A single oral dose of fructose induces some features of metabolic syndrome in rats: role of oxidative stress.

BACKGROUND AND AIMS: To determine if a single oral dose of fructose to rats reproduces some features of metabolic syndrome observed after chronic administration and if so, to investigate its mechanisms. METHODS AND RESULTS: Systolic blood pressure was measured in rats before and after oral administration of fructose, and in animals pretreated with lipoic acid, methyldopa, losartan or streptozotocin. In other rats, glucose, insulin, uric acid, and insulin sensitivity index, were determined before and after fructose or lipoic acid plus fructose. Glutathione was measured in liver before and after fructose administration. In aortic rings from other rats, incubation with mannitol, fructose, or fructose plus lipoic acid was evaluated on the relaxation by acetylcholine. Fructose produced a moderate increase in blood pressure, which was prevented by lipoic acid or streptozotocin. Methyldopa and losartan decreased the pressor response minimally. Fructose increased oxidized glutathione, plasma glucose, insulin and uric acid, and diminished the insulin sensitivity index, and the reduced glutathione. Lipoic acid prevented hyperglycemia and hyperuricemia, and improved the insulin sensitivity index. Finally, endothelial dysfunction was prevented by lipoic acid. CONCLUSION: A single dose of fructose reproduces some of the features of metabolic syndrome, most changes were caused by oxidative stress and insulin resistance.

Preparation and evaluation of a new nano pharmaceutical excipients and drug delivery system based in polyvinylpyrrolidone and silicate.

PURPOSE: This work describes the preparation of new nanocomposites based on lamellar silicates (AAM-alkyl ammonium montmorillonite) obtained by the intercalation of PVP K30 and glyceril monostearate. METHODS: By XRD, TGA and DSC analysis the AAM was characterized and its compactation characteristics, functionality and toxicity were also tested. The AAM/PVP K-30 and AAM/GME nanocomposite obtained were evaluated to identify the interlamellar spacing values by XRD diffratograms. Tablets were prepared using methyldopa and theophylline as model drugs and the dissolution tests were carried out in simulated gastric fluid and simulated enteric fluid. RESULTS: AAM showed a good compactability and compressibility characteristics for tablets preparation. The intercalation yields (approximately 25%) of the nanocomposites were efficient. The AAM/PVP K-30 nanocomposites were successfully tested as dissolution enhancers and sustained release matrixes. CONCLUSIONS: The results also suggested the promising use of AAM (viscogel B8) and the new nanocomposite prepared by clay/PVP K-30 intercalation as a new matrix for sustained release and the feasibility of using these new nanocomposites as dissolution enhancer.

Uso de la alfa-metildopa en pacientes mayores de 50 años / Uso de la alfa-metildopa en pacientes mayores de 50 años / Uso de la alfa-metildopa en pacientes mayores de 50 años / Uso de la alfa-metildopa en pacientes mayores de 50 años / Uso de la alfa-metildopa en pacientes mayores de 50 años / Alpha metildopa use in patients older than 50 years / Alpha metildopa use in patients older than 50 years / Alpha metildopa use in patients older than 50 years / Alpha metildopa use in patients older than 50 years / Alpha metildopa use in patients older than 50 years

Se realiza un estudio de utilización de medicamento, correspondiente a la clasificación indicación–prescripción, con el objetivo de identificar problemas relacionados con la prescripción de metildopa en mayores de 50 años del Policlínico Universitario “Mártires del 4 de Abril” de Guantánamo, en el período comprendido desde enero de 2001 hasta agosto de 2005. Se encuentra una prescripción inadecuada en la mayoría de los pacientes (77.6 por ciento), con un elevado desconocimiento sobre el fármaco y reacción de los medicamentos en el 100 por ciento de los pacientes, así como un alto índice de insatisfacción después del uso de alfa-metildopa. Se emiten recomendaciones y conclusiones(AU)

Se realiza un estudio de utilización de medicamento, correspondiente a la clasificación indicación–prescripción, con el objetivo de identificar problemas relacionados con la prescripción de metildopa en mayores de 50 años del Policlínico Universitario “Mártires del 4 de Abril” de Guantánamo, en el período comprendido desde enero de 2001 hasta agosto de 2005. Se encuentra una prescripción inadecuada en la mayoría de los pacientes (77.6 por ciento), con un elevado desconocimiento sobre el fármaco y reacción de los medicamentos en el 100 por ciento de los pacientes, así como un alto índice de insatisfacción después del uso de alfa-metildopa. Se emiten recomendaciones y conclusiones(AU)

