Statins and selective inhibition of Rho kinase protect small conductance calcium-activated potassium channel function (KCa2.3) in cerebral arteries

Background: In rat middle cerebral and mesenteric arteries the KCa2.3 component of endothelium-dependent hyperpolarization (EDH) is lost following stimulation of thromboxane (TP) receptors, an effect that may contribute to the endothelial dysfunction associated with cardiovascular disease. In cerebral arteries, KCa2.3 loss is associated with NO synthase inhibition, but is restored if TP receptors are blocked. The Rho/Rho kinase pathway is central for TP signalling and statins indirectly inhibit this pathway. The possibility that Rho kinase inhibition and statins sustain KCa2.3 hyperpolarization was investigated in rat middle cerebral arteries (MCA). Methods: MCAs were mounted in a wire myograph. The PAR2 agonist, SLIGRL was used to stimulate EDH responses, assessed by simultaneous measurement of smooth muscle membrane potential and tension. TP expression was assessed with rt-PCR and immunofluorescence. Results: Immunofluorescence detected TP in the endothelial cell layer of MCA. Vasoconstriction to the TP agonist, U46619 was reduced by Rho kinase inhibition. TP receptor stimulation lead to loss of KCa2.3 mediated hyperpolarization, an effect that was reversed by Rho kinase inhibitors or simvastatin. KCa2.3 activity was lost in L-NAME-treated arteries, but was restored by Rho kinase inhibition or statin treatment. The restorative effect of simvastatin was blocked after incubation with geranylgeranyl-pyrophosphate to circumvent loss of isoprenylation. Conclusions: Rho/Rho kinase signalling following TP stimulation and L-NAME regulates endothelial cell KCa2.3 function. The ability of statins to prevent isoprenylation and perhaps inhibit of Rho restores/protects the input of KCa2.3 to EDH in the MCA, and represents a beneficial pleiotropic effect of statin treatment.

Muscle growth in Nile tilapia (Oreochromis niloticus): histochemical, ultrastructural and morphometric study

Muscle growth in Nile tilapia (Oreochromis niloticus) was studied focusing on histochemical, ultrastructural, and morphometric characteristics of muscle fibers. Based on body length (cm), we studied four groups: G1 = 1.36+/-0.09, G2 = 3.38+/-0.44, G3 = 8.90+/-1.47, and G4 = 28.30+/-3.29 (mean+/-S.D.). All groups showed intense reaction to NADH-TR in subdermal fibers and weak or no reaction in deep layer fibers. In G3 and G4, an intermediate layer was also observed with fibers presenting weak reaction; in G4, groups of fibers with intense reaction were observed in the subdermal region. The myosin ATPase (m-ATPase) activities were acid-stable and alkali-labile in subdermal fibers; most deep layer fibers were alkali-stable and acid-labile. Intermediate fibers were acid-labile and alkali-stable. Two fiber populations were observed near deep muscle layer: one large presenting weak acid- and alkali-stable and the other small alkali-stable.During growth, muscle fiber hypertrophy was more evident in intermediate and white fibers for G3 and G4. However, in these groups, the presence of fiber diameters less than or equal to21 mum suggested that there is still substantial fiber recruitment, confirmed by ultrastructural study, but hypertrophy is the main mechanism contributing to increase in muscular mass. (C) 2003 Elsevier B.V. Ltd. All rights reserved.

Tissue evidence of the testosterone role on the abnormal growth and aging effects reversion in the gerbil (Meriones unguiculatus) prostate

Prostate differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Abundant biological data suggest that androgens play an important role in the development of the prostate cancer and other prostatic diseases. The objective of this work was to evaluate the effects of the testosterone supplementation in gerbil (a new experimental model) at different ages. Tissues from experimental animals were studied by histological and histochemistry procedures, androgen receptor immunohistochemistry assay, morphometric-stereological analysis, and transmission electron microscopy (TEM). After the treatment were observed increase of prostate weight and epithelium height in all ages studied. In some adult and aged treated animals, hyperplasic and displasic process were observed, including prostatic intraepithelial neoplasias and adenocarcinomas. Increase of the thickness of the smooth muscle cell (SMC) layer was observed in pubescent and adult animals and TEM revealed apparent SMC hypertrophy. An apparent increase in the frequency of blood vessels distributed by the subepithelial stroma in the treated animals was noticed. Reversion of the natural effects of aging on the prostate was observed in the aged treated animals in some acini of the gland. These data demonstrate that the gerbil prostate is susceptible to androgenic action at the studied ages and it can serve, for example, as experimental model to studies of prostate neoplasic process induction and hormonal therapy in aged animals.

