AIM: Subsequent pregnancies (SSPs) in patients with peripartum cardiomyopathy (PPCM) have a high risk of heart failure relapse. We report on outcome of SSPs in PPCM patients in South Africa. METHODS AND RESULTS: Of the 18 PPCM patients with a SSP, 3 patients died within 6-months follow-up. Overall relapse rate, left ventricular ejection fraction (LVEF) <50% or death after at least 6 months follow-up, was 30%, with 16% (3/18) mortality. Persistently reduced LVEF (<50%) before entering SSP was present in 44% of patients, while full recovery (LVEF≥ 50%) was present in 85%. Persistently reduced LVEF before SSP was associated with a higher mortality (27% vs 0%) and a lower rate of full recovery at follow-up. Patients obtaining standard therapy for heart failure and bromocriptine immediately after delivery displayed significantly better LVEF at follow-up and a higher rate of full recovery, with no patient dying, compared with patients obtaining standard therapy for heart failure alone. CONCLUSION: Full recovery of LVEF before SSP was associated with lower mortality and better cardiac function at follow-up. Addition of bromocriptine to standard therapy for heart failure immediately after delivery was safe and appeared to be associated with better outcome of SSP in our patients.

ABSTRACT Introduction: Peripartum cardiomyopathy (PPCM) is defined as a disorder of unknown aetiology that occurs between one month antepartum and five months postpartum in women without pre-existing heart disease. While the incidence of PPCM has been reported between 1: 2392 and 15000 live births in the USA, the disease is ubiquitous on the African continent with an incidence ranging from 1: 100 to 1: 1000 deliveries. The mortality rate ranges between 15 and 40.7%, while 23 to 54% of patients recover completely. Aim of this thesis was to describe the clinical profile of 100 PPCM patients, identify predictors of negative outcome, analyze differences in kinetics of cardiac function biomarkers, pro-inflammatory cytokines, markers of re-modeling and prolactin in cardiac function improvers versus non-improvers and investigate a possible autoimmune component in the pathogenesis of PPCM. Methods: We conducted a single centre, prospective study of 100 newly diagnosed patients meeting diagnostic criteria for PPCM. All patients received standard anti-failure therapy with diuretics (furosemide, aldactone), the β-blocker carvedilol, ACE-inhibitor perindopril and digoxin if indicated. Clinical assessment, 2-dimensional echocardiographic studies and blood analysis were systematically performed at time of presentation, after six and twelve months of therapy. Findings: Fifteen patients died within the follow-up period of six months and eight were not available for full follow-up since they moved to remote areas. Patients who completed six months of treatment showed a significant reduction of heart rate, left ventricular dimensions and significant improvement in scintigraphically and echocardiographically derived values for left ventricular ejection fraction (p< 0.0001) and NYHA functional class (p< 0.001). However, normalization of LVEF (>50%) was only observed in 18 (23%) of the patients. Baseline plasma levels of Fas/Apo-1 (OR = 3.56, CI 95% = 1.35–9.42) and NYHA FC (OR = 2.67, CI 95% = 1.04–6.83) were independent predictors of death.extra-cellular loop (RAESDE and DEARRCY), while those from DCMO patients bind to epitopes on the first (30%) and second extra-cellular loop (ARRCYND and PKCCDF). The β1-adrenoreceptor agonist-like antibodies identified in PPCM patients are part of the IgG2 and IgG3 subclass, while those from DCMO patients belong to the IgG2 subclass. Furthermore we demonstrated that β1-adrenoreceptor antibodies in serum of PPCM patients prevented desensitization of the receptor. The β1-adrenoreceptor antibodies in serum of PPCM patients were not detectable in serum of non PPCM peripartum controls and are different from those found in patients with DCMO, suggesting that PPCM forms a distinct disease entity. We demonstrated a positive correlation between the activity of the β1-adrenoreceptor antibodies and serum expression levels of the marker of cardiac function NT-proBNP from baseline to twelve months (rs=0.58, 2- tailed P=0.0228), 95% CI (0.10 to 0.84). Investigating the cause for high prolactin expression levels in serum of PPCM patients, we identified a STAT3 deficit in a PPCM mouse model. Significantly increased levels of cathepsin D cause the cleavage of the physiological 23-kDa form of prolactin into a 16-kDa form in PPCM patients, but not in non-PPCM peripartum controls. This initiated another clinical study, investigating the effect of the prolactin-inhibitor bromocriptine in addition to standard heart failure therapy in known PPCM patients, presenting with a subsequent pregnancy. Comparison of clinical and echocardiographic data of these patients to others on standard heart failure therapy demonstrated preservation or improvement of left ventricular dimensions and systolic function as well as NYHA FC. Conclusion: While a wide range of parameters, reflecting cardiac dysfunction and pro-inflammatory immune activation, were elevated in all PPCM patients at time of first presentation, indicating their involvement in the initiation