Comparaison de deux nouvelles méthodes d’évaluation de la fertilité masculine avec le spermogramme chez des patients ayant recours à la fécondation in vitro

Des facteurs masculins sont identifiés dans près de la moitié des cas d’infertilité. À ce jour, les tests évaluant la fertilité masculine demeurent peu prédictifs de la survenue d’une grossesse. Dans le but de pallier cette lacune, nous avons mis au point deux nouveaux tests mesurant l’intégrité de l’ADN et le temps de survie des spermatozoïdes. Nous avons effectué une étude prospective portant sur 42 couples infertiles suivis en fécondation in vitro (FIV). Le spermogramme a été effectué selon les critères de l’Organisation Mondiale de la Santé (OMS) et le temps de survie des spermatozoïdes exposés à un détergent cationique a été mesuré en observant la mobilité sous microscope. L’intégrité de l’ADN des spermatozoïdes a été vérifiée par la nouvelle méthode de marquage radioenzymatique et par analyse de la structure de la chromatine (SCSA). Tous les tests ont été réalisés sur la partie des échantillons de sperme non utilisée par la clinique de fertilité. Le projet a été approuvé par le comité d’éthique du Centre Hospitalier Universitaire de Montréal (CHUM) et les patients ont préalablement signé un formulaire de consentement éclairé. L’analyse des paramètres du spermogramme et de l’intégrité de l’ADN n’a montré aucune différence statistiquement significative entre les données chez les couples avec ou sans grossesse. Cependant, le taux de grossesse biochimique était statistiquement plus élevé chez les couples dont le temps de survie des spermatozoïdes était long (>250 s) comparativement à ceux dont ce temps était court (≤250 s): 66% vs 27% respectivement (p<0,05). Les taux de grossesse clinique et d’implantation étaient aussi plus élevés, mais les différences n’atteignaient pas le seuil de signification statistique. Nos résultats confirment que le spermogramme et la mesure de la fragmentation de l’ADN des spermatozoïdes ne sont pas de bons facteurs prédictifs des résultats de la FIV. Par contre, le test de survie des spermatozoïdes serait un meilleur indicateur de la possibilité d’une grossesse en FIV. L’amélioration de sa spécificité et un plus grand nombre de sujets sont nécessaires avant de proposer son application en clinique de fertilité.

Product autoregressive models for non-negative variables

When variables in time series context are non-negative, such as for volatility, survival time or wave heights, a multiplicative autoregressive model of the type Xt = Xα t−1Vt , 0 ≤ α < 1, t = 1, 2, . . . may give the preferred dependent structure. In this paper, we study the properties of such models and propose methods for parameter estimation. Explicit solutions of the model are obtained in the case of gamma marginal distribution

Contribuição para o estudo do linfoma no cão em Portugal : análise da casuística em dois centros de referência

O linfoma é um grupo heterogéneo de neoplasias que apresentam morfologia variável e apresentações clínicas diversas, exigindo diferentes abordagens diagnósticas e terapêuticas. O prognóstico difere bastante entre os canídeos afectados. A presente dissertação refere-se a um estudo retrospectivo (2008-2012), de 50 canídeos com linfoma, com o objectivo de comparar os resultados obtidos com a bibliografia publicada, determinando ainda o impacto do imunofenótipo (B ou T) na sobrevida de cães com linfoma. Foi registado o mesmo número de machos e fêmeas e as raças mais frequentes foram o Boxer, Rottweiller e Cocker Spaniel. O diagnóstico da doença foi realizado maioritariamente por histopatologia de linfonodo (56%), revelando 84% de linfomas da forma multicêntrica. Quando determinado, o imunofenótipo mais frequente foi o de células B (69%). A maioria dos canídeos estava em estadios avançados da doença (III-V) (98%) no momento do diagnóstico, revelando 54% dos casos sub-estadio "b" segundo a OMS. O tratamento quimioterápico mais utilizado foi o protocolo CHOP (n=26) seguido do COP (n=9). A toxicidade hematológica e gastrointestinal secundárias à quimioterapia estiveram em igual número (22% cada), não se observando efeitos adversos em 56% dos cães com linfoma. Por último, o tempo médio de sobrevivência registado foi de 393 dias. Não foi encontrada uma relação estatísticamente significativa entre as variáveis (raça, sub-estadio e sexo) e o imunofenótipo de linfoma, sendo os tempos médios de sobrevivência de linfomas T e B semelhantes, 388 e 463 dias, respectivamente. No nosso caso, as principais diferenças encontradas, relativamente à bibliografia publicada, foram uma quantidade elevada de pacientes em sub-estadio "b" e os tempos médios de sobrevivência semelhantes para os diferentes imunofenótipos.

