Prevalence of multiple sclerosis in Buenos Aires, Argentina using the capture-recapture method.

BACKGROUND: Scarce data exist about multiple sclerosis (MS) prevalence in South America. The objective of the study is to determine the prevalence of MS in a high populated area from Argentina (Greater Buenos Aires Metropolitan area) using the capture-recapture methodology. METHODS: Greater Buenos Aires is the generic denomination that refers to the megalopolis comprised by the autonomous city of Buenos Aires and the surrounding conurbation of the province of Buenos Aires. The study was carried out taking July 1996 as the prevalence month. We used capture-recapture method to estimate the prevalence of MS cross matching registries from four MS Centers. RESULTS: A total of 803 registries were obtained from the four lists. Log-linear model for capture-recapture method was used to analyze the data. The population of the area based on the 1990 census was 12,594,974; the number of MS cases estimated amongst sources interactions were between 1833 and 2359; the prevalence estimated ranged from 14 to 19.8 cases per 100,000 inhabitants. CONCLUSIONS: This is the first study to provide epidemiological data on the prevalence of MS in a large population in Argentina (Greater Buenos Aires Metropolitan area). Further epidemiological studies will clarify the true prevalence of MS in South America.

Pharmacokinetics of deflazacort in renal transplanted and hemodialyzed children.

Deflazacort (DFZ) pharmacokinetics was evaluated in fifteen pediatric patients on chronic hemodialysis or after renal transplantation, and in three normal children. After overnight fasting, oral DFZ 0.26+/-0.01 mg/kg (mean +/- SEM) was given. Serial blood samples were collected for 360 min and analyzed by HPLC for 21-hydroxy-DFZ (21-HO-DFZ). Serum concentration profiles and pharmacokinetic parameters were similar in patients on hemodialysis, renal transplant recipients and normal children. Elimination half-life was longer in the 9 cyclosporine-treated subjects (108.0+/-13.6 min) than in the other nine (71.2+/-8.3 min; p <0.02). Our finding suggests that, from a pharmacokinetic point of view, DFZ dose adjustment for renal function is not necessary in children with chronic renal failure or after renal transplantation.

Diastolic pressure underestimates age-related hemodynamic impairment.

It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the prevalence of diastolic hypertension toward a systolic pattern of hypertension with aging. Also, the results suggest that SBP, but not DBP, is a reliable indicator of the underlying hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly.

Effect of dexamethasone on osseointegration: a preliminary experimental study.

The peri-implant reparative process is one of the factors involved in osseointegration. Local and systemic factors may contribute to the peri-implant micro-environment. The aim of this study was to assess the effect of dexamethasone (DXM) on the first stages of the post-implantation reparative process using a quantitative osseointegration experimental model previously developed at our laboratory. A titanium laminar implant was inserted into the right tibiae of nine male Wistar rats under ether anesthesia, following a technique we previously described. Six rats received 120 micrograms/kg/day i.p. doses of DXM (Decadron Sidus, Argentina) for 14 days pre-implantation and 14 days post-implantation. The remaining three (controls) were injected with an equivalent volume of saline. On day 14 post-implantation, all animals were killed, and their tibiae were resected, radiographed, and processed before being embedded in methylmethacrylate. Microscopic observation and histomorphometric studies were performed. Results show that, in this experimental model, the extension of osteogenic peri-implant response was greater in DXM-treated animals than in controls. Thus, our laminar implant test may prove useful to study the effects of corticosteroids on the osseointegration process.

Inhibitory effects of diazepam in rat vas deferens: role of calcium.

