咖啡中赭曲霉毒素A研究进展

综述了咖啡中赭曲霉毒素A的污染情况、检测方法及预防措施等,为进一步研究咖啡中赭曲霉毒素A的污染提供了参考.     

Phototherapeutic effects in hamsters with heart disease

In previous experiments we have shown that hamsters with inherited heart disease--cardiomyopathic hamsters (CMHs)--live longer if they spend their lives in an environment devoid of time cues. The purpose of this experiment was to test the several hypotheses by which life in constant light could extend life in CMHs. To do this, CMHs were allowed to spend their lives in one of six different lighting conditions: constant light, LD 12:12, LD 23:1, LD 1:23, LD 1:23.2, and LD 1:23.6. The only schedule to produce a significant extension of life was LD 1:23.6; in contrast to LD 1:23.2, this schedule is photostimulatory. Of the hypotheses tested to evaluate the life-enhancing effects of constant light, support was found for only the one stating that non-24-h LD regimens are health enhancing. Although some evidence was found relating testicular size to life span, dissociations between these variables indicate that testicular function does not play an overriding role in modulating the phototherapeutic effects.     

Ochratoxin A, ubiquitous mycotoxin contaminating human food

Ochratoxin A (OTA) a mycotoxin produced by molds of the Aspergillus and Penicillium genera, contaminates animal feeds and human foods. It has been shown to induce renal adenomas and hepatocellular carcinomas in rodents. OTA is implicated in Balkan endemic nephropathy, a disease followed by a high incidence of urinary tract tumours. Concerning the genotoxicity of OTA, we have recently shown, using the [32P]-phosphate postlabelling method, that several DNA-adducts are formed in four mice organs treated with OTA. Some of the adducts were specific of every analyzed tissue. These results, allow us to state that OTA metabolism in different from organ to organ. The influence of OTA metabolism on its genotoxic effect was studied. Preliminary results have shown the possibilities of oxidative pathways in OTA metabolism leading to genotoxic compounds. Effects of some vitamins such as retinol (A), ascorbic acid (C) and tocopherol (E), which are known to act as superoxide anion scavengers, were tested on genotoxicity of OTA. Pretreatment of mice by vit E induced a decrease of the DNA-adducts by 80% in kidney, and by 55% in liver. Vit A and vit C decreased DNA-adduct levels by 70% in kidney. In liver, DNA adduct level was essentially decreased by vit C (90%). Vit A decreased only the level by 25% in this organ. The involvement of oxidative metabolism in the genotoxicity of OTA led us to investigate the effect of prostaglandin H synthase (PHS) which is known to cooxidase xenobiotics. Aspirin and indomethacin which inhibit this enzyme were given prior to OTA administration to mice in order to test this metabolic pathway. The decrease observed with aspirin was of about 90% and 30% in kidney and liver respectively, and of 90% and 80% with indomethacin in kidney and liver. These results confirmed that OTA is activated to genotoxic metabolites by cooxydation by the prostaglandin synthase route. Human bronchial epithelial cells (BEAS-2B) expressing or not human cytochrome P450s (CYP) (1A2, 2A6, 2D6, 2E1 and 3A4) were incubated with 0.5 microM OTA for 24 h. DNA-adducts were detected in all cells. Total DNA-adduct levels ranged from 4 to 85 adducts per 10(9) nucleotides. Some adducts were common to all cell types including cells expressing only normal phase II enzymes, but no cytochromes P450. Some other DNA-adducts were only induced by specific CYPs. The highest DNA-adduct level was found in cells where CYP 1A2 was expressed. Nevertheless, more different types of DNA-adducts were formed in cells expressing CYP 2D6.(ABSTRACT TRUNCATED AT 400 WORDS)     

A role for glucose in hypothermic hamsters

Hamsters undergo hypothermia when exposed to a mixture of 80% helium and 20% oxygen at low ambient temperatures. The hypothermic hamster, rectal temperature (Tre) 7 degrees C, becomes hypoglycemic, and reversal of hypoglycemia is effected with glucose infusion. Hypothermic hamsters at Tre 7 degrees C showed a fivefold increase in survival times from 20 to 100.5 h when infused with glucose which maintained a blood level at about 45 mg/100 ml. A potential role for osmotic effects of the infusion was tested and eliminated. There was no improvement in survival of 3-O-methylglucose or dextran 40-infused animals. The fact that death eventually occurs even in the glucose-infused animal after about 4 days and that VO2 undergoes a slow decrement in that period suggests that hypothermic survival is not wholly substrate limited. Radioactive tracer, [U-14C]glucose, showed that localization of the 14C, was greatest in brain tissue and diaphragm, intermediate in heart and kidney, and lowest in skeletal muscle and liver. The significance of the label at sites important to respiration and circulation was presented.     

