Drug metabolism and personalized therapy最新文献

Objectives: Unani physicians have suggested a wide range of anti-dermatophytic remedies, although the scientific evidence is scarce. Thus, the efficacy and safety of Terminalia chebula Retz. fruit powder mixed with vinegar was compared with terbinafine hydrochloride 1% cream in the treatment of tinea corporis in order to establish the non-inferiority of test drugs.

Methods: The primary outcome measures were change in the presence or absence of hyphae on KOH mount test, change in pruritus severity assessed on 100 mm VAS and change in physician's global assessment. Secondary outcome measure was change in the dermatology life quality index (DLQI). Hemograms, serum creatinine, serum bilirubin, and random blood sugar levels were measured at the baseline and after treatment to ensure the safety of the interventions.

Results: A per-protocol analysis was done on 40 participants (21 in the test group and 19 in the control group). The observed differences in the primary and secondary outcomes between the test and control groups were greater than the non-inferiority margin, signifying that the test drugs were not inferior.

Conclusions: It may be inferred that the trial drug Terminalia chebula Retz. fruit powder mixed with vinegar is not inferior to terbinafine hydrochloride cream in the treatment of tinea corporis.

Objectives: Cassia singueana is widely used in northern Nigeria as an herb for the treatment of enamors ailments. Nevertheless the toxicity of the herb on liver architecture; the hepatic lobule and body weight is yet to be authenticated.

Methods: A total of 24 male Wistar rats with an average weight of 150 g were randomly placed into four groups. Each group consisted of 6 rats. Group A served as the control group while groups B, C and D were given 150, 300, and 450 mg of Cassia singueana leaves extract respectively for 14 days. The animals were weighed before, during and after the treatment phase subsequently, they were sacrificed and the liver tissues were processed and stained using hematoxylin and eosin (H&E) stain, Masson's and Trichrome Stain, Gordon and Sweet's Stain, and Periodic Acid Schiff (PAS)Stain.

Results: There was no significant change in the animal's body weight of in all the groups when compared to the control group. Our histology result showed that Cassia singueana induced vascular lesion and hepatocytes degeneration putatively though mechanism of cell death (apoptosis and necrosis). It was also found that Cassia singueana has no toxic effect on the reticular fibers of the liver. High dose of Cassia singueana was found to induce the deposition of PAS positive materials in hepatocytes.

Conclusions: The Cassia singueana leaves extract induce hepatocyte degeneration and vascular lesion in the hepatic lobules of the wistar rats, without affecting the animals' body weight.

Objectives: Abha Guggulu (AG) is a traditional Ayurvedic herbal formulation used for treating joint disorders and bone fractures. Individually, the ingredients are known for their promising anti-inflammatory and rejuvenating actions. The present study attempts to explore the anti-arthritic potential of AG through an exploratory clinical trial.

Methods: The study was conducted using a quasi-experimental model. The clinical trial has been registered in Clinical Trials Registry of India (registration number: CTRI/2019/09/021354). Osteoarthritis patients of both genders (n=12, 40-70 years age group), meeting the inclusion/exclusion criteria, were recruited in the single arm study. AG was administered in tablet form in a dose of 1.5 g, twice daily. The WOMAC score was used as a primary outcome measure. The WOMAC scale of patients was recorded on 0th, 15th and 30th days of treatment.

Results: At the end of treatment, there was a significant difference in the scores of the outcome measure. As per WOMAC total score, participants were significantly improved (p=0.002) after consuming the drug for 1 month.

Conclusions: Overall, the data indicates significant improvement of subjects in both scales and objective measures used for assessment purposes. There were no adverse drug reactions reported during the trial. AG may be used as a safe and effective supplement to reduce symptoms of osteoarthritis. The clinical efficacy of the formulation might be mediated through the synergistic blend of herbal bioactive compounds from AG.

Objectives: Evaluating the knowledge in pharmacogenomics (PGx) is the first step toward the implementation of PGx testing in clinical practice. This survey aimed to evaluate the knowledge of PGx testing among healthcare providing students at the top-ranked university in the West Bank of Palestine.

Methods: First an online questionnaire consisting of 30 questions regarding the demographic, knowledge, and attitude toward pharmacogenomics testing was structured and validated. Then the questionnaire was distributed to 1,000 current students from different fields.

Results: 696 responses was received. The results showed that almost half of the participants (n=355, 51.1%) have never took any courses about PGx during their university training. Only 81 (11.7%) of the students who took the PGx course stated that it helped them understanding how genetic variations affect drug response. The majority of the students were uncertain (n=352, 50.6%) or disagreed (n=143, 20.6%) that the lectures during university education described the effects of genetic variants on drug response. Although most of the students (70-80%) answered that genetic variants can indeed affect the drug's response, only 162 students (23.3%) responded that VKORC1 and CYP2C9 genotypes influence the response to warfarin. In addition, only 94 (13.5%) students were aware that many medicine labels include clinical information about PGx testing provided by the FDA.

Conclusions: It is concluded from the results of this survey that there is a lack of exposure to PGx education associated with poor knowledge of PGx testing among the healthcare providing students in the West Bank of Palestine. It is recommended to include and improve the lectures and courses regarding PGx as this will have a major impact on precision medicine.

