Molecular dynamics study of nanoconfined TIP4P/2005 water: how confinement and temperature affect diffusion and viscosity.

In the past few decades great effort has been devoted to the study of water confined in hydrophobic geometries at the nanoscale (tubes and slit pores) due to the multiple technological applications of such systems, ranging from drug delivery to water desalination devices. To our knowledge, neither numerical/theoretical nor experimental approaches have so far reached a consensual understanding of structural and transport properties of water under these conditions. In this work, we present molecular dynamics simulations of TIP4P/2005 water under different nanoconfinements (slit pores or nanotubes, with two degrees of hydrophobicity) within a wide temperature range. It has been found that water is more structured near the less hydrophobic walls, independently of the confining geometries. Meanwhile, we observe an enhanced diffusion coefficient of water in both hydrophobic nanotubes. Finally, we propose a confined Stokes-Einstein relation to obtain the viscosity from diffusivity, whose result strongly differs from the Green-Kubo expression that has been used in previous works. While viscosity computed with the Green-Kubo formula (applied for anisotropic and confined systems) strongly differs from that of the bulk, viscosity computed with the confined Stokes-Einstein relation is not so much affected by the confinement, independently of its geometry. We discuss the shortcomings of both approaches, which could explain this discrepancy.

[A clinical study of adult autoimmune hepatitis in Valencia, Spain]. / Estudio clínico de la hepatitis autoinmune del adulto en Valencia.

OBJECTIVE: the clinical phenotype of autoimmune hepatitis (AIH) varies among geographical areas. The aim of this study is to determine the salient features of AIH in adult patients from the province of Valencia, Spain. MATERIAL AND METHODS: eighty-one patients with AIH attended to in eight acute-care hospitals between 1994 and 2003. New patients diagnosed with AIH during year 2003 were evaluated prospectively. Data from patients currently attending follow-up visits and diagnosed before 2003 were collected retrospectively. RESULTS: a total of 94% of patients were females. Forty-three percent were asymptomatic, 27% had acute hepatitis, and 30% had chronic hepatitis. Type 1 AIH was diagnosed in 90% of cases. Type 2 AIH was more frequent in younger patients, and presented with an acute pattern. One third of patients had cirrhosis at onset. Patients with cirrhosis were older than 60 years more frequently. Immunosuppressants were given to 57 patients, with complete or partial remission in 87.7%. There were no significant differences in response to immunosuppression according to presentation pattern or AIH subtype. CONCLUSIONS: AIH in Valencia was predominantly diagnosed in asymptomatic women. Most cases were type 1, and in 25% of patients another autoimmune disease coexisted. At the time of diagnosis one third of patients had cirrhosis, particularly those over 60 years.

[Changes in sexual hormones in a male population over 50 years of age. Frequency of low testosterone levels and risk factors]. / Cambios en las hormonas sexuales en varones mayores de 50 años. Prevalencia de niveles bajos de testosterona y factores de riesgo.

OBJECTIVES: To investigate the changes in sexual hormones in a selected male population older than 50 years of age. To assess the frequency of biochemical hypogonadism and which factors are related to testosterone levels. PATIENTS AND METHODS: A Cross-sectional study was carried out on 230 Spanish men older than 50 years of age. Blood tests were performed including: total testosterone, SHBG, calculated free testosterone, dehidroepiandrosterone sulfate, androstendione, estradiol, bioavailable estradiol, FSH, LH, and prolactin. Clinical and socio-demographic backgrounds were investigated. The frequency of biochemical hypogonadism was established using total and free testosterone levels as diagnostic criteria. Factors that may influence testosterone levels were evaluated by univariate and multivariate statistical analysis, and a logistic regression model was used to determine which factors can predict biochemical hypogonadism according to free testosterone levels. RESULTS: Age was associated with a significant decrease (p < 0.05) in total testosterone (0.6% per year), free testosterone (1.3% per year), dehydroepiandrosterone sulfate (1.8% per year) and bioavailable estradiol (0.69% per year). Moreover, an increase in SHBG, LH, and FSH was observed (p < 0.05). According to total testosterone levels, 4.8% of the men were hypogonadal, whereas 24.8% were hypogonadal when free testosterone was considered. In the univariate analysis, obesity, diabetes mellitus and hyperlipemia were related to lower total testosterone levels, while free testosterone levels were lower in men with sedentary life, lower levels of education, obesity or diabetes mellitus. In the multivariate analysis age, diabetes mellitus and obesity were inversely related to total and free testosterone levels. Free testosterone was also inversely related to hyperlipemia. For biochemical hypogonadism, simple logistic regression analysis selected age, sedentary life, obesity and diabetes mellitus. In the multivariate analysis age, obesity and diabetes mellitus had significant independent prognostic value. CONCLUSIONS: Starting from 50 years of age, a significant age-related decrease in total testosterone, free testosterone, dehydroepiandrosterone sulfate and bioavailable estradiol is observed. The frequency of biochemical hypogonadism is higher when free testosterone levels are used for diagnosis. Total testosterone levels were related to age, diabetes mellitus and obesity. Free testosterone was related to age. diabetes mellitus, obesity and hyperlipemia. The probability of suffering low free testosterone levels increases with age, diabetes mellitus and/or obesity.

