Solvent-free microwave-assisted synthesis of aripiprazole

Aripiprazole is a widely used antipsychotic approved by the FDA (Food and Drug Administration) in 2002. Methods for preparation of aripiprazole mainly involve the use of expensive and toxic solvents, and the reaction time can be even several hours long. Our method allows to obtain aripiprazole with a yield of approximately 70–80% over just a few minutes using solvent-free conditions in the presence of PTC (Phase Transfer Catalysts) and microwave radiation

Common variant p.D19H of the hepatobiliary sterol transporter ABCG8 increases the risk of gallstones in children

Introduction Gallstones are increasingly common in children. Genetic analyses of adult cohorts demonstrated that the sterol transporter ABCG8 p.D19H and Gilbert UGT1A1*28 variants enhance the odds of developing gallstones. The genetic background of common lithiasis in children remains unknown. Methods Overall, 214 children with gallstone disease (1 month–17 years, 107 boys) were inclueded. The control cohorts comprised 214 children (age 6–17 years, 115 boys) and 172 adults (age 40–92 years, 70 men) without gallstones. The ABCG8 p.D19H and UGT1A1*28 polymorphisms as well as ABCB4 (c.504C>T rs1202283, c.711A>T rs2109505) and NPC1L1 variants (p.V1296V rs217434, c.−18C>A rs41279633) were genotyped using TaqMan assays. Serum concentrations of plant sterols and cholesterol precursors were measured by gas chromatography/mass spectrometry. Results The ABCG8 risk allele was associated with an increased risk of stones (OR = 1.82, p = .03). Children carrying the p.19H allele presented with lower serum concentrations of surrogate markers of intestinal cholesterol absorption and decreased ratios of phytosterols to the cholesterol precursor desmosterol. Carriers of the common NPC1L1 rs217434 allele had an increased gallstone risk compared with stone-free adults (OR 1.90, p < .01). This variant also affected the ratio of phytosterols to cholesterol precursors (p = .03). Other tested variants were not associated with gallstone risk. Conclusions The p.D19H ABCG8 and, to a lesser extent, NPC1L1 rs217434 variants increase the risk of early-onset gallstone formation. These results point to the presence of a common lithogenic pathway in children and adults

Polish 2010 growth references for school-aged children and adolescents

Growth references are useful in monitoring a child's growth, which is an essential part of child care. The aim of this paper was to provide updated growth references for Polish school-aged children and adolescents and show the prevalence of overweight and obesity among them. Growth references for height, weight, and body mass index (BMI) were constructed with the lambda, mu, sigma (LMS) method using data from a recent, large, population-representative sample of school-aged children and adolescents in Poland (n = 17,573). The prevalence of overweight and obesity according to the International Obesity Taskforce definition was determined with the use of LMSGrowth software. Updated growth references for Polish school-aged children and adolescents were compared with Polish growth references from the 1980s, the Warsaw 1996–1999 reference, German, and 2000 CDC references. A positive secular trend in height was observed in children and adolescents from 7 to 15 years of age. A significant shift of the upper tail of the BMI distribution occurred, especially in Polish boys at younger ages. The prevalence of overweight or obesity was 18.7% and 14.1% in school-aged boys and girls, respectively. The presented height, weight, and BMI references are based on a current, nationally representative sample of Polish children and adolescents without known disorders affecting growth. Changes in the body size of children and adolescents over the last three decades suggest an influence of the changing economical situation on anthropometric indices

A new synthetic ultrasound-assisted method for dibenzoepines

In this study, we have developed a new ultrasonic synthesis method of dibenzoepines using olanzapine and quetiapine, which are well-known drugs for the treatment of schizophrenia and bipolar disorder. The method is based on the N-alkylation reaction of the piperazine fragment in tricyclic compounds with methyl iodide or 2-(2-chloroethoxy)ethanol as the alkylating agent, respectively. The synthesis reactions were carried out in an ultrasonic bath with solvents such as acetonitrile or dimethylformamide in the presence of potassium or sodium carbonate or sodium hydroxide and metal-free, ecological phase transfer catalyst at a temperature of 40–50 °C. This allowed us to obtain olanzapine in 1 h (Y = 67%), and quetiapine in 3 h (Y = 72%). An ultrasonic reactor (Qsonica Q700) was used in the synthesis of olanzapine and made it possible to shorten the reaction time to 10 min and obtain 90% yield with very high purity. The developed method allows obtaining compounds in mild conditions and in a short time, thanks to which the process is more ecological than others described in the literature

Mechanochemical Synthesis Method for Drugs Used in the Treatment of CNS Diseases under PTC Conditions

