Myocardial tissue expression of mRNA and preoperative neutrophil-lymphocyte ratio in children undergoing congenital heart surgery.

Background: The neutrophil-lymphocyte ratio (NLR) is an easily accessible and inexpensive biomarker that has been shown to predict morbidity and mortality in congenital cardiac surgery. However, its regulatory mechanism remains unclear. This study aims to compare and correlate the tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, and IL-10 messenger RNAs (mRNAs) with the NLR in patients with tetralogy of Fallot (ToF) and ventricular septal defect (VSD). Methods: A prospective translational study was conducted on 10 children with ToF and 10 with VSD, aged between 1 and 24 months. The NLR was calculated from the blood count taken 24 hours before surgery. The expression of these mRNAs was analyzed in the myocardial tissue of the right atrium prior to cardiopulmonary bypass. Results: Patients with ToF exhibited a higher NLR [ToF 0.46 (interquartile range; IQR) 0.90; VSD 0.28 (IQR 0.17); P=0.02], longer mechanical ventilation time [ToF 24 h (IQR 93); VSD 5.5 h (IQR 8); P<0.001], increased use of vasoactive drugs [ToF 2 days (IQR 1.75); VSD 0 (IQR 1); P=0.01], and longer ICU [ToF 5.5 (IQR 1); VSD 2 (IQR 0.75); P=0.02] and hospital length of stays [ToF 18 days (IQR 17.5); VSD 8.5 days (IQR 2.5); P<0.001]. A negative correlation was found between NLR and oxygen saturation (SaO2) (r=-0.44; P=0.002). In terms of mRNA expression, the ToF group showed a lower expression of IL-10 mRNA (P=0.03). A positive correlation was observed between IL-10-mRNA and SaO2 (r=0.40; P=0.07), and a negative correlation with NLR (r=-0.27; P=0.14). Conclusions: Patients with ToF demonstrated a higher preoperative NLR and lower IL-10 mRNA expression by what appears to be a pro-inflammatory phenotype of cyanotic patients.

Functionalization of 2,4-Dichloropyrimidines by 2,2,6,6-Tetramethylpiperidyl Zinc Base Enables Modular Synthesis of Antimalarial Diaminopyrimidine P218 and Analogues.

Two routes to the antimalarial diaminopyrimidine P218 were developed based on the C-6 metalation of suitable 2,4-dichloro-5-alkoxy pyrimidines using (TMP)2Zn·2MgCl2·2LiCl base. One approach involves a late-stage modification of the C-6 position, while the other allows for tail fragment modification of P218. Both routes have proven reliable in synthesizing P218, as well as eight analogues. These innovative strategies have the potential to contribute to the search for new antimalarial drugs.

Takotsubo syndrome after mitral valve surgery

INTRODUCTION: Takotsubo Syndrome is a recurrent diagnosis, however, it's rarely seen post cardiac surgery. The disease usually occurs after physical or emotional stress, most prevalent in post-menopausal women. The clinical features may present similar to acute coronary syndrome, with chest pain and electrocardiogram (ECG) alterations, but with this diagnosis being excluded after the absence of obstructive lesions in coronary angiography and encountering typical echocardiogram findings, such as compensatory apical akinesia and basal compensatory hypercontractility. CASE DESCRIPTION: A 56-year-old woman with a history of rheumatoid arthritis, active smoking and percutaneous mitral valvuloplasty in 2007, presents with functional class II dyspnea and transthoracic echocardiogram (TTECO) showing important mitral regurgitation. Patient was submitted to mitral valve replacement surgery with an mechanical prosthesis on March 2022, without complications. In the immediate postoperative care, the patient evolved with cardiogenic shock, requiring vasoactive drugs. The ECG presented with T-wave inversion of precordial leads and TTECO revealed hypercontractility of the basal segments and akinesia of medium-apical segments, with left ventricular ejection (LVEF) of 20%. During hospitalization the patient gradually improved from cardiogenic shock, with normalization of LVEF to 64%. CONCLUSION: Takotsubo Cardiomyopathy is a reversible condition, characterised by transient ventricular dysfunction, with rare cases described in the context of postoperative care due to valve surgery. The surgical intervention can be considered as a trigger for the development of this syndrome.

