RESUMEN
PURPOSE: Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. METHODS: Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson's trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. RESULTS: Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p < 0.05) and 1144 + ALPHA (p = 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. CONCLUSIONS: Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.
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Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Fibrosis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Síndrome Metabólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Testosterona/análogos & derivados , Andrógenos/farmacología , Animales , Fibrosis/etiología , Fibrosis/patología , Inflamación/etiología , Inflamación/patología , Masculino , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , Profármacos/farmacología , Conejos , Testosterona/farmacologíaRESUMEN
BACKGROUND: There is a need to evaluate and implement cost-effective strategies to improve adherence to treatments in coronary heart disease. There are no studies from low- to middle income countries (LMICs) evaluating trained community health worker (CHW)-based interventions for the secondary prevention of coronary heart disease. METHODS: We designed a hospital-based, open randomized trial of CHW-based interventions versus standard care. Patients after an acute coronary syndrome (ACS) were randomized to an intervention group (a CHW-based intervention package, comprising education tools to enhance self-care and adherence, and regular follow-up by the CHW) or to standard care for 12 months during which study outcomes were recorded. The CHWs were trained over a period of 6 months. The primary outcome measure was medication adherence. The secondary outcomes were differences in adherence to lifestyle modification, physiological parameters (blood pressure [BP], body weight, body mass index [BMI], heart rate, lipids), and major adverse cardiovascular events. RESULTS: We recruited 806 patients stabilized after an ACS from 14 hospitals in 13 Indian cities. The mean age was 56.4 (± 11.32) years, and 17.2% were females. A high prevalence of risk factors such as hypertension (43.4%), diabetes (31.9%), tobacco consumption (35.4%), and inadequate physical activity (70.5%) was documented. A little over half had ST-elevation myocardial infarction (53.7%), and 46.3% had non-ST-elevation myocardial infarction or unstable angina. CONCLUSION: The CHW interventions and training for SPREAD have been developed and adapted for local use. The results and experience of this study will be important to counter the burden of cardiovascular diseases in low- to middle income countries.
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Síndrome Coronario Agudo/prevención & control , Servicios de Salud Comunitaria/métodos , Agentes Comunitarios de Salud , Cumplimiento de la Medicación , Educación del Paciente como Asunto/métodos , Proyectos de Investigación , Conducta de Reducción del Riesgo , Prevención Secundaria/métodos , Autocuidado , Adulto , Anciano , Presión Sanguínea , Índice de Masa Corporal , Femenino , Frecuencia Cardíaca , Humanos , India , Lípidos/sangre , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
INTRODUCTION: Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality in low-income countries including India. There is a need for effective, low-cost methods to prevent CVDs in rural India. One strategy is to identify and implement interventions at high-risk individuals using community health workers (CHWs). There is a paucity of CHW-based CVD intervention trials from low-income countries. METHODS: We designed a multicenter, household-level, cluster-randomized trial with 1:1 allocation to intervention and control arms. The CHWs undertook a door-to-door survey and screened 5,699 households in 28 villages from 3 rural regions in India to identify at-risk households. The households were defined as those with ≥1 individual aged ≥35 years and at moderate or high risk for CVD based on the non-laboratory-based National Health and Nutrition Examination Survey score. All at-risk individuals were invited to attend a physician-led village clinic that provided a CVD risk reduction prescription and education about target risk factor levels for CVD control. All households in which at least 1 member at moderate to high risk for CVD had received a risk reduction prescription were eligible for randomization. Households randomized to the CHW-based intervention will receive 1 household visit by a CHW every 2 months, for 12 months. During these visits, CHWs will measure blood pressure, ascertain and reinforce adherence to prescribed therapies, and modify therapy to meet targets. Households randomized to the control arm do not receive CHW visits. At 12 months after randomization, we will evaluate 2 primary outcomes of systolic blood pressure and adherence to antihypertensive drugs and secondary outcomes of INTERHEART risk score, body mass index, and waist-to-hip ratios. At 18 to 24 months after randomization and 6 to 12 months after the last intervention, we will record these outcomes to evaluate sustainability of intervention. RESULTS: Community health workers screened a total of 5,033 households that included 9,248 individuals and identified 2,571 households with 3,784 at-risk individuals. We randomized 2,438 households (1,219 to intervention and 1,219 to control groups). CONCLUSION: Our large trial of CHWs in rural India will provide important information regarding a promising approach to primary prevention of CVDs.
