Recombinant streptokinase vs phenylephrine-based suppositories in acute hemorrhoids, randomized, controlled trial(THERESA-3)

AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) and phenylephrine-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(14 sites), randomized(1:1), open, parallel groups, active controlled trial was done. After inclusion, subjects with acute symptoms of hemorrhoids, who gave their written, informed consent to participate, were centrally randomized to receive, as outpatients, rSK(200000 IU) or 0.25% phenylephrine suppositories, which had different organoleptic characteristics. Treatment was administered by the rectal route, one unit every 6 h during 48 h for rSK, and up to a maximum of 5 d(20 suppositories) for phenylephrine. Evaluations were performed at 3, 5 and 10 d postinclusion. The main end-point was the 5th-day complete clinical response(disappearance of pain and edema, and ≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were evaluated too. RESULTS: 5thday complete response rates were 83/110(75.5%) and 36/110(32.7%) with rSK and phenylephrine suppositories, respectively. This 42.7% difference(95%CI: 30.5-54.2) was highly significant(P < 0.001). The advantage was detected since the early 3rdday evaluation(37.3% vs 6.4% for the rSK and active control groups, respectively; P < 0.001) and was kept even at the late 10thday assessment(83.6% vs 58.2% for rSK and phenylephrine, respectively; P < 0.001). Time for complete response was significantly shorter(P = 0.031; log-rank test) in the rSK group(median: 4.9 d; 95%CI: 4.8-5.0) with respect to the active control(median: 9.8 d; 95%CI: 9.8-10.0). Thrombectomy was necessary in 1/59 and 8/57 patients with baseline thrombosis in the rSK and phenylephrine groups, respectively(P = 0.016). There were no adverse events attributable to the experimental treatment. CONCLUSION: rSK suppositories showed a significant advantage over a widely used over-the-counter phen-ylephrine preparation for the treatment of acute hemorrhoidal illness, with an adequate safety profile.

Comparison the effect of ephedrine and phenylephrine in treatment of hypotension after spinal anesthesia during cesarean section

Background and Objective: The effectiveness of ephedrine and/or phenylephrine, in treatment of hypotension secondary to spinal anesthesia for cesarean section and their effects on fetal/neonatal outcome were studied. Methods and Materials: Sixty healthy parturients were randomly assigned to two groups;group E (n = 33) received boluses 5 mg/ml increments ephedrine and group P (n = 27) received a boluses of phnylephrine 100 μg/ml increments for treatment of hypotension after spinal block during cesarean section. Changes in maternal blood pressure and heart rate, and incidence of nausea-vomiting, neonatal Apgar score at 1 and 5 minutes of delivery, and umbilical arterial blood gas values were recorded. Results: There were no differences in treatment of hypotension following sympathectomy after spinal block with two drugs. Neonatal outcome was similar in two groups. There were not significant differences in umbilical arterial values in two groups. Conclusion: Ephedrine and phenylephrine are both effective vasopressores for treatment of hypotension associated to spinal block during cesarean section without adverse effects on infants/neonates.

Effects of Isoprenaline，Phenylephrine on Heart and Influence of Nifedipine on These Effects

In a perfused isovolumetrically contracting rat heart model, the effects of isoprenaline(IPN) and phenylephrine (PE) on myocardial contraction and relaxation were investigated,and the influence of nifedipine on these effects was studied. Both IPN and PE increased the myocardial contraction and improved its relaxation, but some differences existed.Nifedipine (10 nmol/L)substantially inhibited the PE-mediated inotropic effect, but in case of IPN-mediated inotropic ones, it did not.It was assumed that there may be various types of slow channels, one was activated by IPN,and the other, by PE.

Clinical value of phenylephrine testing in the upper and lower eyelids of patients with aponeurotic and congenital eyelid ptosis

