Acute toxicity, 28-day repeated-dose toxicity and toxicokinetic study of timosaponin BII in rats

Timosaponin BII (TBII), a major steroidal saponin isolated from Anemarrhena asphodeloides Bge., displays a variety of promising pharmacological activities, such as neuroprotection, enhancement of learning and memory, vascular protection and inhibition of platelet aggregation; therefore, it has been developed as a pharmaceutical for prevention or treatment of dementia. Given the safety concerns surrounding timosaponins and the absence of studies on the safety of TBII, the potential toxicity of TBII was evaluated in toxicity and toxicokinetic studies in rats. In the acute oral toxicity study, loose stools were observed in rats receiving 4000 mg/kg, and the symptoms recovered within 1 day. In the 28-day repeated-dose oral toxicity and toxicokinetic study, rats receiving 540 mg/kg showed loose stools and a slight deceleration of body weight growth in both sexes, and the females also showed a slight decrease in food consumption. Moreover, urinalysis indicated reversible treatment-related toxicity in rats receiving 540 mg/kg. The toxicokinetic study demonstrated a dose-dependent increase in systematic exposure to TBII after 28 successive days of oral treatment with TBII. The accumulation coefficients of TBII were 4.35, 1.70 and 1.81, respectively, in rats that received 60, 180 and 540 mg/kg. The no-observed-adverse-effect level (NOAEL) is proposed to be 180 mg/kg.     

Neuropharmacological and acute toxicological evaluation of ethanolic extract of Allamanda cathartica L. flowers and plumieride

Psychiatric diseases affect more than 350 million people all over the world, and medicinal plants have been considered the basis for pharmacological research. The study investigates the anticonvulsant and antidepressant-like activities and acute toxicological effects of ethanolic extract of Allamanda cathartica flowers, and plumieride. The extract was analyzed by HPLC and plumieride was isolated. Toxicity studies were carried out on females Wistar rats (2000 mg/kg). Toxicity was evaluated by measuring biochemical parameters and conducting histopathological analysis. For pharmacological evaluation different doses of the extract (100, 150 and 300 mg/kg, p.o.) and plumieride (0.5, 1 and 2 μg/kg, i.p.) were administered before the Forced-Swimming Test (FST), pentylenetetrazole seizure test (PTZT) or Tail-Suspension Test (TST) in mice. Furthermore, hemolytic activity, cytotoxicity and micronucleus test were performed. In addition, mutagenicity and reproductive/developmental toxicity were estimated by TEST-software analysis. Data show that both treatments induce significant antidepressive-like effect in FST and TST, but not anticonvulsant effect. The effect of plumieride last up to 4 h after treatment. No signs of toxicity, mutagenicity, cytotoxicity or hemolytic activity were observed. The TEST-software demonstrated that plumieride present reproductive/developmental toxicity. Together, the data obtained show that the flowers extract and plumieride present antidepressant-like effect and did not present signals of acute toxicity.     

A comprehensive study on in vitro and in vivo toxicological evaluation of Artemisia capillaris

Artemisia capillaris (AC) has been used as an alternative therapy in obesity, atopic dermatitis, and liver diseases through several biological activity including anti-steatotic, antioxidant, and anti-inflammatory activities. Despite its ethnomedicinal benefits, no sufficient background information is available about the long-term safety and genotoxicity of the AC extract. Therefore, the present study was carried out to investigate the 13-week subchronic toxicity and genotoxicity of the AC extract according to the test guidelines published by the Organization for Economic Cooperation and Development. In the 13-week toxicity study using doses of 25, 74, 222, 667, and 2000 mg/kg body weight, oral administration of the AC extract in male and female rats did not result in any significant adverse effects in food/water consumption, body weight, mortality, hematology, serum biochemistry, organ weight and histopathology. Accordingly, the no-observed-adverse-effect level in rats of both genders was established for the AC extract at 2000 mg/kg/day, the highest dose level tested. In addition, the AC extract was not genotoxic in a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay. In conclusion, we demonstrated that the AC extract is considered as a safe traditional medicine for human consumption.     

