Toluene-induced Decrease in Rat Plasma Concentrations of Tyrosine and Tryptophan

Abstract: The organic solvent toluene is demonstrated to cause a decrease in rat plasma concentrations of tyrosine and tryptophan both after intraperitoneal injections and after inhalation. Tyrosine and tryptophan are precursors to neurotransmitters and are transported from plasma into the brain. As the concentrations of these amino acids in plasma could influence the monoamine synthesis in the brain, this phenomenon might be of importance for the pathophysiology behind solvent-induced effects on brain function.     

Excretion of Zinc in Rat Bile – A Role of Glutathione

Abstract: Fractionation of the bile from rats injected with ⁶⁵ZnCl₂ (5 μmol/kg) showed that zinc was mainly bound to low molecular weight compounds eluted corresponding to the zinc-glutathione complexes. Diethylmaleate (3.9 mmol/kg), cyclohexene oxide (4.9 mmol/kg) and acrylamide (3.5 mmol/kg) administered intraperitoneally to rats caused a rapid decrease in the endogenous excretion of both zinc and reduced glutathione into bile. This depression probably reflects the conjugation of the aforementioned substances to glutathione in the liver cells. These results indicate that zinc is transferred from liver to bile by glutathione dependent process and most likely as zinc-glutathione complexes.     

Effect of Age and Route of Administration on LD50 of Lithium Chloride in the Rat *

Abstract: Male inbred rats were used to determine the lethal dose of lithium chloride. The rats were 3 weeks, 6 weeks, 3 months and 6 months old, and lithium chloride was given intraperitoneally, subcutaneously and orally. In relation to age, LD50 was significantly higher in rats of 6 weeks after oral administration than LD50 in rats of 3 and 6 months. No differences were found following intraperitoneal and subcutaneous administration. In relation to route of administration, LD50 was significantly higher in rats of 3 and 6 weeks after oral administration than LD50 after intraperitoneal and subcutaneous administration. This difference was not found in rats of 3 and 6 months. It is concluded that age and route of administration are of significance for LD50 of lithium chloride in the rat.     

The Effect of Long-term Lithium Treatment on the Incorporation and Distribution of 32P-Orthosphosphate into the Phospholipids from Rat Synaptosomes

Abstract: Rats were treated with lithium added to their diet for five weeks (40 mmol LiCl/kg diet). Mean plasma concentration was 0.45 mmol Li⁺/plasma. The investigation was divided into two sections. I) In an in vivo experiment in which the rats were injected with ³²P-orthosphosphate for 20 hours, and with carbamoylcholine for 20 min. prior to their death, the distribution of ³²P in the synaptosomal phospholipids, phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and phosphatidylcholine (PC), was investigated. II) An in vitro experiment which was carried out in order to establish the effect of carbamoylcholine on the incorporation of ³²P into total phospholipids from extracted synaptosomes. In I) the incorporation of ³²P-orthosphosphate into PI from carbamoylcholine-stimulated rats was significantly lower than from unstimulated rats, whereas there was no difference between the incorporation of ³²P into PI from synaptosomes from control animals and lithium-treated animals. In II) the incorporation of ³²P-orthosphosphate was significantly lower in unstimulated synaptosomes from lithium-treated rats than from control rats, while the increase in the ³²P-incorporation after stimulation followed the same pattern with regard to synaptosomes from control rats and lithium-treated rats. The results support the idea of lithium exerting an effect on basal synaptosomal activity but not on stimulated synaptosomal activity.     

The Effect of Lithium on the Incorporation of 3H-Glucosamine into Glycopeptides and the Transformation of 3H-Glucosamine into Sialic Acid in Rat Brain

Abstract: Rats were fed a lithium-containing diet (40 mmol LiCl/kg of diet) for five weeks. The plasma-lithium concentration was 0.48 mmol Li⁺/l of plasma. ³H-glucosamine (400 nCi/kg body weight) was injected intraperitoneally, and 24 hrs later the brain was divided anatomically into hemisphere, cerebellum, pons and thalamus. The brain parts were defatted and the sialic acid-containing glycopeptides were separated by column chromatography before determination of ³H-glucosamine, ³H-sialic acid and total sialic acid. Neither the total amount nor the specific activity of sialic acid were influenced by the lithium treatment. Also the ³H-content of the sialic acid-free glycopeptides remained unchanged.     

Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Background:

The hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium.

Methods:

Nineteen medication-free BD patients (78.9% treatment-naïve and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction.

Results:

At baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with “standard” lithium levels (≥0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time.

Conclusions:

These preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels.     

Central Effects of Lithium in Rats: Lithium Levels,Body Weight and Water Intake

Abstract: Male rats received LiCl for one week either by continuous intracerebroventricular injection from osmotic minipumps or by oral administration in the diet. Control groups received corresponding treatment with NaCl. The intracerebroventricular lithium treatment produced relatively high lithium levels in brain regions (0.6–2.3 mmol/kg) and negligible lithium levels in plasma (less than 0.1 mmol/l) while the oral treatment produced moderate lithium levels in brain regions as well as in blood (0.5–0.9 mmol/kg and 0.5–0.75 mmol/l, respectively). Body weight loss and enhanced water intake occurred in groups given oral lithium treatment as well as in those given lithium via minipumps. The results suggest that administration of lithium by minipumps may be of use to study central actions of lithium.     

无精性不育精浆锌酸性磷酸酶与血清FSH LH测定

目的研究无精性不育精浆锌、酸性磷酸酶（ACP）与血清FSH、LH的关系方法测定了110例无精性不育男子（分为FSH正常组60例和高FSH组50例）和44例正常对照组男子的精浆锌、酸性磷酸酶和血清FSH、LH．结果正常对照组与高FSH组间精浆锌浓度差异有统计学意义（P〈0．05）？在正常FSH组精浆锌与酸性磷酸酶（rs=0．384，P〈0．05）、血清FSH与LH（rs=0．419，P〈0．05）间有相关性。在高FSH组精浆锌与酸性磷酸酶（rS=0．578，P〈0．05）、血清FSH与LH（rs=0．326，P〈0．05）、FSH与精浆锌（rs=－0．490，P〈0．05）、FSH与精浆酸性磷酸酶（FS=－0．326，P〈0．05）间有相关性。结论反映前列腺功能的精浆锌与酸性磷酸酶明显相关，在高FSH组中两者与血清FSH有负相关关系，随着FSH的上升，前列腺的分泌功能越差。精浆锌和酸性磷酸酶与血清LH无关。     

人工虫草菌丝及锌减少肝纤维化大鼠肝脏胶原的沉积

目的观察人工虫草菌丝及葡萄糖酸锌对大鼠四氯化碳实验性肝纤维化肝内胶原沉积的作用.方法用四氯化碳制造雄性Wistar大鼠肝纤维化模型,根据在动物饮水中加入不同药物分为小剂量人工虫草组、大剂量人工虫草组、葡萄糖酸锌组、对照组,并设正常组(不造模).12周后处死动物进行检测.结果造模的4组动物肝脏质量及血清丙氨酸转氨酶(ALT)水平高于正常组,体质量增长低于正常组(均P＜0.05或P＜0.01),人工虫草组及葡萄糖酸锌组动物肝脏羟脯氨酸含量低于对照组(均P＜0.05).病理结果证实对照组肝纤维化程度重于各治疗组.人工虫草组动物尿量多于葡萄糖酸锌组(均P＜0.01).结论人工虫草菌丝和葡萄糖酸锌均可减少大鼠四氯化碳实验性肝纤维化肝内胶原的沉积,机制有待进一步研究.     

