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1.
Ann Pharm Fr ; 81(1): 53-63, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35738438

RESUMEN

OBJECTIVES: To better understand the role of pharmacists in patient education and counselling: describe the perception of knowledge exchange (KE) between asthma/pulmonary arterial hypertension patients and pharmacists (hospital/community) according to four dimensions (4C-typology): cure (C1), care (C2); coordination/supply chain (C3), characteristics of the pathophysiology/disease mechanisms (C4); factors correlated with KE. METHODS: A mixed methods approach was used. Part A: data from semi-structured patient interviews were processed (thematic analysis), and a questionnaire developed. Part B: completed patient questionnaires were processed by correspondence factor analysis. RESULTS: KE (4C-typology) was correlated with pathology, disease severity, disease duration, age, hospital/community pharmacist. Patients expected pharmacists to provide C2/C3 services. KE with pharmacists covered C1/C2/C3, and with physicians, C1/C2/C4. While patients perceived KE as a means of self-learning to improve self-care skills, the two-way nature meant it provided specific experiential information feedback to pharmacists. CONCLUSIONS: This 4C-typology provides a holistic framework for optimising the pharmacists' role in education and counselling of patients with chronic diseases.


Asunto(s)
Asma , Servicios Comunitarios de Farmacia , Hipertensión Arterial Pulmonar , Humanos , Farmacéuticos/psicología , Educación del Paciente como Asunto , Asma/terapia , Consejo , Rol Profesional , Actitud del Personal de Salud
2.
Ann Pharm Fr ; 79(1): 44-52, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32485144

RESUMEN

INTRODUCTION: Cancer patients use complementary and alternative medicines (CAM) to improve their well-being. Little is known about real risks. OBJECTIVE: To highlight 3 different types of axes: 1/cancer patients' perceptions concerning CAM; 2/misinformation/miscommunication about CAM; 3/CAM toxicity (direct toxicity, CAM-anticancer drugs, CAM-cancer interactions). METHOD: A questionnaire was proposed to cancer patients for 2 months. The CAM toxicity was analyzed if patients documented their drugs and CAM. RESULTS: Eighty-five patients responded: 72/85 were taking≥1CAM. In total, 95% patients were satisfied. There was an increasing CAM intake after cancer diagnosis. One hundred and seventeen different CAM were identified (63 herbs, 24 essential oils, 28 food supplements, 2 homeopathic specialities). Only 30/85 were aware CAM could interact with anticancer drugs. No other type of risk was perceived. INFORMATION SOURCES: 43/85 Internet, 38/85 general practitioner, 38/85 community pharmacist, 32/85 entourage, 25/85 other patients, 22/85 oncologist. In total, 81.3% questioned healthcare professionals (HCP) about CAM. Twelve patients noticed HCP lacked knowledge regarding CAM. The toxicity analysis was carried out for 24 patients who consumed 1 to 24CAM. In total, 133CAM were reported, including 87 different CAM. For only 43CAM/87, studies were found. All patients presented≥1risk: 14 at risk of CAM-cancer interactions, 15 of CAM-anticancer drug interactions, 21 of CAM direct toxicities. CONCLUSION: Many CAM are used by patients. The diagnosis of cancer favors their use. The risks are manifold: low perception of risk that can be induced by CAM, diverse and insecure sources of information and many potential toxicities that are not scientifically documented.


