A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution.

Factors Influencing Serum Concentrations of Immunoglobulin D in the Adult Population: An Observational Study in Spain.

Immunoglobulin D (IgD) is the least studied of immunoglobulin classes. This study sought to investigate the potential relationship between demographic, metabolic, lifestyle and immunological factors, and serum IgD concentrations in a general adult population. We measured serum IgD concentrations by means of a commercial turbidimetric assay in 413 individuals (median age, 55 years; 45% males), randomly selected from the adult population of a Spanish municipality. Serum IgD concentrations displayed considerable variation in the population, ranging from undetectable (<6.7 mg/l) to 878 mg/l. Serum IgD concentrations were undetectable in 78 cases (18.9%) and >100 mg/l in 39 cases (9.4%). Median IgD was 21.9 mg/l. Serum IgD concentrations were negatively associated with age and positively associated with smoking, after adjustment for potential confounders. Overweight individuals showed lower concentrations of IgD than did normal-weight individuals. Atopy (positivity of skin tests to aeroallergens) was not significantly associated with IgD concentrations, although non-symptomatic atopics showed higher IgD concentrations. No consistent association was observed between serum IgD concentrations and gender, metabolic syndrome, or alcohol consumption. No significant association was found between baseline IgD concentrations and development of either allergic or immune disease after a median 11.4 years of follow-up. In conclusion, serum IgD concentrations in adults show a wide variation in the population and may be influenced by common factors, particularly age and smoking habit. These factors should be taken into account when defining reference ranges for serum IgD concentrations.

Incidence and factors associated with delayed graft function in renal transplantation at Carlos Van Buren Hospital, January 2000 to June 2008.

Delayed graft function (DGF) is defined as the need for dialysis within the first week after renal transplantation, and slow graft function as persistence of serum creatinine concentration of at least 3 mg/dL on day 5 after the procedure. In the present study, we analyzed the incidence and risk factors for DGF at our center. This retrospective study included 106 patients who underwent renal transplantation between January 2000 and June 2008. Of these, 11 patients were excluded. Two of the remaining 95 patients received organs from living donors, and 93 received cadaver organs. Variables analyzed included donor age, cause of death, cause of chronic renal failure, recipient age, method and time of long-term renal replacement therapy, residual diuresis, panel of reactive antibodies (PRA), HLA mismatch, sex compatibility, cold and warm ischemia times, biopsy-confirmed episodes of acute rejection, urine output in the operating room and in the first 24 hours after the procedure, and intraoperative induction therapy. Data were analyzed using the chi(2) and Fisher exact tests and analysis of variance, and are given as mean (SD) and frequency. Variables associated with DGF at univariate analysis (P < .05) were divided between risk factors and predictors of DGF for inclusion in logistic regression models. The incidence of DGF was 32.6%; slow graft function, 16.8%; and immediate graft function, 50.5%. Cold ischemia time longer than 20 hours (P = .02) and donor age (P = .008) were directly associated with DGF. Twenty-four-hour urine output was a strong predictor of DGF. Patients with DGF demonstrated a 25% incidence of an episode of acute rejection before discharge from the hospital. No difference in DGF was observed for use of intraoperative induction therapy.

Antimicrobial properties of moderately halotolerant bacteria from cenotes of the Yucatan peninsula.

AIMS: Isolation and antimicrobial evaluation of aquatic bacterial strains from two cenotes. METHODS AND RESULTS: A total of 258 bacterial strains were isolated from the water and sediment of two cenotes in the Yucatan peninsula, all of which were screened against six pathogenic micro-organisms. Antimicrobial activity was detected in 46 of the isolated strains against at least one of the target strains tested. Antimicrobially active isolates were identified as: Aeromonas, Bacillus, Burkholderia, Photobacterium, Pseudomonas, Serratia, Shewanella, Stenotrophomonas genera, and 13 remained unidentified. All antimicrobially active strains were able to grow in salt medium at a concentration of 75 g l(-1), thus classifying as moderately halotolerant bacteria. Most of the antimicrobially active strains exhibited a broad action spectrum, where 61% was because of uncharacterized antimicrobial substances, 25% because of bacteriocins and 13% because of siderophores. Ten strains were able to biosynthesize biosurfactant metabolites. CONCLUSIONS: Native bacteria from the Yucatan peninsula showed an interesting antimicrobial activity, diverse mode of action and moderate halotolerance to salt. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on bacterial isolates from cenotes of the Yucatan peninsula and their antimicrobial characterization, with great potential for future biotechnological applications.