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Enfermedades Cardiovasculares/prevención & control , Agentes Comunitarios de Salud , Promoción de la Salud , Cumplimiento de la Medicación , Prevención Primaria/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Algoritmos , Protocolos Clínicos , Humanos , Conducta de Reducción del RiesgoRESUMEN
GRIM-19 (Gene associated with Retinoid-IFN-induced Mortality-19) was originally isolated as a growth suppressor in a genome-wide knockdown screen with antisense libraries. Like classical tumor suppressors, mutations, and/or loss of GRIM-19 expression occur in primary human tumors; and it is inactivated by viral gene products. Our search for potential GRIM-19-binding proteins, using mass spectrometry, that permit its antitumor actions led to the inhibitor of cyclin-dependent kinase 4, CDKN2A. The GRIM-19/CDKN2A synergistically suppressed cell cycle progression via inhibiting E2F1-driven gene expression. The N terminus of GRIM-19 and the fourth ankyrin repeat of CDKN2A are crucial for their interaction. The biological relevance of these interactions is underscored by observations that GRIM-19 promotes the inhibitory effect of CDKN2A on CDK4; and mutations from primary tumors disrupt its ability to interact with GRIM-19 and suppress E2F1-driven gene expression.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Ciclo Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Factor de Transcripción E2F1/metabolismo , Regulación Neoplásica de la Expresión Génica , NADH NADPH Oxidorreductasas/metabolismo , Secuencia de Aminoácidos , Animales , Repetición de Anquirina , Proteínas Reguladoras de la Apoptosis/química , Proteínas Reguladoras de la Apoptosis/deficiencia , Proteínas Reguladoras de la Apoptosis/genética , Línea Celular Tumoral , Ciclina D1/metabolismo , Quinasa 4 Dependiente de la Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/química , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Fase G1 , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Datos de Secuencia Molecular , Mutación , NADH NADPH Oxidorreductasas/química , NADH NADPH Oxidorreductasas/deficiencia , NADH NADPH Oxidorreductasas/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Estructura Terciaria de ProteínaRESUMEN
A total of 2400 patients with pyrexia of unknown origin and or suspected leptospirosis were included in this study. Dark field microscopy detected Leptospira in 690 cases, Leptospira serological Investigations proved positive in 570 out of these 690 patients. Among them 212 had the classical icteric and the other 358 had anicteric type of presentation. Notably eptospira interrogans serovar ictero haemorrhagiae infection was encountered in 212 patients. In 30 patients, who had multi organ dysfunction which included renal failure, hepatic dysfunction or meningitis was due to Leptospira interrogans Serovar cannicola. Coexsistense of leptospirosis and hepatitis B virus infection were noted in 15 patients. Antibody to Leptospira interrogans was demonstrated by Micro agglutination test (MAT) in addition to dark field microscopy positivity in these cases. Similarly HIV antibody was demonstrated in 30 of the 330 anicteric patients. 554 out of 570 cases responded to intra venous penicillin (216), and oral Doxycycline (182) and Augmentin (156), and the remaining 16 patients succumbed to death.
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Leptospira/patogenicidad , Leptospirosis/patología , Enfermedad de Weil/patología , Zoonosis , Adolescente , Adulto , Anciano , Animales , Niño , Preescolar , Femenino , Humanos , Leptospira/clasificación , Leptospira interrogans/clasificación , Leptospira interrogans/patogenicidad , Leptospirosis/tratamiento farmacológico , Leptospirosis/epidemiología , Leptospirosis/transmisión , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/microbiología , Prevalencia , Enfermedad de Weil/tratamiento farmacológico , Enfermedad de Weil/epidemiología , Enfermedad de Weil/transmisiónRESUMEN
AIM: To conduct a systematic review on the prevalence, risk factors, treatments and outcomes of Coronary Artery Disease (CAD) in Indians. METHODS AND RESULTS: We conducted a systematic review of studies in Indians with CAD from Jan 1969 to Oct 2012. Initial search yielded 3885 studies and after review 288 observational studies were included. The prevalence of CAD in urban areas was 2.5%-12.6% and in rural areas, 1.4%-4.6%. The prevalence of risk factors was: smoking (8.9-40.5%), hypertension (13.1-36.9%) and diabetes mellitus (0.2-24.0%). The median time to reach hospital after an MI was 360 min. In hospital rates of drug use were: antiplatelets 68%-97.9%, beta blockers 47.3%-65.8% and ACEIs 27.8-56.8%. CONCLUSIONS: In this first systematic review of CAD in India, prevalence of risk factors is high, treatments delayed and use of evidence based treatments variable.