of the disease, we found significant differences over time between cardiac function improvers and nonimprovers for ΔIFN-gamma (P=0.0181) serum levels, suggesting their role in disease progression. Heightened IFN-gamma expression could indicate an ongoing T-cell mediated autoimmune response and an insult to the cardiac muscle, resulting in fibrosis and inability to improve left ventricular systolic function. Prolactin represents a stimulatory link between the neuroendocrine and immune systems, promoting proinflammatory immune responses. Interestingly, we found significantly higher (P<0.0001) serum prolactin levels in PPCM patients at time of first presentation than in peripartum controls, suggesting the hormone’s role during the initial acute phase of PPCM. Several authors have described the induction of IFN-gamma by prolactin. Disease progression and the ongoing autoimmune insult by beta1-adrenergic autoantibodies appear to be driven by IFN-gamma. This pro-inflammatory cytokine remained high in PPCM nonimprovers, decreased in improvers, was previously implicated in the development of autoimmune disease and its suppression leads to desensitization of β-adrenoreceptors. Together with the β1-adrenoreceptor autoantibodies that we have identified in PPCM patients and their demonstrated property to also prevent desensitization of β1-adrenoreceptors, patients experience an adrenergic overdrive, leading to cardiac myocyte insult. 10 While the pathogenesis of PPCM appears to be multifactorial, our task as scientists remains to find out, how the monolith was erected. Specifically, it appears promising to investigate the effects of bromocriptine in addition to standard heart failure therapy in a randomised, double-blinded clinical study. Although one could argue that prolactin regulated expression of IFN-gamma and other cytokines may explain the gender-specific differences in autoimmunity, it has been shown that elevated serum prolactin concentrations are associated with accelerated autoimmune disease in both female and male mice. Possibly, prolactin does not only play a role in the pathogenesis of PPCM, but also in other forms of cardiomyopathy, affecting males and females alike. It would be interesting to study prolactin serum expression levels in male and female patients with idiopathic DCMO. Clearly, further studies into the unfolding pathogenesis of PPCM are indicated.

Background: Peripartum cardiomyopathy (PPCM) is an incompletely understood disease that causes significant morbidity and mortality in many parts of the world, including Northern Nigeria. The aims of this Thesis were: [1] to determine if selenium deficiency, serum ceruloplasmin and traditional birth practices are risk factors for PPCM, in Kano, Nigeria; [2] to describe the one year survival and left ventricular reverse remodeling (LVRR) in a group of patients with PPCM from three referral hospitals in Kano, Nigeria; [3] to identify potential electrocardiographic (ECG) predictors of PPCM; and [4] to assess right ventricular systolic dysfunction (RVSD) and remodelling in a cohort of PPCM patients in Kano, Nigeria. Materials and Methods: The studies were carried out in 3 referral hospitals in Kano, Nigeria. Study 1: This was a case-control study. Critically low serum selenium concentration was defined as &lt;70μg/L. Study 2: This was a longitudinal study. LVRR was defined as absolute increase in LV ejection fraction (LVEF) by ≥10.0% and decrease in LV end-diastolic dimension indexed to body surface area (LVEDDi) ≤33.0 mm/m2, while recovered LV systolic function as LVEF ≥55%, at 12 months follow-up. Study 3: This was a case-control study. Logistic regression models and a risk score were developed to determine ECG predictors of PPCM. Study 4: This was a longitudinal study and patients were followed up for 12 months. RVSD was defined as the presence of either tricuspid annular plane systolic excursion (TAPSE) &lt;16mm or peak systolic wave (S’) tissue Doppler velocity of RV free wall &lt;10cm/s. Recovery of RV systolic function was defined as an improvement of reduced TAPSE to ≥16mm or S’ to ≥10cm/s, without falling to reduced levels again, during follow-up. Results: Study 1: Total of 39 PPCM patients and 50 controls were consecutively recruited after satisfying the inclusion criteria. Mean serum selenium in patients (61.7±14.9μg/L) was significantly lower than in controls (118.4±45.6μg/L) (p&lt;0.001). The prevalence of serum selenium &lt;70μg/L was significantly higher among patients (76.9%) than controls (22.0%) (p&lt;0.001). The mean ceruloplasmin and prevalence of socio-economic indices, multiparity, pregnancy-induced hypertension, obesity and twin pregnancy were not different between the groups (p&gt;0.05). Logistic regression showed that rural residency significantly increased the odds for serum selenium &lt;70μg/L by 2.773 fold (p=0.037). Study 2: A total of 33 patients were followed-up. Of the 17 survivors at 12 months, 8 patients (47.1%) satisfied the criteria for LVRR, of whom 5 (29.4%) had recovered LV systolic function, but LVRR was not predicted by any variable in the regression models. The prevalence of normal LV diastolic function increased from 11.1% at baseline to 35.3% at twelve months (p=0.02). At one year follow-up, 41.4% of patients