RESUMEN
Introducción: El cuidado del adulto mayor disfuncional o dependiente, es un trabajo complejo que requiere paciencia y gusto de ayudar, ante ello es importante tomar en cuenta que las enfermeras (os) que brindan su servicio hacia este grupo etario en su día a día se enfrentan a distintos retos en su área de trabajo o incluso en su sociedad, mismos que se convierten en factores estresantes y colocan al profesional de enfermería en riesgo de adquirir trastornos de salud. Sin embargo, existen también elementos que permiten que el personal de enfermería pueda mantener un cuidado humano dirigido al adulto mayor, entre ellos se encuentran valores, la empatía y el apego. Objetivos: Analizar el cotidiano del profesional de enfermería en el cuidado dirigido a adultos mayores e identificar los factores que favorecen u obstaculizan el cuidado del profesional de enfermería a los adultos mayores hospitalizados. Los autores del fundamento teórico son Henri Lefebvre y Jean Watson. Estudio cualitativo, descriptivo, se realizaron entrevistas en profundidad a once licenciados en enfermería. Resultados: Se encontraron dos categorías con sus correspondientes subcategorías: 1. Praxis del cuidado transpersonal al adulto mayor (1.1 Tolerancia y respeto, 1.2 Empatía y relación de ayuda-confianza y 1.3 El tiempo y la creación de lazos afectivos) y Retos en el cotidiano del cuidado del adulto mayor (2.1 Sobrecarga de trabajo en el cotidiano, 2.2 Falta de recursos para la praxis diaria, 2.3 Espacio compartido con familiares del adulto mayor y 2.4 Falta de reconocimiento social ). Consideraciones finales: En el cotidiano del profesional de enfermería se encuentran distintos factores externos que pueden obstaculizar su sano desempeño como trabajador, entre ellos la sobrecarga de trabajo, la falta de recursos e incluso la falta de reconocimiento social sobre su labor; sin embargo, la praxis del cuidado tiene una naturaleza de humanismo respaldada por los valores de formación de cada profesional que les permite otorgar un cuidado de calidez.
The care of the dysfunctional or dependent older adult is a complex task that requires patience and a willingness to help, before it is important to take into account that the nurses who offer their services to this age group in their daily routine face different challenges in their area of work or even in their society, which become stressors and place the nursing professional at risk of acquiring health disorders However, there are also elements that allow nursing staff to maintain human care directed to the elderly, including values, empathy and attachment. Objectives: To analyze the daily routine of the nursing professional in the care directed to the elderly and to determine the factors that favor or hinder the care of the nursing professional to hospitalized older adults. The authors of the theoretical foundation are Henri Lefebvre and Jean Watson. Qualitative, descriptive study, interviews were conducted in depth to eleven graduates in nursery.Results: There were two categories with their corresponding subcategories: 1. Praxis of transpersonal care for the elderly (1.1 Tolerance and respect, 1.2 Empathy and good treatment and 1.3 Time and the creation of affective bonds) and Challenges in the daily care of the (2.1 Workload in daily life, 2.2 Lack of resources for daily praxis, 2.3 Shared space with relatives of the elderly and 2.4 Lack of social recognition) Final considerations: In the daily routine of the nursing professional are different external factors that may hinder their healthy performance as a worker, including work overload, lack of resources and even lack of social recognition of their work; However, the praxis of care has a nature of humanism backed by the values of training of each professional that allows them to provide a warmth care.