Asunto(s)
Terapias Complementarias/efectos adversos , Neoplasias/terapia , Adolescente , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Comunicación , Suplementos Dietéticos , Interacciones Farmacológicas , Femenino , Francia , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Materia Medica , Persona de Mediana Edad , Educación del Paciente como Asunto , Preparaciones de Plantas , Medición de Riesgo , Encuestas y Cuestionarios , Adulto Joven
3.
Ann Pharm Fr ; 79(5): 582-588, 2021 Sep.
Artículo en Francés | MEDLINE | ID: mdl-33516720

RESUMEN

Medical device made to measure by 3D printing are now emerging in hospital. In order to improve the precision of surgery and facilitate the treatment of complicated cases, patient specific surgical guides for dental implantology are made by stereolithography in our facial surgical unit. This new activity requires to ensure the safety of patients and health personnel by validating the various step of the manufacturing circuit. In this context, the goal of this work was to study the quality of autoclave sterilisation of the patient specific surgical guide made to measure in our hospital. A protocol of sterility test was designed and validated. Sterility of implantology guides 0, 7, 14 and 28 days after sterilisation was checked. The impact of the autoclave sterilisation on the medical device structure was evaluated by visual check and during surgeries. The sterility of the implantology guides up to 28 days after sterilisation was also validated. The protocol of sterility test executed can be extended to other hospitals interested in validating a sterility test. No deformation was observed by surgeons during the dental implant process. Future studies may be necessary to check the accurate impact of sterilisation on surgical guide structure.


Asunto(s)
Infertilidad , Cirugía Asistida por Computador , Diseño Asistido por Computadora , Hospitales , Humanos , Esterilización
4.
Ann Pharm Fr ; 75(6): 480-488, 2017 Nov.
Artículo en Francés | MEDLINE | ID: mdl-28818320

RESUMEN

OBJECTIVES: The economic impact of therapeutic innovations on the hospital patient management cannot be easily estimated. The objective of this study is to illustrate the use of a Delphi survey as a support tool to identify the changes following the use of idarucizumab in dabigatran-treated patients with uncontrolled/life-threatening bleeding or who required emergency surgery/urgent procedures. METHODS: The Delphi questionnaires have been administrated to 8 emergency physicians or anesthetists from 6 different hospital centers. Following the answers, an economic valorization has been carried out on every parameter on which a consensus was reached (at least 4 answers showing an identical trend). A mean management cost for each etiology with and without the use of idarucizumab has thus been identified. RESULTS: For gastro-intestinal and other life-threatening bleedings (excepted intracranial bleedings), the total management cost of the hospital stay was respectively 6058 € (-35%) and 6219 € (-34%) following the use of the reversal agent. The hospital management cost for intracranial bleeding is slightly increasing to 9790 € (+3%). The cost of a stay for emergency surgery decreases to 6962€ (-2%). CONCLUSIONS: This study shows a positive economic impact following the use of the dabigatran-specific reversal agent for patients with uncontrolled/life-threatening bleeding excepted in the case of intracranial bleeding. Moreover, it points out that a Delphi survey is an easy way to predict the hospital economic impact of a therapeutic innovation when no other evaluation is possible.


Asunto(s)
Anticuerpos Monoclonales Humanizados/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antitrombinas/farmacología , Dabigatrán/antagonistas & inhibidores , Economía Hospitalaria/tendencias , Hemorragia/tratamiento farmacológico , Hemorragia/economía , Antitrombinas/economía , Dabigatrán/economía , Dabigatrán/farmacología , Técnica Delphi , Costos de los Medicamentos , Francia , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/economía , Hemorragia/inducido químicamente , Humanos , Encuestas y Cuestionarios
5.
Int J Clin Pharm ; 41(1): 42-48, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30610545