Se realiza un estudio de utilización de medicamento, correspondiente a la clasificación indicación–prescripción, con el objetivo de identificar problemas relacionados con la prescripción de metildopa en mayores de 50 años del Policlínico Universitario “Mártires del 4 de Abril” de Guantánamo, en el período comprendido desde enero de 2001 hasta agosto de 2005. Se encuentra una prescripción inadecuada en la mayoría de los pacientes (77.6 por ciento), con un elevado desconocimiento sobre el fármaco y reacción de los medicamentos en el 100 por ciento de los pacientes, así como un alto índice de insatisfacción después del uso de alfa-metildopa. Se emiten recomendaciones y conclusiones(AU)

Se realiza un estudio de utilización de medicamento, correspondiente a la clasificación indicación–prescripción, con el objetivo de identificar problemas relacionados con la prescripción de metildopa en mayores de 50 años del Policlínico Universitario “Mártires del 4 de Abril” de Guantánamo, en el período comprendido desde enero de 2001 hasta agosto de 2005. Se encuentra una prescripción inadecuada en la mayoría de los pacientes (77.6 por ciento), con un elevado desconocimiento sobre el fármaco y reacción de los medicamentos en el 100 por ciento de los pacientes, así como un alto índice de insatisfacción después del uso de alfa-metildopa. Se emiten recomendaciones y conclusiones(AU)

Se realiza un estudio de utilización de medicamento, correspondiente a la clasificación indicación–prescripción, con el objetivo de identificar problemas relacionados con la prescripción de metildopa en mayores de 50 años del Policlínico Universitario “Mártires del 4 de Abril” de Guantánamo, en el período comprendido desde enero de 2001 hasta agosto de 2005. Se encuentra una prescripción inadecuada en la mayoría de los pacientes (77.6 por ciento), con un elevado desconocimiento sobre el fármaco y reacción de los medicamentos en el 100 por ciento de los pacientes, así como un alto índice de insatisfacción después del uso de alfa-metildopa. Se emiten recomendaciones y conclusiones(AU)

Pharmacokinetic and pharmacodynamic alterations of methyldopa in rats with aortic coarctation. A study using microdialysis.

A pharmacokinetic-pharmacodynamic study of methyldopa (MD) was made in anesthetized sham operated (SO) and aortic coarctated (ACo) rats by using a vascular shunt probe for arterial microdialysis and simultaneous blood pressure recording. Anesthetized Wistar rats were used 7 days after aortic coarctation or sham operation. A vascular shunt probe was inserted into the carotid artery and a concentric probe was placed into the striatum or posterior hypothalamus. MD and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the dialysates by HPLC-EC. MD (50 mg kg(-1)i.p.) induced an increase of heart rate in SO (Delta HR: 108 +/- 22 bpm, n= 6) and in ACo rats (Delta HR: 55 +/- 10 bpm, n= 6, P< 0.05, one way ANOVA). Moreover, MD also reduced the mean arterial pressure (MAP) of SO rats (Delta MAP: -10 +/- 4 mmHg, n= 6) and ACo animals (Delta MAP: -51 +/- 9 mmHg, n= 6, P< 0.05, one way ANOVA). Analysis of the arterial blood dialysates showed a lower half-life of MD in ACo rats (t(1/2): 1.5 +/- 0.3 h, n= 6, P< 0.05, 't' test) than in SO rats (t(1/2): 3.7 +/- 1.0 h, n= 6). A low accumulation and a fast decay of striatal MD levels were seen in ACo rats. However, peak levels of drug were greater in the hypothalamic dialysates of ACo rats than in SO animals samples. On the other hand, MD also induced an increase of DOPAC levels in the hypothalamic dialysates of ACo rats. In conclusion, the aortic coarctation modifies the pharmacokinetic and cardiovascular effect of MD in the rat. The action of this drug on dopaminergic neurotransmission is also altered in the ACo animals.

