Keisuke Hagihara

Osaka University | Handai · Department of Advanced Hybrid Medicine

Introduction Maternal depression is one of the important problems of postpartum women. For its early detection and appropriate treatment, it is necessary to identify women at high risk for depression quickly and easily. Materials and methods A simple screening scale for depression from physical aspects, the multidimensional physical scale (MDPS),...

The population of postpartum women suffering from mental illness is increasing steadily, particularly under conditions of the COVID-19 pandemic. Identifying factors that contribute to resilience in postpartum women is urgently needed to decrease risks of poor physical and psychological functioning. Studies have linked variations in the intestinal m...

Donepezil, an acetylcholinesterase inhibitor, is associated with gastrointestinal symptoms, such as nausea, vomiting, and anorexia, which may affect adherence to continuous therapy. Since Rikkunshi-To, a Japanese herbal medicine, activates the ghrelin signaling pathway and promotes gastrointestinal function, it is administered to prevent gastrointe...

Frailty is one of the most important problems in a super-aged society. It is necessary to identify frailty quickly and easily at the bedside. We developed a simple patient-reported frailty screening scale, the Japan Frailty Scale (JFS), based on the aging concept of Kampo medicine. Eight candidate questions were prepared by Kampo medicine experts,...

Background/aim: To investigate factors associated with increased bone mineral density (BMD) of the neck of femur in rheumatoid arthritis or collagen diseases receiving denosumab, focusing on body composition calculated by bioelectrical impedance analysis (n=90, 78 females). Patients and methods: We defined Δfemur as BMD (12 months minus baseline...

Ketogenic diets, which are carbohydrate-restricted high-fat diets, may have therapeutic effects on various diseases, including cancer. However, ketogenic diets are often not standardized and, therefore, results are difficult to interpret. We previously investigated the usefulness of ketogenic diets in cancer therapy, where ketogenic formulas (KF) w...

Processed aconite root (PA), the tuberous root of Aconitum carmichaelii prepared by autoclaving, is a crude drug used in Japanese traditional Kampo medicine and traditional Chinese medicine for the symptoms of kidney deficiency, that is related to the muscle atrophy in modern medicine. The objective of the present study is to evaluate the effective...

Frailty develops due to multiple factors, such as sarcopenia, chronic pain, and dementia. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine used for age-related symptoms. We have reported that GJG improved sarcopenia, chronic pain, and central nervous system function through suppression of tumor necrosis factor-alpha (TNF-α) producti...

Frailty develops due to multiple factors, such as sarcopenia, chronic pain, and dementia. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine used for age-related symptoms. We have reported that GJG improved sarcopenia, chronic pain, and central nervous system function through suppression of TNF-α production. In the present study, GJG...

Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor ne...

A ketogenic diet is expected to be an effective support therapy for patients with cancer, but the degree and duration of carbohydrate restriction are unclear. We performed a case series study of a new ketogenic diet regimen in patients with different types of stage IV cancer. Carbohydrates were restricted to 10 g/day during week one, 20 g/day from...

Goshajinkigan (GJG) is a traditional Japanese Kampo medicine used clinically to treat muscle pain in Japan. However, its underlying mechanism remains unclear. Since voltage-gated sodium channel (Nav) 1.4 is involved in skeletal muscle contraction, we investigated the possibility that GJG may affect Nav1.4 currents. By using an electrophysiological...

Teriparatide is clinically used for the treatment of osteoporosis; however, nausea is often observed in patients. Its insufficient control affects the ability to continue teriparatide therapy. Rikkunshi-To (RKT), a traditional Japanese herbal medicine, improves the gastrointestinal function via activation of the ghrelin-signaling system. We investi...

In Japan, which is entering a super-aged society, the prevention of long-term care and bedridden caused by frailty and sarcopenia have been recognized as an urgent need. The pathology of frailty and sarcopenia includes broad problems of senility. A traditional herbal medicine is known to improve symptoms across the organs, many herbal medicines adm...

