Evidence supporting a mitogenic role for substance P in amphibian limb regeneration. Involvement of the inositol phospholipid signaling pathway.
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Animals↗
Biomedical subjects
M Globus
Publications and source records attributed to M Globus.
A search for immunoreactive substance P and other neural peptides in the limb regenerate of the newt Notophthalmus viridescens.
Immunochemical studies demonstrate that the undecapeptide substance P (SP) may be detected by radioimmunoassay in newt limb regenerates and that SP is localized in the blastemal epidermis by immunofluorescence and peroxidase-antiperoxidase staining. Immunoreactive SP is predominantly distributed at the periphery of epidermal cells, suggesting the presence of SP binding sites on the cell surface; the basal germinative layer of the epidermis and blastemal mesenchyme cells remain unreactive. The pattern of SP immunoreactivity in the blastema was compared with that of four other tachykinin-family peptides (eledoisin, kassinin, substance K, and neuromedin K) and with three non-tachykinin neural peptides (bombesin, neurotensin, and metenkephalin). With the exception of neurotensin, which showed weak staining in the basal layer but an absence in the peripheral layers of the epidermis, none of the peptides examined exhibited immunoreactivity in the blastema epidermis comparable to that of SP.
Animals↗
Control of blastema cell proliferation by possible interplay of calcium and cyclic nucleotides during newt limb regeneration.
The effects of the divalent cation ionophore A23187, papaverine, and chlorpromazine on the mitotic index and cyclic nucleotide levels in newt limb regeneration blastemata (Notophthalmus viridescens) were assessed. The results of the experiments suggest that an intracellular increase in divalent cation (Ca2+) concentration results in elevated cGMP levels, suppressed cAMP levels, and a corresponding increase in blastema cell proliferation. The results also suggest that the converse conditions, namely, calcium efflux or inhibition of calmodulin activation (i.e., inhibition of Ca2+ binding), yields elevated cAMP levels, suppressed cGMP levels, and a corresponding decrease in blastema cell divisions.
Adenosine Monophosphate↗
Biochemical effects of chronic L-dopa treatment in rats: implications for emergence of tolerance phenomena in patients with Parkinson's disease.
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3,4-Dihydroxyphenylacetic Acid↗
[Measurement of cognitive functions in Parkinson's disease].
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Cognition Disorders↗
Effect of insulin on cyclic nucleotide levels and promotion of mitosis by insulin and ionophore A23187 in cultured newt blastemata.
The levels of cyclic GMP (cGMP) and cyclic AMP (cAMP) were assayed, using radioimmunoassay, in newt blastemata cultured with and without insulin. Our observations show that insulin significantly increases the levels of cGMP over the control values, whereas the levels of cAMP remain unaltered. Our in vitro studies also show that Ca2+-carrying ionophore A23187, albeit capable of promoting blastema cell proliferation, is unable to replace the insulin effect. The possible role of cGMP and Ca2+ as mediators of insulin action in regeneration is discussed.
Animals↗
Dissociation of the effects of castration and testosterone replacement on sexual behavior and neural metabolism of dopamine in the male rat.
Sexually experienced, adult male rats were either castrated, castrated and implanted SC with a Silastic capsule containing testosterone (T), or sham operated. Coital performance of castrates gradually declined such that 4 weeks after surgery no males in this group ejaculated whereas 89% and 100%, respectively, of the rats in the castrated, T-treated and the sham-operated groups displayed ejaculation. Males in all three groups were decapitated 33-34 days post-operatively after 10 min exposure either to the behavioral test chamber, with an estrous female restrained in one corner behind a wire mesh screen, or to a home cage. Brains were quickly removed and the caudate-putamen, nucleus accumbens, septum, and preoptic area/anterior hypothalamus were frozen and saved for later estimation of dopamine (DA) and two neural metabolites of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The concentrations of DA, DOPAC, and HVA, as well as the ratio of DOPAC/DA, did not differ significantly in any of the 4 brain regions assayed among males in the three endocrine groups, regardless of whether they were killed after exposure to an estrous female or a home cage. The results fail to support the hypothesis that T-induced alterations in neurotransmission in nigro-striatal, mesolimbic, or incertohypothalamic DA pathways mediate the activational effect of this steroid on masculine sexual behavior.
3,4-Dihydroxyphenylacetic Acid↗
Regional cerebral blood flow in patients with Parkinson's disease under chronic levodopa therapy: measurements during "on" and "off" response fluctuations.
