Shojiro Kyotani

Effects of Sho-saiko-to extract on liver fibrosis in relation to the changes in hydroxyproline and retinoid levels of the liver in rats.

To examine the effects of Sho‐saiko‐to extract on liver fibrosis, the drug was administered to rats with dimethylnitrosamine‐induced liver‐injury at various doses. Hydroxyproline and retinoid levels in the liver were measured as indicators of liver function.

Natural Products: Effects of Sho-saiko-to Extract on Fibrosis and Regeneration of the Liver in Rats

Sho‐saiko‐to, one of the most widely used Chinese herbal preparations, has long been used for the treatment of chronic liver diseases. We have investigated its effect in retarding the process of liver fibrosis and accelerating liver regeneration, especially its effect on Ito cells that are thought to be deeply involved with liver fibrosis.

Effect of Sho‐saiko‐to Extract on HGF and TGF‐β Levels of Intraorgans in Liver‐injured Rats after Partial Hepatectomy

To examine the effects of Sho‐saiko‐to extract on liver regeneration, Sho‐saiko‐to extract (0.75%, 1.5% or 3.) was administered to 70% partial hepatectomized rats with dimethyl‐nitrosamine‐induced liver‐injury.

Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non-alcoholic steatohepatitis

Objectives Non‐alcoholic steatohepatitis is associated with the deposition of lipid droplets in the liver, and is characterised histologically by the infiltration of inflammatory cells, hepatocellular degeneration and liver fibrosis. Oxidative stress may play an important role in the onset and deterioration of non‐alcoholic steatohepatitis. We previously reported that an Eriobotrya japonica seed extract, extracted in 70% ethanol, exhibited antioxidant actions in vitro and in vivo. In this study, we examined the effect of this extract in a rat model of non‐alcoholic steatohepatitis.

Effect of orally administered Eriobotrya japonica seed extract on allergic contact dermatitis in rats

The anti‐allergic activity of Eriobotrya japonica seeds extract (ESE) was investigated. Oral administration of ESE dramatically inhibited ear swelling due to allergic contact dermatitis caused by repeated application of two antigens, 4‐ethoxymethylene‐2‐phenyl‐2‐oxazolin‐5‐one (oxazolone) and dinitrofluorobenzene (DNFB), respectively. The increase of histamine content in inflamed ear tissue induced by oxazolone and DNFB was significantly antagonized by orally administered ESE. Eosinophil peroxidase and myeloperoxidase activity in both models was suppressed by orally administered ESE. Tumour necrosis factor‐α in the inflamed region caused by repeated application of DNFB was also significantly suppressed. The findings suggest that ESE may be effective for treating allergic contact dermatitis.

Animal studies supporting the inhibition of mast cell activation by Eriobotrya japonica seed extract

Objectives The potent antioxidant activity of Eriobotrya japonica seed extract (ESE) and its usefulness in the prevention and treatment of various disorders has been reported previously. Its antioxidant activity associated with β‐sitosterol and polyphenols contained in the extract was also validated. In this study, anti‐allergic activity of Eriobotrya japonica seed extract was investigated.

Marked efficacy of combined three-drug therapy (Sodium Valproate, Topiramate and Stiripentol) in a patient with Dravet syndrome

Dravet syndrome (DS) is an intractable epilepsy syndrome. The three‐drug combination therapy of sodium valproate (VPA), clobazam (CLB) and stiripentol (STP) is recommended worldwide.

Influence of nanoparticle size on the skin penetration, skin retention and anti-inflammatory activity of non-steroidal anti-inflammatory drugs

