Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to investigate tolerability and possible neurotrophic effects of growth hormone (GH) in treatment of multiple system atrophy (MSA). In this double-blind pilot study, MSA patients were randomized to recombinant human growth hormone (r-hGH, n = 22), 1 mg every second day (6 months) followed by alternating daily injections of 1 mg and 0.5 mg (6 months), or matched placebo (n = 21). Safety analysis demonstrated no obvious between-group differences. In both groups, there was progressive worsening of Unified Parkinson's Disease Rating Scale total score, which tended to be less in r-hGH-treated patients (12.9% at 6 months, 25.3% at 12 months) than in placebo (17.0% and 35.7%). Similarly, there was a trend to less worsening in Unified MSA Rating Scale total score with r-hGH (13.2% and 21.2%) than with placebo (21.1% and 36.5%). Cardiovascular reflex autonomic testing also tended to show less deterioration with r-hGH than with placebo at 12 months. However, 95% CI did not indicate treatment differences for any efficacy measures. In conclusion, r-hGH administration in MSA patients for up to 1 year appears safe and might influence disease symptoms, signs and, possibly, progression. The results support further studies utilizing higher doses in more patients.
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PMID:Safety and tolerability of growth hormone therapy in multiple system atrophy: a double-blind, placebo-controlled study. 1746 98

Acute levodopa (LD) application and exercise release human growth hormone (GH). An earlier trial showed, that combined stimulus of exercise and LD administration is the best provocative test for GH response in healthy participants. Objective was to show this combined effect of LD application and exercise on GH response and to investigate the impact on LD metabolism in 20 previously treated patients with Parkinson's disease (PD). We measured GH- and LD plasma concentrations following soluble 200 mg LD/50 mg benserazide administration during endurance exercise and rest on two separate consecutive days. GH concentrations significantly increased on both days, but GH release was significantly delayed during rest. LD metabolism was not altered due to exercise in a clinical relevant manner. Exercise induced a significant faster LD stimulated GH release in comparison with the rest condition. We did not find the supposed increase of LD induced GH release by endurance exercise. We assume, that only a limited amount of GH is available for GH release in the anterior pituitary following an acute 200 mg LD administration. GH disposal also depends on growth hormone releasing hormone (GHRH), which is secreted into hypothalamic portal capillaries. During the exercise condition, the resulting higher blood pressure supports blood flow and thus GHRH transport towards the GH producing cells in the pituitary. This might additionally have caused the significant faster GH release during exercise.
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PMID:Endurance exercise modulates levodopa induced growth hormone release in patients with Parkinson's disease. 1759 May 11

The arginine growth hormone (GH) stimulation test differentiates the Parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine GH stimulation test in distinguishing between PSP, MSA-P, and PD. We measured the GH response to arginine in serum samples of 26 MSA-P, 23 PSP, and 26 PD patients, and in 80 healthy controls. We used ANOVA followed by the Bonferroni test to compare GH values and peaks among groups. We used receiver operating characteristic curve analysis to establish the arginine cut-off level that best differentiated between MSA-P, PSP, and PD. The GH peak was significantly lower (P < 0.01) in MSA-P (1.46 +/- 0.29 microg/L) than in both PD (8.74 +/- 0.98 microg/L) and PSP (6.64 +/- 0.82 microg/L) patients, and controls (8.59 +/- 0.44 microg/L). Growth hormone peaked later in PSP patients than in PD patients and controls. At a cut-off level of 4 microg/L, arginine test distinguished MSA-P from PD with a sensitivity of 92% and a specificity of 96%, and MSA-P from PSP with a sensitivity of 78% and a specificity of 96%. The GH response to arginine differentiates MSA-P from PD and PSP with a good diagnostic accuracy. The neuroendocrine response to arginine of PSP patients differed from that of MSA-P patients, but was not identical to that of normal controls and PD patients. Our results suggest that the impairment of the central mechanisms modulating GH release differs between PSP and MSA-P.
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PMID:The arginine growth hormone stimulation test in bradykinetic-rigid parkinsonisms. 1854 99