Quality of blood pressure monitoring and control in primary care in Trinidad and Tobago - abstract

This study evaluated the quality of blood pressure (BP) monitoring and control among primary care attenders, aged o30 years, and not diabetic or currently pregnant, in Trinidad and Tobago. Data were collected from 1616 clinic records (92 percent retrieval rate for eligible cases): 1041 attended eighteen government health centres and 575 attended eight private general practitioner (GP) offices. Overall, 1469 (91 percent) patients had BP recorded at some time and 1217 (75 percent) within the previous 12 months. The proportion with no BP measurement was higher for GP patients (19 percent) than for health centre patients (4 percent). Only 73 (5 percent) of patients had BPo160/100 mm Hg and were not treated with drugs, but 164 (10 percent) had BPo140/90 and < 160/100 mm Hg and were not treated with drugs. Patients aged o 65 [Odds Ratio (OR) 3.29 (95 percent Confidence Interval (CI) 1.54 to 7.07)] and patients attending GPs [(OR 2.31 (CI 1.20 to 4.43)] were more likely to have untreated BPo160/100 mm Hg. Among 784 patients treated for hypertension only 143 (18 percent) had BP < 140/90 mm Hg. Advice on non-drug treatment was recorded for only 164 (10 percent) of all patients. Health centres mainly prescribed methyldopa and Brinerdin while GPs prescribed ACE inhibitors and calciun antagonists as well as thiazides and Brinerdin. Most primary care attenders had BP measurements recorded and most patients with hypertension received treatment but control of hypertension in those treated was unsatisfactory, more so for those attending GPs than for those attending health centres (AU)

Successful pregnancies in patients with antiphospholipid syndrome treated with low-dose aspirin.

Four patients with bad obstetrical histories and with positive lupus anticoagulant tests were treated with low-dose aspirin, prednisone or heparin. They had pre-term deliveries of live babies who all survived.

Action of alpha-methyldopa on human umbilical circulation in vitro.

To determine the possible effects of alpha-methyldopa on the motility of human umbilical artery, a total of 53 arterial segments were perfused with different concentrations of the drug as follows: 38 segments with 125, 250 and 500 ng/ml of the drug, 9 segments with 500 ng/ml alpha-methyldopa in combination with 10(-7) M yohimbine, and 6 segments with 10(-7) M yohimbine alone. alpha-Methyldopa had a vasoconstrictor effect at all doses employed, with a clear dose-effect correlation (p less than 0.01). The vasoconstrictor effect of 500 ng/ml alpha-methyldopa was fully inhibited in the presence of 10(-7) M yohimbine. These results suggest that alpha 2-adrenergic receptors are present in the umbilical circulation and that alpha-methyldopa may play a role in the control of this circulation.

[Use of alphamethyldopa during the pregnancy-puerperium cycle in hypertensive patients and evaluation of their offspring up to their 3rd year of life]. / Uso de alfametildopa no ciclo gravídico-puerperal de pacientes hipertensas e avaliação dos conceptos até o terceiro ano de vida.

PURPOSE: To evaluate the effects of alpha methyldopa in pregnant women with mild to moderate arterial hypertension as well as in the offsprings. MATERIAL AND METHODS: Thirty one pregnant hypertensive women, mean age 31 years, six (10.35%) primigravids, after the 12th week of pregnancy received alpha methyldopa, initial 250 mg/day, weekly increased depending to the response. Blood pressure was measured in supine and standing positions and the patients were submitted to a laboratory evaluation including: hemoglobin, hematocrit, leukocytes, platelets, urea, creatinine, glucose, transaminases, bilirubin, alkaline phosphatase, uric acid, Coombs, creatinine clearance, as well as obstetric ultrasonography and electrocardiogram. The labor, childbirth conditions and puerperal evolution, were evaluated as well as the development of the offspring up 3 years of age. RESULTS: Alpha methyldopa was administered for an average period of 14.2 weeks, mean dose of 685 mg/day. In thirty patients (96.77%) blood pressure was efficiently controlled. Clinical and laboratory adverse experiences were not observed. The use of drug was not associated with abnormalities during the labor, in the puerperium, in the newborn and during the development of the children up 3 years of age. CONCLUSION: Alpha methyldopa is efficacious and well tolerated in the control of mild to moderate hypertension in pregnant women, and is not associated with unfavorable consequences during the pregnancy, puerperal cycle an in the development of the children in the study period.

Uso de alfametildopa no ciclo gravídico-puerperal de pacientes hipertensas e avaliaçäo dos conceptos até o terceiro ano de vida / Effects of alpha methyldopa in hypertensive pregnant women and evaluation of the offsprings up to 3 years.