Perception of body size among Mexican teachers and parents.

Obesity in Mexico has reached epidemic proportions; and body image and body satisfaction might be culturally related. Body dissatisfaction has been related to low self-esteem. The aim of this study was to assess the range of perception among Mexican teachers and parents of the ideal body size of adults, boys and girls. Two-hundred and five teachers and eighty parents from Tijuana and Tecate schools participated in the study. Participants were asked to indicate the ideal body size for each group, as well as their own ideal body size. Average perception of ideal body weight for adults 35 to 45 years of age was 4.0 +/- 0.84. Average perception for boys and girls was 4.6. Positive correlations were shown between self-perception of body size and body mass index (0.62, P < 001), waist circumference (0.55, P < 0.001). Self-perception of body size was associated with perception of ideal body size for boys (0.23, P 0.001) and girls (0.22, P < 0.001), but BMI was not associated to perception of ideal body size for boys and girls. These results suggest that teachers and parents should be taught to more accurately assess excess weight status and to initiate action to prevent or correct excessive weight among children and adults.

[Evaluation of an immunoassay kit to measure free testosterone]. / Evaluación de una técnica de inmunoanálisis para la determinación de testosterona libre.

INTRODUCTION AND OBJECTIVES: The best indicators to the diagnosis of hypogonadism are free and bioavailable testosterone circulating levels. Free and bioavailable testosterone measurements are complex. However, simple kits for direct measurement of free testosterone by analog immunoassay are available. We examined the utility of an enzymoimmunoassay kit for free testosterone measurement. MATERIAL AND METHOD: One hundred thirty-three healthy males were included. Total testosterone, SHBG, albumin and free testosterone was measured. We used two different methods to free testosterone estimation: direct measurement by enzymoimmunoassay and mathematical calculation with Vermeulen's formula, which uses albumin concentration, total testosterone and SHBG to calculate free testosterone (method recommended by the International Society for the Study of the Aging Male). We compared the two methods means values and a linear regression study was performed. RESULTS: Mean age was 37 +/- 11 years. Mean serum concentration for total testosterone was 21.43 +/- 6.8 nm ol/L. The mean value for free testosterone measured by direct and mathematical method was 0.0508 +/- 0.0118 nmol/L and 0.474 +/- 0.123 nmol/L respectively. In linear regression study exists a positive correlation between both methods (p< 0.05), although correlation coefficient is very low (r = 0.25). CONCLUSIONS: There are significant statistical differences between the measurements of free testosterone by direct and mathematical methods. Although certain correlation is observed, this is very low. In conclusion, free testosterone measurement by enzymoimmunoassay is not reliable.

Effect of N-acetylcysteine and deferoxamine on endogenous antioxidant defense system gene expression in a rat hepatocyte model of cocaine cytotoxicity.

