scholarly journals Pneumocystis pneumonia in patients with rheumatic diseases receiving prolonged, non-high-dose steroids—clinical implication of primary prophylaxis using trimethoprim–sulfamethoxazole

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Won Park ◽  
Jeffrey R. Curtis ◽  
Min Jung Kim ◽  
Hajeong Lee ◽  
Yeong Wook Song ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Rheumatic Diseases ◽  
Dose Group ◽  
Low Dose ◽  
Pneumocystis Pneumonia ◽  
Control Group ◽  
High Dose ◽  
Number Needed To Treat ◽  
Medium Dose

Abstract Objectives To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis. Methods This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim–sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis. Results One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001–0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2–1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1–8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001–2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3–71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17–226)) was lower than the number needed to harm by serious ADR (45 (15–∞)). Conclusion Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.

scholarly journals Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids

2017 ◽  
Vol 77 (5) ◽  
pp. 644-649 ◽  
Author(s):  
Jun Won Park ◽  
Jeffrey R Curtis ◽  
Jinyoung Moon ◽  
Yeong Wook Song ◽  
Suhnggwon Kim ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Cox Regression ◽  
Fatal Case ◽  
Pneumocystis Pneumonia ◽  
Stevens Johnson Syndrome ◽  
Control Group ◽  
High Dose ◽  
Number Needed To Treat ◽  
Primary Analysis ◽  
Prophylaxis Group

ObjectivesTo investigate the efficacy and safety of trimethoprim/sulfamethoxazole (TMP-SMX) as primary prophylaxis for pneumocystis pneumonia (PCP) in patients with rheumatic diseases receiving high-dose steroids.MethodsThe study included 1522 treatment episodes with prolonged (≥4 weeks) high-dose (≥30 mg/day prednisone) steroids in 1092 patients over a 12-year period. Of these, 262 treatment episodes involved TMP-SMX (prophylaxis group) while other episodes involved no prophylaxis (control group). Differences in 1-year PCP incidence and its mortality between the two groups were estimated using Cox regression. To minimise baseline imbalance, propensity score matching was performed and efficacy outcome was mainly assessed in the postmatched population (n=235 in both groups).ResultsDuring a total of 1474.4 person-years, 30 PCP cases occurred with a mortality rate of 36.7%. One non-fatal case occurred in the prophylaxis group. TMP-SMX significantly reduced the 1-year PCP incidence (adjusted HR=0.07(95% CI 0.01 to 0.53)) and related mortality (adjusted HR=0.08 (95% CI 0.0006 to 0.71)) in the postmatched population. The result of the same analysis performed in the whole population was consistent with that of the primary analysis. Incidence rate of adverse drug reactions (ADR) related to TMP-SMX was 21.2 (14.8–29.3)/100 person-years. Only two serious ADRs (including one Stevens-Johnson syndrome case) occurred. The number needed to treat for preventing one PCP (52 (33–124)) was lower than the number needed to harm for serious ADR (131 (55–∞)).ConclusionTMP-SMX prophylaxis significantly reduces the PCP incidence with a favourable safety profile in patients with rheumatic disease receiving prolonged, high-dose steroids.

scholarly journals The Effect of Lactobacillus plantarum BW2013 on The Gut Microbiota in Mice Analyzed by 16S rRNA Amplicon Sequencing

2021 ◽  
Vol 70 (2) ◽  
pp. 235-243
Author(s):  
TONG TONG ◽  
XIAOHUI NIU ◽  
QIAN LI ◽  
YUXI LING ◽  
ZUMING LI ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Dose Group ◽  
Low Dose ◽  
Amplicon Sequencing ◽  
Control Group ◽  
High Dose ◽  
Treatment Groups ◽  
16S Rrna Amplicon Sequencing ◽  
Medium Dose

Lactobacillus plantarum BW2013 was isolated from the fermented Chinese cabbage. This study aimed to test the effect of this strain on the gut microbiota in BALB/c mice by 16S rRNA amplicon sequencing. The mice were randomly allocated to the control group and three treatment groups of L. plantarum BW2013 (a low-dose group of 108 CFU/ml, a medium-dose group of 109 CFU/ml, and a high-dose group of 1010 CFU/ml). The weight of mice was recorded once a week, and the fecal samples were collected for 16S rRNA amplicon sequencing after 28 days of continuous treatment. Compared with the control group, the body weight gain in the treatment groups was not significant. The 16S rRNA amplicon sequencing analysis showed that both the Chao1 and ACE indexes increased slightly in the medium-dose group compared to the control group, but the difference was not significant. Based on PCoA results, there was no significant difference in β diversity between the treatment groups. Compared to the control group, the abundance of Bacteroidetes increased in the low-dose group. The abundance of Firmicutes increased in the medium-dose group. At the genus level, the abundance of Alloprevotella increased in the low-dose group compared to the control group. The increased abundance of Ruminococcaceae and decreased abundance of Candidatus_Saccharimonas was observed in the medium-dose group. Additionally, the abundance of Bacteroides increased, and Alistipes and Candidatus_Saccharimonas decreased in the high-dose group. These results indicated that L. plantarum BW2013 could ameliorate gut microbiota composition, but its effects vary with the dose.