Assessment of aquo-ethanolic extract of Camellia sinensis against Carbapenem Resistant Escherichia coli: In Vivo Trials in a Murine Model

The prevalence of Carbapenem Resistant Escherichia coli (CRE) has increased considerably during the last decade, which can be ascribed to relative scarcity of effective non toxic antimicrobial agents. The present study was conducted to evaluate the antimicrobial activity of aquo-ethanolic (1:1) extract of leaves of Camellia sinensis (PTRC-31911-A) against Carbapenem Resistant Escherichia coli at preclinical level using peritonitis infection model in Sprague Dawley rats. Efficacy analysis of PTRC-31911-A involved enumeration of CRE colonies in blood and urine samples of test animals for a period of 5 days from infection. A reduction in microbial count of biological fluids was considered as the primary endpoint of the selected murine model. Physical, biochemical, hematological and histological indices of toxicity were employed as secondary relative indicators of the induced disease. Physical manifestations of infected rats included significantly high body temperature (Temp_Infected = 103.18 °F, ∼5% increase) and noteworthy reduction in weight (Weight_Infected = 126.83 g, ∼15% decrease) as compared to control. Significant (P < 0.05) increase in total white blood cells, eosinophil and monocyte counts as well as a significant decrease (P < 0.05) in erythrocytes count, hematocrit volume, red blood cell distribution width and hemoglobin concentration were observed in the infected group as compared to the control group. Furthermore, noteworthy increase in liver and kidney function test parameters were observed in case of infected groups. All the hematological and biochemical parameters were found to be within optimum range in case of treatment group, indicating restoration of homeostasis. Histopathological studies also presented symptoms of hemorrhage and glomerular damage with structural distortion in glomerular capillary loops of infected groups, which were later recovered in treated groups, indicating the nephro-protective potential of PTRC-31911-A. The study clearly points out that Camellia sinensis extract (PTRC-31911-A; single dose of 5 mg/Kg bwt; oral, + 24 h) is highly effective against Carbapenem Resistant Escherichia coli owing mainly to the presence of flavonoids and polyphenolic compounds, identified by LCMS. Ongoing studies are expected to further unravel the mechanism of action and bioactivity determinants of this broad spectrum plant extract.     

儿童微量元素铁含量与红细胞参数的相关性分析

目的探讨儿童红细胞参数红细胞平均体积（MCV）、红细胞平均血红蛋白浓度（MCHC）与微量元素铁含量的相关性。方法用血细胞分析仪和微量元素机对不同年龄段的儿童和正常成人的血液进行分析。结果儿童红细胞参数（MCV、MCHC）和微量元素铁含量均较成人低（P〈0．05）。结论缺铁是儿童MVC、MCHC比正常成人低的原因之一。     

A 90-day subchronic toxicity study of nivalenol, a trichothecene mycotoxin, in F344 rats.

A subchronic toxicity study of nivalenol (NIV), a trichothecene mycotoxin, was conducted in male and female F344 rats fed diet containing 0, 6.25, 25 or 100 ppm concentration for 90 days. Decrease of body weight and loose stools were observed at 100 ppm in both sexes from the start of the experiment, and body weight reduction was also observed at 25 ppm in males from week 6. At necropsy, many organs demonstrated reduced absolute weights at 100 ppm in both sexes, mostly due to the reduction in the body growth, with reduction of relative thymus weight also being evident in females. Hematologically, decrease of the white blood cell count was found at 100 ppm in males and from 6.25 ppm in females. In addition, decreased platelet counts in both sexes, red blood cell counts in males, and the hemoglobin concentration in females were detected at 100 ppm. Histopathologically, treatment-related changes were predominantly observed in the hematopoietic and immune organs and the anterior pituitary in both sexes and female reproductive organs at 100 ppm, such as thymic atrophy, hypocellularity in the bone marrow, diffuse hypertrophy of basophilic cells with increase of castration cells in the anterior pituitary, and increase of ovarian atretic follicles. Based on the hematological data, the no-observed-adverse-effect level of NIV was determined to be less than 6.25 ppm (0.4 mg/kg body weight/day for both males and females).     