In the present study we investigated on cultures of hepatocytes from phenobarbital-pretreated rats, the effect of the antioxidants, 0.5 mM N-acetylcysteine (NAC) or 1.5 mM deferoxamine (DFO), previously incubated for 24 h and coincubated with cocaine (0-1000 microM) for another 24 h. Cocaine cytotoxicity was monitored by either the lysis of the cell membranes or apoptosis. Lysis of the cell membranes was evidenced by lactate dehydrogenase leakage, apoptosis was observed by detecting a hypodiploid peak (<2C) in DNA histograms obtained by flow cytometry, peroxide production was quantified with 2', 7'-dichlorodihydrofluorescein diacetate and gene expression of the antioxidant enzymes: Mn- and Cu,Zn-superoxide dismutases, catalase and glutathione peroxidase were measured by Northern blot analysis. NAC and DFO significantly decreased the extent of lysis of cell membranes and apoptosis, and the antiapoptotic effect was parallel to peroxide generation. By the effect of NAC and DFO, significant increases were detected in the levels of mRNA of catalase, manganese superoxide dismutase and glutathione peroxidase. From these results we conclude that NAC or DFO, when incubated in the presence of cocaine, exerted a protective effect against cocaine toxicity at the level of both lysis of the membranes and apoptosis. This protective effect, in the case of NAC, was directed towards an increase in antioxidant enzyme expression, and in the case of DFO against reactive oxygen species generation.

Markov chains: computing limit existence and approximations with DNA.

We present two algorithms to perform computations over Markov chains. The first one determines whether the sequence of powers of the transition matrix of a Markov chain converges or not to a limit matrix. If it does converge, the second algorithm enables us to estimate this limit. The combination of these algorithms allows the computation of a limit using DNA computing. In this sense, we have encoded the states and the transition probabilities using strands of DNA for generating paths of the Markov chain.

Necrotizing retinopathy after intraocular inoculation of murine cytomegalovirus in immunosuppressed adult mice.

A light microscopic study was done to investigate retinal changes in healthy and immunosuppressed mice after intraocular inoculation of murine cytomegalovirus (MCMV). A 0.01-ml inoculum containing 10(5) plaque-forming units of MCMV was placed behind the lens in 138 4-week-old Swiss Webster mice. Ninety-eight mice were immunosuppressed with 0.2 mg/g of cyclophosphamide given intraperitoneally at the time of inoculation and 0.1 mg/g of cyclophosphamide every 5 days thereafter. Selected eyes were examined on postinoculation days 5, 10, 15, and 16-20. Evidence of viral infection was most prominent in uveal tissue. Uveal infection developed whether or not animals received cyclophosphamide, but retinal necrosis developed only in immunosuppressed mice. Focal retinal necrosis, primarily involving the outer retinal layers and retinal pigment epithelium, was first observed in an eye examined on day 10. Retinopathy from MCMV was present in three of five eyes (60%) examined on day 15, and in six of 16 eyes (37.5%) examined between days 16-20. Retinal disease was characterized by full-thickness retinal necrosis, scattered cytomegalic cells, intranuclear and intracytoplasmic viral inclusions, and acute and chronic inflammation. These results indicate that MCMV can produce a necrotizing retinopathy in mice and that immunosuppression facilitates infection. Although ocular MCMV infection in immunosuppressed adult mice is a potential model for study of human CMV retinopathy, many differences exist between human CMV and MCMV and between the ocular diseases they produce.

Influence of aminoguanidine on parameters of liver injury and regeneration induced in rats by a necrogenic dose of thioacetamide.

1. When aminoguanidine, a nucleophilic hydrazine compound, was administered to rats (50 mg kg(-1) body wt) 30 min before a necrogenic dose of thioacetamide (500 mg kg(-1) body wt), significant changes related to liver injury and hepatocellular regeneration were observed. 2. The extent of necrosis was noticeably less pronounced, as detected by the peak of serum aspartate aminotransferase activity. Depletion of hepatic glutathione (GSH) and the increase in malondialdehyde concentration as markers of oxidative stress, produced by thioacetamide metabolism, were significantly diminished. However, the activity of microsomal FAD monooxygenase, the system responsible for thioacetamide oxidation, did not show significant alterations. Antioxidant enzyme systems involved in the glutathione redox cycle, such as glutathione reductase and glutathione peroxidase activities, slightly decreased following aminoguanidine pretreatment. 3. Primary cultures of peritoneal macrophages from control rats, when incubated in the presence of serum collected following thioacetamide intoxication, showed a significant decrease in nitric oxide (NO) release at 24 h, that was more pronounced in the group pretreated with aminoguanidine. However, the sharp and progressive increase in macrophage NO release, when incubated in the presence of serum obtained at 48, 72 and 96 h, were increased by aminoguanidine-pretreatment. 4. The cell population involved in DNA synthesis sharply increased in both groups at 48 h of intoxication, although the values at 0, 24, 72 and 96 h were markedly higher in the group pre-treated with aminoguanidine. Polyploidy at 72 and 96 h of intoxication was delayed by the effect of aminoguanidine and a progressive increase in the hypodiploid hepatocyte population, which reached 16% of the total at 96 h, was observed. 5. These results indicate that a single dose of aminoguanidine before thioacetamide administration, markedly diminished the severity of the liver injury by decreasing oxidative stress and lipoperoxidation, but hepatocellular regeneration was apparently unaffected probably due to an enhanced mitogenic activity.