Prenatal exposure to environmental toxin: A test of the multiple effects model.

The multiple effects model of teratological exposure predicts that neonatal deficits associated with intrauterine exposure to small doses of a potentially teratogenic agent will vary considerably across individuals. This hypothesis was tested in a sample of 242 newborns exposed prenatally to low levels of polychlorinated biphenyls (PCBs) from maternal consumption of contaminated lake fish and 71 control infants whose mothers did not eat these fish. Behavioral outcomes were assessed using the Brazelton Neonatal Behavioral Assessment Scale (NABS). Contaminated fish consumption predicted motoric immaturity, poorer lability of states, a greater amount of startle, and more abnormally weak (hypoactive) reflexes. The most highly exposed Ss were more likely than controls to be classified as "worrisome" on 3 NBAS clusters. Results from a stepwise regression analysis are consistent with the multiple effects model, indicating that some affected Ss were born small and/or early, whereas others exhibited one or another of the behavioral deficits. The analysis indicated that 12.2% of the variance in contaminated fish consumption was associated with measurable neonatal deficits. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal effects of drugs of abuse on brain development

Drugs of abuse modify signaling of neurotransmitter systems and intracellular messengers. Recent studies of central nervous system development show that these same neurotransmitters may serve as molecules that regulate specific aspects of cell proliferation, survival, migration, circuit formation and establishment of topography. Moreover, the convergence of neurotransmitter, growth factor and hormone activity on similar intracellular signaling systems suggests the potential for significant interactions among molecular components that regulate development. The application of modern strategies used by developmental and cell biologists to the question of whether prenatal drug exposure alters brain structure and function has led to discoveries of specific, targeted changes. Studies of the mechanisms of drug action that lead to altered neural development are now reality.     

Long-term effects of clenbuterol on diaphragm morphology and contractile properties in emphysematous hamsters

The most reliable prognostic factors for patients with primary malignant brain tumors remain histology, age, and functional status. Management of these individuals might be improved by quantifying pertinent molecular markers. We have measured the gene dosage of the epidermal growth factor receptor (EGFR), mouse double minute 2 (MDM2), and cyclin-dependent kinase 4 (CDK4) genes in a series of brain tumor specimens and correlated their amplification status with standard prognostic factors and survival. Individual tumor DNA was successively hybridized with probes for EGFR, MDM2, and CDK4. The signal was quantified by densitometry, and amplification was defined as gene signal > or = 2 times normal. Survival, age, Karnofsky performance status, and histology were correlated with gene amplification. Nineteen astrocytomas, 20 anaplastic astrocytomas, and 70 glioblastomas had complete data available. Median survival with and without any form of gene amplification was 70.7 and 88.6 weeks, respectively (P = 0.0369). For the EGFR gene alone, those with and without amplification had a median survival of 58.9 and 88.6 weeks, respectively (P = 0.0104). By Cox analysis, only tumor histology (P = 0.04) and Karnofsky performance status (P = 0.0157) were significant independent predictors of survival. Gene amplification by itself was not predictive of survival, even for glioblastomas (P = 0.8249). The lack of correlation between gene amplification and survival for patients with primary malignant brain tumors may be because EGFR, MDM2, and CDK4 are only portions of larger signaling systems. Therefore, the lack of a direct correlation between a single gene and outcome is not entirely unexpected.     

Time course of VMN lesion effects on lordosis and ultrasound production in hamsters

Lesions of the ventromedial hypothalamus (VMN) depress lordosis but increase ultrasonic vocalization in female hamsters. These changes are consistent with the behavioral incompatibility of lordosis and ultrasound production and suggest that the VMN coordinates short-term changes in these behaviors. In keeping with past results, unilateral lesions disrupted lordosis responses to contralateral flank stimulation. The change appeared within 15 min after the lesion and was much more rapid than the corresponding effect in rats. For hamsters, these findings support other evidence suggesting VMN mediation of somatosensory, not just hormonal, influences on lordosis. In a companion study, ultrasound rates became depressed within 15 min of bilateral lesion of the VMN, suggesting a role for the VMN in the short-term control of ultrasound production. Calling at later time intervals was facilitated by the lesions. The direction and time course of the lesion effects on lordosis and ultrasound production suggest that the VMN cannot easily account for the behavioral incompatibility of these 2 responses.     

