Biomedical subjects

S Laurent

Publications and source records attributed to S Laurent.

At least 91 records · Page 5Linked to original sources

PubMed1999

[Molecular and cellular determinants of arterial stiffness: role of cell-matrix connections].

Increased large artery stiffness is believed to be a cardiovascular risk factor independent from mean arterial pressure. The mechanical properties of large arteries depend not only on the amounts of their main constituents (elastin, collagen, and smooth muscle cells) but also on the spatial organization and mechanical interactions among these components. These interactions may be mediated by extracellular matrix adhesion proteins and their membrane receptors or integrins. From a mechanical viewpoint, a key element may be the dense plaque, which is composed of cytoskeletal proteins linked to matrix proteins via membrane integrin receptors. Integrin expression in normal and diseased blood vessels is currently the focus of active research. In humans, hypertension-related arterial hypertrophy is not associated with an increase in intrinsic arterial wall stiffness. Aortic fibronectin expression is increased in spontaneously hypertensive rats (SHRs). By increasing cell-matrix anchoring, fibronectin may contribute to protect arterial wall components from the increased mechanical loads associated with hypertension. In atherosclerosis, the increase in cell-matrix anchoring plays a key role in preventing atheroma plaque rupture. To determine the exact role of adhesion molecules in arterial stiffness, there is a need for studies involving use of specific anti-integrin agents and of transgenic animal models.

Animals↗

PubMed1999

[Treatment of border-line dilatation of the ascending aorta using the Robicsek intervention].

The technique and the results of the external contention of the dilated ascending aorta by the application of an external Dacron graft are reported. This technique, without replacing the usual graft interposition, can efficiently and expeditiously treat borderline dilatation of the ascending aorta, as frequently encountered in aortic valve disease. If the sinotubular junction is not dilated, this technique may stop the aneurysmal evolution of the ascending aorta.

Aorta↗

PubMed1998

Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats.

We compared the chronic effects in spontaneously hypertensive rats (SHR) of low doses of an angiotensin converting enzyme inhibitor, trandolapril, a Ca2+ channel antagonist, verapamil, and their combination (trandolapril-verapamil), on arterial mechanical properties, arterial wall hypertrophy and extracellular matrix proteins. Four-week-old SHR were randomly allocated to oral treatment with verapamil (50 mg kg(-1) day(-1)), trandolapril (0.3 mg kg(-1) day(-1)), the combination of verapamil (50 mg kg(-1) day(-1)) plus trandolapril (0.3 mg kg(-1) day(-1)), or placebo for 4 months. A group of Wistar Kyoto (WKY) control rats received placebo for the same period of time. At the end of the treatment, mean blood pressure was lower in verapamil-trandolapril than in trandolapril SHR, but remained higher than in WKY. Verapamil had no effects on blood pressure. Equivalent reduction in aortic wall hypertrophy was obtained in all treated SHR. Trandolapril and verapamil-trandolapril combination produced a significant reduction of aortic collagen density compared with placebo SHR. Carotid total fibronectin, EIIIA fibronectin isoform and alpha5beta1 integrin, were higher in the media of placebo SHR than in WKY. EIIIA fibronectin isoform and alpha5beta1 integrin were reduced in verapamil-SHR compared with placebo-SHR and normalized in trandolapril and verapamil-trandolapril-SHR compared with WKY. SHR-placebo and SHR treated with either verapamil or trandolapril as single-drug treatment showed a 4-fold increase in total fibronectin compared to the WKY. Only SHR treated with verapamil-trandolapril combination had total fibronectin not significantly different from that of WKY. Carotid arterial distensibility increased only in verapamil-trandolapril treated rats. Multivariate analysis showed arterial distensibility to be negatively correlated to mean blood pressure (P < 0.0001) and total fibronectin (P < 0.01). In conclusion, chronic treatment with the verapamil-trandolapril combination significantly improved in vivo arterial distensibility in SHR. The most important effects of the combination on arterial mechanics compared to those of verapamil or trandolapril alone may have been the consequence of its stronger action on arterial pressure, arterial wall hypertrophy and total fibronectin density. However we suggest that, in addition to the structural effects, complete normalization of blood pressure is necessary to obtain normal arterial distensibility.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Effects of norepinephrine on the mechanical properties of the human radial artery in vitro.