Serum cytokeratins in alcoholic liver disease: contrasting levels of cytokeratin-18 and cytokeratin-19.

Serum cytokeratin (CK) levels are widely used as tumor markers. Serum levels of CK-18, a tumor marker also known as tissue polypeptide specific antigen (TPS), are increased in patients with alcoholic liver disease. Cytokeratin-18 is the main component of Mallory bodies, a hallmark of alcoholic hepatitis, which may also contain CK-19. Serum levels of CK-18 and CK-19, a tumor marker also known as CYtokeratin FRAgment 21-1 (CYFRA 21-1) were investigated in (a) heavy drinkers with alcoholic liver disease (n=15), (b) patients with malignancy (n=22), and (c) healthy controls (n=10). Serum levels of CYFRA 21-1 (CK-19) were markedly increased in patients with malignancy, but were similar in heavy drinkers and healthy controls. In contrast, serum levels of TPS (CK-18) in heavy drinkers were higher than those of healthy controls, and even tended to be higher than those of patients with malignancy. Both CK-19 and CK-18 levels were higher in cases of alcoholic hepatitis than in cases of fatty liver. Correlation with hepatocyte CK inclusions was stronger for serum TPS (CK-18) than for CYFRA 21-1 (CK-19). In conclusion, serum CYFRA 21-1 (CK-19) and TPS (CK-18) show a different pattern of increase that could reflect the composition of the altered hepatocyte CK network in alcoholic liver disease. Their usefulness as tumor markers, particularly that of serum TPS (CK-18), may be limited in patients with alcoholic liver disease.

Serum levels of tissue polypeptide specific antigen are correlated with hepatocyte cytokeratin expression in alcoholic liver disease.

BACKGROUND: Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease. METHODS: Twenty-four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2-reactive cytokeratin inclusions was compared with serum TPS levels. MAIN RESULTS AND CONCLUSIONS: The vast majority of alcoholics (95%) showed increased (>100 units/liter) serum TPS levels. Serum TPS levels were significantly correlated with the number of hepatocyte cytokeratin inclusions. Serum TPS levels can predict hepatocyte cytokeratin expression in patients with alcoholic liver disease.

La enfermedad de chagas induce una supersensibilidad colinergica muscarinica en ventrículo derecho de ratas chagásicas sprague dawley / Chagas's disease induce a muscarinie cholinergic supersensibility in right ventricle of chagas rats spargue dawley

La Enfermedad de Chagas constituye un problema de salud pública en Venezuela, cuyas alteraciones están representadas fundamentalmente por el desarrollo de miocardiopatías incapacitantes. En la actualidad, las causas de las miocardiopatías no son realmente conocidasy tampoco existe tratamiento; sin embargo, dentro de la teoria neurogénica se ha postulado que el Sistema Colinérgico est  involúcrado en su desarrollo. Con el fin de dilucidar el estado de Receptor Colinérgico Muscarínico (RCM) en ésta enfermedad, se establecieron dos grupos de animales: Control (ratas sanas) y Experimental (ratas con Enfermedad de Chagas en etapa crónica), posteriormente las ratas fueron sacrificadas, disecando en corazón Ventrículo Izquierdo (VI), Ventrículo Derecho (VD), Tabique Interventricular (TIV), Aurícula (Au) y en el encéfalo Tronco Encefálico (TE). Se determinó la cantidad de proteínas mediante el método de Lowry, la densidad de RCM y los efectos de agonistas (Carbacol) y antagonistas selectivos (Pirenzepina, Metoctramina, 4-DAMP y Tropicamida) por medio de ensayos de radioligandos usando [³H]-QNB como marcador radioactivo. Los resultados mostraron en TE una disminución significativa de la cantidad de proteínas en ratas con Enfermedad de Chagas; en VD se encontró una supersensibilidad significativa del RCM en ratas Chagásicas, mientras que en TIV, VI y Au no se observaron diferencias significativas entre ambos grupos. En las curvas de desplazamiento de [³H]-QNB por agonistas y antagonistas selectivos, no se encontraron diferencias significativas en el perfil de desplazamiento y en los valores de CI50, al comparar los dos grupos. En conclusión la expresión de proteínas y del RCM se encuentran alteradas en TE y VD, respectivamente.