had died (two thirds of them within the first 6 months), but mortality wasn’t predicted by any variable including LVRR. Study 3: A total of 54 PPCM and 77 controls were studied. A rise in heart rate by 1 beat/minute increased the odds of PPCM by 6.4% (p=0.001), while presence of ST-T-wave changes increased the odds of PPCM by 12.06 fold (p&lt;0.001). In patients, QRS duration modestly correlated (r=0.4; p&lt;0.003) with LV dimensions and end-systolic volume index (LVESVI), and was responsible for 19.9% of the variability of the latter (R2 = 0.199; p=0.003). A risk score of ≥2 had a sensitivity of 85.2%, specificity of 64.9%, negative predictive value of 86.2% and area under the curve of 83.8% (p&lt;0.0001) for potentially predicting PPCM. Study 4: A total of 45 patients were studied. RV systolic function recovery occurred in a total of 8 patients (8/45; 17.8%), of whom 6 (75.0%) recovered in 6 months after diagnosis. The prevalence of RVSD fell from 71.1% at baseline to 36.4% at 6 months (p=0.007) and 18.8% at one year (p=0.0008 vs baseline; p=0.41 vs 6 month). Although 83.3% of the deceased had RVSD, it didn’t predict mortality in the regression models (p&gt;0.05). Conclusion: These studies have shown that selenium deficiency seems to be a risk factor for PPCM in Kano, Nigeria, related to rural residency. However, serum ceruloplasmin, customary birth practices and some other characteristics were not associated with PPCM in the study area. They have also shown that PPCM patients had modest LVRR but high mortality at one year. In addition, using the ECG risk score could help to streamline the diagnosis of PPCM with significant accuracy, prior to confirmatory investigations in postpartum women. Finally, RVSD and reverse remodelling were common in Nigerians with PPCM, in whom the first 6 months after diagnosis seem to be critical for RV recovery and survival. / Summary

A growing body of research has emerged about effective treatments for postpartum depression, specifically how the internet could become a pivotal and vital option for women with postpartum symptoms. With that in mind, the purpose of this quantitative study was to investigate whether women suffering from postpartum depression preferred traditional therapy treatment or internet therapy treatment. The nonexperimental survey design was used to assess differences between groups related to stigma, satisfaction with treatment, and perceived quality of treatment received. Data collected from a sample of 78 adult females, who had previously received postpartum depression therapy treatment, indicated there was no difference experienced between the treatment modalities. Results were calculated using an independent sample t-test, noninferiority design, and it was determined that participants perceived no difference in their experience of stigma, treatment satisfaction, and perception of credibility and quality between the two therapy modalities. This study adds to the growing body of literature that suggests internet therapy may be a viable option for some women. The results encourage positive social change in that psychologists may advance clinical practice through incorporating technology into their treatment plans, thereby benefiting women who suffer from this condition and who may not be able to readily access a therapist's office on a weekly basis.

Peripartum depression is the most common complication associated with childbearing yet there are many barriers to diagnosis and treatment. Motherhood is an especially vulnerable time for Hispanic women who experience additional barriers that prevent them from seeking maternal mental health care. Due to these barriers, researchers have increased their interest in prevention. They have found that low social support is a modifiable risk factor with one of the strongest predictive values. Doulas are specifically trained to provide physical, social, and emotional support to mothers during pregnancy, labor, and/or postpartum periods. In this context they may be considered a powerful tool to lower barriers and improve maternal psychosocial wellbeing. However, significant limitations from prior studies have prevented the acceptance of using doulas routinely for at-risk mothers. By identifying and incorporating components of other successful social support interventions in my literature review, I hope to eliminate some of these limitations. This study will select participants with low social supports and other risk factors to be randomized into home-visiting doula intervention group or standard of care control group. Maternal mental health and perceived social support will be evaluated from the first trimester to 6 months postpartum. If there are significant differences between these groups, there is a potential to increase doula training and recruitment for prevention of postpartum depression for minorities. Hopefully the results will guide law makers to increase insurance coverage and guide practitioners to routinely offer doula services for at-risk mothers who need additional supports to receive adequate mental health care. Finally, I aim to increase the perceived value of doulas in the setting of improving maternal mental health/ social wellbeing and increase their acceptance within the medical community.

