Ischemic preconditioning does not prevent placental dysfunction induced by fetal cardiac bypass.

BACKGROUND: Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. METHODS: Eighteen fetal lambs were divided into three groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for four cycles of a 5-min period, followed by a 2-min reperfusion period. Both study groups underwent 30 min of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. RESULTS: The CB rIPC group achieved higher bypass flow rates (p < .001). After CB start, both study groups developed significant decreases in PaO2 , mixed acidosis, and increased lactate levels (p < .0004). No significant differences in tissular edema were observed on fetal lungs and placenta (p > .391). Expression of Toll-like receptor 4 and intercellular adhesion molecule-1 in the placenta and fetal lungs did not differ among the three groups, as well as with vascular cell adhesion molecule-1 (VCAM-1) of fetal lungs (p > .225). Placental VCAM-1 expression was lower in the rIPC group (p < .05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 min post-CB in the CB rIPC group (p < .05). There were no significant differences in tumor necrosis factor-α, prostaglandin E2, IL-6, and IL-10 plasma levels of the three groups at 60-min post-bypass (p > .133). CONCLUSION: Although rIPC allowed increased blood flow during fetal CB and decreased IL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.

Antivirus applied to JAR malware detection based on runtime behaviors.

Java vulnerabilities correspond to 91% of all exploits observed on the worldwide web. The present work aims to create antivirus software with machine learning and artificial intelligence and master in Java malware detection. Within the proposed methodology, the suspected JAR sample is executed to intentionally infect the Windows OS monitored in a controlled environment. In all, our antivirus monitors and considers, statistically, 6824 actions that the suspected JAR file can perform when executed. Our antivirus achieved an average performance of 91.58% in the distinction between benign and malware JAR files. Different initial conditions, learning functions and architectures of our antivirus are investigated. The limitations of commercial antiviruses can be supplied by intelligent antiviruses. Instead of blacklist-based models, our antivirus allows JAR malware detection preventively and not reactively as Oracle's Java and traditional antivirus modus operandi.

Reversible pulmonary trunk banding: Myocardial vascular endothelial growth factor expression in young goats submitted to ventricular retraining.

BACKGROUND: Ventricle retraining has been extensively studied by our laboratory. Previous studies have demonstrated that intermittent overload causes a more efficient ventricular hypertrophy. The adaptive mechanisms involved in the ventricle retraining are not completely established. This study assessed vascular endothelial growth factor (VEGF) expression in the ventricles of goats submitted to systolic overload. METHODS: Twenty-one young goats were divided into 3 groups (7 animals each): control, 96-hour continuous systolic overload, and intermittent systolic overload (four 12-hour periods of systolic overload paired with 12-hour resting period). During the 96-hour protocol, systolic overload was adjusted to achieve a right ventricular (RV) / aortic pressure ratio of 0.7. Hemodynamic evaluations were performed daily before and after systolic overload. Echocardiograms were obtained preoperatively and at protocol end to measure cardiac masses thickness. At study end, the animals were killed for morphologic evaluation and immunohistochemical assessment of VEGF expression. RESULTS: RV-trained groups developed hypertrophy of RV and septal masses, confirmed by increased weight and thickness, as expected. In the study groups, there was a small but significantly increased water content of the RV and septum compared with those in the control group (p<0.002). VEGF expression in the RV myocardium was greater in the intermittent group (2.89% ± 0.41%) than in the continuous (1.80% ± 0.19%) and control (1.43% ± 0.18%) groups (p<0.023). CONCLUSIONS: Intermittent systolic overload promotes greater upregulation of VEGF expression in the subpulmonary ventricle, an adaptation that provides a mechanism for increased myocardial perfusion during the rapid myocardial hypertrophy of young goats.

Dual-drugs delivery in solid lipid nanoparticles for the treatment of Candida albicans mycosis.

Nowadays, a combinatorial drug delivery system that simultaneously transports two or more drugs to the targeted site in a human body, also recognized as a dual-drugs delivery system, represents a promising strategy to overcome drug resistance. Solid lipid nanoparticles loaded with clotrimazole (CLZ) and alphalipolic acid (ALA), considered as an effective agent in the reduction of reactive oxygen species, can enhance anti-infective immunity being proposed as a non-toxic and mainly non-allergic dual-drugs delivery system. In this study, uncoated and cationic CLZ-ALA-loaded SLN were prepared and compared. Suspensions with a narrow size distribution of particles of mean size below 150 nm were obtained, having slight negative or highly positive zeta potential values, due to the presence of the cationic lipid, which also increased nanoparticles stability, as confirmed by Turbiscan® results. Calorimetric studies confirmed the rationale of separately delivering the two drugs in a dual-delivery system. Furthermore, they confirmed the formation of SLN, without significant variation in presence of the cationic lipid. In vitro release studies showed a prolonged drug release without the occurrence of any burst effect. In vitro studies performed on 25 strains of Candida albicans showed the antimicrobial drug activity was not altered when it was loaded into lipid nanoparticles. The study has proved the successfully encapsulation of CLZ and ALA in solid lipid nanoparticles that may represent a promising strategy to combine ALA protective effect in the treatment with CLZ.