Objectives: Cystathionine-gamma-lyase (CSE) in the transsulfuration pathway generates hydrogen sulfide (H₂S), suggested regulating cardiovascular function. The G1208T polymorphism in the CTH gene, rs1021737, has, in addition to MTHFR, been found to increase homocysteine, related to myocardial infarction (MI) risk. This study aimed, for the first time, to investigate the associations of the polymorphisms CTH G1208T, MTHFR C677T, and A1298C with the prospective risk of developing a fatal or non-fatal first MI.

Methods: This case-referent study included 545 cases later developing a first-ever MI and 1,054 referents from the Northern Sweden Health and Disease Study. Fatal MI was defined as death within 28 days after MI symptoms.

Results: Women, but not men, had a positive association between fatal MI and the CTH G1208T, odds ratio [95% confidence interval] 3.14 [1.16-8.54] for heterozygotes, and the dominant model 3.22 [1.22-8.51], and for the MTHFR A1298C heterozygotes 3.24 [1.26-8.34] and the dominant model 2.63 [1.06-6.50]. The MTHFR C677T polymorphism was not related to MI.

Conclusions: This study indicates that the minor alleles of CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk for a fatal MI among women but not for non-fatal MI. No association was found in men.

Objectives: Leflunomide is a commonly used treatment for rheumatoid arthritis. It acts by inhibiting dihydroorotate dehydrogenase through its active metabolite teriflunomide. The objective of the study was to investigate the relation between plasma-concentration of teriflunomide and disease-activity in rheumatoid arthritis.

Methods: Data were collected from patients with rheumatoid arthritis on a stable leflunomide dose for at least 2 months. Socio-demographic data, disease characteristics and DAS28 score were recorded. Blood samples were taken for determination of teriflunomide concentration.

Results: A total of 32 serum concentration-time measurements were collected. The concentration of teriflunomide was positively correlated with disease duration of RA (r²=0.2264) and the number of swollen joints (r²=0.2413). There was a trend towards a positive correlation between Health Assessment Questionnaire (HAQ) and plasma teriflunomide concentration (r²=0.1699). Weight was negatively correlated with the residual plasma concentration of teriflunomide (r²=0.2483). However, there was no significant correlation between residual-plasma-concentration of teriflunomide and the following parameters: age, sex, number of tender painful joints, patient-global-assessment, C-reactive protein (CRP) and duration of prescription of leflunomide. We did not find association between disease-activity and residual-plasma-concentration of teriflunomide (r²=0.0021) and haven't been able to define the threshold value of residual-plasma-concentration of leflunomide predictive of a good-response.

Conclusions: We did not find a concentration-effect-relationship. However, therapeutic drug monitoring of teriflunomide may be useful to ensure adherence and evaluate toxic-levels in case of adverse-events.

Objectives: To analyze the phytochemicals, antioxidant, and anticancer activities on MCF-7 human breast cancer cell line using aqueous, hydro-ethanol, and methanol extracts of different Unani drugs, e.g., Halela Siyah, Aftimoon, Bisfayej, Ustukhudoos, and Kutki.

Methods: The qualitative examination (alkaloids, terpenoids, tannins, and saponins), anticancer activity, and an antioxidant assay of the three different extracts were done by MTT assay and DPPH assay, respectively, using different Unani drugs.

Results: The qualitative examination confirmed the substantive presence of phytochemical constituents in all the extracts of these drugs. The Methanolic extract of Halela Siyah had the highest DPPH scavenging activity (91%), while Bisfayej had the lowest (58%). Similarly, the hydro-ethanolic extract showed approximately identical activity for Halela Siyah (89%), Aftimoon (88%), Bisfayej (84%), Kutki (82%), and Ustukhudoos (81%). The aqueous extracts of Halela Siyah (88%) had the highest DPPH scavenging activity, whereas Bisfayej (73%) had the lowest. The methanolic extract of Aftimoon demonstrated the greatest anticancer activity (IC₅₀ - 108), while Aftimoon showed the least activity (IC₅₀ - 316). Halela Siyah (IC₅₀ - 175) and Aftimoon (IC₅₀ - 178) showed substantially the same activity in aqueous extracts. Ustukhudoos hydro-ethanol extracts had the highest (IC₅₀ - 130) activity, whereas Aftimoon had the lowest (IC₅₀ - 204).

Conclusions: In conclusion, our findings evaluated the presence of phytochemicals, good antioxidant activity, and anticancer activity in different extracts of drugs used in this study. The study shows these drugs have potential anticancer activity against breast cancer in MCF-7 cell lines.

Viruses are obligatory protein-coated units and often utilize the metabolic functions of the cells they infect. Viruses hijack cellular metabolic functions and cause consequences that can range from minor to devastating, as we have all witnessed during the COVID-19 pandemic. For understanding the virus-driven pathogenesis and its implications on the host, the cellular metabolism needs to be elucidated. How SARS-CoV-2 triggers metabolic functions and rewires the metabolism remains unidentified but the implications of the metabolic patterns are under investigation by several researchers. In this review, we have described the SARS-CoV-2-mediated metabolic alterations from in vitro studies to metabolic changes reported in victims of COVID-19. We have also discussed potential therapeutic targets to diminish the viral infection and suppress the inflammatory response, with respect to evidenced studies based on COVID-19 research. Finally, we aimed to explain how we could extend vaccine-induced immunity in people by targeting the immunometabolism.