Go-sha-jinki-gan (GJG), a traditional Japanese herbal medicine has a clinical implication to alleviate age-related symptoms, especially in some motor disorders. However, the scientific evidence is limited, and there is a possibility to expand the medical application range of GJG. Using senescence-accelerated mice, our group showed that GJG exerted...

International standards regarding traditional medicine – particularly the International Organization for Standardization/Technical Committee (ISO/TC) 249 – are currently being debated. Kampo extract formulations of standardized quality are one area in which Japanese kampo medicines have a global advantage. While there is increasing medical evidence...

The aim of this observational, non-randomized study was to clarify the unknown effects of switching oral bisphosphonates (BPs) to denosumab (DMAb) or daily teriparatide (TPTD) in patients with rheumatoid arthritis (RA). The characteristics of the 194 female patients included in the study were 183 postmenopausal, age 65.9 years, lumbar spine (LS) T...

We experienced a case of paranoid schizophrenia whose negative symptoms such as fatigue and depression were successfully treated with kamishoyosan and hochuekkito. The combination of medical herbal extracts did not affect positive symptoms. Herbal medicine may play not only a supporting role in treating mental disorders in general but also an impor...

Background Alternative medicine is noted for its clinical effect and minimal invasiveness in the treatment of neuropathic pain. Go-sha-jinki-Gan, a traditional Japanese herbal medicine, has been used for meralgia and numbness in elderly patients. However, the exact mechanism of GJG is unclear. This study aimed to investigate the molecular mechanism...

Background Receptor activator of nuclear factor kappa-B ligand (RANKL) is a key inducer of osteoclast differentiation and activation, which plays a crucial role in osteoporosis and bone erosion of rheumatic diseases. Denosumab (DSM) is an anti-RANKL antibody approved for the treatment of postmenopausal osteoporosis, while its effect in rheumatic di...

In Japan, a traditional herbal medicine, Tokishigyakukagoshuyushokyoto (TJ-38), is often used for the treatment of peripheral coldness, which is a common complaint among Japanese women. However, the effects of this herbal medicine have yet to be examined in a randomized controlled trial. In the current study, the effect of TJ-38 on the peripheral b...

Sarcopenia is characterized by age-associated skeletal muscle atrophy and reduced muscle strength; currently, no pharmaceutical treatment is available. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine that is used to alleviate various age-related symptoms, especially motor disorders. Here, we investigated the effect of GJG on aging-...

Background/aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in patients with rheumatoid arthritis (RA) but have several side effects including mucosal damage in the small intestine. We aimed to evaluate whether the small bowel injury is ameliorated by switching from nonselective NSAIDs to celecoxib in patients with RA. Methods:...

Background: Recently tocilizumab, a humanized anti-interleukin-6 receptor antibody (IL-6R Ab), was clinically demonstrated to ameliorate metabolic syndrome. However, it is unknown whether blocking the IL-6R with tocilizumab directly impacts the adiponectin and fatty acid-binding protein 4 (FABP4) levels.

Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosis, a crucial...

Objectives: The retention of the anti-rheumatic agent tocilizumab (TCZ) has not been well documented in patients with rheumatoid arthritis (RA). We conducted an observational study to compare the retention of TCZ and anti-tumour necrosis factor (TNF) drugs in the treatment of patients with RA. Method: We reviewed continuation rates and causes of...

Systemic sclerosis (SSc) presents stiffness of extremities due to sclerosis of the tissue especially at fingers, hands, and forearms. Here we report the case of a patient with diffuse cutaneous SSc who was administered anti-interleukin-6 receptor antibody tocilizumab (TCZ). Skin condition of SSc is evaluated by pinching the skin according to the Ro...

Background: Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosi...

Background A humanized anti-interleukin-6 receptor, tocilizumab, has been approved as a biological drug for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis and Castleman's disease. Since dysregulation of IL-6 production also plays a pathologic role in other various autoimmune and allergic diseases, we tested whether to...

Background The prevalence of allergic diseases has increased all over the world during the last 2 decades. Dietary change is considered to be one of environmental factors that cause this increase and worsen allergic symptoms. If it is the case, an appropriate intake of foods and beverages with antiallergic activity is anticipated to prevent the ons...