Mitochondrial involvement in cocaine-treated rat hepatocytes: effect of N-acetylcysteine and deferoxamine.

The cytotoxicity of cocaine (0 - 1000 microM), was studied on parameters related to the mitochondrial role and the cascade of events that lead to apoptosis in hepatocyte cultures from phenobarbitone (PB) pretreated rats. Cytotoxicity was dose-dependent and LDH leakage was significantly enhanced above 100 microM cocaine. Apoptosis was visualized by DNA fragmentation on agarose gel, and appeared at 50 and 100 microM cocaine. Cocaine induced biphasic changes in mitochondrial transmembrane potential and significantly increased the mitochondrial release of cytochrome c, the caspase-3 like DEVDase activity and the level of 20 kDa subunit, a product of pro-caspase-3 cleavage. The protective effect of N-acetylcysteine (NAC) and deferoxamine (DFO) on all these parameters confirmed the involvement of oxygen radicals in cocaine-induced necrosis/apoptosis. We conclude: first, that the biphasic changes recorded in mitochondrial inner membrane potential by the effect of cocaine, were parallel to apoptosis; second, that caspase-3 activity and cleavage to it p20 subunit increased sharply in parallel to the translocation of cytochrome c from mitochondria to cytosol; and third, that the antioxidants, NAC or DFO exerted a noticeable protective role in counteracting the cytotoxicity of cocaine, these effects being more pronounced in the case of DFO than NAC. These findings demonstrate that cocaine cytotoxicity involves mitochondrial damage.

Induction of cell proliferation by cyclosporine A in primary cultures of rat hepatocytes.

Cyclosporine A (CsA) has been reported to be able to promote cell proliferation, although the precise mechanism by which CsA stimulates cell growth remains uncertain. In the present study, we examined, in hepatocyte cultures, the effect of CsA on parameters related to the cell cycle as well as the levels of proteins involved in the control and progression of the cycle. Flow cytometry analysis detected an increase in the percentage of cells involved in the S phase of the cycle, which correlated with increases in the levels of cyclins D1 and E (two G1-progression regulators), as well as in those of PCNA (proliferating cell nuclear antigen), and without modification in p27, an inhibitory protein of CDKs. We also examined in nucleus the levels of nuclear factor kappaB (a nuclear factor involved in the transcription of the cyclin D1 gene) and found that this transcription factor increased in the presence of CsA. We conclude that the increases in cyclin D1, PCNA, and cyclin E, together with the invariable level of p27, clearly show that CsA induces hepatocytes to proliferate. These results reinforce the idea of the growth-promoting effect of CsA in cultured hepatocytes.

Changes in antioxidant defence systems induced by cyclosporine A in cultures of hepatocytes from 2- and 12-month-old rats.

The in vitro effect of cyclosporine A (CsA) was studied in reference to the production of reactive oxygen species (peroxides and superoxide anion) and to cell enzyme-mediated antioxidant defence in hepatocytes isolated from rats aged 2 and 12 months. Primary cultures of hepatocytes were incubated in the presence of concentrations of cyclosporine in the range of 0 to 50 microM for 24 hr, and the release of lactate dehydrogenase into the culture medium was evaluated as a parameter of cytotoxicity and membrane lysis. Peroxides were quantified by using 2',7'-dichlorodihydrofluorescein diacetate, and superoxide anion levels were evaluated by the fluorescence of dihydroethidium. Enzyme activity and gene expression of catalase and Mn- and Cu,Zn-superoxide dismutase were also assayed. CsA cytotoxicity was significantly higher in hepatocytes from rats aged 12 months when compared to those aged 2 months. Intracellular peroxide content resulted in a dose-dependent increase, while the anion superoxide intracellular level slightly decreased as CsA increased from 0-50 microM. The progressive increase in intracellular peroxides in cell cultures in the range from 0-50 microM CsA was associated with the loss of cell viability and accompanied by significantly higher levels of Mn- and Cu, Zn-superoxide dismutase enzyme activities and mRNAs, and slight increases in catalase activity and mRNA. We conclude that, in primary hepatocyte cultures, the cytotoxicity of CsA was dose-dependent in both age groups and significantly higher in cultures from 12-month-old rats when compared to those from 2-month-old animals. The non-coordinated regulation of the gene expression of antioxidant enzyme systems, i.e. catalase and Mn- and Cu,Zn-superoxide dismutases, evidenced to a greater extent in hepatocytes from the older group of rats, could be one of the mechanisms involved in CsA toxicity.

