Development, physical-chemical stability and release studies of four alcohol-free spironolactone suspensions for use in pediatrics

Dissolution studies have become of great significance because, in most cases, drug dissolution is the rate-limiting step in the absorption process. As occurs with solid oral dosage forms, heterogeneous disperse systems (suspensions) could also have some problems with their in vitro dissolution. The objective of this study was to evaluate influence of the excipients on the release of spironolactone from four alcohol free suspensions (pharmaceutical compounding) of spironolactone 5 mg/mL suitable for pediatric use. Also the comparison of the physical and chemical stability of the suspensions stored at 4, 25 and 40 ºC over a 60- day period has been studied. Rheological behavior, particle size, a prediction of long-term physical stability, pH and assay of spironolactone by HPLC were assessed at prefixed times. The dissolution profile of each suspension was determined and compared with that of the commercial tablets. A microbiological study of the best formula was also performed. Chemically, the four spironolactone suspensions were stable for 60 days stored at three temperatures; Suspension IV had optimum pH values and the highest recovery percentage. In terms of physical stability, sedimentation occurred in Suspension IV and flotation of spironolactone in Suspensions I, II and III. Suspension III had the highest viscosity and the slowest drug release. Suspension IV was also microbiologically stable for 60 days. In conclusion, Suspension IV had the best properties and the least suitable form was Suspension III, as its high viscosity made it difficult to achieve homogeneous redispersion, and it had the slowest dissolution profile.

Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial

Background: Few clinical studies have focused on the alcoholindependent cardiovascular effects of the phenolic compounds of red wine (RW). Objective: We aimed to evaluate the effects of ethanol and phenolic compounds of RW on the expression of inflammatory biomarkers related to atherosclerosis in subjects at high risk of cardiovascular disease. Design: Sixty-seven high-risk, male volunteers were included in a randomized, crossover consumption trial. After a washout period, all subjects received RW (30 g alcohol/d), the equivalent amount of dealcoholized red wine (DRW), or gin (30 g alcohol/d) for 4 wk. Before and after each intervention period, 7 cellular and 18 serum inflammatory biomarkers were evaluated. Results: Alcohol increased IL-10 and decreased macrophage-derived chemokine concentrations, whereas the phenolic compounds of RW decreased serum concentrations of intercellular adhesion molecule- 1, E-selectin, and IL-6 and inhibited the expression of lymphocyte function-associated antigen 1 in T lymphocytes and macrophage-1 receptor, Sialil-Lewis X, and C-C chemokine receptor type 2 expression in monocytes. Both ethanol and phenolic compounds of RW downregulated serum concentrations of CD40 antigen, CD40 ligand, IL-16, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1. Conclusion: The results suggest that the phenolic content of RW may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of RW may modulate soluble inflammatory mediators in high-risk patients. The trial was registered in the International Standard Randomized Controlled Trial Number Register at http://www. isrctn.org/ as ISRCTN88720134

Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial

Background: Few clinical studies have focused on the alcoholindependent cardiovascular effects of the phenolic compounds of red wine (RW). Objective: We aimed to evaluate the effects of ethanol and phenolic compounds of RW on the expression of inflammatory biomarkers related to atherosclerosis in subjects at high risk of cardiovascular disease. Design: Sixty-seven high-risk, male volunteers were included in a randomized, crossover consumption trial. After a washout period, all subjects received RW (30 g alcohol/d), the equivalent amount of dealcoholized red wine (DRW), or gin (30 g alcohol/d) for 4 wk. Before and after each intervention period, 7 cellular and 18 serum inflammatory biomarkers were evaluated. Results: Alcohol increased IL-10 and decreased macrophage-derived chemokine concentrations, whereas the phenolic compounds of RW decreased serum concentrations of intercellular adhesion molecule- 1, E-selectin, and IL-6 and inhibited the expression of lymphocyte function-associated antigen 1 in T lymphocytes and macrophage-1 receptor, Sialil-Lewis X, and C-C chemokine receptor type 2 expression in monocytes. Both ethanol and phenolic compounds of RW downregulated serum concentrations of CD40 antigen, CD40 ligand, IL-16, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1. Conclusion: The results suggest that the phenolic content of RW may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of RW may modulate soluble inflammatory mediators in high-risk patients. The trial was registered in the International Standard Randomized Controlled Trial Number Register at http://www. isrctn.org/ as ISRCTN88720134

