Planimetric and histological study of the aortae in atherosclerotic chickens treated with nifedipine, verapamil and diltiazem.

Calcium appears to be involved in many of the cellular events which are thought to be important in atherogenesis. Calcium channel blockers have been shown to reduce arterial lipid accumulation in animals without altering serum cholesterol. Avian models of atherosclerosis offer economic and technical advantages over mammalian models. In this study, we examine the effects of nifedipine, verapamil and diltiazem at clinical and higher doses, on the extent of atherosclerosis of egg-fed chickens. In order to assess the extent of atherosclerosis quantitatively, the aortic lesions of the thoracic and abdominal aorta, aortic arch and supraaortic regions were measured by planimetry. Atherosclerotic lesions were evaluated histologically. Statistically significant reductions in the lipid deposition of the aorta were found in all the treated groups. The extent and distribution of atherosclerotic lesions were decreased in a significant way by verapamil, nifedipine and diltiazem. The higher the dosage used, the higher the regression of the atherosclerotic lesions. At clinical dosage, nifedipine showed the highest decrease of the lesions. In addition, the chicken atherosclerosis model has proved itself useful and very suitable for in vivo drug intervention studies.

Inducibility of HBD-2 in acute burns and chronic conditions of the lung.

The respiratory tract produces a number of molecules that act in the first line of host defense to protect against pathogenic colonization and tissue invasion. Most of the innate antimicrobial activity can be attributed to airway fluid proteins, such as lysozyme, lactoferrin, and secretory leukoproteinase inhibitor, and peptides, such as defensins. Human beta-defensins are cationic antimicrobial peptides with broad and potent microbicidal activity that have been shown to play a role in protecting the healthy lung from infection. To determine the effect of thermal injury on the production of the inducible beta-defensin, human beta-defensin-2 (HBD-2), we measured the concentration of HBD-2 by Western blot analysis in bronchoalveolar lavage samples from the lungs of burned patients with and without inhalation injury. Our data demonstrates an increased amount of HBD-2 in the pulmonary airways with thermal injury compared to normal lung. A further substantial increase in levels was noted in chronic lung conditions.

[Ex vivo gene therapy in the treatment of Parkinson s disease]. / Terapia génica ex vivo en el tratamiento de la Enfermedad de Parkinson.

OBJECTIVE: Taking into account the growing development and application of in vivo and ex vivo gene therapy in neurodegenerative disorders we review this kind of therapy applications in Parkinson s disease. DEVELOPMENT: Gene therapy carried out to this illness includes the liberation of genes encoding biosynthetic enzymes for dopamine synthesis: tyrosine hydroxylase, AADC and GTP cyclohydrolase and neurotrophic factors like GDNF which promotes the survival and maintenance of dopamin rgic neurons. Ex vivo gene therapy allows the control of the gene transfer before implantation, however one of the fundamental problems of this procedure is given by the immunologic rejection, so the use of autologous sources is recommended. CONCLUSIONS: Ex vivo gene therapy is advantageous in relation to in vivo gene therapy because it allows the control of gene transfer before the implantation; looking for cellular sources of neural origin or pluripotent stem cells which can be differenciated toward a wanted cellular type in order to achieve the structural and functional integration of the cells implanted in the central nervous system are recommended; however it becomes necessary the development of vectors of new generation to avoid biosafety problems involved in the gene therapy.

Terapia génica ex vivo en el tratamiento de la enfermedad de Parkinson / Ex vivo gene therapy in the treatment of Parkinson´s disease

Objetivo. Teniendo en cuenta el creciente desarrollo y aplicación de la terapia génica tanto in vivo como ex vivo en las enfermedades neurodegenerativas, se revisan las aplicaciones de este tipo de estrategia en la enfermedad de Parkinson. Desarrollo. La terapia génica aplicable a esta enfermedad incluye la introducción de los genes que codifican enzimas que intervienen en la ruta biosintética de la dopamina: tirosina hidroxilasa, AADC y GTP ciclohidrolasa y factores neurotróficos como el GDNF, que promueve la supervivencia y mantenimiento de las neuronas dopaminérgicas. La terapia génica ex vivo permite el control del proceso de transferencia génica antes del proceso de implantación celular; sin embargo, uno de los problemas fundamentales de este procedimiento está dado por el rechazo inmunológico, por lo que se recomienda el uso de fuentes autólogas. Conclusiones. La terapia génica ex vivo presenta ventajas considerables en relación a la terapia in vivo, pues permite mantener el control de la transferencia génica antes del proceso de implantación celular; se recomienda buscar fuentes celulares de origen neural o células madres pluripotentes a las cuales se les puede inducir la diferenciación hacia el tipo celular deseado y , de esta manera, lograr la integración estructural y funcional de las células implantadas al sistema nervioso central. Sin embargo, se hace necesario el desarrollo de vectores de nueva generación que permitan solucionar los problemas de bioseguridad implícitos al utilizar la terapia génica (AU)

Purification and characterization of murine beta-nerve growth factor.

