New Compounds Hybrids 1H‐1,2,3‐Triazole‐Quinoline Against Plasmodium falciparum

Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost‐effective antimalarial drug with a relatively robust safety profile, or therapeutic index. However, chloroquine is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of chloroquine‐resistant strains, which have also been reported for Plasmodium vivax. However, the activity of 1,2,3‐triazole derivatives against chloroquine‐sensitive and chloroquine‐resistant strains of P. falciparum has been reported in the literature. To enhance the anti‐P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline‐1H‐1,2,3‐triazole hybrids with different substituents in the 4‐positions of the 1H‐1,2,3‐triazole ring, which were assayed against the W2‐chloroquine‐resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone, chloroquine‐resistant, with IC₅₀ values ranging from 1.4 to 46 μm . None of these compounds was toxic to a normal monkey kidney cell line, thus exhibiting good selectivity indexes, as high 351 for one compound ( 11 ).     

Postnatal development of pups from nursing rats treated with Gingko biloba

The Gingko biloba extract is contraindicated during pregnancy and lactation due to the lack of information about its effects on these reproductive phases. Previous studies have shown that G. biloba extract contains components with estrogenic and antiestrogenic activities, thus nursing dams treated with the extract of this plant could show reduction in milk production, resulting in malnutrition and poor development of pups. This work analyzes the postnatal development of pups, whose mothers were treated with G. biloba extract during the lactation period. Nursing Wistar rats received 3.5 mg/kg/day of G. biloba aqueous extract, corresponding to the highest human dose. Clinical signs of maternal toxicity were evaluated. The growth rate, viability, survival during treatment and lactation indices of the pups were calculated. The physical, motor and sensorial development of the pups was also evaluated. No maternal signs of toxicity were observed. As there were no biological differences between control and G. biloba treated pups, it is possible to assume that, in this experimental design, the administration of G. biloba aqueous extract to nursing rats during the lactation period seems to be devoid of toxic effect to mothers and to the physical, motor and sensory development of the pups.     

KIT activation in uterine cervix adenosquamous carcinomas by KIT/SCF autocrine/paracrine stimulation loops

ObjectivesUterine adenosquamous carcinoma (ASC) is an uncommon, yet, one of the most aggressive cervical cancer subtype. The successful treatment of some tumors, such as gastrointestinal stromal tumors (GISTs), by anti-KIT inhibitors fosters the study of this receptor tyrosine kinase in other malignancies. In the present study, we intended to molecularly characterize KIT in ASC.MethodsIn a series of 30 cases, we studied KIT (CD117), KIT phosphorylated / activated form, as well as KIT ligand, stem cell factor (SCF), by immunohistochemistry. We further screened for KIT hotspot mutations (exon 9, 11, 13 and 17) by PCR-SSCP and for KIT gene amplification by Quantitative real-time PCR in CD117 positive cases.ResultsWe observed CD117 expression in ～ 13% of cases, with ～ 7% co-expressing SCF, which resulted in KIT phosphorylation/activation. No KIT activating mutations or gene amplification were found, despite the presence of 4q aneuploidy in one case.ConclusionsThis is the first study assessing KIT activation and molecular alterations in a large series of rare ASC. Our findings showed the absence of KIT molecular alterations and suggested the presence of KIT activation in a small proportion of cases through KIT/SCF co-expression.     

Molecular analysis of the β-catenin gene in patients with the Mayer-Rokitansky-Küster-Hauser syndrome

Purpose

To study the β-catenin gene in a group of Mayer-Rokitansky-Küster-Hauser patients.

Methods

Twelve patients with the Mayer-Rokitansky-Küster-Hauser syndrome were included in this study. DNA was extracted from peripheral blood and the region codifying β-catenin GSK-3β phosphorylation sites on exon 3 was amplified. PCR products were purified and directly sequenced.

Results

No mutations were found in the GSK-3β phosphorylation sites on exon 3 of β-catenin gene in this group of patients with the MRKH syndrome.

Conclusions

β-catenin gene mutations are an unlikely cause of the MRKH syndrome.     

Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix

OBJECTIVE: We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated. METHODS: We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40. RESULTS: Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells. CONCLUSIONS: Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.     

