggregant effects, likely mediated by flow-dependent endothelium-derived factors, prevail over its direct platelet aggregating effects.

Adenosine Diphosphate↗
PubMed1994

[Vasoselective, substance-specific actions of isradipine on the great arteries of hypertensives in comparison to metoprolol].

The effects of isradipine (Lomir, CAS 75695-93-1) and metoprolol (CAS 37350-58-6) on geometry and arterial compliance of the arteria brachialis of 14 patients each with essential hypertension were compared acutely and after three months of therapy by means of pulsed Doppler sonography and the determination of pulse wave velocity. A calculation model was used that allowed to determine the drug-specific effects on arterial diameter and compliance under isobaric conditions. Isradipine increased measured and isobaric diameter during short-term (p < 0.05) and long-term administration (p < 0.05) whereas metoprolol did not change it. Isradipine increased measured and isobaric compliance during short-term (p < 0.05) and long-term administration (p < 0.05). Metoprolol reduced measured compliance acutely (p < 0.01) and isobaric compliance acutely (p < 0.05) and long-term (p < 0.05). Drug-specific effects on compliance were different during short-term and long-term administration (p < 0.01); the diameter was influenced differently only during short-term administration (p < 0.05). These opposite drug effects on the A. brachialis are probably due to a vasoselective relaxation of smooth muscle in large arteries by isradipine and-in the case of metoprolol-arterial constriction. The increase of arterial compliance by isradipine reduces very effectively the load on the heart and could form the basis for the improvement in the prognosis of the hypertensive patient.

Adult↗
PubMed1994

Immunohistochemical localization of L-dopa and aromatic L-amino acid-decarboxylase in the rat retina.

PURPOSE: The purpose of this study was threefold: to determine if some catecholaminergic amacrine cells of the rat retina use L-DOPA as their neurotransmitter, especially the small (2CA) cells that are immunoreactive to tyrosine hydroxylase but not to dopamine; to understand better the possible existence of serotoninergic cells in the rat retina; and to clarify the role of serotonin in the metabolism of melatonin. METHODS: Immunohistochemistry using antibodies against tyrosine hydroxylase (TH), L-DOPA, aromatic L-amino acid decarboxylase (AADC), dopamine (DA), and tyramine in rat retinal wholemounts, serial sections, and various combinations of double labeling. RESULTS: Paired wholemounts immunoreacted with anti-TH/AADC antibodies did not show a significant difference in densities of TH+ and AADC+ amacrine cells. All the TH+ cells exhibited AADC immunoreactivity. There were no AADC-immunoreactive cells lacking TH. A few TH+ cells exhibited L-DOPA immunoreactivity; they also contained AADC. The inner segments of photoreceptor cells were labeled by the anti-AADC antibody. The antibody to tyramine did not label any cells in the rat retina. CONCLUSIONS: L-DOPA can be excluded as a candidate active substance for the small TH+ amacrine cells that do not exhibit DA-immunoreactivity. The L-DOPA-immunoreactivity restricted to a small number of large TH+ amacrine cells probably does not represent an end product. Tyramine also does not appear to constitute a neurotransmitter in the rat retina. We confirm that there are no serotonin-synthesizing amacrine cells in the rat retina. The localization of AADC-immunoreactivity in the photoreceptor cell inner segments is possibly related to the biosynthetic pathway of melatonin from 5-hydroxytryptophan.

Animals↗
PubMed1993

[Early diagnosis of silent atherosclerosis and detection of cardiovascular risk factors. A new strategy for the approach of cardiovascular prevention].