Association of alcohol consumption with total serum immunoglobulin E levels and allergic sensitization in an adult population-based survey.

BACKGROUND: Chronic alcoholism is associated with increased total serum IgE levels. OBJECTIVE: The study aimed to investigate the relationship between alcohol intake and both total serum IgE levels and allergic sensitization in a general adult population. MATERIALS AND METHODS: A total of 720 subjects was randomly selected (stratified by age) from the population older than 18 years of A-Estrada (Spain) and invited to participate in the study. From 697 eligible subjects, 469 (67%, median age 54 years, range 18 to 92 years, 44% males, 75% of cases from a rural environment) agreed to participate. A battery of 13 skin prick tests to common aeroallergens was performed in all subjects. Cases with at least one positive test (n = 121, 26%) were considered to have allergic sensitization. The most frequent sensitisers were mites and pollens (24% and 10% of subjects, respectively). Total serum IgE was measured in 465 subjects (99%). Alcohol consumption was registered as the number of standard (approximately 10 g) drinking units habitually consumed per week. A total of 244 subjects (52%) were alcohol consumers (median intake, 14 units/week, range 1 to 147 units/week). Abstainers (n = 225, 48%) constituted the reference category. RESULTS: Alcohol consumption of more than 14 units/week was associated with an increase in serum IgE levels after adjusting for age, gender, allergic sensitization and smoking (P = 0.02). Alcohol consumption was not significantly associated with either overall allergic sensitization or mite sensitization after adjusting for age, gender and smoking. However, alcohol consumption of more than 14 units/week was associated with an increased prevalence of pollen sensitization (adjusted OR 3.15, 95% CI 1.19 to 8.34, P = 0.02). CONCLUSION: Alcohol consumption above a certain threshold is associated with an increase in total serum IgE levels. Alcohol consumption may also be associated with an increased prevalence of pollen sensitization.

Simultaneous tyrosine and serine phosphorylation of STAT3 transcription factor is involved in Rho A GTPase oncogenic transformation.

Stats (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that on a specific stimulus migrate to the nucleus and exert their transcriptional activity. Here we report a novel signaling pathway whereby RhoA can efficiently modulate Stat3 transcriptional activity by inducing its simultaneous tyrosine and serine phosphorylation. Tyrosine phosphorylation is exerted via a member of the Src family of kinases (SrcFK) and JAK2, whereas the JNK pathway mediates serine phosphorylation. Furthermore, cooperation of both tyrosine as well as serine phosphorylation is necessary for full activation of Stat3. Induction of Stat3 activity depends on the effector domain of RhoA and correlates with induction of both Src Kinase-related and JNK activities. Activation of Stat3 has biological implications. Coexpression of an oncogenic version of RhoA along with the wild-type, nontransforming Stat3 gene, significantly enhances its oncogenic activity on human HEK cells, suggesting that Stat3 is an essential component of RhoA-mediated transformation. In keeping with this, dominant negative Stat3 mutants or inhibition of its tyrosine or serine phosphorylation completely abrogate RhoA oncogenic potential. Taken together, these results indicate that Stat3 is an important player in RhoA-mediated oncogenic transformation, which requires simultaneous phosphorylation at both tyrosine and serine residues by specific signaling events triggered by RhoA effectors.

Increased serum IgE in alcoholics: relationship with Th1/Th2 cytokine production by stimulated blood mononuclear cells.

