scholarly journals Spironolactone Improves the All-Cause Mortality and Re-Hospitalization Rates in Acute Myocardial Infarction with Chronic Kidney Disease Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiang Qu ◽  
Hui Yao ◽  
Changxi Chen ◽  
Shuting Kong ◽  
Lingyue Sun ◽  
...  
Keyword(s):  
Treatment Group ◽  
Dose Group ◽  
Low Dose ◽  
Standard Treatment ◽  
High Dose Group ◽  
High Dose ◽  
Single Center ◽  
All Cause Mortality ◽  
Standard Treatment Group

Background: Mineralocorticoid receptor antagonists (MRA) improve outcomes in chronic kidney disease (CKD) and acute myocardial infarction (AMI) patients. However, the lack of evidence regarding long-term clinical outcomes in the use of MRA, including spironolactone, in patients with AMI combined with CKD.Objectives: This study aimed to investigate whether spironolactone could significantly reduce the risk of all-cause mortality and re-admission in patients with AMI and CKD.Methods: In this single center, observational, retrospective, registry based clinical study, a total of 2,465 AMI patients were initially screened; after excluding patients with estimated glomerular filtration rate more than 60 ml/min/1.73 m2, 360 patients in the standard treatment group and 200 patients in the spironolactone group met the criteria. All enrolled patients follow-up for 30 months. The primary outcomes were all-cause mortality and re-admission. The key safety outcome was hyperkalemia rates during the 30 months follow-up period.Results: 160 (44.4%) and 41 (20.5%) patients in the standard treatment and spironolactone groups died, respectively [hazard ratio (HR): 0.389; 95% confidence interval (CI): 0.276–0.548; p < 0.001]. Re-admission occurred in 217 (60.3%) and 95 (47.5%) patients in the standard treatment and spironolactone groups, respectively (HR: 0.664; 95% CI: 0.522–0.846; p = 0.004). The spironolactone group was divided into two based on the daily dose, low dose group (no more than 40 mg) and high dose group (more than 40 mg); the differences in the mortality rate between low dose group (16.7%) and the standard treatment group (44.4%) (HR: 0.309; 95% CI: 0.228–0.418; p < 0.001) and high dose group (34.1%) (HR: 0.429; 95% CI: 0.199–0.925; p = 0.007) were significant. The differences in re-hospitalization rate between low dose group (43.6%) and the standard treatment group (60.3%) (HR: 0.583; 95% CI: 0.457–0.744; p < 0.001) and high dose group (61.4%) (HR: 0.551; 95% CI: 0.326–0.930; p = 0.007) was significant. Hyperkalemia occurred in 18 (9.0%) and 18 (5.0%) patients in the spironolactone group and standard treatment group, respectively (HR: 1.879; 95% CI: 0.954–3.700; p = 0.068). Whereas, Hyperkalemia occurred in high dose group (20.5%) significantly more often than in the standard treatment group (p < 0.001) and low dose group (5.8%) (p = 0.003).Conclusion: Using MRA, such as spironolactone, may substantially reduce the risk of both all-cause mortality and re-admission in patients with AMI and CKD; the use of low-dose spironolactone has the best efficacy and safety. However, this was a relatively small sample size, single center, observational, retrospective, registry based clinical study and further prospective evaluation in adequately powered randomized trials were needed before further use of spironolactone in AMI with CKD population.

scholarly journals Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 52 (12) ◽  
pp. 841-849
Author(s):  
Chunmei Xu ◽  
Ping Wang ◽  
Huikai Miao ◽  
Tianyue Xie ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Dose Group ◽  
Low Dose ◽  
Radioiodine Therapy ◽  
Meta Analysis ◽  
High Dose Group ◽  
High Dose ◽  
Fixed Effects Model ◽  
Recombinant Human Thyrotropin

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Long-Term Follow-up and Analysis of Dose Groups with Ibrutinib in Relapsed Follicular Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2706-2706 ◽  
Author(s):  
Nathan Fowler ◽  
Thomas E Boyd ◽  
Jeff P. Sharman ◽  
Sonali M. Smith ◽  
Fong Clow ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Dose Group ◽  
Low Dose ◽  
Single Agent ◽  
High Dose Group ◽  
Fixed Dose ◽  
High Dose ◽  
Grade 3