Diazepam and Ro5-4864 effects on noradrenaline-induced rat vas deferens contractions were studied. We investigated whether central or peripheral type benzodiazepine receptors were involved, by studying the effects of the selective central or peripheral benzodiazepine receptor antagonists, flumazenil (Ro 151788) or PK 11195 respectively. Diazepam interactions with GABA, adenosine, theophylline, and hypercalcic medium (3.5 mM) were studied. Also, we investigate diazepam effect on KCl depolarized vas deferens. Results showed that diazepam (10(-4) to 1.7 x 10 (-4) M) and Ro 5-4864 (10(-5) to 5.5 x 10(-5) M) inhibited NA-induced vas deferens contractions and that neither flumazenil nor PK 11195 antagonized diazepam or Ro 5-4864 inhibitory effects respectively. GABA, adenosine and theophylline did not modify neither NA vas deferens response nor diazepam inhibitory action. Diazepam effect was significantly reduced in and 3.5 mM calcium medium and KCl vas deferens response was inhibited by diazepam 1.3 x 10(-5) and 1.3 x 10(-4) M. It is concluded that in rat vas deferens diazepam effect seems to be related with calcium mobilization.

Influencia de la siesta sobre la presión arterial en pacientes hipertensos esenciales / Afternoon nap influence on blood pressure in essential hypertensives

Hay suficientes evidencias que demuestran que el descenso nocturno de la presión arterial es consecuencia de la inactividad y no depende de una hora determinada, ya que la presión arterial desciende cuando los individuos duermen durante el día. Comparamos la presión arterial sistólica, diastólica y la frecuencia cardíaca durante la siesta, el período nocturno de actividad y el sueño nocturno en 59 pacientes (32 mujeres, 27 hombres) hipertensos sin medicación (edad promedio: 53 ñ 14 años, rango: 26-84 años). La presión arterial y la frecuencia cardíaca fueron registradas utilizando un Pressurometer Del Mar IV 1990. Veintidós pacientes durmieron dos horas por lo menos luego de almorzar, 17 descansaron sin dormir y 20 permanecieron activos en el período posprandial. Evaluamos la media, el área bajo la curva y el desvío estándar de la presión arterial sistólica, diastólica y frecuencia cardíaca durante el período posprandial, el sueño nocturno y el resto del día. Tanto el sueño nocturno como el sueño posprandial disminuyeron la presión arterial sistólica, diastólica y la frecuencia cardíaca. Durante el descanso posprandial la presión arterial diastólica fue similar a la presión arterial diastólica nocturna y durante la siesta disminuyó más que durante el sueño nocturno

Influencia de la siesta sobre la presión arterial en pacientes hipertensos esenciales / Afternoon nap influence on blood pressure in essential hypertensives

Hay suficientes evidencias que demuestran que el descenso nocturno de la presión arterial es consecuencia de la inactividad y no depende de una hora determinada, ya que la presión arterial desciende cuando los individuos duermen durante el día. Comparamos la presión arterial sistólica, diastólica y la frecuencia cardíaca durante la siesta, el período nocturno de actividad y el sueño nocturno en 59 pacientes (32 mujeres, 27 hombres) hipertensos sin medicación (edad promedio: 53 ñ 14 años, rango: 26-84 años). La presión arterial y la frecuencia cardíaca fueron registradas utilizando un Pressurometer Del Mar IV 1990. Veintidós pacientes durmieron dos horas por lo menos luego de almorzar, 17 descansaron sin dormir y 20 permanecieron activos en el período posprandial. Evaluamos la media, el área bajo la curva y el desvío estándar de la presión arterial sistólica, diastólica y frecuencia cardíaca durante el período posprandial, el sueño nocturno y el resto del día. Tanto el sueño nocturno como el sueño posprandial disminuyeron la presión arterial sistólica, diastólica y la frecuencia cardíaca. Durante el descanso posprandial la presión arterial diastólica fue similar a la presión arterial diastólica nocturna y durante la siesta disminuyó más que durante el sueño nocturno (AU)

Vasodilatory effects of propylthiouracil in patients with alcoholic cirrhosis.

