Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
Volume 13, Issue 3
Displaying 1-10 of 10 articles from this issue
Original Articles
  • Nobuo Oishi, Hiroki Iwata, Noriko Kobayashi, Kazuko Fujimoto, Katsunor ...
    Article type: research-article
    2019 Volume 13 Issue 3 Pages 128-132
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    Advance online publication: June 14, 2019
    JOURNAL FREE ACCESS

    Atopic dermatitis (AD) is a common chronic, pruritic inflammatory skin condition. AD is most commonly treated with topical corticosteroids, and the finger-tip unit (FTU) should be used as a guideline for the amount to be used per application. In this study, we investigated the adequacy of pharmacists' instructions on the amount of topical steroids to be applied and the way in which they enhance the effect of pharmaceutical interventions. A self- administered anonymous questionnaire was distributed using QLifePro to 300 pharmacists working in insurance pharmacies that filled at least one dermatologist's prescription per month on average in Japan. Out of 300 pharmacists, 196 (65.3%) recognized the Japanese Dermatological Association's 2016 guidelines for the treatment AD, 107 (35.6%) gave instructions using the FTU as an index of external dose of topical steroids, 157 (52.3%) explained the amount of steroid application using an index other than FTU, and 61 (38.9% of 157) had inadequately instructed AD patients to apply steroids as a thin layer. Pharmacists who had read the guidelines for AD tended to give an appropriate instruction using FTU as an index of external dose of topical steroids (p < 0.001). We found that many pharmacists in pharmacies gave inadequate instructions on the amount of topical steroid application and deviated from the guidelines for AD, mainly because of inadequate knowledge of the guidelines.

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  • Masaki Ishii, Yasuhiko Matsumoto, Toshiaki Katada, Kazuhisa Sekimizu
    Article type: research-article
    2019 Volume 13 Issue 3 Pages 133-136
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    JOURNAL FREE ACCESS

    Using a silkworm evaluation system, we previously evaluated various substances that suppress postprandial hyperglycemia. Enterococcus faecalis YM0831, a lactic acid bacterium that inhibits glucose uptake by the human intestinal Caco-2 cell line, exhibited hyperglycemia-suppressing effects in the silkworm system. In the present study, we found that Kothala himbutu (Salacia reticulata) extract, a traditional medicine containing α-glucosidase inhibitors, suppressed sucrose-induced hyperglycemia in the silkworm system. Moreover, combined oral administration of lactic acid bacteria YM0831 with Kothala himbutu extract had stronger suppressive effects on sucrose-induced hyperglycemia than single administration of either component. These findings suggest that the silkworm system provides a simple way to evaluate the effects of supplements on the suppression of blood glucose level induced by sucrose ingestion.

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  • Takeshi Seta, Yoshimitsu Takahashi, Yukitaka Yamashita, Takeo Nakayama
    Article type: research-article
    2019 Volume 13 Issue 3 Pages 137-144
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    JOURNAL FREE ACCESS

    Existing evidence suggests that protease inhibitors (PIs) used to prevent or treat pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) are ineffective, and their use is not recommended by clinical practice guidelines. However, in Japan, PIs are administered with the aim to prevent or treat post-ERCP pancreatitis. This study aimed to clarify the gap between guideline recommendations and contents of practice. We used the health insurance claims database of Japan Medical Data Center. Among patients who had undergone ERCP, those with acute pancreatitis or post-ERCP pancreatitis recorded in claims as disease names were defined as post-ERCP pancreatitis patients. The study period was divided into three terms according to the date of publication of clinical practice guidelines for acute pancreatitis. Among 2,945 patients who had undergone ERCP, 2,847 were eligible for analysis. Of these, 1,375 (48.3%) patients had claims with pancreatitis recorded as the disease name; PIs were prescribed to 1,238 (90.0%). Rates of prescription of PIs were 72.3% in 2005-07, 70.9% in 2008-09, and 83.6% in 2010-15, showing a significant increase (p < 0.001). In conclusion, PIs are administered in clinical practice in Japan for the purpose of preventing or treating pancreatitis, with an increasing trend in prescription in recent years.