Abstract Introduction: As outcomes in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) remain suboptimal, new, effective treatment options with a favorable safety profile are needed. Ibrutinib is a first-in-class, oral, covalent inhibitor of Bruton's tyrosine kinase (BTK), a key component of B-cell signaling involved in B-cell survival, proliferation and function. In lymphomas, ibrutinib is FDA-approved for treatment of mantle cell lymphoma in pts with ≥1 prior therapy. A phase 1 dose-escalation study with ibrutinib showed single-agent activity in pts with R/R B-cell malignancies (overall response rate [ORR] 60%; complete remission [CR] in 16%) including FL (Advani JCO 2013). In this trial, the 560 mg/day fixed dose was well tolerated and led to full BTK occupancy. We evaluated the efficacy, safety, and tolerability of single-agent ibrutinib by low- vs. high-dose groups with longer follow-up in pts with relapsed FL. Methods: Data were analyzed for pts with R/R FL (N=16) treated with oral ibrutinib in the phase I study (PCYC-04753), where pts received escalating doses of ibrutinib 1.25-12.5 mg/kg/day per cycle (1 cycle = 28 days + 7 days rest) or continuous doses of ibrutinib 8.3 mg/kg/day or 560 mg/day fixed dose (1 cycle = 35 days). Pts with stable disease or better, who received therapy for 6 months, continued ibrutinib at a fixed dose of 560 mg/day in the extension study (PCYC-1103) until progression or unacceptable toxicity. Pt data categories included low-dose (1.25 mg/kg/day, 2.5 mg/kg/day, or 5 mg/kg/day) or high-dose (8.3 mg/kg/day or 12.5 mg/kg/day) groups. Results: Eight pts each were categorized into low-dose and high-dose groups. Baseline characteristics were similar, but median treatment duration was longer for the high-dose group (Table; 12 vs. 4 months). Increased ORR (63% vs. 25%) and CR rates (38% vs. 0%) were observed in the high-dose compared with low-dose group (Table). Median duration of response (DOR) was longer in the high-dose group (12 vs. 3 months), as was median progression-free survival (PFS; 24 vs. 9 months). Median overall survival (OS) was not reached (NR) in either group. Grade ≥3 adverse events (AEs) occurred in 3 pts in each group. Common grade ≥3 AEs reported in ≥3 pts in the combined groups included (low-dose, high-dose) diarrhea (n=2, 6), fatigue (n=3, 4), nausea (n=2, 4), cough (n=3, 2), myalgia (n=1, 3), headache (n=0, 3), muscle spasms (n=1, 2), pruritus (n=0, 3), and rash (n=0, 3). Serious AEs occurred in 3 pts in the low-dose and 1 pt in the high-dose group. AEs leading to treatment discontinuation occurred in 2 pts in each group. No fatal AEs occurred. Among 4 pts (high-dose group) receiving ibrutinib beyond 1 year (range, 18 to 61 months), no unexpected or increased AEs were observed; 1 pt experienced 2 grade 3 AEs (non-cardiac chest pain and vomiting), both within 60 days from start of treatment and lasting 1 day. No other grade ≥3 AEs occurred among these 4 pts. Conclusions: Higher doses of single-agent ibrutinib were associated with increased response rates and prolonged PFS in pts with R/R FL. A higher dose was not associated with increased AEs or with cumulative toxicity during extended therapy. In the current analysis, pts with FL derived the most benefit from ibrutinib doses at 8.3 mg/kg/day or higher. A study testing single-agent ibrutinib at 560 mg/day in pts with R/R FL is ongoing (Bartlett Blood 2014) as is a phase 2 study evaluating ibrutinib 560 mg/day in chemoimmunotherapy refractory FL. Table 1. Patient Characteristics and Efficacy Low dose(n=8) High dose(n=8) Median age, yrs (range) Age ≥ 70 yrs, n (%) 57 (48-70)1 (13) 62.5 (41-71)1 (13) Median no. of prior therapies (range) 3 (1-4) 2 (1-5) Ann Arbor stage III/IV disease, n (%) 6 (75) 6 (75) FLIPI score, % (low / intermediate / high)* 25 / 38 / 38 13 / 38 / 50 Median treatment duration, months (range) 3.8 (0.5-11.1) 12.4 (0.2-61.5) ORR, n (%) CR, n (%) 2 (25)0 (0) 5 (63)3 (38) Median DOR, months (range) n=2; 3.4 (1.8-4.9) n=5; 12.3 (4.8-51.3) Median PFS, months (95% CI) 9.2 (0.5, 13.4) 23.7 (2.2, NE) 10-month PFS, % 35.7 70 Median OS, months (95% CI) NR NR 10-month OS, % 100 100 *FLIPI scores from baseline data. NE, not estimable Disclosures Off Label Use: single-agent ibrutinib therapy in patients with relapsed FL. Boyd:Celgene: Research Funding, Speakers Bureau; Genentech: Research Funding; US Oncology: Research Funding; GSK: Research Funding. Sharman:Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; TG Therapeutics, Inc.: Research Funding; Janssen: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Calistoga: Honoraria. Smith:Pharmacyclics: Consultancy; Celgene: Consultancy. Clow:Pharmacyclics LLC, an AbbVie Company: Employment. Chu:Pharmacyclics LLC, an AbbVie Company: Employment.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

