Malaria remains a global health burden. Elimination of the hypnozoite is required in patients infected with
P. vivax
to prevent relapse. In this report, the safety of a single dose of tafenoquine was ...similar to that of a 14-day course of primaquine in patients with normal G6PD activity.
The learning of new skills is characterized by an initial phase of rapid improvement in performance and a phase of more gradual improvements as skills are automatized and performance asymptotes. ...Using in vivo striatal recordings, we observed region-specific changes in neural activity during the different phases of skill learning, with the associative or dorsomedial striatum being preferentially engaged early in training and the sensorimotor or dorsolateral striatum being engaged later in training. Ex vivo recordings from medium spiny striatal neurons in brain slices of trained mice revealed that the changes observed in vivo corresponded to regional- and training-specific changes in excitatory synaptic transmission in the striatum. Furthermore, the potentiation of glutamatergic transmission observed in dorsolateral striatum after extensive training was preferentially expressed in striatopallidal neurons, rather than striatonigral neurons. These findings demonstrate that region- and pathway-specific plasticity sculpts the circuits involved in the performance of the skill as it becomes automatized.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The genetic influence in obesity prevalence is well described, but the role of genetic markers related to athletic strength/ endurance performance remains controversial. We investigated associations ...between obesity and the genetic polymorphisms alpha-actinin-3 (ACTN3) R577X and angiotensin-converting enzyme (ACE) I/D in schoolchildren aged 4-13 years from Southern Brazil. We collected sociodemographic data from parents through a questionnaire and conducted an anthropometric assessment. DNA was extracted from buccal cells and genotyping was performed by PCR. We found that 1.9% of the individuals were classified as low weight-for-age, 57.6% as normal weight and 40.5% as overweight/ obesity. Regarding allelic distribution, we found that 52.5% of individuals were DD, 30.8% ID, and 16.7% II for ACE; and 38.8% of individuals were RR, 40.2% RX and 21.0% XX for ACTN3. When both polymorphisms were combined, we observed a clear association between the composed genetic profile of these alleles and severe obesity in schoolchildren. Our data suggest that the combined analysis of ACTN3 R577X and ACE I/D polymorphisms may serve as a predictor for the risk of severe obesity in children. These data can contribute to a better understanding of the relationship between these polymorphisms and the body weight development of school-age children.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, and it has a significant prevalence in the male population (X chromosome linked). The ...purpose of this study was to estimate the frequency of impaired fasting glucose and diabetes among G6PD-deficient persons in Manaus, Brazil, an area in the Western Brazilian Amazon to which malaria is endemic. Glucose-6-phosphate dehydrogenase-deficient males had more impaired fasting glucose and diabetes. This feature could be used as a screening tool for G6PD-deficient persons who are unable to use primaquine for the radical cure of Plasmodium vivax malaria.
The western Amazon basin is an important endemic area for malaria by P. vivax. In recent years, several reports showed the treatment failure with chloroquine, which can be related to resistance. The ...assessment of chloroquine resistance requires the evaluation of drug exposure, and when possible, the estimation of the pharmacokinetic parameters. However, there is no data on the pharmacokinetics of chloroquine in this endemic area. Moreover, the influence of the early reappearance of parasites in blood on the exposure to the drug was low exploited in the literature. The present study described the pharmacokinetic parameters of chloroquine in whole blood of adult patients with P. vivax malaria from the western Brazilian Amazon basin and compared the area under the curve (AUC) with the parasitological outcome at day 28. A total of 19 patients with parasite recurrence within 28 days and 20 patients with no recurrence were included in the study. Chloroquine was measured by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters were estimated by non-compartmental modeling. The maximum concentration ranged from 1285 to 2030 ng/mL. The terminal half-life varied from 5.3 to 12.8 days. The volume of distribution from 1090 to 2340 L/kg, and the area under the curve to the last measurable concentration from 247 to 432 ng/mL.h. The pharmacokinetic parameters were similar in both groups, which suggests the lack of influence of early reappearance of parasites on chloroquine pharmacokinetics.