The authors present a new strategy for cardiovascular disease prevention based on risk factor detection in occupational medicine and silent atherosclerosis detection in a specialized investigation centre. Employees from several firms in the Paris region were searched, in their working place, for cardiovascular risk factors, including blood cholesterol measurement. The subjects at risk thus selected underwent non-invasive explorations aimed at an early detection of silent atherosclerosis. Extracoronary plaques in the carotid, aorta and femoral arteries were detected by high-resolution ultrasonography, and coronary calcifications by ultrafast CT. The prevalence of arterial lesions and their relationship with risk factors were analysed in a subgroup of 208 untreated male subjects with high blood cholesterol level: 74 percent of these subjects had extracoronary plaques and 65 percent had coronary calcifications. This high prevalence of silent arterial lesions suggested that hypercholesterolaemia, even when moderate, has an early but inconsistent atherogenic effect. Moreover, extracoronary plaques and coronary calcifications were related to risk factors other than blood lipids, and among these factors age was predominant. The simultaneous detection of extracoronary and coronary lesions has demonstrated that extracoronary ultrasonography of several arteries is a good diagnostic test predicting the presence of coronary calcifications in the absence of coronary symptoms. Detection of silent atherosclerosis in subjects at risk therefore is an original and helpful complement to risk factor detection. It should better refine and individualize the diagnosis of risk and evaluate the effects of preventive cardiovascular treatments on atherosclerosis.

Adult↗
PubMed1993

Radioimmunoligand characterization and immunohistochemical localization of dopamine D2 receptors on rods in the rat retina.

The retinal neurotransmitter dopamine (DA), elaborated from intrinsic dopaminergic neurons as amacrine and interplexiform cells, is known to modulate several complex functions mediated by D1 and D2 receptors in the vertebrate retina. In this paper, we characterized and localized DA receptors of the D2 family on rod outer segments (ROS) of the rat retina by a radioimmunoligand binding assay and by immunohistochemistry. Anti-anti-DA conjugated antibodies (or anti-idiotypic antibodies Ab2) were used as ligand; BSA-glutaraldehyde-conjugated spiperone, eticlopride (D2 antagonists) and DA were used as displacers. The linear Scatchard transformation indicated that data were best fit to the one-site model. By using the peroxidase-antiperoxidase technique, an intense labeling was located on rods. These results supported the paracrine action of DA on the photoreceptor cell.

Animals↗
PubMed1993

The site of action of pantoprazole in the gastric H+/K(+)-ATPase.

Pantoprazole is a pyridinyl-2-methylenesulfinyl-2-benzimidazole derivative. This compound inhibits the vesicular gastric H+/K(+)-ATPase (cytoplasmic side out) under acid transporting conditions by accumulating in the acid space generated by the pump. Pantoprazole is then converted in an acid-catalysed reaction to a cationic sulfenamide and reacts with cysteines available in or from the acidic extracytoplasmic space. This compound binds to the hog gastric H+/K(+)-ATPase with a stoichiometry of 3 nmol per mg protein, resulting in 94% inhibition of ATPase activity. Tryptic cleavage of the intact vesicles which had been reacted with [14C]pantoprazole at a 1 to 4 trypsin to protein ratio removed most of the cytoplasmic domain leaving the pairs of membrane spanning segments and their connecting extracytoplasmic loops intact. The peptides remaining in the membrane were dissolved in SDS and available cysteine residues labelled with fluorescein-5-maleimide. The peptides were separated on Tricine gradient gels, transferred to PVDF membranes and identified by fluorescence and radioactivity. From N-terminal sequence, fluorescence and molecular mass, it is concluded that pantoprazole is able to label both Cys-813 and Cys-822. These cysteines are predicted to be located in the extracytoplasmic loop connecting membrane segments 5 and 6 and in membrane segment 6. The major cytoplasmic tryptic cleavage site at this location moved from position 776 in unmodified enzyme to positions 784 and 792 following pantoprazole labelling, showing that the configuration of this region changed with pantoprazole labelling. A similar result was obtained by reduction of the enzyme with dithiothreitol. Covalent binding of the cationic sulfenamide to this region of the enzyme is able to block the conformation necessary for phosphorylation of the enzyme by ATP, accounting for its inhibitory effect on acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Relations of cardiovascular risk factors to aortic pulse wave velocity in asymptomatic middle-aged women.