Bakgrund: Föräldraskapet inkluderar fysiska och mentala utmaningar, vilket kan vara påfrestande för båda föräldrarna. Då peripartum depression (PPD) drabbar modern kan både föräldraskapet och upplevelsen av att vara förälder påverkas negativt. Faderns upplevelser av situationen då modern drabbas av PPD innebär ofta ett lidande även för honom, vilket är ett perspektiv som länge försummats. Syfte: Att beskriva fäders erfarenheter av föräldraskapet då modern drabbats av peripartum depression. Metod: En litteraturstudie innehållandes tio vetenskapliga artiklar av kvalitativ metod, utvalda genom systematiska sökningar i flera databaser. Analysen utfördes med en kvalitativ analysmodell, där jämförelser av likheter och skillnader genererade teman och subteman. Resultat: Fäderna påverkades främst av partnerns PPD genom att de upplevde utmaningar i faderskapet och behovet av stöd från samhället efterfrågades. Följande teman och subteman identifierades, (1) Utmaningar i faderskapet, subteman: Effekten av att inte vara förberedd, PPDs påverkan på familjelivet och Möjligheter till anknytning. (2) Samhällets inverkan, subteman: Stödbarriärer - Hinder att övervinna förnödvändigt stöd och Behovet av stöd och resurser. Konklusion: Ett begrepp genomsyrade studiens samtliga teman; barriärer. Fäder stötte på flera hinder som motverkade ambitionen att vara den fadersfigur de ville vara. Dessa barriärer har formats utifrån samhälleliga normer samtur ett vårdsystem som påvisar brister gällande kunskap och förståelse för PPDs inverkan på familjelivet, samt inkludering av fadern, den bortglömda föräldern. / Background: Parenting includes physical and mental challenges, which can be stressful for both parents. As peripartum depression (PPD) affects the mother, both parenting and the experience of being a parent can be negatively affected. The fathers’ experiences of the situation when the mother suffers from PPD often mean suffering even for him, which is a perspective that has long been neglected. Aim: To describe fathers' experiences of parenthood when the mother suffered from peripartum depression. Method: A literature study involving ten scientific articles of qualitative method, selected through systematic searches in several databases. Analysis was carried out using a qualitative analysis model where comparisons of similarities and differences generated themes and sub themes. Result: Fathers were primarily affected by their partner’s PPD by experiencing challenges in paternity and the need for support from society was highlighted. Following themes and sub themes were identified, (1) Challenges in paternity, sub themes: The impact of not being prepared, PPD´s impact on family life and Opportunities for Attachment (2) Societal impact, sub themes: Support barriers – Obstacles to overcome for necessary support and The need for support and resources. Conclusion: A concept permeated all the themes of the study; Barriers. Fathers encountered several obstacles that thwarted the ambition to be the father figure they wanted to be. These barriers have been constructed by societal norms as well as from a care system that demonstrates a lack of knowledge and understanding of PPD's impact on family life and the inclusion of the father, the forgotten parent.

