Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.

Background/Objectives: This study aimed to evaluate the degradation of omeprazole suspension under various pH conditions and to propose recommendations for preparing compounded suspensions. Given the clinical need for alternative dosage forms for pediatric and geriatric patients and those with dysphagia, the research focused on assessing whether modifications in formulation composition—specifically the inclusion of sodium bicarbonate—could improve omeprazole stability, thus enhancing its bioavailability. Methods: Three formulations were prepared: O1, based on crushed enteric-coated pellets from a commercial product; O2, with crushed pellets suspended in an 8% sodium bicarbonate solution with glycerin; and O3, with pure omeprazole suspended in an 8% sodium bicarbonate solution with glycerin. Release studies were conducted using basket or paddle apparatus under conditions simulating fasted (pH 1.2 and 6.8) and fed (pH 6, 4.5, and 3) gastric and intestinal juices at 37 °C over 120 min. At predetermined intervals, samples were withdrawn and analyzed by a validated HPLC method with UV detection to quantify the released omeprazole. Results: The commercial enteric-coated product showed no release at a low pH, confirming its protective coating. In contrast, formulation exhibited significant degradation in acidic environments. The O2 formulation, benefiting from the buffering effect of sodium bicarbonate, showed improved stability compared to O1. Notably, formulation O3 yielded the highest drug recovery, with approximately 74% released at pH 6 and 65% at pH 6.8, demonstrating significantly better performance, as confirmed by statistical analysis (p < 0.05). Conclusions: The composition of omeprazole suspensions substantially influences the drug stability and release profiles. The O3 formulation, based on pure omeprazole with sodium bicarbonate, is recommended for immediate-release suspensions to enhance bioavailability. Further studies are needed to optimize conditions for pediatric use.

Genetic factors may predispose persons to decreased pain excitability. One of the interesting modulators affecting pain perception may be polymorphisms of the cannabinoid receptor type 1 (CNR1) gene. In this study, we examined the association between three-nucleotide repeats (AAT) polymorphism located in the 3′UTR non-translational region of CNR1 and the patient’s quality of life after total hip arthroplasty. Our study examined the degree of pain sensation, hip function, and the patient’s performance at defined intervals after elective hip replacement due to degenerative changes. The study included 198 patients (128 women and 70 men). The average age was 67 years. PCR genotyping assay was used to identify the (AAT)n triplet repeat polymorphism in the CNR1 gene. The (AAT)n repeat number was determined by sequencing using a standard sequencing protocol. Our study found no statistically significant association between the degree of pain, hip function, and the change in the degree of disability and the (AAT)n polymorphism in the CNR1 gene, no statistically significant correlations between clinical symptoms, the patient’s age, and the number of AAT repeats, no association between the length of the allele and the degree of pain, hip function, and the change in disability.

Background: Diclofenac is a phenylacetic acid derivative classified as a non-selective COX inhibitor. Similar to other NSAIDs, it is characterized by anti-inflammatory, antipyretic, and analgesic effects. Long-term therapy with diclofenac might also lead to severe gastrointestinal, renal, or cardiovascular systems disorders. Aim of the study was to compare own formulation prepared from pharmaceutical raw materials with ready-to-use diclofenac product. Methods: In the in vitro permeation experiments, human skin was excised from the abdomen of living patients as a result of plastic surgery. The transdermal semi-solid formulations were compounded using Pentravan^®, a ready-to-use transdermal base and hydrophilic gel base (Celugel). In vitro Penetration Studies, HPLC analysis, optical microscopy imaging, and a spreadability test were conducted. Rheological analysis provided insights into flow behavior, structure, and thixotropy. Results: Combination of Celugel with diclofenac sodium and the addition of substances acting as absorption enhancers, e.g., menthol, may provide an interesting alternative for enteral drugs, especially in patients with multimorbidity and polypharmacy. Conclusions: Topical diclofenac sodium with of addition of permeation enhancers like menthol might provide higher drug concentrations in the surrounding tissues and better analgesic and anti-inflammatory effects in compare to commercially available product and may provide optimum effectiveness with minimal risk of adverse effects, particularly in elderly and polymedicated patients.

Background: The COMT gene encodes the enzyme catechol-O-methyltransferase, which is a key modulator of dopaminergic and adrenergic neurotransmission. Hip osteoarthritis is accompanied by reduced mobility and some level of disability. In our study, we analyzed the association between some COMT gene polymorphisms and reduced mobility in patients after total hip replacement (THR). Methods: The operative procedures were performed on 195 patients with symptomatic and radiologically advanced hip osteoarthritis. In the postoperative follow-up, we assessed hip function with the Harris Hip Score (HHS) and the degree of disability with the Oswestry Disability Index (ODI). These procedures were repeated three times at defined intervals (one week, six weeks, and six months) after the total hip replacement. Genomic DNA was extracted from peripheral blood. SNPs in the COMT genes rs4680:A>G, rs6269:A>G, rs4633:C>T, and rs4818:C>G were genotyped. Results: Our findings suggest an association between COMT gene variability and the level of disability measured by the Oswestry Disability Index (ODI) in patients after total hip replacement (THR). Conclusions: A higher number of COMT G alleles (rs4818) is an independent factor in a significant reduction in disability degree at both one week and six months after total hip replacement (THR), regardless of age or gender.