scholarly journals Effects of aqueous leaf extract of Telfairia occidentalis on haematological parameters and liver enzymes in male Wistar rats

2020 ◽  
Vol 6 (1) ◽  
pp. 44-50
Author(s):  
IO Osonuga ◽  
AS Faponle ◽  
EN Ezima ◽  
TK Adenowo ◽  
AA Adelegan
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Liver Enzymes ◽  
Blood Parameters ◽  
Control Group ◽  
High Dose ◽  
Leaf Extracts ◽  
Telfairia Occidentalis ◽  
Male Wistar Rats ◽  
Medium Dose

Background: The leaves of Telfairia occidentalis (locally known as Ugu) are widely consumed as part of a staple in the southern region of Nigeria. Its nutritional benefits include its rich mineral contents and antioxidant properties. It has been suggested that the leaf extracts may affect blood parameters. Objectives: To investigate the effects of aqueous extracts of T. occidentalis leaves on haematological indices and liver enzymes in rats. Methods: Twenty-four male Wistar rats weighing between 150g and 200g were used for the study. They were categorized into four groups of six rats each viz: high-dose, medium-dose, low-dose, and control groups. The leaf extract was administered in doses of 300mg/kg, 200mg/kg, and 100 mg/kg, respectively, while the control group received distilled water rather than leaf extracts.  Results: There was a dose-dependent decrease in the concentrations of liver enzymes and an increase in blood parameters. There was a significant difference (p = 0.000) in the mean red blood cells countof the control group (7.5±0.2×1012/L) compared to the low-dose group (9.1±0.1×1012/L), the medium-dose group (11.7±0.2×1012/L) and the high-dose group (13.3±0.2×1012/L).For the liver enzymes, there was a significant decrease in the mean AST levels in the high-dose group (42.8±3.5 IU/L), the medium-dose group (53.7±5.7IU/L) and the low-dose group (68.5±3.5IU/L) were compared to the value for the control group (88.6 ±2.5× 1012/L). Conclusions: Using an animal model, Telfairia occidentalis may have hepatoprotective and haemopoietic properties.

scholarly journals Risk-benefit analysis of isoniazid monotherapy to prevent tuberculosis in patients with rheumatic diseases exposed to prolonged, high-dose glucocorticoids

2020 ◽  
Author(s):  
Jun Won Park ◽  
Jeffrey R Curtis ◽  
Hajeong Lee ◽  
Jung-Kyu Lee ◽  
Yeong Wook Song ◽  
...  
Keyword(s):  
High Risk ◽  
Rheumatic Diseases ◽  
Interferon Γ ◽  
Control Group ◽  
High Dose ◽  
Number Needed To Treat ◽  
Risk Patients ◽  
Release Assay ◽  
Risk Benefit Analysis ◽  
Number Needed To Harm

Abstract Objective To investigate the incidence of tuberculosis (TB) in patients with rheumatic diseases receiving high-dose glucocorticoids and to evaluate the preventive effect of isoniazid (INH). Methods This study included 1618 treatment episodes of prolonged (≥4 weeks), high-dose steroids (≥30mg/day of prednisone) in 1160 patients. Of these, INH was administered in 152 (9.4%) treatment episodes (INH group), while others received no prophylaxis (control group). The high-risk subgroup (n=92) was defined as patients with 1) incomplete adherence to treatment of previous TB, 2) positive interferon-γ release assay, and/or 3) linear/reticular fibrotic lesions on chest radiographs. Primary outcome was 1-year incidence of TB in each group. Results During 1579.8 person-years, 21 cases of TB occurred. The high-risk subgroup showed a significantly higher TB incidence than the non-high-risk subgroup (Incidence rate ratio=8.29). INH did not significantly affect the 1-year TB incidence in the whole population but numerically reduced it only in the high-risk subgroup [adjusted hazards ratio=0.48 (95% CI, 0.003–5.46)]. The incidence of adverse drug reactions (ADRs) related to INH was 111.6 (89.3–137.9)/100 person-years, including one fatal occurrence of fulminant hepatitis. The number needed to treat (NNT) to prevent one case of TB was lower than the number needed to harm (NNH) for one case of serious ADR only in the high-risk subgroup (3 vs. 11). Conclusion INH treatment to prevent TB might be effective in high-risk patients but has a risk of frequent ADRs, which limits its use in general practice in patients not at a high risk of developing TB.

