Consumo do Álcool e das Drogas Ilícitas nos Grupos de Gangues/Thugues das Cidades do Mindelo e da Praia

Este trabalho intenta analisar as relações existentes entre o consumo abusivo do álcool e das drogas ilícitas nos grupos gangues ou thugues, sua relação com o aumento da delinquência juvenil nas cidades do Mindelo e da Praia. A estrutura familiar, os aspectos personológicos, psicossociais, geográficos, culturais, a escola e outros fenómenos como o desemprego, influenciam a vida dos jovens em grupos, despertando-os o interesse para o consumo de drogas, que por sua vez irá funcionar como factor de dependência, quando instalada a dependência, os meios para alcançar a droga despoletam, na violência juvenil. Daí que torna-se relevante a compreensão dos fenómenos psicossociais que estão por detrás do consumo de drogas e sua implicação na delinquência juvenil nas cidades do Mindelo e da Praia, as duas principais estruturas humanas de Cabo Verde, também consideradas as duas cidades mais inseguras do país. Para o efeito foi recolhido uma amostra de 120 indivíduos destas duas cidades, que têm uma relação directa com estes grupos e foi aplicado um questionário de 47 perguntas abertas e fechadas. Os resultados práticos apontam para o aumento do consumo da cocaína em forma de crack e da cocaína em forma de pó inalada na camada juvenil, a primeira mais acentuada na cidade do Mindelo e a segunda mais na cidade da Praia, enquanto isso os resultados teóricos apontam para os efeitos estimulantes que essas drogas trazem ao sistema nervoso central, bem como os comportamentos a volta do acesso e consumo, drogas com grande capacidade de dependência física e psicológica. Quanto as drogas mais utilizadas pelos jovens, o estudo aponta a padjinha e o álcool como as drogas mais consumidas pelos jovens nessas duas cidades, quanto as formas de violência mais praticados pelos grupos ressalta a agressão física, brigas entre grupos rivais e os assaltos como os mais frequentes, resultados importantes que ajuda-nos a compreender melhor essa relação.

Los Factores Socioculturales y el Consumo de las Drogas. Un Estudio desde la Isla de San Vicente. Cabo Verde

La tesis titulada “Los factores socioculturales y consumo de droga. Un estudio desde la isla de San Vicente. Cabo Verde”, tiene como objetivo explicar los factores socioculturales asociados a la trayectoria del consumo de la droga en la sociedad sanvicentina, a los efectos de poder ofrecer recomendaciones encaminadas al perfeccionamiento de las políticas sociales. La tesis esta estructura en tres capítulos. El primero centra las atenciones en los referentes que ofrece la sociología de la cultura para explicar una trayectoria del consumo de la droga vinculada a los factores socioculturales que devienen en prácticas socializadas en el ámbito de la familia. En el capitulo segundo se precisa el contexto caboverdiano y mindelense, con lo cual se justifica la necesidad de la presente investigación. Se introducen los conceptos factores socioculturales estructurantes, factores socioculturales estructuradores de grupo social consumidor de drogas y trayectoria cultural del consumo de la droga para connotar el lado de las significaciones. Con el capítulo tercero se concluye el análisis científico al revelar a través de sus tres epígrafes, como se articulan las prácticas culturales (ritos y ceremonias), factores sociales (condiciones de precariedad de vida y a los conflictos familiares), con el consumo de sustancias en la población juvenil. En el nivel de las políticas públicas, se propone un modelo de educación cultural que propicia el desarrollo de estrechas relaciones interinstitucionales para hacer visible el lado cultural en el consumo de la droga.

Iodine-131-labeled MAb F(ab')2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinoma grafted in nude mice.

