Positive Effects of Uyakujunkisan Therapy (Kampo Medicine) for Postherpetic Neuralgia With Concomitant Pregabalin: Two Case Reports With a Literature Review.

Context • The hallmark of herpes zoster (HZ) is a painful, blistering rash, but neuropathic pain can persist beyond the clearing of the rash and is diagnosed as postherpetic neuralgia (PHN), a chronic pain syndrome. However, the pain in PHN is often refractory to treatment. Objective • The study investigated the ability of Uyakujunkisan (UJS), or Kampo medicine, a traditional herbal medicine, to treat PHN successfully. Design • The study was observational, with discussion of 2 cases. Setting • The study took place in the Department of Japanese Oriental Medicine at Gunma Central and General Hospital (Maebashi, Gunma, Japan). Participants • The participants in cases 1 and 2 were a 70-y-old male and a 70-y-old female, respectively. The woman in case 2 also had rheumatoid arthritis. Both had been treated for HZ with antiviral drugs but continued to experience pain and were diagnosed with PHN. Intervention • Both participants were treated with a decoction of UJS that was administered 3 ×/d before meals. Outcome Measures • The patients completed a visual analogue scale. Results • In case 1, the patient's pain had almost disappeared after 8 wk of treatment. In case 2, the patient's pain had disappeared by 4 mo after starting the UJS treatment. Conclusions • Treatment with UJS may be a useful option as a therapeutic strategy for refractory PHN, especially in older adults.

Immunoglobulin G4-Related Retroperitoneal Fibrosis Treated with Hochuekkito, a Kampo Medicine, following Steroid Treatment.

We report a case of immunoglobulin G4 (IgG4)-related retroperitoneal fibrosis (RF) with complete remission and no relapses after therapy with steroids and Hochuekkito, a Kampo (i.e. traditional Japanese herbal) medicine. A 62-year-old Japanese man was admitted to our hospital for treatment of a retroperitoneal mass detected by computed tomography. The mass had a maximum diameter of 11.0 cm; it involved the left ureter and was associated with left hydronephrosis. After inserting a ureteral stent, we performed a biopsy by laparotomy. Histopathology revealed IgG4-related RF. The lesion disappeared after 7 months of steroid therapy. We subsequently used Hochuekkito as an alternative maintenance treatment because of steroid-related complications. The patient has not relapsed in the 3 years since starting the medication. To the best of our knowledge, this is the first case of IgG4-related RF treated with Hochuekkito as a maintenance treatment.

Investigation of clinical characteristics as predictive factors for the humoral immune response to the influenza vaccine in patients with rheumatoid arthritis.

The objective of this observational study is to determine characteristics as predictive factors for the humoral immune response to the influenza vaccine in patients with rheumatoid arthritis (RA). Fifty-seven RA patients who visited our department between 2011 and 2012 were recruited for the present study. The anti-influenza antibody titers of a trivalent influenza subunit vaccine (A/California/7/2009 (H1N1)-like strain (A/H1N1 strain), A/Victoria/210/2009 (H3N2)-like strain (A/H3N2 strain), and B/Brisbane/60/2008-like strain (B strain)) were measured at baseline and 4 weeks after the vaccination using the hemagglutination inhibition assay. Associations between the immune response to the influenza vaccine and clinical characteristics such as background, clinical parameters, and "having treatments or not" were examined to determine predictive factors for the immune response to the influenza vaccine. The titers of the three strains were significantly increased in all RA patients after the influenza vaccination. Concerning predictive factors of the immune response, no significant differences were observed in background (age and sex) or clinical parameters (peripheral lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, matrix metalloproteinase-3, and disease activity score-28). No significant differences were observed in the titers of anti-influenza antibodies between the treatment (methotrexate, prednisolone, salazosulfapyridine, or tacrolimus) and no-treatment groups. In contrast, there was a significant difference in A/H3N2 strain between the patients with biologics and without biologics. The only factor that affected anti-influenza antibody titers was "having biologics or not"; therefore, the immune response to the influenza vaccine may not be predicted from the viewpoints of background and clinical parameters.

The long-term effects of a kampo medicine, juzentaihoto, on maintenance of antibody titer in elderly people after influenza vaccination.