BACKGROUND/AIMS: An experimental study has shown that propylthiouracil increases portal blood flow in normal rats. Whether propylthiouracil has a similar effect in patients with alcoholic cirrhosis remains to be demonstrated. The aim of this study was to evaluate the effects of oral propylthiouracil (300 mg) on systemic and portal hemodynamics in patients with alcoholic cirrhosis. METHODS: Plasma propylthiouracil levels were also measured by high performance liquid chromatography in five patients with alcoholic cirrhosis. In eight patients with cirrhosis, mean arterial pressure, cardiac output and portal blood flow were evaluated before and after placebo and propylthiouracil administration. Hemodynamic measurements were performed by the Doppler technique. The plasma peak level of propylthiouracil was achieved at 1.4 +/- 0.1 h in patients with alcoholic cirrhosis. This time was chosen to express hemodynamic changes. RESULTS: Propylthiouracil administration caused a significant increase in portal blood flow (+16.5%, p < 0.05) in patients with alcoholic cirrhosis. This effect was associated with a mild and significant rise in cardiac output (from 5.8 +/- 0.2 to 6.1 +/- 0.3 l/min, p < 0.05) and a decrease in peripheral vascular resistance (from 1171 +/- 69 to 1070 +/- 67 dyn . s-1 . cm-5, p < 0.01). A significant correlation was observed between changes in portal blood flow and peripheral vascular resistance (r = 0.79, p < 0.05). No significant changes were observed after placebo. CONCLUSIONS: Our findings show that propylthiouracil has a vasodilatory effect in patients with alcoholic cirrhosis. We postulate that this effect could be the mechanism by which propylthiouracil decreases hypermetabolic state, and increases oxygen delivery to the liver, in patients with alcoholic liver diseases.

Effects of calcium and its antagonists on histamine-induced leakage in rat skin.

Evans blue extravasation in rat skin was used to study the effects of calcium, lanthanum, L-type calcium channel blockers and trifluoperazine on histamine-induced leakage. Histamine effect was inhibited by calcium 1-2.5 mM, lanthanum 1-10 mM, nifedipine 0.1 and 1 microM and trifluoperazine 30 and 100 microM. The effects of calcium decreased progressively as its concentrations rose up to 10 mM. The association of nifedipine 0,1 microM or trifluoperazine 30 microM with calcium 3 microM increased the inhibitory effects. Calcium 10mM reversed the effect of nifedipine 0.1 microM but not that of lanthanum 1 mM or trifluoperazine 30 microM. It is proposed that the effect of calcium on histamine-induced leakage is the expression of a balance between an extracellular inhibitory effect and an intracellular enhancing effect.

Effects of calcium and its antagonists on histamine-induced leakage in rat skin.

Evans blue extravasation in rat skin was used to study the effects of calcium, lanthanum, L-type calcium channel blockers and trifluoperazine on histamine-induced leakage. Histamine effect was inhibited by calcium 1-2.5 mM, lanthanum 1-10 mM, nifedipine 0.1 and 1 microM and trifluoperazine 30 and 100 microM. The effects of calcium decreased progressively as its concentrations rose up to 10 mM. The association of nifedipine 0,1 microM or trifluoperazine 30 microM with calcium 3 microM increased the inhibitory effects. Calcium 10mM reversed the effect of nifedipine 0.1 microM but not that of lanthanum 1 mM or trifluoperazine 30 microM. It is proposed that the effect of calcium on histamine-induced leakage is the expression of a balance between an extracellular inhibitory effect and an intracellular enhancing effect.

Steady-state hydroxyflutamide plasma levels after the administration of two dosage forms of flutamide.

A bioavailability study of randomized cross-over design was carried out in eight volunteers who were given a 48-h flutamide treatment consisting of 250-mg tablets three times daily or 400-mg sustained-release tablets twice daily, followed 3 weeks later by the alternative dosage form. Just before the last dose and 15 times during the subsequent 24 h, blood samples were obtained for the determination of plasma hydroxyflutamide (the active metabolite of flutamide) levels by high-performance liquid chromatography. No statistically significant differences between the two dosage forms were found for the lag time, rate of initial increase in concentration, peak plasma concentration, mean hydroxyflutamide concentration within one dosing interval or 24-h AUC value. One subject presented mild and transient nausea during both treatment periods. After the first treatment period (250-mg tablets), an increase in serum bilirubin was observed in another volunteer, who was withdrawn from the study. It may be concluded that both dosage forms were bioequivalent.

Effects of enalapril on renal parameters in patients with primary glomerulopathies associated with chronic renal failure.