BACKGROUND: The human radial artery has been proposed as an alternative to coronary grafts in subjects with coronary ischemic disease. Because this muscular artery is known to be prone to spasm, changes in its mechanical properties in response to catecholamines are important to investigate. METHODS: We describe a new echo-tracking technique of high resolution that allows investigation, in vitro, of the diameter and the wall thickness of arterial cylindrical segments. In addition, a classic tissue bath experiment is used to study the vasoreactivity of arterial rings. Mechanical properties of the radial artery are determined over a 0 to 200 mm Hg range of transmural pressure in the presence and absence of norepinephrine in the perfusion medium. RESULTS: With tissue bath experiments, the norepinephrine dose-response curve was characterized by an EC50 value of 1.48+/-1.09 10(-6) mol/L and a maximal developed tension at 10(-5) mol/L. The results obtained with pressurized segments gave similar results with an EC50 value of 8.1+/-2.3 10(-7) mol/L and a maximal change in diameter at 10(-5) mol/L norepinephrine. Under the influence of 10(-5) mol/L norepinephrine, the radial artery constriction reached 22%, significantly affecting the unstressed diameter. Compliance did not show any significant change in the overall transmural pressure range, whereas distensibility significantly increased and elastic modulus significantly decreased. CONCLUSION: The study shows that the capacitive properties of the human muscular radial artery are maintained with norepinephrine not only through decreased stiffness of wall material but also through reduced unstressed diameter. Thus drugs inducing smooth muscle relaxation may be helpful in preventing radial artery spasm after coronary grafts.

Aged↗

PubMed1998

Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients.

OBJECTIVES: The present study was designed to assess whether a diuretic- or an angiotensin-converting enzyme inhibitor-based treatment can reduce arterial wall hypertrophy of a distal muscular medium-sized artery--the radial artery--and the stiffness of a proximal large elastic artery--the common carotid artery. BACKGROUND: Large-artery wall thickness and stiffness are increased during sustained essential hypertension and contribute to the increased risk of complications. Whether antihypertensive treatment can normalize the wall hypertrophy of conducting arteries has not yet been determined. METHODS: Seventy-seven elderly hypertensive patients were randomized to receive 9 months of double-blind treatment with perindopril (2 to 8 mg/day) or the diuretic combination of hydrochlorothiazide (12.5 to 50 mg/day) plus amiloride (1.25 to 5 mg/day) after a 1-month placebo washout period. If systolic blood pressure remained at >160 mm Hg after 5 months, chlorthalidone or atenolol was added, respectively. Arterial variables, including radial artery mass and common carotid artery compliance, were calculated from noninvasive measurements of internal diameter and wall thickness with the use of high resolution echo-tracking systems at baseline and after 5 and 9 months. RESULTS: During treatment, blood pressure and arterial variables changed to the same extent in both groups. After a 9-month treatment, systolic, diastolic and pulse pressures and radial artery wall thickness, mass and thickness/radius ratio decreased significantly (p < 0.01), whereas carotid compliance increased (p < 0.001). The decrease in radial artery thickness/radius ratio after a 9-month treatment was significantly related to the reduction in pulse pressure (p < 0.01), whereas the improvement in carotid compliance was related to the reduction in mean arterial pressure (p < 0.01). In healthy subjects and untreated hypertensive patients, radial artery diameter, wall thickness and thickness/radius ratio and carotid artery compliance did not change significantly during a 9-month observation period. CONCLUSIONS: These results indicate that in elderly hypertensive patients, both angiotensin-converting enzyme inhibitor- and diuretic combination-based treatments can reduce radial artery wall hypertrophy and improve carotid artery compliance.

Aged↗

PubMed1998

Multinuclear magnetic resonance characterization of paramagnetic contrast agents. The manifold effects of concentration and counterions.

