HPLC-MS/MS method for determination of betamethasone in human plasma with application to a dichorionic twin pregnancy pharmacokinetic and placental transfers studies

Abstract Betamethasone (BET) is a synthetic glucocorticoid recommended for pregnant women at imminent risk of preterm birth before 34 weeks to reduce neonatal complications. There are different techniques to describe BET plasma quantification. However, none quantified the plasmatic concentration of BET in dichorionic (DC) twin pregnancies using LC-MS. Our objectives were to develop and validate a method for quantifying BET by LC-MS for pharmacokinetic (PK) and placental transfer studies in DC twin pregnancies. Blood samples were collected after intramuscular administration of a single BET dose containing 6 mg disodium phosphate + 6 mg acetate. BET was determined in plasma by liquid-liquid extraction. The method showed linearity in the range of 2-250 ng/mL, as well as precision and accuracy with a coefficient of variation and relative standard errors ≤ 15%. Additionally, the method presented selectivity and did not present matrix or carry-over effect. Stability tests also presented coefficient of variation and relative standard errors ≤ 15%. This is the first study which describe maternal and fetal plasma concentrations of BET in a DC twin pregnancy. The BET PK parameters were AUC0-∞, CL/F, Vd/F, Cmax, Tmax of 292.20 h*ng/mL, 39.08 L/h, 278.72 L, 25.55 ng/mL and 0.58 h, respectively. The placental transfer ratios of umbilical vein/maternal vein and intervillous space/maternal vein were 0.14 and 0.19 and 0.40 and 0.27 for both twins, respectively. However, a clinical study with more subjects is imperative to confirm this higher concentration of BET in the intervillous space

Detection of free DNA septin 9 gene methylation in plasma / 中南大学学报(医学版)

OBJECTIVES@#To explore the correlation between cytosine-phosphoric-guanylic (CpG) site of Septin 9 gene and colorectal cancer, and to develop a real-time PCR detection system in plasma in patients with colorectal cancer.@*METHODS@#The methylation of training samples was detected by high-throughput sequencing technology, and the sites highly consistent with the clinical information of colorectal cancer were identified. Then the detection system of real-time PCR was designed to analyze the consistency of plasma and tissue based on methylationa sensitive enzyme digestion. Finally, 100 clinical trials were conducted to evaluate the performance of the detection system with the methylation sensitive enzyme digestion-real-time PCR.@*RESULTS@#The highly consistent sites, which were selected by high-throughput sequencing from 71 training set samples, was the 38th CpG. Based on the detection region, the screened methylation sensitive enzymes were @*CONCLUSIONS@#The 38th CpG site of Septin 9 detected by the detection system of methylation sensitive enzyme digestion-real-time PCR can highly predict the occurrence of colorectal cancer with great clinical application value.

Influência do tratamento do substrato com plasma não térmico na resistência de união em cimentação adesiva / Influence of the substrate treatment with non-thermal plasma on bond strength of adhesive cementation