Cocaine cytotoxicity in hepatocyte cultures from phenobarbital-induced rats: involvement of reactive oxygen species and expression of antioxidant defense systems.

The present study was designed to investigate whether cocaine modifies the production of reactive oxygen species, affects cellular enzyme-mediated antioxidant defense systems and, subsequently, promotes apoptosis and/or necrosis of hepatocytes. Primary cultures of hepatocytes isolated from phenobarbital-induced rats were exposed to cocaine (0-1000 microM) for 24 hr, and cell death (apoptosis or necrosis), antioxidant enzyme activities and mRNA levels, and peroxide generation were determined. Cocaine cytotoxicity by apoptosis was observed by detecting apoptotic nuclei using optic microscopy and by measurement of the hypodiploid peak (<2C) in DNA histograms obtained by flow cytometry. Necrosis was evidenced by lactate dehydrogenase (LDH) leakage, and peroxide production was quantified with 2',7'-dichlorodihydrofluorescein diacetate. Low concentrations of cocaine (less than 100 microM) resulted in an increase in dichlorofluorescein fluorescence, associated with an enhancement in apoptotic cell death and sharp decreases in the enzyme activities and RNAs of catalase and manganese-superoxide dismutase (Mn-SOD). The progressive decrease in peroxide production in cell cultures detected in the range of 250-1000 microM cocaine was associated with increases in LDH leakage and decreases in the percentage of apoptotic cells, accompanied by low levels in catalase and Mn-SOD enzyme activities and mRNAs, without apparent changes in apoptosis. These data indicate that oxygen radicals may contribute directly or indirectly to cocaine-induced apoptosis in cultured hepatocytes. We conclude that, in primary hepatocyte cultures, cocaine-induced cell death by necrosis was dependent on cocaine concentration, while cell death by apoptosis was parallel to peroxide concentration. The down-regulation of the gene expression of antioxidant enzyme systems should be one of the mechanisms involved in cocaine toxicity.

The microvascular distribution of cardioplegic solution in the piglet heart. Retrograde versus antegrade delivery.

The uniform distribution of cardioplegic solution to all areas of the microvasculature is considered critical for myocardial protection. Despite this, little information exists regarding the ability of retrogradely infused cardioplegic solution to perfuse the microvasculature of the heart. In this report, the microvascular distribution of retrogradely delivered cardioplegic solution was studied by means of a technique to quantitatively demonstrate capillary perfusion. Duroc piglet hearts were subjected to either antegrade (n = 4) or retrograde (n = 8) perfusion fixation with 2.5% glutaraldehyde and subsequently perfused with NTB-2 (an intracapillary marker). The results indicate that retrogradely delivered NTB-2 consistently perfused the anterior half of the intraventricular septum and the anterior and lateral free walls of the left ventricle but inconsistently perfused the posterior half of the intraventricular septum, the posterior wall of the left ventricle, and a small paraseptal region of the right ventricle. The remainder of the right ventricle was not perfused. In contradistinction, all regions of the heart were consistently perfused by the antegrade technique. In regions of the heart in which retrograde microvascular perfusion occurred, no statistical difference was found in the quantitative degree of capillary perfusion achieved by either the antegrade or retrograde technique. These results have important implications for planning strategies of myocardial protection and suggest that further investigation concerning the microvascular distribution of retrogradely delivered cardioplegic solution in human beings is merited.

Can improved microvascular perfusion be achieved by using both antegrade and retrograde cardioplegia?