Asunto(s)
Humanos , Anciano , Riesgos Laborales , Anciano , Salud Laboral , Rol de la Enfermera , Atención de EnfermeríaRESUMEN
Twenty-five healthy volunteers were given 100 mg caffeine orally and several estimates of cytochrome P450 1A2 (CYP1A2) activity were evaluated. The validation was performed by correlation of different parameters in plasma, saliva, and urine to two measures of caffeine clearance, CL(oral) and CL(137X-->17X) that served as standards of reference. Two subjects were excluded because of noncompliance with a caffeine-free diet. In the remaining 23 subjects, both plasma and saliva total clearances of caffeine were highly correlated with each other (r(s) = 0.97, p < 0.0001). The ratio 17X/137X restricted to one sampling point taken 4 hours after dose, showed a high correlation (r(s)) with CL(oral) and CL(137X-->17X) in plasma (0.84/0.83) and saliva (0.82/0.77) (p < 0.0001 for all the correlation values) where 17X is 1,7-dimethylxanthine (paraxanthine) and 137X is 1,3,7-trimethylxanthine (caffeine). Additionally, the ratio (AFMU + 1U + 1X + 17U + 17X)/137X in a 0-24 hours urine sampling showed the highest correlation with CL(137X-->17X) (r(s) = 0.85, p < 0.001) where AFMU is 5-acetylamino-6-formylamino-3-methyluracil, 1U is 1-methyluracil, 1X is 1-methylxanthine, and 17U is 1,7-dimethyluric acid. The major estimates of CYP1A2 activity were significantly less in nonsmoking females, and this probably was related to the use of oral contraceptives in this subpopulation. In summary, among caffeine-based approaches for CYP1A2, the authors recommend either plasma or saliva 17X/137X ratio and the urinary (AFMU + 1U + 1X + 17U + 17X)/137X ratio during a sampling interval of at least 8 hours, starting at time zero since caffeine intake. These indices are simple, reliable, and relatively inexpensive estimates of CYP1A2 activity to be used in the study of human populations.
Asunto(s)
Cafeína/farmacocinética , Citocromo P-450 CYP1A2/metabolismo , Saliva/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The aim of this study was to find whether endogenous substances could modulate CYP3A activity. There is evidence that CYP3A, a major phase-I xenobiotic metabolizing enzyme, is present in human brain but, at the present time, endogenous substrates for such an enzyme remain to be identified. A possible linkage between the CYP2D6 enzyme and serotonergic transmission has been recently reported by our group. In the same manner, structurally related enzymes such as CYP3A could also be related to endogenous compounds. METHODS: CYP3A activity was measured using the enzyme-specific substrate midazolam in human liver microsomes. Several neurotransmitters, precursors, and their metabolites, corresponding to three different metabolic routes, were assayed as putative modulators of CYP3A enzyme activity. These comprised serotonergic, catecolaminergic, and GABAergic transmitters and precursors. The inhibitory capacity of ketoconazole, a competitive inhibitor of CYP3A, was also analyzed for comparison. RESULTS: The kinetic analysis of the midazolam 1-hydroxylase activity measured in microsomes from five human liver samples indicated Km values (mean +/- SD) of 5.8 +/- 4.9 microM, and Vmax values of 1.7 +/- 1.4 nmol min(-1) per mg microsomal protein in all the samples used in the study. Of the 14 substances analyzed, adrenaline, serotonin, and 5-hydroxytriptofol were full inhibitors of CYP3A enzyme activity (Ki values of 42.3, 26.4, and 43 microM, respectively). The remaining substances were weak inhibitors or had no inhibitory effect. CONCLUSION: Brain CYP3A activity could be modulated by some neurotransmitters and precursors.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/metabolismo , Epinefrina/metabolismo , Microsomas Hepáticos/metabolismo , Midazolam/metabolismo , Neurotransmisores/metabolismo , Oxidorreductasas N-Desmetilantes/metabolismo , Serotonina/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Citocromo P-450 CYP3A , Inhibidores Enzimáticos/farmacología , Epinefrina/farmacología , Humanos , Hidroxitriptofol/metabolismo , Hidroxitriptofol/farmacología , Técnicas In Vitro , Cetoconazol/farmacología , Microsomas Hepáticos/enzimología , Neurotransmisores/farmacología , Isoformas de Proteínas/metabolismo , Serotonina/farmacología , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
This study investigated to what extent fluvoxamine affects the pharmacokinetics of thioridazine (THD) in schizophrenic patients under steady-state conditions. Concentrations of THD, mesoridazine, and sulforidazine were measured in plasma samples obtained from 10 male inpatients, aged 36 to 78 years, at three different time points: A, during habitual monotherapy with THD at 88 +/-54 mg/day; B, after addition of a low dosage of fluvoxamine (25 mg twice a day) for 1 week; and C, 2 weeks after fluvoxamine discontinuation. After the addition of fluvoxamine, THD concentrations relative to time point A significantly increased approximately threefold from 0.40 to 1.21 micromol/L (225%) (p < 0.002), mesoridazine concentrations increased from 0.65 to 2.0 micromol/L (219%) (p < 0.004), and sulforidazine levels increased from 0.21 to 0.56 micromol/L (258%) (p < 0.004). The THD-mesoridazine and THD-sulforidazine ratios remained unchanged during the study. Mean plasma THD, mesoridazine, and sulforidazine levels decreased at time point C, but despite fluvoxamine discontinuation for 2 weeks, three patients continued to exhibit elevated concentrations of THD and its metabolites. In conclusion, fluvoxamine markedly interferes with the metabolism of THD, probably at the CYP2C19 and/or CYP1A2 enzyme level. Therefore, clinicians should be aware of the potential for a clinical drug interaction between both compounds, and careful monitoring of THD levels is valuable to prevent the accumulation of the drug and resulting toxicity.