Background: This study aims to evaluate the influence of nanoparticle size on the in vitro percutaneous penetration and retention and in vivo anti‐inflammatory efficacy of percutaneously delivered non‐steroidal anti‐inflammatory drugs. Methods: Indomethacin, ketoprofen and piroxicam were incorporated into nanoparticles. The nanoparticles, or the bulk‐drug equivalents, were suspended in a hydrophilic ointment and compared for their ability to facilitate percutaneous drug penetration and retention in vitro. The formulations were applied cutaneously in a carrageenan‐induced footpad inflammation model (acute inflammation) and an adjuvant‐induced arthritis model (chronic inflammation) in rats and were assessed for their anti‐inflammatory efficacy and potency. Results: The nanoparticle formulations demonstrated a substantially smaller particle size compared with the bulk‐drug formulations. The nanoparticles notably increased drug penetration and retention in vitro. In both the acute and chronic inflammation models, the nanoparticle formulations demonstrated significantly higher anti‐inflammatory activity than that of their corresponding bulk‐drug formulation at an equivalent dose, and produced better overall healing. Conclusion: The nanoparticle formulations are highly effective as percutaneous drug carriers, and demonstrate that decreasing particle size leads to increased efficacy and potency. The exploitation of such nanotechnology could drive the development of more effective percutaneous therapeutics.

A study of oxidative stress and the newer antiepileptic drugs in epilepsy associated with severe motor and intellectual disabilities

Background Patients with severe motor and intellectual disabilities (SMID) are those who have both severe intellectual disabilities and severe physical disabilities. Intractable epilepsy is often associated with SMID. The purpose of this study was to elucidate the relationship between epilepsy associated with SMID and oxidative stress, and to clarify the safety and efficacy of the newer antiepileptic drugs (newer AEDs), lamotrigine and levetiracetam. Methods This study was conducted in 27 SMID patients with epilepsy who were treated with the newer AEDs. The patient characteristics and the safety and efficacy of the newer AEDs were investigated. The reactive oxygen metabolite (d‐ROM) and biological antioxidant potential (BAP) levels were measured as indicators of the degree of oxidative stress. The relationship between the investigation results (the patient characteristics, and the safety and efficacy of the newer AEDs) and the results of measurements of the d‐ROMs/BAP were analyzed. Results All the patients who discontinued the newer AEDs had abnormal plasma d‐ROM levels. In addition, all the patients who developed adverse events also had abnormal d‐ROM levels. Furthermore, there was a trend toward a lower response rate in patients with higher plasma d‐ROM levels. Conclusion The results of this study suggested that d‐ROM levels are useful for predicting the safety and efficacy of the newer AEDs (lamotrigine, levetiracetam) in SMID patients with intractable epilepsy. Therefore, d‐ROMs could be important biomarkers for determining the safety and efficacy of drug therapy in SMID patients with epilepsy.

Preparation and Clinical Evaluation of Streptokinase Jelly for Intractable Decubitus and Skin Ulcer

For the purpose of treating intractable decubitus and skin ulcer, streptokinase (SK) jellies containing different types of thickening agents were prepared. Adhesion to the affected sites, the spreading ability of the jelly preparation, and the properties of the SK in the jelly, which are all considered to greatly affect the clinical efficacy, were examined pharmaceutically using the viscosity, spreading area, and release and stability of SK as indexes. Regarding the viscosity and spreading area which are thought to affect both adhesion and spreading greatly, when sodium polyacrylate (PANa) was used as a thickener, higher viscosity and smaller spreading area were obtained in comparison with carboxymethylcellulose sodium (CMCNa) and sodium alginate (Alg Na). In addition, the viscosity and the spreading area obtained with PANa were also slightly more affected by temperature than with CMCNa and AlgNa. Regarding the release of SK from the jelly preparations, with PANa no initial burst was observed and SK was continuously released at a constant rate in contrast with CMCNa and AlgNa, thus obviously showing the superiority of PANa in the retention of SK. Although no loss of the potency of SK was found in the jellies containing PANa, CMCNa or AlgNa at 5°C, for 30 days, the remaining potency was greatly decreased to 49-62% at 25°C after 30 days and 33-42% at 37°C after 30 days. These results showed that the adhesion, spreading ability and SK-release were greatly different among the tested thickening agents, and the properties of PANa were found to be clearly superior to those of the other agents. According to these results, SK jelly containing 2% PANa was used for the treatment of intractable decubitus and skin ulcer, and an excellent therapeutic effect was obtained.