Protease inhibitor and metabolic alteration / Inhibidor de la proteasa y alteraciones metabólicas

Protease inhibitors (PIs), part of HAART (Highly Active Antiretroviral Therap) are selective, competitive inhibitors of protease, a crucial enzyme to viral maturation, infection and replication. A lipodystrophic syndrome has been reported in individuals treated with HAART, and associated to hyperglycemia, hypercholesterolemia, hypertrigliceridemia, hyperlipidemia, hypertension and hypreinsulinemia. The HAART-associated metabolic abnormalities were first associated with protease inhibitors, Ritonavir mostly, but the mechamisns that underlie these metabolic alterations are to date, not completely understood. Since PIs are candidate to be the drug of choice for other diseases treatment, such as the Hepatitis C, malaria and some types of cancer, it seems to be important to clarify the metabolic alterations associated to PIs. Wistar rats were treated twice a week with 30mg/kg Ritonavir for 4 and 8 weeks. Total cholesterol, HDL, LDL, VLDL, triglycerides and glycemic levels were measured by the end of each period of time selected. To avoid confunding effects of food intake, the animals were fasted 16 hours before. Our results showed rapid increase in serum triglycerides, total cholesterol, LDL-C and glycemic levels. No significant differences were observed for HDL-C or VLDL serum levels. Our study addresses the importance to observe the possible family history of dyslipidemia or diabetes, and control any other cardiovascular and diabetes risk factors when using protease inhibitors.

Los inhibidores de la proteasa (IP), que forman parte de la terapia HAART (terapia antirretroviral altamente activa), son inhibidores selectivos y competitivos de la proteasa, enzima crucial para la maduración, infección y replicación viral. Un síndrome lipodistrófico, asociado a hiperglucemia, hipercolesterolemia, hipertrigliceridemia, hiperlipidemia, hipertensión e hiperinsulinemia, ha sido relatado en pacientes tratados con HAART. Las anomalías metabólicas asociadas a la HAART fueron relacionadas, inicialmente, a los inhibidores de la proteasa, principalmente el Ritonavir, pero los mecanismos que relacionados a estas alteraciones metabólicas son poco comprendidos. Dado que los IP son posibles candidatos a fármacos de elección para tratamiento de otras enfermedades, como hepatitis C, malaria y algunos tipos de cáncer, es importante esclarecer las alteraciones metabólicas asociadas a los inhibidores de la proteasa. Ratas Wistar fueron tratadas dos veces por semana con 30 mg/kg de Ritonavir por 4 y 8 semanas. Fueron determinados los niveles de colesterol total, HDL, LDL, VLDL, triglicéridos y glucemia, al final de cada período considerado. Para evitar la interferencia de la ingestión de alimentos en las determinaciones de laboratorio, los animales fueron sometidos a un ayuno previo de 16 horas. Nuestros resultados mostraron un rápido aumento sérico de los niveles de triglicéridos, colesterol total, LDL-C y glucemia. No se observaron diferencias significativas para los niveles séricos de HDL-C o VLDL. Nuestro estudio apunta a la importancia de considerar los posibles antecedentes familiares de dislipidemia o diabetes, y controlar cualquier otro factor de riesgo cardiovascular y de diabetes cuando se utilizan los inhibidores de la proteasa.

Oral leishmaniasis: a clinicopathological study of 11 cases.

Leishmaniasis is a parasitic disease with diverse clinical manifestations, and considered a public health problem in endemic countries such as Brazil. Mucosal lesions usually involve the upper respiratory tract, with a predilection for nose and larynx. Oral involvement is unusual and in most cases it becomes evident after several years of resolution of the original cutaneous lesions. Oral lesions classically appear as mucosal ulcerations, mainly in the hard or soft palate. This report describes the clinicopathological data of 11 cases of mucocutaneous leishmaniasis with oral manifestations. Two cases of Leishmania (Viannia) braziliensis and one case of Leishmania (Leishmania) amazonensis were confirmed by polymerase chain reaction-restriction fragment length polymorphism or DNA sequencing in mucosal samples.