Predisposition to self-administer amphetamine: the contribution of response to novelty and prior exposure to the drug

 The present experiment examined the contribution of locomotor response to novelty and prior exposure to amphetamine to rats’ predisposition to self-administer a low dose of the drug. Rats were screened for their locomotor response to a novel environment and divided into high (HR) or low (LR) responders based on whether their locomotor scores were above or below the median activity level of the subject sample. Animals were then pre-exposed to nine daily injections of either saline (1 ml/kg, IP) or amphetamine (1.5 mg/kg, IP). Starting 1 week after pre-exposure, animals in the four different groups (HR pre-exposed to saline or amphetamine; LR pre-exposed to saline or amphetamine) were given the opportunity, in each of ten daily sessions, to lever press for a low dose of amphetamine (10 μg/kg per infusion) in a two lever (active versus inactive) continuous reinforcement operant task. Initial lever press performance revealed no difference in active versus inactive lever pressing between amphetamine and saline pre-exposed animals. However, in agreement with previous reports, with successive test sessions amphetamine pre-exposed rats maintained higher levels of active versus inactive lever pressing for drug while saline pre-exposed rats showed a progressive decrease in the pressing of either lever. Interestingly, this enhanced active lever pressing was observed in HR but not LR rats pre-exposed to amphetamine. In addition, HR saline pre-exposed animals showed initial active versus inactive lever pressing equivalent to that of HR amphetamine pretreated rats but this enhanced responding for drug diminished over days and by the last day of self-administration was indistinguishable from that of LR animals having been pre-exposed either to amphetamine or saline. These findings confirm that prior exposure to amphetamine promotes the subsequent self-administration of the drug and suggest that response to novelty may be a predictor more closely linked to an animal’s propensity to become sensitized to the facilitatory effects of the drug rather than to an animal’s current sensitization state and predisposition to self-administer the drug. Received: 6 July 1996 / Final version: 5 October 1996     

The effect of previous exposure to amphetamine on drug-induced locomotion and self-administration of a low dose of the drug

Rationale and objectives: In order to assess directly the relationship between locomotor activity and drug self-administration, the present experiment simultaneously measured these two behaviors in rats with different histories of pre-exposure to amphetamine either following or in the absence of priming injections of the drug. Methods: Different groups of rats were exposed to ten daily injections of either saline (1.0 ml/kg, i.p.) or amphetamine (1.5 mg/kg, i.p.) and, in each of 13 daily sessions starting 10 days later, were given the opportunity to lever press for a low dose of amphetamine (10 μg/kg per i.v. infusion) in a two-lever (active versus inactive) continuous reinforcement task. Animals were administered a priming injection of amphetamine (1.0 mg/kg, i.p.) immediately before testing on the first 8 days, a saline injection (1.0 ml/kg, i.p.) on the next 3 days and amphetamine on the final 2 days of testing. Results: Consistent with previous reports, prior exposure to amphetamine led to an enhanced locomotor response to the priming injection of amphetamine on the first day of testing. Little pressing for drug was observed on this day. Following priming injections on the subsequent test days, evidence for enhanced locomotion by amphetamine-pre-exposed rats diminished and both groups showed comparable and progressive increases in active versus inactive lever pressing. When priming injections were not made, however, only animals previously exposed to amphetamine maintained lever pressing for the drug. Under these conditions, these animals emitted more active lever presses and time-out responses and exhibited higher levels of locomotor activation in proximity to the active drug administering lever than did saline-pre-exposed rats. Conclusions: These results are consistent with the view that previous exposure to amphetamine produces a long-lasting enhancement in the behavioral activation animals will direct toward stimuli associated with the drug. This enhancement was displayed initially as a sensitized locomotor response to amphetamine on the first day of testing and was subsequently observed on those test days when no priming injections were given when animals continued to self-administer a low dose of amphetamine under a simple schedule of reinforcement. The implications of these findings for our understanding of the excessive expression of drug-directed behaviors are discussed. Received: 23 November 1998 / Final version: 19 June 1999     

Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review

Rationale: Functional imaging studies have revealed overactivity of the hippocampus in schizophrenic patients. Neuropathological data indicate that hyperactivity of excitatory hippocampal afferents and decreased hippocampal GABA transmission contribute to this overactivity. In rats, excitation of the ventral hippocampus, e.g. by NMDA, results in hyperactivity and disruption of sensorimotor gating measured as prepulse inhibition (PPI) of the acoustic startle response, behavioral effects related to psychotic symptoms in humans. Objective: The present study examined whether disinhibition of the ventral hippocampus by the GABA_A antagonist picrotoxin would result in similar psychosis-related behavioral disturbances (hyperactivity, decreased PPI) as NMDA stimulation. Methods and results: Wistar rats received bilateral infusions of subconvulsive doses of picrotoxin (100 or 150 ng/0.5 μl per side) into the ventral hippocampus and were then immediately tested for open field locomotor activity or startle reactivity and PPI. Only the higher dose induced hyperactivity and decreased PPI. Both doses decreased acoustic startle reactivity to a similar extent. The decreased PPI appeared not to result from decreased startle reactivity, but was associated with a diminished potency of the prepulses to inhibit the startle reaction to the startle pulse, indicating a sensorimotor gating deficit. All effects were temporary, i.e. disappeared when the rats were tested 24 h after infusion. Conclusions: Decreased GABAergic inhibition in the ventral hippocampus of rats yielded psychosis-related behavioral effects, very similar to those induced by NMDA stimulation. Thus, a concurrence of decreased GABAergic inhibition and increased afferent excitation in the hippocampus of schizophrenic patients might contribute to psychotic symptoms. Electronic Publication     

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Aim： Prenatal nicotine exposure （PNE） alters the hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods： Maternal Wistar rats were injected with nicotine （1.0 mg/kg, sc） twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results： UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical ＂catch-up＂ growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration （caused further increases in the serum ACTH and corticosterone levels）, but also significantly changed the glucose and lipid metabolism after UCS （caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids）. The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion： PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.     

外周疼痛模型大鼠脊髓背角环氧化酶表达时程的研究

Objective To compare the expression of two cyclooxygenase (COX) isoforms (COX-1 and COX-2) in the spinal cord of rats with inflammatory pain following peripheral formalin injection. Methods Experiments were performed on adult male Sprague-Dawley rats. 100μl of 5% formalin were injected subcutaneously into plantar hind paw of 30 rats to induce pain. The changes of COX-1 and COX-2 expression were evaluated by western blot in 30 rats, respectively at 2 hours, 6 hours, 1 day, 3 days, 7 days and 14 days after injection. The control group rats were injected with 100 μl of 0.9% saline instead of formalin in 20 rats. Results The expression of COX-1 significantly increased at 1day, 3 days, 7 days and 14 days, but the expression of COX-2 only transiently increased at 2 hours. Conclusions COX-1 and COX-2 are increasingly expressed in the spinal cord, furthermore,spinal COX-2 expression is induced early and transiently increased. COX-1 is up-regulated later and remains elevated for long time, which may explain the long-term hyperalgesia evoked by formalin injection.     

外周疼痛模型大鼠脊髓背角环氧化酶表达时程的研究

Objective To compare the expression of two cyclooxygenase (COX) isoforms (COX-1 and COX-2) in the spinal cord of rats with inflammatory pain following peripheral formalin injection. Methods Experiments were performed on adult male Sprague-Dawley rats. 100μl of 5% formalin were injected subcutaneously into plantar hind paw of 30 rats to induce pain. The changes of COX-1 and COX-2 expression were evaluated by western blot in 30 rats, respectively at 2 hours, 6 hours, 1 day, 3 days, 7 days and 14 days after injection. The control group rats were injected with 100 μl of 0.9% saline instead of formalin in 20 rats. Results The expression of COX-1 significantly increased at 1day, 3 days, 7 days and 14 days, but the expression of COX-2 only transiently increased at 2 hours. Conclusions COX-1 and COX-2 are increasingly expressed in the spinal cord, furthermore,spinal COX-2 expression is induced early and transiently increased. COX-1 is up-regulated later and remains elevated for long time, which may explain the long-term hyperalgesia evoked by formalin injection.     