RESUMEN

Background Citalopram and escitalopram can both induce dose-dependent QT prolongation. The risk of arrhythmia may be increased with concomitant use of other drugs that induce QT prolongation. Objective To evaluate the prevalence and impact of pharmacist interventions on the combination of citalopram or escitalopram with other drugs that induce QT prolongation. Setting A French hospital with 517 computerized beds. Method All cardiac adverse drug reactions (ADRs) related to citalopram or escitalopram reported to the French pharmacovigilance database (FPDB) were analyzed. Then, over a 6-month period, all computerized prescriptions including citalopram or escitalopram and drug-drug interactions (DDI) were analyzed by pharmacists using a computerized provider order entry system (DXCare®, Medasys). Results Only 27 cardiac ADRs related to citalopram or escitalopram were reported in the database. Among the 57,857 prescriptions and 2116 contraindicated DDIs (3.7 %) that were analyzed. 444 DDIs (0.8 %) were considered to be clinically relevant by pharmacists and physicians and 168 (i.e., approximately 30 %) were related to a combination including citalopram or escitalopram. Most of the prescriptions related to DDIs including citalopram or escitalopram were discontinued in response to a pharmacist intervention when initiated during the hospital stay. Conclusion A high number of hospital prescriptions including citalopram or escitalopram with another QT-prolonging drug occurred, highlighting the importance of involvement of clinical pharmacists in prevention of potential ADRs related to such contraindications.


Asunto(s)
Citalopram/efectos adversos , Interacciones Farmacológicas/fisiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/prevención & control , Farmacéuticos/normas , Adulto , Anciano , Antiarrítmicos/administración & dosificación , Antiarrítmicos/efectos adversos , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/prevención & control , Citalopram/administración & dosificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Síndrome de QT Prolongado/epidemiología , Masculino , Persona de Mediana Edad , Farmacovigilancia , Servicio de Farmacia en Hospital/normas , Rol Profesional
6.
Diabetes Metab ; 32(6): 611-6, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17296515

RESUMEN

It's established that adherence rates to treatment are bad in chronic illnesses. The number of medicines prescribed and the rates of daily dosages have been shown to be of major influence for therapeutic compliance in AIDS or hypertension. Nevertheless, data on adherence to prescribed medications amongst diabetics are scarce. The aim of our study was to evaluate parameters influencing therapeutic compliance in type 2 diabetes. Adherence to treatment was evaluated by a questionnaire filled out during patient's hospitalisation in the diabetology department of a French general hospital of 450 beds. Factors influencing compliance were quantified taking into account demographic characteristics of our population, the treatments used, biological and medical data. 94 patients hospitalised for uncontrolled diabetes, aged 41-89 years, were studied. Non-adherence rate was high, 33 of them showed poor adherence to their drug treatment. Non-compliers were younger than compliant patients (56.5+/-12.1 vs. 65.5+/-12.5 years old; P<0.0001) and with a lower social position. Clinically, they were characterised by a shorter duration of diabetes and a lower number of clinical complications as macroangiopathy (6.9 vs. 33.3%; P=0.006). The number of daily doses or medicines didn't affect adherence rate. Improved control in therapeutic compliance may lead to better diabetic patients education. The implication is that instead of increasing the dose, changing the medication, or adding a second drug when glucose and HbA(1c)levels are high, clinicians should consider counselling patients on how to improve therapeutic compliance.


Asunto(s)
Diabetes Mellitus Tipo 2/psicología , Cooperación del Paciente/psicología , Negativa del Paciente al Tratamiento/estadística & datos numéricos , Adulto , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino
7.
Hypertension ; 32(1): 166-9, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9674655

RESUMEN

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.


Asunto(s)
Aorta Abdominal/fisiología , Hipertensión/fisiopatología , Músculo Liso Vascular/citología , Adaptación Fisiológica , Animales , Aorta Abdominal/patología , Aorta Abdominal/ultraestructura , Fenómenos Biomecánicos , Citoplasma , Elastina/fisiología , Matriz Extracelular/fisiología , Técnicas Histológicas , Hipertensión/patología , Masculino , Microscopía Electrónica , Músculo Liso Vascular/fisiopatología , Orgánulos , Ratas , Ratas Endogámicas SHR , Ratas Wistar
8.
Hypertension ; 26(2): 337-40, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7635544