RATIONALE AND OBJECTIVES: Proper fitting of the nuclear magnetic resonance dispersion (NMRD) profiles to the numerous factors governing nuclear relaxation in paramagnetic systems requires knowledge of some parameters usually obtained by other techniques. The rotational correlation time (tau R) for example can be measured by carbon-13, hydrogen-2, or oxygen-17 NMR. Discrepancies between values reported in the literature might be attributed to the different concentration ranges used so far in these modalities. In the present work focussing on commercial nonspecific contrast agents, the influence of the solution composition (type and concentration of the complexes and of the counterions) has been examined with regard to the water proton relaxation enhancement and molecular dynamics. METHODS: The proton relaxation rate enhancement of Magnevist, Dotarem, Omniscan, and ProHance was measured in aqueous solution up to a concentration of 0.5 M. In the same concentration window, the rotational correlation times were obtained from the study of deuterium relaxation rates of the diamagnetic deuterated analogs (lanthanum complexes) of the gadolinium chelates. RESULTS: Above 50 mM, the relaxation rate enhancement versus concentrations strongly deviates from linearity. Magnevist, a clinical formulation containing two meglumine counterions per molecule of paramagnetic complex, exhibits the largest concentration effect. A slowing down of the molecular dynamics accounts for this behavior as confirmed by the analysis of the rotational correlation times obtained by deuterium relaxometry. At low concentrations (< or = 50 mM), tau R values obtained by proton NMRD analysis and by deuterium relaxation are in very good agreement. CONCLUSIONS: This study shows that NMR analyses of small molecular weight complexes should be carried out on solutions containing no more than 50 mM to avoid the biaising effects of concentration. On the other hand, the benefitting relaxivity enhancement induced by highly concentrated solutions has to be taken into account in the context of bolus injection or vesicular entrapment.

Contrast Media↗

PubMed1998

Fibronectin expression and aortic wall elastic modulus in spontaneously hypertensive rats.

Recent studies have shown that large-artery wall remodeling per se does not reduce distensibility in hypertension, indicating qualitative or quantitative changes in arterial components. The aim of the study was to determine in 1-year-old spontaneously hypertensive rats (SHRs) the changes in the elastic properties of large arteries, as assessed by the incremental elastic modulus (E(inc)), and the changes in the extracellular matrix, including fibronectin (FN) and alpha5beta1-integrin. The relationship between E(inc) and circumferential wall stress was calculated from in vivo pulsatile changes in blood pressure and arterial diameter by using a high-resolution echo-tracking system at the site of the abdominal aorta and in vitro medial cross-sectional area. E(inc)-stress curves and FN and integrin alpha5-subunit contents were determined for each animal. Mean stress and E(inc) were higher in SHRs than in Wistar rats. However, in a common range of stress, E(inc)-stress curves for SHRs were superimposable on those for Wistar rats, indicating that wall materials in both strains have equivalent mechanical behavior. Immunohistochemistry indicated that total FN, EIIIA FN isoform, and alpha5-integrin increased in the SHRs aortas without changes in elastin and collagen densities. Total FN was also increased in SHRs as determined by Western blot analysis. No differences in FN and alpha5-subunit mRNAs were detected between SHRs and Wistar rats. These results indicate that the aortic wall material of SHRs and Wistar rats have equivalent mechanical properties, although in SHRs it is subjected to a higher level of stress. By increasing cell-matrix attachment sites, FN may participate in the mechanical adaptation of both cellular and matrix components in SHRs.

Animals↗

PubMed1998

Opposite effects of remodeling and hypertrophy on arterial compliance in hypertension.

