Upper limits of brain blood flow autoregulation in stable infants of various conceptional age

In healthy adults cerebral blood flow is autoregulated and kept constant over a wide range of mean arterial blood pressures (MAP) between 60 and 150 mmHg. In 27 stable infants with different conceptional ages ranging from 33 to 50 weeks, Doppler measurements of mean flow velocity at the anterior cerebral artery have been recorded simultaneously with mean arterial blood pressures (MAP) during a period of 6 h. The range of autoregulation and its upper limit could thus be determined. The upper limit was found to increase with advancing age. In the infants with conceptional ages between 33 and 35 weeks, the upper limit of autoregulation varied between 45 and 60 mmHg, while the upper limit shifted to a MAP of 100 mmHg at 47 weeks conceptional age. A significant positive linear relationship existed between the upper limit of autoregulation and conceptional age.     

Marijuana,alcohol and actual driving performance

The objective of the current study was to assess the separate and combined effects of marijuana and alcohol on actual driving performance. Eighteen subjects were treated with drugs and placebo according to a balanced, 6-way, crossover design. On separate evenings they were given weight calibrated Delta(9)-tetrahydrocannabinol (THC) doses of 0, 100 and 200 &mgr;g/kg with and without an alcohol dose sufficient for achieving blood alcohol concentrations (BAC) of 0.04 g/dl while performing a Road Tracking and Car Following Test in normal traffic. Main outcome measures were standard deviation of lateral position (SDLP), time driven out of lane (TOL), reaction time (RT) and standard deviation of headway (SDH). Both THC doses alone, and alcohol alone, significantly impaired the subjects performances in both driving tests. Performance deficits were minor after alcohol and moderate after both THC doses. Combining THC with alcohol dramatically impaired driving performance. Alcohol combined with THC 100 and 200 &mgr;g/kg produced a rise in SDLP the equivalent of that associated with BAC=0.09 and 0.14 g/dl, respectively. Mean TOL rose exponentially with SDLP. Relative to placebo mean RT lengthened by 1.6 s under the combined influence of alcohol and THC 200 &mgr;g/kg. Changes in SDH ranged between 0.9 and 3.8 m. Low doses of THC moderately impair driving performance when given alone but severely impair driving performance in combination with a low dose of alcohol. Copyright 2000 John Wiley & Sons, Ltd.     

Morphologically normal, CD30-negative B-lymphocytes with chromosome aberrations in classical Hodgkin's disease: the progenitor cell of the malignant clone?

A recent study observed that numerical chromosome abnormalities in Hodgkin's disease (HD) are detected not only in morphologically abnormal Hodgkin/Reed-Sternberg cells, but also in a fraction of morphologically normal cells. However, the phenotypic constitution of these genetically abnormal, morphologically normal cells and their relationship to the malignant Hodgkin/Reed-Sternberg cells could not be established in the earlier cases studied, because of the low frequency of these cells. The present study investigated two cases of classical Hodgkin's disease containing a relatively large population of such apparently normal cells with aberrant chromosome copy numbers. The phenotype and their position within the developmental route of the malignant compartment were examined by a combined in situ hybridization and immunocytochemistry approach. Numerical abnormalities for chromosome 1 in one case and for chromosomes X, Y, and 1 in the other case were observed not only in CD30-positive Hodgkin/Reed-Sternberg cells, but also in CD30-negative, morphologically normal cells. It was shown that these genetically aberrant cells expressed the B-cell antigen CD19, thus confirming their B-cell nature. These studies indicate a relationship between the genome aberrations in these genetically abnormal, morphologically normal B-cells and the Hodgkin/Reed-Sternberg cells, suggesting that they are progenitor cells of the malignant cell fraction.     

Detection of Melanocortin-3 Receptor mRNA in Immature Rat Pituitary: FUnctional Relation to γ3-MSH-Induced Changes in Intracellular Ca2+ Concentration?

We have previously shown that gamma3-MSH stimulates DNA replication in lactotrophs, somatotrophs and thyrotrophs of early postnatal rat pituitary in culture. Since the melanocortin-3 (MC-3) receptor is the only known receptor displaying high affinity for gamma3-MSH, the present study explored whether mRNA of the latter receptor is present in the pituitary and whether the receptor is functional. RT-PCR of RNA extracts from 14-day-old rat pituitary revealed the presence of MC-3 receptor mRNA in both the anterior and the neurointermediate lobe. The identity of the amplified products was confirmed by sequence analysis. Dispersed cells of 14-day-old female rats (24 h in culture) were exposed to gamma3-MSH, and changes in intracellular free calcium levels ([Ca2+]i) were assessed by means of fluo-3 video imaging. Gamma3-MSH evoked a rapid and maintained oscillating [Ca2+]i increase in 5%, 10% and 15% of the cells at a dose of 0.1, 1 and 10 nM, respectively. The MC-3/MC-4 receptor antagonist Ac-Nle4-c[Asp5,(D-Nal(2)7,Lys10]alpha-MSH-(4-10)-NH2 (SHU 9119) blocked the effect of gamma3-MSH in about 50% of the responsive cells. The present data suggest that the MC-3 receptor is expressed in the rat pituitary but that this receptor mediates only half of the effects of its putative ligand, gamma3-MSH, on [Ca2+]i. Part of the effect of gamma3-MSH may be mediated by a MC-3 receptor in a functional state different from the one studied previously in transfected cell lines or by a hitherto unidentified MC receptor.     

