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.     

L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition

Type 4 phosphodiesterases (PDE4) inhibitors are emerging therapeutics in the treatment of a number of chronic disorders including asthma, chronic obstructive pulmonary disease (COPD) and cognitive disorders. This study delineates the preclinical profile of L-454,560, which is a potent, competitive and preferential inhibitor of PDE4A, 4B, and 4D with IC50 values of 1.6, 0.5 and 1.2 nM, respectively. In contrast to the exclusive binding of cilomilast and the preferential binding of roflumilast to the PDE4 holoenzyme state (Mg2+-bound form), L-454,560 binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. The intrinsic enzyme potency for PDE4 inhibition by L-454,560 also results in an effective blockade of LPS-induced TNFalpha formation in whole blood (IC50 = 161 nM) and is comparable to the human whole blood potency of roflumilast. The cytokine profile of inhibition of L-454,560 is mainly a Th1 profile with significant inhibition of IFNgamma and no detectable inhibition of IL-13 formation up to 1 microM. L-454,560 was also found to be efficacious in two models of airway hyper-reactivity, the ovalbumin (OVA) sensitized and challenged guinea pig and the ascaris sensitized sheep model. Furthermore, L-454560 was also effective in improving performance in the delayed matching to position (DMTP) version of the Morris watermaze, at a dose removed from that associated with potential emesis. Therefore, L-454,560 is a novel PDE4 inhibitor with an overall in vivo efficacy profile at least comparable to roflumilast and clearly superior to cilomilast.     

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.     

Use of phytotherapy in dentistry

Over the past decade, interest in drugs derived from medicinal plants has markedly increased. This study was aimed at a literature review focusing on studies investigating herbal drugs and other natural products, as well as their therapeutic application, side effects and possible drug interactions. Few studies were found to support their rational use in dentistry. Since there is an increasing use of phytotherapeutic agents in dentistry, further studies are needed to evaluate their safety and effectiveness for clinical use.     

The opposing effects of the flavonoids isoquercitrin and sissotrin, isolated from Pterospartum tridentatum, on oral glucose tolerance in rats

The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose levels of normal Wistar rats was investigated in a situation of oral glucose challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the first 30 min after glucose challenge but then the blood glucose levels rose above those of the control group, indicating the presence of compounds with different effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons were identified in the extract by HPLC-ESI-MS(n), four of them being identified for the first time in this species. The isoflavone sissotrin and the flavonol derivative, isoquercitrin, were selected for the oral glucose tolerance test. Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium-dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast, sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In conclusion, these preliminary results indicate that the effect of the extract on blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally, as far as is known, these are the first in vivo results on the acute antihyperglycaemic potential of isoquercitrin.     

The relationship between cesarean delivery and gestational age among US singleton births

The increasing trend of delivering at earlier gestational ages has raised concerns of the impact on maternal and infant health. The delicate balance of the risks and benefits associated with continuing a pregnancy versus delivering early remains challenging. Among singleton live births in the United States, the proportion of preterm births increased from 9.7% to 10.7% between 1996 and 2004. The increase in singleton preterm births occurred primarily among those delivered by cesarean section, with the largest percentage increase in late preterm births. For all maternal racial/ethnic groups, singleton cesarean section rates increased for each gestational age group. Singleton cesarean section rates for non-Hispanic black women increased at a faster pace among all preterm gestational age groups compared with non-Hispanic white and Hispanic women. Further research is needed to understand the underlying reasons for the increase in cesarean section deliveries resulting in preterm birth.