One-year chronic toxicity study of Aloe arborescens Miller var. natalensis Berger in Wistar Hannover rats. A pilot study.

This study was conducted to evaluate the chronic toxicity of Aloe arborescens Miller var. natalensis Berger (ALOE) in the diet at doses of 4.0%, 0.8% or 0.16% to groups of male and female Wistar Hannover rats. No deaths occurred at any dose level throughout the treatment period. Both sexes receiving 4.0% showed diarrhea, with a reduced body weight gain. Increase of WBCs in the male 4.0% group, decrease of Hb in the female 4.0% and 0.8% groups, decrease of IP in the male 4.0% and 0.8% groups and female 4.0% group, and decrease of Ca and ALT in the female 4.0% group were observed. Relative kidney weight showed increase in the female 4.0% group and relative heart and brain weights were decreased in the female 4.0% and 0.8% groups. Histopathologically, both sexes receiving 4.0% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. In conclusion, the no observed adverse effect level (NOAEL) for ALOE was the 0.16% in diet, which is equivalent to 87.7 and 109.7 mg/kg/day in males and females, respectively.     

Short-term toxicity of pentachlorophenol in rats

Pentachlorophenol (PCP) was fed to rats at dietary levels of 0, 25, 50 and 200 ppm for 12 weeks. Growth was decreased in the group of female rats fed 200 ppm. The treatment had no effect on food intake and behaviour. Liver weight was increased at the 50 and 200 ppm dose levels accompanied by an increased activity of microsomal liver enzymes. In week 6 higher haemoglobin and haematocrit values were found in the groups of males fed 50 and 200 ppm. In week 11 the haemoglobin values and the number of erythrocytes were decreased in the same groups of males. A possible explanation is discussed. A striking dose-related decrease of calcium deposits in the kidney is found. The no-toxic-effect level for all criteria is considered to be 25 ppm.     

Short-term toxicity of strontium chloride in rats

A range-finding experiment with strontium chloride hexahydrate (0, 3, 30, 300 and 3000 ppm in the diet) and subsequently a 90-day test with the same compound at dose levels of 0, 75, 300, 1200 and 4800 ppm in a semi-purified diet was carried out with SPF-derived Wistar-rats. The diet contained adequate levels of Ca, Mg, P and Vit.D₃. Growth, food intake, behavior and mortality were measured, extensive haematology and clinical biochemistry carried out, organ weights determined, X-ray photographs of the bones taken and complete histopathological examination was performed. In addition Sr-content of blood, bone and muscles was determined. Thyroid weights were significantly increased in the males of the 1200 and 4800 ppm group. Histological evidence for increased thyroid activity was noticed in the males of the 4800 ppm group. Pituitary weights were significantly decreased in the females of the 300 ppm and 4800 ppm group, but not of the 1200 ppm group. A histologically confirmed glycogen depletion of the liver was noted biochemically in the highest dose group (4800 ppm).Sr-content in bone was increased at all dose levels having a constant level from 4 weeks onwards, thus indicating that a no effect level cannot be established. If the increased Sr-concentration in the bone can be considered a non-toxic effect, the non-toxic effect level appears to be 300 ppm.     

乳糜血标本对平均红细胞血红蛋白浓度复检规则临床应用的影响

目的 探讨乳糜血标本对system XE-2100全自动血细胞分析仪复检规则中平均红细胞血红蛋白浓度复检规则临床应用的影响.方法 采用system XE-2100全自动血细胞分析仪对4 817例患者的静脉血标本进行血细胞分析及三酰甘油测定,对乳糜血标本在该仪器复检规则中平均红细胞血红蛋白浓度复检规则的临床应用进行分析.结果 本组严重乳糜血（三酰甘油≥5.64 mmol·L^-1）标本101份,平均红细胞血红蛋白浓度为（365.73±8.79）g·L^-1;乳糜血标本对平均红细胞血红蛋白浓度的影响未触动复检规则（≥380 g·L^-1）.结论 本仪器严重乳糜血标本对平均红细胞血红蛋白浓度的影响未触动复检规则,建议将平均红细胞血红蛋白浓度的复检标准由≥380 g·L^-1调至≥365 g· L^-1.     

Interactions between essential and toxic elements in lead exposed children in Katowice, Poland

Objectives: To determine the influence of the essential element status on blood concentrations of lead and other toxic metals.

Design and methods: A group of 157 children from Katowice, an industrial area in Poland, was investigated for concentrations of lead and cadmium in whole blood, and mercury, selenium, zinc, copper, and magnesium in whole blood and serum. Relations between these elements, serum ferritin, hematological parameters, as well as serum selenoprotein P and glutathione peroxidase (GSH-px) were examined. Conversion factors for element concentrations (μmol to μg): lead 207.19, cadmium 112.41, mercury 200.59, selenium 78.96, magnesium 24.31, copper 63.55, and zinc 65.

Results: Blood lead was negatively associated with concentrations of selenium in whole blood and serum as well as selenoprotein P and glutathione peroxidase in serum. The association was mainly apparent at low blood lead concentrations, which may indicate an influence of selenium on the kinetics of lead, rather than an effect of lead on the selenium status. Children with low serum ferritin levels had statistically higher blood cadmium levels and a tendency for higher blood lead levels, indicating increased gastrointestinal absorption of these metals at reduced iron stores. Blood lead was negatively correlated with mean corpuscular hemoglobin concentration, which may reflect the effect of lead on hemoglobin synthesis. There was an association between blood mercury and selenium, indicating a common source of intake through fish consumption.