RESUMEN

The purpose of the present study was to determine the effects of chronic sinoaortic denervation on the mechanical properties and composition of the abdominal aorta in Wistar rats. We used a high-resolution echotracking system to determine in situ under physiological conditions of blood flow and arterial wall innervation the aortic diameter-, compliance-, and distensibility-pressure curves in 16-week-old anesthetized rats that had been denervated at 10 weeks of age for 6 weeks (n = 8). Compared with sham-operated rats (n = 8) we observed a marked reduction of baroreflex response and increase in overall mean blood pressure variability as measured by standard deviation and spectral analysis in sinoaortic-denervated rats. Mean blood pressure was not affected by sinoaortic denervation in both conscious and anesthetized rats. Sinoaortic denervation significantly shifted the distensibility-pressure curve toward lower levels of distensibility, indicating a decreased aortic distensibility for a given level of arterial pressure. Sinoaortic denervation produced a significant increase of aortic wall cross-sectional area and collagen content, one of the less-distensible components of the arterial wall. These results suggest that intact arterial baroreceptors are necessary for maintaining normal functional and structural properties of large arteries in rats. The reduction in arterial distensibility in chronic sinoaortic-denervated rats may have resulted from different factors, including the initial hypertensive phase, aortic wall hypertrophy, and increase in collagen content. The changes in aortic wall structure and related reduction in aortic distensibility, in addition to other mechanisms, might have been direct consequences of an increased blood pressure variability.


Asunto(s)
Aorta/inervación , Aorta/fisiopatología , Hemodinámica/fisiología , Animales , Colágeno/análisis , Desnervación , Elastina/análisis , Masculino , Ratas , Ratas Wistar , Túnica Media/metabolismo , Túnica Media/patología , Resistencia Vascular/fisiología
9.
Eur J Pharmacol ; 311(2-3): 241-8, 1996 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-8891605

RESUMEN

We have previously shown that rat atrial natriuretic peptide (ANP) reduces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endothelin-1 has been described as a secretagogue for natriuretic peptides in vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 secretion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of this study was to determine whether ANP attenuated the endothelin-1-induced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular myocytes in response to endothelin-1, chicken natriuretic peptide (ChNP), and both. We also used Northern blot analysis to study the time course of ChNP expression in response to endothelin-1. Endothelin-1 (10(-8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 x 10(-7) M) did not significantly change the amplitude of contraction in basal conditions, it prevented the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min after endothelin-1 exposure (P < 0.05). Endothelin-1 significantly increased the accumulation of ChNP mRNA in chick ventricular myocytes as early as the 30 min after exposure (P < 0.05), with a maximal effect after 2 h of stimulation (P < 0.01); no effect was observed after 4 h. These data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile function of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interaction.


Asunto(s)
Factor Natriurético Atrial/farmacología , Endotelina-1/farmacología , Contracción Miocárdica/efectos de los fármacos , Análisis de Varianza , Animales , Northern Blotting , Células Cultivadas/efectos de los fármacos , Embrión de Pollo , Endotelina-1/antagonistas & inhibidores , Expresión Génica , Humanos , ARN Mensajero/aislamiento & purificación , Ratas
10.
Life Sci ; 62(14): 1271-80, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9570342

RESUMEN

In an experimental study we measured changes in hematological, biochemical and cortisol parameters in 6-week-old Swiss mice continuously exposed to ELF generated by a transformer station and high current bus bars. Mean daily exposure of 5.0 microT was maintained for 350 days. Hematological parameters were compared to those of control mice (n=12) exposed to a field level lower than 0.1 microT. Serum biochemical parameters (sodium, potassium, chloride, calcium, magnesium, phosphorus, amylase, creatine phosphokinase, and lactate dehydrogenase) were measured after 28 days of exposure and serum cortisol after 90 and 190 days. Granulocyte/macrophage colony-forming cells (GM-CFC) were counted at the end of the 350-day exposure. On day 20, exposed animals showed a significant decrease in leukocyte, erythrocyte, lymphocyte and monocyte counts and in hemoglobin and hematocrit values, while MCV increased. On days 43 and 63 no significant difference was observed in leukocyte and erythrocyte values, as if hemopoiesis had recovered. On day 90, a significant fall in the leukocyte, polynuclear neutrophil and eosinophil counts was observed in the exposed animals. No significant difference was noted in the biochemical parameters studied. On day 190, exposed animals had neutropenia and a decrease in the cortisol value. On day 350, no significant difference in hematological parameters was noted. Individual differences in sensitivity were observed, as 8 mice in the exposed group showed a significant decrease in the leukocyte, polymorphonuclear neutrophil and GM-CFC counts, while in two mice there was a significant increase in these same values compared to those unexposed mice.


