RESUMEN
OBJECTIVE AND DESIGN: The aim of the study was to evaluate the vasoconstrictive activity of four new galenic preparations of hydrocortisone and to compare it with concentration-equivalent reference preparations. The study comprised two study phases: the pilot study phase and the main study phase. During open, nonrandomized pilot study, the optimal administration period was tested. The main study was performed in a randomized, double-blind intraindividual comparative design. SUBJECTS: Twenty male and female volunteers with healthy skin who responded to topically applied clobetasol-17-propionate before entering the trial participated in this study. TREATMENT: All subjects received the same treatments. The test preparations new galenic formulation (NGF) hydrocortisone 0.25% cream, NGF hydrocortisone acetate 0.25% cream, NGF hydrocortisone 0.5% cream, and NGF hydrocortisone 1.0% cream were compared with the respective reference preparations Soventol hydrocortisone (hydrocortisone acetate 0.25%), Hydroderm HC 0.5% cream (hydrocortisone 0.5%), Hydrogalen cream (hydrocortisone 1.0%) and placebo (vehicle of test preparations). METHOD: The topical preparations were applied occlusively for 2 h (pilot study) or 24 h (main study) on outlined areas (5 x 5 cm with a distance of 3 cm) of both forearms (4 areas for each). Assessment of vasoconstriction was performed before treatment, and 0.5, 4, 6 and 24 h after treatment (observation period) using a subjective rating scale (OLSEN vasoconstriction score) and measuring the colorimetric parameter a* (redness) by use of the Chroma-Meter (Minolta company, Ahrensburg, Germany). RESULTS: A significant vasoconstriction (positive blanching effect) was measured by use of chromametry for test preparations hydrocortisone 0.25% cream, hydrocortisone 0.5% cream, hydrocortisone 1.0% cream and for the reference preparation Hydrogalen cream compared to placebo 30 min after the end of treatment. In contrast, the reference preparations Soventol hydrocortisone and Hydroderm HC 0.5% did not differ significantly from placebo 30 min after treatment. No statistically significant effect of all formulations was observed 4-24 h after treatment in comparison with placebo. CONCLUSIONS: The vasoconstrictive efficacy of test preparations was mostly stronger than the concentration-equivalent reference preparations. This effect was achieved by use of new galenics of test preparations resulting in enhanced skin penetration and improved efficiency. No unwanted side effects were observed during the course of the study despite increased efficacy of the topically applied test preparations.
Asunto(s)
Antiinflamatorios/farmacología , Hidrocortisona/farmacología , Piel/irrigación sanguínea , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Administración Cutánea , Adulto , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Antiinflamatorios/metabolismo , Bioensayo/métodos , Bioensayo/normas , Química Farmacéutica , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Hidrocortisona/administración & dosificación , Hidrocortisona/análogos & derivados , Hidrocortisona/química , Hidrocortisona/metabolismo , Masculino , Persona de Mediana Edad , Pomadas , Proyectos Piloto , Estándares de Referencia , Absorción Cutánea , Factores de Tiempo , Vasoconstrictores/administración & dosificación , Vasoconstrictores/química , Vasoconstrictores/metabolismoRESUMEN
METHODS: A double-blind multicenter study involving 89 patients with mild-to-moderate essential hypertension was performed to compare the efficacy and tolerability of amlodipine and enalapril. Following a placebo-controlled run-in phase, treatment was initiated with a daily dose 5 mg amlodipine or enalapril. In the second week of treatment, the daily dose of enalapril was increased to 10 mg. After two weeks of treatment, the amlodipine dose was increased from 5 to 10 mg, the enalapril dose from 10 to 20 mg if the diastolic seated blood pressure exceeded 90 mmHg. RESULTS: Mean systolic and diastolic blood pressures decreased in the amlodipine group from, respectively, 158 +/- 17/101 +/- 6 mmHg to 142 +/- 14/87 +/- 11 mmHg, and in the enalapril group from 157 +/- 15/102 +/- 5 mmHg to 140 +/- 16/88 +/- 12 mmHg. The reduction in blood pressure was statistically significant in both groups (p < 0.0001), but the difference in blood pressure lowering effect of the two treatments was not statistically significant. The target blood pressure (diastolic BP seated < 90 mmHg) was achieved in 24 patients (75%) in the amlodipine group, and 23 patients (68%) in the enalapril group. Neither group experienced any severe adverse reactions. Side effects were seen in 3 patients of the amlodipine group and in 6 of the enalapril group.
Asunto(s)
Amlodipino/administración & dosificación , Enalapril/administración & dosificación , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Amlodipino/efectos adversos , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Enalapril/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In 1980 Oehme and co-workers [11] reported that Substance P (SP) has a dual effect on nociception, which is related to the pain threshold before SP administration. Our recent results showed that the N-terminal part of the SP sequence may be important to the hyperalgesic action, and the C-terminal part to the analgesic action of this peptide. The hyperalgesic effect of SP (and N-terminal fragments of SP) seems to be related to the "anti-stress" effect which was first demonstrated by Hecht and co-workers [5] and Oehme and co-workers [12]. Interaction of SP with opioid peptides could be the common reason of both the "anti-stress" effect and the hyperalgesic activity of SP.