O sucesso da adaptação imediata para a vida extrauterina depende da apropriada função pulmonar. Em neonatologia humana, é estabelecido que a cesariana eletiva aumenta o risco de angústia respiratória, como resultado da reduzida remoção do fluido pulmonar. Neste contexto, este estudo objetivou avaliar a influência da condição obstétrica no desempenho respiratório dos recém-nascidos caninos no período de transição, em especial os fatores que determinam a remoção do fluido pulmonar. Para tal, foram selecionadas 20 fêmeas caninas e 37 neonatos, os quais constituíram dois grupos, de acordo com a condição obstétrica: Eutocia Vaginal (n=10 parturientes; n= 17 neonatos) e Cesariana Eletiva (n= 10 parturientes; n= 20 neonatos). A avaliação materna consistiu na dosagem sérica de cortisol e catecolaminas (adrenalina e noradrenalina) em momentos pontuais no pré, intra e pós-parto. Os neonatos foram avaliados por meio do escore de vitalidade neonatal, bem como avaliação das frequências cardíaca e respiratória, aferição da temperatura corpórea e peso corporal, avaliação hemogasométrica venosa, dosagem sérica de cortisol e catecolaminas, lactatemia, glicemia, oximetria de pulso e avaliação radiográfica pulmonar em momentos pontuais no decorrer das primeiras 24 horas de vida. Adicionalmente, foi avaliado a composição eletrolítica e a concentração de cortisol no líquido amniótico de cada filhote. O parto vaginal determinou menor estresse materno, porém, maior concentração de cortisol no líquido amniótico e soro sanguíneo dos filhotes, contribuindo para melhor adaptação cardiorrespiratória e metabólica. Por outro lado, a cesariana eletiva resultou em maior estresse materno, contrariamente ao perfil hormonal dos filhotes e retardou a remoção do fluido pulmonar, resultando em hipoxemia mais severa, além de dificultar a resposta compensatória ao desequilíbrio ácido-básico sanguíneo e termorregulação. Em conclusão, a condição obstétrica impõe diferenças na adaptação pulmonar, interferindo no desempenho respiratório de cães no período de transição feto-neonatal. / The success of immediate adaptation to extrauterine life depends on appropriate lung function. In human neonatology, it is established that elective cesarean section increases the risk of respiratory distress as a result of reduced pulmonary fluid reabsortion. In this context, this study aimed to evaluate the influence of the obstetric condition on the respiratory performance of canine neonates in the transition period, specially the factors that determine the removal of the pulmonary fluid. For this purpose, 20 canine females and 37 neonates were selected, according to the obstetric condition: Vaginal Eutocia (n = 10 bitches, n = 17 neonates) and Elective Cesarian Section (n = 10 bitches, n = 20 neonates). Maternal evaluations were performed to evaluate serum cortisol and catecholamines (adrenaline and noradrenaline) levels at punctual moments in pre, intra and postpartum. Neonates were evaluated for the neonatal vitality score, as well as evaluation of heart and respiratory rates, body temperature and body weight, venous hemogasometric evaluation, serum cortisol and catecholamines, blood lactate, blood glucose, pulse oximetry and radiographic evaluation during the first 24 hours of life. Additionally, the electrolyte composition and cortisol concentration in the amniotic fluid of each puppy was evaluated. The vaginal delivery determined lower maternal stress, however, a higher cortisol concentration in the amniotic fluid and neonatal blood serum, contributing to a better cardiorespiratory and metabolic adaptation. On the other hand, elective cesarean section resulted in higher maternal stress contrary to the neonatal hormonal profile and delayed the removal of the pulmonary fluid, resulting in more severe hypoxemia, besides a less efficient compensatory response to acid-base imbalance and thermoregulation. In conclusion, the obstetric condition imposes differences in pulmonary adaptation, interfering in the respiratory performance of dogs in the transition from fetal to neonatal life.

O objetivo geral desta pesquisa foi avaliar o metabolismo e a resposta imune celular no sangue de vacas leiteiras no período de transição. Foram utilizadas 13 vacas Holandesas, de 2ª a 4ª parição, avaliadas nas semanas M-2, M-1 (pré-parto), M0 (dia da parição), M1, M2 e M3 (pós-parto). Foram realizadas análises das seguintes variáveis: produção leiteira, escore de condição corporal (ECC), mensuração sérica do beta-hidroxibutirato (BHB), ácidos graxos não esterificados (NEFA), IGF-1 (Fator de Crescimento Semelhante à Insulina Tipo 1), glicose (GLIC), colesterol (COL), triglicerídeos, proteína total (PT), albumina (ALB), globulina (GLOB), AST (Aspartato transaminase), GGT (Gamaglutamiltransferase) e cálcio total e cálcio ionizável. Além disso, a resposta imune celular das vacas forma avaliadas pelas interpretações do leucograma e imunofenotipagem dos linfócitos. Foram encontradas medianas do ECC equivalentes a 4,0; 3,8; 3,5; 3,0; 3,5 e 3,5 dos momentos M-2 ao M3. Em relação aos indicadores energéticos, observou-se aumento da concentração de NEFA e BHB no parto e pós-parto, ao contrário, os teores de triglicerídeos, colesterol e IGF- 1 diminuíram. Além disso, foi possível observar