Treatment-resistant diabetic chorea manifesting with psychiatric symptoms: a case report.

We report a case of a 69-year-old man with treatment-resistant diabetic chorea presenting psychiatric symptoms. The right chorea lasted for 3 months and was refractory to control of diabetes mellitus or administration of haloperidol and benzodiazepines. Only administration of tiapride was efficacious. Magnetic resonance spectrometry and dopamine transporter-single photon emission computed tomography suggested that sustained ischemia at the striatum may lead to impaired expression of dopamine transporters, thereby resulting in deterioration in the indirect pathway. Tiapride inhibited dopamine D2 receptors, thereby restoring the function of the indirect pathway and resulting in improvement of diabetic chorea.

[Real-time 3D reconstruction CT-jejunography guided direct percutaneous endoscopic jejunostomy for levodopa-carbidopa intestinal gel treatment in a patient with prior gastrojejunostomy].

A 68-year-old woman with Parkinson's disease, who had previously undergone Roux-en-Y gastrojejunostomy for early gastric cancer, complained of wearing-off and troublesome dyskinesia that had progressed over 7-years. After the introduction of levodopa-carbidopa intestinal gel therapy (LCIG) by nasojejunal tube, she had a good clinical response. Percutaneous endoscopic gastrostomy with a jejunal extension tube was difficult in this case, due to lack of gastrostomy site and fibrous postoperative adhesion. We introduced LCIG by direct percutaneous endoscopic jejunostomy (D-PEJ) which offers a less invasive procedure to operative tube placement. The factors affecting the success of D-PEJ could interfere with transillumination, abdominal thickness and the location of other organs. We determined the optimum site of catheter insertion with the assistance of real-time 3D reconstruction CT-jejunography. She was discharged home on postoperative day 14 without any procedure-related complications. Real-time 3D reconstructive CT-jejunography guided D-PEJ is a useful method for a patient who benefit from LCIG with prior gastrojejunostomy.

Clinical Characteristics of Driving-related Stroke Occurring as a Recurrent Stroke.

BACKGROUND: Although the number of seemingly healthy subjects who suffer a minor stroke increases, there are no data on how frequently they sustain another stroke while driving. METHODS: A single-center, retrospective study was conducted to clarify the clinical characteristics of driving-related stroke occurring as a recurrent stroke by analyzing data prospectively acquired between January 2009 and June 2019 on 3452 acute stroke patients. RESULTS: One hundred-thirty five patients (85 ischemic stroke [IS] and 50 hemorrhagic stroke [HS]) had suffered a driving-related stroke. Of them, 22 (16%) had suffered a prior stroke (recurrent stroke group), while 113 had never suffered a stroke before (first-time stroke group). While the use of anti-thrombotics was significantly more common in the RS group, other variables including the frequency of road traffic accidents, did not differ significantly. The first stroke-recurrent stroke interval ranged from 0.2 to 18 years. The stroke type at the time of recurrence was IS in the majority of patients with prior IS. When compared to 432 patients with recurrent IS unrelated to driving, patients with recurrent IS related to driving (n = 16) had significantly higher frequency of lacunar strokes (56% vs 27%, P = .02) and lower frequency of cardioembolic strokes (6% vs 29%, P = .04). CONCLUSION: The current finding that 16% of patients who presented with driving-related stroke had previously suffered a stroke indicates that drivers with a prior stroke may be at increased risk for recurrent stroke while driving, and prolonged follow-up be necessary for minor stroke patients who resume driving.

[Wilson's disease presenting as Asperger syndrome].

A 24-year-old man, who had been treated for 3 years as Asperger syndrome in adolescence due to behavioral disturbances, lack of social awareness and inability to socialize, was referred to our hospital shortly after tremors developed. On the basis of clinical features, laboratory findings and the brain MRI, a diagnosis of Wilson's disease (WD) was made. WD was further confirmed by genetic testing (the mutation of ATP7B gene). He was started with trientine hydrochloride 500 mg/day, and after 1 year of follow-up, his psychiatric symptoms have improved. Since psychiatric symptoms may precede the neurological symptoms, the possibility of WD should be always considered in the differential diagnosis of psychiatric disorders in young adults.

Stroke while driving: Frequency and association with automobile accidents.

Background Cardiovascular events while driving have occasionally been reported. In contrast, there have been few studies on stroke while driving. Aim The objectives of this study were to (1) report the frequency of stroke while driving and (2) evaluate its association with automobile accidents. Methods Clinical data prospectively acquired between January 2011 and December 2016 on 2145 stroke patients (1301 with ischemic stroke, 585 with intracerebral hemorrhage, and 259 with subarachnoid hemorrhage) were reviewed to identify patients who sustained a stroke while driving. The ratio of driving to performing other activities was evaluated for each stroke type. Furthermore, the drivers' response to stroke was reviewed to understand how automobile accidents occurred. Results Among the 2145 patients, 85 (63 ischemic stroke, 20 intracerebral hemorrhage, and 2 subarachnoid hemorrhage) sustained a stroke while driving. The ratio of driving to performing other activities was significantly higher in ischemic stroke (4.8%) than in intracerebral hemorrhage (3.4%) or subarachnoid hemorrhage (0.8%). A majority of drivers either continued driving or pulled over to the roadside after suffering a stroke. However, 14 (16%) patients were involved in automobile accidents. In most patients, an altered mental status due to severe stroke was the presumed cause of the accident. Conclusion Stroke occurred while driving in 4.0% of all strokes and accidents occurred in 16% of these instances.

Clinical Characteristics of Stroke Occurring while Bathing.

