Blood-bound carbon disulfide: An indicator of carbon disulfide exposure, and its accumulation in repeatedly exposed rats

Carbon disulfide is present in exposed subjects in free and bound or acid-labile forms. Sensitivities of the blood acid-labile CS2 (AL CS2) concentration and the modified iodine-azide test (IAT) were compared as indicators of CS2 exposure. Rats were exposed to 15 (approximately 5 ppm), 30, 60, or 120 mg/m3 of CS2. Exposure to 15 or 30 mg/m3 of CS2 could not be detected by the modified IAT. However, a linear relationship between blood CS2 (free or AL CS2) concentrations and these exposure levels was observed. Free CS2 is eliminated rapidly, while AL CS2 is eliminated very slowly from the exposed subjects. Repetitive daily exposures (8 hr/day) to 120 mg/m3 of CS2 were carried out in rats. Blood AL CS2 concentrations in exposed rats increased with each successive exposure while the free CS2 level remained relatively constant. By the sixth or seventh daily exposure the blood AL CS2 concentration was about 2.5 times that of the first 8-hr exposure and about 3 times the level of free CS2. These results indicated an appreciable accumulation of CS2 in subjects repeatedly exposed to low concentrations of the solvent. Rats were also exposed to CS2 8 hr/day for 5 days. After a 2-day nonexposure period (Days 6 and 7), the animals were reexposed on Day 8. The blood AL CS2 concentration in animals exposed on Day 8 was substantially higher than in those that received a single 8-hr exposure (Day 1), despite the hiatus on Days 6 and 7. These results indicated that blood AL CS2 was not totally eliminated during the 2-day nonexposure period. In in vitro experiments, the binding profile of CS2 to human blood was remarkably similar to that of rats exposed to CS2 by inhalation.     

Production of physical dependence on ethanol by a short drinking episode each day

A 3-hr schedule-induced ethanol polydipsia regimen was used in rats to elevate blood alcohol concentration to a single intoxicating peak each day. After 3 weeks, and again after 3.5 months, animals were tested for the presence of physical dependence by exposure to a brief auditory stimulus (key shaking) at 7 and 11 hr after ethanol polydipsia. Withdrawal signs were observed only at 11 hr when blood ethanol levels had returned to zero. No such signs were observed when animals were made water polydipsic. While sufficient, continuous elevation of blood ethanol concentration is not necessary for the development of a demonstrable physical dependence. A limited daily ethanol binge was sufficient.     

Determination of plasma hydrochlorothiazide levels in humans

A method for determining plasma hydrochlorothiazide levels was developed with a sensitivity of 5 ng/ml. Accuracy and precision were demonstrated over the 5--648-ng/ml range by an overall recovery of 95 +/- 8%. The detector response was linear for the 5--250-ng/ml range. The method was sufficiently sensitive for hydrochlorothiazide bioavailability studies and also was applicable for the determination of whole blood drug levels. Plasma levels in two subjects reached peak levels of 428 and 450 ng/ml at 2.5 and 2 h, respectively, after a 50-mg dose. Whole blood levels at 3 hr after the same dose were 547 and 851 ng/ml and were approximately 2.5 times the 3-hr plasma levels.     

Patterns of extracellular 5-hydroxyindoleacetic acid (5-HIAA) in the paraventricular hypothalamus (PVN): relation to circadian rhythm and deprivation-induced eating behavior

Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in the region of the paraventricular nucleus (PVN), using intracerebral microdialysis combined with high performance liquid chromatography and electrochemical detection. Samples of PVN dialysate, from 11 rats on a 12/12 hr light/dark cycle, were collected and assayed for 5-HIAA every 2 hr for 3 days. During the first 2 days the rats were given free access to food. During the 3rd day they were deprived of food for a 24-hr period and then given food for 4 hr. The results showed that in freely-feeding rats, there was a 24-hr rhythm in the levels of 5-HIAA, with a marked transient peak just after the beginning of the dark portion of the light/dark cycle and stable levels at all other times. When the animals were food-deprived, PVN levels of this metabolite remained stable, and the early dark peak was abolished, suggesting that it might have been consequent to the eating behavior which normally occurred at this time. In the 4-hr refeeding period, there were no changes in 5-HIAA levels, despite the intense eating behavior which occurred during this time. These patterns of 5-HIAA in the PVN region, taken together with previous evidence, suggest that PVN serotonin metabolism may increase in association with feeding specifically in the early portion of the nocturnal eating period, when it may play a role in controlling food intake and macronutrient selection.     

Effects of acute and repeated alcohol ingestion on hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal functioning in normal males.

We investigated the effects of acute and repeated alcohol ingestion on plasma levels of hormones associated with the functioning of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) systems in normal males. In the first experiment, 7 normal male subjects were given ethanol (1.3 g/kg) in the form of a 43% alcohol solution of whiskey and water over a 30-min period (from 19:00 h to 19:30 h); blood samples were collected 30 min and immediately before the beginning of alcohol ingestion and then at intervals of 30 min for 180 min. Blood ethanol levels rose sharply and reached their maximum at 60 min, remaining above 1.0 mg/ml until 180 min. Prolactin levels increased, reaching a peak at 60 min, gradually returning to the initial value at 180 min. Decreased testosterone levels were observed only at 30 min. Luteinizing hormone (LH), adrenocorticotrophic hormone (ACTH) and cortisol levels did not show any increases. In the second experiment, 9 normal males were given the same dose of alcohol, but this was given on 7 consecutive evenings and the hormonal changes were examined on the 1st and 7th days, only at 30 and 60 min after alcohol ingestion began (during the period that blood ethanol levels were ascending to their peak). The results on the 1st day reconfirmed the findings in the first experiment and on the 7th day, the last alcohol ingestion produced increases in prolactin levels and decreases in testosterone levels at 30 and 60 min, but did not change other hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

An injury of the liver caused by ischemia-reperfusion in rat liver. Report 2: Relationship between the damage of the liver and during the period of reperfusion]

Liver injury by 30-min ischemia following reperfusion was examined biochemically and histopathologically. A greater increase in the level of LDH was observed after 1-hr reperfusion. However, the level of LDH decreased in proportion to the period of reperfusion, while the levels of GOT and GPT were also increased rapidly and reached its peak at 12 hr following reperfusion and were almost restored to the control level by 48 hr. A similar increase was obtained in the lipid peroxides of the liver. In addition, cyt. P-450 content and NADPH cyt. c reductase activity decreased in proportion to the period of reperfusion up to 12 hr and then recovered by 96 hr. On the other hand, heme oxygenase activity was significantly increased by ischemia-reperfusion. The ischemia-reperfused liver resulted in various morphological changes with the period of reperfusion. The destruction of Disse's space, vacuolization of the cytoplasm and nonviable hepatocytes were observed after 12-hr reperfusion. These results indicate the greatest damages of the liver induced by 30-min ischemia following reperfusion is observed after 12-hr or 24-hr reperfusion. The liver injury by ischemia-reperfusion could be a useful experimental model to develop for future studies.     

The effect of monoamine oxidase A and B inhibitors on rat serum prolactin

Serum prolactin levels were assayed in rats treated with specific inhibitors of monoamine oxidase (MAO) A or B. Monoamine oxidase A was inhibited by MD780515, clorgyline and Lilly 51641, and MAO B by pargyline and deprenyl (all at 10 mg/kg, p.o.). Serum prolactin levels were significantly reduced 1 hour after treatment with MAO A inhibitors, but were unaltered by MAO B inhibitors. The time-course of the reduction in serum prolactin did not correspond to that of MAO A inhibition. When rats were treated with clorgyline, serum prolactin returned to control values by 6 hr after treatment, whereas MAO A was inhibited by 92–94% over the whole period. At a time when MAO A inhibitors produced no change in serum prolactin (5 hr after treatment) they abolished the rise in serum prolactin induced by reserpine (5 mg/kg, i.p.), indicating a continuing absence of MAO A activity in the neurones regulating prolactin release. Monoamine oxidase B inhibitors did not alter the effect of reserpine on serum prolactin. Possible reasons for the rapid recovery of serum prolactin levels are discussed.     