During one week, beginning 18 days after transplantation, nude mice bearing human colon carcinoma ranging from 115 to 943 mm3 (mean 335 mm3) were treated by repeated intravenous injections of either iodine-131-(131I) labeled intact antibodies or 131I-labeled corresponding F(ab')2 fragments of a pool of four monoclonal antibodies (MAbs) directed against distinct epitopes of carcinoembryonic antigen (CEA). Complete tumor remission was observed in 8 of 10 mice after therapy with F(ab')2 and 6 of the animals survived 10 mo in good health. In contrast, after treatment with intact MAbs, tumors relapsed in 7 of 8 mice after remission periods of 1 to 3.5 mo despite the fact that body weight loss and depression of peripheral white blood cells, symptoms of radiation toxicity, and the calculated radiation doses for liver, spleen, bone, and blood were increased or equal in these animals as compared to mice treated with F(ab')2.

Aspectos jurídicos sobre a repressão do tráfico ilícito de drogas pela via marítima em Cabo Verde

O presente estudo realiza-se no âmbito do Mestrado em Direito Marítimo e Comércio Internacional e tem como título: Aspectos Jurídicos sobre a Repressão do Tráfico Ilícito de Drogas pela Via Marítima, Cabo Verde. Portanto pretende-se iniciar o mesmo esclarecendo possíveis dúvidas que possam surgir referente ao termo “droga” e o contexto histórico da ilegalidade das drogas. Recorde-se que há pouco mais de um século, precisamente no ano 1909, na China realizou-se a primeira conferência sobre o ópio que viria a entrar em vigor a nível mundial no ano de 1919, após ter sido incorporada no tratado de Versalhes. A cannabis entrou na lista de substâncias proibidas após a revisão da Convenção Internacional do Ópio realizada em Genebra no ano 1925. Perante esse cenário, conhecendo os avultados lucros do comércio da droga, os antigos comerciantes não pretendiam desistir dessa prática e encontraram no mar as vulnerabilidades necessárias para continuarem a realizar esse comércio, agora tipificado internacionalmente como crime. Logo, uma vez mais1, a visão antiga do Direito Internacional, principalmente, tratando-se de dois extremos, o Direito à Guerra (ius bellum) e o Direito à Paz (o ius pacis) tornou-se impotente para responder aos novos desafios do Direito Internacional. Assim sendo, o segundo capítulo, visa esclarecer factos relevantes do Direito Internacional que afectam directamente o tráfico ilícito de drogas pela via marítima, partindo da análise das Fontes e princípios do Direito Internacional, distinguindo o Direito Internacional Público do Direito Internacional Privado e evocando questões importantes no âmbito do Direito Penal Internacional que afetam o tráfico de estupefacientes e substâncias psicotrópicas. Embora o Direito do Mar e o Direito Marítimo sejam dois conceitos que aparentam ser semelhantes, o terceiro capítulo esclarece algumas diferenças 1 Tendo em conta que a pirataria no alto mar foi um dos primeiros crimes a explorar as fragilidades jurídicas existentes no âmbito do Direito Internacional publico, mais concretamente, sua subdivisão, Direito do Mar. Aspectos Jurídicos sobre a Repressão do Trafico de Drogas Ilícitas Pela Via Marítima –Cabo Verde entre eles, destacando os princípios que iluminam a relação entre os Estados, as delimitações e os regimes jurídicos aplicados nas áreas marítimas consagrados na Convenção das Nações Unidas Sobre o Direito do Mar, doravante designada de CNUDM. Dará ainda enfase aos principais aspectos sobre as fontes e os princípios do Direito do Mar e os principais fundamentos das competências dos juízes nas diversas áreas marítimas. O quarto e último capítulo visa abordar os instrumentos jurídicos mais importantes no âmbito da repressão ao tráfico ilícito de drogas pela via marítima, enaltecendo, desde já, o princípio da cooperação internacional estabelecido internacionalmente, expressando que, “Todos os Estados devem cooperar para a repressão do tráfico ilícito de estupefacientes e substâncias psicotrópicas praticado por navios no alto mar, com violação das convenções internacionais.”2 Esse pressuposto remete-nos, subitamente, para a análise das Convenções de maior importância criados pela ONU com essa finalidade, nomeadamente, a Convenção Única sobre Narcóticos de 1961, emendada pelo Protocolo de 1972, a Convenção sobre Substâncias Psicotrópicas de 1971 e a Convenção das Nações Unidas contra o Tráfico Ilícito de Narcóticos e Substâncias Psicotrópicas de 1988. O tema se desenvolve, sempre evocando os instrumentos jurídicos caboverdianos, tais como a lei da droga, 78/IV/93 de 12 Julho, o Código Marítimo de Cabo Verde, adiante referido pelas siglas CMCV, o Código Penal de Cabo Verde, doravante referido por CPCV e a lei mãe da nação cabo-verdiana, a Constituição da República de Cabo Verde, adiante designado por CRCV. Para facilitar a compreensão da matéria exposta, será tratado de forma sintetizada, o caso da abordagem a um veleiro de pavilhão norte-americano, realizado por autoridades de Cabo Verde, em conjunto com autoridades do Reino Unido e ocorrida em águas internacionais próximas de Cabo Verde.

