Gastrointestinal cytomegalovirus disease in renal transplant recipients: A case series

The purpose of this article was to report a series of 23 renal transplant recipients with histologically proven and immunohistochemically confirmed cytomegalovirus (CMV) lesions in the gastrointestinal tract (GIT) and to assess the risk factors associated with severe disease/mortality. CMV patients (n=23) were allocated into two groups: those who died (n=6) and those considered cured (n=17). Overall mortality rate was 26% (6/23). Initial symptoms suggestive of lower GIT involvement were observed in all death cases and in 35.3% of those cured (p=0.01). Enterorrhagia was seen in 83.3% of the patients who died. Death risk increased twofold (RR 2 [1.13-3.52], p=0.01) when symptoms of lower GIT involvement were initially observed and sixfold when enterrohagia was present (RR 6 [1.1-35.9], p=0.001). Among death cases, mean time at diagnosis was significantly more distant (2002±2.9×2008±1.6, p=0.04). The difference in mortality rates seen as service practices changed along the years demonstrates the importance of early diagnosis. © 2011 John Wiley & Sons A/S.

Aparecimento de psoríase durante o tratamento das doenças inflamatórias intestinais com infliximabe: A terapia biológica deve ser suspensa?

Context - Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. Objective - To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. Methods - A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. Results - Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. Conclusion - As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma

The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC.

Qualidade microbiológica da água e histopatologia de brânquias de peixes provenientes de pisciculturas do município de itapecuru-mirim, Estado do Maranhão

The present study evaluated the microbiological water quality and tissue lesions in gills from Nile tilapia (Oreochromis niloticus) and hybrid tambacu (Colossoma macropomum female x Piaractus mesopotamicus male). For this, water and gills were collected from fish farming at six locations in Itapecuru- Mirim County, Maranhão State. Microbiological water analyses revealed contamination by total coliforms, Escherichia coli and heterotrophic bacteria. In the gills, we observed a diversity of Gram-positive and Gramnegative bacteria. The tissue lesions were: lamellar fusion, interlamellar hyperplasia, sub-epithelial edema and telangiectasia. Inflammatory lesions were not observed. Significant statistical difference (p > 0.05) was not detected when comparing different gills lesions during rainy and dry season. The correlation between lesion and pond type was statistically different (p < 0.05) for lamellar fusion and interlamellar hyperplasia which occurred more frequently at ground ponds. Regarding the frequency of lesions in the different fish species, there was statistical difference (p < 0.05), and the tambacu was more sensitive to lamellar fusion while tilapia was more sensitive for the other lesions. In relation to the sampling stations, there was statistical difference for all the gill lesions. In conclusion, tissue lesions are nonspecific and function as a defense mechanism against polluted aquatic environments, without infectious character.

Oral granuloma formation after injection of cosmetic filler

The increased use of orofacial fillers in cosmetic procedures has led to new diagnostic challenges for dentists and oral pathologists. Here, we describe a case with multiple oral foreign body granulomas, which were formed after a polymethylmetacrylate injection for cosmetic purposes. © 2011 European Association for Cranio-Maxillo-Facial Surgery.

Cimetidine-induced vascular cell apoptosis impairs testicular microvasculature in adult rats

Cimetidine, an H2 receptor antagonist used for treatment of gastric ulcers, exerts antiandrogenic and antiangiogenic effects. In the testes cimetidine impairs spermatogenesis, Sertoli cells and peritubular tissue, inducing apoptosis in the myoid cells. Regarding the importance of histamine and androgens for vascular maintenance, the effect of cimetidine on the structural integrity of the testicular vasculature was evaluated. Adult male rats received cimetidine (CMTG) and saline (CG) for 50 days. The testes were fixed in buffered 4% formaldehyde and embedded in historesin and paraffin. In the PAS-stained sections, the microvascular density (MVD) and the vascular luminal area (VLA) were obtained. TUNEL method was performed for detection of cell death. Testicular fragments embedded in Araldite were analyzed under transmission electron microscopy. A significant decrease in the MVD and VLA and a high number of collapsed blood vessel profiles were observed in CMTG. Endothelial cells and vascular muscle cells were TUNEL-positive and showed ultrastructural features of apoptosis. These results indicate that cimetidine induces apoptosis in vascular cells, leading to testicular vascular atrophy. A possible antagonist effect of cimetidine on the H2 receptors and/or androgen receptors in the vascular cells may be responsible for the impairment of the testicular microvasculature.