Effects of An-Shen-Bu-Nao Syrup on the inducible nitric-oxide synthase activity and melatonin in brain of sleep deprivation rats

Objective： To study the effects of An-Shen-Bu-Nao Syrup （AS） on the inducible nitricoxide synthase （iNOS） activity and melatonin content in brain of sleep deprivation （SD） rats. Methods： Rats were divided into groups of control, SD model, SD＋AS （0.02ml/kg）, and SD＋ AS （0.06ml/kg） . The rats were fed with AS for 2 weeks and were subjected to sleep deprivation for 4 days, and then the iNOS activity in the front cortex was analyzed, and melatonin in the pineal gland was analyzed with HPLC. Results： Compared with the control rats, SD rats had the significantly elevated iNOS activity in the front cortex. Rats treated with AS （0. 06ml/kg） showed significantly decreased iNOS activity than SD rats.     

Maternal endotoxemia results in increases in blood pressure and body weight in rats

Objective To investigate the effects of prenatal exposure to lipopolysaccharide(LPS)on blood pressure and body weight of offspring in rats.Methods Sixteen healthy pregnant rats were randomly divided into two groups.The rats in LPS group were injected intraperitoneally with LPS(0.79 mg·kg-1)at the 8th,10th,12th day of gestation.Those in the control group were only treated with NS.After delivery,all offspring were weighed and blood pressure was measured by tail-cuff method once every two weeks from the 6th to 24th week.In the 15th week,their food intakes were weighed every day.At the end of the 24th week,the rats were put to death by decapitation.Abdominal adipose tissues were taken to weigh,and serum level of leptin was detected by RIA.Results The offspring with prenatal LPS exposure showed increased systemic arterial pressure,heavier body weight,elevated food intake,increased adipose tissue weight and increased circulating leptin compared with controls.Conclusions Prenatal exposure to LPS leads to increases in blood pressure and body weight in rats.     

Acetylcholine Transmission in Nucleus Accumbens and VTA on Heroin- Seeking Elicited by Contextual and Conditioned Cues

The involvement of cholinergic transmission in heroin self - administration and the reinstatement of heroin - seeking was examined in rats trained to nose - poke for intravenous heroin. Systemic treatment with physostigmine modestly reduced the acquisition and rate of heroin self-administration. Following 10 -14 days of self-administration, rats were left in the home environment for 14 days. Withdrawn animals were evaluated for context-induced nosepokes during the first hour after being returned to the self-administration apparatus. One hr later a conditioned stimulus （ house light, light in the nose-poke hole, sound of the infusion pump） was presented to initiate cue-induced reinstatement.     

Impact of intrauterine hypoxia on adolescent and adult cognitive function in rat offspring: sexual differences and the effects of spermidine intervention

Intrauterine hypoxia(IUH)affects the growth and development of offspring.It remains unclear that how long the impact of IUH on cognitive function lasts and whether sexual differences exist.Spermidine(SPD)has shown to improve cognition,but its effect on the cognitive function of IUH offspring remains unknown.In the present study we investigated the influence of IUH on body weight and neurological,motor and cognitive function and the expression of APP,BACE1 and Tau5 proteins in brain tissues in 2-and 4-month-old IUH rat offspring,as well as the effects of SPD intervention on these parameters.IUH rat model was established by treating pregnant rats with intermittent hypoxia on gestational days 15-21,meanwhile pregnant rats were administered SPD(5 mg·kg^?1·d^?1;ip)for 7 days.Neurological deficits were assessed in the Longa scoring test;motor and cognitive functions were evaluated in coat hanger test and active avoidance test,respectively.We found that IUH decreased the body weight of rats in both sexes but merely impaired motor and cognitive function in female rats without changing neurological function in the rat offspring of either sex at 2 months of age.For 4-month-old offspring,IUH decreased body weight in males and impaired neurological function and increased cognitive function in both sexes.IUH did not affect APP,BACE1 or Tau5 protein expression in either the hippocampus or cortex of all offspring;however,it increased the cortical Tau5 level in 2-month-old female offspring.Surprisingly,SPD intervention prevented weight loss.SPD intervention reversed the motor and cognitive decline caused by IUH in 2-month-old female rat offspring.Taken together,IUH-induced cognitive decline in rat offspring is sex-dependent during puberty and can be recovered in adult rats.SPD intervention improves IUH-induced cognitive and neural function decline.     