We have performed a broad-ranging analysis of the adjuvant effect of a Kampo medicine, juzentaihoto (JTT), on influenza vaccination in a multicenter randomized controlled trial. In this study, the enhancing effect of JTT on antibody titer after influenza vaccination was studied for 28 weeks in elderly people who were in the high-risk group for influenza infection. In total, 91 subjects over 65 years old were recruited from four long-term-care facilities located in Chiba, Gunma, and Toyama prefectures in Japan. Participants were randomly assigned to the JTT and the control groups. Blood samples were taken at 4 weeks before vaccination, at the time of vaccination, and then at 4, 8, 12, and 24 weeks after vaccination. The hemagglutination inhibition (HI) titers against A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008 were then manually measured. A significant increase in HI titer against H3N2 was observed at week 8 after vaccination in the JTT group compared with the control group (P = 0.0229), and the HI titer of the JTT group significantly increased from 4 to 24 weeks (P = 0.0468), compared with the control group. In conclusion, our results indicated that JTT increased and prolonged antibody production against A/Victoria/210/2009 (H3N2), in particular, after influenza vaccination.

Recent clinical applications of Japanese oriental (Kampo) medicine for rheumatoid arthritis: search for Kampo responder.

Rheumatoid arthritis (RA) is a heterogeneous disease. In rheumatology, researchers have not identified useful clinical markers to predict the effects of biological agents or of nonbiological, antirheumatic drugs before administration. Since the advent of biological agents, therapeutic strategies for RA have focused on early detection and early intensive treatment. Although responders to Japanese Oriental (Kampo) medicine exist, physicians first have had to diagnose RA using the practices of conventional medicine. They could identify those patients who would benefit from administration of Kampo medicine only by administering the treatment. Only the presence of a positive response could confirm the benefits for a particular individual. In this article, the author discusses the clinical importance of Kampo medicine within the context of the present RA classification criteria and therapeutic treatment and discusses the use of the basal value of anti-CCP antibody (aCCP) titer as a prognostic factor for use of Kampo medicine for RA. The author then defines a methodology for determining who should receive the treatment.

Benzofuran derivatives inhibit 11ß-hydroxysteroid dehydrogenase type 1 activity in rat adipose tissue.

Excess glucocorticoids promote visceral obesity and insulin resistance. The main regulator of intracellular glucocorticoid levels are 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which converts inactive glucocorticoid into bioactive glucocorticoid such as cortisol in humans and corticosterone in rodents; therefore, the inhibition of 11ß-HSD1 has considerable therapeutic potential for metabolic diseases including obesity and diabetes. Benzofuran is a key structure in many biologically active compounds such as benzbromarone, malibatol A and (+)-liphagal. The aim of this study was to investigate the inhibitory effect of benzofuran derivatives on 11ß-HSD1 in mesenteric adipose tissue from rodents. 11ß-HSD1 activity was determined by incubation of rat mesenteric adipose tissue microsomes in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) with and without benzofuran derivatives (Compounds 1-14). The corticosterone produced was measured by HPLC. More than 40% of 11ß-HSD1 inhibition was observed in Compounds 1, 5, 7 and 8. Moreover, Compounds 7 and 8 inhibited the 11ß-HSD1 activity in adipose microsomes dose- and time-dependently, as well as in 3T3-L1 adipocytes. Compounds 7 and 8 did not inhibit 11ß-HSD type 2 (11ß-HSD2), whereas Compounds 1 and 5 inhibited 11ß-HSD2 by 18.7% and 56.3%, respectively. Further, a kinetic study revealed that Compounds 7 and 8 acted as non-competitive inhibitors of 11ß-HSD1. Ki (nmol/h/mg protein) values of Compounds 7 and 8 were 17.5 and 24.0, respectively, with IC50 (µM) of 10.2 and 25.6, respectively. These data indicate that Compounds 7 and 8 are convincing candidates for seed compounds as specific inhibitors of 11ß-HSD1 and have the potential to be developed as anti-obesity drugs.

The observation of humoral responses after influenza vaccination in patients with rheumatoid arthritis treated with Japanese oriental (kampo) medicine: an observational study.

Objective. The efficacy of influenza vaccination in patients treated with Japanese Oriental (Kampo) Medicine is unknown. The objectives of this study were to observe the efficacy of influenza vaccination in RA patients treated with Kampo. Methods. Trivalent influenza subunit vaccine was administered to 45 RA patients who had received Kampo. They were divided into 2 groups: RA patients treated without MTX ("without MTX group") and treated with MTX ("with MTX group"). Antibody titers were measured before and 4 weeks after vaccination using hemagglutination inhibition assay. Results. Geometric mean titers (GMTs) of anti-influenza antibodies significantly increased for all influenza strains. Response to the influenza vaccination in RA patients treated with Kampo was not lower than that of healthy subjects and the response in the "with MTX group" had a tendency to be higher than that in RA patients treated with MTX in the previous study. There was no significant difference in the GMT after 4 weeks between the "with MTX group" and the "without MTX group." A decreased efficacy in both seroprotection and seroconversion was not found in the "with MTX group." Conclusion. These observations may open the way for further clinical trials to establish the efficacy for the influenza vaccination in RA patients treated with Kampo.

