Impact of high doses of Statins on testosterone level in males with atherosclerotic coronary artery disease

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Walid Said Ibrahim ◽  
Mohamed Moustafa Farouk ◽  
Mazen Tawfik ◽  
Sherif Samir Elzahwy
Keyword(s):  
Testosterone Level ◽  
Dose Group ◽  
Low Dose ◽  
De Novo ◽  
Medical Center ◽  
Health Effect ◽  
High Dose Group ◽  
High Dose ◽  
High Doses ◽  
The Impact

Abstract Background Concern has always existed that statins might impair testosterone production either by reducing availability of its preferred substrate, that is, locally produced de novo cholesterol in the gonads and elsewhere, or by inhibiting steps in the steroidogenesis process, but this concern has been considered of little clinical significance. Objective To demonstrate the impact of high doses of statins on testosterone level in ischemic heart disease patients and to compare it with the impact of low doses of statins. Patients and Methods This study was approved by Ain Shams University. 90 candidates were randomly enrolled in the study divided into two groups, high dose group consisting of 45 patients and Low dose group including 45 patients. All patients were recruited from International Medical Center in Cairo, they were selected randomly from the outpatient clinic from the cardiology department. Results In our study there were a significant reduction in total cholesterol, LDL and TGs in both low dose and high dose groups, but the effect on testosterone was quite different between them, the reduction in testosterone was about 33% from the baseline in the high dose group while in the low dose there was no significant reduction in the testosterone level. Conclusion This study shows that statins reduce testosterone level. This finding does not demonstrate that androgens mediate any health effect of statins, but raises the question as to whether testosterone modulation plays a role in statins' effects on health, particularly among men where testosterone is an important hormone.

scholarly journals Improved Outcome of Biliary Atresia with Postoperative High-Dose Steroid

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Rui Dong ◽  
Zai Song ◽  
Gong Chen ◽  
Shan Zheng ◽  
Xian-min Xiao
Keyword(s):  
Biliary Atresia ◽  
Dose Group ◽  
Low Dose ◽  
Oral Prednisolone ◽  
High Dose Group ◽  
High Dose ◽  
High Dose Steroid ◽  
Steroid Group ◽  
Native Liver ◽  
The Impact

Objective. The dosage, duration, and the benefits of high-dose steroid treatment and outcome in biliary atresia (BA) remain controversial. In this study, we evaluated the impact of high-dose steroid therapy on the outcome of BA after the Kasai procedure.Methods.Intravenous prednisolone administration was started 1 week after surgery, followed by 8 to 12 weeks of oral prednisolone. Total bilirubin (TB) levels (3, 6, and 12 months after surgery), early onset of cholangitis, and two-year native liver survival were evaluated.Results.53.4%, 56.9%, and 58.1% of the patients in the high-dose steroid group were jaundice-free 3, 6, and 12 months after surgery, respectively; these values were significantly higher than the 38.7%, 39.4%, and 43.3% of the low-dose steroid group. One year after surgery, the incidence of cholangitis in the high-dose group (32.0%) was lower than that in the low-dose group (48.0%). Infants with native liver in the high-dose group had a better two-year survival compared to those in the low-dose steroid group (53.7% versus 42.6%).Conclusions.The high-dose steroid protocol can reduce the incidence of cholangitis, increase the jaundice-free rate, and improve two-year survival with native liver after the Kasai operation.

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.

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.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

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 CD8+ T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

2003 ◽  
Vol 77 (24) ◽  
pp. 13323-13334 ◽  
Author(s):  
Yang Wang ◽  
Mario Lobigs ◽  
Eva Lee ◽  
Arno Müllbacher
Keyword(s):  
T Cells ◽  
Dose Group ◽  
Low Dose ◽  
Neuronal Degeneration ◽  
High Dose ◽  
West Nile ◽  
Activation Markers ◽  
High Doses ◽  
The Brain ◽  
Deficient Mice

ABSTRACT C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (108 PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (103 PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8+, but not CD4+, T cells. CD8+ T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8+ T-cell-deficient mice infected with 103 PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8+ T cells are involved in both recovery and immunopathology in WNV infection.

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.

Effects of long-term continuous GnRH administration on the pituitary–gonadal axis in Eld's deer stags (Cervus eldi thamin)

1995 ◽  
Vol 73 (9) ◽  
pp. 1609-1619 ◽  
Author(s):  
S. L. Monfort ◽  
J. L. Brown ◽  
T. C. Wood ◽  
M. Bush ◽  
L. R. Williamson ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
High Dose ◽  
Fertile Period ◽  
Nonbreeding Season ◽  
Testosterone Secretion ◽  
High Doses ◽  
Seasonal Decline ◽  
Seasonally Breeding

Eld's deer stags (Cervus eldi thamin) (in groups of three) were continuously administered gonadotropin-releasing hormone (GnRH) in control, low, medium, or high doses (0, 20.1 ± 0.7, 83.3 ± 2.6, and 292.9 ± 4.9 ng∙kg−1∙d−1, respectively) via osmotic minipumps for ~80 d to investigate the potential for precociously reactivating the pituitary–testicular axis during the nonbreeding season. Secretory patterns of LH, FSH, and testosterone concentrations were qualitatively similar among treatments. However, in the low-dose group, basal LH and FSH concentrations were both increased (p < 0.05) and pituitary responsiveness to a superimposed GnRH challenge was augmented (p < 0.05) after 12 weeks of treatment compared with all other groups. Despite these endocrine changes, continuous low-dose GnRH administration was not effective for precociously inducing testicular activity in this seasonally breeding species. High-dose GnRH administration initially induced a transient increase in LH, FSH, and testosterone secretion and delayed, but did not prevent, the seasonal decline in spermatogenesis. After 6–12 weeks of high-dose GnRH administration, however, attenuated pituitary responsiveness appeared to delay the normal seasonal reactivation of the pituitary–gonadal axis. In conclusion, prolonged, continuous low-dose GnRH administration did not effectively translate into a precocious onset of testicular activity; therefore, this specific approach is unlikely to be useful for prolonging the fertile period in this seasonally breeding species.

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.

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