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Enfermedad de la Arteria Coronaria , Manejo de la Enfermedad , Medición de Riesgo , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/terapia , Humanos , India/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
Current evidence suggests that CD38, a lymphocyte differentiation antigen, has been found to be functionally indistinguishable from the native form when it was expressed as a soluble and non-glycosylated protein in yeast. Studies were conducted to evaluate the functional role of glycosylation on the membrane-bound CD38 in mammalian cells. The stable transformants of CHO cells were established with pXJ41-CD38 construct and the recombinant CD38 was detected at the surface of CHO cells using a polyclonal antibody to rat CD38 by immunocytochemistry. The recombinant protein displaying ADP-ribosyl cyclase activity was purified from CHO cells, which appeared as 42 and 46 kDa bands on immunoblot under non-reducing and reducing conditions, respectively. The recombinant CD38 was then subjected to deglycosylation with N-glycosidase F that resulted in a 33 kDa band on immunoblot under reducing condition. Further the partial deglycosylation of the recombinant CD38, performed at various time intervals, resulted in a series of bands (33-46 kDa) on immunoblot. Kinetic analysis indicated that deglycosylation of the recombinant CD38 showed a considerable decrease in Vmax and an increase in K(m) of ADP-ribosyl cyclase activity. These observations clearly suggest that glycosylation plays an important role to maintain the enzymatic activity and substrate affinity of CD38/ADP-ribosyl cyclase for mediating the signalling events in mammalian cells.
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Antígenos CD , Antígenos de Diferenciación/metabolismo , NAD+ Nucleosidasa/metabolismo , ADP-Ribosil Ciclasa , ADP-Ribosil Ciclasa 1 , Animales , Antígenos de Diferenciación/química , Antígenos de Diferenciación/genética , Células CHO , Cricetinae , Glicosilación , Inmunohistoquímica , Cinética , Glicoproteínas de Membrana , Peso Molecular , NAD+ Nucleosidasa/química , NAD+ Nucleosidasa/genética , Ratas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transformación GenéticaRESUMEN
Apoptosis is a tightly regulated mechanism that controls the proliferation of cells in metazoans. In mammals, multiple genes are required to regulate cell death. We have employed a gene expression knockout technique to isolate cell death-related genes. One such gene, gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), is essential for tumor cell death induced by interferon-beta (IFN-beta) and retinoic acid (RA). Here, we describe the localization of GRIM-19 to human chromosome 19p13.2. This region is essential for prostate tumor suppression. Together with its death-inductive role in the IFN-retinoid-regulated pathways and the tumor-suppressive function of this locus, the data suggest that GRIM-19 may be a novel tumor suppressor.
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Cromosomas Humanos Par 13 , Genes Supresores de Tumor , Interferón beta/farmacología , Tretinoina/farmacología , Neoplasias de la Mama , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Mapeo Cromosómico , ADN sin Sentido , Femenino , Biblioteca Genómica , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Células Tumorales CultivadasRESUMEN
New layered matrix systems designed for zero-order sustained release are presented. The devices consist of a hydrophobic middle layer and press-coated hydrophillic and/or hydrophobic barrier layer(s). The systems overcome the inherent disadvantage of non-linear release associated with diffusion-controlled matrix devices by providing additional releasing surface with time to compensate for the decreasing release rate. The in vitro release of pseudoephedrine hydrochloride as a model compound from the matrices was examined. Modulation of release from a selected matrix containing aminophylline was evaluated in a crossover study using nine beagle dogs. Preliminary in vitro/in vivo correlation was also studied. The systems described in this paper can potentially be scaled up to commercial production.