Effect of kampo medicine on pain and range of motion of osteoarthritis of the hip accompanied by acetabular dysplasia: case report and literature review.

We report a 52-year-old female with end-stage osteoarthritis of the hip accompanied by acetabular dysplasia in whom quality of life (QOL) was improved by Kampo treatment.When she was 42 years old, she developed pain in the left hip joint, and early-stage OA of the hip was diagnosed by hip joint x-ray. Therefore, she took NSAIDs, and received conservative therapies such as diet and muscle training. However, pain in the hip joint increased and her activity of daily life (ADL) decreased at the age of 50, although she continued to receive the conservative therapies. At the age of 52, she consulted our department requesting Japanese Oriental (Kampo) Medicine. Kampo formulae; Keishikaryojutsubuto (12Tab/day: Kuracie Co. Ltd. Japan), and Boiougito (7.5 g/day: Kuracie Co. Ltd. Japan), were administered. Treatment for 3 months resulted in a decrease in the left hip joint pain using visual analogue scale (VAS) and improvement of her ADL. One year later, her joint symptoms have not increased, and both the Harris hip score and the clinical evaluation criteria of osteoarthritis of the hip have improved.The course of this disease varies depending on the lifestyle of the patient, and Kampo formulations may offer safe, potent supplemental treatment.

Edematous erythema at the hands and feet probably caused by the traditional herb "radix astragali".

OBJECTIVE: To describe a patient with erhythema and edema after Radix Astragali was added to a kampo formula. CASE SUMMARY: A 21-year-old male, who was diagnosed as having atopic dermatitis in 1989, demonstrated systemic dry eruptions and consulted our department for treatment with traditional herbal medicine (THM) in 2004. The oral administration of herbal medicine resulted in decreased symptoms as well as a reduction in the serum IgE level. In August 2007, he complained of sweating on the neck and we added Radix Astragali to the previous formula. About 18 hours after he ingested the new formula including Radix Astragali, erhythema appeared with swelling of the bilateral hands and feet. Administration of the formula was discontinued and about 48 hours later, his symptoms had almost disappeared. Astragaloside, which is the main ingredient of Radix Astragali, was negative on lymphocyte transforming test (LTT) and we could not determine the ingredient that induced erhythema. CONCLUSION: We consider that the Radix Astragali induced acute erhythema with swelling based on the clinical course. Acute edematous erythema due to THM is very rare and we discuss allergic reactions to traditional herbs and review the litrature.

Traditional herbal medicines (Kampo) for patients with rheumatoid arthritis receiving concomitant methotrexate: a preliminary study.

OBJECTIVE: To assess the clinical effectiveness and safety of traditional herbal medicines (THM: Kampo) used in combination with oral methotrexate (MTX) in order to control the disease activity of rheumatoid arthritis (RA) in patients whose disease remains active despite treatment with MTX. METHODS: Patients (n=13; male:female = l:12) with RA who achieved only a suboptimal response to MTX therapy (> or =6 mg/week and > or =6 months) were enrolled in this assessment. All patients were treated with Keishinieppiittokaryojutsubu (KER; decoction) according to the traditional diagnostic system. Every 3 months, joint symptoms were examined, and routine blood analysis and general serological tests including anticyclic citrullinated peptide antibody (aCCP) were performed, and then we calculated the disease activity score of 28 joints (DAS28). RESULTS: One patient withdrew from the study after 4 weeks and discontinued consultations with our department for unknown reasons. Five (41.7%) of the twelve patients were defined as responders, and seven patients (58.3%) were classified as nonresponders based on DAS28-CRP findings. On comparison between responders and nonresponders, there was no significant difference with regard to age or disease duration and the dosages of concomitant prednisolone at baseline. KER responders had lower levels of aCCP at baseline than nonresponders (mean +/- standard deviation: 329.2 +/- 113.9 U/mL vs 623.8 +/- 242.8 U/mL, respectively) (P = .046, Mann-Whitney test). Furthermore, responders to KER showed a significant decrease in the serum levels of aCCP. The annual cost for KER treatment is much less than that for other new drugs. CONCLUSION: In patients whose active RA persists despite treatment with MTX, KER in combination with MTX is safe and well tolerated and provides clinical and economic benefits. Furthermore, pretreatment serum levels of aCCP are a useful predictor of a good response to KER treatment, and a decrease in serum levels of aCCP may be an adjunctive indicator in predicting the efficacy of this kind oftreatment.