BACKGROUND: Increased serum immunoglobulin (Ig) E values are frequently found in alcoholics. Cytokines produced by T-helper-2 (Th2) lymphocytes are required for IgE synthesis. Chronic alcoholism is associated with altered cytokine balance. This study analyzed the relationship between Th1 and Th2 cytokine production by stimulated peripheral blood mononuclear cells (PBMCs) and serum IgE levels, both in atopic and nonatopic alcoholics. METHODS: Twenty-five patients admitted to the hospital with alcohol withdrawal syndrome were included in the study. Five were classified as atopic and 20 as nonatopic by means of skin-prick tests. Interleukin-4 (IL-4), IL-10, IL-12, IL-13, and interferon gamma were measured in the supernatants of 48-hr cultures of PBMCs stimulated with phytohemagglutinin. Total serum IgE was measured by chemiluminescent enzyme immunoassay. Results were compared with those of 15 healthy controls (seven atopics and eight nonatopics). RESULTS: Total serum IgE concentrations were higher in alcoholics than in controls, in both atopic and nonatopic subjects. The ratio of IL-4 to interferon gamma production by phytohemagglutinin-stimulated PBMCs (as an approach to Th2/Th1 balance) was significantly lower in alcoholics than in healthy controls, both in the atopic and in the nonatopic group. No difference was observed regarding IL-10, IL-12, and IL-13 production between alcoholics and controls. No correlation was demonstrated between cytokine production and total serum IgE levels in any group. CONCLUSIONS: Increased total serum IgE is observed in alcoholics together with a paradoxically low ratio of Th2 to Th1 cytokine production by phytohemagglutinin-stimulated PBMCs. These findings are independent of the atopic status of patients.

Total serum IgE levels in chronic hepatitis C: influence of interferon alpha therapy.

BACKGROUND: Liver disease has been considered a prominent cause of IgE elevation. No data on serum IgE levels in chronic hepatitis C have been reported. Interferon-alpha is a standard therapy for chronic hepatitis C. Cytokine use is a promising type of immunomodulation in the treatment of IgE-mediated diseases. The effects of interferon-alpha therapy on serum IgE have not been fully evaluated. The aim of the study was to evaluate both serum IgE levels in patients with chronic hepatitis C and the course of these levels after interferon-alpha therapy. PATIENTS AND METHODS: Serum IgE was determined in 100 adult patients with chronic hepatitis C (24 atopics according to positive skin prick tests and 76 nonatopics) and in 75 healthy controls (25 atopics and 50 nonatopics). Serum IgE measurements were repeated at 1 and 3 months of therapy with recombinant interferon-alpha (3 x 106 units s.c. 3 times weekly) in 34 of these patients. RESULTS: Serum IgE levels were similar in chronic hepatitis C patients and in controls when adjusted for atopic status. Among patients with chronic hepatitis C, serum IgE levels were unrelated to liver necroinflammatory activity. A modest but statistically significant increase of IgE values was observed after interferon-alpha therapy, particularly in patients with no virological response. CONCLUSIONS: Chronic hepatitis C is not a significant cause of increased total serum IgE values. Serum IgE increase in some patients with liver disease may be related to the cause of liver injury and not to liver disease per se. Interferon-alpha therapy in patients with chronic hepatitis C is followed by no modification or even a moderate increase of serum IgE values.

Cecal ligation and puncture as a model of sepsis in the rat: influence of the puncture size on mortality, bacteremia, endotoxemia and tumor necrosis factor alpha levels.

BACKGROUND: Cecal ligation and puncture is a widely used experimental model of sepsis. AIM OF THE STUDY: The present study was aimed to evaluate the influence of the size of the cecal puncture on mortality, bacteremia, endotoxemia and plasma TNF-alpha levels. MATERIALS AND METHODS: Female Sprague-Dawley rats underwent cecal ligation and puncture, divided into the following groups, defined by the diameter of the cecal puncture: 0.5-cm blade incision (n = 25), 13-gauge (n = 25), 16-gauge (n = 25), 18-gauge puncture (n = 25) and 4 punctures with a 22-gauge needle (n = 25). A sham operation was performed in another 25 rats. Three animals of each group were sacrificed 5 h after the procedure for blood cultures as well as determination of plasma endotoxin and TNF-alpha. The remaining animals were followed up for a week after cecal ligation and puncture for evaluation of mortality. RESULTS: Five hours after cecal ligation and puncture, bacteremia was present in all animals, independently of the puncture size. Endotoxemia and plasma TNF levels tended to increase along with the diameter of the cecal puncture. Mortality gradually increased with the puncture size, from 27% with a 22-gauge needle to 95% with the blade incision. CONCLUSIONS: The severity of sepsis obtained with cecal ligation and puncture in rats can be easily modulated varying the size of the puncture.

Pharmacological modification of the serotonergic transmitter system and beta-N-acetylhexosaminidase activity in rats.

