α-Synuclein (140 amino acids), one of the causative proteins of Parkinson's disease, forms amyloid fibrils in brain neuronal cells. In order to further explore the contributions of the C-terminal region of α-synuclein in fibril formation and also to understand the overall mechanism of fibril formation, we reduced the number of negatively charged residues in the C-terminal region using mutagenesis. Mutants with negative charges deleted displayed accelerated fibril formation compared with wild-type α-synuclein, demonstrating that negative charges located in the C-terminal region of α-synuclein modulate fibril formation. Additionally, when tyrosine residues located at position 125, 133, and 136 in the C-terminal region were changed to alanine residue(s), we found that all mutants containing the Tyr136Ala mutation showed delays in fibril formation compared with wild type. Mutation of Tyr136 to various amino acids revealed that aromatic residues located at this position act favorably toward fibril formation. In mutants where charge neutralization and tyrosine substitution were combined, we found that these two factors influence fibril formation in complex fashion. These findings highlight the importance of negative charges and aromatic side chains in the C-terminal region of α-synuclein in fibril formation.
Metabolic syndrome is a reliable predictive factor for the prevalence of GERD, and medical therapy for metabolic syndrome may modify the risk of GERD occurrence.
Background:
Glucagon inhibits digestive motility and is used for endoscopic premedication; however, its effect on cardiopulmonary function during endoscopy has not yet been fully investigated.
Aim:
To clarify the efficacy and safety of glucagon compared with butyl scopolamine bromide as upper gastrointestinal endoscopy premedication.
Methods:
Two hundred and forty consecutive patients over 40 years of age, referred for upper gastrointestinal endoscopy, without any complications, were studied. These patients were randomly premedicated with butyl scopolamine bromide (SC group) or glucagon (G group). Time course changes in blood pressure, arterial oxygen saturation, heart rate and the number of retching episodes during endoscopy were examined. The efficacy of glucose tablets after upper gastrointestinal endoscopy to prevent hypoglycaemia caused by glucagon was evaluated. Cardiopulmonary parameters were also examined in 77 complicated patients with glucagon premedication (GC group).
Results:
A continuous increase in heart rate during upper gastrointestinal endoscopy was observed in the SC group, but not in the G and GC groups. Blood pressure, arterial oxygen saturation and number of retching episodes were not different between the groups. Hypoglycaemia‐related symptoms were frequent in the G group without glucose tablets, but were prevented by the administration of glucose.
Conclusions:
Glucagon has a weaker effect on cardiopulmonary function during upper gastrointestinal endoscopy than butyl scopolamine bromide. Glucose administration prevents hypoglycaemia‐related symptoms caused by glucagon.
This study clarified that NUD is also one of the most prevalent disorders in the Japanese, although its characteristics may be somewhat different from those in Western countries.
More than 1 percent of Japanese blood donors were infected with HGV/GBV-C, and the prevalence was much higher in those with HCV RNA. Should persistent infection with HGV/GBV-C induce any hepatotoxic sequelae, either alone or in concert with the other hepatitis viruses, screening of blood units for HGV/GBV-C would deserve consideration.
The detection of TT virus DNA, at a frequency higher in donors with elevated ALT than in those without, strengthens the association of TT virus with non-A to -G hepatitis.
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