Sustained hypertension is associated with a reduction in large artery compliance. However, we previously showed that, at the site of the radial artery, a distal muscular artery, the compliance of hypertensive patients was not significantly different from those of normotensive controls when the two groups were studied at their respective mean arterial pressures, despite increased wall thickness in hypertensives. To determine whether this paradoxical finding could be related to a specific pattern of geometrical changes, we studied arterial compliance in never-treated hypertensive patients characterized either by radial artery hypertrophy or remodeling, and compared them to normotensive controls. By analogy with Devereux's classification for left ventricular hypertrophy, we defined remodeling as an increased thickness to radius ratio (h/r) and a normal vascular mass (VM), and arterial hypertrophy as an increased VM irrespective of the values of h/r. Internal diameter and wall thickness were measured at the site of the radial artery using a high resolution echo-tracking system. The lumen cross-section-pressure curve was determined from the two simultaneous and continuous recordings of arterial diameter and blood pressure. Then, the cross-sectional compliance (CC)-pressure curve was calculated. Isobaric compliance was calculated at 100 mm Hg. Thresholds for h/r and VM were determined according to gender as the 95th percentile of a group of 100 normotensive subjects. The group of hypertensive patients included 58 patients with hypertrophy (h/r: 0.25+/-0.04; VM: 31+/-6 mg/cm; mean+/-SD) and 25 patients with remodeling (h/r: 0.29+/-0.06; VM: 20+/-4 mg/cm) and was compared to a group of 50 age- and gender-matched normotensives (h/r: 0.16+/-0.02; VM: 17+/-4 mg/cm). Compared to normotensives, isobaric compliance of the radial artery was increased in hypertensive patients with hypertrophy (HH) whereas it was not different in hypertensive patients with remodeling (RH). These results indicate that compliance is dependent on hypertrophy or remodeling pattern and suggest that in the face of hypertension, only arterial hypertrophy is an adaptive process leading to normal operating compliance through an increased isobaric compliance.

Blood Pressure↗

PubMed1998

Connection of smooth muscle cells to elastic lamellae in aorta of spontaneously hypertensive rats.

We have recently demonstrated that in large arteries of spontaneously hypertensive rats (SHR), there is no increase of stiffness despite the increase in wall thickness, a sign of mechanical adaptation of the arterial wall to the higher level of stress. Because the dense plaques of smooth muscle are a major site of anchorage between the muscle cells and extracellular matrix, we determined by electron microscopy the distribution of dense plaques and their connections to elastic lamellae in the abdominal aorta of 1-year-old SHR and control Wistar rats. In vivo echo-tracking measurement of aortic distensibility and elastic modulus indicates a reduction of arterial stiffness in SHR compared with Wistar rats when they are studied over a common range of blood pressure. The media thickness to body weight ratio was higher in SHR than in Wistar rats. In the media, the percentage of sectional area occupied by extracellular matrix was not different between Wistar rats and SHR. The average number of dense plaques per muscle cell was not different between Wistar rats and SHR. However, the percentage of cell surface occupied by dense plaques was increased in SHR, and the percentage of cell surface connected to the elastic lamellae was twice as high in SHR compared with Wistar rats (9.4+/-1.5% versus 3.8+/-1.1%). These results suggest that the elastin network plays a major role in the mechanical adaptation of the arterial wall in SHR, not through variations of its total amount but through variations of the extent of anchorage to the muscle cells.

Adaptation, Physiological↗

PubMed1998

Smooth muscle tone and arterial wall viscosity: an in vivo/in vitro study.

The relationships between steady and pulsatile pressures, smooth muscle tone, and arterial viscoelastic behavior remain a matter of controversy. We previously showed that arterial wall viscosity (AWV) was 3-fold lower in vivo than in vitro and suggested that in vivo active mechanisms could minimize intrinsic AWV to improve the efficiency of heart-vessel coupling energy balance. The aim of the present study was to determine the role of smooth muscle tone on AWV, under various levels of steady and pulsatile pressures, both in vivo and in vitro. AWV of rat abdominal aorta was studied first in vivo after bolus injections of phenylephrine (PE) or sodium nitroprusside (SNP), then in vitro in response to PE or SNP. In vitro, arterial segments were submitted first to steady pressure (0 to 200 mm Hg) by increments of 20 mm Hg, then to increasing levels of pulse pressure (20 to 50 mm Hg) at various mean arterial pressures (75 to 150 mm Hg). AWV was quantified as the area of the pressure/diameter relationship hysteresis, issued from the simultaneous measurements of pressure (Millar micromanometer) and diameter (NIUS echotracking device). In vivo, AWV increased after PE and decreased after SNP, in parallel with pressure changes. In vitro, AWV was not significantly influenced by PE and SNP. After both PE and SNP, AWV increased with pulse pressure but was not influenced by mean arterial pressure. At any given pulse pressure, AWV was higher in vitro than in vivo. The relation between AWV and pulse pressure was significantly steeper in vitro than in vivo. These results show that AWV is strongly influenced by steady and pulsatile mechanical load but not by smooth muscle tone, both in vivo and in vitro. Factors other than sustained smooth muscle activation should be explored to explain the minimization of AWV in vivo compared with intrinsic in vitro values.