Anti-60kDa heat shock protein antibodies in fetal serum : a biomarker for unexplained small for gestational age fetuses

Rapport de synthèseObjectifsLe retard de croissance intrautérin (RCIU) est un problème affectant 10% des grossesses et est associé à une morbidité périnatale importante. Dans environ 80% des cas, une étiologie ou un facteur de risque majeur peuvent être identifiés. Mais près de 20% des cas sont considérés comme inexpliqués. La heat shock protéine 60kDa (HSP60) est une protéine fortement immunogène dont la synthèse est considérablement augmentée lors de conditions non- physiologiques. Les HSP60 humaines et bactériennes partagent un haut degré d'homologie de séquence ce qui peut engendrer une maladie auto-immune à la suite d'une infection bactérienne. Nous avons supposé que les RCIU inexpliqués pourraient être la conséquence d'une sensibilisation à l'HSP60 humaine.MéthodesLes RCIU inexpliqués ont été identifiés par mesure échographique avec un doppler normal, sans anomalies décelables chez la mère ou le foetus. Les sera foetaux ont été obtenus par cordocentèse, effectuée lors d'analyse du caryotype en cas de RCIU inexpliqué (groupe d'étude) ou pour le dépistage d'une incompatibilité Rhésus (groupe témoin). Ils ont été testés pour l'antigène HSP60 et les IgG et IgM anti-HSP60 par ELISA ainsi que pour d'autres paramètres immunitaires et hématologiques.RésultatsLes paramètres maternels sont similaires entre les 12 cas du groupe d'étude et les 23 cas du groupe contrôle. L'âge gestationnel moyen lors de la cordocentèse est de 29 semaines. Les IgM anti-HSP60 sont détectés dans 12 cas d'étude (100%) mais dans aucun cas contrôle (p <0,00017), les IgG anti-HSP60 dans 7 cas d'étude (58%) et un seul dans le groupe contrôle (p <0,001). Trois des quatre cas avec les taux d'IgM les plus élevés sont décédés. Il n'y a pas de différences entre les deux groupes quant aux taux d'antigène HSP60 ou d'autres marqueurs immunologiques ou hématologiques.ConclusionLes foetus avec un RCIU inexpliqué expriment un taux élevé d'anticorps IgM et IgG contre l'HSP60 humaine et le taux d'IgM est un facteur prédictif de la mortalité foetale. La détection de ces anticorps indique qu'une perturbation placentaire et une réaction auto-immune foetale liée à l'HSP60 sont associées à ce retard de développement chez le foetus.

