Trends in Mortality from Ischemic Heart Disease in the Region of the Americas, 2000–2019

Background:In latest decades, mortality rates from ischemic heart disease (IHD) had declined steadily in most of the world as a consequence of improvements in prevention and therapy.Objective:The aim of this study was to analyze trends in mortality caused by IHD in the region of the Americas from 2000 to 2019.Methods:Estimates of the age-adjusted mortality rate (AAMR) due to IHD were extracted from the Data Portal on Noncommunicable Diseases, Mental Health, and External Causes (ENLACE), Pan American Health Organization. We used Joinpoint regression to analyze significant changes in mortality trends by country, gender, geographical sub-region, and country income, according to the World Bank classification. We also calculated the average annual percent change (AAPC) mortality rate for the overall period in the Americas as a whole and by country and sub-region.Results:In the region of the Americas, the AAMR from IHD decreased from 117.80 (95% uncertainty interval (UI)) 106.64–135.90) in 2000 to 73.64 (62.65–92.66) per 100,000 in 2019. In males, from 149.08 (95% UI 138.23–168.08) to 96.02 (95% UI 83.48–117.19) and in females 92.36 (95% UI 81.35–109.42) to 54.84 (95% UI 45.28–71.76). The AAPC mortality rate in the region decreased –2.5% (95% CI: –2.7, –2.3), with joinpoints in 2007 and 2012, –2.3% (95% CI: –2.5, –2.1) in men and –2.7% (95% CI: –3.0, –2.5) in women. According to the sub-region analysis, the highest decrease was recorded in North America, AAPC –3.1% (95% CI: –3.3, –3.0) with one joinpoint in 2011, whereas there was a stagnation of the mortality rate in Central America, Mexico, and Latin Caribbean with an AAPC of 0.1 (–0.2, 0.3) with one joinpoint in 2007.Conclusions:Age-adjusted mortality rate from IHD between 2000 and 2019 has decreased in the region of the Americas. However, different trends were observed, North America had the highest reduction in AAPC, while Central America, Mexico, and Latin Caribbean Region had a stagnation. This trend was highly influenced by country income.     

Mecanismos moleculares de los efectos benéficos de la alicina sobre la enfermedad cardiovascular

Cardiovascular diseases (CVD) include a group of diseases whose common denominator is the affection of the blood vessels, heart, and heart rate. The treatment of CVD represents high costs to the health systems and is focused on the control of risk factors. Despite the existence of a great variety of treatments of the CVD, these continue as the main cause of mortality mainly due to the multifactorial origin, and therefore more than one drug is required. In this context, allicin, a compound derived from garlic, has shown regulate the expression of signaling pathways and risk factors associated with the progression of CVD. Therefore, the objective of this work is to review the cellular and molecular mechanisms through which allicin exert its therapeutic effects and to describe the scientific evidences why allicin represents a potential candidate to assist in the treatment of CVD.     

Effect of d-amphetamine repeated administration on rat antioxidant defences

The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances (TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ. A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx, GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-β-d-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences. The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs. Received: 19 October 1998 / Accepted: 11 January 1999     

Synthesis and purification of the aflatoxin B1-lysine adduct

This work reports the chemical synthesis of aflatoxin B₁ (AFB₁)-lysine based on procedures available in the literature, but using lysine without a protection group in the α-amine group. AFB₁-exo-8,9-epoxide was obtained by epoxidation of AFB₁ with chloroperoxybenzoic acid in dichloromethane and phosphate buffer. Purification and identification of the AFB₁-lysine were conducted by liquid chromatography (LC), and its structure was confirmed by LC with mass spectrometer and diode-array detection. The preparation of AFB₁-lysine using lysine without a protection group in the α-amine group was completed in 24?h, being a practical modification of available methods that can be reproduced in analytical laboratories.     

Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae

Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25 microg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=10 and 16, respectively). The extracts from Desmopsis panamensis, Pseudomalmea boyacana, Rollinia exsucca and Rollinia pittieri showed good antiplasmodial activity (IC50 < 10 microg/ml). No correlation between antiplasmodial activity and inhibition of beta-hematin production was found. The present study gives specific and useful information about antiprotozoal and cytotoxic activities of some Annonaceae extracts. Results presented here also demonstrate which plants and/or plant parts could be useful in the treatment of leishmaniasis, Chagas' disease and malaria.     

Phase II study of preoperative radiotherapy and concomitant weekly intravenous oxaliplatin combined with oral capecitabine for stages II–III rectal cancer

Introduction

A prospective phase II study was conducted to assess the clinical activity and tolerability of oxaliplatin, capecitabine, and radiotherapy (RT) for neoadjuvant therapy of stages II?CIII rectal cancer.

Materials and methods

Patients with histologically confirmed stages II?CIII (T3?CT4 and/or N+) resectable rectal adenocarcinoma were eligible. Capecitabine was administered at 825?mg/m² twice daily for 5?days/week and oxaliplatin at 50?mg/m² on day 1 weekly for 5?weeks starting the first day of RT (before RT). RT consisted of a total dose of 45?Gy delivered in 25 fractions of 1.8?Gy, 5?days per week, for 5?weeks.

Results

A total of 46 patients were included (35 male, 10 female, median age 62?years). TNM Stage was T3 in 43 patients and T4 in 2. Twenty-eight patients had suspected nodal involvement. The intended chemoradiation treatment was completed in 94?% patients. Grade 3/4 toxicity included lymphocytopenia (6 patients), diarrhea (4 patients), emesis (2 patients), asthenia (3 patients), anorexia (1 patient), and hepatic toxicity (1 patient). Grade 1 neurotoxicity occurred in 18 patients, Grade 2 neurotoxicity in 3, and Grade 1 palmoplantar erythrodysesthesia in 2. Forty-two patients underwent surgery (complete resection 95?%, sphincter-saving operation 55?%). The overall pathologic response rate was 83?%, with a pathologic complete response (pCR) rate of 11.9?% (95?% CI 4.0?C25.6).

Conclusions

The pCR rate observed with oxaliplatin plus capecitabine and RT did not reach the pre-specified criteria of efficacy in this trial, which is in line with recent results of randomized phase III trials.     

Baccharis trimera: effect on hematological and biochemical parameters and hepatorenal evaluation in pregnant rats

AIM OF THE STUDY: This investigation evaluated the effect of a hydroethanolic extract of Baccharis trimera on pregnant Wistar rats, once the plant is well-known consumed in pregnancy and little is known on its potentially toxic effects on pregnant women. MATERIAL AND METHODS: Thirty-five female rats were distributed into three groups. Those in treatments 1 and 2 were given 8.4 mg/kg of the extract orally from gestational day (GD) 1 to 19 and from GD 6 to 15, respectively, whereas those in the control group received distilled water orally from GD 1 to 19. Body weights were recorded on GD 1, 6, 15, and 20. On GD 20 animals were anesthetized, blood samples were collected and maternal livers, kidneys, and spleens were weighed and processed for histological studies. RESULTS: No clinical signs of maternal toxicity and no changes in hematological parameters were observed. Urea levels and kidney weights differed significantly between animals receiving treatment 1 and controls. Histopathological alterations were found in kidneys and livers in both treatment groups. CONCLUSIONS: The hydroethanolic extract of Baccharis trimera administered to pregnant rats at 8.4 mg/kg was toxic to maternal kidney and liver cells, although such alterations are reversible once administration is discontinued.     

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.