UPLC-MS/MS测定大鼠血浆中紫花前胡素的血药浓度及其药动学研究

目的 建立UPLC-MS/MS测定大鼠血浆中紫花前胡素的血药浓度,并用于口服和静脉注射后紫花前胡素的药动学特征研究。方法 大鼠血浆样本采用乙腈沉淀法去除蛋白。使用地西泮作为内标,UPLC BEH C₁₈柱（2.1 mm×50 mm,1.7 μm）为分离柱,以乙腈-0.1%甲酸为流动相,进行梯度洗脱,流速为0.4 mL·min^-1,分析时间为4.0 min。用电喷雾离子源（ESI）,正离子检测,多反应监测方式进行定量分析,紫花前胡素m/z 329.0→229.0和内标m/z 285.1→193.3。结果 紫花前胡素在1~60 ng·mL^-1内线性关系良好,定量限为1 ng·mL^-1。日内、日间精密度RSD均<14%,准确度范围在88.5%~107.5%,回收率>93.3%,基质效应在89.3%~93.5%。结论 本方法具备灵敏、快速、选择性好的特点,可应用于紫花前胡素大鼠药动学研究。     

高效液相色谱法测定人血浆中氯氮平浓度

目的 建立测定人血浆中氯氮平浓度的高效液相色谱法. 方法 以DiamonsilTM C18反相柱（150 mm×4.6 mm,5 μm）为色谱柱,流动相为0.03 mol&#8226;L^-1醋酸铵 甲醇（25：75）;流速0.8 mL&#8226;min^-1,柱温40 ℃,检测波长 254 nm. 以醋酸乙酯与二氯甲烷（80：20）为提取剂. 结果 氯氮平的高、中、低（1 000.0,400.0,10.0 ng&#8226;mL^-1）3种浓度平均回收率分别为98.28%,97.63%,101.41%,日内、日间精密度RSD均＜7%（n＝5）;分析方法 的检测限为5.0 ng&#8226;mL^-1;线性范围为10.0～1 000.0 ng&#8226;mL-1. 曲线方程：C＝25.69F＋3.47,r＝0.999 7（n＝10）. 结论 该方法 灵敏、准确、简单、快速,可用于临床血药浓度监测和药动学研究.     

RP-HPLC法测定人血浆中米氮平的浓度

目的:建立以反相高效液相色谱法测定人血浆中米氮平浓度的方法。方法:色谱柱为KromasilC18,流动相为甲醇-水-1mol·L-1乙酸铵-5mol·L-1氨水(900:100:10:3),流速为1.0mL·min-1,内标为盐酸普萘洛尔,柱温为室温,检测波长为294nm。结果:米氮平血药浓度在20.0～500.0μg·L-1范围内线性关系良好(r=0.9990);平均回收率为98.56%,日内、日间RSD分别为3.42%～4.87%、4.25%～5.88%。结论:本方法操作简便、回收率高、精密度好,可用于米氮平的治疗药物监测。     

精浆白细胞锌酸性磷酸酶测定

目的研究精液白细胞增多与精浆锌和酸性磷酸酶（ACP）的关系。方法测定少精和弱精症的不育男子及正常对照组精液常规和精浆中白细胞、锌、酸性磷酸酶浓度。结果少精和（或）弱精症的不育男子精液白细胞明显多于正常对照组,且精浆锌、酸性磷酸酶浓度均低于对照组。白细胞与锌和ACP呈负相关;锌与精子密度,ACP与A级精子比率,精子密度与A级比率存在相关关系。结论少精和（或）弱精症的男子不育与精液中高浓度的白细胞以及锌、酸性磷酸酶的下降有关。     

Whole Blood Chromium Level and Chromium Excretion in the Rat after Zinc Chromate Inhalation

Abstract Studies on absorption and excretion of chromium in the rat exposed to known atmospheric concentrations of zinc chromate in an inhalation chamber and the influence of diurnal variations in physical activity have been carried out. Chromium analyses were performed on samples of blood, urine and faeces using a method for determining chromium in small samples of biological material based on flameless atomic absorption spectrometry. Zinc chromate is absorbed quickly during exposure and excreted mainly via urine. An accumulation of chromium in blood was observed, followed by a slow elimination. It is suggested that chromium from zinc chromate enters the blood in the hexavalent state.     