concentração máxima de glicose no momento da parição. Em relação ao metabolismo proteico e hepático, observam-se menores concentrações de proteína total e globulina no momento do parto; os teores de albumina diminuíram no pós-parto. A atividade sérica da AST aumentou a partir da parição, porém não foi possível detectar variações para a GGT. As concentrações de cálcio sério total e ionizado foram menores a partir da parição. A análise do leucograma das vacas no período de transição revelou leucocitose por linfocitose no momento do parto, apesar de não ter sido observada variações no número absoluto e relativo dos linfócitos durante o período de transição, foi possível observar que os linfócitos sanguíneos apresentaram-se elevados durante todo o período de estudo. O aumento no número de linfócitos decorreu da elevação dos linfócitos B (CD21+). A partir desse resultado realizou-se exame sorológico para o vírus da Leucose Enzootica Bovina, detectando 12/13 (92,30%) vacas soropositivas. O linfócito T (CD3+) e suas subpopulções auxiliar (CD3+CD4+) e citotóxica (CD3+CD8+) apresentaram ligeiras oscilações durante o período de estudo. Com base nos resultados obtidos pode-se concluir que: a) As vacas Holandesas apresentaram variações nos parâmetros do perfil energético indicadoras de balanço energético negativo e mobilização lipídica, caracterizados especialmente pela diminuição do ECC e elevações nos teores séricos de NEFA e BHB; b) os teores de PT e GLOB apresentaram variações em decorrência da colostrogênese e infecções uterinas pós-parto. A albumina apresentou diminuição no pós-parto, decorrente do aumento da demanda nutricional para a produção de leite e uso de aminoácidos como precursor energético no processo de gliconeogênese; c) os valores de IGF-I apresentaram acentuada redução no momento do parto, sinalizando para mobilização lipídica e desacoplamento do eixo somatotrópico a partir da parição; d) as vacas apresentaram hipocalcemia, especialmente na parição e primeira semana pós-parto; e) a infecção pelo Vírus da Leucose Enzoótica Bovina influenciou na resposta imune observada no período de transição, caracterizada por linfocitose e aumento da população de linfócitos B (CD21+). / The general aim of this research was to evaluate the metabolism and cellular immune response in blood of dairy cows in transition period. Was evaluated 13 Holstein cows, from 2nd to 4th parturitions in the weeks M-2, M-1 (pre-partum), M0 (parturition day), M1, M2 and M3 (post-partum). Paremeter analysis were performed: milk production, body condition score (BCS), beta-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), IGF-1 (growth factor Insulin-like similar to insulin type 1), glucose (GLUC), cholesterol (CHOL), triglycerides, total protein (TP), albumin, globulin (GLOB), AST (aspartate transaminase), GGT (gamma-glutamyl transferase), total calcium and ionized calcium. Furthermore, cows cellular immune response was evaluated by WBC and lymphocyte immunophenotyping. Was find for BCS median 4.0; 3.8; 3.5; 3.0; 3.5 and 3.5 between the moments M-2 to M3. Regarding to energy indicators, an increase of NEFA and BHB in parturition and postpartum was observed, in contrast, the values of triglycerides, cholesterol and IGF-1 decreased. Moreover, it was possible to obtain maximum glucose concentration at parturition time. Regarding to protein and hepatic metabolic was find lower values of total protein and globulin was observed in pre-partum and parturition in relation to postpartum; values of albumin decreased in post-partum. The Aspartate aminotransferase activity increased from calving, but it was not possible to detect GGT variations. The concentration of total and ionized calcium serum were lower from calving. The analysis of cows leukogram in the transition period revealed leukocytosis by lymphocytosis at delivery, although no variation in the absolute and relative number of lymphocytes was observed during the transition period. The increase of lymphocytes number occurred due to the increase of B lymphocytes (CD21 +). From this result, serological test for the Enzootic Bovine Leukosis Virus was developed, detecting 12/13 (92,30%) of seropositive cows. T lymphocytes (CD3 +) and subpopulations T helper (CD3+ CD4+) and T cytotoxic (CD3+ CD8+) showed slight fluctuations during period. Based on the results, we can conclude the following: a) Holstein cows showed variations in the parameters of the energy profile indicator of negative energy balance and lipid mobilization, characterized especially by the decreasing of BCS and elevations in serum NEFA and BHB; b) the levels of TP and GLOB showed variations due to colostrogenesis and postpartum uterine infections. The albumin decreased in postpartum, due to increased nutrient requeriment for milk production and use of amino acids as energy precursor in the gluconeogenesis; c) the amounts of IGF-I showed significant reduction at delivery, signaling lipid mobilization and uncoupling of the somatotropic axis after calving; d) cows showed hypocalcemia, especially in calving and first week post-partum; e) Infection with Enzootic Bovine Leukosis Virus influenced the immune response observed in the transition period, characterized by lymphocytosis and the increase of B lymphocytes (CD21 +) population.