Effect of Different Doses of Propofol and Nerve block Combined with General Anesthesia on The Intraoperative Anesthesia and Postoperative Awakening and Cognitive Function in Elderly Patients with Knee Osteoarthritis

2021 ◽  
Vol 7 (4) ◽  
pp. 697-705
Author(s):  
Jianhui Ma ◽  
Meimei Pang ◽  
Xin Ding ◽  
Shirong Fang ◽  
Lichao Chu
Keyword(s):  
Cognitive Function ◽  
Elderly Patients ◽  
General Anesthesia ◽  
Nerve Block ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Knee Oa ◽  
Different Doses

Objective. To explore the effect of different doses of propofol and nerve block combined with general anesthesia on the intraoperative anesthesia and postoperative awakening and cognitive function in elder patients with knee osteoarthritis (OA). Methods. According to the inclusion criteria for research object, we selected 98 elderly patients with knee OA who needed surgery and were admitted to our hospital from January 2019 to January 2021 for the study. Patients were divided into the low dose group (given 2 mg/kg propofol by pumping under constant speed during surgery) and the high dose group (given 4 mg/kg propofol by pumping during surgery) by the number table method to compare their indicators including the intraoperative anesthesia effect, with 49 cases in each group. Results. No between-group difference was shown in the anesthesia time and postoperative VAS scores, but the awakening time of the low dose group was significantly shorter than that of the high dose group (P<0.05); the differences in heart rate (HR) values at various time points between the two groups were not obvious, but the high dose group obtained significantly higher HR values at T4 than the low dose group; the mean arterial pressure (MAP) values of both groups were significantly reduced at Ti and then returned to the level before anesthesia (P>0.05); the bispectral index scores (BIS) of both groups experienced a marked drop at Ti and then recovered gradually, but failed to return to the level at T0 till the end, and a between-group difference in BIS indexes presented at Ti; the plasma corticosterone (CORT) concentration at Ti of both groups were significantly lowered and then returned to the level at T0, with no between-group difference; and compared with the low dose group, the high dose group achieved slightly lower mini-mental state examination (MMSE) scores at 24-72 h after surgery, with no significant difference between them (P>0.05). Conclusion. The therapy of different doses of propofol and nerve block combined with general anesthesia has no significant effect on the cognitive function in elderly knee OA patients after surgery. With the nerve block improving the analgesic effect, a low dose of propofol is good for the postoperative awakening of patients. Different doses of propofol inhibited the stress response to a different degree and produced good anesthesia outcomes in elderly patients, but comparatively speaking, a low-dose propofol ensures more smooth indexes and less effect on the intraoperative hemodynamics.

scholarly journals Comparison of the in-vivo Effect of Two Tranexamic Acid Doses on Fibrinolysis Parameters in Adults Undergoing Valvular Cardiac Surgery with Cardiopulmonary Bypass - A Pilot Investigation

2020 ◽  
Author(s):  
Zhen-feng ZHOU ◽  
Wen Zhai ◽  
Li-na YU ◽  
Kai SUN ◽  
Li-hong SUN ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Placebo Group ◽  
Cardiopulmonary Bypass ◽  
Plasminogen Activator ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Pai 1

Abstract Background: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB, which has not been systematically elucidated.Methods: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed.Results: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (p <0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (p <0.05); TAFI concentrations also decreased at the T5 in low-dose group (p <0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. No significant differences were observed in the levels of the coagulation proteins at any points between the groups.Conclusions: The vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass, and we recommend a low dose TXA regimen for those patients.Clinical trial number and registry URL: ChiCTR-IPR-17010303; http://www.chictr.org.cn, Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.

scholarly journals Research on the Effects of the Extract of Polygala fallax Hemsl on Sex Hormones and ?-EP in Perimenopausal Rat Models

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Siyuan Yang ◽  
Zhiyong Cao ◽  
Jiabao Chen ◽  
Gang Fang
Keyword(s):  
Menstrual Cycle ◽  
Sex Hormones ◽  
Dose Group ◽  
Low Dose ◽  
Normal Group ◽  
Dose Effect ◽  
High Dose Group ◽  
High Dose ◽  
Model Group ◽  
Rat Models

