Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
16 巻, 5 号
選択された号の論文の10件中1~10を表示しています
Original Article
  • Atsushi Miyashita, Kazuhisa Sekimizu, Chikara Kaito
    原稿種別: research-article
    2022 年 16 巻 5 号 p. 204-209
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/09/06
    ジャーナル フリー

    Male crickets emit acoustic signals (i.e., songs) by chirping using their forewings. Although the mechanisms and adaptive functions of these songs are well studied, knowledge about how songs develop within a generation is relatively scarce. Our previous work demonstrated a stable peak frequency at 5.7 kHz in the calling songs recorded from mature adult male crickets (Gryllus bimaculatus). In the present study, we monitored changes in the frequency component over time from the sexual maturity stage (early adult stage). We recorded 300 calling songs from a pool of 122 adults. The peak frequency distribution was lower and unstable (i.e., greater coefficient of variance) in the early adult stage. The mean peak frequency was 4.9 kHz on day 3, but gradually converged to 5.8 kHz over the 2-week adult stage. Immature adult males (emitting immature songs) produced an appropriately tuned song with a peak frequency of 5.8 kHz in an environment of 80% helium and 20% oxygen. These results suggest that the frequency component of the calling song is acquired during the early to mid-adult stage, and may be related to sexual maturation in males. Findings from the helium substitution experiment revealed that physical resistance from surrounding gas molecules negatively affect the stability of male singing, and that muscle development and forewing hardening may contribute to the maturation of singing, suggesting that females may adaptively select sexually mature males based on song traits.

  • Mitsuru Nozawa, Ako Gannichida, Yuko Wada, Miyuki Kumazawa, Fumiyoshi ...
    原稿種別: research-article
    2022 年 16 巻 5 号 p. 210-216
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/20
    ジャーナル フリー

    The aim of this study was to evaluate patient satisfaction and usability scores of different tape treatments and examine the scores in relation to the mechanical characteristics of the tape formulation. A questionnaire for the assessment of comfort level and satisfaction with two brand-name (Naboal, Voltaren) and four generic tapes (Yutoku, Teikoku, Rakool, Towa) containing sodium diclofenac was developed and then applied to 12 healthy volunteers. Results showed that Voltaren was difficult to apply to the skin and easier to peel off the skin than Naboal (p < 0.01). Moreover, Rakool was easier to peel than Naboal (p < 0.05). The mechanically measured peeling force was associated with pain during peeling off (r = –0.65), and the measured value of bending rigidity was associated with ease of peeling off (r = –0.97). The knowledge obtained regarding the influence of pharmaceutical properties on the degree of satisfaction with and usability of different tape formulations may be useful for supporting the selection of generic tapes tailored to individual needs or pharmacist preferences, and thus improve treatment adherence and clinical outcomes.

  • Kenzo Koyama
    原稿種別: research-article
    2022 年 16 巻 5 号 p. 217-224
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/13
    ジャーナル フリー

    The purpose of this study is to compare the efficacy and safety of pharmacotherapies for chronic pain due to osteoarthritis (OA) between a group with duloxetine (DLX) and S-flurbiprofen plaster (SFPP) (the SFPP group) and a group with DLX and conventional non-steroidal anti-inflammatory drugs (NSAIDs) (the control group). The subjects were 49 patients (17 men and 32 women). The evaluation of factors associated with treatment termination due to symptoms improvement showed that significantly more women terminated treatment than did men, and significantly more members of the SFPP group terminated treatment than did members of the control group. The visual analogue scale (VAS) score in the SFPP group was significantly improved from 6.6 ± 1.7 before treatment to 3.6 ± 2.1 one month later and showed significant difference until nine months later. The VAS score in the control group was significantly improved from 6.7 ± 1.9 to 4.1 ± 2.8 one month later. The VAS score improvement rate was significantly higher in the SFPP group than in the control group, suggesting that the DLX-SFPP combination had higher efficacy than the DLX-conventional NSAIDs combination. The incidence of adverse drug reactions was 55% in the SFPP group, which is not significantly different from 50% incidence in the control group. The treatment discontinuation rate due to adverse drug reactions, however, was 60% in the control group and 19% in the SFPP group. It was suggested that the efficacy and safety of the DLX-SFPP combination for chronic pain due to OA are equal to or higher than that of the DLX-conventional NSAIDs combination.