The enzyme activity and activation energy of plasma beta-N-acetylhexosaminidase (Hex) was determined in rats whose serotonergic system had been pharmacologically altered. In the group of animals treated with 5-hydroxytryptophan, in the different dissected brain regions (brain stem, cortex and hippocampus) significantly higher levels of serotonin and 5-hydroxyindolacetic acid were found, and significantly lower in the group treated with p-chlorophenylalanine, than in the control group. In the total number of animals studied (n = 21), a statistically significant correlation was found between the plasma concentration of 5-hydroxyindolacetic acid and the levels of this metabolite in the different brain regions (p < 0.001). No significant differences were found for the activity of Hex in the plasma, or for its activation energy, which is a marker of its isoenzyme composition, among the three groups of animals. The results obtained using our experimental model in rats do not confirm the hypothesis of other authors who suggest that the Hex responds secondary to increases or decreases of serotonin turnover, and could be a biological test to monitor the serotonin status in psychiatric patients.

Influence of acute alcohol intake and alcohol withdrawal on circulating levels of IL-6, IL-8, IL-10 and IL-12.

Cytokine balance alterations are responsible for some of the systemic and hepatic manifestations of alcoholism. The present study was aimed to evaluate the influence of both acute alcohol abstinence (in alcoholics) and acute alcohol intake (in healthy subjects) on serum IL-6, IL-8, IL-10, and IL-12 levels. Serum cytokine concentrations were determined on admission and after a median of 6 days of ethanol abstinence in 29 patients with alcohol withdrawal syndrome. The same determinations were made in five healthy volunteers at baseline and after 36 h of a single 60 g-dose alcohol intake. Increased serum levels of IL-6, IL-10 and, to a lesser extent IL-8, declined in the few days after alcohol abstinence in patients with alcohol withdrawal syndrome. Serum IL-8 values increased after alcohol intake in healthy subjects. Rapid variation of serum cytokine levels along with alcohol intake or abstinence should be taken into account in cytokine studies in alcohol abusers.

Increased serum tissue polypeptide specific antigen (TPS) in alcoholics: a possible marker of alcoholic hepatitis.

BACKGROUND: Serum tissue polypeptide specific antigen (TPS) is widely used as a tumor proliferation marker. There is some evidence of an increase in serum TPS in benign liver diseases. The aim of the study was to evaluate serum TPS levels in alcoholics. METHODS: Seventy-seven alcoholics (64 men and 13 women) admitted to the hospital with ethanol withdrawal syndrome entered the study. Twenty-three patients were biopsied (12 of them had alcoholic hepatitis and 11 steatosis or fibrosteatosis). Serum TPS was determined by enzyme immunoassay in all cases. Results were compared with those of 24 healthy controls. RESULTS: Serum TPS levels were significantly increased in alcoholic patients compared with controls (median 365 units/liter and range 41-6400 units/liter versus median 79 units/liter and range 19-235 units/ liter, respectively, p < 0.0001). Seventeen alcoholics (22%) had a TPS value 10 times higher than the upper normal threshold level (> or = 1000 units/liter). Among alcoholics, serum TPS levels were higher in patients with alcoholic hepatitis than in those with steatosis or fibrosteatosis (median 1486 units/liter and range 176-5023 units/liter versus median 106 units/liter and range 41-221 units/liter, respectively, p = 0.0001), offering a better discriminant value for the diagnosis of alcoholic hepatitis than usual liver function parameters. Serum TPS values showed significant correlation with liver cell necrosis and Mallory's hyaline degeneration. TPS values decreased after alcohol abstinence during hospital admission. CONCLUSIONS: Serum TPS is frequently increased in alcoholics and may be a marker of alcoholic hepatitis. Specificity of this molecule as a tumor marker is limited in alcoholics.

Relationship between plasma ammonia concentration and beta-N-acetylhexosaminidase isoenzyme activities in liver cirrhosis.

Ammonia is known to increase the secretion of beta-N-acetylhexosaminidase (Hex) to the extracellular medium in cultured human fibroblasts and Hep G2 cells. We examined 35 patients with liver cirrhosis and the results revealed a significant increase for the plasma activities of total Hex and its isoenzymes Hex A and Hex B (p < 0.001). The partial correlations, with other biochemical markers of liver injury constant, between plasma ammonia concentration and the activity (r = 0.658) and the proportion in percentage of the Hex B isoenzyme (r = 0.692) were statistically significant (p < 0.001). The increased concentration of ammonia could explain, at least partially, an increased secretion of Hex B isoforms to the plasma in patients with liver disease.

