Transport kinetics of chromium in perfused human placental lobule in late gestation: in vitro study

Objective: Reports relating to maternal-fetal transport kinetics of chromium, an essential trace element in the human pregnancies are scanty. Hence, we thought it interesting to investigate the transport kinetics of this trace element in the human placenta in late gestation in vitro.

Methods: Human placentae were collected immediately after delivery from normal uncomplicated pregnancies. Chromium chloride solution (GFS Chem Inc, Ohio, USA) at 10 times the physiological concentrations and antipyrine (Sigma Chem Co., St. Louis, USA) as internal reference marker was injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples were collected from maternal and fetal circulations over a study period of 5?minutes. National culture and Tissue collection medium, diluted with Earle’s buffered salt solution was used as the perfusate. Serial perfusate samples were collected from fetal venous perfusate for a period of 30?minutes. Chromium concentration in perfusate samples was determined using atomic absorption spectrophotometry and the concentration of reference marker, antipyrine was measured by spectrophotometry. Transport kinetics and transport parameters of study and reference markers were assessed using well-established parameters.

Results: Differential transport rates of chromium and antipyrine in 10 perfusions differed significantly for 10 and 50% efflux fractions (ANOVA test, p?antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of chromium and antipyrine was statistically significant (Student’s t-test, p?p?Conclusions: Our studies report for the first time maternal-fetal transport kinetics of chromium in human placenta in vitro. Considering the restricted transfer of this essential trace element from maternal to fetal circulation despite its small molecular weight, we hypothesize an active transport of chromium across the human placental membrane. Further studies relating to placental transport kinetics of this trace element in various pregnancy-related disease states are in progress.     

Exercise-induced oxidative stress in older adults as a function of habitual activity level

OBJECTIVES: It has been suggested that regular physical activity might maintain and promote the antioxidant defense capacity against oxidative stress. Therefore, we assessed exercise-induced oxidative stress in relation to habitual physical activity level (PAL) in older adults. DESIGN: The study included a 2-week observation period for the measurement of average daily metabolic rate (ADMR) and PAL. Exercise-induced oxidative stress was measured during a 45-minute cycling test at submaximal intensity. SETTING: A university medical research center. PARTICIPANTS: Twenty-six subjects volunteered for the study (n = 26; mean age +/- standard deviation 60 +/- 1; body mass index 27 +/- 1 kg/m2). MEASUREMENTS: PAL was determined as ADMR combined with a measurement of basal metabolic rate (BMR): PAL = ADMR/BMR. ADMR was measured over 2 weeks with the doubly labeled water method, preceded by a BMR measurement with a ventilated hood. Antipyrine oxidation was used as marker for oxidative stress in vivo. Reaction of antipyrine with hydroxyl radicals results in the formation of para-hydroxyantipyrine (p-APOH) and ortho-hydroxyantipyrine (o-APOH), where o-APOH is not formed through alternative oxygenetic pathways. RESULTS: PAL was inversely related to the exercise-induced increase in the ratio of o-APOH to native antipyrine (r = 0.49, P = .010). The relationship between PAL and exercise-induced increase in the ratio of p-APOH (r = 0.30, P = .140) or thiobarbituric acid reactive species (r = 0.31, P = .130) did not reach the level of significance. CONCLUSION: Physically active older adults have a reduced exercise-induced oxidative stress than older adults with a lower level of physical activity. It seems that regular physical activity improves the antioxidant defense capacity.     

Increased Susceptibility to Liver Disease in Relation to Alcohol Consumption in Women

Sex-related differences were prospectively studied in patients with the first presentation of alcoholic liver disease. Among 42 patients the diagnosis was cirrhosis in 8 women and 15 men, alcoholic hepatitis in 4 women and 1 man, steatosis in 6 women and 6 men, and no histologic changes were found in the liver biopsy specimens from 2 men (p > 0.1). The median (range) antipyrine clearance was 14.6 (1.0–64) versus 17.2 (3.0–83) ml/min and the clinical score in accordance with the Pugh modification of the Child-Turcotte classification was 8 (5–13) versus 8 (5–11) in the women and men, respectively (p > 0.05). In 5 women and only 1 man the antipyrine clearance was less than 5 ml/min, indicating an almost total loss of functional liver mass (p < 0.05), whereas the Pugh score was above 11 in 6 women, but not in any of the men (p < 0.05). On an average, the men estimated their total lifetime consumption of alcohol to be 2.1 times greater and the number of days they had consumed more than 5 drinks 2.9 times higher than the women (p < 0.05). These ratios are reduced to 1.4 and 1.7, respectively (p > 0.05), if the female alcohol intake is adjusted to the average male volume of distribution. The results support the concept that women may develop similar, and sometimes even more severe, liver disease after consumption of less alcohol than men. The apparent difference in susceptibility to alcohol may be partly explained by differences in volume of distribution.     