Idiopathic Parkinson's disease and dopaminergic medication may influence pituitary hormone secretion. The present study aimed to reveal any abnormalities of the somatotrophic system induced by the disease itself and/or the dopaminergic therapy. Investigations of other pituitary hormones under basal and stimulated conditions, as well as an analysis of body composition, were also performed. This was a controlled diagnostic study in which luteinising hormone-releasing hormone, thyroid-releasing hormone, corticotrophin-releasing hormone and arginine hydrochloride were administered to ten patients with idiopathic Parkinson's disease under dopaminergic medication. Basal and stimulated hormone concentrations and bioelectrical impedance analyses were compared with those of healthy, age-matched controls. Basal growth hormone (GH) at -30 and 0 min was higher in Parkinsonian patients (2.74 +/- 3.79 ng/ml versus 0.53 +/- 0.10 ng/ml and 2.12 +/- 2.44 ng/ml versus 0.51 +/- 0.03 ng/ml; P < 0.05). The area under the GH curve after stimulation was greater in Parkinsonian patients (502.4 +/- 202.6 ng x min/ml versus 312.0 +/- 98.5 ng x min/ml; P < 0.05), depending on higher basal GH levels, rather than a greater arginine response. No differences in insulin growth factor (IGF)-1 or IGF-BP3 concentrations were detected. There were no differences between the groups in basal and stimulated gonadotrophic, corticotrophic and thyrotrophic function, or body composition. Prolactin was below the detection limit in the patients during the course of the study. Parkinsonian patients experience marked hypoprolactinaemia and repeated stimulation of GH secretion during chronic dopaminergic therapy. Our findings suggest a peripheral GH resistance in these chronically-treated patients.
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PMID:Pituitary function and the somatotrophic system in patients with idiopathic Parkinson's disease under chronic dopaminergic therapy. 1808 58

Ghrelin, a stomach-derived hormone which induces growth hormone release and promotes positive energy balance, has been reported to inhibit cell apoptosis in endotheliocytes, osteoblasts and cardiocytes. Recent evidence has shown that ghrelin can also inhibit neuronal apoptosis of the hypothalamus and the hippocampus. However, little is known about the effects of ghrelin on the substantia nigra pars compacta (SNpc) neurons in which ghrelin's receptor, growth hormone secretagogue receptor (GHSR)-1a, is highly expressed. In the present study, we investigated whether ghrelin could protect nigral dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. We observed that ghrelin, acting through GHS-R 1a, inhibited MPTP-induced dopaminergic neuronal loss in the SNpc as well as dopamine depletion in the striatum. Ghrelin could also reverse the down-regulated the expression of Bcl-2, up-regulated the expression of Bax, and caspase-3 activation caused by MPTP. This study demonstrated that ghrelin might be a potential protector of dopaminergic neurons in a therapeutic strategy for Parkinson's disease.
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PMID:Ghrelin antagonizes MPTP-induced neurotoxicity to the dopaminergic neurons in mouse substantia nigra. 1857 98

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) acting to stimulate growth hormone release. In the previous study, we have observed the neuroprotective effects of ghrelin on dopaminergic neurons in vivo in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -treated Parkinson's disease mice. In order to illustrate the underlying mechanisms, in the present study, we conducted our experiment in vitro in 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells that could express GHS-R1a. Ten- to 1,000-micromol/L MPP(+) treatment caused decreased cell viability, with increased lactate dehydrogenase leakage. A 200-micromol/L MPP(+) treatment was chosen to do the further experiments. MES23.5 cells treated with 200 micromol/L MPP(+) showed decreased mitochondrial transmembrane potential, an elevated level of reactive oxidative species production and activation of caspase-3. Additionally, these cells also showed apoptotic morphological changes. Pretreatment with different doses of ghrelin (10(-12)-10(-7) mol/L) could abolish the MPP(+)-induced apoptotic changes in a dose-dependent manner. These results suggested that ghrelin could antagonize MPP(+)-induced apoptosis in MES23.5 cells. The protective effects of ghrelin involved the restoration of mitochondria function.
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PMID:Ghrelin antagonized 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptosis in MES23.5 cells. 1905 22

The aim of this study was to investigate the role of circulating growth hormone (GH), insulin growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and nitric oxide (NO) concentrations in the patients suffering from Parkinson's disease (PD). The study groups were consisted of 25 patients with PD and 25 matched healthy subjects as a control. The NO level of patients in PD group (2.3 +/- 0.4 micromol/L) was significantly lower than that in the control group (2.8 +/- 0.6 micromol/L) (P:.011). Although there were no statistically significant differences in the GH, IGF-1, and IGF BP-3 levels among the two groups, in this preliminary study, we found low NO and mildly elevated IGF-1 levels in the patients with PD. The results may be associated with adaptation or protective mechanisms in the neurodegenerative disease processes such as seen in the PD. Further studies should be carried out to confirm our results.
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PMID:Serum insulin-like growth factor-1 and nitric oxide levels in Parkinson's disease. 1930 May 21