Alcohol effects on naloxone-stimulated luteinizing hormone, prolactin and estradiol in women

Plasma luteinizing hormone (LH), estradiol, prolactin and progesterone levels were measured in nine normal adult women prior to and following administration of naloxone and oral ingestion of ethanol or placebo-control solution. Each subject served as her own control in a double-blind study carried out during the midluteal phase of the menstrual cycle. The mean (+/- SD) progesterone level was 13.9 +/- 1.3 during control conditions and 13.9 +/- 1.7 during alcohol conditions. The mean peak blood alcohol level was 100 +/- 13 mg/dl within 45-60 min after initiation of drinking. Under placebo-control conditions, naloxone stimulated a significant increase in plasma LH and prolactin but did not increase estradiol or progesterone. Alcohol did not attenuate the significant naloxone stimulation of LH, and progesterone levels were equivalent under alcohol and control conditions. Alcohol significantly enhanced naloxone stimulation of prolactin and estradiol. Alcohol administration significantly augmented the naloxone-induced increase in plasma prolactin levels. After alcohol administration, naloxone also induced a significant increase in plasma estradiol levels, which was sustained throughout the 180-min sampling period. The mechanisms underlying alcohol's enhancement of naloxone-stimulated prolactin and estradiol remain to be determined. The alcohol-related increase in naloxone-stimulated prolactin secretion may reflect increased hypothalamic and/or pituitary sensitivity to alcohol following endogenous opioid blockade by naloxone or an effect of increased estrogen levels. The significant increase in plasma estradiol levels following concurrent naloxone and alcohol administration may occur as a consequence of alterations in steroid biotransformation associated with intrahepatic ethanol catabolism.     

2-Methoxyacetic acid dosimetry-teratogenicity relationships in CD-1 mice exposed to 2-methoxyethanol.

The teratogen 2-methoxyethanol (2-ME), an industrial solvent, was administered to pregnant CD-1 mice either as a single subcutaneous (sc) bolus dose (100-250 mg/kg) or via constant-rate infusion from sc implanted osmotic minipumps (34.7 or 69.4 mg/kg/hr for up to 12 hr) on gestation Day 11, when embryonic paw development is maximally sensitive to perturbation by this agent. The sc entry route most closely reflects likely human exposures via dermal penetration, while bolus and constant-rate infusion administrations were contrasted to mimic potential occupational exposure scenarios. The pharmacokinetic profiles of 2-methoxyacetic acid (2-MAA), the proximate toxic metabolite of 2-ME, were quantitated, generating peak concentration (Cmax) and total 2-MAA exposure values (24-hr area under the concentration-time curve; AUC) in the maternal plasma, extraembryonic fluid, and embryo. The total 2-ME dose (mg/kg) required to achieve similar 2-MAA levels (Cmax or AUC) in these compartments was 2- to 3-fold higher by constant-rate infusion than by bolus injection; therefore, no simple association existed between 2-MAA levels and the total 2-ME dose, when the dose rate was not considered. Similarly, there was no good correlation between the combined total 2-ME doses and the fetal malformation rate, although clear dose-response patterns for paw malformations were observed in litters and fetuses for each individual dosing regimen. However, the combined 2-MAA pharmacokinetic data from each of the dosing regimens demonstrated that during the phase of maximum susceptibility of paw morphogenesis to disruption by 2-MAA (from gd 11 to gd 11.5), a strong linear correlation existed between fetal malformation incidence and 2-MAA AUC levels in either maternal plasma or embryonic compartments (linear correlation coefficient, r2 0.91-0.92). The correlation with Cmax was less favorable (r2 0.74-0.81) over the dose range studied. In a further experiment designed to investigate the importance of AUC vs Cmax regarding 2-ME teratogenicity, infusion of 2-ME (34.7 mg/kg/hr for 8 hr) beginning 2.5 hr after bolus loading (175 mg/kg) provided an increased 24-hr 2-MAA AUC without increased Cmax. This resulted in greater than 70% of the fetuses having various digit malformations (micro-, syn-, ectro-, and polydactyly), compared to only 32-35% of fetuses with mostly stunted digits when either dose was applied singularly. These data support total 2-MAA exposure (AUC levels), rather than peak 2-MAA concentrations, as the principle determinant of teratogenesis following exposure to 2-ME.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dichloromethane inhalation, carboxyhemoglobin concentrations, and drug metabolizing enzymes in rabbits.