Subclinical muscle injuries in dogs infected with Leishmania (Leishmania) infantum chagasi

Although canine visceral leishmaniasis (CVL) has been extensively studied, muscular damage due to Leishmania (Leishmania) infantum chagasi infection remains to be fully established. The aim of this study was to describe the electromyographic and histological changes, as well as search for the presence of amastigote forms of Leishmania spp, CD3+ T-lymphocytes, macrophages and IgG in skeletal muscles of dogs with visceral leishmaniasis (VL). Four muscles (triceps brachial, extensor carpi radialis, biceps femoris and gastrocnemius) from a total of 17 naturally infected and six healthy dogs were used in this study. Electromyographic alterations such as fibrillation potentials, positive sharp waves and complex repetitive discharges were observed in, at least, three muscles from all infected dogs. Myocyte necrosis and degeneration were the most frequent muscular injury seen, followed by inflammatory reaction, fibrosis and variation in muscle fibers size. Immunohistochemistry in muscle samples revealed amastigote forms in 4/17 (23. 53%), IgG in 12/17 (70. 58%), CD3+ T-lymphocytes in 16/17 (94. 12%) and macrophages in 17/17 (100%) dogs. Statistically positive correlation was observed between: inflammatory infiltrate (p=0. 0305) and CD3+ immunoreaction (p=0. 0307) in relation to the number of amastigote forms; inflammatory infiltrate (p=0. 0101) and macrophage immunoreaction (p=0. 0127) in relation to the amount of CD3+; and inflammatory infiltrate (p=0. 0044) and degeneration/necrosis (p<0. 0001) in relation to the presence of macrophages. Our results suggest that different mechanisms contribute to the development of myocytotoxicity, including celular and humoral immune responses and direct muscular injury by the parasite. Nevertheless, the catabolic nature of the disease can probably interact with other factors, but cannot be incriminated as the only responsible for myositis.

Squamous cell lung carcinoma in a cat

Primary lung neoplasms are rare in small animals and present variable clinical signs. Here we report a case of a 4-year-old male cat which presented with apathy, dyspnea and pleural effusion. The cytological analysis of the pleural effusion revealed massive presence of atypical cells and the histopathological examination of the lung demonstrated tissue infiltration by atypical cells arranged in solid nests. The cytological and histopathological findings were compatible with squamous cell lung carcinoma.

Possible mechanism by which zinc protects the testicular function of rats exposed to cigarette smoke

Background: The aim of this study was to evaluate the changes in testicular function of rats due to cigarette smoke exposure and the possible mechanism by which zinc protects against these alterations. Methods: MaleWistar rats (60 days old) were randomly divided into 3 groups: control (G1, n = 10); exposed to cigarette smoke (G2, n = 10; 20 cigarettes/day/9 weeks) and exposed to cigarette smoke and supplemented with zinc (G3, n = 8; 20 cigarettes/day/9 weeks; 20 mg/kg zinc chloride daily for 9 weeks, by gavage). After the treatment period, the animals were euthanized, and materials were collected for analyses. Results: G2 rats showed a reduction in body mass; impaired sperm concentration, motility, morphology and vitality; and increased malonaldehyde and thiol group levels and superoxide dismutase activity as compared to G1. Zinc prevented the reduction of sperm concentration and the excessive increase of lipid peroxidation and induced an increase in plasma testosterone levels, wet weight of testis and thiol group concentration. Conclusions: Exposure to cigarette smoke led to harmful effects on testicular function at least partially due to the exacerbation of oxidative stress. Supplementary zinc had an important modulator/protector effect on certain parameters. The mechanism of zinc protection can be through an increase of SH concentration. Thus, zinc supplementation may be a promising addition to conventional treatments for male infertility related to smoking. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.

Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals: Radiochemical and real-time video-microscopy studies

Understanding the biological activity profile of the snake venom components is fundamental for improving the treatment of snakebite envenomings and may also contribute for the development of new potential therapeutic agents. In this work, we tested the effects of BthTX-I, a Lys49 PLA2 homologue from the Bothrops jararacussu snake venom. While this toxin induces conspicuous myonecrosis by a catalytically independent mechanism, a series of in vitro studies support the hypothesis that BthTX-I might also exert a neuromuscular blocking activity due to its ability to alter the integrity of muscle cell membranes. To gain insight into the mechanisms of this inhibitory neuromuscular effect, for the first time, the influence of BthTX-I on nerve-evoked ACh release was directly quantified by radiochemical and real-time video-microscopy methods. Our results show that the neuromuscular blockade produced by in vitro exposure to BthTX-I (1 μM) results from the summation of both pre- and postsynaptic effects. Modifications affecting the presynaptic apparatus were revealed by the significant reduction of nerve-evoked [3H]-ACh release; real-time measurements of transmitter exocytosis using the FM4-64 fluorescent dye fully supported radiochemical data. The postsynaptic effect of BthTX-I was characterized by typical histological alterations in the architecture of skeletal muscle fibers, increase in the outflow of the intracellular lactate dehydrogenase enzyme and progressive depolarization of the muscle resting membrane potential. In conclusion, these findings suggest that the neuromuscular blockade produced by BthTX-I results from transient depolarization of skeletal muscle fibers, consequent to its general membrane-destabilizing effect, and subsequent decrease of evoked ACh release from motor nerve terminals. © 2012 Elsevier Ltd.

Myenteric denervation in gastric carcinogenesis: Differential modulation of nitric oxide and annexin-A1

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

First record of chilodonella hexasticha (ciliophora: Chilodonellidae) in brazilian cultured fish: A morphological and pathological assessment

Chilodonelids are small ciliated protozoans found worldwide and can be dangerous in culture conditions. This study presents morphometric data on the ciliate Chilodonella that is found in cultured Nile tilapia (Oreochromis niloticus), native bait fish tuvira (Gymnotus aff. inaequilabiatus) and native pacu (Piaractus mesopotamicus) and includes a histopathological assessment of the changes that occur in the pacu. For parasitic diagnosis, skin and gill samples were scraped onto slides, dried at room temperature, stained with Giemsa or impregnated with silver nitrate, and the measurements were obtained from photomicrographs. In the diseased pacu, the first gill arch was collected and fixed in a 10% buffered formalin solution for histopathological analysis. Parasite specimens from the different collection sites were identified morphologically as C. hexasticha Kiernik (1909). Diseased fish exhibited depigmentation, skin ulceration, scale loss, excessive mucus production and gill lesions. Histopathological analysis of pacu gills displayed epithelial proliferation with mononuclear inflammatory infiltrate, hemorrhages, and scattering necrosis. In Brazilian-farmed fish this is the first record of C. hexasticha, which has great pathogenic potential in cultured freshwater species. In addition, two new hosts are presented. © 2012 Elsevier B.V.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. © 2012 Elsevier B.V.

Fractal dimension and Shannon's entropy analyses of the architectural complexity caused by the inflammatory reactions induced by highly crystalline polyvinyl alcohol) microspheres implanted in subcutaneous tissues of the Wistar rats

The results of the histopathological analyses after the implantation of highly crystalline PVA microspheres in subcutaneous tissues of Wistar rats are here in reported. Three different groups of PVA microparticles were systematically studied: highly crystalline, amorphous, and commercial ones. In addition to these experiments, complementary analyses of architectural complexity were performed using fractal dimension (FD), and Shannon's entropy (SE) concepts. The highly crystalline microspheres induced inflammatory reactions similar to the ones observed for the commercial ones, while the inflammatory reactions caused by the amorphous ones were less intense. Statistical analyses of the subcutaneous tissues of Wistar rats implanted with the highly crystalline microspheres resulted in FD and SE values significantly higher than the statistical parameters observed for the amorphous ones. The FD and SE parameters obtained for the subcutaneous tissues of Wistar rats implanted with crystalline and commercial microparticles were statistically similar. Briefly, the results indicated that the new highly crystalline microspheres had biocompatible behavior comparable to the commercial ones. In addition, statistical tools such as FD and SE analyses when combined with histopathological analyses can be useful tools to investigate the architectural complexity tissues caused by complex inflammatory reactions. © 2012 WILEY PERIODICALS, INC.