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Preparaciones de Acción Retardada , Aminofilina/farmacocinética , Animales , Difusión , Perros , Técnicas In Vitro , Modelos Biológicos , Propiedades de Superficie , Comprimidos , Teofilina/farmacocinéticaRESUMEN
Statistical designs were used to study the effect of certain matrix formulation variables on the vitro release of a model compound, pseudoephedrine hydrochloride, from layered diffusional matrices designed for zero-order sustained release. These matrices consist of non-swellable, hydrophobic middle layers containing the active drug to which hydrophilic and/or hydrophobic barrier layers are press-coated. In general, linear release profiles can be obtained by applying hydrophilic barrier layers on both faces of a hydrophobic matrix tablet, or by applying a hydrophilic barrier layer on one face and a hydrophobic barrier layer on the other face of the matrix tablet. However, formulation and matrix variables in the barrier layers need to be controlled in order to achieve zero-order drug release from a hydrophobic matrix tablet coated with hydrophobic barrier layers on both faces.
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Preparaciones de Acción Retardada , Difusión , Efedrina/administración & dosificación , MatemáticaRESUMEN
A study was carried out to determine the effect of excess surfactant on transport kinetics in emulsions, using surface-active (phenobarbital, barbital) and non-surface-active (phenylazoaniline, benzocaine) model drugs (pH 7.0). Mineral oil was chosen as the oil phase, and the ionic surfactant cetyltrimethylammonium bromide (CTAB) was chosen as the emulsifier. The effect of nonionic surfactant Brij 97 on transport kinetics of these model drugs were determined by authors elsewhere. Model drug transport in the triphasic systems was investigated using side-by-side diffusion cells mounted with hydrophilic dialysis membranes (molecular weight cutoffs 1 kD and 50 kD) and a novel bulk equilibrium reverse dialysis bag technique. Emulsion stability was determined by droplet size analysis as a function of time, temperature, and the presence of model drugs using photon correlation spectroscopy. Mineral oil/water partition coefficients and aqueous solubilities were determined in the presence of surfactant. The droplet size of the CTAB-stabilized emulsion system is bigger than that of the Brij 97-stabilized system because of the relatively less dense interfacial packing of the cationic surfactant. CTAB forms a complex with the model drugs because of ionic interaction between CTAB and the aromatic and azo groups of the model drugs. This complexation is expected to increase emulsion stability and affect model drug transport kinetics. The transport rates of model drugs in emulsions increased with increases in CTAB micellar concentrations up to 0.5% w/v and then decreased at higher surfactant concentrations. Total transport rates of phenobarbital and barbital were faster than those of phenylazoaniline and benzocaine. Excess surfactant affected the transport rates of the model drugs in the emulsions depending on drug surface activity and lipophilicity. The transport profiles of the model drugs appeared to be governed by model drug oil/water partition coefficient values and by micellar shape changes at higher surfactant concentrations.
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Preparaciones Farmacéuticas/química , Tensoactivos/química , Barbital/química , Benzocaína/química , Transporte Biológico , Cetrimonio , Compuestos de Cetrimonio/química , Diálisis/instrumentación , Emulsiones , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Membranas Artificiales , Micelas , Aceite Mineral , Modelos Biológicos , Tamaño de la Partícula , Preparaciones Farmacéuticas/metabolismo , Fenobarbital/química , Reología , Propiedades de Superficie , Agua , p-Aminoazobenceno/químicaRESUMEN
The effect of surfactant concentration on transport kinetics in emulsions using surface-active (phenobarbital, barbital) and non- surface-active (phenylazoaniline, benzocaine) model drugs is determined. Mineral oil was chosen as the oil phase and the nonionic surfactant polyoxyethylene-10-oleyl-ether (Brij 97) was chosen as the emulsifier. Model drug transport in the triphasic systems was investigated using side-by-side diffusion cells mounted with hydrophilic dialysis membranes (molecular weight cutoffs 1 kd and 50 kd) and a novel bulk equilibrium reverse dialysis bag technique. Emulsion stability was determined by droplet size analysis as a function of time, temperature, and the presence of model drugs, using photon correlation spectroscopy. Mineral oil/water (O/W) partition coefficients and aqueous solubilities were determined in the presence of surfactant. The transport rates of model drugs in emulsions increased with an increase in Brij 97 micellar concentrations up to 1.0% wt/vol and then decreased at higher surfactant concentrations. The transport profiles of the model drugs appeared to be governed by model drug O/W partition coefficient values and by micellar shape changes at higher surfactant concentrations. Total transport rates of phenobarbital and barbital were faster than those of phenylazoaniline and benzocaine. Excess surfactant affected the transport rates of the model drugs in the emulsions depending on drug surface activity and lipophilicity.