Asunto(s)
Antipsicóticos/farmacocinética , Fluvoxamina/farmacocinética , Esquizofrenia/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Tioridazina/farmacocinética , Adulto , Anciano , Antipsicóticos/sangre , Antipsicóticos/uso terapéutico , Citocromo P-450 CYP2D6/genética , Interacciones Farmacológicas , Fluvoxamina/sangre , Fluvoxamina/uso terapéutico , Humanos , Masculino , Mesoridazina/sangre , Mesoridazina/farmacocinética , Mesoridazina/uso terapéutico , Persona de Mediana Edad , Esquizofrenia/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/sangre , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tioridazina/sangre , Tioridazina/uso terapéuticoRESUMEN
This is the first report describing the use and pharmacological characterization of nasal patency by both pressure rhinometry and acoustic rhinometry (AcR) in an experimental cat model of nasal congestion. In pressure rhinometry studies, aerosolized compound 48/80 (0.1-3.0%), a mast cell liberator, increased nasal airway resistance (NAR) 1.2 +/- 0.6, 5.8 +/- 0.5, 8.6 +/- 1.1 and 7.9 +/- 1.5 cmH2O.L/minute, respectively. Increases in NAR produced by compound 48/80 were associated with a 395% increase in histamine concentration found in the nasal lavage fluid. Pretreatment with the alpha-adrenoreceptor agonist, phenylpropanolamine (PPA; 0.1-3.0 mg/kg, i.v.), and the NO synthetase inhibitor, NG-nitro-L-arginine (L-NAME; 10 mg/kg, i.v.) attenuated the increases in NAR produced by compound 48/80. The histamine H1 antagonist chlorpheniramine (1.0 mg/kg, i.v.) and the H2 antagonist, ranitidine (1.0 mg/kg, i.v.) had no decongestant activity. Also without decongestant activity were the muscarinic antagonist atropine, the cyclooxygenase inhibitor indomethacin, and the 5-HT blocker methysergide. Aerosolized histamine (0.1-1.0%) also produced a dose dependent increase in NAR. In studies using acoustic rhinometry (AcR), intranasal application of compound 48/80 (0.1-1.0%) elicited pronounced decreases in nasal cavity volumes and minimum cross-sectional area (Amin). Pretreatment with PPA (3 mg/kg, i.v. or 10 mg/kg, p.o.) attenuated the decreases in nasal volume and Amin. The effects of topical intranasal histamine (0.1-1.0%) on nasal geometry were similar to compound 48/80. We conclude that the cat is a useful model for evaluating the pharmacological actions of potential nasal decongestants. Furthermore, we also conclude that AcR is a useful method for noninvasive assessment of nasal patency in a preclinical setting.