Electroconvulsive therapy,depression, the immune system and inflammation: A systematic review

Background

The management and treatment of major depressive disorder are major public health challenges, the lifetime prevalence of this illness being 4.4%–20% in the general population. Major depressive disorder and treatment resistant depression appear to be, in part, related to a dysfunction of the immune response. Among the treatments for depression ECT occupies an important place. The underlying cerebral mechanisms of ECT remain unclear.

采用ROC曲线评价血液学指标对单基因缺失型珠蛋白生成障碍性贫血的诊断价值

目的 采用ROC曲线探讨血液学指标对单基因缺失型珠蛋白生成障碍性贫血（俗称地中海贫血,简称地贫）的诊断价值,确定平均红细胞体积（MCV）、平均红细胞血红蛋白含量（MCH）、平均红细胞血红蛋白浓度（MCHC）、红细胞计数（RBC）及血红蛋白（Hb）筛查单基因缺失型珠蛋白生成障碍性贫血的最佳截断值（cutoff值）.方法 对基因确诊的124例单基因缺失型珠蛋白生成障碍性贫血患者（实验组）和126例健康体检者（对照组）进行血常规检查,采用ROC曲线分析血液学指标MCV,MCH,MCHC,RBC和Hb,评价其筛查单基因缺失型珠蛋白生成障碍性贫血临床诊断价值.结果 ①对照组与实验组的血液学指标MCH,MCV,MCHC,Hb和RBC分别为（29.9±1.18 vs 26.1±3.01）pg,（88.8±3.38 vs80.2±7.13）fl,（337±10.06 vs 321±18.4）g/L,（133±10.8 vs 123±20.6）g/L和（4.48±0.39 vs4.75±0.61）x10^12/L.与对照组比较,实验组血液学指标MCV,MCH,MCHC和Hb均明显降低,RBC明显增高,差异具有统计学意义（t=-12.09,-13.13,-8.23,-5.09和4.11,P值均＜0.01）.②以基因诊断的结果为金标准,MCH,MCV,MCHC,Hb和RBC的ROC曲线下面积（AUC）分别为0.941,0.894,0.799,0.688,0.630;最佳cutoff值分别为28.35 pg,84.75 fl,329.5g/L,125.5 g/L,4.17×10^12/L;对应的灵敏度和特异度,分别是MCH（88.7％,90.5％）,MCV（77.4％,89.7％）,MCHC（69.5％,77.0％）,Hb（61.3％,78.6％）,RBC（51.6％,75.4％）.③在AUC＞0.75的三项指标中,MCH的诊断灵敏度最高,明显高于MCV和MCHC（P＜0.05,卡方值5.62,14.02）,MCH和MCV的特异度明显高于MCHC（P＜0.05,卡方值8.42,7.31）,差异具有统计学意义.结论 用ROC曲线分析的结果表明MCV,MCH,MCHC对单基因缺失型珠蛋白生成障碍性贫血有较好的诊断价值（AUC＞0.75）,其中MCH的诊断价值最高（AUC＞0.9）,以MCV,MCH和MCHC的最佳cutoff值作为单基因缺失型珠蛋白生成障碍性贫血筛查指标具有较好的临床诊断?     

缺铁性贫血MCHC结果分析

在实际工作中常发现部分缺铁性贫血(IDA)患者用阻抗型血液分析仪得出的红细胞平均血红蛋白浓度(MCHC)结果不符合理论数据,给临床和教学工作带来不便.为弄清形成这种结果的原因同时了解该型血液分析仪在贫血形态学诊断中的价值,我们观察了阻抗型血液分析仪对103例IDA患者红细胞参数测定结果进行了比较和分析.     

冷凝集对血细胞分析多项参数检测结果的影响

目的 探讨红细胞冷凝集对血细胞分析各项检测参数的影响及处理方法.方法 选择福建省肿瘤医院2017年12月至2020年2月有红细胞冷凝集的全血标本73份.应用Sysmex XN-9000全自动血细胞分析仪对标本进行检测,比较37℃水浴前后红细胞(RBC)、血细胞比容(HCT)、平均红细胞体积(MCV)、平均红细胞血红蛋白...