BACKGROUND: The complete and uniform distribution of cardioplegia to the microvasculature of the heart is considered critical for myocardial protection. This study explores the hypothesis that enhanced microvascular perfusion can be achieved by using both antegrade and retrograde cardioplegia. METHODS: Infant piglet hearts (n = 15) were arrested with antegrade blood cardioplegia, excised, and fixed with 2.5% glutaraldehyde by retrograde perfusion. Hearts were then perfused retrograde with an inert intracapillary marker (NTB-2). Six of these hearts served as controls (group 1) to anatomically demonstrate the degree of capillary perfusion achieved by the retrograde delivery route. Nine experimental hearts (group 2) underwent a subsequent infusion of antegrade blood cardioplegia to wash out NTB-2 capillaries coperfused by both the antegrade and retrograde delivery techniques. Sections of the left ventricular free wall and anterior-mid interventricular septum were taken and examined by light microscopy at four separate sites (average, 126 capillaries per section). RESULTS: In control hearts, 91.9% +/- 0.9% of ventricular capillaries and 91.4% +/- 5.8% of septal capillaries were perfused by retrograde cardioplegia. After antegrade blood cardioplegia washed out group 2 hearts, 14.0% +/- 4.1% of capillaries in the ventricle still contained NTB-2, as did 12.5% +/- 5.4% of capillaries in the septum. CONCLUSIONS: In this experimental model, antegrade blood cardioplegia did not coperfuse (and therefore washout) 12.5% to 14% (p < 0.05) of capillaries perfused by retrograde cardioplegia. This suggests that an additional 12.5% to 14% of capillaries within the myocardium may receive cardioplegia if retrograde cardioplegia is used in addition to antegrade cardioplegia. We conclude that by combining both antegrade and retrograde cardioplegia, there is a potential for enhanced overall microvascular perfusion.

Gross and microvascular distribution of retrograde cardioplegia in explanted human hearts.

In this report, explanted hearts from transplant recipients with the diagnosis of idiopathic cardiomyopathy underwent a blood cardioplegia arrest and extended subatrial resection to preserve their coronary sinus venous system. The coronary sinus and left and right coronary arteries were then cannulated and warm blood cardioplegia retrograde infused at a pressure of 30 to 40 mm Hg. Effluent from the coronary arteries and thebesian veins was then collected. Hearts were subsequently fixed with retrograde glutaraldehyde perfusion and perfused retrograde with NTB-2 (an inert intracapillary marker). Histologic sections were examined from 12 separate sites. There was no significant difference in the percentage of capillaries perfused by retrograde-delivered cardioplegia between corresponding regions of the left and right ventricles. However, effluent analysis indicated that 67.2% +/- 6.4% of retrograde-delivered blood cardioplegia was shunted through thebesian veins, thereby bypassing the microvasculature, whereas 29.3% +/- 6.3% and 3.5% +/- 3.1% traversed the myocardium supplied by the left and right coronary arteries, respectively. The results indicate that all regions of both ventricles are perfused by retrograde blood cardioplegia. However, they also suggest that nutrient flow to the microvasculature of the right ventricle is minimal during retrograde cardioplegia.

Potentiation of thioacetamide hepatotoxicity by phenobarbital pretreatment in rats. Inducibility of FAD monooxygenase system and age effect.

The ability of phenobarbital to induce the expression and activity of microsomal drug monooxygenases in the liver presents one of the most important issues in the field of chemical interactions and in the toxicity of xenobiotics. The model of rat liver injury induced by a single dose of thioacetamide (500 mg/kg intraperitoneally) was used to study the effect of phenobarbital (80 mg/kg/day intraperitoneally) for 5 days prior to thioacetamide. Serum parameters of liver injury such as aspartate aminotransferase activity, gamma-glutamyl transferase activity and the total bilirubin levels, as well as the activities of hepatic FAD and cytochrome P450 microsomal monooxygenases, were assayed in 2- and 12-month-old rats. Samples of blood and liver were obtained from controls (injected at 0 h with 0.5 ml of 0.9% NaCl) and at 12, 24, 48, 72 and 96 h of thioacetamide intoxication either to non-treated or phenobarbital pretreated rats. Potentiation of thioacetamide hepatotoxicity by phenobarbital pretreatment was demonstrated at morphological level, and by significant increases in the activities of serum aspartate aminotransferase and gamma-glutamyl transferase, and in the levels of total bilirubin. The extent of potentiation of thioacetamide-induced liver injury by phenobarbital pretreatment was similar in both age groups. Microsomal FAD monooxygenase activity, the enzyme responsible for thioacetamide biotransformation, was significantly enhanced (twofold) by phenobarbital pretreatment, and also underwent a further increase following thioacetamide, preceding the peak of necrosis. Cytochrome P450 monooxygenases were induced by phenobarbital pretreatment more than sixfold, and sharply decreased when phenobarbital was withdrawn and thioacetamide administered, showing at 48 h intoxication values close to basal. Phenobarbital pretreatment potentiated thioacetamide necrogenicity, and this potentiation was parallel to the induction of the microsomal FAD monooxygenase system, both by phenobarbital and by thioacetamide itself. The extent of thioacetamide-induced liver injury was significantly higher in 12-month-old rats, but the effect of phenobarbital pretreatment was similar in both age groups.

