Les plus anciens mammifères terrestres du Miocène marin de Lisbonne - le gisement du Km 10

For the first time, small mammals were found at the earliest marine level in the northeastern part of the lower Tagus basin, to the NE of Lisbon. At this new locality, at the 10 kilometer of the Lisbon-Oporto A1-IP1 highway,conglomerates yielded, along with marine fossils, more or less abraded teeth and bones from insectivores,lagomorphs, rodents and small artiodactyls (sec Tableau 1). Age may he ascribed to the lower Miocene, MN 2b Neogene mammal unit (about 22 My), but an early MN 3 age cannot be entirely excluded. That corresponds to latest Aquitanian (or less probably earliest Burdigalian) (sec Tableau 2). This is the first hitherto found locality with small mammals of this age as far as Portugal is concerned, as well as the oldest locality so far known in the Tagus basin. Km 10 is somewhat older than the localities of Universidade Católica and Avenida do Uruguay in Lisbon (ANTUNES & MEIN, 1986). Hence we can rather accurately date the age of the first marine transgression in the northeastern part of the lower Tagus basin. This shows that in this region there are no marine equivalents of the "Venus ribeiroi beds" (Aquitanian,Division 1 of the Lisbon Miocene series). Correlation between this unit and the uppermost levels of the essentially paleogene "Complexo de Benfica" may be possible. Fossils at km 10 point out to shallow, coastal, highenergy marine environments. Sedimentological features are compatible with this model. Dry land and swamps with brackish (or ev en fresh) waters were present nearby. From those areas came remains of mammals, crocodylians, as well as oysters and charophytes that were later transported to the sea. Sea was warmer than the extant Atlantic at the same latitudes, even if conditions were not strictly tropical then. These conditions surely influenced climate in the nearby regions. Ecological data concerning mammalian faunas distinctly point out to nearby forest-rich environments, much more so than for Universidade Católica and Avenida do Uruguay localities, from where drier, even steppe environment forms largely prevail.

Molecular details of INH-C-10 binding to wt KatG and Its S315T mutant

Isoniazid (INH) is still one of the two most effective antitubercular drugs and is included in all recommended multitherapeutic regimens. Because of the increasing resistance of Mycobacterium tuberculosis to INH, mainly associated with mutations in the katG gene, new INH-based compounds have been proposed to circumvent this problem. In this work, we present a detailed comparative study of the molecular determinants of the interactions between wt KatG or its S315T mutant form and either INH or INH-C10, a new acylated INH derivative. MD simulations were used to explore the conformational space of both proteins, and results indicate that the S315T mutation did not have a significant impact on the average size of the access tunnel in the vicinity of these residues. Our simulations also indicate that the steric hindrance role assigned to Asp137 is transient and that electrostatic changes can be important in understanding the enzyme activity data of mutations in KatG. Additionally, molecular docking studies were used to determine the preferred modes of binding of the two substrates. Upon mutation, the apparently less favored docking solution for reaction became the most abundant, suggesting that S315T mutation favors less optimal binding modes. Moreover, the aliphatic tail in INH-C10 seems to bring the hydrazine group closer to the heme, thus favoring the apparent most reactive binding mode, regardless of the enzyme form. The ITC data is in agreement with our interpretation of the C10 alkyl chain role and helped to rationalize the significantly lower experimental MIC value observed for INH-C10. This compound seems to be able to counterbalance most of the conformational restrictions introduced by the mutation, which are thought to be responsible for the decrease in INH activity in the mutated strain. Therefore, INH-C10 appears to be a very promising lead compound for drug development.

Novel coordination polymers with (Pyrazolato)-based tectons: catalytic activity in the peroxidative oxidation of alcohols and cyclohexane

Coupling five rigid or flexible bis(pyrazolato)based tectons with late transition metal ions allowed us to isolate 18 coordination polymers (CPs). As assessed by thermal analysis, all of them possess a remarkable thermal stability, their decomposition temperatures lying in the range of 340-500 degrees C. As demonstrated by N-2 adsorption measurements at 77 K, their Langmuir specific surface areas span the rather vast range of 135-1758 m(2)/g, in agreement with the porous or dense polymeric architectures retrieved by powder X-ray diffraction structure solution methods. Two representative families of CPs, built up with either rigid or flexible spacers, were tested as catalysts in (0 the microwave-assisted solvent-free peroxidative oxidation of alcohols by t-BuOOH, and (ii) the peroxidative oxidation of cydohexane to cydohexanol and cydohexanone by H2O2 in acetonitrile. Those CPs bearing the rigid spacer, concurrently possessing higher specific surface areas, are more active than the corresponding ones with the flexible spacer. Moreover, the two copper(I)-containing CPs investigated exhibit the highest efficiency in both reactions, leading selectively to a maximum product yield of 92% (and TON up to 1.5 x 10(3)) in the oxidation of 1-phenylethanol and of 11% in the oxidation of cydohexane, the latter value being higher than that granted by the current industrial process.

