Protein palmitoylation inhibition by 2-bromopalmitate alters gliding, host cell invasion and parasite morphology in Toxoplasma gondii.

Protein palmitoylation is the reversible covalent attachment of palmitic acid onto proteins. This post-translational modification has been shown to play a part in diverse processes such as signal transduction, cellular localization and regulation of protein activity. Although many aspects of protein palmitoylation have been identified in mammalian and yeast cells, little is known of this modification in Toxoplasma gondii. In order to determine the functional role of protein palmitoylation in T. gondii, tachyzoites were treated with the palmitoylation inhibitor 2-bromopalmitate (2-BP). Parasites treated with 2-BP displayed a significant increase in non-circular trails which were longer than those trails left by non-treated parasites. Furthermore, 2-BP treatment reduced the invasion process to the host cells. Long-term treatment of intracellular tachyzoites resulted in major changes in parasite morphology and shape in a dose-dependent manner. These results suggest that palmitoylation could be modifying proteins that are key players in gliding, invasion and cytoskeletal proteins in T. gondii.

[Intravenous proton-pump inhibitor for acute peptic ulcer bleeding--is profound acid suppression beneficial to reduce the risk of rebleeding?]. / Inhibidores de la bomba de protones por vía intravenous en la hemorragia por úlcera péptica: es necesaria la supresión ácida máxima para disminuir el resangrado?

OBJECTIVE: To compare two regimens of pantoprazole administered intravenously in patients with ulcerative gastrointestinal bleeding (UGB), and a high risk of presenting with persitent or recurrent hemorrhage. MATERIAL AND METHOD: Patients were randomized into two groups: group 0--treatment with a 80 mg bolus of pantoprazole administered intravenously, followed by continuous infusion of 8 mg/h for 72 hours; group 1--treatment with 40 mg of pantoprazole administered intravenously on a daily basis. The percentage of hemorrhagic persistence/recurrence in both groups was analyzed, as were transfusion requirements, need for surgery, and mortality resulting from the hemorrhagic episode. RESULTS: There were 20 patients in group 0 and 21 in group 1. No differences were found between groups in terms of gender, age, smoking habits, use of NSAIDs, presence of hemodynamic instability or stigmata in ulcer crater (Forrest Ia: 5 vs. 14.3%, p = 0.322; Forrest Ib: 30 vs. 33.3%, p = 0.819; Forrest IIa: 60 vs. 50.1%, p = 0.753). In group 0, 90% of patients received endoscopic treatment, versus 100% in group 1, p = 0.232. In group 0, 50% of patients had a transfusion, as compared to 52.4% in group 1, p = 0.879. In group 0, 2 patients (10.5%) presented with recurrent hemorrhage, versus 3 patients (14.3%) in group 1. Surgery was required by 1 person from each group, and 1 patient in group 0 died. CONCLUSIONS: Maximum acid inhibition with a bolus and then a continuous infusion of pantoprazole does not yield better results than treatment with conventional doses in acute hemorrhagic episodes.

Inhibidores de la bomba de protones por vía intravenosa en la hemorragia por úlcera péptica: ¿es necesaria la supresión ácida máxima para disminuir el resangrado? / No disponible

Objetivo: comparar dos pautas de pantoprazol por vía intravenosaen pacientes con hemorragia digestiva alta (HDA) ulcerosade alto riesgo para presentar persistencia o recidiva hemorrágica.Material y método: se randomizaron los pacientes en dosgrupos: grupo 0: tratamiento con bolo de 80 mg i.v. de pantoprazoly perfusión continua a 8 mg/h durante 72 horas; grupo 1: tratamientocon 40 mg i.v. de pantoprazol diarios. Se analizó el porcentajede persistencia/recidiva hemorrágica entre ambos grupos,requerimientos transfusionales, necesidad de cirugía y mortalidaddel episodio hemorrágico.Resultados: se incluyeron 20 pacientes en el grupo 0 y 21en el grupo 1. No se encontraron diferencias entre ambos gruposen cuanto al sexo, edad, hábito tabáquico, consumo de AINE,presencia de inestabilidad hemodinámica, estigma sobre el nichoulceroso (Forrest Ia 5 vs. 14,3%, p = 0,322; Forrest Ib 30 vs.33,3%, p = 0,819; Forrest IIa 60 vs. 50,1%, p = 0,753). El 90%de los pacientes del grupo 0 recibió tratamiento endoscópico vs.el 100% del grupo 1, p = 0,232. El 50% de los pacientes del grupo0 recibió transfusión vs. el 52,4% del grupo 1, p = 0,879. Dospacientes (10,5%) del grupo 0 presentaron recidiva hemorrágicavs. 3 pacientes (14,3%) del grupo 1, precisando cirugía 1 pacientede cada grupo y falleciendo 1 paciente del grupo 0.Conclusiones: la inhibición ácida máxima de la secreción ácidagástrica mediante bolo e infusión continua de pantoprazol noofrece resultados superiores al tratamiento con dosis convencionalesen el episodio hemorrágico agudo

