RESUMEN
BACKGROUND: Introduction of cyclosporine (CsA) for clinical use has greatly enhanced the outcome of organ transplantation. However, CsA can cause nephrotoxicity and hypertension (HTN). This study was designed to test the hypothesis that CsA-induced HTN is related to depressed nitric oxide (NO) production. METHODS: Urinary excretion of NO metabolites (NOx) and endothelial and inducible NO synthase (eNOS and iNOS) proteins were determined in thoracic aortas and kidneys of CsA-treated (given CsA 18 mg/kg/day for 3 weeks) and placebo-treated rats. In addition, renal tissue eNOS and iNOS mRNA and aorta iNOS activity were measured. RESULTS: CsA administration resulted ina significant rise in arterial blood pressure (BP) coupled with a steady decline in urinary NOx excretion, suggesting depressed NO production. This was accompanied by a significant reduction in iNOS protein abundance in the kidney and thoracic aorta but no change in eNOS protein abundance. The fall in renal iNOS protein in CsA-treated rats was accompanied by a parallel decline in iNOS mRNA abundance and enzymatic activity. CONCLUSION: Administration of CsA for three weeks resulted in a significant rise in BP together with marked reductions in urinary NOx excretion, and renal and vascular iNOS expression. These observations suggest that CsA-induced HTN may be, in part, related to impaired NO production. If true, strategies designed to restore NO availability may mitigate HTN and other vascular complications of CsA therapy.
Asunto(s)
Aorta/enzimología , Ciclosporina/toxicidad , Hipertensión/inducido químicamente , Riñón/enzimología , Óxido Nítrico Sintasa/efectos de los fármacos , Animales , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hipertensión/enzimología , Masculino , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Nitroprusiato/farmacología , Ratas , Ratas Sprague-Dawley , omega-N-Metilarginina/farmacologíaRESUMEN
In vitro and in vivo Ca(2+)-uptake by the liver is increased by ferric lactate. In vitro albumin and deferoxamine inhibit ferric lactate effects. Electrophoresis demonstrates the binding of ferric lactate to albumin. In vivo, ferric lactate induces a significant increase of Ca(2+)-uptake by liver, with a maximum of 2.9 nmol/g against 0.66 nmol/g for control livers (P less than 0.005) between 5 and 24 h after administration. This uptake modification is reversible, while the amount of iron (measured as 59Fe taken up) remains constant throughout the experiment. The affinity of ferric lactate for protein and the iron mass-dependence of Ca(2+)-uptake increase support for the hypothesis of a ferric lactate-cell membrane interaction rather than an iron-catalyzed cell injury by lipid peroxidation as the major event leading to an increased Ca(2+)-uptake.
Asunto(s)
Calcio/metabolismo , Lactatos/farmacología , Hígado/metabolismo , Animales , Transporte Biológico Activo/efectos de los fármacos , Radioisótopos de Calcio , ATPasas Transportadoras de Calcio/metabolismo , Deferoxamina/farmacología , Relación Dosis-Respuesta a Droga , Compuestos Férricos/farmacología , Técnicas In Vitro , Hierro/metabolismo , Radioisótopos de Hierro , Cinética , Ácido Láctico , Hígado/efectos de los fármacos , Ratones , Unión Proteica , Albúmina Sérica Bovina/metabolismo , Albúmina Sérica Bovina/farmacologíaRESUMEN
Using [59Fe] ferric lactate, a direct relationship between iron concentration and [59Fe] uptake by Ehrlich ascites tumor cells was found. Deferoxamine and albumin inhibited this uptake. Electrophoresis showed that both molecules complexed iron from ferric lactate. [45Ca] uptake in the presence of ferric lactate showed the same inhibition, and an iron mass-dependence, these findings suggest an iron--cell membrane interaction as the cause of this phenomenon. The implication of iron--tumor cell membrane interaction in tumor growth regulation is discussed.
Asunto(s)
Calcio/metabolismo , Carcinoma de Ehrlich/metabolismo , Homeostasis/fisiología , Hierro/farmacocinética , Animales , Calcio/farmacocinética , Radioisótopos de Calcio , Carcinoma de Ehrlich/patología , División Celular/fisiología , Deferoxamina/farmacología , Electroforesis , Homeostasis/efectos de los fármacos , Hierro/metabolismo , Radioisótopos de Hierro , Cinética , Lactatos/metabolismo , Lactatos/farmacocinética , Ácido Láctico , Ratones , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Prospective surveillance of nosocomial infection was conducted at seven skilled proprietary nursing facilities in Orange County, Calif., USA. The average incidence of facility-acquired infection was 5.2 infections/1,000 patient days. The most common source of infection was urinary tract (47%), followed by respiratory tract (26%) and skin (14%). The four most common pathogens isolated were Proteus spp. (20%), Escherichia coli (17%), Staphylococcus aureus (13%) and Pseudomonas spp. (11%). Trimethoprim-sulfamethoxazole (20%) was the most frequently used antibiotic among all prescriptions, followed by ampicillin (16%) and ciprofloxacin (14%). Among all residents surveyed, 33% received at least one course of antibiotics during the study. Of special significance was the fact that 4 (22%) of the 18 strains of Pseudomonas were gentamicin resistant as were 12 of 80 (15%) of the strains of Enterobacteriaceae. Furthermore, 9 of 29 (31%) strains of Pseudomonas tested were found resistant to norfloxacin as were 15 of 129 (12%) strains of enterobacteriaceae. Susceptibility patterns of the isolated pathogens were similar to those of the acute care hospital. This study indicates that infection continues to be a major problem in the skilled nursing facility and that antibiotic-resistant pathogens will be a challenge for the future.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/epidemiología , Infección Hospitalaria/epidemiología , Instituciones de Cuidados Especializados de Enfermería/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/tratamiento farmacológico , California/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Farmacorresistencia Microbiana , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Calidad de la Atención de SaludRESUMEN
The study of the interaction between complexed iron and tumor cells in the presence of 67Ga-citrate indicates that a phenomenon of iron-binding related to the thermodynamic constant of stability of the iron complex, and a hydrolysis (or anion penetration) of the interaction product determine the uptake of 67Ga. The effects of various parameters such as ionic composition of the medium, nature of the iron complex, time of incubation and number of cells are discussed.