Medial prefrontal cortex is involved in the discriminative stimulus effects of nicotine in rats

Rationale: Central nicotinic receptors have been reported to be involved in the discriminative stimulus (DS) effects of nicotine. Objectives: The purpose of the present study was to investigate the role of the medial prefrontal cortex (mPFC) and the medial habenular nucleus (mHb) in the DS effects of nicotine. Methods: Substitution tests with nicotine administered into mPFC and mHb were conducted in rats trained to discriminate nicotine (0.5 mg/kg, SC) from saline in a two-lever, food reinforced, operant task. Results: Nicotine (40 μg) administered into mPFC substituted for nicotine (0.5 mg/kg, SC), whereas nicotine administered into mHb did not. Conclusions: Together with our previous study indicating that the nucleus accumbens and the ventral tegmental area are partially involved in the DS effects of nicotine, the present study suggests that mPFC is primarily involved in the DS effects of nicotine. Received: 18 January 1999 / Final version: 24 March 1999     

Sensitivity to the effects of opioids in rats with free access to exercise wheels: µ-opioid tolerance and physical dependence

Rationale Exercise stimulates the release of endogenous opioid peptides and increases nociceptive (i.e. pain) thresholds in both human and animal subjects. During chronic, long-term exercise, sensitivity to the effects of morphine and other μ opioids decreases, leading some investigators to propose that exercise may lead to the development of cross tolerance to exogenously administered opioid agonists. Objective The purpose of the present investigation was to examine the effects of chronic exercise on sensitivity to μ opioids, and to determine whether these effects can be attributed to the development of opioid tolerance and dependence. Methods Rats were obtained at weaning and housed singly in standard polycarbonate cages (sedentary) or modified cages equipped with exercise wheels (exercise). After 6 weeks under these conditions, opioids possessing a range of relative efficacy at the μ receptor (morphine, levorphanol, buprenorphine, butorphanol, nalbuphine) were examined in a warm-water tail-withdrawal procedure. Results Morphine, levorphanol and buprenorphine produced maximal levels of antinociception in both groups of rats, but all were more potent in sedentary rats than in exercising rats. Butorphanol and nalbuphine produced maximal levels of antinociception in sedentary rats under some conditions in which they failed to produce antinociception in exercising rats. Sensitivity to the effects of buprenorphine was decreased in sedentary rats that were transferred to cages equipped with exercise wheels, and increased in exercising rats that were transferred to sedentary housing conditions. In the latter group, exercise output prior to housing reassignment was positively correlated with increases in sensitivity to buprenorphine following housing reassignment. Naloxone administration precipitated a mild withdrawal syndrome in exercising rats that was not readily apparent in sedentary rats. Conclusions These data suggest that chronic exercise leads to the development of μ-opioid tolerance and physical dependence, and that these effects are similar to those produced by chronic opioid administration.     

Central cholinergic regulation of respiration： nicotinic receptors

Nicotinic acetylcholine receptors （nAChRs） are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of α4＊ nAChRs in the preBotzinger Complex （preBotC）, an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBotC inspiratory neurons, leading to increases in respiratory frequency, nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post- and/or extra-synaptic α4＊ nAChRs on hypoglossal （XII） motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome （SIDS）, we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.     