Objetivo: avaliar a influência do tratamento de superfície com plasma não térmico de argônio (PLA) na resistência de união de cimentos resinosos ao esmalte, à dentina e à cerâmica de dissilicato de lítio. Observar, no esmalte e na dentina, através de espectroscopia de infravermelho por transformada de Fourier (FTIR) os compostos inorgânicos e da cromatografia gasosa a alteração dos compostos orgânicos voláteis nas condições experimentais propostas. Material e Método: Foram avaliados 3 cimentos resinosos: Variolink Esthetic LC e N (Ivoclar Vivadent), e Panavia V5 (Kuraray). Foram utilizados 240 dentes bovinos, dos quais 150 tiveram a superfície do esmalte exposta e 90 a de dentina. Foram obtidas 150 lâminas de cerâmica de dissilicato de lítio (12 x 14 x 0,5 mm). Os grupos foram divididos de acordo com o tratamento de superfície e o substrato. Os tratamentos para as superfícies de esmalte e dentina foram: EA (esmalte/ácido fosfórico); DA (dentina/ácido fosfórico); EPS (esmalte/PLA 30 s); EPM (esmalte/PLA 1 min); DPS (dentina/PLA 30 s); EAPS (esmalte/ácido fosfórico/PLA 30 s) e EAPM (esmalte/ácido fosfórico/PLA 1 min); e, DAPS (dentina/ácido fosfórico/PLA 30 s). Os tratamentos para as superfícies da cerâmica foram: CA (cerâmica/ácido fluorídrico), CPS (cerâmica/PLA 30 s); CPM (cerâmica/PLA 1 min); CAPS (cerâmica/ácido fluorídrico/PLA 30 s) e CAPM (cerâmica/ácido fluorídrico/PLA 1 min). Posterior aos tratamentos, cilindros dos cimentos resinosos (0,8 mm/1,5 mm) foram confeccionados sobre as superfícies dos substratos. Após 48 h, os espécimes foram submetidos ao ensaio mecânico de microcisalhamento (10 Kgf/1 mm/min) até a fratura. A área fraturada foi analisada em estereomicroscópio. As superfícies tratadas e a interface adesiva foram analisadas por Microscopia Eletrônica de Varredura (MEV). Através do FTIR foram observados os espectros de amostras tratadas de esmalte e dentina. Os dados da resistência de união foram submetidos à análise estatística ANOVA e teste de Tukey (5%). Resultados: Para o esmalte os tratamentos de superfície não apresentaram diferença estatisticamente significante entre si; para a dentina o grupo DPS apresentou os maiores valores de resistência de união; e, para a cerâmica o tratamento CA apresentou os maiores valores de resistência de união. Para esmalte e dentina, o FTIR, mostrou alterações do conteúdo da água, carbonato e fosfato e a cromatografia gasosa das substâncias orgânicas voláteis. Conclusão: O tratamento de superfície com PLA não influencia a resistência de união de cimentos resinosos ao esmalte, aumenta à dentina e diminui ao dissilicato de lítio. As análises observacionais no FTIR sugerem que o plasma não altera compostos do esmalte e da dentina(AU)

Objective: to evaluate the influence of surface treatment with non - thermal argon plasma (PLA) on bond strength of resin cements to enamel, dentin and lithium disilicate glass ceramic; and, to observe, through Fourier Transform Modified Infrared Spectroscopy (FTIR), the inorganic compounds and through gas chromatography, the alteration of the volatile organic compounds, on the enamel and dentin, under the experimental conditions. Material and Method: Three resin cements: Variolink Esthetic LC and N (Ivoclar Vivadent) and Panavia V5 (Kuraray) were evaluated. Twenty hundred and forty bovine teeth were used, among which 150 specimens with enamel surface exposure and 90 with dentine exposure. One hundred and fifty lithium disilicate glass ceramic slices (12 x 14 x 0.5 mm) were obtained. The groups were divided according to the substrate and surface treatment. The treatments for enamel and dentin surfaces were: EA (enamel / phosphoric acid); DA (dentin / phosphoric acid); EPS (enamel / PLA 30 s); EPM (enamel / PLA 1 min); DPS (dentin / PLA 30 s); EAPS (enamel / phosphoric acid / PLA 30 s) and EAPM (enamel / phosphoric acid / PLA 1 min); and, DAPS (dentin / phosphoric acid / PLA 30 s). The treatments for the ceramic surfaces were: CA (ceramic / hydrofluoric acid), CPS (ceramic / PLA 30 s); CPM (ceramic / PLA 1 min); CAPS (ceramic / hydrofluoric acid / PLA 30s) and CAPM (ceramic / hydrofluoric acid / PLA 1 min). After the treatments, resin cement cylinders (0.8 mm / 1.5 mm) were built on the substrate's surfaces. After 48 h storage bond strength tests (µSBS) were performed in a universal testing machine (10 Kgf / 1 mm / min) until failure to fracture, and failure mode was analyzed under a stereomicroscope. The treated surfaces and the adhesive interface were analyzed by Scanning Electron Microscopy (SEM). The FTIR was used to observe the spectra of enamel and dentin treated samples. Bond strength data were submitted to ANOVA and Tukey test (5%). Results: for the enamel there was not a statistically significant difference among surface treatments; for the dentin, the DPS group presented the highest bond strength; and for the ceramic the AC treatment presented the highest values of bond strength. For the enamel and the dentin samples, the FTIR observations showed changes in water, carbonate and phosphate contents and the gas chromatography in the volatile organic substances. Conclusion: Surface treatment with PLA does not influence the bond strength of resin cements to the enamel, increases the bonding to dentin and decreases to the lithium disilicate. Observational analysis on FTIR suggest that non-thermal plasma does not alter enamel and dentin compounds(AU)