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Preparaciones Farmacéuticas/química , Tensoactivos/química , Barbital/química , Benzocaína/química , Transporte Biológico , Diálisis/instrumentación , Emulsiones , Concentración de Iones de Hidrógeno , Cinética , Membranas Artificiales , Micelas , Aceite Mineral , Modelos Biológicos , Peso Molecular , Tamaño de la Partícula , Preparaciones Farmacéuticas/metabolismo , Fenobarbital/química , Aceites de Plantas/química , Polietilenglicoles/química , Reología , Propiedades de Superficie , Agua , p-Aminoazobenceno/químicaRESUMEN
Mathematical models were developed for the prediction of surface-active and non- surface-active drug transport in triphasic (oil, water, and micellar) emulsion systems as a function of micellar concentration. These models were evaluated by comparing experimental and simulated data. Fick's first law of diffusion with association of the surface-active or complexation nature of the drug with the surfactant was used to derive a transport model for surface-active drugs. This transport model assumes that the oil/water (O/W) partitioning process was fast compared with membrane transport and therefore drug transport was limited by the membrane. Consecutive rate equations were used to model transport of non-surface-active drugs in emulsion systems assuming that the O/W interface acts as a barrier to drug transport. Phenobarbital (PB) and barbital (B) were selected as surface-active model drugs. Phenylazoaniline (PAA) and benzocaine (BZ) were selected as non- surface-active model drugs. Transport studies at pH 7.0 were conducted using side-by-side diffusion cells and bulk equilibrium reverse dialysis bag techniques. According to the surface-active drug model, an increase in micellar concentration is expected to decrease drug-transport rates. Using the Microsoft EXCEL program, the non-surface-active drug model was fitted to the experimental data for the cumulative amount of the model drug that disappeared from the donor chamber. The oil/continuous phase partitioning rates (k1) and the membrane transport rates (k2) were estimated. The predicted data were consistent with the experimental data for both the surface-active and non- surface-active models.
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Preparaciones Farmacéuticas/química , Tensoactivos/química , Algoritmos , Barbital/química , Benzocaína/química , Transporte Biológico , Cationes , Cetrimonio , Compuestos de Cetrimonio/química , Diálisis/instrumentación , Difusión , Emulsiones , Concentración de Iones de Hidrógeno , Cinética , Micelas , Aceite Mineral , Modelos Biológicos , Preparaciones Farmacéuticas/metabolismo , Fenobarbital/química , Aceites de Plantas/química , Polietilenglicoles/química , Propiedades de Superficie , Agua , p-Aminoazobenceno/químicaRESUMEN
Sink conditions are often violated when using conventional release methods for dispersed systems. A novel reverse dialysis bag method was designed to overcome this problem. Model drug transport rates from submicron emulsions obtained using the conventional diffusion cell method and this novel method were compared. In the side-by-side diffusion cell method, emulsions were placed in the donor chamber and surfactant/buffer solutions in the receiver chamber. In the novel dialysis bag method, emulsions were diluted infinitely in the donor phase and surfactant/buffer solutions were placed in the receiver phase (dialysis bags). Slow release rates and linear release profiles were obtained using the side-by-side diffusion cell method apparently due to limited model drug solubility in the donor chamber resulting in violation of sink conditions. Biphasic release profiles were obtained using the dialysis bag method apparently due to an initial rapid release of free and micellar solubilized model drug from the donor to the receiver chambers followed by slow release from the oil droplets. Using both release methods, an initial increase and latter decrease in release rates were observed with increase in surfactant concentration. The initial increase was considered to be due to a decrease in the model drug oil-in-water partition coefficients and the subsequent decrease in release rates was due to micellar shape change (spheres to rods) causing a decrease in diffusion rates. Sink conditions were violated using the side-by-side diffusion cell method but were maintained in the dialysis bag method since emulsions were diluted infinitely in the donor phase.