The relationship between inhaled dichloromethane (DCM) and percentage of carboxyhemoglobin (% COHb) in blood has been investigated in rabbits. After a single 20-min exposure to DCM, % COHb rose to a maximum within 2–3 hr and usually declined to basal values within 8 hr. The maximum COHb concentration and the time to reach that value were DCM concentration-dependent. In rabbits given a 4-hr exposure to DCM, % COHb increased over the first 2–3 hr, reaching a peak by about 4 hr with a return to basal levels within 24 hr. Studies were carried out to determine whether treatment with modifiers of hepatic mixed-function oxidase changed the % COHb response after DCM exposure. Of the compounds investigated, only CCl₄ and phenobarbital altered % COHb resulting from DCM inhalation. As expected, CCl₄, a potent hepatotoxin, reduced the % COHb resulting from DCM inhalation. Contrary to expectations phenobarbital also lowered the COHb response from DCM inhalation although the decrease was not as marked as that caused by CCl₄.     

Determination of the proximate teratogen of the mouse fetal alcohol syndrome: 2. Pharmacokinetics of the placental transfer of ethanol and acetaldehyde

CD-1 mice were treated ip on Day 10 of gestation with 4, 6, or 7 g/kg ethanol. Maternal and embryonic tissues were analyzed for ethanol and acetaldehyde levels by head-space gas chromatography 5 min to 24 hr after treatment. Dose-dependent ethanol concentrations were observed in maternal blood and liver. Ethanol rapidly crossed the placenta and appeared in the embryo 5 min after treatment. Acetaldehyde was detectable in maternal blood following all treatments and in maternal liver and embryos following treatment with 7 g/kg ethanol. Coadministration of 100 mg/kg 4-methylpyrazole, an alcohol dehydrogenase inhibitor, with 4 or 6 g/kg ethanol on Day 10 of gestation significantly reduced the rate of ethanol elimination in all tissues examined. This reduction was manifested as a prolongation in the half-life of ethanol detectable in maternal and embryonic tissues but not in an increase in maximum ethanol concentrations. Within 5 min of maternal ip treatment with 200 mg/kg acetaldehyde on Day 10 of gestation, acetaldehyde was detectable in the embryo. These data suggest that both ethanol and acetaldehyde are accessible to the embryo during a critical period of development.     

Influence of the dosing interval on prolactin release after remoxipride.

1. The prolactin response following administration of the D2-dopamine receptor antagonist remoxipride was studied in eight healthy male volunteers. The purpose of the study was to investigate the duration of a refractory period of prolactin release following two doses of remoxipride. A further aim was to compare the prolactin response following remoxipride and thyrotropin release hormone (TRH) during the refractory period. The subjects received two 30 min intravenous (i.v.) infusions of remoxipride 50 mg with different time intervals between the two doses, in a randomized six period crossover design. The time intervals between the two remoxipride doses were 2, 8, 12, 24 and 48 h. On one occasion the remoxipride dose was followed by an i.v. injection of TRH after 2 h. 2. The plasma peak prolactin concentrations obtained after the first remoxipride dose correspond to a maximal release of prolactin according to earlier studies. A small second peak of prolactin was observed after 2 h. The release was gradually increased with longer time intervals between the consecutive doses. The refractory period for a second prolactin release similar to the first one after remoxipride was found to be 24 h for most of the subjects. 3. TRH resulted in a faster and higher increase in prolactin response of a shorter duration than after remoxipride administered 2 h after the first dose.     