Animals↗

PubMed1998

Lack of association between renin-angiotensin system, gene polymorphisms, and wall thickness of the radial and carotid arteries.

To investigate the relationship between polymorphisms of the angiotensin-converting enzyme (ACE) and the angiotensin II type 1 receptor (AT1R) genes and structural phenotypes of arteries, we studied a cohort of 340 subjects (aged 49+/-12 years) without evidence of cardiovascular disease and who had never been treated previously with any cardiovascular treatments. Structural phenotypes (wall thickness and internal diameter) were evaluated for the common carotid and the radial arteries using high-resolution echo-tracking devices (NIUS-02 and Wall Track System). The influence of ACE insertion/deletion (I/D) and AT1R A/C1166 polymorphism genotypes on structural parameters was tested by ANOVA and logistic regression analysis. For the radial artery, mean wall thickness among subjects according to the ACE I/D or AT1R A/C1166 genotypes was not different. This lack of association persisted in a logistic regression analysis or when the comparison was restricted to a subgroup of subjects potentially at high genetic risk (DD and CC or AC) compared with subjects at low genetic risk (AA and II or ID). Also, no association was observed between the carotid artery intima-media thickness and the 2 polymorphisms. In conclusion, the ACE I/D and the AT1R A/C1166 gene polymorphisms are not markers of vascular hypertrophy in subjects with no evidence of cardiovascular disease. These results suggest that these gene polymorphisms have an undetectable role in the geometry of the radial and carotid arteries compared with usual determinants such as blood pressure and age.

Adult↗

PubMed1998

[Female fertility prognosis and diethylstilbestrol. Personal data and review of the literature].

Diethylstilbestrol (DES) exposure in utero in females is a cause of clear-cell adenocarcinoma of the cervix and of several anatomical and functional disorders of the genital tract. DES exposure must be evoked whenever counselling women for reproductive disorders. In France around 80,000 women have had in utero DES exposure. The cases of 4 young women who consulted our Reproduction Center for reproductive disorders illustrate the usual difficulties faced by these patients. In spite of their difficult past reproductive history (uterine malformations, repeated miscarriages, ectopic pregnancies) and low fertility rate, all four women conceived successfully, either after spontaneous or induced ovulation. We stress the need for adapted psychological and medical care which can lead to successful childbearing in the vast majority of these high-risk patients.

Adult↗

PubMed1998

The importance of repeated risk assessment for pressure sores in cardiovascular surgery.

BACKGROUND: Patients undergoing cardiovascular surgery are at high risk for sores because of impaired perfusion, the time spent on the operating room table, and restricted mobility in the immediate postoperative period. OBJECTIVE: To identify risk factors for sores. METHODS: In a 900-bed teaching hospital, 163 patients who underwent cardiovascular interventions were enrolled. Risk measurement included skin assessment, Braden and Norton scales, physic and biologic data and specific risk factors. The development of the most severe stages of pressure sores was followed (Stages II and III). RESULTS: Forty-eight (29.5%) patients totalized 75 pressure sores. In univariate analyses, Norton and Braden scores, hemoglobin concentration, presence of ulcers at admission, use of antihypertensive drugs, systemic use of corticosteroids, nosocomial infection, re-intervention and readmission in intensive care units were associated with sores. In a logistic regression model, hemoglobin concentration at admission (p=0.0007), postoperative Braden score (p=0.0002), and postoperative steroid therapy (p=0.020) were the only predictors of sores. Total length of stay was 6 days higher (p=0.03) for patients with pressure sores. CONCLUSIONS: The detection of risks is recommended during the entire stay. Identification of patients at risk is required to provide preventive resources appropriately, which can lessen the incidence of pressure sores and reduce patient discomfort, length and costs of hospital stay.

Aged↗

PubMed1997

Antibodies to several conformation-dependent epitopes of gp120/gp41 inhibit CCR-5-dependent cell-to-cell fusion mediated by the native envelope glycoprotein of a primary macrophage-tropic HIV-1 isolate.

