Clinical recurrence and antiplatelet drug resistance among patients with lower limb ischemia.

There is a high prevalence rate of peripheral artery disease worldwide, with estimated cases exceeding 200 million. Most patients are under-diagnosed and under-treated, and there is a lack of knowledge regarding the best therapeutic regimen and therapy duration, which leads to many cases of recurrence, complications, and amputations. This study aims to explore clinical recurrence, which was defined as the worsening of chronic peripheral artery disease requiring hospital admission, and its relationship with antiplatelet drug resistance among patients with lower limb ischemia. This cohort study includes both retrospective and prospective recruitment of patients with chronic lower limb ischemia. Platelet aggregation tests were offered to the patients. Between February 2018 and November 2020, 147 patients were recruited from King Abdullah University Hospital and followed up for at least 1 year. Platelet aggregation tests were done for 93 patients who agreed to participate in this part of the study. The prevalence of chronic lower limb ischemia was higher in young male patients who are current smokers with co-morbid diseases such as hypertension, diabetes mellitus, and/or dyslipidemia. There was a significant association only of clinical recurrence with younger age (P = .011) and with low platelets count in severe stages of the disease (P = .047). No significant association was found in terms of laboratory resistance. The clinical recurrence rates of chronic lower limb ischemia were higher in younger patients and among those with low platelet counts in the severe stages of the disease. Despite the laboratory responsiveness to anti-platelet therapy, we observed significant clinical resistance and increased recurrence rates.

Effects of CYP2B6 Genetic Variants on the Propofol Dose and Response among Jordanian Arabic Patients Undergoing General Anesthesia.

BACKGROUND: Propofol is the most commonly used general anesthetic drug in many countries, including Jordan. However, there is a wide variation in the propofols' dose and response among the patients. Genetic variation in the cytochrome (CYP) 2B6 gene affects propofol metabolism and might affect propofol dose and response. AIMS: This study aimed to determine the influence of major genetic alleles of the CYP2B6 gene, CYP2B6*2A, *6A, *3, *4A, and *5A, on the required propofol dose and response among Jordanian Arabic patients attending The University of Jordan Hospital. METHODS: A total of 155 patients were administrated propofol. The propofol response was evaluated by monitoring the time to reach the bispectral index of 60 (BIS60) for every patient. The CYP2B6 genetic variants were genotyped by polymerase chain reaction followed by restriction through specific enzymes for CYP2B6 variants. RESULTS: It is found that patients with variant CYP2B6*2A and *4A alleles required significantly (P < 0.05) lower propofol doses, while patients with variant CYP2B6*6A, *3, and *5A alleles required higher propofol doses in comparison with patients carrying the wild CYP2B6 alleles. Patients with variant CYP2B6*2A and *3 alleles needed a significantly (P < 0.05) shorter while patients with variant CYP2B6*5A allele needed longer time of BIS60 than patients with wild CYP2B6*2A, *3, and *5A alleles. CONCLUSION: It is concluded that CYP2B6 genetic variants affect propofol dose and can explain, at least partly, the inter-individual variation in the propofol response. Further clinical studies with a larger sample size are needed to confirm the findings of this study.

Effects of the genetic variants of organic cation transporters 1 and 3 on the pharmacokinetics of metformin in Jordanians.

BACKGROUND: Human response to the antidiabetic metformin is influenced by some factors, such as genetic variants in the SLC22A genes. This study aimed to determine the frequency of main SLC22A1 and SLC22A3 genetic variants and their influence on metformin pharmacokinetics among healthy unrelated Arab Jordanians. PATIENTS AND METHODS: The SLC22A1 and SLC22A3 genes were genotyped by DNA sequencing of exons 1, 3, 7, and 9 in the SLC22A1 gene and exons 6, 7, and 9 in the SLC22A3 gene. Then, a clinical pharmacokinetic study was conducted on 26 healthy volunteers. The pharmacokinetic parameters were calculated using non-compartmental model analysis. The study was an open-label, randomized study with single 1000 mg metformin administration. RESULTS: Results showed that volunteers with SLC22A3 rs8187722 variant had higher (χ2, p<0.05) metformin Cmax and AUC values than the wild SLC22A3 volunteers, whereas T½ and Kel were not affected. In addition, volunteers with the heterozygote SLC22A3 rs2292334 variant had significantly higher (χ2, p<0.05) metformin Cmax and AUC and lower Kel values than the wild-type SLC22A3 genotype. CONCLUSIONS: The SLC22A3 rs8187722 and rs2292334 genetic variants affected metformin pharmacokinetics among a clinical sample of Jordanians. The findings may increase our understanding of the inter-individual and inter-ethnic variations in metformin response.

DNA threading bis(9-aminoacridine-4-carboxamides): effects of piperidine sidechains on DNA binding, cytotoxicity and cell cycle arrest.

We describe the synthesis of a series of DNA-threading bis(9-aminoacridine-4-carboxamides) comprising ethylpiperidino and N-methylpiperidin-4-yl sidechains, joined via neutral flexible alkyl chains, charged flexible polyamine chains and a semi-rigid charged piperazine linker. Their cytotoxicity towards human leukaemic cells gives IC(50) values ranging from 99 to 1100 nM, with the ethylpiperidino series generally being more cytotoxic than the N-methylpiperidin-4-yl series. Measurements with supercoiled DNA indicate that they bisintercalate.