Current pathophysiological concepts and management of pulmonary hypertension

Pulmonary hypertension (PH), increasingly recognized as a major health burden, remains underdiagnosed due mainly to the unspecific symptoms. Pulmonary arterial hypertension (PAH) has been extensively investigated. Pathophysiological knowledge derives mostly from experimental models. Paradoxically, common non-PAH PH forms remain largely unexplored. Drugs targeting lung vascular tonus became available during the last two decades, notwithstanding the disease progresses in many patients. The aim of this review is to summarize recent advances in epidemiology, pathophysiology and management with particular focus on associated myocardial and systemic compromise and experimental therapeutic possibilities. PAH, currently viewed as a panvasculopathy, is due to a crosstalk between endothelial and smooth muscle cells, inflammatory activation and altered subcellular pathways. Cardiac cachexia and right ventricular compromise are fundamental determinants of PH prognosis. Combined vasodilator therapy is already mainstay for refractory cases, but drugs directed at these new pathophysiological pathways may constitute a significant advance

Tissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose administered through intramuscular delivery

In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system

Prótese Peniana Maleável: Avaliação do grau de satisfação do doente e da parceira – Experiência do Serviço de Urologia do Hospital Fernando Fonseca no período de 2005 a 2008

Analisamos a experiência do nosso serviço na colocação de próteses penianas maleáveis, com a finalidade de avaliar o grau de satisfação sexual do doente e da sua parceira. Nesta análise retrospectiva, foram avaliados 36 homens com disfunção eréctil submetidos a implante de prótese maleável (Acu-form® e Genesis®), entre Maio de 2005 e Dezembro de 2008. Foram enviados por via postal, ao doente e parceira, os questionários Inventário de Satisfação do Tratamento da Disfunção Eréctil, versão para o doente e versão para a parceira respectivamente, modificados e adaptados. Um total de 36 homens com uma idade média de 55,4 anos (entre 35 e 68) à data do implante, foram avaliados após a colocação de prótese maleável. O período de foi de 3 a 34 meses. Completaram e devolveram o questionário 31 (86%). Oitenta e oito por cento dos homens mantêm actividade sexual regular e com coito penetrante. Noventa e um por cento responderam não ter tido dificuldade na aprendizagem do manuseamento e do posterior uso da prótese. Setenta e sete por cento mencionaram ter rigidez satisfatória para o coito. A satisfação global dos doentes e das suas parceiras foi de 85% e 76% respectivamente. Como causa de insatisfação, dezoito por cento das parceiras referiram a não naturalidade da erecção e 15% referiram a sensação de pénis frio. Oitenta e um por cento dos doentes e 70% das parceiras recomendariam a colocação de prótese a outro doente e repetiriam o mesmo procedimento.O implante de próteses maleáveis é um método com boa aceitação e satisfação entre os pacientes, embora exista uma percentagem significativa de parceiras não satisfeitas devido à não naturalidade da erecção

Seropositivity for Coxiella burnetii in Wild Boar (Sus scrofa) and Red Deer (Cervus elaphus) in Portugal

Q fever is caused by the pathogen Coxiella burnetii and is a zoonosis that naturally infects goats, sheep, and cats, but can also infect humans, birds, reptiles, or arthropods. A survey was conducted for the detection of antibodies against C. burnetii in a sample of 617 free-ranging wild ruminants, 358 wild boar (Sus scrofa) and 259 red deer (Cervus elaphus), in east-central Portugal during the 2016-2022 hunting seasons. Only adult animals were sampled in this study. Antibodies specific to C. burnetii were detected using a commercial enzyme-linked immunosorbent assay (ELISA; IDVet(R), Montpellier, France) according to the manufacturer's instructions. The seroprevalence of C. burnetii infection was 1.5% (n = 9; 95% confidence interval [CI]: 0.7-2.8%). Antibodies against C. burnetii were detected in 4/358 wild boar (1.1%; 95% CI: CI: 0.3-2.8%) and 5/259 red deer (1.9%; 0.6-4.5%). Results of the present study indicate that antibodies against C. burnetii were present in wild boar and red deer in Portugal. These findings can help local health authorities to focus on the problem of C. burnetii in wildlife and facilitate the application of a One Health approach to its prevention and control

Activation profile of pro-inflammatory cytokines in acute cardiac overload

INTRODUCTION:Pro-inflammatory cytokines have been implicated in ventricular remodeling during heart failure progression. In the present study, we investigated the effects of acute volume and RV pressure overload on biventricular hemodynamics and myocardial gene expression of IL-6 and TNF-alpha.METHODS:Male Wistar rats (n = 45) instrumented with RV and LV tip micromanometers were randomly assigned to one of three protocols: i) acute RV pressure overload (PrOv) induced by pulmonary trunk banding in order to double RV peak systolic pressure, for 120 or 360 min; ii) acute volume overload (VolOv) induced by dextran40 infusion (5 ml/h), for 120 or 360 min; iii) Sham. Free wall samples from the RV and LV were collected for mRNA quantification.RESULTS:In the RV, acute overload induced IL-6 and TNF-alpha gene expression, higher in VolOv (IL-6: + 669.7 +/- 263.4%; TNF-alpha: + 5149.9 +/- 1099.0%; 360 min) than in PrOv (IL-6: + 64.9 +/- 44.2%; TNF-alpha: + 628.1 +/- 229.3%; 360 min). In PrOv, TNF-alpha mRNA levels in the LV were increased, in the absence of ventricular overload. IL-6 and TNF-alpha mRNA levels did not correlate in the LV, while in the RV a positive correlation was found (r = 0.574; p < 0.001).CONCLUSIONS:Acute cardiac overload induces overexpression of pro-inflammatory cytokines. This gene activation is not uniform, being higher in volume overload and involving both load-dependent and load-independent mechanisms

Urolume – permanent urethral stent: technique of the past, complications of the present

O UroLume - Stent Uretral Permanente, foi desenvolvido como forma de tratamento de apertos da uretra. No entanto, o longo período de seguimento revelou uma alta taxa de falência e complicações. Apesar da contra-indicação nos apertos de etiologia traumática, a sua utilização manteve-se durante vários anos. A reestenose é comum nestes doentes, podendo ser abordada endoscopicamente ou através de reconstrução uretral. Apresentamos 2 casos clínicos de doentes com reestenose após a colocação de stent uretral para tratamento de aperto uretral traumático e o desafio cirúrgico da sua resolução

Catástrofe Peniana. Infecção de Prótese Peniana – A propósito de um Caso Clínico

A infecção de prótese peniana é uma das complicações mais devastadoras da cirurgia de implante, dada a magnitude da situação, podendo assumir consequências catastróficas. Relatamos o caso clínico de infecção de prótese peniana, de difícil controlo, tendo terminado em Uretrostomia Perineal e contrução de “Pseudo Pénis”, isto apesar do cumprimento rigoroso da técnica cirúrgica e da profilaxia antibiótica sistémica e local