Phase transfer catalysis (PTC) is an excellent possibility in the synthesis of organic compounds as it allows the reactions to be carried out under the conditions of green chemistry, while maintaining high yields and selectivity. The great advantage of these reactions is also the possibility of carrying out the reactions not only under conventional conditions, but also mechanochemically in solvent-free processes. Bearing this in mind, we decided to develop a new method for the synthesis of known biologically active compounds from the group of long-chain arylpiperazines (LCAPs). The first mortar trials were very promising and prompted us to carry out a series of ball mill reactions. One of the technological problems that we encountered while conducting reactions in the ball mill was the difficulty in extracting the post-reaction mixture. We tested the effects of additives improving the insulation of the product, such as, e.g., starch, zeolites, and silica. Research has proven that with appropriate process conditions using TBAB as a catalyst and in the presence of potassium carbonate and a small amount of Zeolite ZSM5 or silica, aripiprazole can be obtained with a yield of 90% in just five minutes. The obtained results are very promising and it is worth considering them as an alternative to the synthesis of other compounds from the LCAPS group

Mechanochemical Synthesis Method for Drugs Used in the Treatment of CNS Diseases under PTC Conditions

Phase transfer catalysis (PTC) is an excellent possibility in the synthesis of organic compounds as it allows the reactions to be carried out under the conditions of green chemistry, while maintaining high yields and selectivity. The great advantage of these reactions is also the possibility of carrying out the reactions not only under conventional conditions, but also mechanochemically in solvent-free processes. Bearing this in mind, we decided to develop a new method for the synthesis of known biologically active compounds from the group of long-chain arylpiperazines (LCAPs). The first mortar trials were very promising and prompted us to carry out a series of ball mill reactions. One of the technological problems that we encountered while conducting reactions in the ball mill was the difficulty in extracting the post-reaction mixture. We tested the effects of additives improving the insulation of the product, such as, e.g., starch, zeolites, and silica. Research has proven that with appropriate process conditions using TBAB as a catalyst and in the presence of potassium carbonate and a small amount of Zeolite ZSM5 or silica, aripiprazole can be obtained with a yield of 90% in just five minutes. The obtained results are very promising and it is worth considering them as an alternative to the synthesis of other compounds from the LCAPS group

Leptin and Adiponectin Serum Levels from Infancy to School Age: Factors Influencing Tracking

Background: Early adiponectin and leptin in children correlate with those measured at a later age. Prenatal and early life factors may influence the pattern of leptin and adiponectin longitudinal changes. We aimed to identify subgroups of children with distinct trajectories of leptin and adiponectin over the first eight years of life, and to explore determinants predisposing an individual to be included in a specific trajectory class. Methods: The analysis was based on data obtained from the EU Childhood Obesity Project (CHOP) cohort. The current study involved 459 children with adiponectin and leptin measured at 6 months, 5 and 8 years of age. Results: Three groups of leptin trajectories were identified: low-decreasing, medium-stable, and high-increasing, and two trajectory groups for adiponectin: lower and higher. The risk to be classified in the high-increasing group was higher than in the low-decreasing group for female gender (OR 10.67; 95% CI 4.94-23.05; p < 0.001); formula feeding (OR 3.34; 95% CI 1.11-10.09; p < 0.05); maternal overweight (OR 4.43; 95% CI 2.20-8.94; p < 0.001); and smoking in pregnancy (OR 4.14; 95% CI 2.07-8.29; p < 0.001). No predictors for being in the higher vs. lower adiponectin group were discovered. Conclusions: Mothers' smoking during pregnancy, maternal overweight, and formula feeding distinguished different courses of leptin trajectories; but the effect may be associated with changes in adiposity.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Longitudinal Associations between Food Parenting Practices and Dietary Intake in preschool Children: The ToyBox Study

Introduction Food Parenting Practices (FPPs) include the practices parents use in the act of feeding their children, which may further influence their health. Objectives To assess associations between changes in FPPs (permissiveness, food availability, guided choices, water encouragement, rules and limits and the use of food as reward) over 1 year and dietary intake (water, energy-dense/nutrient-poor and nutrient-dense foods) at follow-up in 4- to 6-year-old preschool-aged children. Methods Longitudinal data from the control group of the ToyBox study, a cluster-randomized controlled intervention study, was used (NCT02116296). Multilevel ordinal logistic regression analyses including FPP as the independent variables and dietary intake as outcome. Results Nine hundred sixty-four parent-child dyads (50.5% boys and 95.0% mothers) were included. Limited changes on the use of FPPs were observed over time. Nevertheless, in boys, often having F&amp;V at home was associated with higher F&amp;V consumption (OR = 6.92 [1.58; 30.38]), and increasing home availability of F&amp;V was directly associated with higher water consumption (OR = 7.62 [1.63; 35.62]). Also, not having sweets or salty snacks available at home was associated with lower consumption of desserts (OR = 4.34 [1.75; 10.75]). In girls, having F&amp;V availability was associated with higher F&amp;V consumption (OR = 6.72 [1.52; 29.70]) and lower salty snack consumption (OR = 3.26 [1.50; 7.10]) and never having soft drinks at home was associated with lower consumption of sweets (OR = 7.89 [6.32; 9.86]). Also, never being permissive about soft drink consumption was associated with lower soft drink consumption (OR = 4.09 [2.44; 6.85]). Conclusion Using favorable FPPs and avoiding the negative ones is prospectively associated with healthier dietary intake, especially of F&amp;V, and less intake of soft drinks, desserts, and salty snacks