Development of a new HPLC method for in vitro and in vivo studies of haloperidol in solid lipid nanoparticles

ABSTRACT A simple and sensitive HPLC method was developed and validated for the quantification of haloperidol in solid lipid nanoparticles (SLNs). The developed method was used for detection of shelf life of haloperidol in SLNs. Calibration curve of haloperidol was also constructed in rat plasma using loratidine as internal standard. In vivo studies were performed on rats and concentration of haloperidol in brain and blood was measured for the determination of various pharmacokinetic and hence brain targeting parameters. Chromatogram separation was achieved using C18 column as stationary phase. The mobile phase consisted of 100 mM/L potassium dihydrogen phosphate-acetonitrile-TEA (10:90:0.1, v/v/v) and the pH was adjusted with o-phosphoric acid to 3.5. Flow rate of mobile phase was 2 mL/minute and eluents were monitored at 230 nm using UV/VIS detector. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Linearity for haloperidol was in the range of 1-16 µg/mL. The value of LOD and LOQ was found to be 0.045 and 0.135 μg/mL respectively. The shelf life of SLNs formulation was found to be 2.31 years at 4 oC. Various parameters like drug targeting index (DTI), drug targeting efficiency (DTE) and nose-to-brain direct transport (DTP) were determined for HP-SLNs & HP-Sol administered intranasally to evaluate the extent of nose-to-brain delivery. The value of DTI, DTE and DTP for HP-SLNs was found to be 23.62, 2362.43 % and 95.77% while for HP-Sol, values were 11.28, 1128.61 % and 91.14 % respectively.

Effect of natural honey on human platelets and blood coagulation proteins

Present study was conducted to determine the effects of honey on blood hemostasis, in-vitro effect of honey was observed on platelet aggregation and blood coagulation employing, activated partial prothrombin time [aPTT], prothrombin time [PT], thrombin time [TT] and fibrinogen levels in blood. Honey samples showed moderate inhibition of platelet aggregation with IC[50] 5-7.5%. The coagulation assays showed that at higher concentrations [>/= 15%] honey samples increased whole blood clotting time. When assayed in platelet poor plasma [PPP], honey samples significantly [P >/= 0.005] prolonged aPTT, PT, and TT. The honey samples [at 3.75% and 7.5% concentrations] cause mean increment of aPTT = 19 +/- 10% and 62 +/- 10%; PT 6 +/- 5% and 40 +/- 5%; TT 35 +/- 15% and 112 +/- 30% respectively. Moreover, PPP isolated from whole blood pre-incubated with honey samples [9.0% for 10 minutes] showed mean prolongation of aPTT, PT and TT of 45 +/- 21%, 26 +/- 9% and 105 +/- 24% respectively. Interestingly, incubation of honey at 6.25% and 11.75% concentrations in PPP considerably [P >/= 0.005] reduced fibrinogen levels i.e. 13 +/- 4% and 86 +/- 30% respectively. The present study outlines the inhibitory effect of natural honey on platelet aggregation and blood coagulation. These observations provide first line data for modulatory role [s] of honey on process of hemostasis

Effect of lithium metal on the chemical status of glutathione [GSH] present in whole blood [especially in plasma and cytosolic fraction in human blood]