Ghrelin is an endogenous ligand for growth hormone (GH) secretagogue receptor 1a (GHS-R1a) and is produced and released mainly from the stomach. It was recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of Parkinson's disease (PD) neurodegeneration. However, the role of microglia in the neuroprotective properties of ghrelin is still unknown. Here we show that, in the mouse MPTP PD model generated by an acute regimen of MPTP administration, systemic administration of ghrelin significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers through the activation of GHS-R1a. We also found that ghrelin reduced nitrotyrosine levels and improved the impairment of rota-rod performance. Ghrelin prevents MPTP-induced microglial activation in the SNpc and striatum, the expression of pro-inflammatory molecules tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), and the activation of inducible nitric oxide synthase. The inhibitory effect of ghrelin on the activation of microglia appears to be indirect by suppressing matrix metalloproteinase-3 (MMP-3) expression in stressed dopaminergic neurons because GHS-R1a is not expressed in SNpc microglial cells. Finally, in vitro administration of ghrelin prevented 1-methyl-4-phenylpyridinium-induced dopaminergic cell loss, MMP-3 expression, microglial activation, and the subsequent release of TNF-alpha, IL-1beta, and nitrite in mesencephalic cultures. Our data indicate that ghrelin may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that ghrelin may be a valuable therapeutic agent for neurodegenerative diseases such as PD.
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PMID:Neuroprotective effect of ghrelin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease by blocking microglial activation. 1938 67

Ghrelin, a 28-amino acid peptide, is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. Our previous data showed that ghrelin could inhibit apoptosis in Parkinson's disease (PD) models both in vitro and in vivo. There is now growing evidence that oxidative stress has a critical role in the etiology of PD. And ghrelin was reported to possess anti-inflammatory, antioxidant effects. Dose ghrelin protect dopaminergic neurons by its antioxidant effect? In the present study, 1-methyl-4-phenylpyridinium (MPP(+)) was used to evaluate the possible antioxidant effects of ghrelin on MPP(+)-induced neurotoxicity in MES23.5 cells and the underlying mechanisms. Our results showed that MPP(+) significantly increased malonaldehyde (MDA) level and Bax/Bcl2 ratio, reduced the level of Cu-Zn superoxide dismutase (SOD) and catalase (CAT). Ghrelin protected MES23.5 cells against MPP(+)-induced neurotoxicity by reversing these changes. Furthermore, ghrelin pretreatment significantly inhibited MPP(+)-induced nuclear factor-kappaB translocation. These results suggest that the protective effects of ghrelin on MPP(+)-induced cytotoxicity may be ascribed to its antioxidative properties, and the modulation of nuclear factor-kappaB.
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PMID:Ghrelin prevents 1-methyl-4-phenylpyridinium ion-induced cytotoxicity through antioxidation and NF-kappaB modulation in MES23.5 cells. 1993 Dec 50

This study was aimed at comparing the diagnostic accuracy of the growth hormone (GH) response to clonidine, arginine and both combined in order to establish a more reliable test to differentiate parkinsonism type multiple system atrophy (MSA-p) from Parkinson's disease (PD). Twenty-four patients with MSA-p and 26 cases with PD entered the study. They were submitted to treatments of clonidine, arginine and a combination of the two in a random manner on three different nonconsecutive days. The GH peak in serum at different times was evaluated and used as a primary variable for analysis of the stimulation test. By ROC analysis, we compared the sensitivity and specificity of tests of clonidine, arginine and both combined. After clonidine administration, the maximal average was significantly lower in patients with MSA-p than in those with PD (3.62 +/- 0.81 vs. 6.91 +/- 1.13; P < 0.05) with a sensitivity and specificity of 82.61 and 76.92%. After arginine administration, the maximal average GH concentration in serum at 30 min was also significantly lower in patients with MSA-p than in those with PD (4.07 +/- 0.80 vs. 7.89 +/- 1.29; P < 0.05) with a sensitivity and specificity of 78.26 and 73.08%. The sensitivity and specificity in differentiating MSA-p from PD was higher in the clonidine GH stimulation test than in the arginine GH stimulation test. However, when the clonidine and arginine were applied combined, the contrast of the maximal average GH concentration in serum in two groups was markedly increased (5.02 +/- 1.12 vs. 10.75 +/- 1.11; P < 0.05) with a sensitivity and specificity of 73.91 and 92.31%, and the specificity was notably increased in the combined GH stimulation test. Compared to the arginine GH stimulation test, the clonidine GH stimulation displayed a higher sensitivity and specificity; combined GH stimulation test of clonidine plus arginine could significantly enhance the specificity in differential diagnosis of MSA-p from PD.
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PMID:The comparison of clonidine, arginine and both combined: a growth hormone stimulation test to differentiate multiple system atrophy from idiopathic Parkinson's disease. 2040 38


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