[Continuous monitoring of the upper esophageal sphincter with the Dent device, during acid perfusion or distension with balloon of the esophageal body]. / Monitorización contínua del EES mediante el dispositivo de DENT, durante la perfusión de ácido o la distensión con balón del cuerpo esofágico.

The aim of the present study was to evaluate pressure changes of the UES under conditions that simulate the effects of gastroesophageal reflux (GER), that are, balloon esophageal distension and acid perfusion 0.1 N. Studies were performed in eight healthy subjects and fourteen patients with reflux esophagitis (RE), divided in two groups according to symptoms, 6 patients with heartburn and 8 patients with heartburn and regurgitation. We have employed the Dent sleeve to monitor UES pressure. The catheter was located with the help of a side-hole manometric catheter placed in the opposite side of the Dent sleeve; thereafter, it was anchorated. Perfusion of acid at 5 and 10 cm below the UES induces a pressure increase statistically significant, (paired data). This pressure increase is shown when mean values of the 5 minutes are considered as well for every minute. On the after hand, esophageal balloon distension did not produce pressure increases in any of the groups.

[Response of the upper esophageal sphincter to various esophageal stimuli in patients with reflux esophagitis]. / Respuesta del esfínter esofágico superior a diferentes estímulos esofágicos en pacientes con esofagitis por reflujo (EPR).

The clinical symptoms, including oropharingeal dysphagia and bronchial symptoms, have been analyzed in 18 normal controls and in 48 patients with reflux esophagitis. Patients with reflux and pyrosis and regurgitation usually have a disease of longer duration, more bronchial symptoms, greater severity of endoscopic lesions and less pressure in the U.E.S. area than those who only have heartburn. In 10 normals as well as in 28 patients (15 with pyrosis and 13 with both pyrosis and regurgitation) the pressure behavior of the superior esophageal sphincter has been studied with a specially designed instrument after different stimuli: acid perfusion at 5 and 10 cm of the U.E.S. during 5 minutes and esophageal balloon distention at 10 cm. In normal individuals none of the stimuli modified the pressure at rest of the U.E.S., while in patients with reflux esophagitis only HCl perfusion at 5 cm was able to significantly increase pressure. This finding was independent of the clinical symptoms of the patients.

[The efficacy of Plantago ovata as a regulator of intestinal transit. A double-blind study compared to placebo]. / Eficacia del Plantago ovata como regulador del tránsito intestinal. Estudio doble ciego comparativo frente a placebo.

The effect of Plantago ovata on patients with chronic constipation (CC) with or without irritable bowel syndrome (IBS) has been assessed by a double blind study comprising 20 patients with CC of which 10 had associated IBS. A clinical questionnaire, weight of feces and intestinal transit time measured with radiopaque markers were done. Patients were then randomly distributed, 10 receiving PO and 10 placebo. Similar tests were done after treatment one month later. All patients receiving PO had good results against only one in the placebo group. Frequency of stools increased from 2.5 +/- 1 vs 8 +/- 2.2 stools per week, p less than 0.001 for paired data). A decrease in consistency of stools was also observed in the treated group. Fecal weight and colonic transit time were not significantly modified in placebo patients, while weight increase was observed in the treated ones (124 +/- 71 vs 194 +/- 65, gr/d p less than 0.001 for paired data) as well as a decrease in transit time (48 +/- 15 vs 34 +/- 18 hours p less than 0.05 for paired data). No adverse effects were observed and particularly no flatulence as often seen in patients on bran.