Impacto da tomografia computorizada versus radiografia no prognóstico pós-cirúrgico do carcinoma espinocelular oral no cão

Objectivos: Neste estudo retrospectivo pretendeu-se determinar o impacto da tomografia computorizada na sobrevivência pós-cirúrgica do cão com carcinoma espinocelular na cavidade oral, comparativamente à radiografia. Enfatizando desta forma, a sua importância no diagnóstico, no planeamento cirúrgico e prognóstico. O segundo objectivo consistiu em determinar as características tomográficas dos carcinomas espinocelulares da cavidade oral em cães. Material e Métodos: Foram analisados 7 canídeos com diagnóstico de carcinoma espinocelular. Os critérios de inclusão foram: cães com carcinoma espinocelular diagnosticado por biópsia, exame imagiológico complementar (radiografia simples ou tomografia computorizada), elegibilidade para cirurgia, execução de tratamento cirúrgico e acompanhamento pós-cirúrgico durante 2 anos. Foi registada a idade, o sexo, a raça, a localização anatómica, o estadiamento T e N, as características radiográficas e tomográficas dos tumores, o tempo de recorrência e por fim o tempo de sobrevivência global descrito nos registos consultados. Procedeu-se também ao registo das variáveis das imagens radiográficas e tomográficas obtidas: definição das margens neoplásicas, presença ou ausência de reacção perióstea e de destruição de osso cortical adjacente, presença de deslocação dentária e de reabsorção dentária e densidade óssea local. Resultados: Nenhum dos meios imagiológicos permitiu uma visualização bem definida das margens neoplásicas. A nível da destruição de osso cortical adjacente, foi visível em 66,67% dos casos avaliados com radiografia e em todos os casos que foram avaliados com tomografia computorizada (100%). Foi visível reacção perióstea em 33,33% dos canídeos avaliados por radiografia e em nenhum dos avaliados por tomografia (0%). A densidade óssea local estava diminuída em todos os casos avaliados por radiografia simples ou por tomografia. A nível de reabsorção dentária estava presente em 33,33% dos avaliados por radiografia e em 25% dos avaliados por tomografia. Foi possível visualizar deslocação dentária em 66,67% dos avaliados por radiografia e em todos os avaliados por tomografia (100%). A nível de percentagem de casos com recorrência local, nenhum caso avaliado com radiografia recorreu e apenas 1 caso avaliado por tomografia recorreu em 289 dias. O tempo médio de sobrevivência foi superior no grupo dos avaliados com radiografia (1091,7 dias) relativamente ao grupo avaliado por tomografia (404 dias). Ao fim de 2 anos, 66,67% dos casos avaliados por radiografia estavam vivos e somente 25% dos casos avaliados com tomografia sobreviveram. Discussão/conclusão: Não foi possível determinar o impacto real dos dois meios de diagnóstico no prognóstico pós-cirúrgico do carcinoma espinocelular oral no cão, devido à reduzida amostra e aos tumores com pior prognóstico (por localização e estadiamento) terem sido remetidos para tomografia.

Viability of Salmonella enterica subsp. enterica during the preparation and cold storage of Egyptian soft cheeses and ice-cream

Changes occurring in the viability of Salmonella enterica subsp. enterica during the preparation and cold storage of Domiati cheese, Kariesh cheese and ice-cream were examined. A significant decrease in numbers was observed after whey drainage during the manufacture of Domiati cheese, but Salmonella remained viable for 13 weeks in cheeses prepared from milks with between 60 and 100 g/L NaCl; the viability declined in Domiati cheese made from highly salted milk during the later stages of storage. The method of coagulation used in the preparation of Kariesh cheese affected the survival time of the pathogen, and it varied from 2 to 3 weeks in cheeses made with a slow-acid coagulation method to 4-5 weeks for an acid-rennet coagulation method. This difference was attributed to the higher salt-in-moisture levels and lower pH values of Kariesh cheese prepared by the slow-acid coagulation method. A slight decrease in the numbers of Salmonella resulted from ageing ice-cream mix for 24 h at 0degreesC, but a greater reduction was evident after one day of frozen storage at -20degreesC. The pathogen survived further frozen storage for four months without any substantial change in numbers.