Differential distribution of some extracellular matrix fibers in an experimentally denervated rat megaileum

Absence of enteric neurons is associated with thickening of the intestinal muscularis externa in Chagas' disease. The thickening is due to hyperplasia and hypertrophy of the smooth muscle cells and increased extracellular matrix components. The influence of the nervous system on the structure of the smooth muscle cells and its associated matrix has been poorly investigated. An experimental model of denervation of the ileum in rats was performed by application of the surfactant agent benzalkonium chloride that selectively destroys the myenteric plexus. Three months later, ileal tissue samples were obtained and studied by histochemistry and transmission electron microsocopy. Sham operated rats were used as controls. The diameter of collagen fibrils was evaluated in electron micrographs. The histopathological analysis showed thickening of the muscular layer. The thin and weakly arranged collagen and reticulin fibers surrounding the smooth muscle cells, observed in control cases by Picrosirius polarization (PSP) stain method, corresponded to a population of loosely packed thin collagen fibrils of uniform diameters (mean = 29.16 nm) at the ultrastructural level. In contrast, the thick and strongly birefringent fibers around the muscle cells, observed in the treated group, stained by PSP, corresponded to densely packed thicker fibrils with large variation in diameter (mean = 39.41 nm). Comparison of the data demonstrated statistically significant difference between the groups suggesting that the replacement of loosely arranged reticulin fibers by fibrous tissue (with typical collagen fiber), may alter the biomechanical function resulting in impairment of muscular contraction. (c) 2007 Elsevier Ltd. All rights reserved.

High fat-induced obesity associated with insulin-resistance increases FGF-2 content and causes stromal hyperplasia in rat ventral prostate

Obesity affects sex hormone secretion, which can negatively influence prostatic structure, homeostasis, and disease. This investigation aimed to evaluate the repercussions of obesity induced by a high-fat diet on the rat prostate, with or without treatment with the aromatase inhibitor, Letrozole. Adult Wistar rats were fed a high-fat diet (20% saturated fat, O) for 15 weeks to induce obesity or received a balanced diet (4% fat, C). Then, a group of C and O rats were daily treated with Letrozole (1 mg/kg b.w. per day) for 2 weeks (CL and OL, respectively). Subsequently, ventral prostate was processed for analysis by transmission electron microscopy, immunohistochemistry, and Western blotting. Obesity decreased 70% of the testosterone plasma level. The prostate showed epithelial atrophy and dilated acini in the intermediate portion and epithelial wrinkling in the distal tips. The relative frequency of smooth muscle alpha-actin in the O group increased by 67%. Ultrastructurally, epithelial cells in obese animals presented altered secretory organelles, lipid droplets, and thicker subjacent fibromuscular layer. Letrozole treatment caused a partial restoration of the prostatic changes caused by obesity. Obesity increased the prostatic content of fibroblast growth factor-2 (FGF-2) by 150%, and Letrozole treatment increased this protein even more in the control and obese groups. This investigation shows that obesity provokes structural and ultrastructural changes in the epithelium of rat prostate; these changes might affect gland homeostasis and physiology. The epithelial and smooth muscle cell hyperplasia and increased FGF-2 expression observed in this experimental model of obesity/insulin-resistance might explain the high frequency of benign prostatic hyperplasia in insulin-resistant men.

