Time-effect and dose-effect of prasugrel hydrobromide acetic acid compound inhibiting platelet aggregation

Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided into 19 groups （n- 10）： the vehicle control group, the PHAAC groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h） and the prasugrel hydrochloride groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h）. Rats were singly intra- gastic administration of the vehicle, the PHAAC （5 mg·kg^-1） or the prasugrel hydrochloride （5 mg · kg^-1 ）, re- spectively. Blood samples were taken at each time point for the determination of platelet aggregation rate （PAR）. For the dose-effect study, 110 SD rats were devided into 11 groups （n= 10）： the vehicle control group, the PHAAC groups （10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） and the prasugrel hydrochloride groups （ 10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） . Blood samples were taken at 4 h after drug administration for the determination of PAR. Results Compared with the vehicle group, PHAAC has significant anti-platelet ag- gregative effects （P 〈 0.05） at the time of 0.5, 1, 2, 4, 6, 24, 48 h, and the effect at the time of 4 h was the strongest. There were no obvious differences between the effect of PHAAC （5 mg · kg^-1） and prasugrel hydrochlo- ride （5 mg · kg^-1） at each time point. Compared with the vehicle group, intragastic administration of PHAAC at the doses of 10, 5, 2.5, 1, 0.5 mg · kg^-1 could obviously inhibite the platelet aggregation, and showed a dose- dependent manner. There were no significant differences between the effect of PHAAC and prasugrel hydrochloride at the same dose. Conclusion PHAAC can inhibit platelet aggregation in a dose-dependent manner, and the effect at 4 h after drug administration is the strongest. The action strength and duration of PHAAC are similar with that of the prasugrel hydrochloride.

The ED_(50)of Remazolam Toluenesulfonate Combined with a Subthreshold Dose of Esketamine for Inhibiting Cardiovascular Response to Tracheal Intubation in Elderly Patients

Objective:To explore the half-effective dose(ED_(50))of remazolam toluenesulfonate combined with subthreshold amounts of esketamine for inhibiting cardiovascular response to tracheal intubation in elderly patients.Method:We included 42 patients,aged 65-75,who required general anesthesia and single-lumen endotracheal intubation for elective surgery.The first patient was administered remazolam toluenesulfonate at a dose of 0.20 mg/kg.Once the patient lost consciousness,their alertness/sedation score(OAA/S score)was≤1,and their BIS score was≤60,and a subthreshold dose(0.3 mg/kg)of esketamine was given.The subsequent doses were adjusted using a sequential approach based on the cardiovascular response to tracheal intubation observed in the previous patient.The dose was modified in increments or decrements of 0.01 mg/kg.The ED_(50)and 95%CI of remazolam toluenesulfonate were calculated using the Dixon and Massey sequential distribution test method.Result:The inhibition of endotracheal intubation response was positively correlated with the dose of remazolam toluenesulfonate,and the depth of sedation could not be achieved when the amount was≤0.22 mg/kg.The ED_(50)of remazolam toluenesulfonate combined with a subthreshold dose of esketamine in inhibiting cardiovascular response to tracheal intubation in elderly patients was 0.30(0.28,0.33)mg/kg.There was no statistically significant difference in blood pressure between the induction of anesthesia and before the operation.Conclusion:When compounded with 0.3 mg/kg esketamine,the ED_(50)of Remazolam toluenesulfonate in inhibiting cardiovascular response to endotracheal intubation in elderly patients was 0.30 mg/kg(95%CI0.28-0.33 mg/kg).

Progress in the Research of Radix Astragali in Treating Chronic Heart Failure:Effective Ingredients,Dose-Effect Relationship and Adverse Reaction

Radix Astragali,a Chinese herbal medicine possessing important cardiovascular pharmacologic effects,is widely applied for the treatment of chronic heart failure（CHF） in clinical practice.This paper summarizes briefly the researches in the last 10 years on its chemical compositions,effective ingredients for improving cardiac function,dose-effect relationship in treating CHF,and adverse reactions that occurred in clinical practice.

Overall assessment of antibiotic substitutes for pigs:a set of meta-analyses

Background:Antibiotic growth promoters are widely used to improve weight gain.However,the abuse of antibiotics can have many negative effects on people.Developing alternatives to antibiotics is an urgent need in livestock production.We aimed to perform a meta-analysis and network meta-analysis(NMA)to investigate the effects of feed additives as potential antibiotic substitutes(ASs)on bacteriostasis,growth performance,intestinal morphology and immunity.Furthermore,the primary,secondary,and tertiary ASs were defined by comparing their results with the results of antibiotics.Results:Among 16,309 identified studies,37 were summarized to study the bacteriostasis effects of feed additives,and 89 were included in the meta-analysis and NMA(10,228 pigs).We summarized 268 associations of 57 interventions with 32 bacteria.The order of bacteriostasis effects was as follows:antimicrobial peptides(AMPs)≈antibiotics>organic acids>plant extracts>oligosaccharides.We detected associations of 11 feed additives and 11 outcomes.Compared with a basal diet,plant extract,AMPs,probiotics,microelements,organic acids,bacteriophages,lysozyme,zymin,and oligosaccharides significantly improved growth performance(P<0.05);organic acids,probiotics,microelements,lysozyme,and AMPs remarkably increased the villus height:crypt depth ratio(V/C)(P<0.05);and plant extracts,zymin,microelements,probiotics,and organic acids notably improved immunity(P<0.05).The optimal AMP,bacteriophage,lysozyme,microelements,oligosaccharides,organic acids,plants,plant extracts,probiotics,and zymin doses were 0.100%,0.150%,0.012%,0.010%,0.050%,0.750%,0.20%,0.040%,0.180%,and 0.100%,respectively.Compared with antibiotics,all investigated feed additives exhibited no significant difference in effects on growth performance,IgG,and diarrhoea index/rate(P>0.05);AMPs and microelements significantly increased V/C(P<0.05);and zymin significantly improved lymphocyte levels(P<0.05).Furthermore,linear weighting sum models were used to comprehensively estimate the overall impact of each feed additive on pig growth and health.Conclusions:Our findings suggest that AMPs and plant extracts can be used as primary ASs for weaned piglets and growing pigs,respectively.Bacteriophages,zymin,plants,probiotics,oligosaccharides,lysozyme,and microelements can be regarded as secondary ASs.Nucleotides and organic acids can be considered as tertiary ASs.Future studies should further assess the alternative effects of combinational feed additives.