scholarly journals Androgenic Effects of Cinnamomum camphora in Male Sprague-dawley Rats

2019 ◽  
pp. 1-13
Author(s):  
O. H. Ayoade ◽  
G. G. Akunna ◽  
F. I. Duru
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Activity Level ◽  
Control Group ◽  
High Dose ◽  
Activity Levels ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Medium Dose

This study evaluated camphora-induced androgenic and histopathological changes in male Sprague-Dawley rats. Thirty-five animals weighing 200 g±20 g were used for this study and randomly divided equally into five groups, with seven rats in each group. Group A animals (normal control group) were served water and rat chow only; Groups B-D (treatment groups) were orally administered camphora in doses of 1 g/kg (Low-dose), 2 g/kg (Medium-dose) and 4 g/kg (High-dose) respectively while Group E (vehicle group) were orally administered 6 mL/kg olive oil (a solvent for camphora) per day for 56 days. There was a significant decrease (P< .05) in activity levels of Follicle-Stimulating Hormone (FSH); Superoxide Dismutase (SOD) when the treatment was compared with the control group. Also, a significant decrease (P< .05) in activity level of FSH was observed when the Medium-dose group was compared with Low-dose group. Insignificant irregular pattern in activity level of Testosterone was observed across the treatment groups when compared with the control. However, a significant increase (P< .05) in activity level of Testosterone was observed when the High-dose group was compared with the Medium-dose group. There was a significant increase (P< .05) in activity levels of Luteinizing Hormone (LH) and Malondialdehyde (MDA) when the treatment was compared with the control group. Semen analysis showed reduction in sperm concentration, motility and morphology with increasing concentration of camphora. Significant decrease was recorded in testicular weight when High-dose group was compared to Control and Low-dose groups. Histopathological changes were seen in the testes of the camphor administered groups, ranging from mild disintegrated interstitial tissues in Low-dose to severe degeneration and disintegration of both seminiferous and interstitial tissues in the testes in the Medium-dose and High-dose groups. In conclusion, camphora had androgenic and toxic effects on testis and may cause testicular tissue damage.

scholarly journals Effects of DI-(2-Ethylhexyl) Phthalate on Rat Ovarian Function

2011 ◽  
Vol 30 (4) ◽  
pp. 309-316
Author(s):  
Cheng-kang Xu ◽  
Xiao-hong Wang ◽  
Shuang-bo Tang
Keyword(s):  
Estrous Cycle ◽  
Dose Group ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Short Course ◽  
Long Course ◽  
Ethylhexyl Phthalate ◽  
Medium Dose

Effects of DI-(2-Ethylhexyl) Phthalate on Rat Ovarian FunctionThis study aimed to evaluate the effects of di-(2-ethylhexyl)phthalate (DEHP) on estrous cycle, sex hormone levels and ovary histological features. A total of 80 female SD rats were randomly divided into 8 groups (n=10 per group): short-course control group, short-course low-dose group, short-course medium-dose group, and short-course high-dose group, long-course control group, long-course low-dose group, long-course medium-dose group and long-course high-dose group. Intragastrical DEHP was administrated at 1000 mg/kg/d (low dose), 2000 mg/kg/d (medium dose) and 3000 mg/kg/d (high dose) independently for 14 days (short course) or 28 days (long course). Rats in control groups were untreated. Vaginal smearing was used to detect the estrous cycle and rats were weighed at every Monday and Thursday to evaluate the growth status. At the end of study, rats were sacrificed and bilateral ovaries were obtained for histological examination. In addition, ELISA determined levels of serum progesterone, estradiol, testosterone, follicle stimulating hormone and luteinizing hormone. DEHP treatment limited body weight gain (p<0.05), prolonged the estrous cycle (p<0.05), decreased the ovarian mass index (p<0.05) and ovarian weight. No evident degeneration, necrosis or other pathological features were found in the ovaries. The testosterone levels were decreased by DEHP treatment in a dose dependent manner. DEHP treatment could increase serum testosterone level, inhibit ovulation and prolong the estrous cycle of rats, exerting reproductive toxicity in a dose dependent manner. We speculate DEHP can affect the endocrine regulatory function of the ovary and limit the body weight gain, resulting in chronic toxicity.