Objetivo: Avaliar os efeitos do uso de alfametildopa em gestantes portadoras de Hipertensäo arterial leve ou moderada, bem como no concepto. Material e Métodos: Trinta e uma gestantes hipertensas, com idade média de 31 anos, sendo seis (10,35%) primigestas, submetidas, após a 12§ semana de gestaçäo, ao uso de alfametildopa, em dose inicial de 250 mg/dia, aumentada semanalmente de acordo com a resposta. Os níveis tensionais foram medidos em posiçöes supina e ereta e as pacientes submetidas a avaliaçäo laboratorial incluindo verificaçäo das taxas sangüíneas de hemoglobina, hematócrito, leucócitos, bilirrubina, fosfatase alcalina, ácido úrico, além de reaçäo de Coombs, clearance de creatinina, bem como ultrassosnografia obstétrica e eletrocardiograma. Foram analisadas as condiçöes de parto,d e evoluçäo puerperal, de nascimento e de desenvolvimento do concepto até os três anos de idade. Reultados: alfametildopa foi empregada em média por 14,2 semanas, em doses médias de 685 g/dia. Houve eficácia terapêutica no controle dos níveis tensionais em 30(96,77%) pacientes. Näo foram registrados efeitos colaterais de natureza clínica ou laboratorial. A droga näo se associaou a anormalidades no parto, no puerpério, no recém-nato e no desenvolvimento pôndero-estadual das crianças até período de três anos de idade. Conclusäo: A alfametildopa mostrou-se droga eficaz e bem tolerada no controle de Hipertensäo arterial leve ou moderada de gestantes, näo se associando a influências desfavoráveis no decorrer do ciclo gravídico-puerperal e no desenvolvimento da criança no periódo observado

Purpose: To evaluate the effects of alpha methyldopa in pregnant women with mild to moderate arterial hypertension as well as in the offsprings. Material and Methods: Thirty one pregnant hypertensive women, mean age 31 years, six (10.35%) primigravids, after the 12th week of pregnance received alpha methyldopa, initial 250mg/day, weekly increased depending to the response. Blood pressure was measured in supine and standing positions and the patients were submitted to a laboratorial evaluation including: hemoglobin, hematocrit, leukocytes, platelets, urea, creatinin, glucose, transaminases, bilirrubin, alkaline phosphatase, uric acid, Coombs, creatinin clearance, as well as obstetric ultrassonography and electrocardiogram. The labor, childbirth conditions and puerperal evolution, were evaluated as well as the development of the offspring up 3 years of age. Results: Alpha methyldopa was administred for an average period of 14.2 weeks, mean dose of 685 mg/day. In thirty patients (96.77%) blood pressure was efficiently controlled. Clinical and laboratorial adverse experiences were not observed. The use of drug was not associated with abnormalities during the labor, in the purperium, in the newborn and during the development of the children up 3 years of age. Conclusion: Alpha methyldopa is efficacious and well tolerated in the control of mild to moderate hypertension in pregnant women, and is not associated with unfavorable consequences during the pregnancy, puerperal cycle an in the development of the children in the study period.

Treatment of resistant hypertension: 3 years of follow-up with the combination of verapamil and methyldopa.

A combination of verapamil (V), methyldopa (M), and hydrochlorothiazide (H) was tried in hypertensive patients resistant to the usual stepped-care therapy. After at least 60 days with a third-step regimen, placebo was added during the last 2 weeks. Twenty patients whose diastolic blood pressure (DBP) remained greater than 100 mm Hg were assigned to the study. During the initial titration period patients received increasing doses of V (240-480 mg) and M (500-1,500 mg). H was kept at 50 mg/day. Other previously administered drugs were gradually withdrawn. Goal pressure was DBP less than or equal to 95 mm Hg. Follow-up lasted 3 years. Sixteen patients participated in the investigation until the end and all but one reached the goal DBP. Mean systolic BP dropped from 187 +/- 17 to 150 +/- 15 mm Hg (p less than 0.05) and DBP from 118 +/- 12 to 90 +/- 9 mm Hg (p less than 0.01). Adverse effects were rare and mild. Other control measurements did not show any change except improvement of the electrocardiogram of 11 patients, and of the optic fundus of 10 patients. The number of drug unities to be taken dropped from 10 +/- 4 to 7 +/- 2 (p less than 0.05). The abovementioned combination seems to be useful in the control of resistant hypertension. Efficacy was sustained and tolerability was excellent. A potential to reverse target organ damage, namely of the heart and optic fundus, is suggested.

