SummaryPlasminogen activator inhibitor-1 (PAI-1) increases in endotoxemia thus possibly cooperating in altering the hemostatic balance in a prothrombotic direction. The effect of the inhibition of PAI-1 with the monoclonal antibody MA-33B8 was studied systemically and in kidneys in a lapine model of endotoxin-induced disseminated intravascular coagulation (DIC). The increase in plasmatic PAI activity in the control group (n = 9) was inhibited in the MA-33B8 treated rabbits (n = 5). Control rabbits showed renal fibrin deposits, whereas only one of the MA-33B8 rabbits did so. These results were confirmed immunohistochemically in kidneys as PAI-1 immunostaining was seen inside the glomeruli and larger vessels in the control group, whereas MA-33B8 rabbits showed a remarkable decrease, demonstrating that MA-33B8 successfully inhibited PAI-1 in the kidneys as well. Therefore evidence for the important role of PAI-1 in fibrin generation in endotoxin-induced DIC is presented, suggesting that strategies aiming at its reduction can be useful in this pathology.

Summary.We evaluated the effect of r-hirudin and/or tissueplasminogen activator (t-PA) in a model of DIC in rabbits induced by i.v. infusion of 100 mg/kg/h/6 h endotoxin. Rabbits were treated with saline (endotoxin control group), r-hirudin at 0·3 mg/kg/h/6 h, t-PA at 0·3 mg/kg for 90 min and r-hirudin plus t-PA at the doses described above. The best results were achieved when r-hirudin and t-PA were infused together. This treatment reduced the consumption of platelets and protein C and attenuated the increase of PAI-1 more efficiently than r-hirudin or t-PA alone. r-Hirudin plus t-PA also resulted in the lowest formation of fibrin deposits in the kidneys. Finally, mortality at 24 h dropped from 70% in the endotoxin control group to 40%, 10% and 0% in the t-PA, r-hirudin and rhirudin plus t-PA groups respectively. None of the t-PA-infused rabbits which had died by 24 h showed macroscopic signs of haemorrhage. r-Hirudin alone was better than t-PA alone, as was shown by fibrin deposits and mortality. We conclude that r-hirudin and t-PA given simultaneously were more efficient than either given alone in this model of DIC. Effective thrombin inhibition, which could influence other pathophysiological mechanisms apart from coagulation, together with the improvement in fibrinolysis, would explain these results.

The effect of low molecular weight heparin (LMWH) with or without antithrombin III (AT III) has been studied in a rabbit model of disseminated intravascular coagulation (DIC) induced by continuous infusion of 100 microg/kg/hr of Escherichia coli endotoxin for 6 hr. LMWH (5 and 10 IU/kg/hr/6 hr), alone or in combination with AT III (20 U/kg/hr/6 hr), or saline were administered simultaneously with endotoxin. Hemostatic markers at 0, 2, and 6 hr as well as kidney fibrin deposits and the mortality rate at 24 hr were determined. Rabbits receiving only endotoxin showed an impairment in hemostasis, as well as high kidney fibrin deposits and a high mortality rate. LMWH alone did not exert any effect. The simultaneous infusion of LMWH and AT III exerted a beneficial effect on the hemostatic markers and reduced the kidney fibrin deposits as well as the mortality rate in a LMWH dose-dependent manner. Fibrinogen and protein C consumption were significantly higher and renal fibrin deposits more intense in the rabbits that had died in the first 24 hr. There was also a significant positive correlation between kidney fibrin deposits and platelets, fibrinogen, and protein C consumption, taking the whole rabbit population. It is concluded that the simultaneous infusion of LMWH and AT III is useful in this DIC model and would make it possible to reduce significantly the AT III doses used when AT III is given alone.

We are reporting three patients who experienced delayed cutaneous reactions after treatment with paracetamol (acetaminophen). These reactions were confirmed in controlled challenge tests. Patch tests with paracetamol were positive in all patients. A biopsy performed of the case 1 patch test confirmed that the lesion was compatible with delayed hypersensitivity reaction-type allergic contact dermatitis.

RESUMENObjetivo: Describir la frecuencia, los aspectos clínicos, bioquímicos y moleculares de la hipercolesterolemia familiar (HF) en sujetos que acuden a una unidad de endocrinología. Métodos: Estudio observacional, descriptivo en el que se evaluaron 3140 sujetos que fueron atendidos en la Unidad de Endocrinología del Centro Médico Orinoco en Ciudad Bolívar-Venezuela, desde el 7 de Enero del 2013 al 9 de Diciembre del 2016. Los casos índice fueron seleccionados de acuerdo a los criterios de la Red de Clínicas de Lípidos de Holanda. Se midieron lípidos plasmáticos. El análisis molecular se realizó por medio de secuenciación de ADN de los genes LDLR y APOB. Resultados: De los 3140 sujetos evaluados, 10 (0,32%) tuvieron características clínicas y bioquímicas compatibles con HF. Todos, excepto uno, eran de sexo femenino. Tres pacientes tuvieron antecedente familiares en primer grado de enfermedad coronaria prematura y ninguno antecedente personal de esta patología. Tres pacientes tuvieron obesidad, tres hipertensión arterial y ninguno fue diabético. Tres pacientes presentaban xantomas tendinosos y solo uno arco corneal. Los valores de LDL-c oscilaron entre 191 y 486 mg/dL. Solo dos recibían tratamiento con estatinas. En cuatro pacientes se identificó la causa genética de la HF, tres de ellos por mutaciones en el gen LDLR y uno por mutación en el exón 26 del gen APOB. Conclusión: Aproximadamente 1 de cada 314 personas que acuden a consulta en esta unidad de endocrinología presentan HF. Las mutaciones en el gen LDLR son las principales causantes de HF en este grupo de pacientes. Palabras Clave: Hipercolesterolemia familiar, Endocrinología, Colesterol, Xantomas, Venezuela.En este trabajo se estudiaron 3140 sujetos que asistieron a la unidad de endocrinología, de los cuales 10 (0,32%) tuvieron características clínicas y bioquímicas compatibles con HF. En la tabla 2 se presentan los datos clínicos de los 10 pacientes, cuyas edades estuvieron comprendidas entre los 18 y los 57 años. Todos, excepto uno, eran de sexo femenino. Tres pacientes tuvieron antecedente de algún familiar en primer grado con enfermedad coronaria prematura y ninguno comunicó antecedente personal de esta patología, ni de enfermedad arterial periférica o cerebrovascular. Con respecto a las comorbilidades, tres pacientes tuvieron obesidad, tres hipertensión arterial primaria y ninguno fue diabético. En relación a signos clínicos patognomónicos de HF, tres pacientes presentaban xantomas tendinosos y solo uno arco corneal.