Presence of Circulating Levels of Interferon-g, Interleukin-10 and Tumor Necrosis Factor-a in Patients with Visceral Leishmaniasis

Experimental murine L. major infection is characterized by the expansion of distinct CD4+ T cell subsets. The Th1 response is related to production of IFN-g and resolution of infection, whereas Th-2 response with production of IL-4 and IL-10 and dissemination of infection. The objective of this study was to measure the circulating levels of IFN-g, IL-10 and TNF-a in patients with visceral leishmaniasis (VL) before, during and at the end of therapy and to examine the association between cytokine levels and activity of VL. Fifteen patients with VL were evaluated. The cytokine determinations were done by using the enzyme-linked immunoassay (ELISA) before, during and at the end of therapy. At baseline, we detected circulating levels of IFN-g in 13 of 15 patients (median = 60 pg/ml); IL-10 in 14 of 15 patients (median = 141.4 pg/ml); and TNF-a in 13 of 14 patients (median = 38.9 pg/ml). As patients improved, following antimonial therapy, circulating levels of IL-10 showed an exponential decay (y = 82.34 e–0,10367x, r = –0.659; p < 0.001). IFN-g was no longer detected after 7/14 days of therapy. On the other hand, circulating levels of TNF-a had a less pronounced decay with time on therapy, remaining detectable in most patients during the first seven days of therapy (y = 36.99-0.933x, r = –0.31; p = 0.05). Part of the expression of a successful response to therapy may, therefore, include reduction in secretion of inflammatory as well as suppressive cytokines. Since IL-10 and IFN-g are both detected prior to therapy, the recognized cellular immune depression seen in these patients may be due to biological predominance of IL-10 (type 2 cytokine), rather than lack of IFN-g (type 1 cytokine) production.

Protection of C57BL/10 mice by vaccination with association of purified proteins from Leishmania (Leishmania) amazonensis

In the past few years, induction of protective immunity to cutaneous leishmaniasis has been attempted by many researchers using a variety of antigenic preparations, such as living promastigotes or promastigote extracts, partially purified, or defined proteins. In this study, eleven proteins from Leishmania (Leishmania) amazonensis (LLa) with estimated molecular mass ranging from 97 to 13.5kDa were isolated by polyacrylamide gel electrophoresis and electro-elution. The proteins were associated as vaccine in different preparations with gp63 and BCG (Bacilli Calmette-Guérin). The antigenicity of these vaccines was measured by their ability to induce the production of IFN-g by lymphocyte from subjects vaccinated with Leishvacinâ . The immunogenicity was evaluated in vaccinated mice. C57BL/10 mice were vaccinated with three doses of each vaccine consisting of 30 mg of each protein at 15 days interval. One hundred mg of live BCG was only used in the first dose. Seven days after the last dose, they received a first challenge infection with 105 infective promastigotes and four months later, a second challenge was done. Two months after the second challenge, 42.86% of protection was obtained in the group of mice vaccinated with association of proteins of gp63+46+22kDa, gp63+13.5+25+42kDa, gp63+46+42kDa, gp63+66kDa, and gp63+97kDa; 57.14% of protection was demonstrated with gp63+46+97+13.5kDa, gp63+46+97kDa, gp63+46+33kDa, and 71.43% protection for gp63 plus all proteins. The vaccine of gp63+46+40kDa that did not protect the mice, despite the good specific stimulation of lymphocytes (LSI = 7.60) and 10.77UI/ml of IFN-g production. When crude extract of L. (L.) amazonensis was used with BCG a 57.14% of protection was found after the first challenge and 28.57% after the second, the same result was observed for gp63. The data obtained with the vaccines can suggest that the future vaccine probably have to contain, except the 40kDa, a cocktail of proteins that would protect mice against cutaneous leishmaniasis.

Three year seroepidemiological study of varicella-zoster virus in São Paulo, Brazil

A serosurvey of varicella has been carried out in children attending the public school network of São Paulo city, Brazil, from 1992 to 1994. This study was performed in order to establish the age related prevalence of antibodies against varicella-zoster virus (VZV) and its age specific transmission dynamics pattern in these children. Among 2500 schools in the city of São Paulo public network, 304 were randomly selected; 7 children of a given age (ranging from 1 to 15 years) were randomly selected in each school, and blood samples were obtained by fingerprick into filter paper. Blood eluates were analyzed for the presence of antibodies to VZV by ELISA. Proportion of seropositivity were calculated for each age group. Samples consisted of 1768 individuals in 1992, 1758 in 1993, and 1817 in 1994, resulting in 5343 eluates. A high proportion of seropositive children from 1 to 3 years of age was observed, ascending until 10 years of age and reaching a plateau around 90% afterwards. VZV transmission in this community was similar along the three years of the study. In children attending public schools in the city of São Paulo, contact with VZV occurs in early childhood. If immunization against VZV is considered it should be introduced as soon as possible.

Centipede (Scolopendra gigantea Linneaus 1758) envenomation in a newborn

The first case of centipede (Scolopendra gigantea Linneaus 1758) envenomation in a newborn is reported. When first examined, approximately 6 hours after the bite, the 28-day-old girl was irritable, with uncontrollable cry and intense local pain, oedema, local hyperthermia, and blood clots at punctures. Uncontrollable crying in neonates should rise the possibility of an insect or arachnid sting.