Further evidence for effects of ethanol on gonadotrophins and prolactin secretion in female rats

The effect of different doses of ethanol (0.5, 1.0, 2.0 and 4.0 g/kg) on LH, FSH and prolactin levels has been studied in female rats. Ethanol was administered in preovulatory periods (18 hr of diestrous or 9 hr of proestrous) and hormonal levels were measured at the 18 hr of proestrous. Ethanol administered at the 18 hr of diestrous produces a biphasic effect on serum LH levels. High doses of alcohol significantly decreased LH levels, whereas low doses (0.5 g/kg) increased the hormonal levels. When ethanol-treatment was at the 9 hr of proestrous, it only decreased LH levels with the dose of 4.0 g/kg. Serum FSH levels were unaffected by the preovulatory administration of ethanol. Serum prolactin concentrations were significantly elevated after i.p. administration of ethanol at the 18 hr of diestrous and the 9 hr of proestrous. The hyperprolactinemia is more pronounced in the rats treated at the 9 hr of proestrous. The results of these studies suggest that the ability of ethanol to modify LH and prolactin levels is due to a central depression caused for alcohol. These effects of ethanol could be mediated by the hypothalamic releasing factors and/or could be due to a direct action on the pituitary function. The sum of these effects produces important failures of the reproductive function in the female rat.     

Cisplatin-induced loss of kidney copper and nephrotoxicity is ameliorated by single dose diethyldithiocarbamate, but not mesna.

Platinum, copper, and zinc concentrations in kidney and liver were monitored following administration of cis-diamminedichloroplatinum (Cisplatin, CDDP) alone or in combination with diethyldithiocarbamate (DDC) or mercaptoethanesulfonate (mesna). Compounds were administered in saline to F344 female rats as single bolus ip doses: 7.5 mg CDDP/kg body wt; 500 mg DDC/kg body wt 1 hr after CDDP; and 100 mg mesna/kg body wt 1 hr before CDDP, at the same time as CDDP, or 1 hr after CDDP. Tissues were collected at 4 hr, 1 day, 4 days, and 7 days post-CDDP dosing. CDDP alone produced significant increases in blood urea nitrogen (fourfold) and plasma creatinine (threefold) concentrations by Day 4. Concurrent with the toxicity, CDDP lowered kidney copper (-71%) by Day 4, but had little effect on liver copper except in copper-pretreated rats. Copper-pretreated rats initially had a twofold higher kidney copper concentration and a fourfold higher liver copper concentration, but by Day 4, CDDP lowered copper concentrations in both organs to near the noncopper-treated levels. Platinum in kidney and liver rose 72-100% of peak levels within 4 hr post-CDDP and was relatively stable throughout the 7-day test period. Kidney zinc rose significantly by day 4 only in CDDP-treated rats. DDC protected against the kidney toxicity of CDDP and markedly changed kidney copper loss. Within 4 hr, DDC reduced kidney copper 60% while increasing kidney platinum to the highest concentration of any of the treatments. By Day 4, DDC-treated rats had approximately 50% lower kidney platinum while copper returned toward control levels. A single dose of mesna did not significantly protect against CDDP nephrotoxicity and had little effect on kidney platinum, copper, or zinc. The patterns of copper loss and toxicity from CDDP alone or with DDC suggest that copper be further evaluated for its role in the mechanism of CDDP cytotoxicity.     