Arterite de Takayasu: aneurisma de aorta ascendente e doença coronária em jovem de 19 anos / Takayasu's arteritis: ascending aortic aneurysm and coronary artery disease in a 19-year-old

INTRODUÇÃO: A Arterite de Takayasu constitui doença de múltipla apresentação, podendo acometer diversos sistemas. Acomete principalmente mulheres nas primeiras décadas de vida. MÉTODOS: Trata-se de um relato de caso acerca de paciente jovem com diagnóstico de arterite de takayasu que evoluiu com aneurisma de aorta ascendente e doença arterial coronariana. RESULTADOS: Reportamos um caso de paciente com 19 anos de idade com AT, admitida em serviço de referência em Cirurgia Cardiovascular com diagnóstico de aneurisma de aorta ascendente e doença arterial coronariana grave em artéria coronária direita (CD) e tronco de coronária esquerda (TCE), sendo submetida à implante de enxerto de Dacron supra-coronariano em aorta ascendente (e revascularização miocárdica (CRM) com dupla artéria torácica interna. Evoluiu de forma satisfatória no pós-operatório, seguindo em acompanhamento clínico em nosso serviço. CONCLUSÃO: A apresentação dos pacientes com arterite de takayasu é diversa, em associação com DAC, tornam o seguimento dos pacientes mandatário em centro especializado.

Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells.

Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin chloroacrylamide 13 e displayed the lowest IC50 values for both MCF-7 (0.5 µm) and PC3 (0.3 µm) cells, about 26-fold more potent than goniothalamin (1). Besides its higher potency, compound 13 e also displayed much higher selectivity than goniothalamin. In contrast, goniothalamin isobutyramide 13 c was the most potent analogue against Caco-2 cells (IC50 =0.8 µm), about 10-fold more potent and 17-fold more selective than 1. These results reveal the potential of compounds 13 c and 13 e for further in vivo studies, representing the first goniothalamin analogues with IC50 values in the low micromolar range and high selectivity against MCF-7, Caco-2, and PC3 cancer cell lines.

Late ascending aortic prosthesis infection by porphyromonas pogonae: An unexpected infectious complication

Late complications in ascending aortic surgeries are uncommon and may occur by infectious processes, usually caused by gram positive bacteria. We report a case of aortic prosthesis infection by Porphyromonas pogonae, an anaerobic gram-negative coccobacillus that can grow under microaerobic conditions, three years after ascending aortic reconstruction surgery. (AU)

Late ascending aortic prosthesis infection by Porphyromonas pogonae: An unexpected infectious complication.

Late complications in ascending aortic surgeries are uncommon and may occur by infectious processes, usually caused by gram positive bacteria. We report a case of aortic prosthesis infection by Porphyromonas pogonae, an anaerobic gram-negative coccobacillus that can grow under microaerobic conditions, three years after ascending aortic reconstruction surgery.

Goniothalamin-Related Styryl Lactones: Isolation, Synthesis, Biological Activity and Mode of Action.

This review covers the chemistry and biological aspects of goniothalamin-related styryl lactones isolated from natural sources. This family of secondary metabolites has been reported to display diverse uses in folk medicine, but only a limited number of these compounds have been throughly investigated regarding their biological profile. Herein, we cover the goniothalamin-related styryl lactones having a C6-C3-C4 framework which appeared in the literature for the first time in the period 2000-2017, and the reports on the synthesis, biological activity and mechanism of action which were published from 2007-2017.

Design and Synthesis of Novel Deuterated Ligands Functionally Selective for the γ-Aminobutyric Acid Type A Receptor (GABAAR) α6 Subtype with Improved Metabolic Stability and Enhanced Bioavailability.

Recent reports indicate that α6ß2/3γ2 GABAAR selective ligands may be important for the treatment of trigeminal activation-related pain and neuropsychiatric disorders with sensori-motor gating deficits. Based on 3 functionally α6ß2/3γ2 GABAAR selective pyrazoloquinolinones, 42 novel analogs were synthesized, and their in vitro metabolic stability and cytotoxicity as well as their in vivo pharmacokinetics, basic behavioral pharmacology, and effects on locomotion were investigated. Incorporation of deuterium into the methoxy substituents of the ligands increased their duration of action via improved metabolic stability and bioavailability, while their selectivity for the GABAAR α6 subtype was retained. 8b was identified as the lead compound with a substantially improved pharmacokinetic profile. The ligands allosterically modulated diazepam insensitive α6ß2/3γ2 GABAARs and were functionally silent at diazepam sensitive α1ß2/3γ2 GABAARs, thus no sedation was detected. In addition, these analogs were not cytotoxic, which render them interesting candidates for treatment of CNS disorders mediated by GABAAR α6ß2/3γ2 subtypes.

Tratamento cirúrgico da doença valvar aórtica com anel pequeno / Surgical treatment of aortic valve disease with small ring

O presente estudo visa discutir sobre as possibilidades de tratamento cirúrgico em pacientes com valvopatias aórticas e portadores de anéis aórticos pequenos, abordando indicações e contra-indicações dos principais procedimentos existentes, assim como avaliar as próteses mais utilizadas e sua capacidade. Diferentemente de anéis largos ou normais, uma das complicações mais preocupantes é a desproporção prótese-paciente que ocorre quando a área efetiva do orifício da prótese é fisiologicamente muito pequena em relação a superfície corpórea do paciente...