Objective: To study the effects of the ethnic medicine Polygala fallax Hemsl with Guangxi characteristics on the sex hormones and ?-EP in research objective perimenopausal rat models. Methods: 40 female SPF rats were randomly divided into 4 groups, including the normal, model, high-dose and low-dose groups. Rats of three groups except for the normal one were treated with perimenopausal modelling through the method of subcutaneous injection of compound 4-VCD for 15 consecutive days. Rats of the normal and model group were normally fed without any treatment. Rats of the high-dose and low-dose groups were administered by high- and low-dose intragastric administration of the extract of Polygala fallax Hemsl. According to the menstrual cycle of the vaginal smear of the rat, each menstrual cycle is a course of treatment and 6 consecutive courses of treatment would be given. The indexes of serum sex hormones (E2, FSH, LH) and ?-EP of rats in each group were observed after treatment. Results: After the treatment of 6 cycles, for the levels of ?-EP and E2, the model group was lowest (P<0.05), the normal group was highest (P<0.05); and the high-dose group was higher than the low-dose group; For the levels of FSH and LH, the normal group was lowest (P<0.05), the model group was highest (P<0.05), and the high-dose group was lower than the low-dose group. Conclusion: Guangxi characteristic national medicine Polygala fallax Hemsl can effectively improve the levels of serum sex hormones and ?-EP in perimenopausal rat models and relieve the related symptoms with a certain dose-effect relationship.

scholarly journals Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial

2020 ◽  
Vol 105 (5) ◽  
pp. 466-473 ◽  
Author(s):  
Karen Luyt ◽  
Sally L Jary ◽  
Charlotte L Lea ◽  
Grace J. Young ◽  
David E Odd ◽  
...  
Keyword(s):  
Treatment Group ◽  
Randomised Controlled Trial ◽  
Standard Treatment ◽  
Controlled Trial ◽  
Fibrinolytic Therapy ◽  
Ventricular Dilatation ◽  
Cognitive Disability ◽  
Randomised Controlled ◽  
Standard Treatment Group

BackgroundProgressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years.ObjectiveTo assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age.ParticipantsThe RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age.InterventionIntraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device.Primary outcomeCognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability.ResultsOf the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003).ConclusionDRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement.Trial registration numberISRCTN80286058.

Carcinogenesis Bioassay of Propyl Gallate in F344 Rats and B6C3FJ Mice

1983 ◽  
Vol 2 (6) ◽  
pp. 425-433 ◽  
Author(s):  
K. M. Abdo ◽  
J. E. Huff ◽  
J. K. Haseman ◽  
M. P. Dieter ◽  
G. A. Boorman ◽  
...  
Keyword(s):  
Propyl Gallate ◽  
Dose Group ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
High Dose Group ◽  
High Dose ◽  
Preputial Gland ◽  
Rats And Mice ◽  
F344 Rats

Chronic toxicity studies were conducted by maintaining groups of 50 F344 rats and 50 B6C3F1 mice of each sex on nutritionally complete diets containing 0%, 0.6%, or 1.2% propyl gallate for 103 weeks. Survival of rats and mice of both sexes was not significantly affected by the administration of this compound. Dosed rats and mice showed growth retardation and reduced feed utilization efficiency. Increased incidence of hepatic cytoplasmic vacuolization and suppurative inflammation of the prostate gland were observed in dosed male rats and were considered to be related to propyl gallate administration. Tumors of the preputial gland, islet ceil tumors of the pancreas, and pheochromocytoma of the adrenal gland were observed with significantly (p < 0.05) higher incidence in the low-dose male rats; however, there was little evidence of a dose response or of an effect in the high-dose group. Rare tumors (an astrocytoma and a glioma) were found in the brains of two low-dose female rats but none was found in the high-dose group. Malignant lymphoma occurred with a significant (p < 0.05) positive trend in male mice and the incidence in the high-dose group was significantly (p < 0.05) higher than that of the concurrent controls. However, the high-dose incidence was not significantly different from the historical control rate for the laboratory that conducted the bioassay. Under the conditions of the bioassay, propyl gallate was not considered to be clearly carcinogenic for F344 rats, although the increased incidence of preputial gland tumors, islet-cell tumors of the pancreas, and pheochromocytoma of the adrenal glands in low-dose male rats may have been related to compound administration. Thus, the evidence for carcinogenicity in male rats is regarded as being equivocal, while there was no indication of a carcinogenic response in female rats. Propyl gallate was not considered to be carcinogenic for B6C3F1 mice, although the increased incidence of malignant lymphoma in dosed male mice may have been related to administration of the test compound.