Ethanol metabolism in men and women

Data from the Colorado Alcohol Research on Twins and Adoptees project were analyzed to determine whether 63 women and 75 men differ on three measures of ethanol pharmacokinetics: absorption rate, peak blood alcohol level and elimination rate. The data on women were analyzed separately to investigate whether female hormones influenced the measures of ethanol metabolism by comparing groups tested at different phases of the menstrual cycle and a group who were taking oral contraceptives. Subjects were given 0.80 g of alcohol per kg of body weight diluted by 7 parts of carbonated water or a sugar- and caffeine-free soft drink. This dose was calculated to bring their blood alcohol level (BAL) to near 100 mg/dl. Additional doses were given at the end of each of the next 2 hr in an attempt to maintain BAL near peak for approximately 3 hr. An analysis of beta 60 values showed that women metabolized ethanol faster than men, regardless of phase of menstrual cycle or whether they were taking birth control pills. There was a small gender difference in peak BAL and no gender difference in time to peak BAL. It was also found that the peak BAL attained by subjects had a substantial effect on the beta 60. The effects of smoking, age, ponderal index and reported drinking habits on ethanol metabolism were also analyzed.     

The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats

The pharmacokinetics of 1,1,1-trichloroethane (TRI) was studied in male Sprague-Dawley rats in order to characterize and quantify TRI uptake and elimination oby direct measurements of the inhaled and exhaled compound. Fifty or 500 ppm TRI was inhaled for 2 hr through a one-way breathing valve by unanesthetized rats of 325-375 g. Repetitive samples of the separate inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently both during and following TRI inhalation and analyzed for TRI by gas chromatography. Respiratory rates and volumes were continuously monitored during and following exposure and were used in conjunction with the pharmacokinetic data to characterize profiles of uptake and elimination. TRI was very rapidly absorbed from the lung, in that substantial levels were present in arterial blood at the first sampling time (i.e., 2 min). Blood and exhaled breath concentrations of TRI increased rapidly after the initiation of exposure, approaching but not reaching steady state during the 2-hr exposures. The blood and exhaled breath concentrations were directly proportional to the exposure concentration during the exposures. Percentage uptake of TRI decreased 30-35% during the first hour of inhalation, diminishing to approximately 45-50% by the end of the exposure. Total cumulative uptake in the 50 and 500 ppm groups over the 2-hr inhalation exposures was determined to be 6 and 48 mg/kg body wt, respectively. By the end of the exposure period, 2.1 and 20.8 mg, respectively, of inhaled TRI was eliminated from rats inhaling 50 and 500 ppm TRI. A physiological pharmacokinetic model for TRI inhalation was utilized to predict blood and exhaled breath concentrations for comparison with observed experimental values. Overall, values predicted by the physiological pharmacokinetic model for TRI levels in the blood and exhaled breath were in close agreement with measured values both during and following TRI inhalation.     

Facilitation by alcohol of active avoidance acquisition performance in the goldfish

Common goldfish (Carassius auratus) were exposed for 3 hr or 6 hr to alcohol solution (628 mg per 100 ml) or were treated identically but never exposed to alcohol. Following pretraining exposure, fish were given 20 trials of active dark-avoidance training in individual shuttle boxes. Alcohol-treated fish obtained significantly higher mean levels of correct responding during acquisition. The enhancement of acquisition performance was not appreciably altered by 6-hr compared with 3-hr pretraining exposure. Neither was the enhanced acquisition performance attributable to increased general shuttling during the 10-sec shock-free conditioned stimulus period. There was some evidence that alcohol-treated fish, compared with controls, swam into and out of the electrified compartment more often during training; however, this sort of responding correlated with correct responding no better for alcohol-treated than for control fish. In another experiment, alcohol was shown to increase sensitivity to light in goldfish. The explanation of the observed facilitation by alcohol of acquisition performance in goldfish may involve an effect on stress or anxiety; an effect of increased sensitivity to electric shock; or an effect of acute increased availability of central monoamines.     