Lithium remains a mainstay in the acute and prophylactic treatment of bipolar affective disorder. It is used in the augmentation of antidepressant treatment and, less frequently, in the augmentation of antipsychotic treatment of schizophrenia. It is reported to have specific anti-suicidal effects. Thus the effect of Lithium was interesting to study on the glutathione [GSH] level in vivo conditions. Ellman's method has been used to see the effect of lithium on glutathione [GSH] level in whole blood. The time dependent effect of Lithium on the chemical status of glutathione [GSH] was determined in the whole blood [Plasma and cytosolic fraction] of human. The concentration of Glutathione was drastically decreased. The decrease in the glutathione level was concentration and time of interaction dependent, probably due to oxidation of glutathione [GSH] to corresponding disulphide [GSSG]. In this paper the effect of Lithium on the Thiol/GSH level was discussed in vitro, which in principal may present a model of in vivo reaction

Determination of indinavir in human plasma and its use in pharmacokinetic study

We report the development and validation of a new sensitive, accurate and precise HPLC method with ultraviolet detection for the determination of indinavir sulfate (IND) in human plasma and its application to a bioequivalence study of a new generic formulation. The extraction of IND from plasma samples was achieved by using liquid-liquid extraction with a mean recovery of 73.9 percent. The lower limit of quantification was 0.05 µg/mL. Bioequivalence between the products was determined by calculating 90 percent confidence intervals (CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for the test and reference products, within the 0.80-1.25 interval proposed by ANVISA and FDA. Therefore the medications are bioequivalent and inter-exchangeable.

Foi desenvolvido e validado um novo método, sensível, exato e preciso por Cromatografia a Líquido de Alta Eficiência com detecção em UV para a determinação do sulfato de indinavir (IND) em plasma humano. O fármaco foi extraído do plasma através de extração líquido-líquido obtendo recuperação média de 73.9 por cento, com limite inferior de quantificação de 0.05 µg/mL. O método foi aplicado em estudo de farmacocinética para verificar a bioequivalência entre um novo medicamento genérico e seu produto de referência. A bioequivalência entre os produtos foi determinada calculando-se um intervalo de confiança (IC) de 90 por cento para a razão das médias do produto teste e referência compreendidas entre o intervalo de 0.80-1.25 proposto pela ANVISA e O FDA. Os produtos estudados são bioequivalentes e, portanto, intercambiáveis.

Development and validation of a new method for the quantification of norfloxacin by HPLC-UV and its application to a comparative pharmacokinetic study in human volunteers

The development and validation of a simple and accurate method based on HPLC with ultraviolet detection for the quantification of norfloxacin (NFX) in human plasma and its application to a bioequivalence study between two norfloxacin formulations is described. NFX and the internal standard (cyprofloxacin) were extracted from plasma using liquid-liquid extraction. Chromatographic separation of norfloxacin, cyprofloxacin and plasma interferents was achieved with a C-18 column and a mobile phase consisting of 20 mM sodium hydrogen phosphate buffer pH 3.0 and acetonitrile (88:12, v/v) and quantitation was done at 280 nm. The method was linear from 25 to 3000 ng mL-1 (r² > 0.997578), and norfloxacin and cyprofloxacin had an average recovery from plasma of 93.9 percent and 91.2 percent respectively. The RSD of inter-day quality control samples at the lower limit of quantification was less than 15 percent. After a single oral dose (400 mg) of norfloxacin administered to healthy human volunteers using a randomized 2x2 crossover design, pharmacokinetic parameters (AUC0-t, AUC0-00, Cmax, t1/2) were derived from the plasma concentration curves for both formulations. Pharmacokinetic analysis of the data showed that the two formulations were bioequivalent, while no adverse reactions to the drug were observed.

