Parkinson's disease: activity of L-dopa decarboxylase in discrete brain regions

The activity of L-dopa decarboxylase was greatly reduced in the striatum, less so in the hypothalamus, and unchanged in the cortex of brains of patients with Parkinson's disease. However, it appears that even in the striatum enough activity remained to allow for the formation of dopamine from L-dopa in patients treated with large doses of L-dopa.     

Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET

The regional distributions of monoamine oxidase (MAO) types A and B have been identified in human brain in vivo with intravenously injected 11C-labeled suicide enzyme inactivators, clorgyline and L-deprenyl, and positron emission tomography. The rapid brain uptake and retention of radioactivity for both 11C tracers indicated irreversible trapping. The anatomical distribution of 11C paralleled the distribution of MAO A and MAO B in human brain in autopsy material. The corpus striatum, thalamus, and brainstem contained high MAO activity. The magnitudes of uptake of both [11C]clorgyline and L-[11C]deprenyl were markedly reduced in one subject treated with the antidepressant MAO inhibitor phenelzine. A comparison of the brain uptake and retention of the 11C-labeled inactive (D-) and active (L-) enantiomers of deprenyl showed rapid clearance of the inactive enantiomer and retention of the active enantiomer within MAO B-rich brain structures, in agreement with the known stereoselectivity of MAO B for L-deprenyl. Prior treatment with unlabeled L-deprenyl prevented retention of L-[11C]deprenyl. Thus, suicide enzyme inactivators labeled with positron emitters can be used to quantitate the distribution and kinetic characteristics of MAO in human brain structures.     

Mental symptoms in Huntington's disease and a possible primary aminergic neuron lesion

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.     

Dopamine: mediator of brain polysome disaggregation after L-dopa

The disaggregation of brain polysomes which is produced by giving large doses of (L)-dopa to rats is not reproduced by administering its metabolite, 3-O-methyldopa, by giving D-dopa, which also depletes the brain of S-adenosylmethionine but is not converted to catecholamines, or by giving the L-dopa after a decarboxylase inhibitor. Polysome disaggregation is potentiated by the prior administration of a monoamine oxidase inhibitor, indicating that formation of a catecholamine is an obligatory requirement. These observations suggest that the mechanism by which L-dopa disaggregates brain polysomes involves its conversion to dopamine within the majority of brain cells.     

Isolated chromaffin cells from adrenal medulla contain primarily monoamine oxidase B

Cultured chromaffin cells from bovine adrenal medulla were found to contain primarily the B form of monoamine oxidase. This monoamine oxidase B enzyme was somewhat distinct from B enzymes from other sources, in that noradrenaline was a much poorer substrate than serotonin. Nonetheless, studies with selective inhibitors of the A form (clorgyline) and the B form [(-)-deprenyl] confirmed that chromaffin cell monoamine oxidase was the B form. The observation that chromaffin cell monoamine oxidase has poor affinity for catecholamines is consistent with physiological needs that require the cell to synthesize and store large amounts of catecholamines.     

A correlation between platelet monoamine oxidase activity and plasma prolactin concentrations in man

Increases in plasma prolactin concentrations produced by alpha-methyl-p-tyrosine, a catecholamine synthesis inhibitor, varied inversely with baseline platelet monoamine oxidase activity in 12 patients with chronic schizophrenia. In normal volunteers with low monoamine oxidase activity and in unmedicated patients with chronic schizophrenia, plasma prolactin concentrations varied directly with platelet monoamine oxidase activity. No such relationship was found in normal subjects with high platelet monoamine oxidase activity. These data suggest that platelet monoamine oxidase activity reflects monoaminergic activity in the tubero-infundibular system, which in turn affects plasma prolactin concentrations. This relationship may be important in patients with low platelet monoamine oxidase activity, such as some chronic schizophrenics.     

Histochemical demonstration in rat of monoamine oxidase inhibition of beta-phenyl-isopropyl hydrazine

A histochemical method for demonstration of monoamine oxidase activity was found to be almost as sensitive as a biochemical method when used for revealing total inhibition of monoamine oxidase in rat tissues after administration of beta-phenyl-isopropyl hydrazine. The histochemical method is of special value in the study of monoamine oxidase inhibition in the complex structures of the brain.     

Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease

The power of placebos has long been recognized for improving numerous medical conditions such as Parkinson's disease (PD). Little is known, however, about the mechanism underlying the placebo effect. Using the ability of endogenous dopamine to compete for [11C]raclopride binding as measured by positron emission tomography, we provide in vivo evidence for substantial release of endogenous dopamine in the striatum of PD patients in response to placebo. Our findings indicate that the placebo effect in PD is powerful and is mediated through activation of the damaged nigrostriatal dopamine system.     

Iron- and riboflavin-dependent metabolism of a monamine in the rat in vivo

n-Pentylamine enters into intermediary metabolism by the action of monoamine oxidase. [1-(14)C] Pentylamine injected into rats is rapidly converted to (14)CO(2). The rate of catabolism decreases progressively in the course of nutritional iron deficiency, reaching about 60 percent of control values in 3 weeks. Feeding with iron yields control levels within 6 days. The catabolism of amyl alcohol, which shares a common pathway with n-pentylamine by way of valeric aldehyde, is not significantly affected by the deficiency. The results demonstrate that the maintenance of normal monoamine oxidase activity in vivo depends upon an adequate supply of dietary iron.     

铋剂四联疗法根除幽门螺杆菌疗效研究

目的比较不同疗程铋剂四联疗法与经典三联疗法根除幽门螺杆菌(Hp)的疗效。方法 选择403 例符合条件的Hp阳性的消化性溃疡或慢性胃炎患者。随机分为三组,其中A 组138 例、B 组142 例、C 组123 例。A组采用果胶铋200 mg+雷贝拉唑10 mg+阿莫西林1 000 mg+呋喃唑酮100 mg,2次/天,共10 d;B组采用果胶铋200 mg+雷贝拉唑10 mg+阿莫西林1 000 mg+呋喃唑酮100 mg,2次/天,共14 d;C组采用雷贝拉唑10 mg+阿莫西林1 000 mg+呋喃唑酮100 mg,2次/天,共14 d。观察三组患者Hp根除率、不良反应发生率及其成本-效果比。结果 A、B、C三组患者Hp根除率分别为83.33%、83.80%、71.54%,A组与B组Hp根除率比较差异无统计学意义(P>0.05),A组与C组、B组与C组Hp根除率比较均差异有统计学意义(P<0.05)。A、B、C三组患者的不良反应发生率分别为 1.45%、2.11%、0.81%,均差异无统计学意义(P>0.05)。A、B、C三组成本-效果比分别为1.50、2.09、2.04。结论 三种治疗方案均未达到Hp根除率>90%的理想方案。但三种方案的比较中含铋剂10 d与14 d四联疗法Hp根除率较高,接近理想方案。含铋剂10 d四联疗法成本-效果比最好,建议临床使用。14 d三联疗法Hp根除率仅达71.54%,远低于理想标准,不建议临床使用。     

Tyramine-H3: deaminated metabolites in neuroblastoma tumors and in continuous cell line of a neuroblastoma

Neuroblastoma tumors, as well as cultured cells of neuroblastoma, contain high monoamine oxidase activity. The major deaminated metabolite of tyramine-H(3) in the incubation mixtures with the tumors or with the cultured cells is p-hydroxyphenylacetaldehyde. Upon addition of reduced nicotinamide-adenine dinucleotide phosphate, the aldehyde was further metabolized by the reductive pathway to p-hydroxyphenylethanol, whereas upon addition of nicotinamide-adenine dinucleotide phosphate the aldehyde was only metabolized to a minor extent by the oxidative pathway to p-hydroxyphenylacetic acid. Aldehyde dehydrogenase activity is very low in the neuroblastoma tumors and in the cultured neuroblastoma cells. The generation of aldehydes and alcohols by the action of monoamine oxidase suggests that the deaminated metabolites of biogenic amines might exhibit some toxic effects in neuroblastoma patients.     

Reduced monoamine oxidase activity in platelets: a possible genetic marker for vulnerability to schizophrenia

Monoamine oxidase activity in blood platelets was measured, with [(14)C]tryptamine as substrate, in 13 monozygotic twin pairs discordant for schizophrenia and in 23 normal volunteers. The monoamine oxidase activity of both schizophrenic and nonschizophrenic co-twins was significantly lower than it was for the normals, and it was highly correlated between twins. In addition, there was a significant inverse correlation between a measure of the degree of the schizophrenic disorder and the monoamine oxidase activity. These data suggest, but do not prove, that reduced platelet monoamine oxidase activity may provide a genetic marker for vulnerability to schizophrenia.     