The cytokine interleukin (IL)-6 has a wide range of biological activities. It contributes to host defense against pathogens by inducing immune responses, hematopoiesis, and acute-phase reactions. However, dysregulation of IL-6 production plays a significant pathological role in various autoimmune and chronic inflammatory disorders. Because IL-6 blo...

A 65-year-old woman who had suffered from chronic graft-versus-host disease (GVHD) presented with extensive purpura and was diagnosed with acquired hemophilia A. Because she was refractory to corticosteroids and her condition was complicated with diabetes mellitus, glaucoma, and hypoglobulinemia, she was treated with tocilizumab. Tocilizumab treatm...

A 47-year-old female patient with Beh double dagger et's disease had been treated with colchicine, prednisolone, cyclosporine A, and infliximab. Because she relapsed, however, treatment with tocilizumab, a humanized anti-interleukin 6 receptor antibody, was started. This treatment suppressed the patient's clinical manifestations, including ocular a...

サフランは，駆瘀血剤として使用される。瘀血は西洋医学的な病態で考えると，血液の粘稠度亢進と微小循環障害と解釈できる。今回我々は，サフランの臨床的な駆瘀血効果を観察し，血小板活性化の指標である，platelet factor4（PF-4）とbeta-thromboglobulin（β-TG）を瘀血のマーカーとして検討した。リウマチ膠原病アレルギー患者71人（女性66人，男性5人，平均年齢52.3 ± 16.1歳）にサフラン（300mg∼900mg）を投与し，78.7％（n＝37/47）の自覚症状の改善を認めた。投与前後での血漿中PF-4，β-TGともそれぞれ有意な改善を認めた（PF-4：49.6 ± 29.8→24.0 ± 19.6，β-TG：117.5 ± 64.0→64.6 ± 47.1，...

Basophils comprise less than 1% of blood circulating granulocytes and share several similarities with mast cells, including expression of high affinity IgE receptor and the ability to secrete chemical mediators and cytokines. Basophils also express CD40 ligand, which in combination with IL-4 and IL-13 promotes IgE class switching in B cells. Flavon...

SSc is an autoimmune disease characterized by fibrosis of the skin and internal organs. Although the aetiology remains uncertain, many reports have suggested that IL-6 is involved in SSc pathogenesis. Tocilizumab, an anti-IL-6 receptor antibody, is an anti-arthritis medicine that works through the blockade of IL-6 functions. To examine the effect o...

Administration of plasma in our C1q-deficient patient has clearly been therapeutically successful over a decade, demonstrating that this is a valid treatment option in this difficult condition. Rheumatology key message. Chronic plasma infusion is an effective therapy in complement C1q deficiency.

Interferon gamma (IFN-gamma) production is a critical step of antituberculosis (anti-TB) immune response. The purpose of this study was to determine the influences of biologics, including the interleukin (IL)-6 receptor-inhibitor tocilizumab (TCZ), and tumor necrosis factor (TNF) antagonists infliximab (INF) and etanercept (ETA), on Mycobacterium t...

Overgrowth of the synovium plays an important role in the pathogenesis of rheumatoid arthritis (RA). Platelet-derived growth factor (PDGF) is one of the most potent mitogenic factors of synovial cells, and imatinib mesylate (imatinib) is a specific inhibitor of the PDGF receptor tyrosine kinase. The aim of this study was to elucidate the anti-rheum...

Flavonoids are nutrients that exert anti-allergic effects. We investigated the preventative effect of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve the symptoms of Japanese cedar pollinosis. In a parallel-group, double-blind placebo-controlled study design, 24 subjects with Japanese cedar pollinosis took 100mg EMIQ or a place...

Flavonoids exert antiallergic and antioxidant effects. We investigated the efficacy of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve symptoms of pollinosis. In a parallel-group, double-blind placebo-controlled study design, 20 subjects with Japanese cedar pollinosis took two capsules daily of 100 mg EMIQ or a placebo for 8 we...

