Oxidative stress in pregnancy and fertility pathologies

Oxidative stress designates the state of imbalance between reactive oxygen species (ROS) production and antioxidant levels. In a healthy placenta, there is an increase in ROS production, due to formation of new tissues and inherent metabolism, but this is balanced by higher levels of antioxidants. However, this balance is lost in some situations, with a consequent increase in oxidative stress levels. Oxidative stress has been implicated in several placental disorders and pregnancy pathologies. The present review intends to summarize what is known about the relationship between oxidative stress and well-known pregnancy disorders.

Impact of compliance with different guidelines on physical activity during pregnancy and perceived barriers to leisure physical activity

The aims of the this prospective study were to analyze physical activity (PA) engagement during the first and second trimesters, considering the different guidelines published on PA, to document the individual characteristics associated with the accomplishment of these guidelines and to examine pregnant women’s perceived barriers to leisure PA, using a socioecological framework. A sample of 133 pregnant women in two stages – at 10–12 weeks’ gestation (T1) and 20– 22 weeks’ gestation (T2) – were evaluated. PA was assessed by accelerometry during the T1 and T2 evaluation stages. Socio-demographic characteristics, lifestyle factors and barriers to leisure PA were assessed via questionnaire. A large proportion of women (ranging from 32% to 96%) did not reach the levels of PA recommended by the guidelines. There were no significant differences between T1 and T2 with regard to compliance with PA recommendations. A decrease in PA levels from T1 to T2 was noted for all recommendations. No associations were found between participants’ characteristics and adherence to the recommendations in T1 and T2. No significant differences were found in barriers to leisure PA between T1 and T2. The most commonly reported barriers to leisure PA were intrapersonal, not health related. Our results indicate that there were no differences between trimesters regarding compliance of PA recommendations, and perceived barriers were similar in both trimesters.

Infectious agents in coronary atheromas: a possible role in the pathogenesis of plaque rupture and acute myocardial infarction

In this review we report our recent findings of histopathological features of plaque instability and the association with Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) infection, studying thrombosed coronary artery segments (CAS) of patients who died due to acute myocardial infarction. Vulnerable plaques are known to be associated with fat atheromas and inflammation of the plaque. Here we demonstrated that vulnerability is also related with focal positive vessel remodeling that maintains relatively well preserved lumen even in the presence of large atheromatous plaques. This phenomena may explain why the cinecoronariography may not detect large and dangerous vulnerable plaques. Greater amount of these bacteria in vulnerable plaques is associated with adventitial inflammation and positive vessel remodeling: the mean numbers of lymphocytes were significantly higher in adventitia than in the plaque, good direct correlation was obtained between numbers of CD20 B cells and numbers of CP infected cells in adventitia, and between % area of MP-DNA in the plaque and cross sectional area of the vessel, suggesting a cause-effect relationship. Mycoplasma is a bacterium that needs cholesterol for proliferation and may increase virulence of other infectious agents. In conclusion, co-infection by Mycoplasma pneumoniae and Chlamydia pneumoniae may represent an important co-factor for plaque instability, leading to coronary plaque thrombosis and acute myocardial infarction, since larger amount of these bacteria strongly correlated with histological signs of more vulnerability of the plaque. The search of CMV and Helicobacter pilori in these tissues resulted negative.

Mental health promotion during pregnancy and early childhood : an action- research project in primary health care

