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.

[Enzyme typing of species of the genus Candida isolated from the oral cavity]. / Enzimotipagem de espécies do gênero Candida isoladas da cavidade bucal.

The production of phospholipase and proteinase exoenzymes was evaluated in seventy nine samples of Candida isolated from the oral cavity of patients with oral lesions characteristic of candidosis and from individuals presenting a clinically normal mouth, attended at the University of Dentistry of Ribeirão Preto USP. Among the strains of C. albicans isolated from oral lesions, the phospholipase and proteinase were detected in 83.3% and 66.7%, respectively. C. tropicalis and C. parapsilosis produced only proteinase. Regarding the isolated strains from niches without lesions, out of a total of 32 C. albicans, 71.9% presented phospholipase and 68.7% proteinase. C. tropicalis only presented the enzyme proteinase, C. glabrata, C. krusei, C. guilliermondii and Candida spp did not present any of the exoenzymes. Among the samples of C. albicans from both groups, the enzymotype 22 (positive phospholipase and proteinase weakly positive), was prevalent. Different enzymotypes of the same species were detected in samples collected from the same patient.

Effect of acyclovir on rat fetus palate mucosa.

Five pregnant rats were treated during organogenesis with sc injections of acyclovir (50 mg/kg body weight) on days 9, 10 and 11 of pregnancy. The fetuses (N=62) were evaluated on day 20 of gestation and presented decreased body weight as well as delayed differentiation of fetal rat palate epithelium, with increased nuclear volume, decreased cytoplasmic and cellular volumes, decreased epithelial and keratin thicknesses, and increased cellular numerical density.

[Morphometric study of changes in the submandibular gland of aging rats. 2. Ducts]. / Estudo morfométrico das alterações da glândula submandibular do rato, determinadas pelo envelhecimento. II. Ductos.

A decrease in rat submandibular gland parenchyma could be observed with increasing age, consequent to an apparent increase in the proportion of intralobular ducts. Signs of acinar atrophy were noted with nuclei of smaller volume. A great variety of nuclear sizes and shapes was also observed. The blood vessels were smaller, and the connective tissue was increased. These histological data were confirmed in part by application of the technique of Chalkley. The granulous duct cell height is smaller in old animals.

Influence of age on the production of rat spermatozoa, on their concentration in the cauda epididymidis, and on FSH, LH and testosterone plasma levels.

Testis samples were taken from young (3 months), middle-aged (12 months) and aged (24 months) male rats, processed, stained and examined via a light microscope. There were no prominent abnormal germinal epithelium and interstitial tissue. However, the aging process promoted a significant decrease in the mean amount of spermatids 19 per cross tubular section, and in the amount of Sertoli cells per cross tubular section in 24-month-old rats. The concentration of spermatozoa in the cauda epididymidis showed a gradual decrease from 3 to 12 and 24 months. After hCG injection all groups of animals exhibited an increase in plasma testosterone level, although the response was smaller in 12- and 24-month animals compared to the young mature (3 months) ones.

[Relation of the major connector of a removable partial denture (RPD) with mandibular mucosal tissue; clinical case]. / Relação do conector maior de prótese parcial removível (PPR) com os tecidos mucosos mandibulares; caso clínico.

When the performance of removable partial prosthesis is analyzed, it can be seen that failures outnumber the successes. These failures, however, should not be imputed to the prostheses themselves, but rather to the fact that proper biomechanical principles were not observed in the planning of these devices. Each component of a prosthesis should be carefully planned in order to obtain maximum stability with respect to the supporting tissues. One of these principles is concevued to the relieve that must be established between major connectors and mandibular mucosae. It is important to remember that mandibular mucosae is fine, moveable, very sensitive and weak, so that this mucosae be considered very susceptible to mechanical aggression. In this work the authors emphasize the necessity of relieve in the mandibular major connector in order not to pressure the investing tissues. Otherwise serious periodontal damage can occur.