Hipertensión arterial: alfa-metildopa en una sola toma diaria; estudio comparativo entre la forma convencional y una forma de liberación prolongada / Arterial hypertension: alpha-methyldopa in a single daily doSe; comparative study between conventional form and a single form of delayed SeleaSe

Se incluyeron 44 pacientes, de ambos sexos, de 40 a 90 años de edad (media=67 años) portadores de hipertensión arterial esencial leve o moderada y que estaban en tratamiento y estabilizados con alfa-metildopa convencional (MD-C) administrada en 2 o 3 tomas diarias sola o asociada a diuréticos. Después de un periodo de control de 3 semanas, se reemplazó la MD-C por una nueva forma de liberación programada de acción prolongada (MD-AP) en una sola toma diaria, durante otro período de 3 semanas. Los datos registrados y su análisis estadistico (varianza para una categoria) autorizan a concluir que la MD-AP permite el control de la hipertensión arterial leve o moderada, con una única dosis diaria y que dicho efecto se puede obtener con una dosis menor que la dosis total diaria de la forma convencional

Hipertensión arterial: alfa-metildopa en una sola toma diaria; estudio comparativo entre la forma convencional y una forma de liberación prolongada / Arterial hypertension: alpha-methyldopa in a single daily doSe; comparative study between conventional form and a single form of delayed SeleaSe

Se incluyeron 44 pacientes, de ambos sexos, de 40 a 90 años de edad (media=67 años) portadores de hipertensión arterial esencial leve o moderada y que estaban en tratamiento y estabilizados con alfa-metildopa convencional (MD-C) administrada en 2 o 3 tomas diarias sola o asociada a diuréticos. Después de un periodo de control de 3 semanas, se reemplazó la MD-C por una nueva forma de liberación programada de acción prolongada (MD-AP) en una sola toma diaria, durante otro período de 3 semanas. Los datos registrados y su análisis estadistico (varianza para una categoria) autorizan a concluir que la MD-AP permite el control de la hipertensión arterial leve o moderada, con una única dosis diaria y que dicho efecto se puede obtener con una dosis menor que la dosis total diaria de la forma convencional (AU)

Alfa-metildopa versus atenolol no tratamento da hipertensäo arterial / Alphamethyldopa versus atenolol in the treatment of arterial hypertension

Foi comparado o efeito terapêutico de 500 mg de alfa-metildopa e de 100 mg de atenolol, em dose única diária. Dezoito pacientes, 13 mulheres, idade de 50 + ou - 11 anos, receberam alfametildopa (grupo AMD) e 23 pacientes, 22 mulheres, idade 49 + ou - 8 anos, atenolol (grupo ATN). O estudo durou 5 semanas, com uma semana inicial de placebo e 4 semanas de tratamento. No final da 4.- semana houve queda significativa (p < 0,001) da pressäo sistólica (delta maiúsculo = 17 + ou - 25 mmHg) no grupo AMD e 11 + ou - 23 mmHg (p < 0,001) no grupo ATN; a diminuiçäo da pressäo arterial diastólica (PAD) só foi significativa no grupo AMD (delta maiúsculo = 15 + 12 mmHg, p < 0,001). A resposta da PAD por grau de hipertensäo foi significativa em todos os níveis (discreto, moderado e grave) no grupo AMD, e restrita ao subgrupo grave (PAD >= = 120 mmHg) no grupo ATN. Neste grau, as reduçöes foram semelhantes: delta maiúsculo = 22 + ou - 10 mmHg no grupo AMD e 16 + ou - 10 mmHg no grupo ATN. Apresentaram delta maiúsculo PAD >= 10 mmHg 15 pacientes (72%) no grupo AMD e 12 pacientes (52%)no grupo ATN. A queda foi semelhante nos dois grupos: delta maiúsculo = 16 + ou - 13 mmHg no AMD e 21 + ou - 8 mmHg no ATN. A freqüência de paraefeitos foi comparável: 33% no grupo AMD e 22% no grupo ATN, näo implicando na interrupçäo do estudo. Concluiu-se pela eficácia anti-hipertensiva comparável das duas drogas (sendo a do atenolol mais restrita aos casos de hipertensäo arterial grave, provavelmente decorrente da sua açäo (antirenina) e pela boa tolerância no período do estudo

[Autoimmune hemolytic anemia induced by alpha methyldopa]. / Anemia hemolítica autoinmune inducida por alfa-metildopa.

We present in this paper two cases of auto-immune hemolytic anemie caused by ingestion of alpha-metildope Coombs' test positive. We suggest to make Coombs test to every patient in whose treatment has been included the use of alpha-metildope.