·AIM:To characterize the phenylephrine test in aponeurotic and congenital eyelid ptosis,to determine the appropriate timing of the phenylephrine test,and to assess the responses of the upper and lower eyelids.·METHODS:This was a retrospective analysis of 140 eyes of 87 patients(mean age 52.29±16.45 y;22 males,65 females)with upper eyelid ptosis.Totally 88.6%had aponeurotic and 11.4%had congenital ptosis.For the evaluation of the responses of the upper and lower eyelids to topical 2.5%phenylephrine,the scleral show height,the marginal reflex distance(MRD)between the inferior margin of the upper eyelid and pupillary light reflex(MRD1),and between the central portion of the lower eyelid and pupillary light reflex(MRD2)were measured at the 2^(nd),5^(th),and15^(th)minutes.The changes of MRD1 and MRD2 with time(ΔMRD1 andΔMRD2)were evaluated.·RESULTS:The mean MRD1,MRD2.and scleral show heights increased within 5 min after testing,remaining largely stable between the 5^(th)-15^(th)minutes.The percentage of eyes with a greater response in MRD1 increased with increased severity of ptosis(P<0.05).Eyes with aponeurotic ptosis were more responsive to phenylephrine testing than congenital ptosis.The mild ptosis group had lower scleral show measurements and higherΔMRD2 values.TheΔMRD1 andΔMRD2 values were poorly correlated in all measurement times.·CONCLUSION:Performing the phenylephrine test 5 min after instilling the reagent is adequate to assess the maximum response of the upper and lower eyelids.The upper and lower eyelid responses in phenylephrine testing are poorly correlated.However,theΔMRD2 is related with baseline scleral show degree that may be a postoperative predictive factor.Further studies are necessary to determine the relationship between the responses of the lower eyelids to phenylephrine testing.

Effect of administration of phenylephrine immediately after low dose insemination on pregnancy rates in mares

There is considerable pressure on equine veterinarians to achieve good pregnancy rates with very small doses of semen. Phenylephrine administration in the rabbit increased numbers of oviductal, uterine, and cervical sperm, myometrial contractions, and fertilized ova after low dose insemination. The use of phenylephrine to enhance uterine contractility and fertility has not been investigated in the mare. Thus, the objective of this study was to determine if phenylephrine administration would result in clinically acceptable pregnancy rates in mares bred by low dose insemination. The hypothesis (Ha) was that pregnancy rates would be significantly higher in mares receiving phenylephrine compared to saline controls. Six pony mares and eight horse mares were enrolled in this study. Mares were inseminated within 24 hours of ovulation with 30 million progressively motile spermatozoa from a single fertile stallion. Immediately following insemination, mares were administered either phenylephrine (0.06 mg/kg) or 1mL of saline via IV injection. Pregnancy status was determined 14 days following ovulation via transrectal ultrasonography. Pregnancy rates in phenylephrine treated mares were 44% (4/9) while 22% (2/9) in saline-treated mares (P > 0.05).

Effects of ephedrine, phenylephrine and norepinephrine prevent hypotension after spinal anesthesia in cesarean section and comparison of effects on newborns

Objective: To compare the preventive effect of ephedrine, phenylephrine and norepinephrine on hypotension after lumbar anesthesia in cesarean section and their effects on newborns. Methods: 25 cesarean section women in our hospital from December 2016 to January 2018 were selected and divided into three groups according to different surgical medication, namely, ephedrine group (n=40), phenylephrine group (n=45) and norepinephrine group (n=40). Then the vital signs, neonatal blood gas analysis, neonatal Apgar score, adverse reactions of the three groups were compared. Results: The HR at T0~T3, and SBP and DBP at T0 and T1 had no difference among three groups (P>0.05). The HR, SBP and DBP at T3 ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The PCO2 and PO2 had no difference among three groups (P>0.05). The pH ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The SpO2 ranking in a descending order was phenylephrine group, ephedrine group and norepinephrine group (P<0.05). The Apgar score at birth in ephedrine group and norepinephrine group was significantly lower than that in phenylephrine group (P<0.05), while the Apgar score at post-birth 5 min and 10 min had no difference among three groups (P>0.05). The incidence of hypertension, gastrointestinal reaction, hyperhidrosis and palpitation in the phenylephrine group was significantly lower than that in the norepinephrine group (P<0.05). Conclusion: The phenylephrine and norepinephrine have no difference on the preventive effect of hypotension after spinal anesthesia in cesarean section, while safety of norepinephrine for puerpera and neonates is higher.