BACKGROUND: Stroke can occur during any human activity. Although cardiac arrests or drowning accidents while bathing have been studied extensively, there are few studies focusing on stroke occurring while bathing. The objectives of this study were to evaluate the clinical characteristics of stroke occurring while bathing and the association between stroke and drowning accidents. METHODS: Clinical data prospectively acquired between January 2011 and December 2015 on 1939 patients with stroke (1224 cerebral infarctions [CIs], 505 intracerebral hemorrhages [ICHs], and 210 subarachnoid hemorrhages [SAHs]) were reviewed to identify patients who sustained a stroke while bathing. The ratio of bathing-related strokes to strokes occurring during other activities was evaluated. Moreover, the demographics of these 2 groups were compared in each stroke type. RESULTS: Among the 1939 patients, 78 (CI, 32; ICH, 28; and SAH, 18) sustained a stroke while bathing. The ratio of bathing to other activities in the SAH group was the highest (8.6%), followed by the ICH group (5.5%), whereas that in the CI group was the lowest (2.6%). Regardless of stroke type, only a minority of patients were found to have collapsed inside the bathtub. CONCLUSIONS: The higher ratio of bathing in hemorrhagic strokes may indicate that there is a small risk of hemorrhagic stroke while bathing in vulnerable subjects. This retrospective study did not establish a causal relationship between bathing and stroke nor identify risk factors, which means that future prospective studies are warranted. The finding that the great majority of bathing-related stroke patients were found to have collapsed outside the bathtub suggests that the involvement of stroke in drowning accidents in the bathtub may be small.

Identification of glycosylated exendin-4 analogue with prolonged blood glucose-lowering activity through glycosylation scanning substitution.

Exendin-4, a glucagon-like peptide 1 receptor agonist, is a potent therapeutic xenopeptide hormone for the treatment of type 2 diabetes. In order to further improve in vivo activity, we examined the introduction of sialyl N-acetyllactosamine (sialyl LacNAc) to exendin-4. The glycosylated analogue having sialyl LacNAc at position 28 was found to have improved in vivo activity with prolonged glucose-lowering activity.

Chemoenzymatic synthesis of glycosylated glucagon-like peptide 1: effect of glycosylation on proteolytic resistance and in vivo blood glucose-lowering activity.

Glucagon-like peptide 1 (7-36) amide (GLP-1) has been attracting considerable attention as a therapeutic agent for the treatment of type 2 diabetes. In this study, we applied a glycoengineering strategy to GLP-1 to improve its proteolytic stability and in vivo blood glucose-lowering activity. Glycosylated analogues with N-acetylglucosamine (GlcNAc), N-acetyllactosamine (LacNAc), and alpha2,6-sialyl N-acetyllactosamine (sialyl LacNAc) were prepared by chemoenzymatic approaches. We assessed the receptor binding affinity and cAMP production activity in vitro, the proteolytic resistance against dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11, and the blood glucose-lowering activity in diabetic db/db mice. Addition of sialyl LacNAc to GLP-1 greatly improved stability against DPP-IV and NEP 24.11 as compared to the native type. Also, the sialyl LacNAc moiety extended the blood glucose-lowering activity in vivo. Kinetic analysis of the degradation reactions suggested that the sialic acid component played an important role in decreasing the affinity of peptide to DPP-IV. In addition, the stability of GLP-1 against both DPP-IV and NEP24.11 incrementally improved with an increase in the content of sialyl LacNAc in the peptide. The di- and triglycosylated analogues with sialyl LacNAc showed greatly prolonged blood glucose-lowering activity of up to 5 h after administration (100 nmol/kg), although native GLP-1 showed only a brief duration. This study is the first attempt to thoroughly examine the effect of glycosylation on proteolytic resistance by using synthetic glycopeptides having homogeneous glycoforms. This information should be useful for the design of glycosylated analogues of other bioactive peptides as desirable pharmaceuticals.

Innate immunomodulation with recombinant interferon-alpha enhances resistance of rainbow trout (Oncorhynchus mykiss) to infectious hematopoietic necrosis virus.

We examined the in vivo immunostimulatory effects of a recombinant Atlantic salmon (Salmo salar) interferon-alpha2 (rSasaIFN-alpha2). The mature rSasaIFN-alpha2, expressed and purified from Escherichia coli, was administered to rainbow trout (Oncorhynchus mykiss) via the oral, immersion, or intraperitoneal (IP) injection route. Injection of rSasaIFN-alpha2 at 0.1microg/g fish gave significantly greater protection than a phosphate buffered saline (PBS) injection against a lethal challenge of infectious hematopoietic necrosis virus (IHNV), with a relative percent survival of 39%. Relative percent survival (RPS) increased significantly to 92% when the fish were injected with rSasaIFN-alpha2 at 1microg/g fish. Antiviral protection was evident for up to 7 days post-injection of rSasaIFN-alpha2. Administration of rSasaIFN-alpha2 by the oral or immersion route was not protective, and the fish succumbed to virus infection. The level of systemic IFN-induced expression of the Mx1 gene was significantly greater (p<0.01) in the IFN-injected group than in the PBS-injected group, and this was correlated with the fish survival rates in the challenge study. We used relative quantitative real-time polymerase chain reactions to examine the systemic expression of several other IFN-induced genes (including genes for IFN1, IFN regulatory factors 1 and 2, MHC-I, STAT1, vig-1, and GBP) and found that their expression was significantly increased 1-day post-rSasaIFN-alpha2 injection. Expression of the IFN-gamma and interleukin-1beta genes was not significantly increased. Thus, a salmonid rIFN-alpha can modulate the innate immune response of rainbow trout and mediate early antiviral protection against IHNV.