Insulin-Like growth-factor 1 myocardial expression decreases in chronic alcohol consumption

Background Chronic alcohol ingestion may cause severe biochemical and pathophysiological derangements to skeletal muscle. Unfortunately, these alcohol-induced events may also prime skeletal muscle for worsened, delayed, or possibly incomplete repair following acute injury. As alcoholics may be at increased risk for skeletal muscle injury, our goals were to identify the effects of chronic alcohol ingestion on components of skeletal muscle regeneration. To accomplish this, age- and gender-matched C57Bl/6 mice were provided normal drinking water or water that contained 20% alcohol (v/v) for 18-20 wk. Subgroups of mice were injected with a 1.2% barium chloride (BaCl2) solution into the tibialis anterior (TA) muscle to initiate degeneration and regeneration processes. Body weights and voluntary wheel running distances were recorded during the course of recovery. Muscles were harvested at 2, 7 or 14 days post-injection and assessed for markers of inflammation and oxidant stress, fiber cross-sectional areas, levels of growth and fibrotic factors, and fibrosis. Results Body weights of injured, alcohol-fed mice were reduced during the first week of recovery. These mice also ran significantly shorter distances over the two weeks following injury compared to uninjured, alcoholics. Injured TA muscles from alcohol-fed mice had increased TNFα and IL6 gene levels compared to controls 2 days after injury. Total protein oxidant stress and alterations to glutathione homeostasis were also evident at 7 and 14 days after injury. Ciliary neurotrophic factor (CNTF) induction was delayed in injured muscles from alcohol-fed mice which may explain, in part, why fiber cross-sectional area failed to normalize 14 days following injury. Gene levels of TGFβ1 were induced early following injury before normalizing in muscle from alcohol-fed mice compared to controls. However, TGFβ1 protein content was consistently elevated in injured muscle regardless of diet. Fibrosis was increased in injured, muscle from alcohol-fed mice at 7 and 14 days of recovery compared to injured controls. Conclusions Chronic alcohol ingestion appears to delay the normal regenerative response following significant skeletal muscle injury. This is evidenced by reduced cross-sectional areas of regenerated fibers, increased fibrosis, and altered temporal expression of well-described growth and fibrotic factors.

Consumo episódico excesivo de alcohol en adolescentes: su asociación con los estados de ánimo negativos y los factores familiares

Fundamentos: El consumo episódico excesivo de alcohol (CEEA) es una práctica extendida en la población adolescente con graves riesgos para la salud, incluyendo el abuso/dependencia en la edad adulta. El objetivo de este artículo es analizar su asociación con los estados de ánimo negativos y algunas variables familiares entre los adolescentes catalanes. Métodos: Estudio transversal de una muestra representativa de adolescentes (edad 14-18 años) de Cataluña (Segunda oleada del Panel de Familias e Infancia) (2006-2010). Se realizan modelos de regresión logística para mujeres (n = 1.459) y hombres (n= 1.105) para estimar si los estados de ánimo negativos auto-percibidos (tristeza, presión parental, etc.) están asociados con el CEEA, capturado como haberse emborrachado por lo menos dos veces al mes durante el último año. Se estima en qué medida esos efectos son atribuibles a algunos factores familiares. Resultados: El sentimiento crónico de tristeza está asociado con el CEEA entre los varones (OR 2,7), al igual que sentirse presionado/a por los progenitores en ambos sexos (OR 1,8 hombres y OR 2,1 mujeres). Las mujeres de rentas medio-bajas y altas son más proclives al CEEA (OR 1,6 y OR 1,7 respectivamente). La existencia de progenitores de origen inmigrante (OR 0,4) y la fijación parental de un horario de retorno a casa los fines de semana (OR 0,6) presentan una asociación negativa con el CEEA entre las mujeres. Conclusiones: Los estados de ánimo negativos (EAN) están asociados al CEEA. Los efectos de los factores socio-económicos y familiares sobre el CEEA son más relevantes en mujeres que en varones.