Systematic Assessment of Factors Influencing Preferences of Crohn's Disease Patients in Selecting an Anti-TNF agent (CHOOSE TNF TRIAL)

Background a nd A ims: I nfliximab (IFX), adalimumab (ADA)and certolizumab pegol (CZP) have similar efficacy for inductionand maintenance of clinical response and remission in Crohn'sdisease (CD). Given the comparable nature of t hese drugs,patients' p references m ay i nfluence the choice o f the product.Goal: to identify factors contributing to CD patients' decision inselecting one anti-TNF agent over the others.Methods: A p rospectdive s urvey was performed a mong a nti-TNF-naïve CD patients. Prior to completion of a questionnaire,patients were provided with a description of the three anti-TNFagents f ocusing on indications, route of administration, s ideeffects, and scientific evidence of efficacy and safety.Results: One hundred patients (47f/53m, mean age 45±16yrs)completed the questionnaire. Disease location was ileal, colonicand ileocolonic in 33%, 40% and 27% of patients, respectively.Thirty-six percent preferred ADA as medication of choice, while28% and 2 5% p referred CZP and IFX; 11% were u ndecided.Patients' decision in selecting an anti-TNF drug was influencedby t he following f actors: side effects ( 76%), p hysician'srecommendation (66%), route of administration (54%), efficacydata (52%), time required for therapy administration (27%),recommendations by other CD patients (21%) and interactionswith other medications (12%).Conclusions: T he majority of p atients p referred anti-TNFmedications t hat were a dministered by s ubcutaneous i njectionrather t han b y intravenous i nfusion. Side effect profile andphysicians' r ecommendation are t wo m ajor factors influencingthe patients' s election of a specific anti-TNF d rug. Patients'concerns about safety and lifestyle habits should be taken intoaccount when prescribing anti-TNF drugs.

Identification and Characterization of Natural Anti-Breast Cancer Compound: Costunolide

Breast cancer is the most common cancer among women, 23% (1.3 million) of the total of new cases and the second leading cause of cancer death in women exceeded only by lung cancer. Natural medicines have been proven to be a central source of narrative agents with a pharmaceutical potential. Costunolide is sesquiterpene lactones consisting of diverse plant chemicals that exhibit anti cancer action through cytotoxic effects on various cancer cells. The objectives of present study were to explore the effects of natural compounds on the proliferation of MCF-7 cells and to determine the role of ROS in natural compounds-induced apoptosis in breast cancer cells with a therapeutic potential. Results showed that costunolide screened, possess potent anticancer properties against breast cancer MCF-7 cells, Costunolide was observed as strong anti-proliferative agent with IC50 = 50µM. The anti-proliferative effect of costunolide on MCF cells was confirmed by live/dead assay using fluorescent probes calcein AV/PI. The results demonstrated that treatment of cells with costunolide decreased the viability of MCF-7 cells in a dose-dependent manner. To determine the costunolide-induced apoptosis, flow cytometric analysis was carried out. The results showed that costunolide induced apoptosis in a dose-dependent manner in breast cancer MCF-7cells. ROS are well known mediators of intracellular signaling of cascades. The excessive generation of ROS can induce oxidative stress, loss of cell functioning, and apoptosis. In the present study, we assumed that costunolide might arouse ROS level, which could be involved in induction of apoptosis. Therefore, the intracellular ROS level was measured using the ROS-detecting fluorescence dye 2, 7-dichlorofluorescein diacetate (DCF-DA). Interestingly these effects were significantly abrogated when the cells were pretreated with N-acetyl- cysteine (NAC), a specific ROS inhibitor. Costunolide induces apoptosis through extrinsic pathway in MCF-7 breast cancer cells, In order to examine whether costunolide suppresses cell growth inducing apoptotic cell death, we analyzed DNA contents and apoptosis-related proteins expression level by flow cytometry and western blot, respectively in MCF-7 breast cancer cells we investigated whether costunolide activates extrinsic apoptotic pathway. We examined the expression levels of death receptor signaling-related proteins, caspase-3, and PARP. The results showed that procaspase-3 was cleaved to yield 17 and 20kDa fragments and activation of PARP in treated cells with 25 and 50μM of costunolide. Costunolide induce apoptosis through intrinsic mitochondria pathway in MCF-7 breast cancer Cells. We examined the expression levels of mitochondrial apoptotic pathway related proteins such as anti-apoptotic protein, B-cell lymphoma protein-2 (Bcl2), and pro-apoptotic protein Bax. Costunolide involved in the down regulation of Bcl-2 and up regulation of Bax. These results suggest that costunolide may have beneficial effects for the reduction of breast cancer growth, and new therapeutic strategy for the treatment of human cancers.