Antitumour activity of [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride in xenografted Ehrlich's ascites tumour

The effects of a new titanocene compound with an ansa ligand in the cyclopentadienyl rings, the 1,2-di(cyclopentadienyl)-1,2-di(p-NNdimethylaminophenyl)-ethanediyl] titanium dichloride (TITANOCENE X), on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming unit-granulocyte-macrophage (CFU-GM)] and Natural killer (NK) cell activity in Ehrlich's ascites tumour (EAT)-bearing mice were studied. Myelosuppression concomitant with increased numbers of spleen CFU-GM was observed in tumour-bearing mice. Treatment of these animals with TITANOCENE X (2.5-50mg/kg/day) produced an increase in myelopoicsis, in a dose-dependent manner, and reduced spleen colony formation. In addition, the treatment of EAT-bearing mice with 3 doses of 20 or 50 mg/kg TITANOCENE X restored to normal values the reduced Natural killer cell function observed during tumour growth. In parallel, TITANOCENE X prolonged, in a dose-dependent manner, the survival of mice inoculated with Ehrlich's ascites tumour. The highest dose of 50 mg/kg prolonged in 50% the survival time of EAT-bearing mice, compared to non-treated tumour-bearing controls. In comparison with previous results from our laboratory addressing the effects of titanocenes on haematopoiesis, we observed with TITANOCENE X a similar effective profile as for bis(cyclopentadienyl) dithiocyanate titanium(IV), being both less effective than di(cyclopentadienyl) dichloro titanium(IV), since the latter not only prolonged, but also increased the rate of survival. These differences in efficacy may be due to the nature of the ansa-cyclopentadienyl ligand used in TITANOCENE X, since the C, bridge between the two cyclopentadienyl groups will increase the hydrolytic stability by an organometallic chelate effect. Also, the introduction of two dimethylamino substituents increases the water solubility of TITANOCENE X when compared to titanocene dichloride itself (c) 2006 Elsevier B.V. All rights reserved.

MyD88 Signaling Is Required for Efficient Innate and Adaptive Immune Responses to Paracoccidioides brasiliensis Infection

The mechanisms that govern the initial interaction between Paracoccidioides brasiliensis, a primary dimorphic fungal pathogen, and cells of the innate immunity need to be clarified. Our previous studies showed that Toll-like receptor 2 (TLR2) and TLR4 regulate the initial interaction of fungal cells with macrophages and the pattern of adaptive immunity that further develops. The aim of the present investigation was to assess the role of MyD88, an adaptor molecule used by TLRs to activate genes of the inflammatory response in pulmonary paracoccidioidomycosis. Studies were performed with normal and MyD88(-/-) C57BL/6 mice intratracheally infected with P. brasiliensis yeast cells. MyD88(-/-) macrophages displayed impaired interaction with fungal yeast cells and produced low levels of IL-12, MCP-1, and nitric oxide, thus allowing increased fungal growth. Compared with wild-type (WT) mice, MyD88(-/-) mice developed a more severe infection of the lungs and had marked dissemination of fungal cells to the liver and spleen. MyD88(-/-) mice presented low levels of Th1, Th2, and Th17 cytokines, suppressed lymphoproliferation, and impaired influx of inflammatory cells to the lungs, and this group of cells comprised lower numbers of neutrophils, activated macrophages, and T cells. Nonorganized, coalescent granulomas, which contained high numbers of fungal cells, characterized the severe lesions of MyD88(-/-) mice; the lesions replaced extensive areas of several organs. Therefore, MyD88(-/-) mice were unable to control fungal growth and showed a significantly decreased survival time. In conclusion, our findings demonstrate that MyD88 signaling is important in the activation of fungicidal mechanisms and the induction of protective innate and adaptive immune responses against P. brasiliensis.

