Apoptose na infecção experimental de cães domésticos com Ehrlichia canis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Changes in apoptosis and Bcl-2 expression in human hyperglycemic, term placental trophoblast

Apoptosis and its associated regulatory mechanisms are physiological events crucial to the maintenance of placental homeostasis; imbalance of these processes, however, such as occurs under various pathological conditions, may compromise placenta function and, consequently, pregnancy success. Increased apoptosis occurs in the placentas of pregnant women with several developmental disabilities, while increased Bcl-2 expression is generally associated with pregnancy-associated tumors. Herein, we tested the hypothesis that apoptosis-associated disturbs might be involved in the placental physiopathology subjected to different maternal hyperglycemic conditions.Thus, in the present study we investigated and compared the incidence of apoptosis using TUNEL reaction and Bcl-2 expression, in term-placentas of normoglycemic, diabetic and daily hyperglycemic patients. Tissue samples were collected from 37 placentas, being 15 from healthy mothers with normally delivered healthy babies, and 22 from mothers with glucose disturbances. From these latter 22 patients, 10 showed maternal daily hyperglycemia and 12 were clinically diabetics. Both Bcl-2 expression and apoptotic DNA fragmentation were established and quantified in the trophoblasts of healthy mothers. Compared to these reference values, a higher apoptosis index and lower Bcl-2 expression were disclosed in the placentas of the diabetic women, while in the daily hyperglycemic group, values were intermediate between the diabetic and normoglycemic patients. The TUNEL/Bcl-2 index ratio in the placentas varied from 0.02 to 0.09 for pregnant normoglycemic and diabetic women, respectively, revealing a predominance of apoptosis in the diabetic group. Our findings suggest that hyperglycemia may be a key factor evoking apoptosis in the placental trophoblast, and therefore, is relevant to diabetic placenta function. (c) 2006 Elsevier B.V.. All rights reserved.

Inflammation and apoptosis induced by mastoparan Polybia-MPII on skeletal muscle

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exposure of young rats to high estrogen doses leads to degeneration of elongated spermatids

Single high doses of estrogen (35 mg/kg body weight) were administered to young rats aiming to exacerbate its effects on germ cell populations. The short-term (1 week) and medium-term (7 weeks) consequences of this estrogenic treatment (ET) on the testis were evaluated using light and electron microscopies, quantitative methods and TUNEL reaction. Short-term ET led to 50% atrophy of the testis, however, in the medium term the gonado-somatic index was recovered. No histopathological alterations were found at seminiferous epithelium except for short-term severe degeneration of elongated spermatids (EL) and low frequency of these cells in both time intervals. Two morphologically distinct patterns of degeneration were observed: (1) clusters of EL which were TUNEL-negative and exhibited bizarre appearance and nuclear fragmentation, (2) isolated apoptotic EL within the cytoplasm of Sertoli cells (SC). Both degenerative phenomena were more frequent in stages III - VIII of seminiferous cycle, whereas at stages I and II only coiling of flagellum was observed. One week after ET, small amounts of EL were detected in stages IX - XII, suggesting spermiation failure. Signs of functional SC damage such as an accumulation of myelin-like inclusions in their cytoplasm were observed in the short but not medium-term. However, the apoptotic rates still remained five times higher and the number of elongated spermatids was three-fold lower. Our data indicate that exposure to a high dose of estrogen around puberty has stage-specific effects on the testis and causes massive degeneration of elongated spermatids. (c) 2007 Elsevier Ltd. All rights reserved.

Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes

We investigated the effects of doxazosin (Dox), an alpha-adrenoceptor antagonist used clinically for the treatment of benign prostatic hyperplasia (BPH), on the rat prostatic complex by assessing structural parameters, collagen fiber content, cell proliferation, and apoptosis. Adult Wistar rats were treated with Dox (25 mg/kg per day), and the ventral (VP), dorsolateral, and anterior prostate (AP) regions of the prostate complex were excised at 3, 7, and 30 days after treatment. At 24 h before being killed, the rats were injected once with 5-bromodeoxyuridine (BrdU; thymidine analog) to label mitotically active cells. The prostates were weighed and processed for histochemistry, morphometry-stereology, immunohistochemistry for BrdU, Western blotting for proliferating cell nuclear antigen (PCNA), and the TUNEL reaction for apoptosis. Dox-treated prostate lobes at day 3 presented increased weight, an enlarged ductal lumen, low cubical epithelial cells, reduced epithelial folds, and stretched smooth muscle cells. However, at day 30, the prostates exhibited a weight reduction of ∼20% and an increased area of collagen and reticular fibers in the stromal space. Dox also reduced epithelial cell proliferation and increased apoptosis in the three prostatic lobes. Western blotting for PCNA confirmed the reduction of cell proliferation by Dox, with the AP and VP being more affected than the dorsal prostate. Thus, Dox treatment alters epithelial cell behavior and prostatic tissue mechanical demand, inducing tissue remodeling in which collagen fibers assume a major role. © 2007 Springer-Verlag.

Efeitos de doses subletais do imidaclopride no cérebro, ventrículo e túbulo de Malpighi de Apis melifera africanizada

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito do soro fetal bovino e do etossulfato de fenazina sobre o acúmulo lipídico, apoptose e resposta à vitrificação em embriões bovinos produzidos in vitro

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

Ectoplacental Cone Induces Resistance to Apoptosis in High Doses of Interferon (IFN)-gamma-Treated Decidual Cells

Problem In this study, we explored the relationship between decidual cells (DC) and interferon (IFN)-gamma, in the presence or absence of ectoplacental cone (EC) using a coculture system. Method of study Decidual cells and EC were isolated from pregnant mice on gestation day 7.5. DCs were cultured for 48 hr and then treated with fresh EC. After characterization, they were treated with IFN-gamma, and cell death was evaluated. Results Interferon-gamma drastically increased decidual apoptosis, which was partially reverted by the addition of EC to the IFN-gamma-treated decidual culture. Moreover, the addition of EC to non-treated DC cultures was also capable of attenuating death rates. Conclusion Resistance to apoptosis may be induced in DC by the EC. This suggests that EC may participate in the inhibition of IFN-gamma-dependent apoptosis and, therefore, play important role for DC survival in a cytokineenriched placental environment.

