Morphological and biochemical appraisal of the liver and renal effects of indinavir on rat pregnancy

Since indinavir is currently used in combination with other antiretroviral agents, there is a scarcity of studies in the literature on its single-drug perinatal safety. Thus, we decided to examine the gross maternal and fetal effects of indinavir administered alone during the entire period of rat pregnancy. Forty pregnant animals were assigned at random to four groups (C = control) treated with the drug vehicle (distilled water); the experimental groups were treated with indinavir as follows: E1 = 40 mg/kg; E2 = 120 mg/kg; E3 = 360 mg/kg from "zero" up to the 20th day of gestation. Drug or vehicle were administered daily by gavage. Each group consisted of ten animals. At term-pregnancy, the rats were deeply anesthetized and blood samples were collected for alanine aminotransferase (ALT) and aspartate aminotransferase (AST), creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and routinely processed for histopathological study. Serum ALT activity in the E2 group was significantly higher (p < 0.01) than that of the other groups. The concentration of creatinine in blood was lower in the E2 and E3 groups than in group E1 (p < 0.01), whereas blood urea in group E3 was significantly lower than in the other groups (p < 0.01). Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilation. Maternal kidneys in the E2 and E3 groups revealed vascular dilation around the convoluted tubules. Regarding the biochemical determinations, the alterations observed were mild, without biological relevance, thus indicating that the treatment with indinavir during the entire gestation was essentially devoid of hepatic or renal effects which could result in altered metabolic parameters. It is concluded that indinavir was well tolerated in therapeutic and even in 9-fold higher doses. Notwithstanding, discrete morphological alterations occurred in the maternal compartment, but with no functional expression that could indicate deleterious effects on mothers and/or fetuses.     

Primary chemotherapy with sequential docetaxel followed by docetaxel and epirubicin in large operable breast cancer

Primary chemotherapy is increasingly used in patients with large operable breast cancer. Docetaxel and epirubicin are the most active agents in breast cancer treatment. PURPOSE: To evaluate clinical response rate, breast conserving surgery and pathological response rate in patients with large operable breast cancer treated with docetaxel followed by docetaxel and epirubicin as primary chemotherapy. PATIENTS AND METHODS: Patients with operable breast cancer more than 3 cm in the longest diameter with T2N0, T2N1 and T3N0 disease were enrolled. Patients were treated with three cycles of docetaxel 100 mg/m2 followed by three cycles of docetaxel 75 mg/m2 and epirubicin 90 mg/m2 prior to surgery. RESULTS: Sixty-five patients were enrolled between 09/2002 and 12/2005. The median age was 48.9 years and 72.3% were premenopausal. Median tumour size was 4.26 cm, 10.8% were T3 tumours and 38.5% had clinical positive lymph nodes. Of the tumours 58.5% were grade 1/2, 33.9% ER positive and 21.5% c-erb negative. All six cycles were administered to 62 patients; six cycles were delayed and five had dose reductions. Complete clinical response occurred in 41.5% of patients and partial response in 49.2%. Breast conserving surgery was performed in 30% of patients however it was feasible in 57%. Complete pathological response occurred in both primary tumour and nodes in 28%, and in 34% just in the primary tumour. Nine percent of cases had neutropenia and 7.7% febrile neutropenia, and two cases had a hypersensitivity reaction to docetaxel. One associated treatment death occurred. CONCLUSION: Docetaxel followed by epirubicin and docetaxel as primary chemotherapy results in a high clinical and pathological response rate. The majority of adverse events were predictable and manageable.     

Primary peritoneal borderline tumour: report of an unusual case

Primary peritoneal borderline tumour is a rare lesion, histologically indistinguishable from non-invasive peritoneal implants found in association with ovarian tumours of borderline malignancy. We report a case of a primary peritoneal borderline tumour diagnosed in a 30-year-old patient with pelvic pain, infertility and elevated serum CA-125.     

Prenatal sonographic diagnosis of a rare Cantrell's pentalogy variant with associated open neural tube defect - a case report

Cantrell's pentalogy is a very rare congenital anomaly. The hallmark of this condition is the presence of ectopia cordis and an abdominal wall defect. Its association with craniorachischisis is even more infrequent with just a few cases reported in the literature. The authors describe a case of a prenatal ultrasound diagnosis of Cantrell's pentalogy with posterior encephalocele and spinal dysraphism associated.     

Current Evidence of Watermelon (Citrullus lanatus) Ingestion on Vascular Health: A Food Science and Technology Perspective

The amino acid L-arginine is crucial for nitric oxide (NO) synthesis, an important molecule regulating vascular tone. Considering that vascular dysfunction precedes cardiovascular disease, supplementation with precursors of NO synthesis (e.g., L-arginine) is warranted. However, supplementation of L-citrulline is recommended instead of L-arginine since most L-arginine is catabolized during its course to the endothelium. Given that L-citrulline, found mainly in watermelon, can be converted to L-arginine, watermelon supplementation seems to be effective in increasing plasma L-arginine and improving vascular function. Nonetheless, there are divergent findings when investigating the effect of watermelon supplementation on vascular function, which may be explained by the L-citrulline dose in watermelon products. In some instances, offering a sufficient amount of L-citrulline can be impaired by the greater volume (>700 mL) of watermelon needed to reach a proper dose of L-citrulline. Thus, food technology can be applied to reduce the watermelon volume and make supplementation more convenient. Therefore, this narrative review aims to discuss the current evidence showing the effects of watermelon ingestion on vascular health parameters, exploring the critical relevance of food technology for acceptable L-citrulline content in these products. Watermelon-derived L-citrulline appears as a supplementation that can improve vascular function, including arterial stiffness and blood pressure. Applying food technologies to concentrate bioactive compounds in a reduced volume is warranted so that its ingestion can be more convenient, improving the adherence of those who want to ingest watermelon products daily.     