Four cases of dysthymic disorder and general malaise successfully treated with traditional herbal (kampo) medicines: kamiuntanto.

Traditional herbal (Kampo) medicines have been used since ancient times to treat patients with mental disorders. In the present report, we describe four patients with dysthymia successfully treated with Kampo medicines: Kamiuntanto (KUT). These four patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for dysthymic disorder with easy fatigability and sleeplessness, but did not fulfill the criteria for major depressive disorder. Treatment with KUT relieved depressive status, fatigue and sleeplessness in these patients. As a result, their QOL (quality of life) was considerably improved. KUT may be useful as an additional or alternative treatment for dysthymia, especially in the field of primary health care.

Serum levels of anti-cyclic citrullinated peptide antibodies are associated with a beneficial response to traditional herbal medicine (Kampo) in rheumatoid arthritis.

This study investigated the usefulness of biomarkers indicating beneficial response to traditional herbal medicine (THM) among patients with rheumatoid arthritis (RA). We assessed 34 RA patients who received keishinieppiittokaryojutsubu (KER), one of the representative THM. The observational term was 12 months, and we calculated the disease activity score of 28 joints every 3 months and evaluated the response to KER using European League Against Rheumatism (EULAR) response criteria. Additionally, serum levels of anti-cyclic citrullinated peptide antibody (ACPA) were measured by enzyme-linked immunosorbent assay at the baseline and after 6 and 12 months of the treatment with KER. As a result, 14 (41.2%) of the 34 patients were defined as responders, 13 as non-responders and 7 as out of assessment after 6 months, respectively. Pretreatment levels of serum ACPA were lower in KER responders than in non-responders (P = 0.042), although other univariate analysis did not show any significant differences in baseline clinical measures between the two groups. Furthermore, responders to KER showed a significant decrease in the serum levels of ACPA. These findings suggest that pretreatment serum levels of ACPA are a useful predictor of a good response to treatment with KER. Furthermore, a decrease in serum levels of ACPA may be an adjunctive indicator in predicting the efficacy of this kind of treatment.

Pueraria mirifica phytoestrogens improve dyslipidemia in postmenopausal women probably by activating estrogen receptor subtypes.

Impaired lipid metabolism is an important health problem in postmenopausal women with insufficient estrogens, because dyslipidemia is a risk factor for development of atherosclerosis and the incidence of cardiovascular disease markedly increases after menopause. Pueraria mirifica (PM), a Thai herb, has been noticed as a source of phytoestrogens, estrogen-mimicking plant compounds. However, the clinical effects of PM on lipid metabolism and the underlying molecular mechanisms remain undetermined. Therefore, we examined the effects of PM on serum lipid parameters in a randomized, double-blind, placebo-controlled clinical trial. Nineteen postmenopausal women were randomly assigned to receive oral administration of PM powder or placebo. After 2 months of treatment, the PM group showed a significant increase in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-1 (34% and 40%, respectively), and a significant decrease in low-density lipoprotein (LDL) cholesterol and apo B (17% and 9%, respectively), compared with baseline measurements. Moreover, significant decreases were observed in the ratios of LDL cholesterol to HDL cholesterol (37%) and apo B to apo A-1 (35%). Next, we determined the effects of PM phytoestrogens on the activation of estrogen receptor (ER)-mediated transactivation by transient expression assays of a reporter gene in cultured cells. Among PM phytoestrogens, miroestrol and coumestrol enhanced both ERalpha- and ERbeta-mediated transactivation, whereas other phytoestrogens, including daidzein and genistein, preferentially enhanced ERbeta-mediated transactivation. In conclusion, PM has a beneficial effect on lipid metabolism in postmenopausal women, which may result from the activation of gene transcription through selective binding of phytoestrogens to ERalpha and ERbeta.

The effect of traditional herbal medicines; Uyakujunkisan on trigeminal neuralgia in an elderly patient--a case report and literature review.