Beta-nerve growth factor (beta-NGF) is a trophic factor in the nervous system. We aimed to isolate and characterize this protein in view of its potential therapeutic use in neurodegenerative diseases. For purification a two-step ion-exchange procedure was followed. The characterization was performed using separation and immunological techniques, as well as a biological assay. These studies showed that the obtained protein consisted of a mixture of beta-NGF molecules, intact at their NH2-terminal extreme, and molecules which have lost the NH2-terminal octapeptide and exhibit modifications increasing its hydrophobicity. All these molecular species were recognized immunologically and showed biological activity.

Human beta defensin is absent in burn blister fluid.

Defensins are a family of cationic antimicrobial peptides that participate in innate host defence. Human beta defensin-2 (HBD-2) is produced by human keratinocytes, and has a potent bactericidal activity against a wide spectrum of microorganisms. We have recently shown that expression of HBD-2 is present in normal skin and lost in the full-thickness burn wound. Defensins have been found in the blister fluid of chronic wounds. Our study was designed to examine blister fluid from partial-thickness burns for defensin content. Fluid from five patients was collected from partial-thickness burn blisters, and then analysed by sandwich Enzyme-Linked Immunosorbent Assay (ELISA) with a monoclonal antibody and rabbit polyclonal antibody to HBD-2. The assay was validated against a Western blot assay for HBD-2 in samples of bronchoalveolar lavage fluid from patients with inflammatory lung disease. No HBD-2 was detectable in any of the burn blister fluids analysed. HBD-2 is lost in the full-thickness burn wound, and we have now demonstrated its absence in burn blister fluid. This finding represents evidence of a host defence defect within the burn wound and suggests a possible therapeutic role for antimicrobial peptides in the management of burn wounds.

[Nerve growth factor: possibilities and limitations of its clinical application]. / Factor de crecimiento nervioso: posibilidades y limitaciones de su aplicación clínica.

INTRODUCTION: The use of neurotrophic factors for the treatment of degenerative disorders of the nervous system opens up promising new perspectives. DEVELOPMENT: Nerve growth factor (NGF) represents the most known and studied trophic factor, which acts on sensory and sympathetic neurons of the peripheral nervous system, and on basal forebrain and striatal cholinergic neurons of the central nervous system. The specificity and trophic actions of NGF on these neuronal populations and its efficacy at preventing neurodegeneration have led to its proposal of evaluation in the treatment of neurological diseases such as: Alzheimer's disease, diabetic neuropathies and Huntington's diseases. Preclinical and clinical studies carried out in animal models and patients with diagnosis of these diseases have revealed satisfactory results. The difficulties of the NGF central chronic infusion, and the NGF detrimental effects arising from the stimulation of other sensitive neuronal population have stimulated active efforts for the development of more efficacious delivery strategies. Besides, it has also promoted further studies on the relation between the neuropathological stage, the dose and the effects of NGF administration. CONCLUSION: The NGF is a potential therapeutic agent in the treatment of neurodegenerative diseases.

Reduced antimicrobial peptide expression in human burn wounds.

Severely burned skin ceases to perform its natural protective role and surrenders itself as a nidus and portal for bacterial invasion. Antimicrobial peptides are part of a non-specific chemical defence system, separate from cellular and humoral immunity. Two of these peptides, human beta-defensins 1 and 2 have been recently found in skin and are produced by keratinocytes. Beta defensins have potent bactericidal activity against a wide spectrum of bacterial and fungal organisms commonly responsible for burn wound infections. To date, expression of beta defensins has not been examined in the human burn wound. Our findings demonstrate that expression of hBD-2 is greatly decreased in the burn wound whereas hBD-1 appears to be preserved. These results may have important implications in the pathogenesis and treatment of invasive burn sepsis.

[Ureteral valve associated with pyeloureteral stenosis]. / Válvula de ureter asociada a estenosis pieloureteral.

We report a case of ureteric valve associated with pyeloureteral obstruction, exhibited as fistula after pyeloplasty. We analyst different features of ureteric valves: anatomical, location, symptoms and associated congenital anomalies. The writer consider necessary to achieve the sounding of ureteral stretch during the operation of pyeloplasty.

Proenkephalin messenger RNA is expressed both in the rat anterior and posterior pituitary.

The presence of proenkephalin (PENK)-derived opioid peptides in the pituitary gland is well known. However, the cellular sources of their biosynthetic origin in all three pituitary lobes are less clear. In this study we identified the potential sites of synthesis by localizing the mRNA coding for PENK in the rat pituitary gland using in situ hybridization histochemistry. Numerous cells containing PENK mRNA were detected throughout the anterior lobe. Although suggested by previous reports, no mRNA signal could be detected in the intermediate lobe. Surprisingly, high levels of PENK mRNA were found in the posterior lobe. The cellular distribution in the neural lobe implies that pituicytes, a special class of glial cells, may express PENK mRNA.