Compulsive, abnormal walking caused by anticholinergics in akinetic, 6-hydroxydopamine-treated rats

In otherwise profoundly akinetic rats that had been severely depleted of brain catecholamines, anticholinergic drugs caused excessive walking. The effect did not appear until 10 days after surgery and then increased with time, suggesting that a phenomenon analogous to denervation supersensitivity may be involved. If the animals walked into corners, they were unable to turn around or back out. Their gait (extremely short steps) was reminiscent of that of patients with Parkinson's disease. The results are consistent with a mutually antagonistic interaction between cholinergic and dopaminergic brain systems and emphasize certain complexities in this interaction.     

Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease

Parkinson's disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila melanogaster upon directed expression of alpha-synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a major component of proteinaceous Lewy bodies. We report that directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with alpha-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated alpha-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression.     

Role for ganglionic norepinephrine in sympathetic synaptic transmission

Transmission of nerve impulses in superior cervical sympathetic ganglia of cats and rabbits is markedly enhanced after reserpine-induced depletion of ganglionic norepinephrine. Transmission is also enhanced by administration of adrenergic blocking agents. In contrast, reserpine-induced release of ganglionic norepinephrine in animals pretreated with a monoamine oxidase inhibitor results in a pronounced depression of ganglionic transmission, which lasts until the ganglionic norepinephrine disappears. These results support the concept that norepinephrine in ganglia modulates the action of acetylcholine.     

Corrections and clarifications

In the article " Evidence found for a possible ' aggression gene' " by Virginia Morell (Research News, 18 June, p. 1722), the collaborative teams of Peter Seeburg at the University of Heidelberg, Germany; Jean Shih at the University of Southern California; and Creed W. Abell at the University of Texas, Austin, should also have been credited with cloning the human monoamine oxidase (MAO) A and B genes. Seeburg and his colleagues published their research in the July 1988 issue of the Proceedigs of the Nationl Acaderny of Sciences. Xandra Breakefield and her colleagues reported their cloning of the MAO A gene in the October 1988 issue of the Joumal of Neurochemistry. Although Breakefield's group also cloned the MAO B gene, they did not publish this research.     

MELATONIN SYNTHESIS IN THE PINEAL GLAND: CONTROL BY LIGHT

In rats placed in continuous darkness for 6 days, there is a striking increase in the activity of melatonin-synthesizing-enzyme (hydroxyindole-0-methyl transferase) in the pineal gland, but no change in the activity of monoamine oxidase. Since melatonin appears to have a hormonal role in mammals, and its synthesis is confined to the pineal gland, the inhibition of hydroxyindole-O-methyl transferase by light may constitute a mechanism of neuroendocrine regulation.     

On the reported inhibition of monoamine oxidase by an agent with sedative properties

1-Benzyl-2-methyl-5-methoxytryptamine has been reported, on the basis of indirect evidence, to inhibit monoamine oxidase. More direct experiments, however, demonstrate that the drug is devoid of the ability to block monoamine oxidase in brain in vitro or in vivo.     

那瓦斯坦与肝素、罂粟碱治疗动脉硬化闭塞症疗效比较

目的观察比较那瓦斯坦与肝素、罂粟碱治疗动脉硬化闭塞症的疗效及安全性.方法将100例患者随机分为A,B两组,A组（50例）患者给予那瓦斯坦注射液20 mg/次,1次/d,连续给药10 d;B组（50例）患者给予罂粟碱注射液30 mg/次,以250 mL生理盐水注射液稀释,2次/d;肝素5 000 U/次皮下注射,2次/d,给药10 d.观察患者用药后间歇性跛行、麻木等症状改善状况以及药物不良反应.结果 A组患者治疗有效率为84%,B组患者治疗有效率为68%.两组患者都未出现心脑血管及胃肠道出血等严重不良反应.结论两种治疗方法比较,A组更加有效,且起效迅速,A,B两种治疗方法均较安全.     

Neural transplantation: a call for patience rather than patients

Research into embryonic cell grafting in human subjects suffering from Parkinson's disease should not repeat the mistakes made by adrenal autograft investigators, who operated on far more humans than on nonhuman primates because of a single unconfirmed report of dramatic improvement in two Mexican patients. Citing extensive data from experimental transplants conducted as early as 1944, the authors argue that, until a sufficient number of animal studies have been performed to answer many crucial questions about human fetal tissue transplants, researchers should refrain from experimenting on human patients.