Objective: to compare two regimens of pantoprazole administeredintravenously in patients with ulcerative gastrointestinalbleeding (UGB), and a high risk of presenting with persitent or recurrenthemorrhage.Material and method: patients were randomized into twogroups: group 0 - treatment with a 80 mg bolus of pantoprazoleadministered intravenously, followed by continuous infusion of 8mg/h for 72 hours; group 1 - treatment with 40 mg of pantoprazoleadministered intravenously on a daily basis. The percentageof hemorrhagic persistence/recurrence in both groups was analyzed,as were transfusion requirements, need for surgery, andmortality resulting from the hemorrhagic episode.Results: there were 20 patients in group 0 and 21 in group1. No differences were found between groups in terms of gender,age, smoking habits, use of NSAIDs, presence of hemodynamicinstability or stigmata in ulcer crater (Forrest Ia: 5 vs. 14.3%, p =0.322; Forrest Ib: 30 vs. 33.3%, p = 0.819; Forrest IIa: 60 vs.50.1%, p = 0.753). In group 0, 90% of patients received endoscopictreatment, versus 100% in group 1, p = 0.232. In group0, 50% of patients had a transfusion, as compared to 52.4% ingroup 1, p = 0.879. In group 0, 2 patients (10.5%) presentedwith recurrent hemorrhage, versus 3 patients (14.3%) in group 1.Surgery was required by 1 person from each group, and 1 patientin group 0 died.Conclusions: maximum acid inhibition with a bolus and athen a continuous infusion of pantoprazole does not yield betterresults than treatment with conventional doses in acute hemorrhagicepisodes

Prevalencia y significado clínico de resistencia antibiótica de Helicobacter pylori / Prevalence and clinical significance of antibiotic resistance in Helicobacter pylori

OBJETIVO: determinar la tasa de resistencia de H. pylori frente a los principales antibióticos usados en la terapia erradicadora en nuestra área sanitaria y la asociación de diversos factores epiclemiolégicos (edad, sexo, tabaquismo y consumo previo de IBP) con la misma. Conocer la evolución de la resistencia en 3 años (1996-1998) y la influencia de la resistencia previa a claritromicina en el éxito erradicador con pautas triples que incluyen dicho fármaco. PACIENTES Y MÉTODOS: incluimos a 139 pacientes (100 varones), con edad media de 51 +- 15 años, que precisaron estudio endoscópico oral por hemorragia o dispepsia entre enero de 1996 y diciembre de 1998 y que presentaron cultivo positivo para H. pylori en la biopsia antral extraída. En 91 de los 139 iniciales se pudo estudiar el antibiograma de H. pylori frente a cinco antibióticos mediante E-test y frente a omeprazol por dilución en agar. Se procedió a realizar tratamiento erradicador con distintas pautas que contenían ameprazol, claritromicina y amoxicilina (OCA) y se realizó test del aliento con C13 a las 6-8 semanas tras finalizar el tratamiento. RESULTADOS: treinta y cinco de 91 (38,5%) presentaron algún tipo de resistencia, siendo el metronidazol el de mayor tasa (28,6%) seguido de eritromicina y claritromicina (13 y 10%, respectivamente). No encontramos resistencia frente a amoxicilina, tetraciclina u omeprazol. En pacientes que usaron previamente omeprazol se encontró más tasa de resistencia antibiótica respecto al grupo que no hizo uso previo (57% frente al 31%). En menores de 40 años la tasa de resistencia al metronidazol fue del 41,6%, mientras que en mayores de 60 años fue del 11,5%. No encontramos asociación del factor tabaco o sexo con la tasa de resistencia. Se consiguió éxito erradicador en el 74% (37/50) la tasa de resistencia a claritromicina en el grupo erradicado fue del 5% (2/37) frente al 30% (4/13) en el grupo que no erradicó. No apreciamos variación significativa en la tasa de resistencia en los 3 años estudiados, aunque se observó un discreto incremento en el caso del metronidazol: 3% (1996) a 34% (1998). CONCLUSIONES: la resistencia frente a metronidazol y claritromicina es similar a la esperada. Los pacientes jóvenes con uso previo de omeprazol tienen una mayor tasa de resistencia frente al metronidazol, pero no frente al propio omeprazol. La resistencia frente a claritromicina se asocia con fracaso erradicador. No apreciamos diferencias en la tasa de resistencia en los últimos 3 años (AU)

