RESUMEN
Hypertension is a complex pathophysiological state that leads to serious complications, including heart failure, coronary artery disease, and abnormal renal function. While traditional therapies can be effective in controlling the effects of hypertension, they offer no long-term cure and often lead to patient noncompliance, thereby diminishing their effectiveness. These reasons, coupled with the recent developments in gene transfer and somatic cell gene delivery, led researchers to explore alternative options that can produce long-term control of hypertension. Gene therapy offers the potential to yield lasting antihypertensive effects by influencing the genes associated with hypertension. In this review, we will discuss the merits of sense versus antisense strategies in controlling hypertension. We also discuss the advantages and disadvantages of both viral and nonviral vector types for the systemic delivery of genes for hypertension research. Results of our research group on the retrovirus-mediated delivery of the angiotensin type I receptor-antisense on the prevention of hypertension and related cardiovascular pathophysiology will be summarized. Finally, we discuss the future of this gene therapy approach in the reversal and long-term control of hypertension.
Asunto(s)
Terapia Genética/métodos , Vectores Genéticos , Hipertensión/genética , Hipertensión/terapia , Adenoviridae , Animales , Antihipertensivos/uso terapéutico , Aorta Torácica/patología , Presión Sanguínea , Peso Corporal , ADN sin Sentido , ADN Viral , Dependovirus , Corazón , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/prevención & control , Lentivirus , Liposomas , Tamaño de los Órganos , Ratas , Ratas Endogámicas SHR , RetroviridaeRESUMEN
Supercritical fluid extraction (SFE) using CO2 modified with methanol (10%) was employed for the extraction of cocaine from human hair. Extraction conditions were developed by using designed experiments to characterize the effects of pressure, temperature, and percent methanol on the recovery of cocaine from hair. When compared to the conventional acid hydrolysis method for hair analysis, SFE was faster and gave higher recoveries. Amounts of cocaine, benzoylecgonine (cocaine metabolite), codeine, and morphine in a hair standard reference material were determined by SFE-gas chromatography/ mass spectrometry (GC/MS) and found to be in agreement with reported levels. Analyses of hair from forensic case studies are also reported.
Asunto(s)
Cromatografía/métodos , Cocaína/análogos & derivados , Cocaína/análisis , Codeína/análisis , Cabello/química , Morfina/análisis , Dióxido de Carbono/química , Medicina Legal , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Metanol/química , Estándares de Referencia , Reproducibilidad de los ResultadosRESUMEN
Incidence of cardiovascular disease has reached epidemic proportions in spite of recent advances in improving the efficacy of pharmacotherapeutics. This has led many to conclude that drug therapy has reached a plateau in its effectiveness. As a result, our efforts have been diverted to explore the use of gene transfer approaches for long-term control of these pathophysiological conditions. The purpose of this review is to present various approaches that are being undertaken to provide "proof of principle" for gene therapy for cardiovascular diseases. Finally, we will discuss the future of gene therapy and other new technologies that may further advance this field of therapeutics.