Cross-sectional associations between aortic elasticity assessed by carotid to femoral pulse wave velocity (PWV) and cardiovascular risk factors were examined in 429 apparently healthy middle-aged women. PWV was strongly and positively related to blood pressure and hypertension. Weak but significant positive associations were also found between PWV and age, heart rate, some lipids and lipoproteins, blood glucose (either as a continuous or dichotomous variable), body mass index, haematocrit, leucocyte count and family history of diabetes. No associations were observed between PWV and high density lipoprotein cholesterol, apolipoprotein A1, fibrinogen, cigarette smoking, menopausal status and a family history of hypertension or myocardial infarction. After adjustment for systolic blood pressure, PWV remained significantly related to heart rate, leucocyte count, blood glucose (as a dichotomous variable) and a family history of diabetes. Multiple regression analysis showed that systolic blood pressure and, to a lesser extent, heart rate, leucocyte count and a family history of diabetes were all independent determinants of PWV. This pattern of associations suggests that arterial stiffness measured by PWV reflects the sclerotic rather than the atherotic component of atherosclerosis. The potential influence of a family history of diabetes on the elastic properties of the aorta needs to be ascertained in further studies.

Age Factors↗
PubMed1993

Pharmacokinetics and protein binding of 3-ketodesogestrel and gestodene in the serum of women during 6 cycles of treatment with two low dose oral contraceptives.

The serum concentrations of 3-ketodesogestrel (KDG) and gestodene have been measured in 30 and 31 women respectively who took low dose oral contraceptives containing 30 micrograms ethinylestradiol together with either 150 micrograms desogestrel or 75 micrograms gestodene for 6 months. On days 1, 10 and 21 of the first third and sixth treatment cycles blood samples were drawn at 0, 0.5, 1, 1.5, 2, 3, 4 and 24 h. KDG and gestodene levels were measured by radioimmunoassays and were evaluated for Cmax (peak serum concentration), tmax (time to Cmax), and AUC (area under the curve) to 4 and 24 h. The overall total gestodene concentrations were higher and the accumulation of the steroid throughout a cycle greater than that of KDG. For example, the AUC0-4 of gestodene increased in cycle 1 by a factor of 2.8 (day 10 vs. day 1) and 3.6 (day 21 vs. day 1) compared to 2.3 and 2.6 for KDG. The higher concentration of gestodene reflects a lower volume of distribution than KDG, and is consistent with gestodene binding to sex hormone binding globulin (SHBG) with a higher affinity than KDG. Concentrations of KDG and gestodene were higher on day 1 of cycles 3 and 6 than on day 1 of cycle 1. The serum concentrations of KDG and gestodene during multiple dosing cannot be predicted on the basis of single dose pharmacokinetics.

Adolescent↗
PubMed1993

Influence of gestodene and desogestrel as components of low-dose oral contraceptives on the pharmacokinetics of ethinyl estradiol (EE2), on serum CBG and on urinary cortisol and 6 beta-hydroxycortisol.

A randomized controlled clinical trial was undertaken over a 6-month treatment period with two low-dose combined oral contraceptives (OC) to investigate whether the metabolism and elimination of ethinyl estradiol (EE2) is differently influenced by the two progestational components gestodene (G) and desogestrel (D), an issue which has been very controversial recently. The two formulations contained 30 micrograms EE2 each, together with either 75 micrograms G or 150 micrograms D. Of the 40 young women recruited for each formulation, 31 of each group were available for statistical evaluation. The pharmacokinetics of serum EE2 were studied on day 1, 10 and 21 of cycle 1, 3 and 6. There were no significant differences between the two groups in any cycle with respect to parameters measured. This was true for the distinct intracyclical rise in the mean EE2 serum levels from day 1 to day 10 and the smaller further increase between day 10 and day 21, with no change in this respect between the cycles studied. Respective changes were seen with regard to the area under the EE2 serum concentration curve up to 4 and 24 hours (AUC0-4 and AUC0-24), cmax and tmax of serum EE2. The estrogen-dependent corticoid-binding globulin (CBG) increased similarly in the two groups intracyclically and slightly also intercyclically at all times tested. Except for the first treatment cycle, urinary excretion of cortisol and 6 beta-hydroxycortisol displayed a tendency to lower values intracyclically as well as intercyclically, again with no differences between the two groups. Also, the 6 beta-hydroxycortisol-to-cortisol ratio was not different between the groups, showing a slight tendency to rise from about 4 at the beginning of the medication to around 5.5 at the end of the 6th treatment cycle in both groups. It is concluded that G and D as components of low-dose OCs exert comparable effects on the metabolism and elimination of EE2.

