Biomedical subjects

P Nava

Publications and source records attributed to P Nava.

12 recordsLinked to original sources

PubMed2005

Critical role of tight junctions in drug delivery across epithelial and endothelial cell layers.

Epithelia in multicellular organisms constitute the frontier that separates the individual from the environment. Epithelia are sites of exchange as well as barriers, for the transit of ions and molecules from and into the organism. Therapeutic agents, in order to reach their target, frequently need to cross epithelial and endothelial sheets. Two routes are available for such purpose: the transcellular and the paracellular pathways. The former is employed by lipophilic drugs and by molecules selectively transported by channels, pumps and carriers present in the plasma membrane. Hydrophilic molecules cannot cross biological membranes, therefore their transepithelial transport could be significantly enhanced if they moved through the paracellular pathway. Transit through this route is regulated by tight junctions (TJs). The discovery in recent years of the molecular mechanisms of the TJ has allowed the design of different procedures to open the paracellular route in a reversible manner. These strategies could be used to enhance drug delivery across epithelial and endothelial barriers. The procedures employed include the use of peptides homologous to external loops of integral TJ proteins, silencing the expression of TJ proteins with antisense oligonucleotides and siRNAs as well as the use of toxins and proteins derived from microorganisms that target TJ proteins.

Animals↗

PubMed2005

Lymphoma associated chromosomal abnormalities can easily be detected by FISH on tissue imprints. An underused diagnostic alternative.

BACKGROUND: Fluorescence in situ hybridisation (FISH) is useful for detecting specific chromosomal abnormalities in various tumours. In lymphomas, diagnosis is frequently made using paraffin wax embedded tissue. However, FISH performed under these conditions presents potential technical problems and difficulties in interpretation. AIMS: To show that FISH using tissue imprints and cytopreps or alternatively, bone marrow (BM) smears, constitutes an easy and rapid strategy to overcome these constraints. METHODS: The study comprised 46 patients with lymphoma. Sixty nine tissue imprints, cytopreps, or BM smears were analysed by FISH. Dual colour, dual fusion FISH probes were used to detect the t(8;14), t(11;14), and t(14;18) translocations, whereas a dual colour breakapart FISH probe was used to detect chromosomal translocations involving the BCL6 gene. RESULTS: Tissue imprints and cytopreps were successfully hybridised in all 52 cases, whereas hybridisation was successful in 16 of 17 archival BM smears. All patients could be analysed to identify either the presence or absence of chromosomal translocations. CONCLUSIONS: The use of tissue imprints, cytopreps, or BM smears to identify chromosomal abnormalities by FISH is a rapid and useful ancillary approach for diagnostic purposes. Therefore, it could be used on a routine basis whenever fresh samples are available.

Bone Marrow↗

PubMed2003

Tight junction proteins.

A fundamental function of epithelia and endothelia is to separate different compartments within the organism and to regulate the exchange of substances between them. The tight junction (TJ) constitutes the barrier both to the passage of ions and molecules through the paracellular pathway and to the movement of proteins and lipids between the apical and the basolateral domains of the plasma membrane. In recent years more than 40 different proteins have been discovered to be located at the TJs of epithelia, endothelia and myelinated cells. This unprecedented expansion of information has changed our view of TJs from merely a paracellular barrier to a complex structure involved in signaling cascades that control cell growth and differentiation. Both cortical and transmembrane proteins integrate TJs. Among the former are scaffolding proteins containing PDZ domains, tumor suppressors, transcription factors and proteins involved in vesicle transport. To date two components of the TJ filaments have been identified: occludin and claudin. The latter is a protein family with more than 20 members. Both occludin and claudins are integral proteins capable of interacting adhesively with complementary molecules on adjacent cells and of co-polymerizing laterally. These advancements in the knowledge of the molecular structure of TJ support previous physiological models that exhibited TJ as dynamic structures that present distinct permeability and morphological characteristics in different tissues and in response to changing natural, pathological or experimental conditions.

