RESUMEN
Polyethyleneimine (PEI) is well-known as a non-viral gene delivery vector, especially for oligonucleotide delivery. However, its clinical applications are significantly limited due to its high cationic charge, lack of specificity, and interaction with the proteins and nontarget cells in the biological fluids, resulting in high cytotoxicity, poor stability and low transfection efficiency for oligonucleotides transporting. It has been shown that the molecular weight (MW) of PEI, degree of branching, N/P ratio, buffer capacity, oligonucleotide structure, culture medium pH, serum, presence or absence of and method of preparation make a significant difference in the cytoxicity, stability, and transfection efficiency for the PEI-based oligonucleotides delivery systems. Ligands, hydrophobic, hydrophilic, and amphiphilic modification of PEI have been investigated to reduce the cytoxicity and improve the stability, the transfection efficiency, and therapeutic effect. Moreover, various intelligent modifications of PEI, such as pH-responsive (hydrazone bond) and redox sensitive linkers (disulfide bond) can control oligonucleotides release and have attracted much attention. In general, more efficient oligonucleotide delivery can be achieved by the introduction of modifications to PEI and by optimization of parameters of PEI or PEI-based formulations.
Asunto(s)
Portadores de Fármacos/química , Oligonucleótidos/metabolismo , Polietileneimina/análogos & derivados , Línea Celular Tumoral , Portadores de Fármacos/síntesis química , Portadores de Fármacos/metabolismo , Liberación de Fármacos , Endocitosis/fisiología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Peso Molecular , Polietileneimina/síntesis química , Polietileneimina/metabolismoRESUMEN
Plants were the main source for human drugs until the beginning of the nineteenth century when plant-derived pharmaceuticals were partly supplanted by drugs produced by the industrial methods of chemical synthesis. During the last decades of the twentieth century, genetic engineering has offered an alternative to chemical synthesis, using bacteria, yeasts and animal cells as factories for the production of therapeutic proteins. After a temporary decrease in interest, plants are rapidly moving back into human pharmacopoeia, with the recent development of plant-based recombinant protein production systems offering a safe and extremely cost-effective alternative to microbial and mammalian cell cultures. In this short review, we will illustrate that current improvements in plant expression systems are making them suitable as alternative factories for the production of either simple or highly complex therapeutic proteins.
Asunto(s)
Biotecnología , Nanotecnología , Plantas Modificadas Genéticamente/metabolismo , Preparaciones Farmacéuticas/metabolismo , Proteínas Recombinantes/biosíntesisRESUMEN
In Australia, as in other countries that have experienced colonisation, indigenous people are massively overrepresented in all stages of the criminal justice system. If criminal justice agencies are to provide culturally responsive and effective services to this group, it is important that they employ significant numbers of indigenous staff across all levels of their organisations. Despite the positive intentions of many justice agencies to increase the proportion of indigenous staff members they employ, the numbers remain low. In this article, we explore some of the possible reasons for this by reporting the results of focus groups conducted with existing indigenous justice agency employees. The employees raised a number of issues relevant to recruitment and retention. These are discussed in terms of their potential value in improving justice agency indigenous recruitment and retention strategies.
Asunto(s)
Crimen/legislación & jurisprudencia , Crimen/estadística & datos numéricos , Derecho Penal/legislación & jurisprudencia , Policia/legislación & jurisprudencia , Grupos de Población/legislación & jurisprudencia , Retención en Psicología , Australia/epidemiología , Cultura , Humanos , Grupos de Población/estadística & datos numéricosRESUMEN
Options for lower limb percutaneous revascularization are limited especially for complex vessel obstruction. Cutting balloon angioplasty (CBA) has been described in the coronary literature as effective for complex disease. We analyzed our peripheral vascular database and report procedural outcomes along with the clinical success at a mean of 1-year follow-up in 73 patients with symptomatic lower limb ischemia undergoing CBA. CBA was successfully completed in all 73 patients (93 vessels; 100%) with predilation necessary in 4% of vessels. Severe intimal dissection or inadequate hemodynamic result necessitated in adjunctive stenting in 20%. There were no incidents of vessel perforation or surgical target vessel revascularization. One patient (1.5%) died during the periprocedural period due to renal failure. After mean follow-up of 1 year (6-21 months), 89.5% of threatened limbs were salvaged. CBA is a safe and feasible option for the treatment of popliteal and infrapopliteal vessels.
Asunto(s)
Angioplastia de Balón/métodos , Arteriopatías Oclusivas/terapia , Isquemia/terapia , Extremidad Inferior/irrigación sanguínea , Arteria Poplítea , Adulto , Anciano , Anciano de 80 o más Años , Arterias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Type 2 diabetes mellitus and the closely related metabolic syndrome are associated with significant risk for cardiovascular disease. Recent evidence suggests that both conditions are increasing in epidemic proportions. Dyslipidemia is characterized by increased triglyceride-rich lipoproteins; low high-density lipoprotein cholesterol; small, dense low-density lipoprotein particles; increased postprandial lipemia; and abnormal apolipoprotein A1 and B metabolism. All these lipoprotein disturbances accelerate atherosclerosis in these patients. It is likely that many patients will need combinations of lipid-modifying therapy to achieve American Diabetes Association (ADA), Adult Treatment Panel III, and American Heart Association (AHA)/American College of Cardiology (ACC) guidelines to help prevent cardiovascular disease and death.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Anticolesterolemiantes/farmacología , Anticolesterolemiantes/uso terapéutico , Azetidinas/farmacología , Azetidinas/uso terapéutico , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Ezetimiba , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Aceites de Pescado/farmacología , Aceites de Pescado/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/fisiopatología , Hipertrigliceridemia/sangre , Hipertrigliceridemia/fisiopatología , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Síndrome Metabólico/fisiopatología , Niacina/farmacología , Niacina/uso terapéutico , Tamaño de la PartículaRESUMEN
Low-temperature calcite and opal record the past seepage of water into open fractures and lithophysal cavities in the unsaturated zone at Yucca Mountain, Nevada, site of a proposed high-level radioactive waste repository. Systematic measurements of calcite and opal coatings in the Exploratory Studies Facility (ESF) tunnel at the proposed repository horizon are used to estimate the volume of calcite at each site of calcite and/or opal deposition. By estimating the volume of water required to precipitate the measured volumes of calcite in the unsaturated zone, seepage rates of 0.005 to 5 liters/year (l/year) are calculated at the median and 95th percentile of the measured volumes, respectively. These seepage rates are at the low end of the range of seepage rates from recent performance assessment (PA) calculations, confirming the conservative nature of the performance assessment. However, the distribution of the calcite and opal coatings indicate that a much larger fraction of the potential waste packages would be contacted by this seepage than is calculated in the performance assessment.