Asunto(s)
Campos Electromagnéticos , Células Madre Hematopoyéticas/fisiología , Hidrocortisona/sangre , Amilasas/sangre , Animales , Cloruros/sangre , Pruebas Hematológicas , L-Lactato Deshidrogenasa/sangre , Magnesio/sangre , Masculino , Ratones , Potasio/sangre , Sodio/sangre , Factores de Tiempo
11.
Arch Environ Health ; 53(2): 87-92, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9577931

RESUMEN

A survey of neurovegetative and hematologic disorders was conducted in a population (n = 13) exposed occupationally to environmental electromagnetic fields; the population was matched with 13 control subjects. The exposed subjects worked at least 8 h/d for 1-5 y in premises located above transformers and high-tension cables, and the subjects were submitted to low-frequency electromagnetic fields (i.e., 50 Hz) of 0.2 microT-6.6 microT. The subjects were matched with respect to socioeconomic category, sex, and age with a control population of subjects that worked in premises outside of the immediate vicinity of transformers or high-tension cables. The exposed population had a significant increase in degree of certain neurovegetative disorders (i.e., physical fatigue, psychical asthenia, lipothymia, decreased libido, melancholy, depressive tendency, and irritability). In addition, the population experienced a significant fall in total lymphocytes and CD4, CD3, and CD2 lymphocytes, as well as a rise in NK cells. Leukopenia and neutropenia were also observed in two persons permanently exposed to doses of 1.2-6.6 microT. The disorders disappeared when exposure stopped, and they reappeared on reexposure.


Asunto(s)
Depresión/etiología , Campos Electromagnéticos/efectos adversos , Inmunidad Celular/efectos de la radiación , Recuento de Leucocitos/efectos de la radiación , Adulto , Recuento de Linfocito CD4/efectos de la radiación , Suministros de Energía Eléctrica , Electricidad , Monitoreo del Ambiente , Fatiga/etiología , Femenino , Humanos , Células Asesinas Naturales/efectos de la radiación , Leucopenia/etiología , Libido/efectos de la radiación , Masculino , Neutropenia/etiología , Neutrófilos/efectos de la radiación , Centrales Eléctricas
12.
Therapie ; 54(1): 85-91, 1999.
Artículo en Francés | MEDLINE | ID: mdl-10216430

RESUMEN

The objective of the present study was to determine the viscoelastic properties of the common carotid artery in 35 patients with aortic aneurysm before surgery (AAA) (age 71 years, range 61-84), in comparison with 48 patients with essential hypertension (HT: 50 years, range 24-88) and 44 normotensive subjects (NT: 44 years, range 23-85). The second objective was to establish the relations between common carotid artery (CCA) viscoelastic properties and histologic lesions observed on AAA segments, obtained after surgery. CCA diameter was larger and distensibility smaller in AAA patients than in HT and NT. Distensibility of the aortic aneurysm was smaller than that of upstream 'normal' aorta, itself being smaller than control aortas. AAA wall lesions were extensive, associating adventitial and medial fibrosis, elastolysis, smooth muscle rarefaction, neovascularization, inflammation and plaques. The grade of these lesions was not correlated with the mechanical properties of the aorta and CCA; however, they could explain their qualitative alterations. AAA is characterized by severe stiffening and dilatation of large arteries distant from the aneurysm location. Whether this pattern of arterial phenotype is explained by the increase in stiff material (collagen) and the rarefaction of distensible material (smooth muscle and elastin) remains to be determined.