Animals↗

PubMed1999

Insulin-induced endothelin release and vasoreactivity in hypertriglyceridemic and hypertensive rats.

Insulin-elicited endothelin release in hypertriglyceridemic, hypertensive, hyperinsulinemic (HTG) rats was shown. Weanling male Wistar rats were given 30% sucrose in their drinking water for 20-24 wk. In vitro contractions of aorta and femoral arteries were elicited with 40 mM KCl. Endothelin release induced with KCl plus 50 microU/ml insulin resulted in increases in contractile responses: 41 +/- 5.9 and 57 +/- 6% for control and 65.5 +/- 6 and 95 +/- 9% for HTG aortas and femoral arteries, respectively. The endothelin ET(B)-receptor blocker BQ-788 decreased responses to KCl + insulin by 39 +/- 8 and 53 +/- 5% in control and 48 +/- 13 and 79 +/- 3.5% in HTG aortas and femoral arteries, respectively. The ET(A)-receptor antagonist PD-151242 inhibited these responses by 12 +/- 10 and 1 +/- 9% in control and by 51.5 +/- 9 and 58.5 +/- 1% in HTG aortas and femoral arteries, respectively. These results suggest that endothelin may contribute to the hypertension in this model.

Animals↗

PubMed1998

Improving breast cancer control among Latinas: evaluation of a theory-based educational program.

The study evaluated a theory-based breast cancer control program specially developed for less acculturated Latinas. The authors used a quasi-experimental design with random assignment of Latinas into experimental (n = 51) or control (n = 37) groups that completed one pretest and two posttest surveys. The experimental group received the educational program, which was based on Bandura's self-efficacy theory and Freire's empowerment pedagogy. Outcome measures included knowledge, perceived self-efficacy, attitudes, breast self-examination (BSE) skills, and mammogram use. At posttest 1, controlling for pretest scores, the experimental group was significantly more likely than the control group to have more medically recognized knowledge (sum of square [SS] = 17.0, F = 6.58, p < .01), have less medically recognized knowledge (SS = 128.8, F = 39.24, p < .001), greater sense of perceived self-efficacy (SS = 316.5, F = 9.63, p < .01), and greater adeptness in the conduct of BSE (SS = 234.8, F = 153.33, p < .001). Cancer control programs designed for less acculturated women should use informal and interactive educational methods that incorporate skill-enhancing and empowering techniques.

Acculturation↗

PubMed1997

Endothelin mediation of insulin and glucose-induced changes in vascular contractility.

Although the prevalence of hypertension in diabetic patients is high and many factors participate, hyperinsulinemia cannot be discarded as a contributing factor. Insulin could act directly on smooth muscle altering intracellular calcium levels that mediate contraction and glucose transport or could induce the secretion of endothelin by the endothelial cells lining the vessels. The aim of the present report was to study the effect of different glucose and insulin concentrations on rat vascular smooth-muscle contractile characteristics and to determine whether insulin effects are mediated by endothelin. Femoral arteries obtained from Wistar rats were placed in an in vitro chamber and superfused with different glucose and/or insulin solutions. The contractile response to KCl 80 mmol/L, measured by the force generated, showed a significant decrease with high extracellular glucose concentrations (11 mmol/L). Insulin caused a dose-dependent increase in arterial contraction induced by KCl. This increase was significant when arteries were stimulated with 80 mmol/L KCl in the presence of 5.5 mmol/L glucose, but when 40 mmol/L KCl was used, an increase was observed with both 5.5 and 11 mmol/L glucose. The insulin-induced contraction was significantly reduced in the presence of hyperimmune anti-endothelin serum and in the presence of endothelin receptor ET(A) and ET(B) antagonists PD 151,242 and BQ-788, respectively. These results suggest that hyperinsulinemia and hyperglycemia may contribute to hypertension in diabetes and that responses to insulin are mediated partially by endothelin, thus explaining why non-insulin-dependent diabetes mellitus patients show an increase in arterial pressure before the onset of nephropathy.

Animals↗

PubMed1970