Biological properties and production of bacteriocins-like-inhibitory substances by Lactobacillus sp. strains from human vagina.

AIMS: The aim of this study was to characterize Lactobacillus strains for their biological properties and amensalistic activities against genital and nongenital pathogens. METHODS AND RESULTS: For the purpose, some special characteristics (H2 O2 , biofilm and antimicrobial substances production) as well as safety properties of 112 lactobacilli were evaluated. All the strains had good amensalistic characteristics, in particular cell-free supernatants of 10 strains showed antibacterial activity against bacteria, as well as Candida sp. Moreover, these 10 strains were excellent biofilm producers. CONCLUSIONS: These results provide evidence for the possible use as probiotics for vaginal co-therapy in case of dysbiosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Recently, the problem of antibiotic resistance is constantly increasing, even though resources and energy are invested in order to increase knowledge on the mechanisms of action. Bacteriocins have a rapid mechanism of action, act at extremely low concentrations, are generally sensitive to proteases and they usually have a narrow killing spectrum; these characteristics reduce the possibility of the bacterium to develop resistance. This study is focused on the feasibility of a high production of antimicrobial substances and their characterization in order to be exploited as a therapeutic alterative or in co-therapy with antibiotics in case of vaginal dysbiosis.

CXCL9/Mig mediates T cells recruitment to valvular tissue lesions of chronic rheumatic heart disease patients.

Rheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection frequently observed in infants from developing countries. Rheumatic heart disease (RHD), the major sequel of RF, leads to chronic inflammation of the myocardium and valvular tissue. T cells are the main population infiltrating cardiac lesions; however, the chemokines that orchestrate their recruitment are not clearly defined. Here, we investigated the expression of chemokines and chemokine receptors in cardiac tissue biopsies obtained from chronic RHD patients. Our results showed that CCL3/MIP1α gene expression was upregulated in myocardium while CCL1/I-309 and CXCL9/Mig were highly expressed in valvular tissue. Auto-reactive T cells that infiltrate valvular lesions presented a memory phenotype (CD4(+)CD45RO(+)) and migrate mainly toward CXCL9/Mig gradient. Collectively, our results show that a diverse milieu of chemokines is expressed in myocardium and valvular tissue lesions and emphasize the role of CXCL9/Mig in mediating T cell recruitment to the site of inflammation in the heart.

Assessment of a new experimental model of isolated right ventricular failure.

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.

[IV Pulmonary trunk reversible banding: analysis of right ventricle acute hypertrophy in an intermittent loading experimental model]. / Bandagem reversível do tronco pulmonar IV: análise da hipertrofia aguda do ventrículo direito em modelo experimental de sobrecarga intermitente.

OBJECTIVES: Adjustable pulmonary trunk (PT) banding device may induce a more physiologic ventricle retraining for the two-stage Jatene operation. This experimental study evaluates the acute hypertrophy (96 hours) of the right ventricle (RV) submitted to an intermittent pressure overload. METHODS: Five groups of seven young goats were distributed according to RV intermittent systolic overload duration (0, 24, 48, 72 and 96 hours). The zero-hour group served as a control group. Echocardiographic and hemodynamic evaluations were performed daily. After completing the training program for each group, the animals were sacrificed for water content and cardiac masses evaluation. RESULTS: There was a significant increase in RV free wall thickness starting with the 48-hour group (p<0.05). However, a decreased RV ejection fraction, associated with an important RV dilation and a significant increase in the RV volume to mass ratio was observed at 24-hour training period, when compared to 96-hour period (p=0.003), with subsequent recovery throughout the protocol. A 104.7% increase in RV mass was observed in the 96-hour group, as compared to the control group, with no differences in water content between these two groups. The daily mean increase in RV mass during the study period was 21.6% +/- 26.8%. The rate of RV mass acquisition for the overall study period of intermittent systolic overload was 0.084 g/h +/- 0.035 g/h. CONCLUSION: Intermittent PT banding has allowed a significant RV mass acquisition in the 96-hour trained group. No myocardial water content changes were observed in this group, suggesting an increased myocardial protein synthesis.