Y1 receptor knockout increases nociception and prevents the anti-allodynic actions of NPY.

OBJECTIVE: Recent pharmacologic studies in our laboratory have suggested that the spinal neuropeptide Y (NPY) Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY. To rule out off-target effects, the present study used Y1-receptor-deficient (-/-) mice to further explore the contribution of Y1 receptors to pain modulation. METHODS AND RESULTS: Y1(-/-) mice exhibited reduced latency in the hotplate test of acute pain and a longer-lasting heat allodynia in the complete Freund's adjuvant (CFA) model of inflammatory pain. Y1 deletion did not change CFA-induced inflammation. Upon targeting the spinal NPY systems with intrathecal drug delivery, NPY reduced tactile and heat allodynia in the CFA model and the partial sciatic nerve ligation model of neuropathic pain. Importantly, we show for the first time that NPY does not exert these anti-allodynic effects in Y1(-/-) mice. Furthermore, in nerve-injured CD1 mice, concomitant injection of the potent Y1 antagonist BIBO3304 prevented the anti-allodynic actions of NPY. Neither NPY nor BIBO3304 altered performance on the Rotorod test, arguing against an indirect effect of motor function. CONCLUSION: The Y1 receptor contributes to pain inhibition and to the analgesic effects of NPY.

Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats.

Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.

Representações Sociais do Consumo de Álcool e Drogas em Estudantes da Universidade Jean Piaget: um estudo com alunos de Direito e Psicologia.

O presente estudo teve como objectivo conhecer e caracterizar as Representações Sociais do consumo de álcool e drogas em estudantes dos cursos de Direito e Psicologia, na Universidade Jean Piaget de Cabo Verde. Trata-se de um estudo descritivo e exploratório, que adopta uma abordagem quantitativa, realizado com uma amostra com 99 estudantes universitários de ambos os sexos, com idade compreendida entre 18 e 48 anos, do 1º e do 4º ano dos cursos de Direito e Psicologia, que responderam a uma Escala de Representações Sociais sobre o consumo de álcool e drogas e a um questionário sobre dados pessoais.Após a recolha de dados, foram realizadas análises estatísticas de tipo descritivo, correlacional e inferencial, utilizando-se o programa estatístico SPSS (Statistical Package for the Social Science), versão 20.0. Os resultados indicaram ser pouco provável que exista uma relação segura (ou melhor, com significância estatística) entre as variáveis sexo, curso e ano escolar de um lado, e as representações sociais no total da escala, de outro. Entretanto, encontramos evidências de uma associação estatisticamente significativa entre a frequência do consumo de álcool e o total da ERS, e de uma associação estatística e altamente significativa entre a frequência do consumo de álcool e a componente Atitudes. Constatámos, outrossim, diferenças estatisticamente significativas entre os sexos a nível da subescala atitudes, sendo que o sexo masculino apresenta atitudes mais favoráveis e permissivas face ao consumo de álcool e drogas, comparativamente ao sexo feminino.