This report describes the successful treatment of a 72-year-old female with refractory trigeminal neuralgia using a traditional herbal medicine, Uyakujunkisan (UJS). The case report is of a 65-year-old female who developed right-sided trigeminal neuralgia that was partially responsive to carbamazepine (CZ). The pain gradually increased in intensity and at 72 years of age she presented for herbal medicine therapy. Cranial MRI demonstrated vascular compression of the right trigeminal nerve at the cerebellopontine angle by the anterior inferior cerebellar artery. Although microvascular decompression was considered, UJS was prescribed after informed consent. After 3 weeks of treatment with UJS, dramatic improvement of symptoms permitted a decrease in CZ dose.

Efficacy of Nyoshinsan/TJ-67, a traditional herbal medicine, for menopausal symtoms following surgery and adjuvant chemotherapy for premenopausal breast cancer.

We report a 39-year-old woman with premenopausal breast cancer who developed estrogen-deficiency symptoms associated with chemotherapy-related amenorrhea, and was successfully treated with Nyoshinsan/TJ-67, a Japanese traditional herbal medicine (Kampo). Six other breast cancer survivors with menopausal symptoms were also treated with Nyoshinsan/TJ-67, and five of the six patients showed noticeable improvement without adverse effects. Managing estrogen-deficiency symptoms in breast cancer survivors is still problematic, and Nyoshinsan/TJ-67 may be a useful and safe agent for such symptoms in these patients.

[Quality evaluation of magnesium oxide tablets using acid neutralization test and dissolution test].

For the purpose of quality evaluation of commercially available magnesium oxide (MgO) tablets, we studied their acid neutralization and dissolution behaviors. The dissolution test was carried out by the paddle method in 1st fluid (pH 1.2). The dissolution amount of MgO from tablets was determined by chelatometric titration. The medium pH was periodically measured. The neutralization reaction in 750 ml of 1st fluid was markedly different between two kinds of commercial tablets. The pH of medium including Magmit tablet reached 8.9 and the dissolution rate of MgO was 81.1% after 20 min. Contrariwise, the final pH of medium including Maglax tablet was 2.5 and the dissolution rate of MgO was 77.1% after 60 min. These results indicate that the dissolution rate of MgO from tablets should be >81.1% to obtain significant acid neutralization action.

[Effects of copper supplementation on lipid profiles in elderly patients with copper deficiency].

AIM: The purpose of this study was to examine the effects of copper supplementation on lipid profiles in elderly patients with copper deficiency. METHODS: Nine long-term bed-ridden, patients (5 men and 4 women, mean age 83.3+/-8.7 years old) with severe copper deficiency, who had a serum copper of 15 microg/dL or less (normal range 70-140 microg/dL), had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Copper, ceruloplasmin, total cholesterol (TC), triacylglycerides (TG), HDL-cholesterol (HDL-C), c-reactive protein (CRP), creatinine (Cr), zinc (Zn) and albumin (Alb) in the serum were measured before, 4 weeks and 12 weeks after copper supplementation. RESULTS: Serum copper and ceruloplasmin were significantly increased at 4 weeks after copper supplementation. TG was significantly increased at 4 weeks after copper supplementation, but at 12 weeks the increase of TG was not significant. TC, HDL-C, CRP, Cr, Zn and Alb were not changed by copper supplementation. CONCLUSION: TG was transiently increased by copper supplementation in elderly patients with copper deficiency. TC and HDL-C were not changed by copper supplementation.

Insights to clinical use of serial determination in titers of cyclic citrullinated peptide autoantibodies.

Anti-cyclic citrullinated peptide (CCP) antibody is a useful marker for the diagnosis and prognosis of rheumatoid arthritis (RA). Recently, clinical significance of follow-up in anti-CCP antibody titer has been pointed out. Thus, we investigated the serial determination in anti-CCP antibodies titer in RA patients. Six patients with RA, who were followed up for longer than 5 years, were assessed in anti-CCP antibodies and radiographs (Larsen score). Anti-CCP antibodies in frozen sera were measured using ELISA. As a result, 6 patients with RA were divided into two groups: one possessed high titers without variation, and the other was without high titers. Joint damage progressed during observation in 2 out of 3 patients with high anti-CCP titers in a retrospective assessment. In contrast, the RA patient, whose anti-CCP titer decreases although it had been high titer at baseline, did not show increase in the Larsen score. These findings suggest that it might be necessary to analyze changes in anti-CCP to predict the prognosis of joint destruction.