Tècnica d'execució del frontal gòtic de Sant Llorenç de Morunys: a propòsit del dibuix preparatori

Els traços primigenis del dibuix preparatori del Frontal de Sant Llorenç de Morunys, al Museu Diocesà i Comarcal de Solsona, s"observen a ull nu, sense haver d"emprar tècniques sofisticades, a causa d"una pèrdua important de l"estrat pictòric que, de conservar-se, impediria la lectura de les capes més profundes. S"han examinat aquestes traces, font de documentació privilegiada que se"ns ofereix per incrementar el coneixement de l"obra i també, per comprendre el procés d"elaboració d"una pintura sobre taula en el context del bisbat d"Urgell al tombant del segle XIII. Durant l"estudi ha estat possible reconstruir, amb el suport inestimable dels tractats medievals, la seqüència d"execució del dibuix preliminar: primer, la distribució provisional de les línies mestres a mà alçada, amb carbonet, seguit de la seva fixació amb una punta metàl·lica dura; segon, el traçat de l"esbós figuratiu, amb un estil tou, i el posterior repàs definitiu amb una agulla o punta afilada sobre l"estrat preparatori, creant un dibuix incís que romandria visible després de recobrir tota la superfície amb una làmina d"estany. Finalment, s"aplicaria una complexa policromia, que combinaria tècniques opaques i vernissos translúcids. La revisió d"un corpus d"obres catalanes de característiques similars, moltes en les reserves dels museus pel seu precari estat de conservació, podria aportar dades rellevants quant a les diferents tècniques del dibuix preparatori emprades en la pintura sobre taula d"època medieval.

Wine, alcohol, polyphenols and cardiovascular disease

Abstract. Excessive alcohol consumption is associated with increased morbidity and mortality as well as with labour and traffic accidents. However, current evidence suggests beneficial effects of moderate drinking on cardiovascular events including coronary heart disease, ischaemic stroke, peripheral arterial disease and congestive heart failure. The underlying mechanisms to explain these protective effects against coronary heart disease include an increase in high-density lipoprotein cholesterol and an increase in insulin sensitivity, and a decrease in platelet aggregation and circulating concentrations of fibrinogen. However, there are discrepancies regarding the specific effects of different types of beverages on the cardiovascular system, and also whether the possible protective effects of alcoholic beverages are due to their alcohol component (ethanol) or non-alcoholic products containing, mainly polyphenols. Recent randomised clinical trials have shown that wine, a polyphenol-rich alcoholic beverage, provides higher antioxidant and anti-inflammatory effects than some spirits such as gin, a polyphenol-free alcoholic beverage. In addition, dealcoholized red wine decreases blood pressure through a nitric oxide mediated mechanism, suggesting a protective effect of polyphenols on vascular function. Other studies performed in women have observed that daily doses of 1520 g of alcohol as red wine are sufficient to elicit protective effects similar to those observed in men who consumed higher doses of wine. In conclusion, moderate consumption of wine exerts a protective effect on biomarkers related to the progression and development of atherosclerosis due to its alcoholic (ethanol) and non-alcoholic (polyphenols) content. Women are more sensitive to the beneficial effects of wine.

Efectos del alcohol y conducción de vehículos: creencias y conductas de los jóvenes

Traffic accidents are one of the causes of death for people between 1 and 45 years old. Many studies verify that the road accidents are related with the consumption of alcohol. This problem, is especially important in the young people and it is increased during dawns of the weekends. Some studies underline the lack of information and knowledge of many young people concerning law on alcohol consummation when driving and the effects of this drug on consumers. Another problem is the amount of mistaken beliefs on what to do neutralize the alcohol’s effect before drive. The objective of our study is to evaluate, in university students, the knowledge of the rules of driving behavior included in the circulation code and the personal beliefs about the effects of the alcohol in driving, and to find the frequency and the circumstances in which young people drive after alcohol consummation. The results suggest many actions that may be considered in the design of preventive campaigns that promotes safety road behavior in order to increase their effectivity

Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects

The ventral striatum / nucleus accumbens has been implicated in the craving for drugs and alcohol which is a major reason for relapse of addicted people. Craving might be induced by drug-related cues. This suggests that disruption of craving-related neural activity in the nucleus accumbens may significantly reduce craving in alcohol-dependent patients. Here we report on preliminary clinical and neurophysiological evidence in three male patients who were treated with high frequency deep brain stimulation of the nucleus accumbens bilaterally. All three had been alcohol dependent for many years, unable to abstain from drinking, and had experienced repeated relapses prior to the stimulation. After the operation, craving was greatly reduced and all three patients were able to abstain from drinking for extended periods of time. Immediately after the operation but prior to connection of the stimulation electrodes to the stimulator, local field potentials were obtained from the externalized cables in two patients while they performed cognitive tasks addressing action monitoring and incentive salience of drug related cues. LFPs in the action monitoring task provided further evidence for a role of the nucleus accumbens in goal-directed behaviors. Importantly, alcohol related cue stimuli in the incentive salience task modulated LFPs even though these cues were presented outside of the attentional focus. This implies that cue-related craving involves the nucleus accumbens and is highly automatic.