ABSTRACT – Background: Primary Health Care (PHC) is usually the first contact with the health system, and health professionals are key mediators for enabling citizens to take care of their health. In Portugal, great improvements have been achieved in the biometric indicators of maternal and child health during the last decades. Nevertheless, scant attention has been paid to the mental health dimension, in spite of the recognition of its importance, being pregnancy and early childhood crucial opportunities in the lifecycle for mental health promotion, especially in the early years of life, with a strong impact in the health of the child. The impact of early attachment between mother and baby on maternal and child health has long been recognized. This attachment can be influenced by some factors, as the mother’s emotional adjustment. Attention to these factors may facilitate implementation of both positive conditions and preventative measures. Family support during the transition to parenthood has been highlighted as an effective measure and PHC professionals are in a privileged position as information sources as well as mediators. Aims: The project we present describes an action-research process developed together among academic researchers and health professionals to embrace these issues. We intend to enable health professionals to support families in the transition to parenthood thereby promoting children’s mental health. Approach: The project is driven by a participatory approach intended to lead to reorganization of health care during pregnancy and early childhood. Effective change happens when those involved are interested and motivated, what makes their participation so important. Reflection about current practices and needs, and knowledge about evidence-based interventions have been guiding the selection of changes to introduce in clinical practice for family support and development of parenthood skills and self-confidence. Development: We summarize the main steps in development: the initial assessment and the picture taken from the community under study; the decision making process; the training programme of PHC professionals in action; the review of the protocols of maternal consultation, home visits and antenatal education; the implementation planning; the plan for evaluation the effectiveness of the changes introduced in the delivery of maternal and child health care units. The already developed work has shown that motivation, leadership and organizational issues are decisive for process development.-------------------------- RESUMO - Os Cuidados de Saúde Primários são habitualmente o primeiro contacto com o sistema de saúde e os profissionais de saúde são mediadores chave na capacitação dos cidadãos para cuidarem da sua saúde. Em Portugal, nas últimas décadas, têm-se alcançado grandes melhorias nos indicadores biométricos de saúde materno-infantil. Contudo, tem-se dedicado pouca atenção à dimensão de saúde mental, apesar do reconhecimento da sua importância. A gravidez e primeira infância têm sido apontadas como uma oportunidade crucial no ciclo de vida para a promoção da saúde mental. É dado especial enfoque aos primeiros tempos de vida, dado o forte impacto na saúde da criança. O impacte da vinculação precoce entre a mãe e o bebé na saúde da mãe e da criança há muito que é reconhecido. Esta vinculação pode ser influenciada por vários factores, nomeadamente pelo ajustamento emocional da mãe. A focalização nestes aspectos pode facilitar a criação de condições favoráveis e a implementação de medidas preventivas. O suporte familiar durante o período de transição para a parentalidade tem sido enfatizado como uma medida eficaz e os Cuidados de Saúde Primários estão numa posição privilegiada como fontes de informação e como mediadores. O projecto que apresentamos descreve um processo de investigação- acção desenvolvido em parceria entre investigadores académicos e profissionais de saúde para abordar os aspectos referidos. Pretende-se capacitar os profissionais de saúde para apoiarem as famílias na transição para a parentalidade, promovendo assim a saúde mental das crianças. O projecto baseia-se numa abordagem participativa, direccionada para a reorganização dos cuidados durante a gravidez e primeiros tempos de vida. A mudança efectiva acontece quando os envolvidos estão interessados e motivados, o que torna a sua participação tão importante. A reflexão acerca das práticas e necessidades actuais e o conhecimento acerca de intervenções baseadas na evidência têm guiado a selecção das alterações a introduzir na prática clínica, no sentido de promover o suporte familiar e o desenvolvimento de competências parentais e auto-confiança. Neste artigo, apresentamos as etapas principais do desenvolvimento do projecto: avaliação inicial da comunidade em estudo; processo de tomada de decisão; programa de formação dos profissionais dos Cuidados de Saúde Primários; revisão dos protocolos da consulta de saúde materna, visita domiciliária e educação pré-natal; planeamento da implementação; plano de avaliação da efectividade das alterações introduzidas na prestação de cuidados. O trabalho já desenvolvido tem mostrado que a motivação, liderança e aspectos

A Posterior Interosseous Nerve Syndrome Associated With Spontaneous Rupture of the Extensor Pollicis Longus Tendon

Posterior interosseous nerve entrapment syndrome and spontaneous rupture of the extensor pollicis longus tendon are rare conditions. The authors describe the bizarre combination of a spontaneous rupture of the extensor pollicis longus tendon in a 82-year-old lady with a posterior interosseous nerve syndrome. As far as the authors know, this is the first description of such an association in the literature. Surgical exploration revealed compression of the posterior interosseous nerve at the proximal portion of the supinator muscle and at Henry's leash. The nerve was freed, and the tendon of the extensor index proprius was transferred to the extensor pollicis longus. Six months after the procedure, the patient had resumed her daily activities, showing a good functional result.

Immunological response in cases of complicated and uncomplicated bartonellosis during pregnancy

Bartonellosis (Carrion's Disease) during pregnancy is associated with high rates of maternal and perinatal mortality. We report the immunological patterns in two cases of human bartonellosis during pregnancy. One patient had an uncomplicated course while the second patient developed life threatening anasarca and cardiac tamponade. The patient with a complicated course had a Th1 response with a higher elevation of IL-10. This elevation has been associated with poor outcome pregnancies during bacterial infections.