Caracterização do efeito anti-tumoral de complexos organometálicos contendo 1,10-fenantrolina-5,6-diona

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Tumores do Corpo Carotídeo. Experiência de um Serviço no Diagnóstico e Tratamento nos Últimos 10 Anos

INTRODUCTION: Carotid body tumours (CBT) are neoplasms that develop from paragangionic cells of this structure. They are rare, with an estimated incidence of 1:30000 and can be associated with other neuro-endocrine neoplasia. The authors report their experience in the management of the disease, in the last 10 years. MATERIAL AND METHODS: Eight patients (with eight tumours) were treated, all submitted to tumour resection. 75% were female and the mean age was 56 years. We report a 12,5% incidence of neurological sequelae from surgery, and no mortality. In the follow-up (which varied between 1 and 10 years), no local or contralateral recurrence or metastasis were registered. Also, we did not found family cases of this disease. CONCLUSIONS: The authors noticed an unusually high proportion of female patients. The tumour resection was curative in all patients, with a rate of neurological complications inferior to that reported in other published series. These neurological sequelae were reported in patients with large tumours, thus reinforcing the outmost importance of an early diagnosis. Pre-operative selective embolization of these tumours can be helpful in the resection of large tumours, allowing a potential reduction in neurological complications.

Defeitos do Tubo Neural. Experiência de 10 Anos numa Maternidade Central

OBJECTIVES: 1) To determine trends in prevalence of neural tube defects and the impact of therapeutic abortion. 2) To review perinatal management of spina bifida. DESIGN: All spontaneous and therapeutic abortions, still births and live births affected by neural tube defects registered in Alfredo da Costa Maternity in Lisbon, from 1983 to 1992, were retrospectively analysed. RESULTS: Eighty-two cases with neural tube defects are reported and myelomeningocele and anencephaly++ were the most frequent ones. Total prevalence for all defects was 0.78:1000 births with a small upward trend during the last two years. Birth prevalence was 0.6:1000, with a clear downward trend, due to therapeutic abortion. Prenatal diagnosis improved significantly, from 9% of all defects detected in 1983-87 to 77.5% in 1988-92. Since 1989, all cases of anencephaly were detected before birth. Most cases of spina bifida were vaginally delivered, and elective cesarean section occurred in 4. Early closure of the defect was undertaken in 87.6% of the newborns with open spina bifida. CONCLUSION: While total prevalence of neural tube defects remained stable, with only a small upward trend, prenatal diagnosis and therapeutic abortion resulted in a 56.3% fall in birth prevalence. Optimal management of open spina bifida demands a multidisciplinary team with an individual program for each case.

Válvula Aórtica Quadricúspide. Casuística de 10 Anos e Revisão da Literatura

Introdução: A válvula aórtica quadricúspide é uma malformação rara, com uma incidência estimada de 0,003 a 0,043% de todas as cardiopatias congénitas. Surge habitualmente como uma anomalia congénita isolada, podendo igualmente estar associada a outras malformações, sendo as mais frequentes as anomalias das artérias coronárias. A tecnologia actual permite o diagnóstico não invasivo na grande maioria das situações. A sua história natural é a evolução para a insuficiência, rara antes da idade adulta. Objectivos: Revisão dos casos de válvula aórtica quadricúspide diagnosticados nos últimos 10 anos num centro terciário de Cardiologia Pediátrica. Material e Métodos: Revisão retrospectiva do processo clínico dos doentes aos quais foi detectada uma válvula aórtica quadricúspide, entre Janeiro de 2000 e Dezembro de 2009. Resultados: Nos últimos 10 anos, foram diagnosticados quatro casos de válvula aórtica quadricúspide, em crianças com idades compreendidas entre os 6 meses e os 8 anos, duas do sexo masculino. Em três casos, os quatro folhetos eram de dimensões semelhantes, que é o achado mais frequente. Duas das válvulas eram normofuncionantes e duas apresentavam insuficiência mínima. Todos os doentes apresentavam outras malformações cardíacas associadas (uma comunicação interauricular, duas comunicações interventriculares, uma estenoseçupravalvular aórtica e uma válvula pulmonar quadricúspide). Um doente tinha também o diagnóstico de Síndrome de Williams. Com um tempo de seguimento mediano de 2 anos [0 --- 9], todos os doentes se mantiveram assintomáticos e não requereram tratamento médico ou cirúrgico para a válvula aórtica. Conclusão: O diagnóstico de válvula aórtica quadricúspide é raro, sobretudo em idade pediátrica, quando a maioria dos doentes são assintomáticos e apresentam válvulas normofuncionantes. Nesta casuística, metade apresentava insuficiência aórtica mínima. Ao contrário do que está descrito na literatura, todos os doentes apresentavam malformações cardíacas concomitantes. Descrevemos pela primeira vez a associação com a Síndrome de Williams. Estes doentes deverão manter seguimento em ambulatório, de forma a detectar atempadamente o aparecimento ou agravamento de alterações funcionais e permitir uma intervenção terapêutica oportuna.