•There is a paucity of studies describing the pharmacokinetics of chloroquine in patients with vivax malaria from the western area of the Amazon basin.•The presence of Plasmodium in peripheral blood probably changes the disposition of chloroquine.•The pharmacokinetics parameters of chloroquine in this population group corroborate the long half-life and the high distribution of the drug.•The reappearance of parasites after 28 days did not change the pharmacokinetic profile of the drug.
Novel and known ellipticine derivatives exhibit important in vitro inhibition of human malaria parasites.
Ellipticine has been shown previously to exhibit excellent in vitro antiplasmodial activity ...and in vivo antimalarial properties that are comparable to those of the control drug chloroquine in a mouse malaria model. Ellipticine derivatives and analogs exhibit antimalarial potential however only a few have been studied to date. Herein, ellipticine and a structural analog were isolated from Aspidosperma vargasii bark. A-ring brominated and nitrated ellipticine derivatives exhibit good in vitro inhibition of Plasmodium falciparum K1 and 3D7 strains. Several of the compounds were found not to be toxic to human fetal lung fibroblasts. 9-Nitroellipticine (IC50=0.55μM) exhibits greater antiplasmodial activity than ellipticine. These results are further evidence of the antimalarial potential of ellipticine derivatives.
Objective: This study aims to review and synthesize scientific evidence to assess the association between excess body weight and depression among adults.
Methods: The systematic research of ...observational studies was held from January to March 2015 on Pubmed, Web of Science, Scopus, Embase, PsycInfo, Psicodoc, Psycarticles, and Isi Web. A prevalence ratio (PR) was adopted as a summary measurement. All articles were evaluated for methodological quality and risk of bias. Metaregression was used to investigate heterogeneity and to identify the variation between the studies in relation to the estimates of the effects.
Results: In this review, 9 studies (N = 171,701) met the inclusion criteria. All articles obtained adequate methodological quality. Most studies had high or unclear risk of bias. Overweight and obesity were assessed by body mass index. People with obesity were 32% more likely to have depression compared to those who were eutrophic (PR = 1.32; 95% confidence interval CI, 1.26-1.38). After a gender analysis, the results showed statistically significant differences in obese versus eutrophic women (PR = 1.36; 95% CI, 1.28-1.34).
Conclusions: There is consistent evidence that overweight or obesity was associated with depression.
Every year, more than thirty thousand tons of Cashew gum (Anacardium occidentale, family: Anacardiaceae) are produced in Brazil; however, only a small amount is used for different applications in ...foodstuff and in pharmaceutical industries. As a raw material for the production of drug delivery systems, cashew gum is still regarded as an innovative compound worth to be exploited. In this work, cashew gum was extracted from the crude exudate of cashew tree employing four methodologies resulting in a light brown powder in different yields (40.61% to 58.40%). The total ashes (0.34% to 1.05%) and moisture (12.90% to 14.81%) were also dependent on the purification approach. FTIR spectra showed the typical bands of purified cashew gum samples, confirming their suitability for the development of a pharmaceutical product. Cashew gum nanoparticles were produced by nanoprecipitation resulting in particles of low polydispersity (<0.2) and an average size depending on the percentage of the oil. The zeta potential of nanoparticles was found to be below 20 mV, which promotes electrostatic stability. Encapsulation efficiencies were above 99.9%, while loading capacity increased with the increase of the percentage of the oil content of particles. The release of the oil from the nanoparticles followed the Korsmeyer–Peppas kinetics model, while particles did not show any signs of toxicity when tested in three distinct cell lines (LLC-MK2, HepG2, and THP-1). Our study highlights the potential added value of using a protein-, lignans-, and nucleic acids-enriched resin obtained from crude extract as a new raw material for the production of drug delivery systems.
Clearing of the dormant liver stage (the hypnozoite) of
P. vivax
malaria is important to prevent the relapse of infection. In this randomized clinical trial, a single dose of tafenoquine is shown to ...have significant activity against the hypnozoite form of
P. vivax
.
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