Troponina I por Percentil 99 da Definição Universal de Infarto do Miocárdio versus Ponto de Corte de Melhor Acurácia em Síndromes Coronárias Agudas

Background Contemporary diagnosis of ACS and risk stratification are essential for appropriate management and reduction of mortality and recurrent ischemic events, in the acute phase of disease and after hospitalization. The Universal Definition of Myocardial Infarction recommends the detection of troponin levels above the 99^th percentile.Objectives To evaluate the occurrence of early death and acute myocardial infarction (AMI) in patients without elevation of troponin (<0.034 ng/mL), patients with mild elevation (above the 99^th percentile [>0.034 ng/mL and <0.12 ng/mL)], and patients with significant elevation of troponin (above the diagnostic cutoff for AMI defined by the troponin kit (≥0.12 ng/mL)]; and to analyze the impact of troponin on the indication for invasive strategy and myocardial revascularization.Methods Cross-sectional cohort study of patients with ACS with assessment of peak troponin I, risk score, prospective analysis of 30-day clinical outcomes and two-sided statistical tests, with statistical significance set at p<0.05.Results A total of 494 patients with ACS were evaluated. Troponin > 99^th percentile and below the cutoff point, as well as values above the cutoff, were associated with higher incidence of composite endpoint (p<0.01) and higher rates of percutaneous or surgical revascularization procedures (p<0.01), without significative difference in 30-day mortality.Conclusions Troponin levels above the 99^th percentile defined by the universal definition of AMI play a prognostic role and add useful information to the clinical diagnosis and risk scores by identifying those patients who would most benefit from invasive risk stratification and coronary revascularization procedures.     

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.     

Bloqueadores do Receptor de Angiotensina Avaliados por Medida de Consultório e Residencial da Pressão Arterial. Estudo TeleMRPA

BackgroundAdequate treatment of arterial hypertension and achieving arterial hypertension goals in are important in reducing cardiovascular outcomes.ObjectivesTo describe angiotensin receptor blockers in monotherapy or double combination therapy and the rate of arterial hypertension control.MethodsThis cross-sectional study evaluated patients who were using angiotensin receptor blockers between 2017 and 2020. Those using three or more antihypertensive drugs were excluded. The analyzed variables included sex, age, body mass index, valid home blood pressure monitoring (HBPM) measurements, casual and HBPM systolic and diastolic blood pressure measurements, blood pressure variability, and antihypertensive and angiotensin receptor blocker class. Paired t, chi-square, and Fisher’s exact tests were used, as well as overlapping 95% confidence intervals and a significance level of 5% (p < 0.05).ResultsOf 17,013 patients, 12,813 met the inclusion criteria, 62.1% of whom were female. The mean number of valid measurements was 23.3 (SD, 2.0). The mean HBPM and casual measurements for systolic blood pressure were 126.8 (SD, 15.8) mmHg and 133.5 (SD, 20.1) mmHg (p <0.001), respectively, while those for diastolic blood pressure were 79.1 (SD, 9.7 mmHg) and 83.6 (SD, 11.9) mmHg (p <0.001), respectively. Losartan was the most common angiotensin receptor blocker and resulted in the highest blood pressure values. Combinations of angiotensin receptor blockers with diuretics or calcium channel antagonists resulted in lower blood pressure values.ConclusionsMore than half of the patients used losartan, although it was the least efficient drug for reducing and controlling blood pressure.     

Smart Bone Graft Composite for Cancer Therapy Using Magnetic Hyperthermia

Magnetic hyperthermia (MHT) is a therapy that uses the heat generated by a magnetic material for cancer treatment. Magnetite nanoparticles are the most used materials in MHT. However, magnetite has a high Curie temperature (Tc~580 °C), and its use may generate local superheating. To overcome this problem, strontium-doped lanthanum manganite could replace magnetite because it shows a Tc near the ideal range (42–45 °C). In this study, we developed a smart composite formed by an F18 bioactive glass matrix with different amounts of Lanthanum-Strontium Manganite (LSM) powder (5, 10, 20, and 30 wt.% LSM). The effect of LSM addition was analyzed in terms of sinterability, magnetic properties, heating ability under a magnetic field, and in vitro bioactivity. The saturation magnetization (M_s) and remanent magnetization (M_r) increased by the LSM content, the confinement of LSM particles within the bioactive glass matrix also caused an increase in Tc. Calorimetry evaluation revealed a temperature increase from 5 °C (composition LSM5) to 15 °C (LSM30). The specific absorption rates were also calculated. Bioactivity measurements demonstrated HCA formation on the surface of all the composites in up to 15 days. The best material reached 40 °C, demonstrating the proof of concept sought in this research. Therefore, these composites have great potential for bone cancer therapy and should be further explored.