Cytochrome P450 mediated bioactivation of methyleugenol to 1'- hydroxymethyleugenol in Fischer 344 rat and human liver microsomes

Cytochrome P450 mediated metabolism of methyleugenol to the proximate carcinogen 1'-hydroxymethyleugenol has been investigated in vitro. Kinetic studies undertaken in liver microsomes from control male Fischer 344 rats revealed that this reaction is catalyzed by high affinity (Km of 74.9 +/- 9.0 microM, Vmax of 1.42 +/- 0.17 nmol/min/nmol P450) and low affinity (apparent Km several mM) enzymic components. Studies undertaken at low substrate concentration (20 microM) with microsomes from livers of rats treated with the enzyme inducers phenobarbital, dexamethasone, isosafrole and isoniazid indicated that a number of cytochrome P450 isozymes can catalyze the high affinity component. In control rat liver microsomes, 1'- hydroxylation of methyleugenol (assayed at 20 microM substrate) was inhibited significantly (P < 0.05) by diallylsulfide (40%), p- nitrophenol (55%), tolbutamide (30%) and alpha-naphthoflavone (25%) but not by troleandomycin, furafylline, quinine or cimetidine. These results suggested that the reaction is catalyzed by CYP 2E1 and by another as yet unidentified isozyme(s) (most probably CYP 2C6), but not by CYP 3A, CYP 1A2, CYP 2D1 or CYP 2C11. Administration of methyleugenol (0-300 mg/kg/day for 5 days) to rats in vivo caused dose- dependent auto-induction of 1'-hydroxylation of methyleugenol in vitro which could be attributed to induction of various cytochrome P450 isozymes, including CYP 2B and CYP 1A2. Consequently, high dose rodent carcinogenicity studies are likely to over-estimate the risk to human health posed by methyleugenol. The rate of 1'-hydroxylation of methyleugenol in vitro in 13 human liver samples varied markedly (by 37- fold), with the highest activities being similar to the activity evident in control rat liver microsomes. This suggests that the risk posed by dietary ingestion of methyleugenol could vary markedly in the human population.      

Effects of loratadine and cetirizine on actual driving and psychometric test performance,and EEG during driving

Summary Sixteen healthy male and female volunteers took part in a 6-way, double-blind cross-over trial to compare the effects of single doses of cetirizine 10 mg, loratadine 10 mg and placebo, with and without alcohol (0.72 g·kg^–1, lean body mass). Performance was measured in two repetitions of a psychometric test battery, and a standard, over-the-road driving test. EEG was also measured during driving. Alcohol significantly affected almost every performance measure and altered the EEG energy spectrum during driving whilst the blood concentrations declined from 0.37 to 0.20 mg·ml^–1. The effects of cetirizine of on driving performance resembled those of alcohol. It caused the subjects to operate with significantly greater variability in speed and lateral position (weaving motion). The effects of alcohol and cetirizine appeared to be additive. Certain cetirizine-placebo differences in subjective feelings and test battery performance were also significant. Loratadine had no significant effect on any performance parameter. It was concluded that cetirizine, but not loratadine, generally caused mild impairment of performance after a single 10 mg dose.     

Expression of intermediate filament proteins in the adult human vestibular labyrinth.

The immunohistochemical detection of intermediate filament proteins, cytoskeletal constituents that allow the characterization of tissues, was investigated in frozen sections of the chemically fixed, nondecalcified, adult human vestibular labyrinth. Cytokeratins (CKs) were detected in all epithelia (including the sensory epithelia), although substantial differences in the degree of staining between individual cells occurred. The expression of CKs 7, 8, 18, and 19 as detected with our subunit-specific monoclonal antibodies in the vestibular epithelia is typical of "simple" epithelia and is identical to the CK subtypes found in the human cochlea. Although immunostaining for CK 7 was very weak and was limited to certain vestibular wall cells, the other CKs demonstrated a pronounced and rather uniform distribution throughout the different epithelia. All epithelia (including the sensory epithelia) displayed expression of vimentin, thus demonstrating co-expression with CKs. Vimentin was also present in the subepithelial connective tissue fibroblasts and mesothelial lining of the vestibular labyrinth. Neurofilament proteins were detected in all neuronal structures. The intense staining for CKs in the maculae and cristae implies that these sensory organs are rigid structures, a finding that may possibly be of importance in the mechanoelectrical transduction process for the sense of equilibrium.     

中药材X-射线衍射图谱研究

为探讨中药材道地性的客观规律,以期建立相应的评估指标系统,本文选择常用中药材茜草类、贝母类、山药类三组样品,应用X-射线粉末衍射法进行图谱分析,获得了可用于标识中药材的衍射图形几何拓扑规律与图谱特征标记峰,由此观察到:不同产地茜草样品的相似性及其与欧茜草的差别;同属不同种贝母样品的相似性与差异;不同产地山药样品的相似性及与伪品的区别。本文结果预示着这一方法在揭示中药材道地性客观规律方面的广阔应用前景。