Effects of d-amphetamine injected into the nucleus accumbens on ethanol reinforced behavior

Rats, initiated to self-administer 10% (v/v) ethanol in an operant situation using the sucrose-fading procedure, received bilateral n. accumbens microinjections of d-amphetamine prior to operant sessions. Doses of 4 micrograms, 10 micrograms and 20 micrograms/brain were administered and some animals also received a 4 microgram/brain dose of LY171555. Three different effects were observed: increased, decreased and no change in total session responding. There was no clear relation between injection area in the n. accumbens and type of effect observed. For either an increase or decrease in total session responding, momentary response rates were decreased. Both d-amphetamine and LY171555 produced similar results. The data support the hypothesis that dopamine in the n. accumbens is involved with ethanol reinforced operant responding but in a complex manner.     

A theoretical model evaluating the angular distribution of luminescence emission in X-ray scintillating screens.

The aim of this study was to examine the angular distribution of the light emitted from radiation-excited scintillators in medical imaging detectors. This distribution diverges from Lambert's cosine law and affects the light emission efficiency of scintillators, hence it also affects the dose burden to the patient. In the present study, the angular distribution was theoretically modeled and was used to fit experimental data on various scintillator materials. Results of calculations revealed that the angular distribution is more directional than that predicted by Lambert's law. Divergence from this law is more pronounced for high values of light attenuation coefficient and thick scintillator layers (screens). This type of divergence reduces light emission efficiency and hence it increases the incident X-ray flux required for a given level of image brightness.     

Dopaminergic involvement in locomotion elicited from the ventral pallidum/substantia innominata

Microinjection of the indirect GABAA antagonist, picrotoxin, or the mu opioid agonist, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO), into the ventral pallidum and substantia innominata (VP/SI) increases locomotor activity in rats. The VP/SI has direct and indirect projections to the region of the ventral mesencephalon containing dopamine perikarya, and to certain dopamine terminal fields, including the nucleus accumbens. Thus, it is possible that modulation of the mesocorticolimbic dopamine system by pharmacological stimulation in the VP/SI may play a role in the locomotor stimulant response. It was shown that pretreatment with dopamine receptor antagonists, either peripherally or microinjected into the nucleus accumbens significantly attenuated the motor stimulant effect of DAGO or picrotoxin injection into the VP/SI. Injection of either picrotoxin or DAGO into the VP/SI increased the levels of dopamine metabolites in the nucleus accumbens and prefrontal cortex. Thus, the motor stimulant response following pharmacological stimulation of the VP/SI appears to be mediated by increased dopamine neurotransmission via feedback mechanisms to the mesocorticolimbic dopamine system.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

用于筛选天然产物中脲酶抑制剂的脲酶活性测试方法的建立

抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Ｂｅｒｔｈｅｌｏｔ试剂在９６孔培养板上检测重组脲酶活性，其灵敏度指标酚红法每ｍｇ酶蛋白引起的每分钟吸光度变化。△Ａ为６．９，而Ｂｅｒｔｈｅｌｏｔ法每ｍｇ酶蛋白引起的每分钟吸光度比值变化△Ａ为３１３。结果表明用Ｂｅｒｔｈｅｌｏｔ试剂检测重组脲酶活性适宜在９６孔培养板上大规模筛选天然产物中的脲酶抑制剂。     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Substance P modulation of dopamine in the nucleus accumbens

Rats were implanted with bilateral injection cannulae in the nucleus accumbens. While microinjection of substance P (1.0-10.0 micrograms/side) did not alter locomotor or rearing behavior, it did potentiate the motor stimulant effects of intra-accumbens injection with dopamine. Further, substance P injection into the nucleus accumbens significantly elevated the levels of dopamine metabolites in that nucleus. Both the behavioral and neurochemical dose-response curves were biphasic, with 3.0 micrograms of substance P producing a maximal response. These data suggest an interaction between substance P and dopamine in the nucleus accumbens.     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.