Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.
Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.
Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.
Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.
Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity. 相似文献
There is increasing evidence from human and experimental studies that the most important factor governing the outcome in head injury is the severity of diffuse axonal injuries. The authors have experienced 18 cases of severe diffuse axonal injury which showed post-traumatic coma for more than 24 hours and CT findings resembling those of shearing injuries of the cerebral white matter such as have been presented by Zimmerman et al. (1978). The consciousness levels on admission were 6 or less on the Glasgow Coma Scale and all cases were shown clinically to have primary brain stem injury. The main type of head trauma resulted from road traffic accidents (83%). Skull fractures were found in only 5 cases (28%). These findings suggested that acceleration/deceleration injury produce in the patients severe diffuse axonal injury. Initial ICP was below 20 mmHg in 11 cases out of 13 (85%). Parenchymal small hemorrhagic lesions of initial CT were basal ganglia (7 cases), corpus callosum (4 cases), pons (4 cases), midbrain (3 cases) and thalamus (2 cases). Extraparenchymal hemorrhagic lesions included intraventricular hemorrhage (6 cases) and subarachnoid hemorrhage (6 cases). Two autopsied cases of severe diffuse axonal injury (acute case and chronic case) showed remarkable congestion and edema in the deep part of the frontal white matter. Microscopic examination revealed marked axonal degeneration including axonal retraction ball in the corpus callosum, in the internal capsule and in the white matter of the brain stem. Glasgow Outcome Scale of the 18 patients at 3 months after the trauma made us concerned that no patients indicated good recovery or even only moderate disability.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG. 相似文献
The results of experiments with Acanthopanax giraldii polysaccharide (AGP) demonstrated that it inhibited the growth of solid Sarcoma 180 and prolonged the survival time significantly. In tumor-bearing mice, AGP enhanced the phagocytosis and chemiluminescence of macrophages. By the immunofluorescent method, binding of the third component of complement (C3) cleavage product to macrophages and proportion of C3 positive cells were increased. In crossed immunoelectrophoresis, human serum C3 was converted by AGP and appeared as the 3rd peak. The height of the 3rd peak was directly proportional to doses of AGP. The residual CH50 units of human serum decreased dose-dependently. These results suggest that the antitumor activity of AGP is related to the enhancement of immune responses. 相似文献
The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue, [H-Met-(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier was directly demonstrated in-vivo. [125I]Ebiratide (16.9 MBq mL-1) or [14C]sucrose (29.2 MBq mL-1) known to be restrictively transported through the blood-brain barrier was infused into the rat internal carotid artery at a flow rate of 50 microL min-1 for 10 min, and after 15 min infusion the distribution volume of each compound in the brain parenchyma was determined by the capillary depletion method. The distribution volume of [125I]ebiratide was 167.8 +/- 62.2 microL (g brain)-1, which was about seven times higher than that of [14C]sucrose (24.9 +/- 4.0 microL g brain)-1, indicating the uptake of ebiratide into brain parenchymal cells. During the infusion into the internal carotid artery, brain microdialysis was simultaneously performed to directly collect the brain interstitial fluid as the dialysate. Radioactivity was detected in the dialysate during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed that the intact ebiratide accounted for greater than or equal to 80% total radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the brain interstitial fluid were estimated based on the relative recovery obtained in the in-vitro recovery study. The brain interstitial fluid/internal carotid arterial blood concentration ratio for [125I]ebiratide was determined to be 1.47 x 10(-2) +/- 0.17 x 10(-2) and was about eight times higher than that for [14C]sucrose (1.92 x 10(-3) +/- 0.36 x 10(-3)), indicating significant transport of ebiratide to the brain interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
As a design for a biodegradable functional polymer, compositionally homogeneous poly[(sodium acrylate)-co-(vinyl alcohol)] [P(SA-co-VA)], containing varying amounts of vinyl alcohol groups as biodegradable segments were prepared and their biodegradability and builder performance in detergent formulations were analyzed with respect to the successive vinyl alcohol length. It was found that the acrylate copolymers having more than 80 mol-% vinyl alcohol content showed biodegradability. That is, P(SA-co-VA) having a vinyl alcohol chain length of more than about 5–6 is cleaved by PVA-degrading microbes. This indicates that the vinyl alcohol blocks, which act as biodegradable segments, should be incorporated into the polymer chain in such a manner that they are accepted as substrates by the PVA-degrading enzymes. 相似文献