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Preparaciones Farmacéuticas/química , Benzocaína/química , Diálisis/instrumentación , Difusión , Emulsiones , Cinética , Micelas , Solubilidad , Agua , p-Aminoazobenceno/químicaRESUMEN
Anesthetic drugs are frequently mixed or coadministered to optimize anesthetic effects while minimizing adverse effects. Methohexital advantages include its low cost and rapid onset, while propofol provides improved airway anesthesia and extremely rapid clearance from the plasma. Therefore, a mixture of these agents might well be superior to either drug given alone. We wished to determine whether a mixture of methohexital and propofol is chemically and physically stable. A 1:1 mixture of propofol 10 mg/ml and methohexital was prepared. At times varying from 0 to 48 hours, mixtures with an internal standard of thymol kept at room temperature were thrice extracted with a 2:1 v/v mixture of diethyl ether:pentane, dried under nitrogen, and treated overnight with bis-trimethylsilyl-trifluoroacetamide. The resultant derivatives were transferred to microsample vials and analyzed by GC-MS. Drug stability was quantified by electronic integration of peak areas representing characteristic ions for each drug. For each sample, the peak area of the methohexital ion (m/z 239) or propofol ion (m/z 235) relative to the corresponding thymol ion (m/z 207) served as an index of the concentration of the drug in the sample. At times varying from 0 to 48 hours, mixtures without thymol were used to determine mean droplet size of the particles. This was accomplished using both an Accusizer and a Nicomp 370 Particle Sizer. One way ANOVA tested for significant changes in drug concentrations and mean particle size as a function of time. There was no significant breakdown of propofol or methohexital when combined in a 1:1 mixture and allowed to stand for 48 hours, nor was there an increase in particle size suggestive of emulsion instability. We concluded that a 1:1 mixture of propofol and methohexital was stable up to 48 hours after mixing.
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Anestésicos Intravenosos/química , Metohexital/química , Propofol/química , Análisis de Varianza , Biofarmacia , Fenómenos Químicos , Química Física , Combinación de Medicamentos , Estabilidad de Medicamentos , Emulsiones , Cromatografía de Gases y Espectrometría de Masas , Humanos , Tamaño de la Partícula , Factores de TiempoRESUMEN
Indians have high rates of cardiovascular disease. Hypertension (HTN) is an important modifiable risk factor. There are no comprehensive reviews or a nationally representative study of the burden, treatments and outcomes of HTN in India. A systematic review was conducted to study the trends in prevalence, risk factors and awareness of HTN in India. We searched MEDLINE from January 1969 to July 2011 using prespecified medical subject heading (MeSH) terms. Of 3372 studies, 206 were included for data extraction and 174 were observational studies. Prevalence was reported in 48 studies with sample size varying from 206 to 167 331. A significant positive trend (P<0.0001) was observed over time in prevalence of HTN by region and gender. Awareness and control of HTN (11 studies) ranged from 20 to 54% and 7.5 to 25%, respectively. Increasing age, body mass index, smoking, diabetes and extra salt intake were common risk factors. In conclusion, from this systematic review, we record an increasing trend in prevalence of HTN in India by region and gender. The awareness of HTN in India is low with suboptimal control rates. There are few long-term studies to assess outcomes. Good quality long-term studies will help to understand HTN better and implement effective prevention and management programs.
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Concienciación , Hipertensión/epidemiología , Hipertensión/etiología , Femenino , Humanos , Incidencia , India/epidemiología , Masculino , Prevalencia , Factores de RiesgoRESUMEN
An unusual manifestation of breast fusariosis was encountered in a 55-year-old female diabetic patient. Two fine needle aspirates (FNA) from the abscess were done at three days interval and they showed hyaline, septate, branched, fungal hyphae in 10% potassium hydroxide mount. Fungal infection was confirmed by demonstrating the fungal hyphae in the midst of lymphocytes, macrophages and neutrophils in Leishman stained smears. Culture of both FNAs yielded a heavy and pure growth of Fusarium solani. The patient responded to oral ketoconazole 200 mg once daily for 3 weeks. The breast fusariosis reported here is presumably the first case in India.