Lupus and Pregnancy. 15 Years of Experience in a Tertiary Center

This retrospective study was designed to evaluate the outcome of pregnancies in women diagnosed with systemic lupus erythematosus (SLE) followed in a tertiary fetal–maternal center. Data were collected from clinical charts between January 1993 and December 2007, with a total of 136 pregnancies (107 patients). Mean maternal age was 29 years, with the vast majority of patients being Caucasian. Most patients were in remission 6 months prior to pregnancy (93%) and the most frequently affected organs were the skin and joints. Renal lupus accounted for 14% of all cases. Twenty-nine percent of patients were positive for at least one antiphospholid antibody (aPL) and nearly 50% had positive SSa/SSb antibodies. All patients with positive aPL received low-dosage aspirin and low molecular- weight heparin (LMWH). There were no pregnancy complications in more than 50% of cases and hypertensive disease and intrauterine growth restriction were the most common adverse events. There were 125 live births, one neonatal death, eight miscarriages, and three medical terminations of pregnancy. Preterm delivery occurred in 25% of pregnancies. Our results are probably the conjoined result of a multidisciplinary approach together with a systematic management of SLE pregnancies, with most patients keeping their prior SLE medication combined with low-dosage aspirin and LMWH in the presence of aPL.

Burkitt’s Lymphoma Related to Epstein–Barr Virus Infection During Pregnancy

Setting: Burkitt’s lymphoma is a rare form of cancer and is an extremely rare diagnosis during pregnancy. This form of lymphoma is a very fast growing B cell neoplasm and chemotherapy is the treatment of choice for the disease in all its stages. Case report: The authors describe the case of a Caucasian 40-year-old nulliparous woman, with previous known Epstein–Barr virus infection, that presents at 28 weeks gestation with supraclavicular adenopathy and multiple bilateral breast nodules, in which biopsy showed non-Hodgkin lymphoma, Burkitt’s type. Discussion: There are few described cases of Burkitt’s lymphoma during pregnancy and in general the outcomes have been poor. In most of the cases, the patients were not treated by current standards or instead had a late diagnosis. This neoplasia is the most rapidly progressive human tumor, and any delay in initiating therapy can adversely aVect patient’s prognosis. The authors discuss treatment options in pregnancy and its perinatal implications.

Primary Antiphospholipid Syndrome: Pregnancy Outcome in a Portuguese Population

Introduction:Women with antiphospholipid syndrome(APS) may suffer from recurrent miscarriage, fetal death, fetal growth restriction (FGR), pre-eclampsia, placental abruption, premature delivery and thrombosis. Treatment with aspirin and low molecular weight heparin (LMWH) combined with close maternal-fetal surveillance can change these outcomes. Objective: To assess maternal and perinatal outcome in a cohort of Portuguese women with primary APS. Patients and Methods: A retrospective analysis of 51 women with primary APS followed in our institution (January 1994 to December 2007). Forty one(80.4%) had past pregnancy morbidity and 35.3%(n=18) suffered previous thrombotic events. In their past they had a total of 116 pregnancies of which only 13.79 % resulted in live births. Forty four patients had positive anticardiolipin antibodies and 33 lupus anticoagulant. All women received treatment with low dose aspirin and LMWH. Results: There were a total of 67 gestations (66 single and one multiple). The live birth rate was 85.1%(57/67) with 10 pregnancy failures: seven in the first and second trimesters, one late fetal death and two medical terminations of pregnancy (one APS related). Mean (± SD) birth weight was 2837 ± 812 g and mean gestational age 37 ± 3.3 weeks. There were nine cases of FGR and 13 hypertensive complications(4 HELLP syndromes). 54.4% of the patients delivered by caesarean section. Conclusions: In our cohort, early treatment with aspirin and LMWH combined with close maternal-fetal surveillance was associated with a very high chance of a live newborn.

Predictors of adherence to the Mediterranean diet from the first to the second trimester of pregnancy

Background: Although changes in eating patterns may occur during gestation, predictors of these changes have not been explored. This study aimed to identify predictors of adherence to the Mediterranean diet (MD) from the first to second trimester of pregnancy. Methods: A prospective study was conducted with 102 pregnant women aged 18-40, from the city of Porto, Portugal. Socio-demographic and lifestyle characteristics were assessed through a questionnaire. Food consumption was assessed with a three-day food diary completed during the first and second trimesters. Participants were categorized according to their change in adherence to the MD into the negative change group (i.e., women who had low adherence in each trimester or had high adherence in the first trimester and then low adherence in the second) and the positive change group (i.e., women who had high adherence in both trimesters or had low adherence in the first trimester and then high adherence in the second). Conditional stepwise logistic regression models were performed to assess the potential predictors of negative MD change. Results: Among the 102 women, 39.2% had negative change from the first to the second trimester. The logistic model´s results show that being married (OR=0.26, 95%CI: 0.10, 0.76) and having a higher intake of vegetables in the first trimester (OR=0.17, 95%CI: 0.10, 0.43) were associated with lower odds of having a negative change in adherence to the MD from the first to second trimester. Conclusion: Marital status and vegetable consumption seem to be associated with a lower occurrence of negative change in adherence to the MD from early to middle pregnancy.