The beta-chemokine receptor CCR-5 is essential for the efficient entry of primary macrophage-tropic HIV-1 isolates into CD4(+) target cells. To study CCR-5-dependent cell-to-cell fusion, we have developed an assay system based on the infection of CD4(+) CCR-5(+) HeLa cells with a Semliki Forest virus recombinant expressing the gp120/gp41 envelope (Env) from a primary clade B HIV-1 isolate (BX08), or from a laboratory T cell line-adapted strain (LAI). In this system, gp120/gp41 of the "nonsyncytium-inducing," primary, macrophage-tropic HIV-1BX08 isolate, was at least as fusogenic as that of the "syncytium-inducing" HIV-1LAI strain. BX08 Env-mediated fusion was inhibited by the beta-chemokines RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory proteins 1beta (MIP-1beta) and by antibodies to CD4, whereas LAI Env-mediated fusion was insensitive to these beta-chemokines. In contrast soluble CD4 significantly reduced LAI, but not BX08 Env-mediated fusion, suggesting that the primary isolate Env glycoprotein has a reduced affinity for CD4. The domains in gp120/gp41 involved in the interaction with the CD4 and CCR-5 molecules were probed using monoclonal antibodies. For the antibodies tested here, the greatest inhibition of fusion was observed with those directed to conformation-dependent, rather than linear epitopes. Efficient inhibition of fusion was not restricted to epitopes in any one domain of gp120/gp41. The assay was sufficiently sensitive to distinguish between antibody- and beta-chemokine-mediated fusion inhibition using serum samples from patient BX08, suggesting that the system may be useful for screening human sera for the presence of biologically significant antibodies.

Antibodies, Viral↗

PubMed1997

Bivalent binding of a neutralising antibody to a calicivirus involves the torsional flexibility of the antibody hinge.

The structure of a complex between rabbit haemorrhagic disease virus (RHDV) virus-like particles (VLPs) and a neutralising monoclonal antibody mAb-E3 has been determined at low resolution by cryo-electron microscopy and three-dimensional (3-D) reconstruction techniques. The atomic co-ordinates of an Fab were fitted to the cryo-electron microscope density map to produce a binding model. The VLP has a T = 3 icosahedral lattice consisting of a hollow spherical shell with 90 protruding arches. Each dimeric arch presents two mAb binding sites; however, steric hindrance between the variable domains of the Fabs prevents the occupation of both sites simultaneously. Thus the maximum mAb occupation is 50%. Once a mAb is bound to one site it may bind to either of two neighbouring sites related by a local 3-fold axis. The mAbs are bound bivalently on epitopes not related by a 2-fold symmetry axis. This binding geometry implies a torsional flexibility of the mAb hinge region, involving a 60 degrees rotation of one Fab arm with respect to the other. Owing to extreme flexibility of the hinge region, the Fc domains occupy random orientations and are not visible in the reconstruction. The bivalent attachment of mAb-E3 to RHDV suggests that the neutralisation mechanism(s) involves inhibition of viral decapsidation and/or the inhibition of binding to the receptor.

Animals↗

PubMed1997

A multinuclear MR study of Gd-EOB-DTPA: comprehensive preclinical characterization of an organ specific MRI contrast agent.

The characterization of the hepatobiliary contrast agent Gd-EOB-DTPA (gadolinium 3, 6, 9-triaza-3, 6, 9-tris(carboxymethyl)-4-(4-ethoxybenzyl)-undecandicarboxylic acid) in various media (water solution, protein containing solution, phosphorylated metabolites solution, and excised and perfused liver) was performed using different NMR approaches: water 1H nuclear magnetic relaxation dispersion profiles, 2H NMR longitudinal and transverse relaxation rates of labeled complex, water 17O transverse relaxation rates and chemical shifts, 31P relaxation rates and peak area of phosphorylated metabolites. The higher proton relaxivity of Gd-EOB-DTPA in water compared with Gd-DTPA is related to a shorter distance (r) between the water proton and the gadolinium ion and to a longer rotational correlation time (tauR) of the hydrated complex. Although the thermodynamic stability of Gd-EOB-DTPA is identical to the one of Gd-DTPA, its kinetic stability in solutions containing phosphorylated metabolites (ATP, phosphocreatine, and inorganic phosphate) as measured by 31P relaxation rates analysis is higher than for the parent compound. Gd-EOB-DTPA binds noncovalently to serum proteins. Its interaction with human serum albumin is characterized by a dissociation constant of 1-4.1 mM as calculated from proton and deuterium relaxation rates and equilibrium dialysis. This noncovalent interaction involves the subdomain IIA of human serum albumin. 31P spectroscopy of the excised and perfused rat livers was used to monitor the uptake of Gd-EOB-DTPA by the hepatocytes where it enhances the nuclear relaxation of the intracellular metabolites without impairing the adenosine triphosphate metabolism of the cells.