Bandagem reversível do tronco pulmonar IV: análise da hipertrofia aguda do ventrículo direito em modelo experimental de sobrecarga intermitente / IV Pulmonary trunk reversible banding: analysis of right ventricle acute hypertrophy in an intermittent loading experimental model

OBJETIVO: A bandagem ajustável do tronco pulmonar (TP) pode proporcionar treinamento ventricular mais fisiológico para cirurgia de Jatene em dois estágios. Este estudo experimental analisa a hipertrofia aguda (96 horas) do ventrículo direito (VD) submetido à sobrecarga sistólica intermitente. MÉTODOS: Cinco grupos de sete cabritos jovens foram dispostos conforme o tempo de sobrecarga sistólica do VD (0, 24, 48, 72 e 96 horas). O grupo zero hora funcionou como grupo controle. Avaliações ecocardiográficas e hemodinâmicas foram feitas diariamente. Os animais foram sacrificados para avaliação do conteúdo de água e pesagem das massas cardíacas. RESULTADOS: Houve aumento da espessura do VD a partir de 48 horas de treinamento (p<0,05) e rebaixamento da fração de ejeção do VD, com dilatação importante desta câmara nas primeiras 24 horas do protocolo, recuperando-se posteriormente. Houve aumento da relação volume/massa nas primeiras 24 horas do protocolo, em relação ao momento 96 horas (p=0,003). A massa do VD apresentou aumento de 104,7 por cento no grupo 96 horas em relação ao controle. Não houve diferença quanto ao conteúdo de água do VD. A média diária de aumento da massa do VD foi de 21,6 por cento ± 26,8 por cento. A taxa de ganho de massa muscular do VD para todo o período de estudo foi de 0,084 g/h ± 0,035 g/h. CONCLUSÃO: O protocolo de bandagem intermitente do TP permitiu ganho de massa muscular do VD, significativa no grupo de 96 horas de estudo. Esta hipertrofia não foi acompanhada de aumento no conteúdo de água, o que sugere maior síntese protéica nos tecidos cardíacos.

OBJECTIVES: Adjustable pulmonary trunk (PT) banding device may induce a more physiologic ventricle retraining for the two-stage Jatene operation. This experimental study evaluates the acute hypertrophy (96 hours) of the right ventricle (RV) submitted to an intermittent pressure overload. METHODS: Five groups of seven young goats were distributed according to RV intermittent systolic overload duration (0, 24, 48, 72 and 96 hours). The zero-hour group served as a control group. Echocardiographic and hemodynamic evaluations were performed daily. After completing the training program for each group, the animals were sacrificed for water content and cardiac masses evaluation. RESULTS: There was a significant increase in RV free wall thickness starting with the 48-hour group (p<0.05). However, a decreased RV ejection fraction, associated with an important RV dilation and a significant increase in the RV volume to mass ratio was observed at 24-hour training period, when compared to 96-hour period (p=0.003), with subsequent recovery throughout the protocol. A 104.7 percent increase in RV mass was observed in the 96-hour group, as compared to the control group, with no differences in water content between these two groups. The daily mean increase in RV mass during the study period was 21.6 percent ± 26.8 percent. The rate of RV mass acquisition for the overall study period of intermittent systolic overload was 0.084 g/h ± 0.035 g/h. CONCLUSION: Intermittent PT banding has allowed a significant RV mass acquisition in the 96-hour trained group. No myocardial water content changes were observed in this group, suggesting an increased myocardial protein synthesis.

A novel adjustable pulmonary artery banding system for hypoplastic left heart syndrome.

PURPOSE: We describe the first case in which a neonate with hypoplastic left heart syndrome was initially managed using a mini adjustable banding system. DESCRIPTION: Through a mid-sternotomy, a 5-day-old neonate underwent bilateral pulmonary artery banding using this new system, combined with placement of a main pulmonary artery to the innominate artery shunt. EVALUATION: The patient had an uneventful postoperative course. Three percutaneous adjustments of the banding system were necessary to keep the arterial oxygen saturation in the 75% to 85% range. On day 48 of life, she was submitted to stent placement (6 mm) within the atrial septum to treat a restrictive atrial septal defect. Afterward, seven additional percutaneous adjustments of the banding system were necessary. The Norwood operation and the bidirectional Glenn shunt were carried out on the day 106 of life. The bands were removed with no pulmonary artery distortion. CONCLUSIONS: The clinical use of this innovative pulmonary artery banding system was feasible, safe, and effective. This allowed for customization of the pulmonary blood flow according to the underlying clinical needs, resulting in a more precise balance between the pulmonary and systemic circulations.

Effects of a low phosphorus, low nitrogen diet supplemented with essential amino acids and ketoanalogues on serum triglycerides of chronic uremic patients.

The effects were studied of a vegetarian low-protein, low-phosphorus diet supplemented with essential amino acids and ketoanalogues and those of maintenance hemodialysis (MHD) and free diet on the serum triglycerides (STG) of 85 patients with chronic renal failure. Following dietary therapy STG decreased significantly in the 61 male patients (from 185.7 +/- 89.8 to 153.5 +/- 68.7 mg/dl; p less than 0.001), whereas in the females the decrease was not significant (from 189.1 +/- 83.9 to 167.0 +/- 62.2 mg/dl; NS). When patients changed to MHD therapy and free diet STG increased again. We can conclude that the correction of hypogonadism of chronic male uremics largely accounts for the improvement of hypertriglyceridemia, though other factors are likely to contribute.