Asunto(s)
Acústica/instrumentación , Resistencia de las Vías Respiratorias , Modelos Animales de Enfermedad , Obstrucción Nasal/fisiopatología , Nariz/fisiopatología , Otolaringología/métodos , Aerosoles , Resistencia de las Vías Respiratorias/efectos de los fármacos , Animales , Gatos , Relación Dosis-Respuesta a Droga , Liberación de Histamina/efectos de los fármacos , Masculino , Obstrucción Nasal/inducido químicamente , Nariz/efectos de los fármacos , Otolaringología/instrumentación , Otolaringología/estadística & datos numéricos , Presión , Factores de Tiempo , p-Metoxi-N-metilfenetilaminaRESUMEN
Both clozapine (CLZ) and caffeine are CYP1A2 substrates. This study raises the hypothesis of whether caffeine withdrawal from the diet alters the metabolism and/or clinical status of patients receiving CLZ. Seven schizophrenic patients (six men and one woman) receiving monotherapy with CLZ at 271+/-102 mg/day (3.73+/-1.4 mg/kg) participated in the study. CLZ, norclozapine (NOR), and clozapine-N-oxide (NOX) were assayed in plasma by high-performance liquid chromatography at three different time points: A, with concomitant intake of caffeine from the diet; B, after caffeine withdrawal for 5 days; and C, after 2 weeks of rechallenge to habitual caffeine intake. The CYP1A2 activity was determined by means of a urinary caffeine test. After a caffeine-free diet for 5 days, CLZ concentrations relative to time point A decreased from 486 to 306 ng/mL (-47%) (p < 0.02), NOX levels decreased from 66 to 49 ng/mL (-31%) (p < 0.03), and the NOR/CLZ ratio significantly increased from 0.47 to 1.04 (185%) (p < 0.02). All parameters returned to initial figures at time point C. The NOR/CLZ ratio was significantly correlated to the CYP1A2 index (rs = 0.96, p < 0.0005). In conclusion, changes in the habitual caffeine intake alter the metabolism of CLZ in schizophrenic patients. Thus, patient intake of caffeine should be medically supervised, and the monitoring of CLZ and metabolite levels may be warranted. Furthermore, in those patients who receive therapy with CLZ, the NOR/CLZ ratio may provide an additional and valuable estimate of CYP1A2 activity.
Asunto(s)
Antipsicóticos/farmacocinética , Cafeína/efectos adversos , Clozapina/farmacocinética , Esquizofrenia/enzimología , Síndrome de Abstinencia a Sustancias/enzimología , Adulto , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Disponibilidad Biológica , Biotransformación , Cromatografía Líquida de Alta Presión , Clozapina/efectos adversos , Clozapina/análogos & derivados , Clozapina/uso terapéutico , Citocromo P-450 CYP1A2/sangre , Inhibidores del Citocromo P-450 CYP1A2 , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/diagnósticoRESUMEN
Tachykinin NK1 receptors are present on human pulmonary arteries. Addition of the specific tachykinin NK1 receptor agonist, [Met-OMe11]substance P produced a concentration-dependent relaxation (0.1 nM to 100 nM) in pulmonary arteries preconstricted with phenylephrine (30 microM). The EC50 (agonist concentration needed to produce 50% of the maximal relaxation) value for [Met-OMe11]substance P was 3.7+/-0.7 nM. The relaxation induced by [Met-OMe11]substance P was selectively inhibited by the tachykinin NK1 receptor antagonist CP 99994 (1 nM), with a pKb of 9.9+/-0.3. Treatment with the tachykinin NK2 receptor antagonist SR 48968 (100 nM) did not significantly affect the vasorelaxation due to [Met-OMe11]substance P (P > 0.05, one-way analysis of variance; ANOVA).
Asunto(s)
Arteria Pulmonar/fisiología , Receptores de Neuroquinina-1/fisiología , Vasodilatación , Relación Dosis-Respuesta a Droga , Humanos , Fenilefrina/farmacología , Piperidinas/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Receptores de Neuroquinina-1/efectos de los fármacos , Sustancia P/farmacología , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacosRESUMEN
Hydroxylation of midazolam (MDZ) is mediated almost exclusively by CYP3A isoforms. The authors describe a high-performance liquid chromatography assay involving MDZ, 1'-hydroxymidazolam, and 4-hydroxymidazolam in plasma. The compounds were eluted on an Ultrasphere ODS, 3-microm particle size, 7.5 cm x 4.6 mm reversed-phase column and monitored by ultraviolet absorbance at 254 nm. The composition of the mobile phase was 35.2% acetonitrile:4.8% methanol:60% buffer acetate (vol/vol/vol), 0.1 M, pH 4.7; the flow rate was 1 ml/minute. Calibration curves were linear (coefficients of correlation > 0.99) within the range of concentrations established (20 to 640 nM). Within- and between-day coefficients of variation were consistently better than 8%. The overall recovery was >90% and the lowest detectable concentration was 8 nM. This approach provides a simple, rapid, and sensitive assessment of MDZ and metabolites in plasma, with a very good accuracy and precision, which enables it as an in vivo marker of CYP3A activity in humans.