Adenosine Triphosphate↗

PubMed1997

Effects of exogenous and endogenous nitric oxide on the contractile function of cultured chick embryo ventricular myocytes.

Nitric oxide (NO) has been shown to be a ubiquitous intercellular autacoid in the heart and, in cultured rat ventricular myocytes, to decrease the contractile responsiveness to isoproterenol (ISO). The aim of the present study was to investigate whether exogenous (sodium nitroprusside, SNP) or endogenous nitric oxide generated from L-arginine modulated the response to ISO in cultured chick embryo ventricular myocytes. SNP 1 microM or L-arginine 1 mM had no effect on baseline contractile function. Superfusion with ISO 100 nM significantly increased myocyte amplitude of shortening to 1.31 +/- 0.06 (ratio to baseline amplitude). Initial superfusion with SNP 1 microM or L-arginine 1 mM attenuated the response to ISO to 0.89 +/- 0.05 and 1.09 +/- 0.07 respectively (P < 0.05). Potassium ferrocyanide which is not a NO donor and D-arginine the inactive substrate of NO synthase did not attenuate the response to ISO. Myocyte cGMP content was significantly increased by incubation with SNP 1 microM (31.65 +/- 3 fmol/well) but not by L-arginine 1 mM (11.1 +/- 0.3 fmol/well) as compared to myocytes incubated in control medium (11 +/- 0.9 fmol/well). Preincubation with SNP 1 microM or L-arginine 1 mM significantly attenuated the ISO mediated-increase in cAMP content from 4.33 +/- 0.2 pmol/well (ISO 100 nM alone) to 1.48 +/- 0.36 fmol/well and 1.72 +/- 0.21 pmol/well respectively. Potassium ferrocyanide and D-arginine had no effect on myocyte cGMP or cAMP content. Chick embryo myocytes have measurable and LNMMA-inhibited NO synthase activity as measured by the conversion of [3H] L-arginine to [3H] L-citrulline. In conclusion, these results demonstrate that in cultured chick embryo ventricular myocytes both exogenous and endogenous NO elevate cGMP. This may account for the inhibition of beta-adrenergic agonist-stimulated increases in cAMP and amplitude of shortening via an unidentified intracellular negative coupling.

Adrenergic beta-Agonists↗

PubMed1997

Primary care by obstetricians and gynecologists: attitudes of the members of The South Atlantic Association of Obstetricians and Gynecologists.

OBJECTIVE: Our purpose was to determine the extent of primary care delivered by obstetrician-gynecologists and compare practice patterns with published primary care and preventive service guidelines. STUDY DESIGN: All 277 active fellows of The South Atlantic Association of Obstetricians and Gynecologists were mailed a self-administered questionnaire. The type of primary care offered by these physicians and their attitudes about the training of residents in obstetrics and gynecology were surveyed. Physicians were categorized as generalists or specialists on the basis of the completion of a fellowship program. Descriptive statistics and chi 2 analysis were used for statistical analysis. RESULTS: Completed surveys were returned by 82% of the fellows. The majority of the respondents perceived their practice as specialty care for women. Generalists offered recommended screening services to women of all ages with greater frequency than the specialists did (p = 0.05). Both groups did not provide care for the chronic medical illnesses most commonly seen in a primary care practice. The respondents favored more residency training in those common acute illnesses frequently encountered in a primary care setting. CONCLUSIONS: Obstetrician-gynecologists in The South Atlantic Association of Obstetricians and Gynecologists selectively practice primary care. These physicians did not support caring for chronic medical problems frequently treated in an ambulatory care practice.

Attitude of Health Personnel↗