O desenvolvimento e validação de um método simples e preciso por CLAE-UV para quantificação de norfloxacino (NFX) em plasma humano e a sua aplicação a um estudo de bioequivalência entre duas formulações são descritos. NFX e o padrão interno (ciprofloxacino, PI) foram extraídos do plasma através de extração líquido-líquido. A separação cromatográfica do NFX, do PI e dos interferentes do plasma foi realizada com uma coluna C-18 e fase móvel composta de tampão fosfato de sódio 20 mM pH 3,0 e acetonitrila (88/12, v/v) e quantificado em 280 nm. A resposta do detector aos analitos mostrou-se linear entre 25 a 3000 ng mL-1 (r² > 0,997578) e a recuperação média de NFX e PI foi de 93,9 por cento e 91,2 por cento respectivamente. O desvio padrão relativo de amostras analisadas ao nível do limite inferior de quantificação foi menor que 15 por cento. Foi administrada uma dose de NFX (400 mg) por via oral a voluntários humanos em um estudo aberto, aleatório e cruzado 2x2 entre duas formulações. Os parâmetros farmacocinéticos (AUC0-t, AUC0-00, Cmáx, T1/2) foram observados a partir da curva de concentração versus tempo. A análise farmacocinética mostrou que as duas formulações são bioequivalentes entre si. Nenhum efeito adverso foi observado.

Determinações plasmáticas de glicose, colesterol e triglicérides em potras sadias, da raça Brasileiro de Hipismo / Plasma values of glucose, cholesterol and triglycerides of healthy Brasileiro de Hipismo fillies

Utilizaram-se 380 amostras de plasma sangüíneo coletadas de 22 potras Brasileiro de Hipismo, sadias, desde o nascimento até 24 meses de idade. Os valores médios de colesterol foram máximos entre o nascimento e 24 horas de vida, enquanto que para glicose e triglicérides, o maior valor ocorreu entre três e quatro dias de vida. Os valores médios de colesterol e triglicérides diminuíram progressivamente até os 13 meses de idade, quando se estabilizaram. Foi observada redução progressiva das concentrações de glicose até nove meses, estabilizando-se a seguir. Houve influência dos fatores etários sobre as variações de todas as determinações bioquímicas, particularmente no período inicial de vida dos animais estudados.

Plasma biochemical values were determined in 380 samples obtained from 22 clinically normal Brasileiro de Hipismo fillies from birth to 24 months old. Statistical analysis showed higher concentrations of cholesterol between 0-4 hours and 24 hours after birth, while glucose and triglycerides with 3-4 days of age. Glucose concentrations decreased until nine months old, then remained fairly constant. Cholesterol and triglycerides decreased gradually with advancing of age until 13 months and then stabilized. It was concluded that the plasma biochemical values were influenced by age, particularly in the newborn foals considered in the study.

Validation of an electrometric blood cholinesterase measurement in goats

A modified electrometric method was described and validated for measurement of plasma and erythrocyte cholinesterase activities in 6~18 months old goats. The enzymatic reaction mixture contained 3 ml distilled water, 3 ml barbital-phosphate buffer (pH 8.1), 0.2 ml plasma or erythrocytes and 0.1 ml acetylthiocholine iodide (7.5%) as a substrate. The mixture was incubated at 37 degrees C for 40 minutes. The pH of the reaction mixture was determined by a pH meter before and after the incubation. The initial pH was measured before the substrate addition. The enzyme activity was expressed as deltapH/40 min. The coefficients of variation of the described method in measuring plasma and erythrocyte cholinesterase activities were 4 and 2%, respectively. Preliminary reference values (n = 14) of the mean cholinesterase activity (deltapH/40 min) and 95% confidence interval in the plasma were 0.194 and 0.184~ 0.204, respectively, and those of the erythrocytes were 0.416 and 0.396~0.436, respectively. The pseudocholinesterase activity of the plasma cholinesterase was 63.5% as determined by quinidine sulfate inhibition. The organophosphorus insecticides dichlorvos and diazinon at 0.5~4 micrometer and the carbamate insecticide carbaryl at 5~20 micrometer in the reaction mixture significantly inhibited plasma (13.7~85.5%) and erythrocyte (16.4~71.9%) cholinesterases in vitro in a concentration-dependent manner. The results suggest that the described electrometric method is simple, precise and efficient in measuring blood cholinesterase activity in goats.