No objective method to measure skin involvement in SSc has been established. We developed a novel method using a computer-linked device to simultaneously quantify physical properties of the skin such as hardness, elasticity and viscosity. Skin hardness was calculated by measuring the depth of an indenter pressed onto the skin. The Voigt model was u...

C-reactive protein (CRP) is a sensitive marker and mediator of inflammation, whereas IL-6 blocking therapy can normalize serum levels of CRP in chronic inflammatory diseases. We investigated the precise synergistic induction mechanism of CRP gene expression by IL-1 and IL-6 in Hep3B cells. In the early induction phase, IL-1 inhibited IL-6-mediated...

C-reactive protein (CRP) is a sensitive marker and mediator of inflammation, whereas IL-6 blocking therapy can normalize serum levels of CRP in chronic inflammatory diseases. We investigated the precise synergistic induction mechanism of CRP gene expression by IL-1 and IL-6 in Hep3B cells. In the early induction phase, IL-1 inhibited IL-6-mediated...

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The prevalence of allergic diseases has increased all over the world during the last two decades. Dietary change is considered to be one of the environmental factors that cause this increase and worsen allergic symptoms. If this is the case, an appropriate intake of foods or beverages with anti-allergic activities is expected to prevent the onset o...

To screen for autoantibodies associated with systemic lupus erythematosus (SLE), we used proteomic approaches combining 2-D PAGE and Western blot analysis, followed by protein identification by LC-MS/MS analysis, resulting in the identification of aldolase A as a novel autoantigen in SLE. ELISA showed the prevalence of anti-aldolase A antibodies to...

We previously demonstrated a significant association between IL-18 gene polymorphism 105A/C and asthma. In this study, we investigated the relationship of IL-18 gene polymorphism to IL-18 production capability by monocytes. The frequency of gene polymorphisms including IL-18-105A/C and IL-18--137G/C was determined by PCR analyses. The IL-18 product...

Anti-cytokine therapies have been used for rheumatoid arthritis (RA) and their efficacy has been previously reported. Serum amyloid A (SAA) is an acute phase protein and known as a precursor of amyloid fibril in AA amyloidosis. IL-6 blocking therapy normalized the serum levels of SAA, in RA patients, while anti-TNFα or IL-1 therapy did not. From th...

Serum amyloid A (SAA) is a sensitive marker of acute-phase responses and known as a precursor protein of amyloid fibril in amyloid A (AA) (secondary) amyloidosis. Since the serum SAA level is also closely related to activity of chronic inflammatory disease and coronary artery disease, it is important to clarify the exact induction mechanism of SAA...

Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a hu...

We encountered a case of a rapidly progressive HHV-8-associated solid lymphoma with AIDS-associated Kaposi's sarcoma (KS). HHV-8 DNA load in whole blood cells was analyzed quantitatively by real-time PCR using amplification of the HHV-8-encoded ORF26 gene. Ours is the first observation that the rapid increase in the HHV-8 viral load (from 1.9x10(4)...

Serum amyloid A (SAA) is known to be a precursor of amyloid A (AA) protein in AA (secondary) amyloidosis and SAA1 to be mainly involved in AA amyloidosis. We established an SAA isoform real-time quantitative RT-PCR assay and found that beta-2 microglobulin is more stable as an internal control than GAPDH and beta-actin for our system. Either IL-6 a...

To investigate whether interleukin-6 (IL-6) is a regulator of vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA). Serum VEGF levels in RA patients were assayed before and after 8 weeks or 24 weeks of maintenance therapy with humanized anti-IL-6 receptor monoclonal antibody (anti-IL-6R mAb). VEGF secreted by RA synovial fibroblas...

Hyperproduction of Interleukin-6(IL-6) is observed in the rheumatoid arthritis(RA) patients and serum level of IL-6 is closely related to disease activity. IL-6 is a pleiotropic cytokine and its hyperfunctions explain most of the clinical symptoms in RA. Since MRA is humanized antibody from a mouse anti-human IL-6 receptor antibody, MRA can be admi...