Prenatal exposure to cocaine: effects on aggression in Sprague-Dawley rats

Social/aggressive behavior in adult rat offspring (beginning at postnatal Day 180) prenatally exposed to saline, cocaine, or amfonelic acid (AFA) was examined. Pregnant rats received injections of 15 mg/kg of cocaine, or 0.9% saline twice daily, s.c., or on 2 consecutive days at 4-day intervals, or 1.5 mg/kg amfonelic acid daily throughout gestational Days 1-20. Frequency, duration, and latency of 11 social/aggressive behaviors were recorded for two 15-min sessions during which a smaller male intruder replaced an ovariectomized female in the resident's home cage. Subjects received a s.c. saline injection before Session 1 and 2.0 mg/kg of gepirone, a 5HT1a partial agonist, prior to Session 2. Prenatal cocaine treatment resulted in alterations of aggressive behavior. Aggressive behavior was reduced by gepirone in all groups but to a lesser extent in the AFA group.     

Prenatal maternal X-irradiation: Maternal and offspring effects.

Reports an experiment in which Charles River rats, irradiated or sham irradiated on Day 16 of fetal life, were reared by irradiated or nonirradiated foster mothers (n = 24) in a dual-chambered maternity cage. Results show that irradiated mothers spent less time with their litters than controls independent of the nature of the pups. Irradiated Ss weighed less than controls and the prenatal effects on mortality during the immediate postweaning period were influenced by maternal factors. Ss reared by irradiated mothers weighed less, were less emotional, and were more susceptible to the lethal effects of subsequent X-irradiation than Ss reared by nonirradiated mothers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ochratoxin A: a naturally occurring mycotoxin found in human milk samples from Norway

The presence of ochratoxin A (OA) in human milk samples from different regions in Norway was investigated to determine the level of infant exposure to OA from human milk. OA was found in 38 (33%) of 115 human milk samples (range 10-130 ng l(-1)). It was found that 2-26% of the samples contained more than 40 ng l(-1) OA, which will cause a daily intake of OA from human milk exceeding the suggested tolerable dose of 5 ng kg(-1) body weight. Significant regional differences were found.     

Dextrorphan, but not dextromethorphan, exerts weak antidystonic effects in mutant dystonic hamsters

The effects of dextromethorphan and its metabolite dextrorphan on severity of dystonia were examined in mutant dystonic hamsters, an animal model of idiopathic paroxysmal dystonia, in which recent examinations have shown antidystonic effects of selective N-methyl-D-aspartate (NMDA) receptor antagonists. Dextromethorphan and dextrorphan are non-competitive NMDA receptor antagonists which additionally exhibit affinity for sigma receptors. Dextrorphan (20 and 40 mg/kg i.p.) significantly retarded the progression of dystonia at the higher dose, whereas dextromethorphan (20, 40, 60 mg/kg i.p.) failed to exert any antidystonic effects even at high doses which caused severe effects. The lack of antidystonic efficacy of dextromethorphan may be related to its higher affinity to sigma receptors compared with dextrorphan.     

Developmental and withdrawal effects of adolescent AAS exposure on the glutamatergic system in hamsters.

In the Syrian hamster (Mesocricetus auratus) glutamate activity has been implicated in the modulation of adolescent anabolic-androgenic steroid (AAS)-induced aggression. The current study investigated the time course of adolescent AAS-induced neurodevelopmental and withdrawal effects on the glutamatergic system and examined whether these changes paralleled those of adolescent AAS-induced aggression. Glutamate activity in brain areas comprising the aggression circuit in hamsters and aggression levels were examined following 1, 2, 3, and 4 weeks of AAS treatment or 1, 2, 3, and 4 weeks following the cessation of AAS exposure. In these studies glutamate activity was examined using vesicular glutamate transporter 2 (VGLUT2). The onset of aggression was observed following 2 weeks exposure to AAS and continued to increase showing maximal aggression levels after 4 weeks of AAS treatment. This aggressive phenotype was detected after 2 weeks of withdrawal from AAS. The time-course of AAS-induced changes in latero-anterior hypothalamus (LAH)-VGLUT2 closely paralleled increases in aggression. Increases in LAH-VGLUT2 were first detected in animals exposed to AAS for 2 weeks and were maintained up to 3 weeks following the cessation of AAS treatment. AAS treatment also produced developmental and long-term alterations in VGLUT2 expression within other aggression areas. However, AAS-induced changes in glutamate activity within these regions did not coincide with changes in aggression. Together, these data indicate that adolescent AAS treatment leads to alterations in the glutamatergic system in brain areas implicated in aggression control, yet only alterations in LAH-glutamate parallel the time course of AAS-induced changes in the aggressive phenotype. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A study of spatial parameters encoded during exploration in hamsters.

