Histopathology of lesions caused by Pseudocorynosoma constrictum (Acanthocephala: Polymorphidae) in the ileum of blue-winged teal.

Pseudocorynosoma constrictum (Van Cleave, 1918) is a polymorphid acanthocephalan that attaches to the digestive tract of waterfowl to complete its life cycle, causing severe histological damage to its definitive avian hosts. In the present study, we present a histopathological analysis of the lesions that P. constrictum induced in the layers of the ileum of the blue-winged teal Anas discors. The results revealed that worms insert the attachment structures into the inner gut muscular layer, which causes substantial swelling, haemorrhaging and necrosis in the tissue near the parasite's proboscis. We also observed that the number of parasites attached to the tissue can obstruct the intestinal lumen; in the most serious case, we observed more than 30 parasites penetrating completely the walls of the bird intestine.

Cortactin deficiency causes increased RhoA/ROCK1-dependent actomyosin contractility, intestinal epithelial barrier dysfunction, and disproportionately severe DSS-induced colitis.

The intestinal epithelium constitutes a first line of defense of the innate immune system. Epithelial dysfunction is a hallmark of intestinal disorders such as inflammatory bowel diseases (IBDs). The actin cytoskeleton controls epithelial barrier integrity but the function of actin regulators such as cortactin is poorly understood. Given that cortactin controls endothelial permeability, we hypothesized that cortactin is also important for epithelial barrier regulation. We found increased permeability in the colon of cortactin-KO mice that was accompanied by reduced levels of ZO-1, claudin-1, and E-cadherin. By contrast, claudin-2 was upregulated. Cortactin deficiency increased RhoA/ROCK1-dependent actomyosin contractility, and inhibition of ROCK1 rescued the barrier defect. Interestingly, cortactin deficiency caused increased epithelial proliferation without affecting apoptosis. KO mice did not develop spontaneous colitis, but were more susceptible to dextran sulfate sodium colitis and showed severe colon tissue damage and edema formation. KO mice with colitis displayed strong mucus deposition and goblet cell depletion. In healthy human colon tissues, cortactin co-localized with ZO-1 at epithelial cell contacts. In IBDs patients, we observed decreased cortactin levels and loss of co-localization with ZO-1. Thus, cortactin is a master regulator of intestinal epithelial barrier integrity in vivo and could serve as a suitable target for pharmacological intervention in IBDs.

Production optimization of 99Mo/99mTc zirconium molybate gel generators at semi-automatic device: DISIGEG.

DISIGEG is a synthesis installation of zirconium (99)Mo-molybdate gels for (99)Mo/(99m)Tc generator production, which has been designed, built and installed at the ININ. The device consists of a synthesis reactor and five systems controlled via keyboard: (1) raw material access, (2) chemical air stirring, (3) gel dried by air and infrared heating, (4) moisture removal and (5) gel extraction. DISIGEG operation is described and dried condition effects of zirconium (99)Mo- molybdate gels on (99)Mo/(99m)Tc generator performance were evaluated as well as some physical-chemical properties of these gels. The results reveal that temperature, time and air flow applied during the drying process directly affects zirconium (99)Mo-molybdate gel generator performance. All gels prepared have a similar chemical structure probably constituted by three-dimensional network, based on zirconium pentagonal bipyramids and molybdenum octahedral. Basic structural variations cause a change in gel porosity and permeability, favouring or inhibiting (99m)TcO(4)(-) diffusion into the matrix. The (99m)TcO(4)(-) eluates produced by (99)Mo/(99m)Tc zirconium (99)Mo-molybdate gel generators prepared in DISIGEG, air dried at 80°C for 5h and using an air flow of 90mm, satisfied all the Pharmacopoeias regulations: (99m)Tc yield between 70-75%, (99)Mo breakthrough less than 3×10(-3)%, radiochemical purities about 97% sterile and pyrogen-free eluates with a pH of 6.

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.

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.

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.

[Enzymes in gastric juice. An aid in the diagnosis of gastric cancer]. / Enzimas en el jugo gástrico. Una ayuda para el diagnóstico del cáncer gástrico.

In the present study we measured the activities of the following enzymes: LDH (lactic dehydrogenase), beta-glucuronidase, acid maltase, phosphohexoseisomerase (PHI) and acid proteases in the gastric juice of patients with gastric cancer (n = 50) (Case Group), in endoscopically normal subjects (n = 50) and in subjects with different non tumor-like digestive pathologies (n = 55) (Control Groups). In the patients with gastric carcinoma we found a significant increase in LDH, beta-glucuronidase, PHI and acid maltase activities and a decreased activity of acid proteases. The results agree with previous findings from other workers. The variations of enzyme activities in gastric juice can help to differentiate between malignant and benign processes of the gastric mucosa.