o consumo de drogas na adolescência: uma abordagem da enfermagem comunitária

O uso de drogas tem revelado um sério problema de saúde pública. O estudo que se apresenta debruça-se sobre o problema. Especificamente, pretende identificar as intervenções de Enfermagem Comunitária para o consumo de drogas entre adolescentes do bairro de Ilha de Madeira, em São Vicente. Para tal, foi estudada uma amostra de 50 adolescentes de ambos os sexos, com idade compreendida entre os 12 e os 18 anos inclusive, sendo a média de idades 15,98 anos (DP = 1,532). Os dados foram recolhidos com base num questionário. Os resultados revelaram que, a maioria dos adolescentes já experimentaram e continuam a experimentar substâncias psicotrópicas. Alguns dos quais experimentaram ainda na infância. Na globalidade os resultados mostram que o álcool é a substância lícita mais experimentada e, a padjinha, a substância ilícita mais consumida. A história do consumo familiar é outro resultado encontrado. Estes resultados apelam a intervenção de enfermagem comunitária e indicam a necessidade de uma intervenção precoce voltada para práticas de promoção de saúde, delimitando acções educativas que reflictam comportamentos e atitudes assertivos de saúde dos adolescentes e suas respectivas famílias.

Low-replicating viruses and strong anti-viral immune response associated with prolonged disease control in a superinfected HIV-1 LTNP elite controller.

OBJECTIVE: To study the causes for the lack of clinical progression in a superinfected HIV-1 LTNP elite controller patient.¦METHODOLOGY AND PRINCIPAL FINDINGS: We studied host genetic, virological and immunological factors associated with viral control in a SI long term non progressor elite controller (LTNP-EC). The individual contained both viruses and maintained undetectable viral loads for >20 years and he did not express any of the described host genetic polymorphisms associated with viral control. None of four full-length gp160 recombinants derived from the LTNP-EC replicated in heterologous peripheral blood mononuclear cells. CTL responses after SI were maintained in two samples separated by 9 years and they were higher in breadth and magnitude than responses seen in most of 250 treatment naïve patients and also 25 controller subjects. The LTNP-EC showed a neutralization response, against 4 of the 6 viruses analyzed, superior to other ECs.¦CONCLUSIONS: The study demonstrated that a strong and sustained cellular and humoral immune response and low replicating viruses are associated with viral control in the superinfected LTNP-EC.

Atypical EPO profiles in anti-doping analyses

Résumé : Erythropoietin (EPO) is a glycoprotein hormone endogenously produced by the kidney, whose main physiological role is the stimulation of erythropoiesis. Since the beginning of the nineties, recombinant human EPO (rhEPO), a potent anti-anaemia treatment drug, has been manufactured by pharmaceutical industries. However, the erythropoiesis stimulating power of rhEPO was rapidly misused by unscrupulous athletes in order to improve their performances in endurance sports. Endogenous EPO has the same amino-acid backbone as most of recombinant forms; the molecules however differ through their respective glycosylation patterns. This difference constitutes the basis of the usual EPO screening test (IEF) developed in 2000 and still currently used in all anti-doping laboratories of the world. Nowadays, 3 EPO generations have been commercialized. The fight against EPO abuse is a continuous challenge for anti-doping laboratories. The diversity of recombinant EPO forms and the continuous development of new ones considerably confuse the identification of EPO doping. Several facets of this fight were investigated in this work. One of the limiting aspects of doping agents screening is the availability of positive samples. Therefore, 2nd and 3rd generation EPOS, namely NESP and C.E.R.A., were injected to healthy subjects in the frame of pilot clinical studies. These latter allowed to review the current EPO identification criteria defined by the World Anti-Doping Agency (WADA) in the case of NESP and to validate and implement a new assay targeting C.E.R.A. in human serum. Both studies resulted in the determination of the respective detection windows of NESP and C.E.R.A. in biological fluids. Following that, Dynepo, a 1st generation EPO presenting similarities with the endogenous form, was also in the centre of a similar clinical study. Our work aimed to overcome the actual identification criteria, which are not adapted to Dynpeo, and to propose an alternative pattern classification method based on the discriminant analysis of IEF EPO profiles. This method might be validated for other EPO forms in the future. The detection window of this molecule was also determined. Under particular conditions, confounding effects can complicate the identification of EPO in biological matrices. For example, athletes having performed a strenuous physical effort can excrete modified isoforms of endogenous EPO, making it very similar to some recombinant forms. Such phenomena, called effort urines, were reproduced under controlled conditions and, after characterization of effort EPO, an urinary biochemical marker was proposed to unequivocally identify effort urines. It also happens that EPO analyses fail to detect endogenous levels of EPO. Such profiles were thoroughly investigated and potential causes identified. Natural reasons relying on urine properties and test specificity were underlined, but the possible addition of adulterant agents in urine samples was also considered. Therefore, a simple biochemical assay targeting the suspected substances was set up. Our work was based on the characterization of atypical EPO profiles from different origins. Therefore, 3 EPO molecules representing the 3 generations of the drug and 2 confounding effects confusing the results interpretation were studied. These studies resulted in tangible applications for the laboratory, the best example of which being the C.E.R.A. assay, but also in scientific findings allowing to improve our comprehension of EPO doping in sport.