Bolus norepinephrine and phenylephrine for maternal hypotension during elective cesarean section with spinal anesthesia:a randomized,double-blinded study

Background:In recent years,norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia.Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China.Thus,in this randomized,double-blinded study,we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension.Methods:In a tertiary women’s hospital in Nanjing,China,102 women were allocated with computer derived randomized number to receive prophylactic 8 mg norepinephrine(group N;n=52)or 100 mg phenylephrine(group P;n=50)immediately post-spinal anesthesia,followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80%of the baseline.Our primary outcome was standardized maternal cardiac output(CO)reading from spinal anesthesia until delivery analyzed by a two-step method.Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes.Maternal side effects and neonatal outcomes were collected as well.Results:Compared to group P,women in groupNhad a higherCO(standardizedCO5.8±0.9 vs.5.3±1.0 L/min,t=2.37,P=0.02)and stroke volume(SV,standardized SV 73.6±17.2 vs.60.0±13.3 mL,t=4.52,P<0.001),and a lower total peripheral resistance(875±174 vs.996±182 dyne·s/cm5,t=3.44,P<0.001).Furthermore,the incidence of bradycardia was lower in group N than in group P(2%vs.14%,P=0.023),along with an overall higher standardized heart rate(78.8±11.6 vs.75.0±7.3 beats/min,P=0.049).Other hemodynamics,as well as maternal side effects and neonatal outcomes,were similar in two groups(P>0.05).Conclusions:Compared to equivalent phenylephrine,intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia;however,no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

Separation of chiral drugs with sulfobutylether-β-cyclodextrin bycapillary zone electrophoresis

Sulfobutylether－β－cyclodextrin（SBE－β－CD）was used as a chiral selector tor separatingten chlral drugs with resolution 1．2 by capillary zone electrophoresls（CZE）， The backgroundelectrolylc solution comprised of 120 mmol／L Britton－Robinson buffer（BRB） containing1 ～10mmol／L SBE－β－CD with the pH value adjusted from 5．0－6．8． Five of the drugs were better resolvedthan those previously reported with neutral CDs．

Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study

BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney failure.Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is paramount.AIM To identify risk factors associated with delayed graft function(DGF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients.The primary outcome was the occurrence of DGF.RESULTS The incidence of DGF was 27%.Under logistic regression,eight independent risk factors for DGF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressure<110 mmHg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/min.CONCLUSION We delineate the association between DGF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine.

Quantitative Determination of Adrenaline Hydrochloride Injection and Noradrenaline Bitartrate Injection by a New HPLC Method via Substitute for Reference Substance

An HPLC method for quantitative determination of adrenaline hydrochloride injection and noradrenaline bitartrate injection was established and validated with a substitute for the reference substance.Phenylephrine hydrochloride was selected as the substitute for the reference substance of adrenaline and noradrenaline bitartrate.The correction factor of phenylephrine hydrochloride with respect to the reference substance of adrenaline and noradrenaline bitartrate was determined under defined conditions.Adrenaline hydrochloride injection and noradrenaline bitartrate injection were quantified by assaying phenylephrine hydrochloride and a correct factor.The results indicate that the HPLC method with the substitute for reference substance was reliable and feasible for quantitative determination of drugs.

EFFECT OF THE EXCITATION OF ADRENOCEPTORS ON THE PACEMAKER CURRENT I_f OF SHEEP CARDIAC PURKINJE FIBRES IN “ISCHEMIA” SOLUTIO

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Antioxidant Protective Effects of the Resveratrol on the Cardiac and Vascular Tissues from Renal Hypertensive Rats

Background: Accumulating reactive oxygen species (ROS) is involved in cellular signaling and function disturbances due to the oxidative stress, which contributes to several diseases. The consequences of ROS activity represent an im-portant mechanism on the pathogenesis of vascular diseases, such as hypertension. Increased blood pressure observed in renal hypertension of the 2 kidneys-1 clip (2K-1C) model involves increased ROS levels in the cardiovascular system. Resveratrol, a polyphenolic compound primarily found in red wine, has many biological and pharmacological proper-ties. Considering the antioxidant properties of resveratrol, the present study was aimed to investigate the effects of the chronic treatment with resveratrol on cardiovascular system from renal hypertensive rats. Results: 2K-1C hypertension presented increased blood pressure, which was reduced at the end of the fifth week of resveratrol treatment. The cardiac hypertrophy index and the basal levels of ROS in rat aortic rings were also reduced by resveratrol treatment. Conclusions: The present findings clearly show the protective effects from resveratrol on the blood pressure, the car-diac growth and the vascular ROS generation in renal hypertension.