In ten Parkinsonians who developed dose-related response fluctuations under long-term levodopa therapy, regional cerebral blood flow (rCBF) and plasma levodopa levels were measured simultaneously, once during an "off" phase and again at an "on" stage of clinical benefit induced by a single oral dose of levodopa. Although plasma levodopa increased threefold during the "on" period, rCBF and the degree of its reduction from normal age-matched control values remained unchanged and similar to those in the "off" phase. Study suggests that the rCBF decreases in Parkinson's disease are unaffected by levodopa and are not due to deficient dopaminergic neurotransmission in the brain.
Adult↗
In vivo effect of MPTP on monoamine oxidase activity in mouse striatum.
Striatal monoamine oxidase (MAO)-B, but not MAO-A, activity decreased in mice at 2 and 10 days and was back to control values at 20 and 30 days after systemic administration of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Striatal dopaminergic (DA) depletions were maximal at 2 days and were only partially reversed at 30 days post-treatment. In rats, unilateral kainic acid lesions increased MAO-B but not MAO-A activity probably due to reactive gliosis, but MPTP did not affect DA levels in control and kainic acid-lesioned striata. Findings support the importance of MAO-B in the toxicity of MPTP and suggest that resistance of rat DA neurons to the neurotoxin is probably not due to species differences in MAO-B activity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Dopamine but not norepinephrine or serotonin uptake inhibitors protect mice against neurotoxicity of MPTP.
Combined administration of nomifensine, a DA reuptake inhibitor, and MPTP completely prevented the long-term (30 days post-treatment) striatal DA depletions induced by MPTP in mice. Cotreatment with desipramine and clomipramine or fluoxetine, inhibitors of NE and 5-HT, respectively had no effect on DA neurotoxicity of MPTP. The findings indicate that MPTP (or MPP+) is a substrate for the specific DA reuptake system and may explain, in part, its selective toxic effects on DA neurons.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Suppression of MPTP-induced dopaminergic neurotoxicity in mice by nomifensine and L-DOPA.
To examine effects of various pharmacological manipulations of dopamine (DA) metabolism on DA neurotoxicity of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), C57 black mice were injected with MPTP (30 mg/kg s.c., once daily for two days) alone or in combination with apomorphine, bromocriptine, haloperidol, L-DOPA or nomifensine. MPTP markedly decreased neostriatal DA concentrations at 2, 10, 20 and 30 days post-treatment indicating persistent degeneration of nigrostriatal DA neurons. Suppression or acceleration of DA turnover rates by the DA agonists apomorphine and bromocriptine or by the DA antagonist haloperidol, respectively, did not affect MPTP toxicity. MPTP-induced neostriatal DA depletions were markedly suppressed by nomifensine, a DA reuptake inhibitor, and attenuated by exogenous L-DOPA. MPTP may be a substrate for the DA reuptake system and its specific transport into nigrostriatal terminals may be an important factor for its selective neurotoxicity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Mesolimbic dopaminergic neurons are not spared by MPTP neurotoxicity in mice.
In C57 black mice, MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (30 mg/kg X 2, 20 mg/kg X 15, 30 mg/kg X 15, or 35 mg/kg X 1) depleted DA in both striatum and accumbens but not in frontal cortex, hypothalamus and retina. DA decreases were more pronounced in striatum than in accumbens, were maximal at 2 days, partially reversed later but persisted up to 30 days after treatment. DA depletions in nigra were smaller earlier and maximal later. The study suggests that, in mice, MPTP damages nigrostriatal and mesolimbic projections but spares other DA neurons.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Effect of L-DOPA on glucose oxidation and incorporation into glycogen in discrete brain regions of the rat.
Previous reports in which the [14C]deoxyglucose mapping technique was used, have demonstrated that systemic administration of L-DOPA can either increase or decrease glucose utilization in various brain regions. However, in the striatum, which contains a high concentration of dopamine, no conclusive results were found using this technique. In the present study we attempted, by implicating a different technique, to evaluate the effect of L-DOPA on glucose metabolism in the striatum. This approach is based on in vitro measuring of glucose oxidation to CO2 and its incorporation to glycogen. Rats were injected with carbidopa (100 mg/kg) and 1 h later with L-DOPA (50 mg/kg). The rats were sacrificed by decapitation 1 h after L-DOPA injection and the following brain regions were assayed for glucose oxidation to CO2 and its incorporation to glycogen: striatum, hypothalamus, hippocampus and prefrontal cortex. A significant increase of glucose oxidation of 50% was found in the striatum and hippocampus, while no change was demonstrated in the hypothalamus and cortex. The incorporation of glucose to glycogen was markedly reduced in the striatum and hippocampus while no change was found in the hypothalamus or cortex. The present results demonstrate that L-DOPA treatment increases glucose metabolism in specific brain areas. The mechanism involved might be an increase in cellular uptake of glucose and/or activation of enzymes participating in glucose metabolic pathways.