Autolytic Mycobacterium leprae Hsp65 fragments may act as biological markers for autoimmune diseases

Investigating the proteolytic activity of the recombinant Mycobacterium leprae Heat Shock Protein of 65 kDa (rHsp65), chaperonin 2 (cpn2), we observed that it displays high instability. The fragmentation process starts at the C-terminus followed by progressive degradation of the N-terminus, which leads to a stable fragment comprising the middle region of the molecule. Urea was able to prevent autolysis, probably due to its denaturing action, while EDTA increased degradation levels indicating the need for metal ions. Peptides originated from autolysis were purified and analyzed by mass spectrometry, generating a continuous map. Since the bacteria and mammalian Hsp60 are known to be targets of the immune response and have been implicated in autoimmune diseases and chronic inflammation, the in vivo effect of rHsp65 peptides was evaluated in the spontaneous Systemic Lupus Erythematosus (SLE) model developed by the (NZB/NZW)F(1) mouse hybrids, and their individual anti-rHsp65 IgG2a/IgG1 antibody titer ratio was determined. The results showed orientation toward a T(H)1 responsiveness, and the treatment with the rHsp65 peptides diminished the environmental variance of the survival time of treated animals. These results outline the fact that environmental factors may also act through the modified stability expression of Heat Shock Proteins intervening during autoimmune processes. (C) 2011 Elsevier Ltd. All rights reserved.

Use of in vitro critical inhibitory concentration, a novel approach to predict in vivo synergistic bactericidal effect of combined amikacin and piperacillin against pseudomonas aeruginosa in a systemic rat infection model

PURPOSE: This study was undertaken to explore the use of in vitro critical inhibitory concentration (CIC) as a surrogate marker relating the pharmacokinetic (PK) parameters to in vivo bactericidal synergistic effect [pharmacodynamic (PD)] of amikacin + piperacillin combination against Pseudomonas aeruginosa in a systemic rat infection model. METHODS: The in vitro antibacterial activities of amikacin and piperacillin, alone and in combinations at various ratios of the concentrations, were tested against a standard [5 x 10(5) colony-forming units (CFU)/ml] and a large (1.5 x 10(8) CFU/ml) inoculum of P. aeruginosa ATCC 9027 using a modified survival-time method. The CIC of each individual antibiotic for the different combinations was determined using a cup-plate method. In vivo studies were performed on Sprague-Dawley rats using a systemic model of infection with P. aeruginosa ATCC 9027. PK profiles and in vivo killing effects of the combination at different dosing ratios were studied. RESULTS: An inoculum effect was observed with the antibiotics studied. Synergy was seen against both the inocula at the following concentration ratios: 70% C(ami) + 30% C(pip) and 75% C(ami) + 25% C(pip), where C(ami) and C(pip) are the concentrations of amikacin and piperacillin to produce a 1000-fold decrease in bacterial population over 5 h, respectively. The CIC values determined corroborated with the order of in vitro bacterial killing observed for the antibiotic combinations. The dosing ratio of 12.6 mg/kg amikacin + 36 mg/kg piperacillin (a 70:30 ratio of the individual doses) exhibited the greatest killing in vivo when compared to the other ratios. The PK-PD relationships were described by simple, linear regression equations using the area under the in vivo killing curve as a PD marker and the AUCIC(ami)/CIC(ami) + AUCIC(pip)/CIC(pip), AUC(ami)/CIC(ami) + AUC(pip)/CIC(pip), C(max,ami)/CIC(ami) + C(max,pip)/CIC(pip), and AUCIC(ami)/MIC(ami) + AUCIC(pip)/MIC(pip) as PK markers for the amikacin + piperacillin combination. CONCLUSION: The combination of amikacin and piperacillin exhibited synergistic killing effect on P. aeruginosa that could be modeled using CIC as a surrogate marker relating the PK parameters to in vivo bactericidal effect.

Cancer patient preferences for communication of prognosis in the metastatic setting

PURPOSE: To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. PATIENTS AND METHODS: One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. RESULTS: More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P = .047) and average survival (P = .049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P = .03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P = .02). CONCLUSION: Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.