Orientador: José Jurandir Fagliari / Banca: Francisco Guilherme Leite / Banca: Eduardo Harry Birgel Júnior / Resumo: O presente estudo foi constituído por três experimentos: Experimento 1: Foram analisadas as variáveis hematológicas de fêmeas bovinas da raça holandesas mensalmente durante toda a gestação e o periparto. As fêmeas foram distribuídas em 5 grupos: novilhas gestantes (G1), vacas de segunda gestação (G2), vacas de segunda gestação, repetidoras de estro(G3), vacas de terceira gestação (G4) e vacas de terceira gestação, repetidoras de estro(G5). As atividades das enzimas AST e ALP, foram maiores em G1. Houve diferença significativa entre vacas repetidoras e não repetidoras de estro somente nas concentrações séricas de colesterol no início da gestação. No segundo mês de gestação as concentrações de cálcio total e ionizado foram alteradas significativamente em relação ao primeiro mês, em todos os grupos. No terço final da gestação, dia do parto e no pós-parto houve alteração nas concentrações de cálcio, fósforo, ferro, cloretos, creatinina, bilirrubina direta e total, colesterol, triglicerídeos, proteína total, albumina e imunoglobulinas, no número de hemácias e leucócitos, volume globular, nos teores plasmáticos de glicose e hemoglobina e na atividade da enzima AST em todos grupos de animais. As atividades de LDH, ALP e GGT e as concentrações de sódio, potássio e uréia não foram significativamente alteradas durante o experimento. Experimento 2: Os constituintes sanguíneos das vacas do experimento 1 (G1) foram comparados aqueles de vacas acometidas por abortamento G (2) entre 25 (25 DPc) e 45 dias após inseminação artificial ou transferência de embrião (45 DPc). O teor de cálcio ionizado foi significativamente maior no grupo 1 45 dias após a inseminação artificial ou transferência de embrião. Possivelmente esses abortos tem origem metabólica/nutricional... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The present study was constituted by 3 experiments: Experiment 1: Were analysed the blood constituents of Holstein bovine females monthly during the whole gestation and the peripartum. The females were sorted in five groups: pregnancy heifers (G1), second pregnancy cows (G2) repeat-breeders second pregnancy cows (G3), third pregnancy cows (G4) and repeat-breeders third pregnancy cows. The seric activity of AST and ALP enzymes was higher in G1. Only the cholesterol level. The diference was significative between repeat-breeders and non repeat-breeders cows only in the cholesterol seric concentration in the early gestation. In the second month of pregnancy the seric concentration of total calcium and ionized calcium was significant modified compared with the first month of gestation in all groups. In the late gestation, at the partum and in post-partum period the seric concentration of calcium, phosphorus, iron, chlorides, creatinine, direct and total bilirrubins, cholesterol, triglycerides, total protein, albumin, and imunoglobulins, number of eritrocytes and leukocytes, plasmatic concentration of glucose and hemoglobin and AST activity in all of the animal groups. The sodium, potassium and urea concentrations were not significantly modified during the experiment. Experiment 2: The blood constituents of the cows of experiment 1 (G1) was compared with cows that aborted between 25 and 45 days post-breed. Possibly this abortion has metabolic/nutricional cause, because was not found alterations in the acute-phase protein concentrations neither in the leukogram. Experiment 3: The passive immunity transfer to the heifers which were daughters of the females from the experiment 1 was evaluated by measuring seric GGT , total protein and IGg . The heifers got colostrum from their own mothers and there was no significant difference between the groups. The TIP found in all the groups was considered good. / Mestre

Introdução: Apesar de apresentar grandes prevalências e impactos, a depressão no período perinatal é subdiagnosticada, subtratada e ainda não possui uma consistente diferenciação dos episódios depressivos em outras épocas de vida. Sua etiologia engloba aspectos psicossociais e biológicos ainda controversos. Algumas mulheres expostas a estressores ambientais não desenvolvem estados depressivos no período periparto. A predisposição genética pode ser uma explicação. Estudos que avaliaram o papel de fatores genéticos demonstraram resultados inconsistentes, possivelmente por diferenças metodologias, como a época e a forma da mensuração dos sintomas depressivos, os fatores ambientais avaliados, as metodologias de análise e as diferenças étnicas entre as amostras. Este estudo objetivou investigar interações genético-ambientais na etiologia da depressão periparto, tendo como hipóteses: a) eventos estressores ou a experiência subjetiva de estresse associar-se-iam a uma maior probabilidade de desenvolvimento de sintomas depressivos perinatais em indivíduos portadores de polimorfismos associados com maior vulnerabilidade; b) haveria um efeito diferencial da vulnerabilidade genética aos estressores de acordo com a cor da pele do indivíduo. Métodos: 2847 gestantes de uma coorte prospectiva provenientes de duas cidades brasileiras foram avaliadas no pré-natal e no puerpério. Exploraram-se associações entre variáveis sociodemográficas, e fatores estressores e protetores ambientais com o desenvolvimento de sintomas