  • Junko Terada-Hirashima, Manabu Suzuki, Yoshie Tsujimoto, Yoichiro Hama ...
    原稿種別: research-article
    2022 年 16 巻 5 号 p. 225-232
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/26
    ジャーナル フリー

    The aim of this study was to determine the efficacy and safety of ciclesonide in the treatment of novel coronavirus disease 2019 (COVID-19) as gauged by pneumonia progression. This multi-center, open-label randomized trial was conducted with patients recruited from 22 hospitals across Japan. Participants were patients admitted with mild or asymptomatic COVID-19 without signs of pneumonia on chest X-rays. Asymptomatic participants were diagnosed after identification through contact tracing. Trial participants were randomized to either the ciclesonide or control arm. Participants in the treatment arm were administered 400 µg of ciclesonide three times a day over seven consecutive days. The primary endpoint was exacerbated pneumonia within seven days. Secondary outcomes were changes in clinical findings, laboratory findings, and changes over time in the amount of the viral genome. In the treatment group, 16 patients (39.0%) were classified as having exacerbated pneumonia compared to 9 (18.8%) in the control group. The risk ratio (RR) was 2.08 (95% confidence interval (CI): 1.15-3.75), indicating a worsening of pneumonia in the ciclesonide group. Significant differences were noted in participants with a fever on admission (RR: 2.62, 90% CI: 1.17-5.85, 95% CI: 1.00-6.82) and individuals 60 years of age or older (RR: 8.80, 90% CI: 1.76-44.06, 95% CI: 1.29-59.99). The current results indicated that ciclesonide exacerbates signs of pneumonia on images in individuals with mild or asymptomatic symptoms of COVID-19 without worsening clinical symptoms.

  • Yoshikazu Sawaguchi, Zuojun Wang, Hiroyuki Yamamoto, Norio Nakata
    原稿種別: research-article
    2022 年 16 巻 5 号 p. 233-239
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/09
    ジャーナル フリー

    For the treatment of acute ischemic stroke, the current standard of care is thrombolysis by the administration of intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA). Although this approach is proven to be effective, reocclusion within 24 hours occurs in about 20% of patients who receive recanalization by rt-PA. In addition, the administration of anticoagulants within 24 hours after IV rt-PA increases the risk of intracranial hemorrhage; therefore, treatment with anticoagulants is contraindicated in this population. To address the need for an approach to sustain the effects of thrombolysis prevent blood vessel reocclusion without the use of anticoagulants, this study proposes a novel method using a low-intensity ultrasound (US) irradiation. An in vitro thrombus-growth model, in a latex rubber container was developed to study the effect of thrombus-growth suppression by US irradiation at 500 kHz in a 37°C water bath. The US acoustic intensity was set at or below 0.72 W/cm2, which is the maximum allowed for noninvasive acoustic irradiation. Low-intensity US irradiation of the thrombus-growth model resulted in a remarkable suppression of thrombus growth (100.22 ± 10.1 mg vs. 50.22 ± 5.3 mg, p < 0.0001), and the clot-growth inhibition depended logarithmically on acoustic intensity. Thrombus growth can be suppressed by low-intensity US irradiation, opening a new way to combat vascular reocclusion after rt-PA treatment of acute ischemic stroke.

Brief Report
  • Yoko Iio, Yukihiro Mori, Masato Tsurudome, Morihiro Ito
    原稿種別: brief-report
    2022 年 16 巻 5 号 p. 240-244
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/07
    ジャーナル フリー

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease (COVID-19), is found primarily in the respiratory tract secretions of infected individuals with one of the main routes of transmission being direct or indirect contact. In this study, using fluorescent paint, we evaluated the spread of contaminants while playing catch with a baseball. Fluorescent paint was applied to the right hand of a right-handed baseball player who then engaged in playing catch with 10 other right-handed players (partners) for 5 min each. The fluorescent paint was detected on the right hands (inside) and gloves (inside) of all the 10 partners as well as on the ball; in some partners it was also detected on the back of the right hands or the back of the gloves. However, except for their right hands, fluorescent paint was not detected on the surface of the bodies of the partners. These observations indicated that the fluorescent paint (mimicking virus-containing contaminants) on the hand spreads very efficiently from person to person during the throwing and catching of a baseball, suggesting that a thorough and frequent disinfection of the hands and equipment is important in the prevention of infections that may occur while playing baseball.