Some segmental structural features of the aortic wall of domestic chicken (Gallus domesticus)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tensile strength and histological changes of abdominal aorta of malnourished rats

The resistance of the abdominal aorta of rats after 6, 7 and 8 weeks of malnutrition, compared with control animals, was evaluated by longitudinal tensiometry. Weakness of this vessel in malnourished rats was demonstrated; microscopic examination of the aorta stained by Masson, Calleja and hematoxylin-eosin methods showed a decrease in amorphous ground substance and an increase in the width of elastic laminae. There was no visible alteration either in the endothelial lining layer or in the smooth muscle fibers. Such alterations of the aorta are, to the authors' knowledge, the first reported modifications in the peripheral vasculature after malnutrition.

Características estruturais da parede das artérias renal e femoral de coelho (Oryctolagus cuniculus)

In the renal and femoral arteries of rabbit was verified that both vessels had walls structured by myostromal components, despite of their different distributive of blood, being the renal artery a visceral blood vessel and the femoral artery a parietal vessel. This wall pattern in these vessels concerned to presence of connective stromal elements (collagen and elastic fibres and lamellae) and smooth muscle cells coexisting with some equilibrium in the wall structure of the renal and femoral arteries, mainly in the medial layer architecture. An intimal folding pattern was verified around the vascular lumen, possibly related to capacitance of the both arteries regarding to variability of pressure levels in cardiac cycle. Furthermore, myostromal relations of connective elements and smooth muscle cells verified in the medial layer and the network formed by connective elements in the adventitial layer of these arteries contributed to maintenance of wall viscoelasticity properties of the vessels.

Características ultraestruturais do segmento abdominal da aorta de rato albino

The objective of the present research was to investigate the ultrastructural peculiarities of the aortic wall of the rat. Seven young adult rats were used, from which fragments of the infrarenal abdominal aorta were collected. After collection, the vascular segments were fixed and sent for analysis by scanning electron microscope. The elastic lamellae appear interposed with smooth muscular fibers; this pattern was verified mainly at the medial layer structure. Among the mural elements a well defined interrelationship was established through connective lamellae of the arterial wall. The collagen lamellae mainly provided anchoring among the elastic and smooth muscular constituents. The intimal layer showed special ultrastructural features, such as a non-continuous inner elastic lamina presented in certain sites of the vascular wall, followed by endothelial pores. This mural pattern of the abdominal aorta provided support to vascular functions such as shrinkage among the laminar composition of the arterial layers, also acting in mechanical properties of the vascular wall, such as viscoelasticity and contractility - essential actions to blood vessel hemodynamics.

Arquitetura da parede vascular de segmentos torácico e abdominais da aorta de macaco prego (Cebus apella)

The intimal layer of the thoracic and abdominal aortic segments of Cebus apella monkey presented an evident inner elastic lamina. The medial layer of the thoracic aorta segment showed a basic lamellar elastic pattern having a medium average of 23.12 lamellae per analyzed cut sections, which appeared disposed circular and oblique relatively to the aortic lumen. The aortic adventitial layer, at this level, was formed mainly by collagen fibers, irregularly disposed between elastic fibers and smooth muscle cells. The aortic abdominal portion, in this monkey, at the suprarenal level presented a medium number of 19.12 elastic lamellae which showed a relatively disorganized and broken up pattern. At the infrarenal level the aortic medium layer showed a medium average of 11.75 elastic lamellae and next to the emission of the internal iliac arteries it was found only a middle average of 8.37 elastic lamellae intermingled with smooth muscle cells and collagen fibers whose concentration seemed to be increased next to the adventitial layer. The external elastic lamina was only present in the more distal aortic segment near to the emission of the internal iliac arteries.

A new proposed rodent model of chemically induced prostate carcinogenesis: Distinct time-course prostate cancer progression in the dorsolateral and ventral lobes

Background. Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes. Methods. Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes. Results. Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining. Conclusions. There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Copyright © 2013 Wiley Periodicals, Inc.

Morfologia e biometria das glândulas vesiculares e bulbouretrais de ovinos castrados e não castrados da raça Santa Inês

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Morfologia e morfometria da papila mamária em búfalas (Bubalus bubalis, L. 1758)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Resposta celular imune-inflamatória e de células caliciformes no intestino delgado de bezerros búfalos naturalmente infectados por Toxocara vitulorum

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Morphological characteristics of the Pterodoras granulosus digestive tube (Valenciennes, 1821) (Osteichthyes, Doradidae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)