Ocular Toxoplasmosis Reactivation During Pregnancy – A Case Report

Introduction: Toxoplasmosis is caused by Toxoplasma gondii and may be acquired from food or water contaminated with cat feces or by vertical transmission. Severe fetal complications can overcome during pregnancy. There are also rare case-reports of congenital toxoplasmosis from previously immunized pregnant women; usually these women being had prior retinal toxoplasmic lesions. Immunosuppresion is one of the risk factors which accounts for some of these cases. Case report: 30 year-old pregnant woman, OI 2002, brazilian, previously healthy, admitted in Ophtalmology Department because of sudden left eye amaurosis in June, 2010. The fundoscopy revealed retinal scars suggesting previous infections; she was treated with corticoids and spiramycin for ocular toxoplasmosis reactivation. Previous serum analysis (2008) showed immunity to T. Gondii, but in July the IgM was negative and high levels of specific IgG were found (1227UI/mL). The serologic findings were later confirmed by a more accurate laboratory technique which found the IgM to be also positive. An amniocentesis was performed and it was negative for fetal transmission. Clinical and ultrasound follow-up throughout the rest of the gestational period was normal; daily spiramycin intake was maintained. An uneventful term delivery was performed. Neither the newborn’s serum analysis nor the histopathological study of the placenta were positive for congenital infection. Conclusion: Toxoplasmosis reactivation in pregnant women without immunosuppression is rare but is more likely to occur if previous post-infectious retinal scars are present. T. gondii infection is endemic in Brazil, so the geographical origin is important. If risk factors are present, fundoscopy should be performed every three months during pregnancy and one should always be aware of any visual symptoms. If you suspect reactivation, start medical prophylaxis for fetal transmission, perform amniocentesis and regular ultrasound follow-up.

Two Gestational Sacs, Two Locations - Heterotopic Pregnancy - Case Report

Introduction: Heterotopic pregnancy (HP) is defined as two gestational sacs simultaneously present in two different locations, being the uterus and the fallopian tubes the more common. Sporadic HP is a very rare condition (1:30,000 pregnancies). With the use of medically assisted reproduction the prevalence is significantly higher(1:7,000). Considering spontaneous pregnancy, HP is associated with risk factors, being prior inflammatory pelvic disease the most common. The clinical presentation is similar to that of ectopic pregnancy or spontaneous miscarriage although it is usually a more late diagnosis. Case report: 25 year-old pregnant woman, OI 0000, previously healthy; admitted at the Emergency Department (ED) with acute pelvic pain mainly at the right iliac fossa and moderate vaginal bleeding confirmed by speculum examination. She was hemodynamically stable and the bimanual palpation was painful; no prior medically assisted reproduction technique had been performed. The haemoglobin value was within normal range and the serum β-hCG was 2,763mUI/mL. The ultrasonography at the ED showed an in uterus gestational sac and another one inside the right fallopian tube; in both gestational sacs cardiac activity was absent. HP diagnosis was then established and the patient was admitted at the Obstetrics Ward for surveillance and ultrasonographic/laboratorial reassessment; complete miscarriage of the uterine pregnancy occurred but methotrexate was necessary for the treatment of persistent tubarian pregnancy. Conclusion: When evaluating a pregnant woman with pelvic pain and vaginal bleeding one should always be aware of several differential diagnosis amongst which HP should be considered. If the patient has in uterus viable pregnancy the treatment of the ectopic concomitant gestational sac should be as conservative as possible; methotrexate should not be used in that situation as it leads to uterine pregnancy miscarriage in about one third of the patients.

Biological predictors of survival in limphoma and mechanisms underlying follicular lymphoma transformaion into diffuse large B cell lymphoma (vol I e II)