Cadmium-induced lung injury: cell kinetics and long-term effects

The effects of exposure to CdCl2 aerosols followed by hyperoxia were studied in mouse lung. Special emphasis was placed on analysis of cell proliferation following injury. Male Balb/c mice were exposed to aerosols of 4.9 micrograms Cd/liter for 1 hr while controls were exposed to water aerosols. Immediately after, half of each group was placed in 80% O2 for 6 days, while the rest were left in room air. Three endpoints were used to assess lung injury; measurement of hydroxyproline, [14C]thymidine incorporation into DNA, and histopathology. Parenchymal and bronchiolar labeling indices were determined following autoradiography. A 1-hr exposure to CdCl2 aerosols caused marked cell proliferation in the lung with the peak of cell labeling occurring at Day 5. In animals exposed to both CdCl2 + 80% O2, the cell labeling peak was delayed until Day 9. Cell differentiation studies showed a delay in the peak of type II epithelial cell and endothelial cell division when CdCl2 exposure was followed by the 80% O2 treatment. On Day 15 most of the labeled cells were identified as interstitial cells in both treated groups. Bronchiolar cell labeling was suppressed at the early time period in the Cd + O2 group. With time, the histologically visible lung lesions tended to resolve in animals exposed to CdCl2 or CdCl2 and 80% O2, whereas total pulmonary hydroxyproline remained at all times (3, 6, and 12 months) significantly higher in Cd-treated animals when compared to controls. It was concluded that acute lung injury by a toxic inhalant can be amplified if there is an initial delay in pulmonary cell proliferation following an acute insult.     

Patterns of smoking and methadone dose in drug treatment patients

Cigarette smoking prevalence is very high, and cessation rates are very low, among people in methadone treatment. This may in part be due to interactions between methadone administration and cigarette smoking. The present study explores relationships between methadone dose timing and smoking rates. Twenty methadone patients, over a period of 19 days, used electronic cigarette packs to record their smoking patterns and called a voice mailbox daily to report their methadone dose and timing. The average proportion of daily cigarettes smoked was calculated for 2-hr blocks preceding and following methadone dose administration. For all participants, peak smoking rates occurred after methadone administration. Participants smoked a greater proportion of cigarettes in their first 2-hr block after methadone dosing (M = 0.368, SD = 0.135) than during their first 2-hr block of smoking of the day (M = 0.245, SD = 0.010; S = 85.5, p < .0001). The proportion of cigarettes smoked increased by 0.02 from more than 2 hr before methadone to the 2-hr time block before methadone, by 0.04 from the 2-hr time block before methadone to the 2-hr time block after methadone, and by 0.015 from the 2-hr time block after methadone to the next 2-hr time block. From this time block (2-4 hr after methadone), smoking decreased by 0.02 in the 4-plus hr postmethadone dose. All of these changes were statistically significant. Future research should use experimental designs to better examine whether a causal relationship exists and examine the impact of other types of opioid maintenance medications on smoking patterns.     

新型抗精神分裂症药布南色林对催乳素的影响

目的考察中国男性和女性健康受试者多次服用布南色林后血清中催乳素水平的影响变化。方法12名受试者（男女各半）连续给药7d,每天给药2次,每次4mg,于第7天服药前（0h）以及服药后0．5、1、2、4、12h采集肘静脉血4mL测定血清中催乳素水平。结果男性和女性健康受试者服药2h后血清中催乳素水平达到峰值,其中男性催乳素峰值为（965．68±382．2）mIU／L,女性催乳素峰值为（2124．2±889．1）mIU／L,女性催乳素水平显著高于男性,服药12h后,男性和女性受试者催乳素基本恢复至正常水平。结论布南色林不会显著引起催乳素累积增加,关于患者长期服用布南色林对催乳素水平的影响仍需进一步研究。