Piroxicam-zinco: cinética em sangue e linfa e efeito na mucosa gástrica / Zinc-piroxicam: kinetic in blood and lymph and effect on the gastric mucosa

Vários mecanismos foram propostos para reduzir a toxicidade gástrica dos fármacos antiinflamatórios. A complexação com zinco foi proposta considerando-se o fato de que o zinco possui ação protetora sobre a mucosa gástrica. O complexo piroxicam-zinco apresenta atividade antiinflamatória e analgésica semelhantes às do fármaco livre. No entanto, a modificação de propriedades físico-químicas acarretou alteração do perfil cinético do fármaco. A fim de investigar as diferenças farmacocinéticas, o complexo piroxicam-zinco foi estudado quanto à farmacocinética em sangue e linfa de ratos. Estudaram-se também os efeitos do complexo na mucosa gástrica em comparação com o piroxicam livre em modelos de úlcera induzida por ácido acetilsalicílico e por etanol...

Biodisponibilidade dos carotenóides do Buriti (Mauritia flexuosa L.) em ratos / Bioavailability of Carotenoids from Buriti (Mauritia flexuosa) L.) in rats

Considerando a magnitude da hipovitaminose A como problema de saúde pública no mundo e a disponibilidade de frutos ricos em pró-vitamina A na regiäo amazônica, determinou-se biodisponibilidade dos carotenóides do Buriti (Mauritia flexuosa L.) em ratos. Quarenta e oito ratos machos da linhagem Wistar (Rathus novergicus, var. albinus, Rodentia: Mamalia) recém-desmamados, com peso médio nicial de 33,8 + ou - 1,7g, foram distribuídos em cinco grupos, ou seja, Grupos: Deficintes, Controle 1200, controle 2400, Buriti 1200 e Buriti 2400. As Racöes foram elaboradas de acordo com a recomendaçäo do Committee on Laboratory animal Diets (1993). Após o período experimental de 28 dias, todos os animais foram sacrificados para a determinaçäo de vitamina A e caroteno no plasma e no plasma e no fígado. A menor concentraçäo de vitamina A hepática e plasmática foi observada no Grupo Deficiente. Por sua vez, as reservas hepáticas de vitamina A dos animais dos grupos Buriti 1200 e 2400 foram significativamente superiores quando comparados com os grupos Controle 1200 e 2400, respectivamente. Os resultados desse estudo demontraram ser o buriti uma fonte de pró-vitamina A altamente biodisponível, com eficiência relativa de 254,6 porcento (1200ER/Kg raçäo e 179,4 porcento (2400 ER/Kg raçäo) quando comparados com os respectivos grupos controle, indicando a maior biodisponibilidade dos carotenóides em doses próximas à recomendada.

Plasma levels of tumor necrosis factor-alfa in patients with visceral leishmaniasis (Kala-azar): association with activity of the disease and clinical remission following antimonial therapy

Avaliacao de TNF-alfa em pacientes com calazar tem despertado grande interesse devido ao seu papel no sistema imunologico e a sua atividade caquetizante. O objetivo deste estudo foi examinar a associacao entre os niveis plasmaticos de TNF-alfa, medidos atraves de sua imunorreatividade (ELISA) e bioatividade (ensaio citotoxico sobre as celulas L-929), e as manifestacoes clinicas da leishmaniose visceral. Amostras de 19 pacientes foram obtidas para determinacao do TNF-alfa antes, durante e apos a terapia antimonial, utilizando o ensaio de citotoxidade (todos os pacientes) e o ELISA (14 pacientes). Resultados discrepantes entre os ensaios de citotoxidade e o ELISA foram observados...