Dose-dependent effects of pentabrominated diphenyl ethers on sexual hormone and histology of male reproductive system in rats

Polybrominated diphenyl ethers (PBDEs) used as flame retardants are widely used in a variety of consumer products, like textiles, foam and building materials. They are persistent in the environment, and increasing levels of PBDEs have been found both biota and human tissue samples. In the present study we examined the dose-dependent effects of pentabrominated diphenyl ether (PBDE-99) on the serum hormone and histology of reproductive system in male rats. 40 health 4-week-old SD rats were divided into 4 groups randomly. The treated rats were orally administered with BDE-99 at the dose of 60,120 or 180 mg/kg, while controls received equal volume of corn oil. We examined the changes of serum hormone levels, histopathology, and PCNA after 30 days exposure to BDE-99. With increasing doses of BDE-99, testis organ coefficient increased, serum hormone levels lower, PCNA positive expression reduced, and the degeneration of seminiferous epithelium were revealed in treated group. These indicators with significant dose-effect relationship showed that BDE-99 can reduce the serum sex hormone levels and cause severe degeneration of seminiferous epithelium.

不同参数电针对内源性阿片肽系统调节的量效关系

Endogenous opioid peptides(EOP)are the neurochemical basis of the anesthetic and analgesic effects of acupuncture,and the quantity of acupuncture stimulus can be controlled accurately by using electroacupuncture(EA).The present study explores the dose-effect relationship between EA with different parameters and the regulation of EOP system.In this paper,the intervention effects of EA on EOP system were specially discussed in terms of the single factor and the different combinations of the frequency,waveform and current intensity.This study shows that EOP system presents a frequency-response specificity.The low frequency of EA promotes the release of enkephalin,β-endorphin and endomorphin,the high one activates the dynorphin system selectively,and the intermediate frequency works on promoting the release of enkephalin andβ-endorphin,as well as dynorphin.Sparse-dense wave of EA may induce the release of enkephalin,β-endorphin,endomorphin and dynorphin,presenting a synergistic effect.However,the waveform of EA should be selected flexibly in clinical practice.Sometimes the better therapeutic effect can also be obtained with the continuous wave of EA.EOP system is involved in mediating appropriate intensity of EA,while the acupuncture effect generated by an extra strong EA stimulation refers to a kind of stress response of non-opioid mechanism.The different combinations of EA parameters result in various effects.The combination of EA parameters should be optimized in accordance with different diseases,which is valuable for guiding clinical practice and the development of EA therapy.

Clinical Effect of Astragalus Granule of Different Dosages on Quality of Life in Patients with Chronic Heart Failure

Objective：To explore the dose-effect relationship of Astragalus granule（AG） on improving the quality of life（QOL） of the patients with chronic heart failure（CHF）.Methods：Ninety CHF patients of Fei（肺）-qi deficiency and/or Xin（心）-Shen（肾） yang-deficiency syndromes were equally randomized divided with a random number table into three groups;they received the high（7.5 g）,moderate（4.5 g）,and low dosage（2.25 g） of AG orally taken twice a day,respectively,and 4 mg of perindopril tablet once a day for 30 successive days.The heart function grade,patients＇ left ventricular ejection fraction（LVEF） and walking distance in 6 min（6mWD） were measured before and after treatment,and the patients＇ QOL was scored by the Minnesota Questionnaire for QOL evaluation in the patients with CHF at the same time.Results：The heart function grades of all the three groups after treatment were improved compared with those before treatment,but the improvements in high-dose group and moderate dose group were better than that in the low dose group（P0.05）.LVEFs were increased significantly in all the three groups,but the improvements in the high-dose group（59.42%±7.50%） and moderate dose group（61.98%±6.82%） were better than that in the low dose group（51.45%±6.80%,P0.01）; the 6mWDs in the all groups were also significantly increased（P0.01）,up to 419.80136.23 m,387.15134.13 m, and 317.69±39.97 m,respectively;and Minnesota scores in them were lowered to 29.59±4.69 scores,35.74±5.89 scores,and 42.78±6.06 scores,respectively;comparisons in aspects on 6mWD and Minnesota score showed that the effectiveness with high dose is the most effective,moderate dose as the second,and low dose as the lowest（P0.01）.Conclusions：AG was sufficient to display an optimal effect on improving heart contraction at the moderate dose.In aspects of improving the QOL of CHF patients,the effectiveness of AG showed a dosedependent trend.It should be applied discriminatively depending on the actual condition of patients and the aim of treatment in clinic.