In two experiments the exploratory reactions of hamsters to various rearrangements of familiar objects were examined. During two sessions, the subjects were allowed to explore a circular, open field containing four different objects. During a third test session, one or several objects were displaced, changing the shape and/or the size of the area defined by the object set. Significant reexploration was found when the change brought about during the test session affected the geometrical relations between the objects or when an object was removed. In contrast, changes that did not modify the geometrical configuration of the arrangement of the objects, but only modified the distance of one object to another, did not elicit any reexploration. Additionally, it was found that selective reexploration of the actually displaced objects occurred only when the change removed this object a certain distance from the others. These results are discussed in terms of stimulus complexity and more generally with regard to the spatial parameters that are selected, processed, and stored during exploration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tissue and sex-dependent differences in CYP2A activities in hamsters

Three enzymatic activities of the CYP2A subfamily, coumarin 7-hydroxylase (COH), testosterone 15 alpha-hydroxylase (T15 alpha OH) and testosterone 7 alpha-hydroxylase (T7 alpha OH), were characterized in liver, kidney and lung microsomes from control, pyrazole (PYR), 3-methylcholanthrene (MC) and phenobarbital (PB) treated female and male Syrian golden hamsters. Sex-dependent changes in the enzymatic activities were found. Among control animals COH and T15 alpha OH activities were higher in males. T7 alpha OH activity was five times higher in female kidneys than in males. Inducers changed this metabolic profile. MC and PB were potent CYP2A inducers in extrahepatic tissues: significant increases were found in COH (5-fold) and T15 alpha OH (12-fold) activities in female MC lung microsomes and T7 alpha OH (7-fold) in MC male kidney microsomes. PB increased significantly activities of COH (5-fold), T15 alpha OH (3-fold) and T7 alpha OH (10-fold) in male kidney microsomes. All inducers significantly increased T7 alpha OH activity in male kidney microsomes but decreased hepatic T7 alpha OH activity in both sexes. PYR treatment decreased hepatic CYP2A activities. Anti-mouse CYP2A4/5 antibody inhibited COH activity by a variable extent depending on the tissue and pretreatment and recognised three 52-, 49-, 48-kDa bands in liver and two major bands in kidney (48 and 49 kDa) and lung (49 and 52 kDa) microsomes. COH and T15 alpha OH activities correlated well with 49 kDa protein (r = 0.95 and r = 0.99, respectively) in lung microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanistic insights into chemopreventive effects of phenethyl isothiocyanate in N-nitrosobis(2-oxopropyl)amine-treated hamsters

The influence of phenethyl isothiocyanate (PEITC) on cell kinetics in the target organs of N-nitrosobis(2-oxopropyl)amine (BOP) tumorigenicity and on xenobiotic-metabolizing enzymes was investigated in hamsters. Female 5-week-old Syrian hamsters were given a single s.c. dose of 0, 20 or 50 mg/kg of BOP 2 h after receiving PEITC by gavage at a dose of 0, 100 or 250 mumol/animal (0, 16.3 or 40.8 mg/animal). Six and 22 h after the BOP administration, hamsters were killed and tissues were sampled. Proliferating cell nuclear antigen immunohistochemistry demonstrated significant reduction (P < 0.05-0.001) by PEITC of the labeling indices in the pancreatic acini and ducts, bronchioles, and renal tubules of the BOP-treated animals in a dose-dependent manner. In the lungs, the PEITC pretreatment significantly (P < 0.001) reduced the O6-methyldeoxyguanosine levels as compared to the BOP-alone value. Immunoblot analysis of liver cytochrome P450 isoenzymes showed CYP 2B1 to be mainly involved in the metabolic activation of BOP. PEITC significantly (P < 0.05) inhibited the induction of several isoenzymes, including CYP 2B1, while lowering the hepatic glutathione S-transferase activity as well as glutathione levels, regardless of BOP administration. Our results thus suggest that PEITC exerts its chemopreventive activity against BOP initiation of carcinogenesis in hamsters by decreasing cell turnover and DNA methylation in the target organs, and by influencing hepatic xenobiotic-metabolizing phase I enzymes, although the relationship, if any, of the latter with the former events remains to be investigated.     