14 patients (8 male, 6 female), aged 35 to 64 years, with glomerulopathies consisting of membranoproliferative glomerulonephritis (GN) [n = 6], membranous GN (n = 3), focal and diffuse glomerulosclerosis (n = 4), and post-streptococcal GN (n = 1) were studied. Diagnosis was established by renal biopsy in 12 of the 14 patients. All 14 patients had impaired renal function (creatinine clearance = 25 to 55 ml/min) and proteinuria (1.0 to 10.4 g/day). Five normotensive patients received enalapril 20 mg/day, whereas 9 patients with hypertension received 20 to 40 mg/day to control blood pressure. Diuretics were administered concomitantly to 8 patients. Patients attended the clinic every 14 days for 30 months and their diets were closely monitored, with sodium intake limited to between 50 and 100 mEq/day and protein to between 1.0 and 1.2 g/kg/day. Blood pressure was significantly controlled in the patients with hypertension. Serum creatinine, blood urea nitrogen, creatinine clearance and 24-hour urinary protein excretion all significantly improved during the 30-month study. No adverse clinical events were noted. Thus, over a period of time, enalapril therapy may improve the prognosis of patients with glomerulonephritis by maintaining glomerular filtration rates and decreasing proteinuria and blood pressure.

Effects of calcium and EDTA on rat skin capillary permeability and on its response to histamine, serotonin and bradykinin.

Evans blue extravasation in rat skin was used to study the effects of Ca2+ and EDTA on vascular permeability and on its response to mediators of inflammation. Ca2+ induced a concentration-dependent decrease of vascular permeability. The opposite effect was seen with EDTA 0.2 mM or higher. Effects on vascular permeability of intradermically injected histamine 100 micrograms/ml, serotonin 5 micrograms/ml and bradykinin 5 micrograms/ml, were lower when Ca2+ 8 mM was injected in the same site, and higher when EDTA 2 mM was given. EDTA effects were inhibited by Ca2+. The results suggest that, in rat skin, Ca2+ decreases capillary permeability and its response to histamine, serotonin and bradykinin.

Changes in human parotid salivary protein and sialic acid levels during pregnancy.

Saliva was collected with a Carlson-Crittenden device, under citric acid stimulation, in 107 pregnant women, 9 puerperal and 7 non-pregnant controls. No significant changes were found in salivary flow rate, pH and amylase levels. The total protein levels were decreased during pregnancy and the puerperium. The sialic acid levels decreased gradually but markedly during pregnancy, returning to normal levels in the puerperium. These changes in parotid saliva may be related to the hormonal changes of pregnancy.

Effects of calcium and EDTA on rat skin capillary permeability and on its response to histamine, serotonin and bradykinin.

Evans blue extravasation in rat skin was used to study the effects of Ca2+ and EDTA on vascular permeability and on its response to mediators of inflammation. Ca2+ induced a concentration-dependent decrease of vascular permeability. The opposite effect was seen with EDTA 0.2 mM or higher. Effects on vascular permeability of intradermically injected histamine 100 micrograms/ml, serotonin 5 micrograms/ml and bradykinin 5 micrograms/ml, were lower when Ca2+ 8 mM was injected in the same site, and higher when EDTA 2 mM was given. EDTA effects were inhibited by Ca2+. The results suggest that, in rat skin, Ca2+ decreases capillary permeability and its response to histamine, serotonin and bradykinin.

Union de drogas a proteinas plasmaticas. / Union of drugs with plasma proteins

Se discute en detalle la union e las proteinas plasmaticas a las drogas, lo que constituye uno de los aspectos mas importantes de la farmacocinetica de los diferentes farmacos. En esta revision se analizan los mecanismos cineticos moleculares de la union proteina-droga; las tecnicas de estudio de este fenomeno, las modificaciones que acontecen en diferentes condiciones clinicas y terapeuticas en relacion a este importante hecho farmacocinetico. Finalmente, se describen las implicaciones terapeuticas derivadas de las modificaciones en la union proteina-droga que acontece en diferentes condiciones experimentales y clinicas