Serum zinc and serum copper and indices of drug metabolism in alcoholics

Summary Serum zinc and copper levels were studied in relation to in vitro and in vivo drug metabolism in 25 alcoholics, in whom various diseases of the liver had been diagnosed by histology. Serum zinc was elevated in alcoholics with normal or fatty liver and was low in those with alcoholic hepatitis or cirrhosis. There was a significant positive correlation between serum zinc and cytochrome P-450 content of liver biopsies. The relationship between zinc and antipyrine half-life was significant and non-linear. Serum copper level was elevated in all the alcoholics and no significant relationship could be found between copper and drug metabolism in alcoholics. The findings suggest parallelism between changes in serum zinc and indices of drug metabolism in alcoholics.     

利福平对家兔静注安替比林药代动力学的影响

选用健康家兔，分析利福平引起的静注安替比林药代动力学的改变，同时定量评估利福平对肝药酶活性的影响。实验结果表明利福平可使安替比林半衰期有所缩短；清除率由９．９±２．８ｍｌ·ｋｇ－１显著增加至１７．１±７．０ｍｌ·ｋｇ－１·ｍｉｎ－１，平均增加７２％；ＡＵＣ由１０７６．１±２８８．２显著减少至６８３．２±２８９．０ｍｇ·Ｌ－１·ｍｉｎ－１。因此，利福平可加速药物的代谢和排泄，说明利福平可显著提高肝药酶的活性；应用四点方法与３Ｐ８７计算主要药代参数两者无显著差异。提示，当药物消除符合一室模型（或所取数据点在消除相）时，可用该法计算有关的药代参数。     

米格来宁片有关物质和含量测定方法研究

目的：建立米格来宁片有关物质与含量测定的HPLC方法。方法：采用Thermo Acclaim TM 120 C18柱（4.6mm×250mm,5μm）色谱柱;有关物质流动相：以0.01mol/L醋酸钠溶液-乙腈进行梯度洗脱;含量测定流动相为0.01mol/L醋酸钠溶液-乙腈（85:15）;流速1.0mL·min-1;检测波长275nm;进样量10μL。结果：安替比林和咖啡因分别与11种杂质完全分离,分离度大于1.5,测定杂质F校正因子为1.01,采用高分辨液质联用仪和ADMET Predictor软件推断主要未知杂质结构与毒性;含量测定咖啡因在11.0~109.6μg/mL浓度范围内线性关系良好（r=1.0000）,平均回收率为99.03%（n=9）,定量限为4.4ng;安替比林在109.96~1099.6μg/mL浓度范围内线性关系良好（r=1.0000）,平均回收率为100.56%（n=9）,定量限为11.0ng。结论：本方法专属、灵敏、简便,可用于测定米格来宁片中有关物质（杂质F≤0.03%,总杂质≤0.05%）以及安替比林和咖啡因的含量(安替比林：98.8%~101.4%,咖啡因：84.4%~107.5%)。     

普萘洛尔对人体心脏变时性反应及安替比林代谢的影响

 10例正常受试者口服普蔡洛尔10mg，tid，持续7d后，异丙基肾上腺素的变时性剂量（chronotropicdose₂₅，CD₂₅从1．4±0．5μg增加到8．8±4．9μg，平均β－受体阻滞指数为7．1；卧位择时心率明显减慢，安替比林代谢受到抑制。说明短期小量使用普蔡洛尔，能产生β－受体阻滞作用和抑制安替比林代谢。     

The Influence of Net Water Absorption on the Permeability of Antipyrine and Levodopa in the Human Jejunum

Food ingestion can influence the absorption of levodopa in the intestine and thereby contribute to fluctuations of motor functions in Parkinson patients. Obstruction of the active transport of levodopa by amino acids can be one factor. Paracellular drug absorption, a route proposed to be influenced by net transport of water across the intestinal epithelium, might occur for a small and hydrophilic drug such as levodopa. In the present study we studied how luminal L-leucine (60 mmol/L), alone or combined with hypotonicity, might stimulate net water absorption, and levodopa uptake in the human small intestine, since this possibly can contribute to the variable intestinal absorption of levodopa. The Loc-I-Gut perfusion technique was used in 10 healthy volunteers to study the effects of induced net fluid absorption on the small intestinal absorption of levodopa (2.5 mmol/L). An induced net fluid absorption was observed only when L-leucine was combined with a hypoosmolar perfusion solution. However, this did not enhance the intestinal permeability of levodopa. In conclusion, we suggest that the variability in the absorption of levodopa in Parkinsons disease cannot be explained by differences in transmucosal water flux in the human small intestine.     

RP—HPLC法测定复方氨林巴比妥注射液三组分的含量

目的:建立 RP-HPLC 法测定复方氨林巴比妥注射液中三组分的含量。方法:采用 C_(18)色谱柱(250mm×4.6mm,5μm),流动相为乙腈-0.0025 mol·L~(-1)庚烷磺酸钠-三乙胺(35:65:0.05,用50%醋酸调节 pH 至8.0,流速为0.6 mL·min~(-1),检测波长220 nm,柱温30℃。结果:氨基比林、安替比林、巴比妥分离度好,且均有良好的线性关系,r 分别为0.9998,0.9998,0.9997。加样回收率(n=5)分别为100.0%(RSD=0.8%),100.7%(RSD=0.8%),100.6%(RSD=1.2%)。结论:该法专属性强,分离度好,准确简便,为复方氨林巴比妥注射液的含量测定提供实用可靠的方法。