Regresión de hipertrofia ventricular izquierda con isradipino en pacientes hipertensos / Regression of left ventricular hypertrophy with isradipine in hypertensive patients

La hipertrofia ventricular izquierda (HVI) es un factor de riesgo cardiovascular importante, frecuentemente asociado a hipertensión arterial (HTA). Su regresión en estos paciem¿ntes podría asociarse a beneficios en la historia natural de la enfermedad hipertensiva, lo que pareciera depender en alguna medida del control de las cifras de presión arterial. La eficacia en inducir regresión de HVI en seres humanos pudiera ser diferente según el tipo de fármaco antihipertensivo. Hemos evaluado la hipótesis de isradipino, un antagonista del calcio con marcada selectividad vascular, en dosis normotensantes induce regresión de HVI en nuestros pacientes hipertensos que presentan HVI. 19 pacientes (edad promedio 59 años, 9 mujeres) con HTA esencial e HVI (séptum + pared posterior VIò 23 mm) comenzaron a ser tratados con isradipino (Dynacirc SROr) y 18 pacientes completaron 12 meses con una sola dosis diaria matinal normotensante (promedio final 16,4 ñ 3,3 mg/día). En 7 pacientes se complementó con una dosis baja de hidroclorotiazida y triamterene con objeto de mantener cifras tensionales normales. Se realizó ecocardiograma basal, a los 3, 6 y 12 meses de tratamiento, midiéndose séptum VI (sp,mm), pared posterior de VI (pp,mm) y dimensión diastólica (DD,mm), con lo que se calculó la masa ventricular VI. Además de la normotensión mantenida se observó una disminución significativa, a contar del tercer mes de tratamiento de los grosores del sp,pp y diámetros de la cavidad VI, así como de la masa VI, la que alcanzó a los 12 meses un 81 por ciento de la masa inicial del VI. No hubo modificaciones de la función ventricular ni de la frecuencia cardíaca. Tampoco se modificó la función renal. En conclusión, estos resultados demuestran que isradipino, en una sola dosis diaria normotensante, es capaz de inducir regresión significativa de HVI en pacientes con HTA. Esta regresión está dad por disminución tanto del grosor de las paredes como de las dimensiones del VI y comenzó a observarse desde los 3 meses de tratamiento

Dietary polyunsaturated fatty acids, and tissue oxidative stress: the effect of d,l-Ó-tocopherol

The effects of feeding young and aged rats with high doses of polyunsaturated fatty acids from marine oil on the susceptibility of erythrocyte membranes to the induction of oxidative stress, on the level of reduced glutathione of different tissues, and on the antioxidant capacity of blood plasma were studied. The protective effect of the supplementation of the oil with d,l-alpha-tocopherol was also assayed. d,l-alpha-Tocopherol supplementation protects erythrocyte membranes from young rats against the induction of oxidative stress, being unable to protect the membranes from the aged ones. The tripeptide glutathione shows a different behavior depending on the tissue. Blood glutathione is not affected by fish oil ingestion and by the d,l- alpha-tocopherol supplementation either in the young or in the aged animals. Liver glutathione is reduced by fish oil feeding in the aged animals only. Brain glutathione is not affected by the fish oil feeding. The supplementation with d,l-alpha-tocopherol restores the hepatic levels of glutathione and increases the brain level of the tripeptide over the controls, this effect being observed for young and the aged rats. The antioxidant capacity of blood plasma in response to the fish oil feeding increases in the young rats only. This capacity is not affected by the suplementation with d,l-alpha-tocopherol. These metabolic changes are ascribed to possible adaptative responses from the animals to the potential risk of oxidative stress induced by fish oil ingestion. We suggest that metabolic risks may be associated with the consumption of high doses of polyunsaturated fatty acids.

Jaundice in new born and erythrocyte and plasma antioxidant defence system.