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Absceso/microbiología , Enfermedades de la Mama/microbiología , Fusarium/crecimiento & desarrollo , Micosis/microbiología , Absceso/tratamiento farmacológico , Absceso/patología , Antifúngicos/uso terapéutico , Enfermedades de la Mama/tratamiento farmacológico , Enfermedades de la Mama/patología , Femenino , Humanos , Cetoconazol/uso terapéutico , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Micosis/patologíaRESUMEN
A recent finding in epidemiological and laboratory studies suggests that the ratio of selenium to glutathione is lower in breast cancer subjects than its control counterparts. Selenium, an antioxidant and anticarcinogen, can modify the status of glutathione and some associated enzymes by blocking peroxidation of lipids in membranes of cancer subjects. Studies were conducted using female albino rats of Wistar strain bearing mammary tumor induced by 7,12-dimethylbenz(a) anthracene to assess the biological role of selenium on some antioxidant enzymes associated with the maintenance of glutathione status. For induction of mammary tumor, 25 mg DMBA in a 1 ml emulsion of sunflower oil and physiological saline was injected subcutaneously to each rat. One group in each of control and tumor bearing rats, were fed 5 mg sodium selenite/kg diet from the day of tumor induction for 24 weeks. Increase in the reduced glutathione concentration was preceded by significant increase in the oxidized glutathione as well as in the activities of gamma-glutamylcysteine synthetase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, and glucose-6-phosphate dehydrogenase by selenium administration in rats bearing tumor. However, selenium administration to rats bearing tumor decreased the activity of gamma-glutamyl transpeptidase. These observations clearly demonstrate the influence of dietary selenium supplementation in correcting abnormal changes in glutathione turnover and some associated enzymes in tumor induced rats.
Asunto(s)
9,10-Dimetil-1,2-benzantraceno , Glutatión/análisis , Neoplasias Mamarias Experimentales/metabolismo , Selenio/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Femenino , Glutatión/metabolismo , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
Current evidences clearly point out that an increase in lipid peroxidation influences lipid metabolism in cancer patients. Several investigations recognize selenium as a potent antioxidant, as well as an anticarcinogen, in both animal and human systems. Selenium was administered to Wistar rats bearing mammary tumor induced by 7,12-dimethylbenz(a)anthracene (DMBA) to study alterations in the concentration of lipid profiles and in the activities of some lipid metabolising enzymes. Control and tumor-bearing rats administered with selenium, were fed 5 mg sodium selenite/kg diet from the day of tumor induction. Plasma total lipids, total cholesterol, free fatty acids, triglycerides, phospholipids, VLDL and LDL cholesterol were significantly lower in selenium-treated rats bearing tumors, whereas, plasma ester cholesterol and HDL cholesterol were significantly greater due to selenium administration in DMBA induced-tumor rats. Total lipase and lecithin: cholesterol acyltransferase registered greater activities in plasma of selenium administered rats with tumor, while the activity of preheparin lipoprotein lipases in plasma of rats bearing tumors was lower due to selenium administration. These observations clearly indicate the effect of selenium in correcting the abnormalities of lipid metabolism in tumor-induced rats.
Asunto(s)
Antioxidantes/farmacología , Lípidos/sangre , Lipoproteína Lipasa/sangre , Neoplasias Mamarias Experimentales/sangre , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Selenio/farmacología , 9,10-Dimetil-1,2-benzantraceno , Animales , Colesterol/sangre , Lipoproteína Lipasa/efectos de los fármacos , Lipoproteínas/metabolismo , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Fosfatidilcolina-Esterol O-Aciltransferasa/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Familial hypercholesterolemia (FH) is the most commonly recognized disorder of lipoprotein metabolism in childhood. We report a case of FH in a 5-year-old boy with onset of jaundice since birth, and multiple planar, tuberous, palmar and intertrigenous xanthomas covering the trunk and limbs. His total cholesterol was 590 mg/dl and triglycerides were 171 mg/dl. Echocardiography revealed mild aortic stenosis as a result of premature atherosclerosis. He was diagnosed with homozygous FH, and is reported here because of the interesting clinical features.