Animals↗
Regional distribution of prostanoids in rat brain: effect of insulin and 2-deoxyglucose.
Prostaglandin synthesis in the brain has been suggested as a component in the control mechanism of the cerebral circulation. During insulin-induced hypoglycemia there is a significant increase in local cerebral blood flow in various brain regions, however, regional loss of autoregulation occurs under these conditions. In the present study the regional distribution of PGE2, TXB2 (the stable metabolite of thromboxane) and 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) was determined in rat brain following decapitation. Three groups of rats were treated with either saline, insulin or 2-deoxyglucose and their brains were rapidly removed one hour later. Samples from the cortex hypothalamus, hippocampus, striatum, nucleus accumbens and cerebellum were assayed by RIA for the content of PGE2, TXB2 and 6-keto-PGF1 alpha. The levels of all three compounds in control rats were the lowest in the striatum and cerebellum, while in the cortex and hippocampus their levels were 4-6 times higher. Insulin had selective effect on the post decapitation levels of prostanoids. It increased PGE2 in the n. accumbens and TXB2 in the hippocampus, and reduced 6-keto-PGF1 alpha and TXB2 in the cortex. 2-DG reduced all PGs in the cortex and 6-keto-PGF1 alpha in the hypothalamus and hippocampus. The results demonstrate that discrete brain areas have a differential capacity to accumulate PGs following decapitation. This capacity is selectively affected by insulin and 2-DG.
6-Ketoprostaglandin F1 alpha↗
Amphetamine, but not reserpine, protects mice against dopaminergic neurotoxicity of MPTP.
In mice, long-term reductions in striatal DA produced by the neurotoxin MPTP were completely prevented by its combined administration with amphetamine. Depletion of DA from DA terminals by cotreatment with reserpine did not suppress but rather enhanced MPTP-induced DA decrements in striatum. Amphetamine protection against DA neurotoxicity of MPTP in mice is probably not due to increases in DA release and may be related to inhibition of MPTP transport into nigrostriatal terminals via the DA reuptake system.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Pneumatocele formation in a patient with Proteus mirabilis pneumonia.
A rare case of pulmonary pneumatoceles complicating the course of Proteus pneumonia in an adult is described. The pneumatoceles which appeared early in the course of the pneumonia resolved completely without complications. A brief review of the literature regarding formation of cavities in Proteus pneumonia is given.
Female↗
Cerebral blood flow and cognitive impairment in Parkinson's disease.
In Parkinson's disease, there is high prevalence of dementia, reduction of the regional cerebral blood flow (rCBF), and neuronal loss and Alzheimer-like pathologic changes in cerebral cortex. Since rCBF is also decreased in Alzheimer's dementia, it is theoretically possible that both decreases in rCBF and cognitive impairment in parkinsonians are caused by a similar mechanism, eg, reduced metabolic demand or loss of cholinergic neurons innervating cortex and microvessels. We therefore measured rCBF using the 133Xenon inhalation technique and evaluated cognitive function with a detailed neuropsychological test battery in 48 patients with Parkinson's disease. Mean brain, hemispheric, and regional flows were decreased in parkinsonians as compared with those in age-matched controls. Most of the cognitive functions were impaired in patients as compared with those in normal subjects. However, there was no correlation between the magnitude of rCBF reduction and the presence and severity of intellectual deterioration in parkinsonians, suggesting that each may be caused by a different mechanism.
Adult↗
Progressive age-related decrease in regional cerebral blood flow in healthy subjects.
Regional cerebral blood flow (rCBF) was measured by the 133xenon inhalation technique in 103 healthy, nonhospitalized subjects of whom 44 were less than 30 years of age. Mean brain and hemispheric flows and rCBF decreased with advancing age. Moreover, a steep decline in rCBF became apparent as early as the third decade of life. Our findings suggest that the decline of rCBF is not limited to healthy elderly subjects, but is a progressive phenomenon that begins at an earlier age.
Adolescent↗