scholarly journals Risk-benefit analysis of isoniazid monotherapy to prevent tuberculosis in patients with rheumatic diseases exposed to prolonged, high-dose glucocorticoids

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244239
Author(s):  
Jun Won Park ◽  
Jeffrey R. Curtis ◽  
Hajeong Lee ◽  
Jung-Kyu Lee ◽  
Yeong Wook Song ◽  
...  
Keyword(s):  
High Risk ◽  
Rheumatic Diseases ◽  
Interferon Γ ◽  
Control Group ◽  
High Dose ◽  
Number Needed To Treat ◽  
Risk Patients ◽  
Release Assay ◽  
Risk Benefit Analysis ◽  
Number Needed To Harm

Objective To investigate the incidence of tuberculosis (TB) in patients with rheumatic diseases receiving high-dose glucocorticoids and to evaluate the preventive effect of isoniazid (INH). Methods This study included 1618 treatment episodes of prolonged (≥4 weeks), high-dose steroids (≥30mg/day of prednisone) in 1160 patients. Of these, INH was administered in 152 (9.4%) treatment episodes (INH group), while others received no prophylaxis (control group). The high-risk subgroup (n = 92) was defined as patients with 1) incomplete adherence to treatment of previous TB, 2) positive interferon-γ release assay, and/or 3) linear/reticular fibrotic lesions on chest radiographs. Primary outcome was 1-year incidence of TB in each group. Results During 1579.8 person-years, 21 cases of TB occurred. The high-risk subgroup showed a significantly higher TB incidence than the non-high-risk subgroup (Incidence rate ratio = 8.29). INH did not significantly affect the 1-year TB incidence in the whole population but numerically reduced it only in the high-risk subgroup [adjusted hazards ratio = 0.37 (95% CI, 0.002–5.10)]. The incidence of adverse drug reactions (ADRs) related to INH was 111.6 (89.3–137.9)/100 person-years, including one fatal occurrence of fulminant hepatitis. The number needed to treat (NNT) to prevent one case of TB was lower than the number needed to harm (NNH) for one case of severe ADR only in the high-risk subgroup (11 vs. 16). Conclusion INH treatment to prevent TB might be effective in high-risk patients but has a risk of frequent ADRs, which limits its use in general practice in patients not at a high risk of developing TB.

scholarly journals Safety and efficacy of Edaravone Dexborneol versus edaravone for patients with acute ischaemic stroke: a phase II, multicentre, randomised, double-blind, multiple-dose, active-controlled clinical trial

2019 ◽  
Vol 4 (3) ◽  
pp. 109-114
Author(s):  
Jie Xu ◽  
Yilong Wang ◽  
Anxin Wang ◽  
Zhiqiang Gao ◽  
Xiaoping Gao ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Multiple Dose ◽  
Dose Group ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Score Change ◽  
Double Blind ◽  
Significant Difference ◽  
Medium Dose

BackgroundEdaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and (+)-borneol, a food additive with an anti-inflammatory effect in animal ischaemic stroke models. This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke (AIS).MethodsIn this multicentre, randomised, double-blind, multiple-dose, active-controlled, phase II clinical trial, patients with AIS within 48 hours after stroke onset were randomly assigned (1:1:1:1) to low-dose (12.5 mg), medium-dose (37.5 mg) or high-dose (62.5 mg) Edaravone Dexborneol groups, and an active control group with edaravone (30 mg) by 30 min intravenous infusion every 12 hours, for 14 consecutive days. The primary efficacy outcome was the proportion of modified Rankin Scale (mRS)score ≤1 at 90 days and National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 14 days after randomisation. The safety outcome included any adverse event during 90 days after treatment.ResultsOf 385 patients included in the efficacy analysis, 94 were randomised to low-dose group, 97 to medium-dose group, 98 to high-dose group and 96 to the control group. No significant difference was observed among the four groups on mRS score (mRS ≤1, p=0.4054) at 90 days or NIHSS score change at 14 days (p=0.6799). However, a numerically higher percentage of patients with mRSscore ≤1 at 90 days in the medium-dose (69.39%) and high-dose (65.63%) groups was observed than in the control group (60.64%). No significant difference in severe adverse events was found among the four groups (p=0.3815).ConclusionsCompared with edaravone alone, Edaravone Dexborneol was safe and well tolerated at all doses, although no significant improvement in functional outcomes was observed at 90days.Trial registration numberNCT01929096.

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 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).

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