Asunto(s)
Ansiolíticos/sangre , Hidrocarburo de Aril Hidroxilasas , Cromatografía Líquida de Alta Presión , Sistema Enzimático del Citocromo P-450/sangre , Monitoreo de Drogas/métodos , Midazolam/sangre , Oxidorreductasas N-Desmetilantes/sangre , Adulto , Biomarcadores/sangre , Cromatografía Líquida de Alta Presión/métodos , Citocromo P-450 CYP3A , Humanos , Masculino , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
The dopamine D1A receptor subtype was identified in rat kidney with both light microscopic immunohistochemistry and electron microscopic immunocytochemistry. Antipeptide polyclonal antisera were directed to both extracellular and intracellular regions of the native receptor. The use of such receptor-subtype-selective antibodies allows for the identification of specific dopamine receptor subtype clones that are not distinguished by current pharmacological or receptor-ligand binding technology. Selectivity of the antipeptide antisera was validated by their ability to recognize native receptor protein expressed in permanently transfected mouse LTK- cells. In the rat kidney, D1A receptor protein was localized to the juxtaglomerular apparatus (JGA), proximal tubule, distal tubule, cortical collecting duct, and renal vasculature. In the JGA, the receptor was predominantly located in the arteriolar smooth muscle layer within cytoplasmic granules previously shown to contain renin. In the proximal tubules, staining was localized both on the brush-border and basolateral membranes. The D1A receptor, which is present in the central nervous system, is now identified in the rat kidney at those sites previously labeled as DA1 receptor sites on the basis of pharmacological binding studies. These results suggest that at least some of the renal dopamine DA1 receptors correspond structurally to the central dopamine D1A receptor.
Asunto(s)
Riñón/metabolismo , Receptores de Dopamina D1/análisis , Secuencia de Aminoácidos , Animales , Anticuerpos , Arterias/citología , Arterias/metabolismo , Arterias/ultraestructura , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Inmunohistoquímica , Riñón/irrigación sanguínea , Riñón/citología , Corteza Renal/metabolismo , Corteza Renal/ultraestructura , Túbulos Renales Colectores/metabolismo , Túbulos Renales Colectores/ultraestructura , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/ultraestructura , Ratones , Microscopía Inmunoelectrónica , Modelos Estructurales , Datos de Secuencia Molecular , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/ultraestructura , Péptidos/química , Péptidos/inmunología , Estructura Secundaria de Proteína , Ratas , Receptores de Dopamina D1/química , Proteínas Recombinantes/análisis , Proteínas Recombinantes/biosíntesis , TransfecciónRESUMEN
Structural and stereological studies of mouse atrial myocardial cells, carried out in the same fashion as our previous investigations on mouse ventricle, demonstrate an extremely well-developed sarcoplasmic reticulum (SR) in atrial cells. The volume fraction (Vv) of the SR exceeds 12% in mouse atrial cells; perimyofibrillar network SR constitutes the major portion. We have confirmed the findings of Bossen et al. (1981, Tissue Cell 13, 71-77) of a difference between atria in terms of coupling density, the right atrium having a significantly lower incidence of interior junctional SR than the left. The SR of mouse atrium comprises a rich variety of specialized segments, including the IJSR, peripheral junctional SR, corbular SR, cisternal SR (including regions similar to fenestrated collars of striated skeletal muscle SR), as well as a peculiar form of extended junctional SR (EJSR). Although less frequent in occurrence than corbular SR, the EJSR seems closely related, since it occurs in multiple clusters at or near the Z-line regions, contains internal granular densities, and bears surface-connected structures resembling junctional processes. Seen in thin sections, mouse atrial EJSR elements are more complex than corbular SR, being larger in diameter and frequently circular in profile. Thick-section and serial-section analyses reveal that bodies of EJSR are in fact hollow spheroids. The transverse-axial tubular system of mouse atrium is rather poorly developed in comparison to its ventricular counterpart. The Golgi apparatus and associated specific atrial granules are prominent cell components. "Focal ellipsoidal deposits" (FEDs) previously described by Page and co-workers (1986, Amer. J. Physiol.) are consistently located adjacent to the Golgi region, but immunocytochemical staining for two different segments of atrial natriuretic peptide reveals no specific reaction in FEDs, whereas the SAGs are densely labeled for both antibodies.