Enduring effects of photoperiod on affective behaviors in Siberian hamsters (Phodopus sungorus).

The effects of perinatal and postweaning photoperiods on subsequent affective behaviors were examined in adult Siberian hamsters (Phodopus sungorus). Hamsters exposed perinatally to short days (8 hr light/day) exhibited mixed results for adult anxiety-like behaviors and increased some depressive-like behaviors compared with hamsters exposed to long days (16 hr light/day). Postweaning exposure to short days increased depressive- and anxiety-like behaviors compared with long days. Sex differences in affective behaviors were observed. These results suggest that anxiety-like behaviors are organized early in life and endure throughout adulthood, and anxiety- and depressive-like behaviors are modified by postweaning photoperiod. The persistence of photoperiod-induced affective behaviors in rodents supports the hypothesis that symptoms of human affective disorders may reflect ancestral adaptations to seasonal environments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antispermatogenic effects of ethyl methanesulfonate and benzo[a]pyrene in PD4 Lakeview hamsters

Mammalian sperm seems to provide an excellent cell type for monitoring mutagenic and other toxicological damage to the germinal tissue. Studies with mice indicated that most agents known for their mutagenic activity in vivo produced marked elevations in sperm abnormalities. To determine whether this response is typical of other species, groups of inbred Lakeview hamsters were exposed to ethyl methane-sulfonate (EMS) and benzo[a]pyrene (BP) in five daily subacute ip doses ranging from 5 to 125 mg/kg and 2 to 50 mg/kg, respectively. Percentage of abnormal sperm, testis weight, and body weight were monitored at wk 1, 4, and 10 after treatment. EMS exposures increased the frequency of sperm abnormalities and reduced sperm numbers and testis weights. Body weights were also affected. BP exposures did not induce sperm abnormalities; however, there were marked reductions in sperm number and testis weight. These findings are in agreement with results of EMS studies in the mouse; however, BP exposure did induce sperm abnormalities in the mouse.     

Respiratory mechanics in normal hamsters

Lung volumes and quasi-static deflation volume-pressure relationships were measured in male golden hamsters anesthetized with pentobarbital. Volume was measured with a pressure plethysmograph, and pleural pressure was estimated by the use of a water-filled esophageal catheter. Mean body weight +/- SE was 122.3 +/-3.0 g, mean lung weight was 0.74 +/- 0.2 g or about 0.6% of body weight. Mean lung volume at 25 cmH2O transpulmonary pressure (TLC25) was 7.2 +/- 0.14 ml, 9.78 +/- 0.17 ml/g lung weight or 5.92 +/- 0.06 ml/100 g body weight. Mean functional residual capacity was 2.4 +/- 0.06 ml or 33.3% of TLC25. Mean vital capacity was 5.2 +/- 0.13 ml. Mean quasi-static compliance of lung was 0.63 +/- 0.03 ml/cmH2O. Chord compliance of chest wall between lung volumes of 1 and 4 ml above RV was 3.39 +/- 0.53 ml/cmH2O. At FRC, the chest wall recoiled inward, so that pleural pressure was positive (1.4 +/- 0.13 cmH2O) and the lung was resisting further collapse. The slope of the lung's deflation volume-pressure curve changed at FRC, ERV was small (0.36 +/- 0.03 ml), and RV was determined by complete airway closure. Thus the mechanisms determining FRC are unusual and include an influence of airway closure.     

Differential effects of lesions in three limbic areas on ultrasound production and lordosis by female hamsters.

Examined ultrasound production and lordosis in 98 ovariectomized, hormone-primed (estradiol benzoate [10 μg] and progesterone [500 μg]) female golden hamsters before and after sham operations or bilateral electrolytic lesions. During 2-min exposures to synthetic ultrasounds and 1-min exposures to stimulus males, Ss with corticomedial amygdala lesions exhibited reduced ultrasound rates and lordosis durations. Following lesions in the lateral septum/bed nucleus, Ss showed significant increases in ultrasound rates but no change in lordosis. Ablations of the lateral habenula had no effect on calling but were associated with shorter lordosis durations. Results demonstrate that 2 reproductive behaviors, ultrasound production and lordosis, are differentially affected by lesion placement within the limbic system. These differences demonstrate that the neural mechanisms for 2 elements of a single major class of behavior can be distinct, both in terms of the likelihood that particular brain areas will be involved and in the nature of their involvement. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)