Edge effects in patchy seagrass landscapes : the role of predation in determining fish distribution

Predation is often described as an underlying mechanism to explain edge effects. We assessed the importance of predation in determining edge effects in seagrass using two approaches: a video survey to sample predators at small scales across seagrass edges, and a tethering experiment to determine if predation was an underlying mechanism causing edge effects. Underwater videos were placed at four positions: middle of seagrass patches; edge of seagrass; sand immediately adjacent to seagrass and sand distant from seagrass. Fish abundances and the time fish spent in view were measured. The main predatory fish (Australian salmon, Arripis spp.) spent more time over adjacent sand than other positions, while potential prey species (King George whiting, Sillaginodes punctata (Cuvier), recruits) were more common in the middle of seagrass patches. Other species, including the smooth toadfish, Tetractenos glaber (Freminville), and King George whiting adults, spent more time over sand adjacent to seagrass than distant sand, which may be related to feeding opportunities. King George whiting recruits and pipefish (Stigmatopora spp.) were tethered at each of the four positions. More whiting recruits were preyed upon at outer than inner seagrass patches, and survival time was greater in the middle of shallow seagrass patches than other positions. Relatively few pipefish were preyed upon, but of those that were, survival time was lower over sand adjacent to seagrass than at the seagrass edge or middle. Video footage revealed that salmon were the dominant predators of both tethered King George whiting recruits and pipefish. The distribution of predators and associated rate of predation can explain edge effects for some species (King George whiting) but other mechanisms, or combinations of mechanisms, are determining edge effects for other species (pipefish).

Promising pre-clinical validation of targeted radionuclide therapy using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment

Targeted internal radionuclide therapy (TRT) would be an effective alternative to current therapies for dissemi- nated melanoma treatment. At our institution, a class of iodobenzamides has been developed as potent melanoma- seeking agents. This review described the preclinical vali- dations of a quinoxaline derivative molecule (ICF01012) as tracer for TRT application. It was selected for its high, specific and long-lasting uptake in tumour with rapid clear- ance from non-target organs providing suitable dosimetry parameters for TRT. Extended in vivo study of metabolic profiles confirmed durable tumoural concentration of the unchanged molecule form. Moreover melanin specificity of ICF01012 was determined by binding assay with syn- thetic melanin and in vivo by SIMS imaging. Then, we showed in vivo that [131I] ICF01012 treatment drastically inhibited growth of B16F0, B16Bl6 and M4Beu tumours whereas [131I] NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis showed that residual tumour cells exhibit a significant loss of aggres- siveness after treatment. This anti-tumoural effect was associated with a lengthening of the treated-mice survival time and an inhibition of lung dissemination for B16Bl6 model. Results presented here support the concept of TRT using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment.

Aspectos psicológicos do câncer : um estudo em pacientes laringectomizados

A proposta do presente trabalho é abordar as principais questões referentes às relações entre o câncer e sua expressão psicológica, através do trabalho realizado durante a fase de tratamento e reabilitação de pacientes do Instituto Nacional de Câncer -R.J. portadores de câncer de laringe, submetidos à laringectomia total. Tal objetivo deve-se a verificação de que diversas publicações específicas apontam para avaliações das relações citadas ou pela vertente da busca de etiologia psicológica do câncer, ou pela tentativa da formulação de métodos para assistência de pacientes terminais e que mesmo com o avanço da medicina, com o aumento do tempo de vida de seus portadores, ainda constata-se a escassez de investigações no campo da psicologia que -incidam sobre as possibilidades de planejamento terapêutico que visem o problema do tratamento e da readaptação dos pacientes às suas novas condições. Cabe, contudo, o esclarecimento de que esta dissertação não pretende atender à formulação de uma nova teoria sobre a assistência psicológica a pacientes com câncer, ou até a laringectomizados, mas tentará propor formulações, que colhidas através da verificação empírica, possam contribuir para a elaboração de novos estudos e pesquisas no interior desta perspectiva.

Linfoma canino: clínica, hematologia e tratamento com o protocolo de Madison-Wisconsin

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

The effect of phosphoethanolamine intake on mortality and macrophage activity in mice with solid ehrlich tumors

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)