depressivos perinatais, considerando a predisposição biológica, avaliada por meio de dois polimorfismos funcionais, localizados na região promotora do gene para o transportador de serotonina (5HTTLPR) e do gene para o receptor do hormônio liberador de corticotrofina (CRH1). As associações entre variáveis foram testadas por regressão de Poisson. Testaram-se modelos explicativos para os desfechos utilizando a modelagem de equações estruturais. As interações genético-ambientais foram avaliadas por regressão de Poisson e modelos multigrupos. Resultados: 2822 mulheres foram avaliadas na gestação e 1860 reavaliadas no puerpério. A prevalência de provável depressão na gestação foi de 24,4% e no puerpério, 15,9%. Os modelos com hipóteses associativas para a explicação dos desfechos mostraram que o relato de eventos estressores no último ano teve grande parte do seu efeito mediado pelos níveis de estresse percebido. Estresse percebido foi fator de risco tanto para mulheres brancas como negras, mas relato de eventos estressores foi fator de risco apenas para mulheres brancas. Houve um papel de moderação do 5-HTTLPR e dos haplótipos do CRH1 no efeito ambiental nos estados depressivos perinatais, ampliado quando a cor da pele da mãe foi considerada. Na presença de baixos indicadores de estresse, a presença de nenhuma ou uma cópia do haplótipo do CRH1 foi um fator protetor entre mulheres negras. Na depressão puerperal, ser carreadora da variante longa do 5HTTLPR, teve um efeito protetor na ausência de eventos estressores no último ano. Ao separar por cor, este efeito protetor manteve-se significativo apenas entre mulheres de cor negra. Conclusões: No que se refere à vulnerabilidade genética, os resultados apontaram para algumas semelhanças entre a depressão perinatal e a depressão em outros momentos da vida. A depressão perinatal pode ser um evento importante para o entendimento dos aspectos genéticos da fisiopatologia da depressão em outros momentos da vida. / Introduction: Although presents large prevalences and impacts, peripartum depression are under detected, under assisted and yet do not have a consistent differentiation of depressive episodes at other phases of life. Its etiology includes psychosocial and biological aspects still controversial. A few women exposed to environmental stressors did not develop peripartum depressive states. Genetic predisposition may be an explanation. Studies evaluating the role of genetic factors have shown inconsistent results probably due to methodological differences, such as the period and the way of measurement of depressive symptoms, environmental factors evaluated, analysis methods and ethnic differences between the samples. This study aimed to investigate gene-environment interactions in the etiology of peripartum depression, through these hypotheses: a) the occurrence of stressful events or the subjective experience of stress would associate themselves to a greater probability of developing perinatal depressive symptoms in subjects with polymorphisms associated with greater biological vulnerability; b) there would be a differential effect of genetic vulnerability to environmental stressors according to the individual\'s skin color. Methods: 2847 pregnant women from two Brazilian cities in a prospective cohort study were assessed during the prenatal and postpartum period. Associations between socio-demographic, stressors and protective factors with the development of perinatal depressive symptoms was explored. It was considered the biological predisposition evaluated by two functional polymorphisms located in the promoter region of the gene for the serotonin transporter (5HTTLPR) and the gene for the corticotrophin releasing hormone receptor (CRH1). Associations between variables were tested by Poisson regression. We tested explanatory models for outcomes using structural equation modeling. The geneticenvironmental interactions were assessed by Poisson regression and multigroups models. Results: 2822 women were assessed during pregnancy and 1860 were reassessed during the postpartum period. The prevalence of probable depression during pregnancy was 24.4% and 15.9% during the postpartum period. Models with associative hypotheses to explain the outcomes showed that the report of stressful events in the last 12 months had much of its effect mediated by perceived stress levels. Perceived stress was a risk factor for both white women and black women, but reports of stressful events was a risk factor only for white women. There was a moderating role of the 5-HTTLPR and haplotypes of CRHR1 in the environmental effects on perinatal depressive states. These findings are even more significant when skin color was considered. In the presence of low stress indicators, have no copies or one copy of haplotype CRH1 was a protective factor among black women. In postpartum depression, be a carrier of the long variant of the 5 HTTLPR, had a protective effect in the absence of stressful events in the last year. If we separate by color, this protective effect remained significant only among black women. Conclusions: With regard to genetic vulnerability, the results points to similarities between peripartum depression and depression during other phases of life. Perinatal depression can be an important event for the understanding of the genetic aspects of the pathophysiology of depression.