Plasma beta-N-acetylhexosaminidase isoenzyme composition and temperature conversion factors.

Using the chromogenic substrate 3,3'-dichlorophenylsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide for the activity determination of plasma beta-N-acetylhexosaminidase (Hex), the temperature conversion factors (TCF) offer a highly significant positive correlation with the relative proportion of Hex B isoenzyme (P< 0.001). The calculation of TCF 37 degrees/25 degrees C allows the isoenzyme composition of Hex to be determined quickly and cheaply. The results may be superimposed over those obtained in a previously described method based on the calculation of the enzyme's activation energy using four temperatures. However, the use of TCF 37 degrees/30 degrees C does not appear to comply with the required demands.

Characterization of the isoenzyme profile of beta-N-acetylhexosaminidase in the urine of newborns.

The urinary isoenzymes of beta-N-acetylhexosaminidase (Hex) in newborn infants were characterised by chromatography, electrophoresis, thermodynamic analysis and through substrate specificity. No qualitative difference was found for the major Hex A and Hex B isoenzymes between full-term or premature newborns and adults, although in the latter group the relative proportion of Hex B is much lower (18.5 +/- 2.7% vs. 36.3 +/- 1.0%). An additional minor enzyme form was found in some premature newborns, which eluted from the DEAE-cellulose column at a higher concentration of NaCl than Hex A and, like this isoenzyme, is able to hydrolyse 4-methylumbellipheryl-2-acetamido-2-deoxy-beta-D-glucopyranoside-6 -sulphate, which would suggest that it has alpha subunits in its molecule. These results do not confirm the hypothesis of other authors about the existence of a unique fetal Hex isoenzyme in neonatal urine which eluted before the application of the NaCl gradient, similarly to the Hex B.

Thermodynamic characterisation of the mutated isoenzyme A of beta-N-acetylhexosaminidase in GM2-gangliosidosis B1 variant.

Here we report the determination of the activation energies of the plasma isoenzymes of beta-N-acetylhexosaminidase (Hex, EC 3.2.1.52), isolated by chromatography in DEAE-cellulose, using the neutral chromogenic substrate 3,3'dichlorophenylsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide. The activation energy of mutated Hex A isoenzyme (Ea approximately 71.5 kJ/mol) from a patient with GM2-gangliosidosis B1 variant, homozygote for the G533-->A (Arg178His) mutation, was significantly higher than that of normal Hex A (Ea approximately 41.8 kJ/mol) and analogous to that of Hex B isoenzyme (Ea approximately 75.1 kJ/mol). The determination of this thermodynamic variable of Hex in different biological specimens could allow for a straightforward biochemical characterisation of the GM2-gangliosidosis B1 variant.

Serum cytokines and increased total serum IgE in alcoholics.

BACKGROUND: It has been reported that total serum IgE is increased in alcohol abusers, but the mechanisms responsible are not known. Production of IgE depends on B-cell stimulation by both antigens and some cytokines, particularly IL-4 and IL-13. Chronic alcoholism and alcoholic liver disease are accompanied by changes in cytokine production. AIM OF THE STUDY: To evaluate if IgE increase in alcoholics could be associated to a ethanol-induced imbalance of the cytokine profile. PATIENTS AND METHODS: A total of 65 patients (53 males and 12 females, aged 47 +/- 12 years), admitted to the hospital because of ethanol abstinence symptoms entered the study. On admission, total serum IgE was measured by chemiluminescent EIA and serum IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, and interferon-gamma were measured by ELISA. Data were compared with those of 40 healthy control subjects. RESULTS: Serum IgE, IL-6, IL-8, IL-10, IL-12, and IL-13 were found to be high in alcoholic patients compared with healthy volunteers. Some parallelism was observed between serum IgE and both serum IL-10 and IL-13 were increased in alcoholics. CONCLUSIONS: Total serum IgE elevation in alcoholics with abstinence syndrome is accompanied by an increase of some type 2 cytokines. Ethanol-induced alterations in the cytokine profile may contribute to increased IgE levels in alcoholics.