Antimicrobial Activity of Novel C2-Substituted 1,4-Dihydropyridine Analogues

The antimicrobial activity of 3-methyl-5-isopropyl (or ethyl) 6-methyl-4-nitrophenyl-1,4-dihydropyridine-3,5-dicarboxylate derivatives was evaluated. Prokaryotes (bacteria) appeared to be more sensitive to their antimicrobial activity than were eukaryotes (filamentous fungi). The best antibacterial activity was shown by derivative 33, which was able to inhibit the growth of Mycobacterium smegmatis (MIC₃₃ = 9 μg.ml⁻¹), Staphylococcus aureus (MIC₃₃ = 25 μg.ml⁻¹), and Escherichia coli (MIC₃₃ = 100 μg.ml⁻¹). In addition, derivative 4 demonstrated its antibacterial power on the acid-fast bacterial species M. smegmatis and on Gram-positive S. aureus. Focusing on the structure-activity relationship, it appears that the increase in the substituent bulk at the C2 position improved the antibacterial activity of the set of compounds studied. Derivatives 33 and 4, carrying 2-cyano-3-oxo-3-phenylprop-1-en-1-yl and allyliminomethyl groups, respectively, showed significantly higher inhibition activities on all tested microorganisms in comparison with the rest of the derivatives. This enhancement was also in good correlation with different log P values (lipophilicity parameter).     

Adherence and satisfaction of rheumatoid arthritis patients with a long‐term intensive dynamic exercise program (RAPIT program)

Objective

To evaluate adherence and satisfaction of patients with rheumatoid arthritis (RA) in a long‐term intensive dynamic exercise program.

Methods

A total of 146 RA patients started an intensive (strength and endurance training for 75 minutes, twice a week, for 2 years) exercise program (Rheumatoid Arthritis Patients In Training) aimed at improving physical fitness. Program attendance and satisfaction were examined. Additional assessments at baseline were done to find possible predictors of attendance.

Results

Median (interquartile range) age and disease duration of the patients were 54 (45–61) and 5 (3–10) years, respectively. After 2 years, 118 (81%) patients still participated in an exercise class. The median attendance rate of all patients was 74%. Low attendance was weakly associated with high disease activity, low functional ability, and low quality of life at baseline but not with the severity of joint damage at baseline. At the end, 78% of all participants would (strongly) recommend the program to other RA patients.

Conclusion

Adherence and satisfaction of RA patients with an intensive dynamic exercise program over a prolonged time can be high. Disease severity parameters do not strongly predict the compliance of participants in an intensive exercise program.

     

FIP Perspectives: Realising global patient safety goals requires an integrated approach with pharmacy at the core

Patient safety is becoming increasingly recognised as a top priority for action that requires a collective and coordinated response. The leading cause of harm or injury in health care systems is medication errors. As medicines experts, the pharmacy workforce plays a key role in minimising medication errors and mitigating the global challenge of patient safety. Pharmacists’ involvement in ensuring patient safety is crucial. Pharmacists are charged with the responsibility to ensure that when a patient receives and uses a medicine, it will not cause harm or death. The International Pharmaceutical Federation (FIP) recognises the critical role the pharmacy plays in realising global, regional and national patient safety goals; and works with its partners, stakeholders and members around the world to advocate for the role of pharmacy in achieving this global patient safety agenda and to envision a world of safe access to medicines and care.     

Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles

Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxicity studies we discuss potential mechanisms of genotoxicity induced by NPs. Various factors that may influence genotoxic response, including physico-chemical properties and experimental conditions, are highlighted. From 4346 articles on NP toxicity, 112 describe genotoxicity studies (94 in vitro, 22 in vivo). The most used assays are the comet assay (58 in vitro, 9 in vivo), the micronucleus assay (31 in vitro, 14 in vivo), the chromosome aberrations test (10 in vitro, 1 in vivo) and the bacterial reverse mutation assay (13 studies). We describe advantages and potential problems with different methods and suggest the need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo.     

Association of CD33 rs3865444:C˃A polymorphism with a reduced risk of late‐onset Alzheimer's disease in Slovaks is limited to subjects carrying the APOE ε4 allele

CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late‐onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid β42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction–restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25?0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61?1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C?A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4.     

Perfect date—the review of current research into molecular bases of mammalian fertilization

Fertilization is a multistep process during which two terminally differentiated haploid cells, an egg and a sperm, combine to produce a totipotent diploid zygote. In the early 1950s, it became possible to fertilize mammalian eggs in vitro and study the sequence of cellular and molecular events leading to embryo development. Despite all the achievements of assisted reproduction in the last four decades, remarkably little is known about the molecular aspects of human conception. Current fertility research in animal models is casting more light on the complexity of the process all our lives start with. This review article provides an update on the investigation of mammalian fertilization and highlights the practical implications of scientific discoveries in the context of human reproduction and reproductive medicine.