Adult↗
PubMed1993

Conception rate after in vitro fertilization in patients who conceived in a previous cycle.

OBJECTIVE: To evaluate whether a previously successful in vitro fertilization and embryo transfer (IVF-ET) cycle is a favorable prognostic factor for a subsequent cycle. DESIGN: A retrospective comparison between current IVF patients who have previously conceived in an IVF versus natural cycle. SETTING: The IVF unit of a university hospital. PATIENTS: Group A consisted of 51 patients (70 cycles of IVF-ET) who previously conceived in an IVF-ET cycle, and group B included 141 patients (201 cycles of IVF-ET) who previously conceived in a natural cycle. All couples with male factor infertility were excluded. Ovulation induction protocol was identical for both groups and consisted of gonadotropin-releasing hormone agonist pretreatment followed by gonadotropin stimulation. MAIN OUTCOME MEASURES: Pregnancy rate per ET, cumulative pregnancy rate, and livebirth rate in both groups. RESULTS: The following parameters were comparable for both groups: age, menotropin dosage required for an adequate stimulation, ovarian response, mean number of oocytes retrieved per cycle, fertilization and cleavage rates, and the mean number of embryo transferred. Group A attained a significantly higher pregnancy rate (PR) than group B (31.4% versus 19.4%). Group A also achieved a significantly higher livebirth rate (22.9% versus 11.4%) than group B. Similarly, the cumulative PR curves and the cumulative livebirth rate curves for three consecutive IVF-ET cycles differed significantly between the two groups. CONCLUSION: A previous successful IVF cycle is a positive prognostic factor for a repeated IVF attempt. This effect could be because of either an improved endometrial response or a better embryo quality. It may be that this patient population is relatively immune to the known untoward effects of ovulation induction on endometrial development and, therefore, may represent a potential clinical model that can be used to further identify the factors influencing uterine receptivity after ovulation induction.

Adult↗
PubMed1993

The efficacy and safety of zona pellucida drilling by a 193-nm excimer laser.

OBJECTIVE: To examine the efficiency of argon fluoride excimer laser drilling of the zona pellucida of mouse oocytes in improving in vitro fertilization (IVF) at low sperm concentrations and to assess its safety. DESIGN: Oocytes obtained from (Balb/c x C57BL6)CB6F1 female mice were drilled by laser and divided into two groups: group I (89 oocytes) were inseminated with 10(5) sperm cells/mL, and group II (94 oocytes) were inseminated with 10(6) sperm cells/mL. Both groups' fertilization rate and development in vitro was compared with control oocytes that underwent the same preparation steps but no drilling (94 and 88 oocytes for group I and group II, respectively). MAIN OUTCOME MEASURES: The fertilization rate and the development in vitro of the laser-drilled groups is compared with that of the control. In addition, in vivo development of embryos generated from laser-drilled oocytes after transfer to pseudopregnant recipients is assessed. RESULTS: For both sperm concentrations, laser drilling significantly enhanced fertilization over control (67% versus 31% at 10(5) sperm cells/mL and 90% versus 54% at 10(6) sperm cells/mL). The development into the blastocyst stage after 96 hours of incubation was similar for both the laser-drilled and control groups at any sperm cell concentration. However, complete hatching at this point was significantly enhanced by the drilling procedure. Normal litters were obtained from the transfer of embryos developed from zona-drilled oocytes into pseudopregnant recipients. CONCLUSIONS: Excimer laser drilling enhanced IVF at low sperm cell concentration. The procedure is safe and did not interfere with embryo development in vitro or in vivo.