  • Ririka Fujimura, Ayano Asada, Misato Aizawa, Itsuro Kazama
    原稿種別: brief-report
    2022 年 16 巻 5 号 p. 245-250
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/19
    ジャーナル フリー

    Cetirizine, a second-generation antihistamine, and diphenhydramine, a first-generation antihistamine, are among the most widely used anti-allergic drugs. In addition to longer duration of action and less incidence of sedative side effects, recent clinical studies also indicate a higher potency of cetirizine than diphenhydramine in the treatment or prevention of allergic disorders. In the present study, using the differential-interference contrast (DIC) microscopy, we examined the effects of cetirizine and diphenhydramine (1 μM to 1 mM) on the degranulation from rat peritoneal mast cells. Using fluorescence imaging of a water-soluble dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. At relatively higher concentrations (100 μM, 1 mM), both cetirizine and diphenhydramine significantly reduced the numbers of degranulating mast cells. Of note, at 1 mM, cetirizine more markedly reduced the number than diphenhydramine, almost entirely suppressing the degranulation of mast cells. Additionally, 1 mM cetirizine and levocetirizine, another second-generation antihistamine, almost totally inhibited the process of exocytosis in mast cells and washed out the trapping of the lucifer yellow on the cell surface, while diphenhydramine and chlorpheniramine, another first-generation antihistamine, did not. This study provided in vitro evidence for the first time that cetirizine more potently inhibited the process of exocytosis in mast cells than diphenhydramine, indicating its higher potency as a mast cell-stabilizer. Such mast cell-stabilizing property of cetirizine could be ascribed to its counteracting effect on the plasma membrane deformation in degranulating mast cells.

Letter
  • Daichi Miyagi, Osamu Nakahara, Yuki Ohya, Kunitaka Kuramoto, Akira Tsu ...
    原稿種別: letter
    2022 年 16 巻 5 号 p. 251-253
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/07
    ジャーナル フリー

    Patients with liver cirrhosis are at increased risk of various visceral hernia because of persistent ascites and tissue fragility. Here we report successful treatment in a patient with pararectal hernia due to liver cirrhosis by a less invasive approach via para-anal region. The patient was a 73-year-old woman with a history of chronic hepatitis B that had been untreated for at least 20 years. At the age of 68 years, she was referred to our hospital for treatment of persistent ascites and thrombocytopenia due to advanced liver cirrhosis. Neither diuretics nor cell-free and concentrated ascites reinfusion therapy could decrease the ascites. She needed repeated paracentesis. She was referred to the surgical department due to the painful swelling of the left buttock which was diagnosed as the pararectal hernia. The welling was huge enough with the erosion of the covering skin. Surgery was planned in view of concern about the possible rupture of the hernia. Due to the massive ascites with the advanced liver cirrhosis, we were reluctant to do the laparotomic approach, and simple closure of the hernial orifice via direct approach from the cutaneous side was planned and performed. The patient was fortunately discharged seven days after the operation without any complications. One year later, there has been no recurrence of the hernia. Even in cases with massive ascites, direct simple closure of the hernia by percutaneous approach may be one of the options for the treatment of the pararectal hernia in case of urgent situation.

  • Saori Yamada-Kanazawa, Masatoshi Jinnin, Satoshi Fukushima
    原稿種別: letter
    2022 年 16 巻 5 号 p. 254-255
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/07
    ジャーナル フリー

    Nevus of Ota is a dermal melanocytosis that consists of blue-brown spots, patches and plaques along the distribution of the first and second branches of trigeminal nerve. The efficacy of Q-switched ruby laser treatment against nevus of Ota on dark skin has not been described. The present case, a 2-month-old Indonesian girl, showed rare auricular involvement. Because ear has complicated steric structure, whose skin is sensitive and thin, pain and inflammatory reaction are inevitable. We discussed the difficulty of laser treatments on auricular lesions.

  • Haruka Kuriyama, Toshihiro Kimura, Satoru Mizuhashi, Yuki Nishimura, H ...
    原稿種別: letter
    2022 年 16 巻 5 号 p. 256-257
    発行日: 2022/10/31
    公開日: 2022/11/20
    [早期公開] 公開日: 2022/10/23
    ジャーナル フリー

    Combination therapy with BRAF and MEK inhibitors (BRAF/MEKi) has shown significantly prolonged progression-free survival (PFS) and overall survival (OS) for BRAF mutated melanoma. Over 90% of the activating mutations are BRAFV600E or BRAFV600K changes. There are no reports of BRAFV600R in Japanese patients with melanoma. The third most common BRAF mutation is BRAFV600R. In this case, we detected the BRAFV600R mutation with FoundationOne CDx in a Japanese patient with melanoma.. The patient was treated with BRAF/MEKi and maintained stable disease status for 1 year.

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