A new heparin fragment decreases liver ischemia-reperfusion injury

<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca²⁺,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1],     

Baixa Concordância entre a Classificação da NYHA e as Variáveis do Teste de Exercício Cardiopulmonar em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida

BackgroundThe New York Heart Association (NYHA) functional classification is the most commonly used classification system for heart failure (HF), whereas cardiopulmonary exercise testing (CPET) is the gold standard for functional status evaluation in HF.ObjectiveThis study aimed to analyze correlation and concordance between NYHA classes and CPET variables.MethodsHF patients with clinical indication for CPET and ejection fraction (EF) < 50% were selected. Correlation (Spearman coefficient) and concordance (kappa) between NYHA classification and CPET-based classifications were analyzed. A p < 0.05 was accepted as significant.ResultsIn total, 244 patients were included. Mean age was 56 ± 14 years, and mean EF was 35.5% ± 10%. Distribution of patients according to NYHA classification was 31.2%% class I, 48.3% class II, 19.2% class III, and 1.3% class IV. Correlation (r) between NYHA and Weber classes was 0.489 (p < 0.001), and concordance was 0.231 (p < 0.001). Correlation (r) between NYHA and ventilatory classes (minute ventilation/carbon dioxide production [VE/VCO₂] slope) was 0.218 (p < 0.001), and concordance was 0.002 (p = 0.959). Spearman correlation between NYHA and CPET score classes was 0.223 (p = 0.004), and kappa concordance was 0.027 (p = 0.606).ConclusionThere was a moderate association between NYHA and Weber classes, although concordance was low. Ventilatory (VE/VCO₂slope) and CPET score classes had a weak association and a low concordance with NYHA classes.     

Evolução e Estado Atual das Práticas de Implante Transcateter de Válvula Aórtica na América Latina – Estudo WRITTEN LATAM

Background:Transcatheter aortic valve replacement (TAVR) is a worldwide adopted procedure with rapidly evolving practices. Regional and temporal variations are expected to be found.Objective:To compare TAVR practice in Latin America with that around the world and to assess its changes in Latin America from 2015 to 2020.Methods:A survey was applied to global TAVR centers between March and September 2015, and again to Latin-American centers between July 2019 and January 2020. The survey consisted of questions addressing: i) center’s general information; ii) pre-TAVR evaluation; iii) procedural techniques; iv) post-TAVR management; v) follow-up. Answers from the 2015 survey of Latin-American centers (LATAM15) were compared with those of other centers around the world (WORLD15) and with the 2020 updated Latin-American survey (LATAM20). A 5% level of significance was adopted for statistical analysis.Results:250 centers participated in the 2015 survey (LATAM15=29; WORLD15=221) and 46 in the LATAM20. Combined centers experience accounted for 73 707 procedures, with WORLD15 centers performing, on average, 6- and 3-times more procedures than LATAM15 and LATAM20 centers, respectively. LATAM centers performed less minimalistic TAVR than WORLD15 centers, but there was a significant increase in less invasive procedures after 5 years in Latin-American centers. For postprocedural care, a lower period of telemetry and maintenance of temporary pacing wire, along with less utilization of dual antiplatelet therapy was observed in LATAM20 centers.Conclusion:Despite still having a much lower number of procedures, many aspects of TAVR practice in Latin-American centers have evolved in recent years, followingthe trend observed in developed country centers.     

Hepatic Resection for Colorectal Metastasis: Impact of Tumour Size

Background Many colorectal liver metastasis patients are denied surgical resection on the basis of tumour size. The aim of this study was to explore the impact of metastasis size on modern liver resection.Methods Using a prospectively collected database, this was a retrospective analysis of 484 consecutive patients who underwent liver resection for colorectal liver metastases between 1993 and 2003. The cohort was divided into two groups: smaller metastases (<8 cm) and larger metastases (≥ 8 cm). Those with larger metastases were then further stratified into big metastases (8–12 cm) and giant metastases (>12 cm). Demographic, pathological, surgical technique and outcome data were compared between the groups.Results There were 88 (18%) patients with metastases measuring 8 cm or larger. There was an association between higher carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels and larger metastases. The actuarial 5-year survival for patients with larger metastases was 38% compared with 42% for smaller metastases (not statistically significant). Patients with giant metastases had poorer overall and disease-free survival (both nonsignificant) compared with those with big metastases: 29% and 28% at 5 years, respectively.Conclusion Patients with colorectal liver metastasis greater than 8 cm and up to 12 cm in size should not be treated differently from those with smaller lesions.