Animals↗
PubMed1993

The effect of gonadotropin-releasing hormone agonist on embryo quality and pregnancy rate following cryopreservation.

OBJECTIVE: To examine the effect of GnRH analogue (GnRH-a) on the quality of frozen-thawed embryos and the pregnancy rate (PR) resulting from transfer. DESIGN: A retrospective study of two groups of women undergoing transfers of frozen-thawed embryos. In group 1 ovulation induction with hMG was begun after hypophyseal desensitization with GnRH-a for 2 weeks. In group 2 ovulation was induced with hMG only. The freezing and thawing techniques were identical for both groups. SETTING: In vitro fertilization unit at a university hospital. PATIENTS: The study group (group 1) included 108 women who underwent 137 transfer cycles of frozen-thawed embryos, and the control group (group 2) included 44 women in 51 cycles of thawed ETs. INTERVENTIONS: Ovum pick-up and ET techniques were the same for both groups. Methods of embryo freezing and thawing were identical, as were the morphological criteria for grading the embryos. RESULTS: The morphology of embryos was similar in both groups, as was the number of embryos that had at least 50% intact blastomeres (83% +/- 23% and 78% +/- 30% for group 1 and group 2, respectively). The PR (16 of 137 [11.7%] and 6 of 51 [11.8%], respectively) as well as the abortion rate (30%) were similar for both groups. CONCLUSIONS: The use of GnRH-a does not affect the quality of embryos nor the pregnancy outcome. Because the yield of frozen embryos per ovum pick-up is higher in cycles stimulated by GnRH-a/hMG, the PR per pick-up cycle is thus anticipated to be higher.

Abortion, Spontaneous↗
PubMed1993

Interaction between human sperm cells and hamster oocytes after argon fluoride excimer laser drilling of the zona pellucida.

OBJECTIVES: To provide conclusive evidence that sperm cells gain access to the perivitelline space exclusively through a laser-drilled opening. To assess the optimal size of the hole and to evaluate the efficacy of laser drilling in comparison with that of mechanical zona dissection. DESIGN: An interspecies model of human sperm cell that interacts with a laser-drilled or partially zona-dissected hamster oocytes. MAIN OUTCOME MEASURES: Penetration rate into the perivitelline space as related to the size of the opening (group A [5 microns], group B [10 microns], and group C [15 microns]) and to the sperm cell concentrations (1 x 10(6), 5 x 10(6), and 10 x 10(6) cells/mL) used for insemination. RESULTS: For each sperm cell concentration, the penetration rate into the perivitelline space was lowest for group A followed by group C and highest for group B. When penetration was compared for each hole size, it was found that sperm concentration had no effect on the rate of penetration in groups A and C but significantly affected this rate in group B. The highest penetration rate of 73% was observed with a concentration of 10 x 10(6) cell/mL and declined to 58% and 23% at 5 x 10(6) cell/mL and 1 x 10(6) cell/mL, respectively. Oocytes drilled by laser (10-microns hole) demonstrated a significantly higher penetration rate when compared with those treated by partial zona dissection (73% versus 20% and 58% versus 21% for sperm densities of 10 x 10(6) cells/mL and 5 x 10(6) cells/mL, respectively). CONCLUSION: Human sperm cells gain access into the perivitelline space of hamster oocytes exclusively through a hole drilled by an argon fluoride excimer laser. An opening of 10 microns was found to yield optimal results. Laser drilling of the zona pellucida seems to be superior to that of mechanical slitting in terms of sperm oolema interaction.

Animals↗