New potential antitumoral fluorescent tetracyclic thieno[3,2-b]pyridine derivatives: interaction with DNA and nanosized liposomes

Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2-b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[(p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5-d]pyrido[1,2-a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, Ki = (8.7 ± 0.9) × 103 M-1 for compound 1 and Ki = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment

Metabolic Programming during Lactation Stimulates Renal Na+ Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways

BACKGROUND: Several studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na(+)-transporters and on the local angiotensin II (Ang II) signaling cascade in rats were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Female rats received a hypoproteic diet (8% protein) throughout lactation. Control and programmed offspring consumed a diet containing 20% protein after weaning. Programming caused a decrease in the number of nephrons (35%), in the area of the Bowman's capsule (30%) and the capillary tuft (30%), and increased collagen deposition in the cortex and medulla (by 175% and 700%, respectively). In programmed rats the expression of (Na(+)+K(+))ATPase in proximal tubules increased by 40%, but its activity was doubled owing to a threefold increase in affinity for K(+). Programming doubled the ouabain-insensitive Na(+)-ATPase activity with loss of its physiological response to Ang II, increased the expression of AT(1) and decreased the expression of AT(2) receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the α (24%) and ε (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT(2) receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na(+) excretion (80%) and intense proteinuria (increase of 400% in protein excretion). Programmed rats, which had normal arterial pressure at 60 days, became hypertensive by 150 days. CONCLUSIONS/SIGNIFICANCE: Maternal protein restriction during lactation results in alterations in GFR, renal Na(+) handling and in components of the Ang II-linked regulatory pathway of renal Na(+) reabsorption. At the molecular level, they provide a framework for understanding how metabolic programming of renal mechanisms contributes to the onset of hypertension in adulthood

Produção do conhecimento científico de Enfermagem em Nefrologia Producción del conocimiento científico de Enfermería en Nefrología Scientific knowledge production in Nephrology Nursing

Trata-se de uma pesquisa bibliográfica, com abordagem quantitativa, que teve como objetivo conhecer a produção científica das teses e dissertações disponíveis no banco de dados do Centro de Estudos e Pesquisa em Enfermagem (CEPEn) e sua aplicabilidade na área de enfermagem em nefrologia. Foram encontrados 48 resumos de teses e dissertações no período de 1979 a 2007. Os resultados apontam que estas produções se concentram nas regiões Sudeste e Sul. Com relação ao referencial teórico-metodológico, os mais freqüentes foram: método de assistência de enfermagem e abordagem compreensiva; os sujeitos investigados foram em sua maioria, os pacientes renais crônicos. Essa temática ainda é pouco investigada nos cursos de pós-graduação stricto senso, entretanto, há indícios de expansão dos estudos científicos nesta área.<br>Se trata de una búsqueda bibliográfica con abordaje cuantitativo, con el objetivo de conocer la producción científica de tesis y disertaciones disponibles en la base de datos del Centro de Estudios e Investigación en Enfermería (CEPEn) y su aplicabilidad en el campo de la enfermería en nefrología. Se han encontrado 48 resúmenes de tesis y disertaciones en el período 1979 a 2007. Los resultados indican que estos producciones se concentran en el Sudeste y Sur del Brasil. En lo que respecta al marco teórico y a la metodología, los más frecuentes fueron: método de atención de asistencia de enfermería y abordaje comprensiva; los sujetos investigados fueron en su mayoría, los pacientes renales crónicos. Este tema ha sido poco investigado en el postgrado stricto sensu, no obstante, hay pruebas de la ampliación de los estudios científicos en este ámbito.<br>This is a bibliographic research, with quantitative approach, that aimed to know the scientific production of theses and dissertations available in the database of the Center of Studies and Research in Nursing (CEPEn) and its applicability in the nursing area in nephrology. It was found 48 abstracts of theses and dissertations in the period from 1979 to 2007. The results point that these productions are concentrated in the Southeast and Southern regions of Brazil. Regarding the theoretical-methodological referential, the most frequent were: nursing assistance method and comprehensive approach; the investigated individuals were mostly the chronic renal patients. This thematic is still little investigated in the post-graduation stricto senso courses, however there are signs of expansion of the scientific studies in this area