Effects of GSM 1800 MHz on dendritic development of cultured hippocampal neurons

Aim： To evaluate the effects of global system for mobile communications （GSM） 1800 MHz microwaves on dendritic filopodia, dendritic arborization, and spine maturation during development in cultured hippocampal neurons in rats. Methods： The cultured hippocampal neurons were exposed to GSM 1800 MHz microwaves with 2.4 and 0.8 W/kg, respectively, for 15 min each day from 6 days in vitro （DIV6） to DIV14. The subtle structures of dendrites were displayed by transfection with farnesylated enhanced green fluorescent protein （F-GFP） and GFP-actin on DIV5 into the hippocampal neurons. Results： There was a significant decrease in the density and mobility of dendritic filopodia at DIV8 and in the density of mature spines at DIV14 in the neurons exposed to GSM 1800 MHz microwaves with 2.4 W/kg. In addition, the average length of dendrites per neuron at DIV10 and DIV14 was decreased, while the dendritic arborization was unaltered in these neurons. However, there were no significant changes found in the neurons ex- posed to the GSM 1800 MHz microwaves with 0.8 W/kg. Conclusion： These data indicate that the chronic exposure to 2.4 W/kg GSM 1800 MHz micro- waves during the early developmental stage may affect dendritic development and the formation of excitatory synapses of hippocampal neurons in culture.     

三种不同手术方式对翼状胬肉的疗效比较

Objective Compared the clinical effect of simple excision of pterygium, limbal epithelium and conjunctiva autografting combined excision and combined excision of pterygium with stem cell transplantation of comeal limbus.Methods Two hundreds and ten cases(230 eyes) were divided into three groups according to operative method, the first group(75 eyes) were treated with simple excision, the secondgroup(77 eyes) were treated with limbal epithelium and conjunctiva autografting combined excision, the third group(78 eyes) were treated with combined excision of pterygium with stem cell transplantation of corneal limbus.Comea healing, limbal neovascular and tissue like pterygium hyperplasia were observed.Resulst: Following up was 4-28 months(averaged 14.30 ± 7.42). Recurrence rate was 26.67% in group A, 10.39% in group Band 8.97%in group C.The recurrence of epithelium in the group A was higher than those of the other two groups, But there were no significant differences between group B and group C .The average repair time of epithelium in the group C and group B were 2.30 ± 0.31 days and 6.15 ± 0.40 days ,the differences were remarkable in two groups(P< 0.05).Conclusions Limbal epithelium and conjunctiva autografting combined excision and combined excision of pterygium with stem cell transplantation of corneal limbus can reduce the recurrence significantly, the latter can lower the repair time of epithelium remarkably.     

The role of corticosterone in food deprivation-induced reinstatement of cocaine seeking in the rat

Rational and objectives. Acute 1-day food deprivation stress reinstates heroin seeking in rats, but the generality of this effect to other drugs, and its underlying mechanisms, are largely unknown. Here we studied whether food deprivation would reinstate cocaine seeking and whether the stress hormone, corticosterone, is involved in this effect. Methods. Rats were trained to press a lever for cocaine for 10–12 days (0.5–1.0 mg/kg per infusion, IV, 4 h/day) and were then divided into four groups that underwent different manipulations of plasma corticosterone levels: (1) bilateral adrenalectomy (ADX) surgery, (2) ADX surgery+50-mg corticosterone pellets (ADX+P), (3) ADX surgery+50-mg corticosterone pellets+4-h access (0800–1200 hours) to corticosterone (50 μg/ml) dissolved in a drinking solution (ADX+P/W), or (4) sham surgery. Next, rats were given 7–12 days of extinction training (during which lever presses were not reinforced with cocaine), and after reaching an extinction criterion they were tested for reinstatement of cocaine seeking following exposure to 21 h of food deprivation. Results. Food deprivation was found to reinstate cocaine seeking in sham-operated rats, but not in rats in which circulating corticosterone was removed (ADX group). In addition, the effect of food deprivation on reinstatement of cocaine seeking was significantly attenuated in rats maintained on basal diurnal levels of corticosterone (ADX+P group). However, food deprivation reinstated cocaine seeking in rats with limited daily access to additional corticosterone in the drinking water (ADX+P/W group). In this group, corticosterone levels were twice as high as the ADX+P group but were significantly lower than those of sham rats. Conclusions. The present data, together with previous work on footshock-induced reinstatement of drug seeking, suggest that corticosterone plays a permissive role in stress-induced reinstatement of cocaine seeking, yet its effects are not associated with the stressor-induced increases in plasma corticosterone levels.     