Alteration in the antioxidant defence mechanism of erythrocytes with rise in serum unconjugated bilirubin level in neonates has been observed. The cellular glutathione level was found to be significantly low. The activity of glutathione reductase in erythrocyte increased to combat the cellular loss of reduced glutathione in neonatal jaundice. In plasma fraction the level of glutathione (reduced) was found to be significantly higher with lowering of glutathione reductase level. Glutathione peroxidase was reduced in cellular level whereas an increase was observed in plasma fraction. Gamma glutamyl transpeptidase level was barely detectable in erythrocyte whereas an increase was observed in plasma fraction. In all the cases erythrocyte G-6-PDH activity level was found within normal limits.

Enfermedad de la orina olor a jarabe de arce / Maple syrup urine disease

La enfermedad de la orina olor a jarabe de arce, es una afección metabólica producida por deficiencia en la descarboxilación oxidativa de los quetoácidos provenientes de los aminoácidos ramificados valina, isoleucina y leucina. Los pacientes parecen normales hasta los 5 a 7 días de vida, cuando muestran rechazo a la alimentación, vómitos, olor a jarabe de arce en la orina y la piel y deterioro neurológico progresivo, que lleva rápidamente al coma. Se presentan tres niños con enfermedad de la orina olor a jarabe de arce clásica, leucina >2 000 µmol/1, que fueron diagnosticados a los 10, 20 y 21 días de vida, iniciándose inmediatamente el tratamiento en base a la dieta especial. el seguimiento está basado en evaluaciones clínicas, nutricionales y bioquímicas periódicas, para adecuar los requerimientos nutricionales a la evolución de la enfermedad. La evaluación psicométrica, escala de Bayley, mostró que el coeficiente de desarrollo mental estaba entre 50 y 82, relacionándose éste con la edad de diagnóstico. Actualmente los niños tienen entre 2 y 3 años de edad, se encuentran con dieta restringida en los 3 aminoácidos ramificados. Su control debe ser frecuente para evitar desbalances metabólicos y prevenir daños neurológicos ocasionados por éstos

Efecto comparativo de aceites de origen vegetal o marino y suplementación de colesterol en lípidos de plasma e hígado de rata / Comparative effect of vegetable or marine oils and cholesterol supplementation on plasma and liver lipids of the rat

Los aceites poseen una composición acil grasa característica, responsable de muchos de sus efectos biológicos, que pueden modificarse por la ingestión concomitante de colesterol. En el estudio se evaluó el efecto de la ingestión de aceites de maíz, avellana y pescado, y la suplementación con colesterol, sobre los niveles de lípidos plasmáticos y hepáticos. Ratas macho se alimentaron con dieta que contenía 15 por ciento de aceite, sin/con 1 por ciento colesterol, durante 20 días. El grupo con avellanas exhibió la mayor concentración plasmática de colesterol, p<0,001, en tanto que el grupo con aceite de pescado presentó los niveles más bajos, p<0,001. El grupo con maíz/colesterol exhibió menos concentración de HDL, p<0,001, la cual aumentó en el grupo con aceite de pescado/colesterol. El peso del hígado fue mayor en el grupo con maíz/colesterol, p<0,001. El colesterol indujo un incremento de los lípidos hepáticos en los grupos con aceites vegetales. Los lípidos hepáticos fueron más bajos al ingerir aceite marino/colesterol, p<0,001. Los resultados indican que el aceite de pescado indujo los niveles más bajos de lípidos en plasma, en tanto que el de avellana es hipercolesterolémico, mostrando estrecha relación entre las grasas dietarias (ácidos grasos y colesterol) y los lípidos plasmáticos y hepáticos

Incidência da gengivite dilantínica e sua possível correlaçäo com dados clínicos e laboratoriais / Prevalence of dilantin gingivitis and its possible correlation with clinical and laboratorial dates

Os autores tentaram correlacionar a presença ou ausência da gengivite dilantínica frente a dados clínicos (exame clínico e anamnese) e laboratoriais (dosagem das concentraçöes plasmáticas e salivar), levando-se em consideraçäo sexo, faixa etária, tempo de uso e dosagem da droga e higiene bucal. Os dados näo permitem conclusöes, porém, é salientada a importância da suscetibilidade individual à difenilhidantoina, considerando-a como ponto inicial da problemática