Asunto(s)
Nociceptores/efectos de los fármacos , Estrés Fisiológico/fisiopatología , Sustancia P/farmacología , Analgésicos/administración & dosificación , Analgésicos/farmacología , Animales , Inyecciones Intraperitoneales , Ratones , Dolor/fisiopatología , Umbral Sensorial/efectos de los fármacos , Estrés Fisiológico/tratamiento farmacológico , Relación Estructura-Actividad , Sustancia P/administración & dosificaciónRESUMEN
Substance P-like immunoreactivity (SPLIR) has been found in fibres and the surroundings of ganglion cells and in a new cell type of rat adrenal medulla, using the indirect immunohistochemical method. These SPLIR-cells are characterized by their localization in the connective tissue in close vicinity of vessels and by acidophilic staining in HE-procedure. Relationships are discussed between the localization of substance P in the adrenal medulla and possible interactions with catecholamines with respect to stress.
Asunto(s)
Médula Suprarrenal/metabolismo , Sustancia P/metabolismo , Médula Suprarrenal/citología , Animales , Histocitoquímica , Inmunoquímica , Masculino , Ratas , Sustancia P/inmunologíaRESUMEN
Using Gly-Pro-pNa as a substrate, the authors photometrically determined the dipeptidyl peptidase activity in organic homogenates and serum of Wistar rats at two pH values. The activity of the serine peptidase DP IV was measured at pH = 7.6; a mixed activity (DP MA) which is composed of the activities of several dipeptidyl peptidases, at pH = 5.0. Particularly high DP IV activities were determined in the kidney, lung, adrenal gland, liver and aortic arch, the differences among the enzyme activities measured in the single organic homogenates at pH = 5.0 being smaller. The DP IV activities and the values found for DP MA in the structures of the nervous system were in general lower. Maximum DP IV values were measured in the spinal ganglion, cerebral cortex and spinal bulb; and maximum DP MA values, in the hypothalamus, cerebellum and cerebral cortex. The results obtained are discussed from the aspects of the participation of these enzymes in peptidergic regulatory mechanisms and of a possible relation to blood-pressure regulation.
Asunto(s)
Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Endopeptidasas/metabolismo , Animales , Encéfalo/enzimología , Concentración de Iones de Hidrógeno , Masculino , Ratas , Ratas EndogámicasRESUMEN
Patients with essential hypertension (n = 45) had significantly lower substance P plasma levels (13.6 +/- 2.30 pg/ml) in comparison with a group of 24 normotensive subjects (45.4 +/- 7.18 pg/ml) analyzed by radioimmunoassay. Prazosin treatment for 2 weeks with 4.5 mg/day enhanced the substance P plasma level depending on its antihypertensive effect. Norepinephrine concentration in plasma was also elevated by prazosin. Dipeptidylpeptidase IV, dopamine-beta-hydroxylase and plasma renin activity were not changed significantly. The results indicate the participation of substance P in pathophysiological processes of human essential hypertension.
Asunto(s)
Hipertensión/sangre , Prazosina/uso terapéutico , Quinazolinas/uso terapéutico , Sustancia P/sangre , Adulto , Presión Sanguínea/efectos de los fármacos , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/metabolismo , Dopamina beta-Hidroxilasa/metabolismo , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Norepinefrina/sangre , Renina/sangreAsunto(s)
Hipertensión/fisiopatología , Dolor/fisiopatología , Envejecimiento , Animales , Electrofisiología , Ratas , Ratas Endogámicas , Umbral SensorialRESUMEN
1. In the hippocampal region of the rat brain GABA was demonstrated with a modified reaction according to WOLMAN (1971). 2. In the various regions of hippocampus different intensities of GABA-fluorescence were demonstrable: A maximum of intensity being present in the area dentata and in the CA 3 region; it is very low in the CA 1 and CA 4 region. 3. The fluorescence of GABA was found to be localized around the pyramidal neurons and the dentate granule cells, respectively.
Asunto(s)
Hipocampo/análisis , Ácido gamma-Aminobutírico/análisis , Animales , Hipocampo/ultraestructura , Masculino , Microscopía Fluorescente , RatasRESUMEN
1. GABA was demonstrated in rat brain in fluorescence histochemistry. The alteration by application of submaximal doses of drugs of the distribution and intensity of the transmitter fluorescence was studied in hippocampus and cerebellum. 2. Isonicotinic acid hydrazide and Penicillamine leads to a distinct grain formation and diminishing of the fluorescence product, normally appearing homogenous. These effects are considered to reflect an enzyme (GAD) inhibition. 3. By Cycloserine a distinct increase of the GABA fluorescence is effected, presumably by inhibiting GABA-transaminase-activity. 4. Chloropromazine causes diminishing, grain formation and dislocation as well of the fluorescent product, supposedly due to an affection of the membrane binding properties of GABA. 5. Hypotheses concerning the chemical events of the GABA-reaction are worded.