Alcohol is an important risk factor for human oesophageal cancer. There is evidence from epidemiological studies that some
specific alcoholic drinks, e.g. Calvados apple brandy, are associated with a greater risk than others. Alcohol induces cytochrome
P450 2E1 (CYP2E1) and the hypothesis was tested that different alcoholic beverages, containing a variety of alcoholic compounds,
could differentially induce expression of cytochrome P450 enzymes. Twelve groups of five rats each were treated for 3 days
with different alcoholic beverages (ethanol alone, whisky, farm-produced or commercial Calvados brandy, beer, cider, wine)
adjusted to 4, 10 or 20% of ethanol in drinking water. Immunoblotting using a monoclonal antibody specific for rat CYP2E1
revealed a single protein band in liver microsomes. Densitometric quantitation of microsomal proteins demonstrated a significant
two-, three- and sixfold increase in band intensity after treatment with ethanol concentrations of 4, 10 and 20% respectively,
compared to control rats drinking water alone. There was a dose-dependent increase in liver microsomal metabolism of CYP2E1
substrates (para-nitrophenol and dimethylnitrosamine) in ethanol-treated rats. However, there were no significant differences
in the level of CYP2E1 protein or enzymatic activity between the different alcoholic beverages at the same ethanol concentration.
There was a slight increase in hepatic CYP1A-related enzymatic activities in the alcohol-treated rats compared to the controls,
but no difference between the treated groups either with dose of ethanol or type of beverage. These data show that induction
of CYP2E1 with acute alcohol treatment is predominantly determined by the ethanol content of the beverage.
Received: 10 February 1997 / Accepted: 26 May 1997 相似文献
Schistosoma mansoni infection, both in humans and in animal models, is known to induce granulomas in the liver and intestine. It has also been
reported that in humans the eggs of this parasite can reach the brain, causing psychiatric and neuropathological disorders.
Whether this also occurs in rodents is unknown. To answer this question, mice were infected with this parasite and the central
nervous system (CNS) examined at various time intervals. The results show that schistosomiasis induced granulomas in several
regions of the CNS and increased nerve growth factor (NGF) levels in the cortex, hypothalamus and brain stem, but not in the
hippocampus. The infection also caused paw hyperalgesia, as determined by the hot-plate test, and a local increase in NGF,
but not in substance P. These findings indicate that the murine model of infection can be used for studying mechanisms leading
to human neuroschistosomiasis and suggest that the neuropathological disorders and the sensory deficits observed in human
schistosomiasis are associated with impaired levels of NGF in the peripheral and central nervous system.
Received: 18 January 1996 / Revised, accepted: 16 April 1996 相似文献
The development of catecholaminergic neuronal systems in the brain of a teleost, the three-spined stickleback, was studied through embryonic to early larval stages by immunocytochemistry using specific antibodies against dopamine, tyrosine hydroxylase and dopamine β-hydroxylase. By analysing the spatiotemporal patterns of development for the catecholaminergic nuclei, possible homologies with nuclei in amniote brains have been identified.
The noradrenergic neurons in the isthmus region of the rostral rhombencephalon originate in the same manner as the A4–A7 + subcoeruleus group in mammals. Their developmental characteristics show the largest similarities with the subcoeruleus group of birds and mammals, although some features are shared with developing A6 (locus coeruleus) neurons.
Catecholaminergic neurons never appear during development in the ventral mesencephalon of the three-spined stickleback. A group of large dopaminergic neurons that accompany the cerebrospinal fluid (CSF)-contacting neurons follows the border between the hypothalamus and the ventral thalamus into the caudal hypothalamus, where they are continuous with the dopaminergic neurons in the posterior tuberculum. They are thus topologically comparable with the dopaminergic neurons of the zona incerta in mammals.
The dopaminergic CSF-contacting neurons that line the median, lateral and posterior recesses of the third ventricle do not contain tyrosine hydroxylase-immunoreactivity at any developmental stage. This indicates that they take up and accumulate exogenous dopamine or
-dihydroxyphenylalanine, and do not synthesize dopamine from tyrosine at any developmental stage. Tyrosine hydroxylase-immunoreactive neurons appear in the pineal organ on the day of hatching (120 h post-fertilization). They were still observed in 240-h-old larvae, but are absent in the pineal organ of adult sticklebacks.
The initial appearance and subsequent differentiation of catecholaminergic neurons in the stickle-back embryo follow essentially the same spatial and temporal pattern as in amphibian, avian and mammalian embryos. This observation supports the hypothesis that morphologically, topologically and chemically similar monoaminergic neurons in different vertebrate classes are homologous. 相似文献