The retroviral protease of human immunodeficiency virus (HIV) is an excellent target for antiviral inhibitors for treating HIV/AIDS. Despite the efficacy of therapy, current efforts to control the disease are undermined by the growing threat posed by drug resistance. This review covers the historical background of studies on the structure and function of HIV protease, the subsequent development of antiviral inhibitors, and recent studies on drug-resistant protease variants. We highlight the important contributions of Dr. Stephen Oroszlan to fundamental knowledge about the function of the HIV protease and other retroviral proteases. These studies, along with those of his colleagues, laid the foundations for the design of clinical inhibitors of HIV protease. The drug-resistant protease variants also provide an excellent model for investigating the molecular mechanisms and evolution of resistance. 相似文献
Epilepsy is a common neurologic disorder, which is efficiently treated with carbamazepine and valproic acid. Moreover, Saudi Ministry of Health implemented a new E-system for Poison Control Centers called Awtar to enhance technology utilization in ensuring patients’ satisfaction and to improve treatment outcomes. Therefore, we conducted this study to assess appropriateness of indication of requests and therapeutic levels of carbamazepine and valproic acid in Tabuk area, North West Saudi Arabia. This is a retrospective observational study conducted in Poison Control & Forensic Chemistry Center, Tabuk, Saudi Arabia. Patients’ data were obtained for years 2018 and 2019. The blood levels of carbamazepine and valproic acid were measured by Therapeutic Drug Monitoring (TDM) Unit. We selected patients treated with either valproic acid or carbamazepine alone without any history of drug allergy. Data of 264 patients were extracted from Awtar E-system. Serum carbamazepine levels were within therapeutic range in 114 patients (75.50%), above-therapeutic range in 13 patients (8.61%) and sub-therapeutic levels in 24 patients (15.89%). Regarding serum valproic acid, it is within therapeutic range in 62 patients (54.87%), above-therapeutic range in 11 patients (9.73%) and sub-therapeutic levels in 40 patients (35.40%). In conclusion, this study gives information about partial appropriateness of usage of carbamazepine and low level of appropriateness of valproic acid. However, more efforts are needed to improve results of appropriateness of indication of antiepileptic drugs. 相似文献
Objective: Longitudinal data on cardiometabolic effects of egg intake during adolescence are lacking. The current analyses aim to evaluate the impact of usual adolescent egg consumption on lipid levels, fasting glucose, and insulin resistance during late adolescence (age 17–20?years).
Methods: Data from 1392 girls, aged 9 to 10 at baseline and followed for 10?years, in the National Heart, Lung, and Blood Institute’s National Growth and Health Study were used to examine the association between usual egg intake alone and in combination with other healthy lifestyle factors and late adolescent lipid levels, fasting glucose, and insulin resistance, measured as homeostasis model assessment of insulin resistance (HOMA-IR). Diet was assessed using 3-day food records during eight examination cycles. Girls were classified according to usual weekly egg intake, ages 9–17?years:?<1 egg/wk (n?=?361), 1 to <3 eggs/wk (n?=?703), and ≥3 eggs/wk (n?=?328). Analysis of covariance modeling was used to control for confounding by other behavioral and biological risk factors.
Results: Girls with low, moderate, and high egg intakes had adjusted low-density lipoprotein cholesterol levels of 99.7, 98.8, and 95.5 mg/dL, respectively (p?=?0.0778). In combination with higher intakes of fiber, dairy, or fruits and vegetables, these beneficial effects were stronger and statistically significant. There was no evidence that ≥3 eggs/wk had an adverse effect on lipids, glucose, or HOMA-IR. More active girls who consumed ≥3 eggs/wk had the lowest levels of insulin resistance.
Conclusion: These results suggest that eggs may be included as part of a healthy adolescent diet without adverse effects on glucose, lipid levels, or insulin resistance. 相似文献
Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs. 相似文献
The current literature suggests that the antibacterial effect of leukocyte- and platelet-rich plasma (L-PRP) is directly related to platelet and leukocyte concentrations. The aim of this study was twofold: first, to evaluate the antimicrobial effect of L-PRP against selected bacterial strains in vitro, and second, to correlate this effect with leukocyte and platelet content in the final concentration. Blood was collected from 20 healthy males, and L-PRP, acellular plasma (AP), and autologous thrombin were consecutively prepared. Flow cytometry analysis of the blood, L-PRP, and AP was performed. The L-PRP gel, liquid L-PRP, and thrombin samples were tested in vitro for their antibacterial properties against seven selected bacterial strains using the Kirby–Bauer disk-diffusion method. There was notable antimicrobial activity against selected bacterial strains. No statistically significant correlations between antimicrobial activities and the platelet concentration in L-PRP were observed. Statistically significant positive correlations between selected leukocyte subtypes and antimicrobial activity were noted. A negative correlation was found between elevated monocyte count and antimicrobial activity of L-PRP against one bacterial strain studied. L-PRP possesses antimicrobial activity and can be potentially useful in the fight against certain postoperative infections. The bactericidal effect of L-PRP is caused by leukocytes, and there exists a relationship among selected leukocyte subtypes and L-PRP antimicrobial activity. 相似文献