Frontal gòtic de Sant Llorenç de Morunys. Estudi del suport de fusta: tècnica de construcció i estat de conservació

Estudi preliminar realitzat a partir de la inspecció visual d’un frontal d’altar a les sales de reserva del Museu Diocesà i Comarcal de Solsona, lloc on es custodien les restes del que fou aquesta magnífica obra policromada de tombants del segle XIII executada en l’àmbit del bisbat d’Urgell. Avui en dia, la capa pictòrica ofereix un precari estat de conservació, però encara es conserven els estats preparatoris i una gran part del suport ligni. Les dades per a l’elaboració d’aquest estudi han estat recollides en diferents visites al museu durant els anys 2008-09. El suport del frontal de Sant Llorenç, de fusta de conífera, està constituït per quatre llargues posts disposades en sentit horitzontal que formen un plafó perfectament encaixat dins un marc que, en origen, tancava el conjunt. Actualment, les parts superior i inferior d’aquest marc no existeixen, degut a les nombroses vicissituds sofertes per l’obra al llarg del temps.L’encadellat de totes les peces es resolgué mitjançant espigues o clavilles de fusta, no detectant-se cap unió amb elements metàl·lics. Observant el revers del frontal amb llum rasant, s’aprecien les marques de l’eina que va desgruixar la superfície del suport, l’aixa. Pel sentit dels senyals deixats en la fusta, sembla que cada post va ser desbastada per separat. Després s’uniformaren els gruixos de cadascuna, tot passant un ribot per la zona que toca els cantells i es rebaixà la fusta tocant al perímetre del plafó per a facilitar l’encadellat del marc. Les labors de rebaix i allisat es durien a terme un cop el panell ja estava muntat. L’estat de conservació del suport ligni no és bo. La mancança de les peces superior i inferior del marc afecten l’estabilitat del conjunt que, al no quedar ben travat, acusa certs moviments de les peces amb les manipulacions i els trasllats, moviments que es transmeten també als estrats superiors, portadors de l’escassa policromia. Pel revers de l’obra es poden observar diverses pèrdues, de més o menys entitat, ocasionades per un antic i agressiu atac de xilòfags, de greus conseqüències per l’estructura lígnia, ja que ha debilitat molt les zones perimetrals del frontal, fent-les esdevenir poroses i fràgils.

Seguimiento de dependientes del alcohol y/o de la cocaina despues de su salida de una Comunidad Terapeutica: estudio piloto

Introducción Los avances en farmacoterapia del alcoholismo podrían propiciar un cambio de paradigma, basado en los nuevos programas de reducción del consumo de alcohol. Material y Método Este estudio revisa los fundamentos neurobiológicos y farmacoterapéuticos del alcoholismo, centrándose en los antagonistas opioides, el tratamiento orientado a la abstinencia y el orientado hacia la reducción del consumo de alcohol. Resultados 1. Los programas de tratamiento de la dependencia del alcohol presentan sólo una eficacia pequeña o moderada. 2. Los pacientes presentan una elevada motivación para reducir el consumo de alcohol pero una baja motivación para abandonar de manera continuada al consumo de alcohol. 3. El programa de reducción continuada del consumo de alcohol, asociado a un tratamiento intermitente con naltrexona, puede ser de utilidad en los pacientes con una baja gravedad de la dependencia del alcohol. Discusión Aunque los pacientes que presentan una grave dependencia del alcohol deberían ser tratados en programas orientados hacia la abstención continuada, los que presentan una baja gravedad pueden beneficiarse de los programas de reducción del consumo de alcohol, los cuales pueden conseguir a corto plazo una reducción el número de consumiciones por día de consumo y, a largo plazo, incluso una progresiva reducción de la"obsesión" por beber, la conducta de búsqueda de alcohol y los trastornos médicos, conductuales y sociales, causados por el consumo excesivo de alcohol. Para poder llevar a cabo este cambio de paradigma en el tratamiento del alcoholismo, se requieren futuros ensayos clínicos controlados para evaluar su eficacia y su tolerabilidad.