Failure of oxygen radical scavengers to modify fatigue in electrically stimulated muscle

1991 ◽  
Vol 69 (10) ◽  
pp. 1470-1475 ◽  
Author(s):  
Ian Shrier ◽  
Sabah Hussain ◽  
Sheldon Magder
Keyword(s):  
Blood Flow ◽  
Dose Group ◽  
Gastrocnemius Muscle ◽  
Low Dose ◽  
Muscle Tension ◽  
Oxygen Radical ◽  
High Dose Group ◽  
High Dose ◽  
Partial Recovery ◽  
Radical Scavengers

We used in situ gastrocnemius muscle of anaesthetized dogs to test the hypothesis that O2 radical production during muscle contraction contributes to fatigue. Muscle tension was measured with a force transducer and blood flow was monitored with an electromagnetic flow probe. Muscle contractions were produced by stimulating the nerve for 15 min at 20 Hz, 12 trains/min, and a duty cycle of 0.25. Three groups of seven animals were given an infusion of 0.2 mL∙min−1 of either saline, low-dose oxygen radical scavengers (250 IU∙mL−1 superoxide dismutase, 640 IU∙mL−1 polyethylene glycol (PEG)-catalase, 0.25 mg∙mL−1 deferoxamine, and 0.1 mg∙mL−1 oxypurinol), or high-dose oxygen radical scavengers (3300 IU∙mL−1 uperoxide dismutase, 6600 IU∙mL−1 PEG-catalase, 2.5 mg∙mL−1 deferoxamine, and 0.1 mg∙mL−1 oxypurinol). Blood flow and vascular resistance of the gastrocnemius muscle during stimulation did not differ among groups. After 15 min of stimulation, the developed tension (represented as a percentage of initial tension developed) was 66 ± 7% in the saline treated group, 70 ± 6% in the low-dose group, and 70 ± 4% in the high-dose group. The change in tension during recovery was not significant in the control or low-dose groups. However, there was partial recovery in the high-dose group. In conclusion, in this preparation, oxygen radical scavengers did not delay the development of decreased muscle tension.Key words: muscle fatigue, oxygen free radicals, resistance, flow.

scholarly journals Adequacy of maternal anesthesia depth with two sodium thiopental doses in elective caesarean section: a randomized clinical trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Golnar Sabetian ◽  
Farid Zand ◽  
Fatemeh Mirhadi ◽  
Mohammad Reza Hadavi ◽  
Elham Asadpour ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cesarean Section ◽  
Apgar Score ◽  
Dose Group ◽  
Low Dose ◽  
Newborn Infants ◽  
High Dose Group ◽  
High Dose ◽  
Depth Of Anesthesia ◽  
Sodium Thiopental

Abstract Background Administration of an optimal dose of anesthetic agent to ensure adequate depth of hypnosis with the lowest risk of adverse effects to the fetus is highly important in cesarean section. Sodium thiopental (STP) is still the first choice for induction of anesthesia in some countries for this obstetric surgery. We aimed to compare two doses of STP with regarding the depth of anesthesia and the condition of newborn infants. Methods In this clinical trial, parturient undergoing elective Caesarian section were randomized into two groups receiving either low-dose (5 mg/kg) or high-dose (7 mg/kg) STP. Muscle relaxation was provided with succinylcholine 2 mg/kg and anesthesia was maintained with O2/N2O and sevoflurane. The depth of anesthesia was evaluated using isolated forearm technique (IFT) and bispectral index (BIS) in various phases. Additionally, infants were assessed using Apgar score and neurobehavioral test. Results Forty parturient were evaluated in each group. BIS was significantly lower in high-dose group at skin incision to delivery and subcutaneous and skin closure. Also, significant differences were noticed in IFT over induction to incision and incision to delivery. Apgar score was significantly lower in high-dose group at 1 min after delivery. Newborn infants in low-dose group had significantly better outcomes in all three domains of the neurobehavioral test. Conclusion 7 mg/kg STP is superior to 5 mg/kg in creating deeper hypnosis for mothers. However, it negatively impacts Apgar score and neurobehavioral test of neonates. STP seems to has dropped behind as an acceptable anesthetic in Cesarean section. Trial registration IRCT No: 2016082819470 N45, 13/03/2019.

Sign in / Sign up

Export Citation Format

Share Document