Conclusions: The results indicate that selenium and iron status may influence the kinetics of lead.     

The estimation of ammonia in kidney slices in the presence of added glutamine and other amino acids.

This paper reports a study of changes in red blood cell enzymes and some serum parameters during and after treatment of protein-calorie malnutrition. The red cell GSH levels were low during the crisis, together with the levels of GSSG:NADPH reductase, GSH:H₂O₂ peroxidase, aspartate aminotransferase and alanine aminotransferase. After treatment the levels of all these enzymes increased significantly to normal values.Of the serum parameters investigated, significant reduction in the activity of the enzymes cholinesterase, catecholamine oxidase, total proteins, albumin, urea and electrolytes were obvious, and returned to normal values after treatment. Ceruloplasmin activity remained low even after three weeks' treatment and could not be related to copper levels.The results are discussed in relation to anemia and liver damage that may accompany the syndrome.     

Pre-clinical safety evaluation of the synthetic human milk,nature-identical,oligosaccharide 2′-O-Fucosyllactose (2′FL)

In order to match the composition of human breast milk more closely, it is now possible to supplement commercial infant formula (IF) with synthesised oligosaccharides that are chemically identical to human milk oligosaccharides. The safety data generated on a new human-identical milk oligosaccharide (HiMO), 2′-O-Fucosyllactose (2′FL), are presented. Standard in vitro genotoxicity tests were performed. To investigate the toxicological profile in a model representative of the intended target population, 2′FL was administered via gavage in a juvenile adapted sub-chronic rat study at dose levels of 0, 2000, 5000 and 6000 mg/kg bw/day. Fructooligosaccharide (FOS), currently acknowledged as safe and approved for use in IF, was used as a reference high-dose control at 6000 mg/kg bw/day. 2′FL was non-mutagenic in the in vitro assays. Oral administration up to 5000 mg/kg bw/day to rats over 90 days was not associated with any adverse effects based on clinical observations, body weight gain, food consumption, ophthalmoscopy, clinical pathology, organ weights and histopathology findings. Based on this 90-day study, a No Observed Adverse Effect Level (NOAEL) of 5000 mg/kg bw/day for both male and female rats was established for 2′FL. These findings support the safety of synthetic 2′FL for possible use in infant food.     

Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats

The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000–2000 mg/kg body weight (bw) in male and 500–1000 mg/kg bw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100 mg/kg bw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study.     

The clock gene Per2 is required for normal platelet formation and function

Introduction

Apoptotic cell death is a highly regulated genetic program, which has been observed in mature megakaryocytes fragmenting into platelets. The clock gene Per2, a key component of core clock oscillator, was involved in affecting both cell cycle control and apoptosis. Thus, loss of Per2 function may be considered potential influence of platelet formation and function.

Methods

Per2-null mice and C57BL/6 mice were used in the study. Bleeding time, platelet count, megakaryocyte count, megakaryocyte ploidy, megakaryocyte apoptosis, rate of proplatelet formation, clot retraction, platelet aggregation and secretion were performed to evaluate thrombopoiesis and hemostasis. Quantitative RT-PCR was employed to analyze genes expression in liver, bone marrow and enriched megakaryocytes.

Results

The Per2-null mice had nearly 50% platelet counts in peripheral blood. Per2-null platelets were compromised in their ability to aggregate and secretion, consistent with a marked reduction in the number of dense and a-granules. Megakaryocytes from Per2-null mice showed no significant variation in number but increased in ploidy. Ultrastructural examination of Per2-null megakaryocytes revealed many vacuoles in demarcation membranes and reduction in platelet granules. Megakaryocytes from Per2-null bone marrow decreased the rate of proplatelet formation and impaired apoptosis. Per2-null mice showed increased both in Tpo in livers and its receptors C-mpl in bone marrow, and the megakaryocytes from these mice decreased P53 expression, consequently increased Bcl-xl and Bcl-2 level.

Conclusions

The clock gene Per2 modulating the apoptosis of megakaryocytes was required for platelet formation and function.     

Safety assessment of yerba mate (Ilex paraguariensis) dried extract: results of acute and 90 days subchronic toxicity studies in rats and rabbits

Acute toxicity of yerba mate dried extract (YMDE) was investigated in Wistar rats (6/sex/group) from single dose of 2g/kg body weight by intragastric administration and 14days monitoring. Subchronic toxicity was investigated in Wistar rats, by intragastric administration (10/sex/group), and in New Zealand rabbits by oral administration (3/sex/group) of 2g/kg body weight for 12weeks. Toxicological parameters included clinical signs, body weight, water, and food consumption, hematological and serum parameters, and histopathological assessment. Acute YMDE administration showed no effects on survival, clinical observations, macroscopic examination of organs, body weight or food, and water consumption. Sub-chronic administration of YMDE did not change behavior, body weight, and histopatological assessment of stomach, kidney, liver, and small gut. Moreover, most of biochemical and hematological parameters remained unchanged. In summary, the results of our preclinical toxicological investigation are indicative that the YMDE is well tolerated for both single and chronic administration.