RESUMO: Os biomarcadores tumorais permitem identificar os doentes com maior risco de recorrência da doença, predizer a resposta tumoral à terapêutica e, finalmente, definir candidatos a novos alvos terapêuticos. Novos biomarcadores são especialmente necessários na abordagem clínica dos linfomas. Actualmente, esses tumores são diagnosticados através de uma combinação de características morfológicas, fenotípicas e moleculares, mas o prognóstico e o planeamento terapêutico estão quase exclusivamente dependentes de características clínicas. Estes factores clínicos são, na maioria dos linfomas, insuficientes numa proporção significativa dos doentes, em particular, aqueles com pior prognóstico. O linfoma folicular (LF) é, globalmente, o segundo subtipo mais comum de linfoma. É tipicamente uma doença indolente com uma sobrevida média entre os 8 e 12 anos, mas é geralmente fatal quando se transforma num linfoma agressivo de alto grau, habitualmente o linfoma difuso de grandes células B (LDGCB). Morfologicamente e funcionalmente, as células do LF recapitulam as células normais do centro germinativo na sua dependência de sobrevivência do microambiente não-tumoral, especialmente das células do sistema imunológico. Biomarcadores preditivos de transformação não existem pelo que um melhor conhecimento da biologia intrínseca de progressão do LF poderá revelar novos candidatos. Nesta tese descrevo duas abordagens distintas para a descoberta de novos biomarcadores. A primeira, o estudo da expressão global de genes ('genomics') obtidos por técnicas de alto rendimento que analisam todo o genoma humano sequenciado, permitindo identificar novas anomalias genéticas que possam representar mecanismos biológicos importantes de transformação. São descritos novos genes e alterações genómicas associados à transformação do LF, sendo especialmente relevantes as relacionadas com os eventos iniciais de transformação em LDGCB. A segunda, baseou-se em várias hipóteses centradas no microambiente do LF, rico em vários tipos de células nãomalignas. Os estudos imunoarquitectural de macrófagos, células T regulatórias e densidade de microvasos efectuado em biopsias de diagnóstico de doentes com LF tratados uniformemente correlacionaram-se significativamente, e independentemente dos critérios clínicos, com a evolução clínica e, mais importante, com o risco de transformação em LDGCB. Nesta tese, foram preferencialmente utilizadas (e optimizadas) técnicas que permitam o uso de amostras fixadas em parafina e formalina (FFPET). Estas são facilmente acessíveis a partir das biopsias de diagnóstico de rotina presentes nos arquivos de todos os departamentos de patologia, facilitando uma transição rápida dos novos marcadores para a prática clínica. Embora o FL fosse o tema principal da tese, os novos achados permitiram estender facilmente hipóteses semelhantes a outros subtipos de linfoma. Assim, são propostos e validados vários biomarcadores promissores e relacionados com o microambiente não tumoral, sobretudo dependentes das células do sistema imunológico, como contribuintes importantes para a biologia dos linfomas. Estes sugerem novas opções para a abordagem clínica destas doenças e, eventualmente, novos alvos terapêuticos.------------- ABSTRACT: Cancer biomarkers provide an opportunity to identify those patients most at risk for disease recurrence, predict which tumours will respond to different therapeutic approaches and ultimately define candidate biomarkers that may serve as targets for personalized therapy. New biomarkers are especially needed in the management of lymphoid cancers. At present, these tumours are diagnosed using a combination of morphologic, phenotypic and molecular features but prognosis and overall survival are mostly dependent on clinical characteristics. In most lymphoma types, these imprecisely assess a significant proportion of patients, in particular, those with very poor outcomes. Follicular lymphoma (FL) is the second most common lymphoma subtype worldwide. It is typically an indolent disease with current median survivals in the range of 8-12 years, but is usually fatal when it transforms into an aggressive high-grade lymphoma, characteristically Diffuse Large B Cell Lymphoma (DLBCL). Morphologically and functionally it recapitulates the normal cells of the germinal center with its survival dependency on non-malignant immune and immunerelated cells. Informative markers of transformation related to the intrinsic biology of FL progression are needed. Within this thesis two separate approaches to biomarker discovery were employed. The first was to study the global expression of genes (‘genomics’) obtained using high-throughput, wholegenome-wide approaches that offered the possibility for discovery of new genetic abnormalities that might represent the important biological mechanisms of transformation. Gene signatures associated with early events of transformation were found. Another approach relied on hypothesis-driven concepts focusing upon the microenvironment, rich in several non-malignant cell types. The immunoarchitectural studies of macrophages, regulatory T cells and microvessel density on diagnostic biopsies of uniformly treated FL patients significantly predicted clinical outcome and, importantly, also informed on the risk of transformation. Techniques that enabled the use of routine formalin fixed paraffin embedded diagnostic specimens from the pathology department archives were preferentially used in this thesis with the goal of fulfilling a rapid bench-to-beside” translation for these new findings. Although FL was the main subject of the thesis the new findings and hypotheses allowed easy transition into other lymphoma types. Several promising biomarkers were proposed and validated including the implication of several non-neoplastic immune cells as important contributors to lymphoma biology, opening new options for better treatment planning and eventually new therapeutic targets and candidate therapeutics.