RESUMO
The safety of rAd5-hTERTC27, a replication defective adenovirus vector carrying hTERTC27 for possible use against hepatocellular carcinoma (HCC) was assessed. In single-dose evaluations, intravenous dose levels of up to 2×10(11)VP/kg in rats and 9×10(10)VP/kg in monkeys were well tolerated with no abnormal changes in general signs, body weight and food consumption, and no significant differences in biochemical parameters, urinalysis, ECG, and systemic necropsy observations between the rAd5 groups and solvent control group except that slight hematological change was observed. No hemolytic effect using rabbit blood, local perivasculitis following intravenous injection in rabbits or systemic anaphylaxis in guinea pigs following intravenous dosing was seen. No effects on the central nervous system of mice occurred following intravenous dosing with the exception of an increase in sleep duration at the dose of 1.2×10(11)VP/kg (p<0.05) but not at lower doses of 2×10(10) and 6×10(10)VP/kg in the hypnotic synergism test. These results demonstrate that administration of rAd5-hTERTC27 was well tolerated in an initial set of safety studies as part of an evaluation to allow human trials for the treatment of HCC.
Assuntos
Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Telomerase/administração & dosagem , Telomerase/genética , Adenoviridae/genética , Adenoviridae/fisiologia , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Cobaias , Células HEK293 , Haplorrinos , Humanos , Injeções Intravenosas , Masculino , Camundongos , Coelhos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Sono/efeitos dos fármacos , Replicação ViralRESUMO
Noise and linearity performances are critical characteristics for radio frequency integrated circuits (RFICs), especially for low noise amplifiers (LNAs). In this paper, a detailed analysis of noise and linearity for the cascode architecture, a widely used circuit structure in LNA designs, is presented. The noise and the linearity improvement techniques for cascode structures are also developed and have been proven by computer simulating experiments. Theoretical analysis and simulation results showed that, for cascode structure LNAs, the first metallic oxide semiconductor field effect transistor (MOSFET) dominates the noise performance of the LNA, while the second MOSFET contributes more to the linearity. A conclusion is thus obtained that the first and second MOSFET of the LNA can be designed to optimize the noise performance and the linearity performance separately, without trade-offs. The 1.9GHz Complementary Metal-Oxide-Semiconductor (CMOS) LNA simulation results are also given as an application of the developed theory.