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  • Daniel Don Nwibo, Suresh Panthee, Hiroshi Hamamoto, Kazuhisa Sekimizu
    Article type: research-article
    2019 Volume 13 Issue 3 Pages 145-149
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    Advance online publication: June 23, 2019
    JOURNAL FREE ACCESS

    Antibiotic resistance crisis occasioned by sporadic appearance of multi-drug resistance (MDR) in human pathogens to clinically applied antimicrobials is a serious threat to global health. In this study, we investigated the drug resistant phenotype of Gram-positive cocci isolates from environment. Staphylococcus capitis and Staphylococcus haemolyticus colonies were isolated on mannitol-salt agar plates supplemented with tetracycline. Antibiotic susceptibility profile of the isolates via minimum inhibitory concentration (MIC) determination was examined. Isolates showed decreased sensitivity to clinically applied antimicrobial agents: tetracycline, kanamycin, erythromycin, norfloxacin, teicoplanin, and ampicillin. Genomic analysis demonstrated the presence of multiple antibiotic resistant genes in these bacteria, suggesting the origin of the multiple antimicrobials resistant phenotype. Tetracycline resistance of these isolates was transduced to Staphylococcus aureus-RN4220 strain. These findings indicate the presence of multiple antimicrobials resistant S. capitis and S. haemolyticus strain in a non-hospital setting. Moreover, the presence of plethora of genes responsible for MDR suggest that these strains could present potential threat to human health by serving as reservoir for lateral transference of antimicrobial resistance conferring foreign genetic elements to other clinically relevant pathogens.

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  • Mitsuru Nozawa, Miho Goto, Yuko Wada, Kayo Yotsukura, Ako Gannichida, ...
    Article type: research-article
    2019 Volume 13 Issue 3 Pages 150-156
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    Advance online publication: June 28, 2019
    JOURNAL FREE ACCESS

    With respect to diclofenac sodium-containing tape preparations of nonsteroidal antiphlogistic drug, we compared the pharmaceutical properties (pH, elongatedness, water-vapor permeability, adhesive force, and peeling-force) of 11 medicinal drugs (2 brand-name and 9 generic drugs) to obtain evidence for product selection in line with the needs of the patient. The elongatedness of the generic drugs Teikoku (1.39), Yutoku (1.40), and Nippon-zoki (1.43) were significantly higher than the brand-name drug Voltaren® (1.22). The adhesive force was measured using the probe tack test and the inclined ball tack test. The probe tack test results of Naboal® (6.8 N/cm2), Teikoku (6.1 N/cm2), Yutoku (5.9 N/cm2), Nippon-zoki (6.2 N/cm2), and Rakool (6.2 N/cm2) were higher than that of Voltaren (2.0 N/cm2). The inclined ball tack test results of Naboal (18.0), Teikoku (24.0), Yutoku (21.5), and Nippon-zoki (22.7) were also higher than that of Voltaren (7.2). Concerning peeling-force measurement, the 90° peeling-forces of Naboal (0.95 N), Teikoku (0.96 N), Yutoku (0.94 N), and Nippon-zoki (1.01 N) were higher than that of Voltaren (0.68 N). These results show that there were marked differences in the feeling of use of each product between the brand-name and generic drugs. The pharmacist indicates the basis for selection of a preparation according to the feeling of use desired by each patient. It has become possible to recommend products suitable for each patient, which will allow pharmacists to provide products according to the needs of each patient when a brand-name drug is changed to a generic one.

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  • Eiji Kasumi, Yoshie Kuzumaki, Megumi Sadakata, Hiroyuki Kuzuoka, Norif ...
    Article type: research-article
    2019 Volume 13 Issue 3 Pages 157-163
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    JOURNAL FREE ACCESS

    Enteral nutrition is beneficial support administered as oral supplements or via tube feeding for patients with long-term inability to meet nutritional requirements orally. However, because of the high volumes administered, vomiting and gastroesophageal reflux are often encountered in patients receiving enteral nutrition. EN-P05 is a novel, highly concentrated enteral nutrition formula that was developed to reduce dosing volume and that satisfies the Japanese recommended daily allowance for most vitamins and trace elements, even in patients who require low-calorie control, such as home-care patients. However, whether EN-P05 can provide nutritional management equivalent to that provided by approved formulas has remained unknown. To investigate the nutritional effectiveness of EN-P05, we evaluated body weight gain, serum chemistry parameters, nitrogen balance, and fat absorption in 7-week-old gastrostomized rats that received either EN-P05 or OSN-001 for 2 weeks. No difference in organ or carcass weight was found between the groups. No significant between-group differences were observed in serum albumin, total protein, triglycerides, or total cholesterol, nor in nitrogen retention or fat absorption rate. No adverse effects associated with administration of EN-P05 were found. These results suggest that EN-P05 can provide the same nutritional management as approved formulas, even when administered in smaller volume.

