Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study

We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly (P=0.006) improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant (P=0.037) in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (JapicCTI-121994).

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Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human

Nutrients ◽

10.3390/nu13061875 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1875

Author(s):

Su-Jin Jung ◽

Ji-Hyun Hwang ◽

Eun-Ock Park ◽

Seung-Ok Lee ◽

Yun-Jo Chung ◽

...

Keyword(s):

Alcohol Dehydrogenase ◽

Blood Levels ◽

Double Blind ◽

Excessive Alcohol Consumption ◽

Bifidobacterium Species ◽

Placebo Capsule ◽

Safety Parameters ◽

Excessive Alcohol ◽

Clinically Significant ◽

Acetaldehyde Metabolism

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

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Very Early Neurophysiological Study in Guillain-Barre Syndrome

European Neurology ◽

10.1159/000494261 ◽

2018 ◽

Vol 80 (1-2) ◽

pp. 100-105 ◽

Cited By ~ 1

Author(s):

Jiaoting Jin ◽

Fangfang Hu ◽

Xing Qin ◽

Xuan Liu ◽

Min Li ◽

...

Keyword(s):

Nerve Conduction ◽

Nerve Conduction Velocity ◽

Tibial Nerve ◽

Early Stage ◽

Motor Nerve ◽

Sensory Nerve ◽

Sensory Nerves ◽

Motor Nerve Conduction ◽

Abnormal Rate ◽

Motor Nerves

Purpose: The diagnosis of Guillain-Barre syndrome (GBS) in the very early stage may be challenging. Our aim was to report the neurophysiological abnormalities in GBS within 4 days of clinical onset. We expected that GBS will be diagnosed by the assistance of neurophysiological study in the very early stage. Methods: We prospectively recruited patients with a diagnosis of GBS discharged from First Affiliated Hospital of Xi’an Jiaotong University and Xi Jing Hospital. Patients were classified into 3 groups according to the onset of symptoms to electromyography examination interval (OEI). The neurophysiological findings were carried out using standard procedures. All patients were examined by the same experienced neurophysiologist. Results: There were not significant group differences in abnormal rate, distal motor latency (DML), motor nerve conduction velocity (MNCV), F response (FR), compound muscle action potential (CMAP), conduction block (CB), sensory nerve action potential (SNAP), and sensory nerve conduction velocity among OEI ≤4 days, 4< OEI ≤10 days, and OEI > 10 days groups. Motor nerves were more affected than sensory nerves in neurophysiological presentation in very early stage patients. The difference of motor nerves and sensory nerves was statistically significant in lower limbs, but was not in upper limbs. In motor nerve conduction studies, the abnormal rate of DML, MNCV, FR, CB was more common seen in ulnar and peroneal nerve than median and tibial nerve, the abnormal rate of CMAP was the same in ulnar, median, peroneal and tibial nerve. In sensory nerve conduction studies, the abnormal rate of ulnar nerve and median nerve was higher than the superficial peroneal nerve and sural nerve. The OEI was not correlated with the SNAP decrease rate of median (r = 0.10, p = 0.23) and ulnar (r = 0.26, p = 0.06) but was statistically correlated with sural SNAP decrease rate (r = 0.29, p = 0.04). The sural-sparing pattern phenomenon was the most commonly discovered phenomenon in very early stage patients (OEI ≤4 days), followed by patients with 4< OEI ≤10 days, ultimately found in patients with OEI > 10 days. Conclusions: We suggest performing neurophysiological examination as soon as possible for suspected GBS patients, particularly focusing on multi-spots inspection of ulnar and peroneal nerves, and paying close attention to sural-sparing patterns.

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Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Levetiracetam as Add-On Therapy in Japanese Patients with Uncontrolled Partial Seizures

Journal of the Japan Epilepsy Society ◽

10.3805/jjes.28.3 ◽

2010 ◽

Vol 28 (1) ◽

pp. 3-16 ◽

Cited By ~ 8

Author(s):

Kazuichi Yagi ◽

Shigeki Kameyama ◽

Sunao Kaneko ◽

Mitsukuni Murasaki ◽

Toshio Yamauchi

Keyword(s):

Japanese Patients ◽

Controlled Study ◽

Partial Seizures ◽

Double Blind

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TrkA inhibitor promotes motor functional regeneration of recurrent laryngeal nerve by suppression of sensory nerve regeneration

Scientific Reports ◽

10.1038/s41598-020-72288-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Hiroshi Suzuki ◽

Koji Araki ◽

Toshiyasu Matsui ◽

Yuya Tanaka ◽

Kosuke Uno ◽

...

Keyword(s):

Recurrent Laryngeal Nerve ◽

Nerve Regeneration ◽

Vocal Fold ◽

Compound Muscle Action Potential ◽

Motor Nerve ◽

Sensory Nerve ◽

Laryngeal Nerve ◽

Sensory Nerves ◽

Nucleus Ambiguus ◽

Functional Regeneration

Abstract Recurrent laryngeal nerve (RLN) injury, in which hoarseness and dysphagia arise as a result of impaired vocal fold movement, is a serious complication. Misdirected regeneration is an issue for functional regeneration. In this study, we demonstrated the effect of TrkA inhibitors, which blocks the NGF-TrkA pathway that acts on the sensory/automatic nerves thus preventing misdirected regeneration among motor and sensory nerves, and thereby promoting the regeneration of motor neurons to achieve functional recovery. RLN axotomy rat models were used in this study, in which cut ends of the nerve were bridged with polyglycolic acid-collagen tube with and without TrkA inhibitor (TrkAi) infiltration. Our study revealed significant improvement in motor nerve fiber regeneration and function, in assessment of vocal fold movement, myelinated nerve regeneration, compound muscle action potential, and prevention of laryngeal muscle atrophy. Retrograde labeling demonstrated fewer labeled neurons in the vagus ganglion, which confirmed reduced misdirected regeneration among motor and sensory fibers, and a change in distribution of the labeled neurons in the nucleus ambiguus. Our study demonstrated that TrkAi have a strong potential for clinical application in the treatment of RLN injury.