Asunto(s)
Aorta Abdominal/fisiopatología , Aneurisma de la Aorta Abdominal/fisiopatología , Arteria Carótida Común/fisiopatología , Matriz Extracelular/fisiología , Hipertensión/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/cirugía , Arteria Carótida Común/fisiología , Elasticidad , Matriz Extracelular/química , Matriz Extracelular/patología , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/fisiología , Músculo Liso Vascular/fisiopatología , Valores de Referencia , Viscosidad
15.
J Mol Cell Cardiol ; 29(2): 677-87, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9140825

RESUMEN

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.


Asunto(s)
Ventrículos Cardíacos/citología , Contracción Miocárdica/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacología , Agonistas Adrenérgicos beta/farmacología , Animales , Arginina/metabolismo , Arginina/farmacología , Calcio/metabolismo , Calcio/farmacología , Embrión de Pollo , AMP Cíclico/química , AMP Cíclico/metabolismo , Ferrocianuros/farmacología , Ventrículos Cardíacos/embriología , Isoproterenol/farmacología , Óxido Nítrico Sintasa/metabolismo , Nitroprusiato/farmacología , Nucleótidos Cíclicos/química , Nucleótidos Cíclicos/metabolismo , Especificidad por Sustrato , Vasodilatadores/farmacología
16.
Can J Physiol Pharmacol ; 74(7): 842-9, 1996 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8946071

RESUMEN

This article reviews the effects of aging and hypertension on geometrical (lumen and arterial wall thickness) and functional (distensibility) properties of large and medium-sized arteries in humans. Several clinical and animal studies show that arterial wall hypertrophy does not increase the elastic modulus of the arterial wall material during sustained essential hypertension. The structural changes associated with either hypertension or aging have opposing effects on arterial distensibility, under similar transmural conditions: the former increasing it, the latter decreasing it. Thus, hypertension cannot be assimilated to aging. The structural and functional changes of the arterial wall material that are associated with the hypertension-induced hypertrophy could be a means by which medium-sized arteries maintain their distensibility characteristics despite increased distending pressure, and large arteries compensate for the age-induced decrease in arterial compliance.


Asunto(s)
Envejecimiento/fisiología , Arterias/fisiopatología , Hipertensión/fisiopatología , Animales , Arterias/patología , Arteria Carótida Común/fisiopatología , Hemodinámica/fisiología , Humanos , Hipertensión/patología , Hipertrofia
17.
Pathol Biol (Paris) ; 47(7): 669-76, 1999 Sep.
Artículo en Francés | MEDLINE | ID: mdl-10522257

RESUMEN

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.


Asunto(s)
Arterias/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Matriz Extracelular/patología , Animales , Arterias/patología , Enfermedades Cardiovasculares/patología , Humanos , Factores de Riesgo
18.
J Clin Pharm Ther ; 22(2): 135-40, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9373812