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Case Report
  • Yutaka Sawai, Yuki Katsuya, Aya Shinozaki-Ushiku, Akiko Iwasaki, Masas ...
    Article type: case-report
    2019 Volume 13 Issue 3 Pages 164-167
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    Advance online publication: June 28, 2019
    JOURNAL FREE ACCESS

    Immune checkpoint inhibitors are associated with a wide spectrum of immune-related adverse events (irAEs) that are typically transient but are sometimes severe or even fatal. No consensus exists for the treatment of severe immune-mediated pneumonitis that is refractory to corticosteroids. Here, we report an autopsy case of pembrolizumab-induced pneumonitis that was transiently improved using infliximab. A 67-year-old male with advanced lung adenocarcinoma developed pneumonitis two weeks after a single dose of first-line pembrolizumab. The pneumonitis was refractory to corticosteroids, and the patient required mechanical ventilation. Addition of a single dose of infliximab rapidly improved the respiratory status and chest CT showed resolution of ground-glass opacities in the right upper and middle lobes. However, the patient died from re-exacerbation of pneumonitis 17 days after infliximab administration. The autopsy confirmed organizing phase diffuse alveolar damage in the right lower lobe, while the right upper lobe remained almost intact consistent with the CT findings, which is suggestive of the therapeutic effect of infliximab. The half-life of infliximab is 7-12 days, and a second dose of infliximab two weeks after the first dose is sometimes required for the treatment of gastrointestinal toxicity induced by anti-CTLA4 antibodies. Although the current guidelines do not recommend repeated administration of infliximab for immune-mediated pneumonitis, the present case suggests that repeated infliximab therapy may be beneficial in the treatment of immune-mediated pneumonitis.

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  • Yusuke Morinaga, Kouhei Nii, Kimiya Sakamoto, Ritsurou Inoue, Takafumi ...
    Article type: case-report
    2019 Volume 13 Issue 3 Pages 168-171
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    JOURNAL FREE ACCESS

    Paroxysmal sympathetic hyperactivity (PSH) is a clinical condition characterized by abnormal paroxysmal surges in sympathetic nervous system activity. PSH is known to occur after severe head injury and hypoxic encephalopathy. Cases of PSH that develop after stroke have been reported worldwide; however, PSH is not commonly reported in the field of stroke research in Japan. Some studies have suggested that gabapentin may improve the symptoms of PSH. To our knowledge, this is the first case report demonstrating the efficacy of trazodone for the treatment of PSH that developed after thalamic hemorrhage. A 45-year-old woman presented to our clinic with headache and paralysis of the left side of her body after experiencing right thalamic hemorrhage; a conservative treatment was initiated at our hospital. Immediately upon hospitalization, she developed high fever, tachycardia, tachypnea, constipation, and overactive bladder and had breathing difficulties. Blood sampling revealed elevated levels of myocardial escape enzymes; however, coronary angiography did not show any significant stenosis or occlusion. The patient's symptoms improved after the administration of trazodone. She was diagnosed with catecholamine cardiomyopathy associated with PSH after intracranial hemorrhage and was subsequently transferred to a recovery and rehabilitation hospital unit where the oral administration of trazodone continued. Prolonged PSH contributes significantly to the impairment of daily activities in patients with stroke; therefore, early diagnosis and treatment are critical. Here, we report on the efficacy of trazodone as an effective treatment option for improving clinical outcomes and reducing the stay in the stroke care unit.

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Letter
  • Qi Tang, Hongzhou Lu
    Article type: letter
    2019 Volume 13 Issue 3 Pages 172-174
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    Advance online publication: June 18, 2019
    JOURNAL FREE ACCESS

    Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) ranks eighth in the global burden of disease, making seriously threatens to global health. Given there is not yet a cure for HIV infection, antiretroviral therapy (ART) holds a key role not only in improving the prognosis of the patients, but also reducing the risk of HIV transmission. The immediate initiation of ART has been recommended in domestic and foreign policies and guidelines, yet the implementation of this strategy is not satisfactory. In developing countries and even in some developed countries, it still takes a long time for patients to go from the diagnosis of HIV infection to the acceptance of ART. Clarifying the obstacles to the implementation of immediate ART and finding strategies to cope with them have emerged as key problems in response to HIV/AIDS.

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  • Haruka Kuriyama, Ikko Kajihara, Hisashi Kanemaru, Yuki Nishimura, Tosh ...
    Article type: letter
    2019 Volume 13 Issue 3 Pages 175-176
    Published: June 30, 2019
    Released on J-STAGE: July 22, 2019
    JOURNAL FREE ACCESS

    This is the first case of an angiosarcoma patient with brain abscess, and it might be responsible for skin defect and cranial bone necrosis by surgical excision and radiation. Our patient was treated with 10 courses of triweekly paclitaxel therapy, radical radiotherapy (70 Gy), and surgical excision (2 cm margin apart from a lesion) for angiosarcoma. At two years after the operation he was diagnosed as brain abscess. Brain abscess was managed with antibiotic drugs and drainage, his clinical symptoms improved by these treatments. He achieves replace free survival without the exacerbation of angiosarcoma and brain abscess for three years.

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