Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Lysine clonixinate in the treatment of primary dysmenorrhea

The efficacy tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post-and menstrual periods: possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptons. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24,24/24 and only 2 out of the patients, respectively. Concomitant symptons consisted in headache (12), mastalgia (14) and disconfort (12). Results were obtained by averaging the data from the 3 tratment periods with each drug. Menstrual pain was reduced from 2.9 + 0.7 to 1.9 + 0.7 with P administration and to 0.66 + 0.4 with the administration of LC, a highly significant difference between tratments (p<0.0001). Premenstrual pain was reduced nonsignificantly from 0.79 per cent to 0.58 per cent with P administration and significantly to 0.29 per cent with administration of LC (p<0.001). Intramenstrual pain affection all patients at baseline was reduced significantly by 8 per cent with P and also significantly by 50 per cent with LC p<0.001). No differences were encontered in encomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p<0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.

Prevalencia de diabetes en una población escolar de Avellaneda, Argentina / Diabetes prevalence in a school population of Avellaneda, Argentina

Para establecer la prevalencia de la diabetes en la población escolar de Avellaneda se encuentaron por entrevista personal 56.199 alunmos, entre 3 y 20 años de edad, lo que constituye el 60.5 por ciento del total de esa población. El estudio se realizó en 178 de las 201 escuelas de la comuna. La prevalencia de diabetes en la población escolar fue de 0,45 por ciento entre 3 y 12 años; 1,25 por ciento entre 13 y 20 años y 0,59 por ciento para el total encuestado, cifras éstas similares a las halladas en países desarrollados. Se identificaron 33 escolares diabéticos (18 del sexo femenino y 15 del sexo masculino) con una edad media de 12 años y 6 meses. Sus síntomas de comienzo de la enfermedad más frecuentes fueron los signos cardinales de la diabetes, en tanto el 15 por ciento inició su enfermedad con acidosis o coma diabético. Los diabéticos estaban tratados con insulina o con régimen en casos de remisión. El antecedente familiar de diabetes estaba presente en el 48,5 por ciento de los niños diabéticos y en el 24,5 por ciento de los no diabéticos. Se desarroló una metodologia operativa original en la que participaron 25 personas para el trabajo de campo

Tratamiento de la hipertension arterial esencial con acebutolol en dosis unica diaria. / Treatment of essential arterial hipertension with acebutolol in daily single dose

Se estudio la accion antihipertensiva de acebutolol en dosis unica en 26 enfermos hipertensos tratados en la Primera Catedra de Medicina. El acebutolol fue administrado en dosis unicas de 200 a 400 mg. Quince pacientes normalizaron sus cifras tensionales, ocho las mejoraron y en tres no se obtuvo mejoria. No se registraron efectos secundarios en ningun caso

Prueba de la lisozima en el sindrome Sicca y en la hiposecrecion lagrimal. / Lysozyme test in the Sicca Syndrome and in lacrimal hyposecretion

Se describe la tecnica de la ejecucion del Test de la Lisozima y la interpretacion de su informacion. Se hace un estudio comparativo de las distintas pruebas y sus resultados, senalando su valor en el diagnostico del sindrome Sicca y la Hiposecrecion lagrimal.Se recalca la importancia de la secrecion lagrimal basica en el mecanismo defensivo trofico de la cornea y la conjuntiva