Penetration and binding of radiolabeled anti-carcinoembryonic antigen monoclonal antibodies and their antigen binding fragments in human colon multicellular tumor spheroids.

The binding and penetration of two 125I-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) and their F(ab')2 and Fab fragments were measured in multicellular spheroids of poorly (HT29) and moderately well differentiated (Co112) human colon adenocarcinomas which express different amounts of CEA. Spheroids cultured in vitro model tumor microenvironments where poor vascular supply may modulate antigen expression and accessibility. The two MAb studied, 202 and 35, were shown previously to react with different CEA epitopes and to have high affinities of 1.2 and 5.8 X 10(9) M-1, respectively. MAb 202 has also been shown to cross-react with antigens present on human granulocytes and normal epithelial cells from human lung and pancreas. Specific binding of intact MAb and fragments of both antibodies was demonstrated for both types of human colon carcinoma spheroids compared to mouse colon carcinoma (CL26) and mammary tumor (EMT6/Ro) spheroids. Total binding of MAb and fragments was greater (1.5- to 2.5-fold) after 4 h compared to 1 h of exposure; the amount of binding compared to control IgG1 was 5- to 30-fold greater after 1-h incubation and 15 to 200 times greater after 4 h. This binding was stable as demonstrated by short and long wash experiments at 37 degrees and 4 degrees C. The binding of F(ab')2 and Fab fragments of the anti-CEA MAb 35 to spheroids of human colon Co112 was almost 2-fold greater than that of the intact MAb. However, for MAb 202, the binding of intact MAb and F(ab')2 was greater than that of Fab fragments. In addition the binding of both intact and F(ab')2 fragments of MAb 202 was greater than that obtained with MAb 35. Specific binding of both antibodies to HT29 spheroids, which express less CEA, was decreased for MAb and fragments of both 202 and 35. Autoradiography and immunoperoxidase experiments were performed to determine the penetration of MAb and fragments after incubation with intact spheroids. Comparisons were made with labeled MAb directly applied to frozen sections of spheroids. F(ab')2 and Fab fragments of both antibodies were bound at the surface of intact spheroids and penetrated to eight to ten cells, but the intact MAb were localized mainly at the spheroid surface and the outer one to three cell layers. There was much less binding at the surfaces of HT29 compared to Co112 spheroids. An enzyme immunoassay using MAb 35 and 202 demonstrated that Co112 spheroids produced about 8-fold more CEA/mg of cell protein than did monolayer cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

A Variant of Higher-Order Anti-Unification

We present a rule-based Huet’s style anti-unification algorithm for simply-typed lambda-terms in ɳ long β normal form, which computes a least general higher-order pattern generalization. For a pair of arbitrary terms of the same type, such a generalization always exists and is unique modulo α equivalence and variable renaming. The algorithm computes it in cubic time within linear space. It has been implemented and the code is freely available