中西药相互作用研究:茵陈蒿与对乙酰氨基酚

The purpose of this study is to evaluate the interaction effects of In-Chen-How （Artemisia capillaries Thunb. ） on the pharmacokinetics of acetaminophen and on liver microsomal cytochrome P450 enzyme activity in rats. The rats were divided into control group （ n = 8 ） without In-Chen-How and the pretreated group （ n = 8 ） administered with In-Chen-How （ approximately 1.0 mL · kg^-1, according to weight） for 5 consecutive days. Rats in the control group received water simultaneously. Each rat was then given acetaminophen. The pharmacokinetic parameters of acetaminophen of the two groups were significantly different. In the In-Chen-How pretreated group, the maximum concentration of acetaminophen and the area under the plasma concentration-time curve were reduced about 58.4% , 56.7% and 55.4%. To further explain the results, liver microsomal suspensions were obtained from rats that were randomly divided into control and In-Chen-How pretreated group. The levels of CYP1A2 and CYP2E1 in hepatic microsomal protein from pretreated group were increased as compared to that from the control group. It indicated that In-Chen-How can stimulate the activity of CYP isozymes. The changes in the pharmacokinetics of acetaminophen resulting from the administration of In-Chen-How are related to an increase in metabolic activity of CYP1A2 and CYP2E1.     

Oral self-administration of sweetened nicotine solutions by rats

Oral self-administration of sweetened nicotine solutions in rats was studied in two ways. In the first experiment, one group had continuous access to a water bottle containing a sucrose solution and nicotine (10 μg/ml), while another group had access to an identical sucrose solution without nicotine. All rats had continuous access to water. While consumption of nicotine increased with increasing concentrations of sucrose, consumption of the sucrose + nicotine solution never exceeded the intake of sucrose alone. In subsequent experiments, the delivery of the solutions was made contingent upon an operant response. The sucrose + nicotine solution was found to maintain responding to higher response/reinforcer ratiosthan the sucrose only solution. These data demonstrate that rats will self-administer sweetened nicotine solutions and that sucrose + nicotine solutions are more reinforcing than sucrose solutions alone. Free accessconsumption is not a good predictor of the response maintaining properties of nicotine solutions.     

OLTIPRAZ对小鼠日本血吸虫病的初步治疗

Oltipraz is a new drug against Schistosomiasis mansoni and was used to treat mice Schistosorniasis japonica in our laboratory. The results showed that 48 h after oral administraction of oltipraz at a single dose of 900 mg/kg, 97% Schistosomes in mice infected with Schistosomiasis japonica schifted to the liver of the host. About half of these worms returned to the mesenteric veins in 96 h. Infected mice was given oltipraz orally at the dose of 900 mg/kg.d for 3～5 days, and killed in 28 days after the last dose. Over 95% total worm reduction rate was found.Schistosomes in infected mice treated with oltipraz were collected for histological observation. The results showed that the tegument of schistosomes were damaged and host cells invaded into the worm body; and granuloma formation of dead worm was observed.During the treatment, food uptake and body weight of the infected mice were decreased, but regained soon after the cessation of the treatment.     

Increase in sphingolipid catabolic enzyme activity during aging

Aim： To understand the contribution of sphingolipid metabolism and its metabolites to development and aging. Methods： A systemic analysis on the changes in activity of sphingolipid metabolic enzymes in kidney, liver and brain tissues during development and aging was conducted. The study was conducted using tissues from 1-day-old to 720-day-old rats. Results： Catabolic enzyme activities as well as the level of sphingomyelinase （SMase） and ceramidase （CDase） were higher than that of anabolic enzyme activities, sphingomyelin synthase and ceramide synthase. This suggested an accumulation of ceramide and sphingosine during development and aging. The liver showed the highest neutral-SMase activity among the tested enzymes while the kidney and brain exhibited higher neutral-SMase and ceramidase activities, indicating a high production of ceramide in liver and ceramide/sphingosine in the kidney and brain. The activities of sphingolipid metabolic enzymes were significantly elevated in all tested tissues during development and aging, although the onset of significant increase in activity varied on the tissue and enzyme type. During aging, 18 out of 21 enzyme activities were further increased on day 720 compared to day 180. Conclusion： Differential increases in sphingolipid metabolic enzyme activities suggest that sphingolipids including ceramide and sphingosine might play important and dynamic roles in proliferation, differentiation and apoptosis during development and aging.