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Blonanserin versus haloperidol in Japanese patients with schizophrenia: A phase 3, 8‐week, double‐blind, multicenter, randomized controlled study

Neuropsychopharmacology Reports ◽

10.1002/npr2.12057 ◽

2019 ◽

Vol 39 (3) ◽

pp. 173-182 ◽

Cited By ~ 3

Author(s):

Philip D. Harvey ◽

Hiroshi Nakamura ◽

Mitsukuni Murasaki

Keyword(s):

Japanese Patients ◽

Randomized Controlled Study ◽

Controlled Study ◽

Phase 3 ◽

Double Blind ◽

Randomized Controlled

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Efficacy and safety of galcanezumab for prevention of migraine headache in Japanese patients with episodic migraine: A phase 2 randomized controlled clinical trial

Cephalalgia Reports ◽

10.1177/2515816320932573 ◽

2020 ◽

Vol 3 ◽

pp. 251581632093257 ◽

Cited By ~ 1

Author(s):

Fumihiko Sakai ◽

Akichika Ozeki ◽

Vladimir Skljarevski

Keyword(s):

Migraine Headache ◽

Japanese Patients ◽

Episodic Migraine ◽

Secondary Outcome ◽

Controlled Study ◽

Controlled Clinical Trial ◽

Life Questionnaire ◽

Efficacy And Safety ◽

Double Blind ◽

Secondary Endpoints

Objective: This study was designed to assess the efficacy and safety of galcanezumab in comparison with placebo for the prevention of migraine in Japanese patients with episodic migraine. Methods: In this double-blind, placebo-controlled study, which was conducted over 6 months, randomized adult patients received subcutaneous injections of galcanezumab (120 mg n = 115, 240 mg n = 114) or placebo ( n = 230) once monthly. The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days. The key secondary outcome measures were response rates (≥50%, ≥75%, and 100%); the Migraine-Specific Quality-of-Life Questionnaire Role Function-Restrictive score; monthly migraine headache days requiring acute treatment; and Patient Global Impression of Severity (PGI-S). Results: The mean change from baseline in monthly migraine headache days over months 1–6 was significantly ( p < 0.001) greater for the 120-mg galcanezumab dose (−3.60 days) and the 240-mg galcanezumab dose (−3.36 days) compared with placebo (−0.59 days). Both the 120-mg and 240-mg doses of galcanezumab were superior compared with placebo for each of the key secondary endpoints except for PGI-S (only the 240-mg dose was superior). The most commonly reported treatment-emergent adverse events were local injection-site reactions; erythema, swelling, pruritus, and pain were more commonly reported by patients who were treated with galcanezumab than those treated with placebo. Conclusion: The number of monthly migraine headache days was reduced with both doses of galcanezumab, and both doses were safe and well tolerated in Japanese patients with episodic migraine.

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Short-Term Outcomes of Percutaneous Trephination with a Platelet Rich Plasma Intrameniscal Injection for the Repair of Degenerative Meniscal Lesions. A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study

International Journal of Molecular Sciences ◽

10.3390/ijms20040856 ◽

2019 ◽

Vol 20 (4) ◽

pp. 856 ◽

Cited By ~ 9

Author(s):

Rafal Kaminski ◽

Marta Maksymowicz-Wleklik ◽

Krzysztof Kulinski ◽

Katarzyna Kozar-Kaminska ◽

Agnieszka Dabrowska-Thing ◽

...

Keyword(s):

Platelet Rich Plasma ◽

Meniscal Tear ◽

Controlled Study ◽

Control Group ◽

Double Blind ◽

Non Union ◽

Parallel Group ◽

Significant Difference ◽

Clinically Significant ◽

Patient Related Outcome

Meniscal tears are the most common orthopaedic injuries, with chronic lesions comprising up to 56% of cases. In these situations, no benefit with surgical treatment is observed. Thus, the purpose of this study was to investigate the effectiveness and safety of percutaneous intrameniscal platelet rich plasma (PRP) application to complement repair of a chronic meniscal lesion. This single centre, prospective, randomized, double-blind, placebo-controlled study included 72 patients. All subjects underwent meniscal trephination with or without concomitant PRP injection. Meniscal non-union observed in magnetic resonance arthrography or arthroscopy were considered as failures. Patient related outcome measures (PROMs) were assessed. The failure rate was significantly higher in the control group than in the PRP augmented group (70% vs. 48%, P = 0.04). Kaplan-Meyer analysis for arthroscopy-free survival showed significant reduction in the number of performed arthroscopies in the PRP augmented group. A notably higher percentage of patients treated with PRP achieved minimal clinically significant difference in visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) symptom scores. Our trial indicates that percutaneous meniscal trephination augmented with PRP results in a significant improvement in the rate of chronic meniscal tear healing and this procedure decreases the necessity for arthroscopy in the future (8% vs. 28%, P = 0.032).

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