Dissimilar Effects of Lithium and Valproic Acid on GABA and Glutamine Concentrations in Rat Cerebrospinal Fluid

• 1.This study compared the effects of the antimanic drugs, lithium and valproic acid, on GABA and glutamine CSF concentration and on head-shakes during hyponatremia.
• 2.Hyponatremic and normonatremic rats were treated with 2 mEq/kg lithium and 360 mg/kg valproic acid. Behavioral observation was conducted for 120 min after which blood and CSF collection were performed under anesthesia.
• 3.Peritoneal dialysis with glucose induced moderate hyponatremia and doubled glutamine CSF concentrations. Both lithium and valproic acid significantly increased GABA CSF levels in normonatremic and hyponatremic animals. Valproic acid induced head-shakes and increased CSF glutamine concentration.
• 4.The results suggest that both antimanic drugs have similar effects on GABA, but lithium is preferred if the increase in glutamine concentration poses a problem, either in the presence or absence of hyponatremia.

     

经皮给药后尼索地平在大鼠体内血药浓度的LC-MS法测定

建立了液相色谱-质谱法测定大鼠血浆中的尼索地平,并考察尼索地平微乳凝胶经皮给药后在大鼠体内的药动学.采用电喷雾离子源(ESI源),正离子检测,选择离子监测(SIM),监测离子对为m/z 411(尼索地平)和m/z 441(尼莫地平,内标).血浆中尼索地平在0.5～50 ng/ml浓度范围内线性关系良好,方法回收率为95％～102％,RSD≤5.8％.血浆中药物的提取回收率大于70％.采用雄性SD大鼠考察微乳凝胶经皮给药后的体内药动学行为并与口服混悬剂进行比较.含尼索地平20 mg的微乳凝胶经皮给药后的主要药动学参数分别为tmx (42.00±6.92)h,cmax (27.53±1.88) ng/ml,AUC0→72h(1736.31±106.59) ng·h·ml1,AUC0→∞(1999.66±119.26) ng·h·ml-1,MRT (44.02±0.77)h和t1/2 (7.61±0.70)h.     

HPLC-UV法同时测定人血浆中对乙酰氨基酚和双氢可待因的浓度

目的:建立同时测定人血浆中对乙酰氨基酚和双氢可待因浓度的方法。方法:血浆经乙酸乙酯、正己烷萃取后,采用高效液相色谱-紫外法进行测定,其中色谱柱为ZorbaxXDB-C18,流动相为乙腈-0.1%三氟乙酸(TFA)-水(12∶40∶48),流速为1.0mL·min-1,检测波长为230nm(0～5.0min)和210nm(5.0～6.2min)。结果:对乙酰氨基酚、双氢可待因血药浓度分别在0.10～20.00mg·L-1(r=0.9997)、2.5～150.0μg·L-1(r=0.9994)范围内线性关系良好,定量下限分别为0.1mg·L-1、2.5μg·L-1;低、中、高3种浓度的相对回收率分别为(100.38±2.19)%、(98.59±1.71)%、(100.30±0.83)%以及(97.52±3.33)%、(97.42±3.13)%、(99.60±2.98)%;日内RSD分别为1.65%～2.24%和2.73%～5.02%,日间RSD分别为1.57%～1.97%和3.80%～5.21%。结论:本方法准确可靠、简便快速,适用于人血浆中对乙酰氨基酚和双氢可待因浓度的同时测定。     

Uric Acid Levels in Tissues and Plasma of Mice during Aging

Here we quantified the uric acid (UA) levels in 11 tissues and plasma of C57BL/6 male mice to track its turnover during 3 to 30 months of aging. UA levels in the adrenal glands, heart, and spleen increased with aging until 30 months of age. Similarly, UA levels in the liver, kidneys, pancreas, and testes increased until the mice were 24 months old. UA levels also rose in the lungs and skeletal muscles from 3 to 6 months and 6 to 12 months, respectively, and then remained at almost the same levels until 30 months of age. In the skin, UA decreased from 3 to 6 months and then stayed nearly constant until 30 months of age. Moreover, the small intestines and plasma had quite stable UA levels during aging. Thus, our assessment of 11 tissue types from mice showed that the UA levels increased in most tissues during aging.