AIMS: to determine the rates of resistance of H. pylori to antibiotics and proton pump inhibitors (PPI) in an area of southern Spain, and the evolution of resistance during the last 3 years. To study the relationship between the resistance profile of H. pylori and age, sex, smoking habit, previous treatment with PPI and successful eradication. METHODS: one hundred and thirty-nine patients with positive H. pylori culture were enrolled in the study. In 91 patients, sensitivity studies were done for erythromycin, clarithromycin, metronidazole, tetracycline and amoxicillin using E-tests, and for omeprazole using the agar dilution test. Treatment with omeprazole, clarithromycin and amoxicillin was started and the urea breath test was used to confirm successful eradication. RESULTS; thirty-five patients (38.5%) showed some antibiotic resistance: 26 cases (299ú) against metronidazole, 9 (100%) against clarilhromydn, and 11 (13%) against erythromycin. No patients showed resistance against amoxicillin, omeprazole or tetracycline. Previous omeprazole treatment was related with a higher rate of metronidazole resistance (57% vs 31%; p < 0.05), as was age (41% in patients younger than 40 years vs 11% in patients older than 60 years; p < 0.005). There was no correlation between smoking or sex and resistance. Clarithromycin resistance was related to unsuccessful eradication (33% vs 75%; p < 0.05). Metronidazole resistance did not influence the effectiveness of clarithromycin-based triple therapy. Clarithromycin resistance changed little during the 3-year study period, but he rate of metronidazole resistance rose, although the change was not significant (23% in 1996 vs 34% in 1998; p = NS). CONCLUSIONS: resistance to metronidazole and clarithromycin were similar to the rates in other areas of Spain. Younger patients with previous omeprazole treatment were more frequently resistant to metronidazole, but not to omeprazole. Clarithromycin resistance was related to unsuccessful eradication with clarithromycin-based triple therapy. During the 3-year study period there were no changes in resistance rates (AU)

[Prevalence and clinical significance of antiphospholipid antibodies in chronic hepatitis C]. / Prevalencia y significado clínico de los anticuerpos antifosfolipídicos en la hepatitis crónica por virus C.

BACKGROUND: To know the prevalence of antiphospholipid antibodies in chronic hepatitis C and their relationship with disease progression. METHODS: One hundred and twenty-eight patients with chronic hepatitis C and 93 healthy controls were enrolled up. We determined platelets, ALT, gamma GT, RNAHCV in serum and liver and non-organ specific antibodies, grade and stage in liver biopsy, risk factors, duration of disease and alcohol intake were also included. Portal hypertension and liver function parameters were studied. Antiphospholipid antibodies (APA): lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) (IgG and IgM) were measured by EIA. Anti-beta 2 glycoprotein I antibodies were also detected by EIA in ACA positive patients. RESULTS: Thirty one out of 128 (25%; 95% CI: 17.8%-33.4%) showed positive antiphospholipid antibodies. Positive ACA-IgG was higher in patients than controls (22% vs 3.2%; p < 0.05), whereas, ACA-IgM was similar (5% vs 3.2%; p = NS), and LA was absent in both groups. ALT levels, viraemia, viral load in liver, platelets, or ANA titre were similar in patients with and without positive ACA-IgG. Risk factors, duration of disease or alcohol intake were not related yet. Patients with staging F1 showed positive ACA-IgG 4 of 44 (9%; 95% CI: 2.5%-21.7%), in staging F2 7 of 39 (18%; 95% CI: 7.5%-33.5%) and in staging F4 17 of 45 (38%; 95% CI: 23.8%-53.5%; p < 0.005). ACA-IgG was significantly related to portal hypertension, Child-Pugh stage and presence of cirrhosis complications. Anti-beta 2 glycoprotein I antibodies were detected in ten (43.5%; CI 95%: 23.2%-65.5%) out of 23 ACA positive patients. CONCLUSIONS: ACA-IgG seems to be associated with chronic hepatitis C, and could play a potential role in fibrosis progression and liver disease in these patients.

[Non-immunoallergic hepatotoxicity due to mesalazine]. / Hepatotoxicidad no inmunoalérgica por mesalazina.

Mesalazine is an aminosalicillic derivative considered as a safe alternative to the relative frequency (5-55%) of adverse effects observed with sulfasalazine. The well known hepatoxicity associated with sulfasalazine and attributed to its sulfamidic fraction is limited to few cases described in the treatment with mesalazine. We herein present a new case of hepatoxicity by mesalazine in a patient with lymphocytic colitis. The possible pathogenic mechanism is also commented upon.

[Acute severe hypersensitivity reaction to salazopirin]. / Reacción de hipersensibilidad aguda grave a la salazopirina.

Sulphasalazine is the drug most widely used in intestinal inflammatory disease given its efficacy and low cost. Nonetheless, its administration is not lacking adverse effects. Two cases of severe hypersensitivity are herein described. Moreover, the diagnostic difficulties observed and their implication in the management of the underlying disease are discussed.