The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: an intravital microscopy study in mice

BACKGROUND: The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. METHODS: In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. RESULTS: Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. CONCLUSION: Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases.

TRPV1 receptors are involved in protein nitration and Muller cell reaction in the acutely axotomized rat retina

We report here the protein expression of TRPV1 receptor in axotomized rat retinas and its possible participation in mechanisms involved in retinal ganglion cell (RGC) death. Adult rats were subjected to unilateral, intraorbital axotomy of the optic nerve, and the retinal tissue was removed for further processing. TRPV1 total protein expression decreased progressively after optic nerve transection, reaching 66.2% of control values 21 days after axotomy. The number of cells labeled for TRPV1 in the remnant GCL decreased after 21 days post-lesion (to 63%). Fluoro-jade B staining demonstrated that the activation of TRPV1 in acutely-lesioned eyes elicited more intense neuronal degeneration in the GCL and in the inner nuclear layer than in sham-operated retinas. A single intraocular injection of capsazepine (100 mu M), a TRPV1 antagonist, 5 days after optic nerve lesion, decreased the number of GFAP-expressing Muller cells (72.5% of control values) and also decreased protein nitration in the retinal vitreal margin (75.7% of control values), but did not affect lipid peroxidation. Furthermore, retinal explants were treated with capsaicin (100 mu M), and remarkable protein nitration was then present, which was reduced by blockers of the constitutive and inducible nitric oxide synthases (7-NI and aminoguanidine, respectively). TRPV1 activation also increased GFAP expression, which was reverted by both TRPV1 antagonism with capsazepine and by 7-NI and aminoguanidine. Given that Muller cells do not express TRPV1, we suppose that the increased GFAP expression in these cells might be elicited by TRPV1 activation and by its indirect effect upon nitric oxide overproduction and peroxynitrite formation. We incubated Fluorogold pre-labeled retinal explants in the presence of capsazepine (1 mu M) during 48 h. The numbers of surviving RGCs stained with fluorogold and the numbers of apoptotic cells in the GCL detected with TUNEL were similar in lesioned and control retinas. We conclude that TRPV1 receptor expression decreased after optic nerve injury due to death of TRPV1-containing cells. Furthermore, these data indicate that TRPV1 might be involved in intrinsic protein nitration and Muller cell reaction observed after optic nerve injury. (C) 2010 Elsevier Ltd. All rights reserved.

A-REIT seasoned equity offerings : determinants and market reaction

The paper examines the decision by Australian Real Estate Trusts (A-REITs) to issue seasoned equity offerings from 2000 - 2008 and stock market reaction to the offerings using panel data and event study methodologies, respectively. The global financial crisis has resulted in freezing of the Australian bond markets, with several A-REITs left with seasoned equity issuance and asset sales as the only viable modes of raising additional capital. The findings review that leverage and operating risk are negative significant determinants of seasoned equity offerings; profitability and growth opportunities are positive significant determinants. Of the structure and type of properties held by the A-REIT, only stapled management structure and international operations are significant determinants. Type of properties held by A-REITs show inconsistent results. Similar to previous studies of seasoned equity offerings, we find a significant negative abnormal return associated with their announcement and no evidence of excessive leakage of information. Cross-sectional regressions show that the issued amount raised and leverage are significant factors affecting abnormal returns.

Stability and convergence of an implicit numerical method for the non-linear fractional reaction-subdiffusion process

In this paper, we consider the following non-linear fractional reaction–subdiffusion process (NFR-SubDP): Formula where f(u, x, t) is a linear function of u, the function g(u, x, t) satisfies the Lipschitz condition and 0Dt1–{gamma} is the Riemann–Liouville time fractional partial derivative of order 1 – {gamma}. We propose a new computationally efficient numerical technique to simulate the process. Firstly, the NFR-SubDP is decoupled, which is equivalent to solving a non-linear fractional reaction–subdiffusion equation (NFR-SubDE). Secondly, we propose an implicit numerical method to approximate the NFR-SubDE. Thirdly, the stability and convergence of the method are discussed using a new energy method. Finally, some numerical examples are presented to show the application of the present technique. This method and supporting theoretical results can also be applied to fractional integrodifferential equations.

Who needs it? An exploratory investigation into the reaction of small and medium enterprises to mobile data technologies

The technological environment in which contemporary small and medium-sized enterprises (SMEs) operate can only be described as dynamic. The seemingly exponential nature of technological change, characterised by perceived increases in the benefits associated with various technologies, shortening product life cycles and changing standards, provides for the small and medium-sized enterprise a complex and challenging operational context. The development of infrastructures capable of supporting the Wireless Application Protocol (WAP)and associated 'wireless' applications represents the latest generation of technological innovation with potential appeal to SMEs and end-users alike. The primary aim of this research was to understand the mobile data technology needs of SMEs in a regional setting. The research was especially concerned with perceived needs across three market segments; non-adopters of new technology, partial-adopters of new technology and full-adopters of new technology. Working with an industry partner, focus groups were conducted with each of these segments with the discussions focused on the use of the latest WP products and services. Some of the results are presented in this paper.