RESUMEN

BACKGROUND AND OBJECTIVES: FK 506 is an immunosuppressive macrolide advocated for prevention of graft rejection. Plasma or blood FK 506 levels must be determined to strike a balance between FK 506 toxicity and graft rejection. The first aim of this study was to compare an automated microparticle enzyme immunosorbent assay (MEIA) method (on whole blood) with the reference enzyme-linked immunosorbent assay (ELISA) method (on plasma). A second aim was to compare the two methods for prediction of FK 506 nephrotoxicity. PATIENTS AND METHODS: Forty-seven patients were studied comprising 128 samples. All were treated with FK 506 on a compassionate basis. For each patient, the concentrations of FK 506 were determined in plasma by means of ELISA and in whole blood by MEIA. RESULTS: The repeatability and the reproducibility of these two methods were similar. The inter-patient correlation coefficient between MEIA and ELISA, determined on 128 samples from 47 liver recipients, was satisfactory (r = 0.82). From these 47 patients, the intra-patient correlation coefficients were calculated for 17 of them. The intra-patient correlation coefficients were between 0.63 and 0.98 for 15 patients, and between 0.26 and 0.55 in the remaining two cases. Mean creatinine plasma levels in the 55 samples below the median FK 506 value in the MEIA method and in the 55 with values above the median (120 and 134 mumol/litre, respectively) were significantly different (P < 0.05), as were those using the reference ELISA methods (115 and 139 mumol/litre, P < 0.01). In contrast, there was no significant difference between the mean creatinine plasma levels in the 55 samples with FK 506 levels below the median using both methods or between those above the median. CONCLUSION: The automated MEIA method, being simpler and more rapid than the ELISA method, should now be preferred for therapeutic monitoring of FK 506.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Inmunosupresores/sangre , Trasplante de Hígado/inmunología , Tacrolimus/sangre , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Inmunosupresores/farmacocinética , Masculino , Persona de Mediana Edad , Estadística como Asunto , Tacrolimus/farmacocinética
19.
Arterioscler Thromb Vasc Biol ; 18(7): 1027-34, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9672062

RESUMEN

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.


Asunto(s)
Aorta/fisiopatología , Fibronectinas/genética , Expresión Génica , Hipertensión/fisiopatología , Animales , Antígenos CD/análisis , Antígenos CD/genética , Northern Blotting , Elasticidad , Matriz Extracelular/fisiología , Fibronectinas/análisis , Hemodinámica , Hipertensión/genética , Integrina alfa5 , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Estrés Mecánico
20.
Arterioscler Thromb Vasc Biol ; 17(7): 1346-55, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9261266

RESUMEN

Arterial wall viscosity (AWV) is a potential source of energy dissipation in circulation. That arteries, which are known to be markedly viscous in vitro, have lower viscosity in vivo has been suggested but not demonstrated under similar pressure conditions. Endothelium, which may modulate AWV through smooth muscle tone, could contribute to the low level of viscosity in vivo. Our objectives were first to compare AWV of the rat abdominal aorta, in vivo and in vitro, with similar pulse-pressure waves, and second, to determine whether endothelial function influences AWV in vivo and in vitro. The diameter of the abdominal aorta and distending pressure were measured in vivo and in vitro with a high-resolution echotracking system and a micromanometer, respectively. AWV was calculated as the area of the pressure-volume curve hysteresis. After in vivo examination, the arterial segments were isolated in vitro and submitted to resynthesized pressure waves identical to those recorded in vivo. Deendothelialization was performed in vivo by balloon rubbing; then arteries were examined either in vivo or in vitro. AWV was markedly lower in vivo than in vitro (6.6 +/- 0.7 versus 22.7 +/- 3.7 J.m-1.10(-5), respectively; P < .001). After deendothelialization, a sustained 40% increased AWV was observed during a 15-minute follow-up (P < .01). In vitro, deendothelialized arteries have a 64% higher AWV than segments with endothelium (P < .01). Our results indicate that the physiological effective viscosity, measured in vivo in intact animals, is threefold lower than the intrinsic viscosity of the arterial wall, measured in vitro. Endothelium removal determines a sustained increase in AWV, either in vivo or in vitro. These results suggest that active mechanisms compensate for intrinsic viscosity under physiological conditions. One of these energy-saving mechanisms might be dependent on normal endothelial function.


Asunto(s)
Aorta Abdominal/fisiología , Endotelio Vascular/fisiología , Animales , Presión Sanguínea , Elasticidad , Técnicas In Vitro , Masculino , Músculo Liso Vascular/fisiología , Ratas , Ratas Wistar , Vasodilatación , Viscosidad
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