Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
Volume 14, Issue 5
Displaying 1-10 of 10 articles from this issue
Review
  • Yohei Okawa
    Article type: review-article
    2020 Volume 14 Issue 5 Pages 213-217
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    Functional gastrointestinal disease is one in which gastrointestinal symptoms persist chronically or recurrently. This disease is challenging because it does not have an organic cause that can be detected in routine laboratory tests. Among them, the symptoms of irritable bowel syndrome (IBS), which is a type of functional gastrointestinal tract disease, include abnormal bowel movements associated with abdominal pain. However, no specific test has been established to definitively diagnose these diseases, including IBS. The traditional Rome IV diagnostic criteria are used to diagnose IBS by assessing subjective symptoms. However, it has been suggested that IBS is difficult to diagnose using the Rome IV criteria among unconscious or cognitively impaired patients. It is recommended that abdominal ultrasonography be used to assess IBS with diarrhea and constipation. Previously, constipation among elderly people who ingested food orally was objectively assessed by ultrasound, and colonic fecal distribution patterns were classified in constipated patients and healthy people. Objective visualization of the large intestine was used to assess constipation. Therefore, fecal retention among adults and elderly individuals was reported using ultrasonography. It was suggested that stool retention could be confirmed by observing the hyperechoic region of the rectum. Strong hyperechoic regions with acoustic shadows in the rectum indicate the presence of hard stools, thus enabling medical workers to identify constipation. In the future, ultrasonography may be useful for diagnosing IBS in unconscious patients or those with cognitive decline.

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Original Article
  • Junkichi Kanda, Megumi Furukawa, Nobuo Izumo, Taketoshi Shimakura, Nor ...
    Article type: research-article
    2020 Volume 14 Issue 5 Pages 218-225
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    Recently, it has been suggested that glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), which play important roles in the homeostasis of glucose metabolism, could be involved in the regulation of bone metabolism. Inhibitors of dipeptidyl peptidase 4 (DPP-4), an enzyme that degrades GIP and GLP-1, are widely used clinically as a therapeutic agent for diabetes. However, the effects of DPP-4 inhibitors on bone metabolism remain unclear. In this study, we investigated the effects of linagliptin, a DPP-4 inhibitor, on bone fragility induced by type 2 diabetes mellitus (T2DM). Non-diabetic mice were used as controls, and T2DM mice were administered linagliptin orally on a daily basis for 12 weeks. In T2DM mice, decreased bone mineral density was observed in the lower limb bones along with low serum osteocalcin levels and high serum tartrate-resistant acid phosphatase-5b (TRAP) levels. In contrast, the decreased serum osteocalcin levels and increased serum TRAP levels observed in T2DM mice were significantly suppressed after the administration of linagliptin 30 mg/kg. Bone histomorphometric analysis revealed a reduced osteoid volume and osteoblast surface with an increase in the eroded surface and number of osteoclasts in T2DM mice. This decreased bone formation and increased bone resorption observed in the T2DM mice were suppressed and trabecular bone volume increased following the administration of 30 mg/kg linagliptin. Collectively, these findings suggest that linagliptin may improve the microstructure of trabecular bone by inhibiting both a decrease in bone formation and an increase in bone resorption induced by T2DM.

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  • Farhan Fazal, Nitin Gupta, Ankit Mittal, Animesh Ray
    Article type: research-article
    2020 Volume 14 Issue 5 Pages 226-231
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    Diagnosis and management of hemophagocytic lymphohistiocytosis (HLH) in patients with human immunodeficiency virus (HIV) infection are scarcely described in the published literature. The aim of this systematic review was to delineate the triggers of HLH in patients with HIV and understand the role of steroids in the management. We conducted a comprehensive search of English medical literature via the Medline ⁄ PubMed database using different synonyms of "HIV" AND "HLH". The review was registered in PROSPERO (CRD42018099987). The titles and abstracts of the 185 articles between January 1986 and April 2018 were reviewed. The final analysis was done from 42 articles with 52 patients. HLH was associated with malignancy in 17 patients, while infection was found in 25 patients. No cause was identified in eight patients, out of which four had acute HIV infection. Death was reported in 21 patients. Presence of either malignancy (p = 0.051) or opportunistic infection (p = 0.69) was not associated with increased chances of death by univariate analysis. A total of 26 patients were treated with steroids, while etoposide was used in only four patients. Administration of steroids as a treatment of HLH was associated with more chances of death (p = 0.048). Malignancy and Opportunistic infections are important triggers for HLH in patients with HIV. Acute HIV by itself can act as a trigger for HLH. Evidence on the use of steroids as a treatment of HLH in patients with HIV is not convincing.

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  • Ayako Hayashi, Hidenori Oguchi, Yumi Kozawa, Yukiko Ban, Junji Shinoda ...
    Article type: research-article
    2020 Volume 14 Issue 5 Pages 232-238
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    The objective of this study was to explore the factors associated symptoms of depression among pregnant women with gestational diabetes mellitus (GDM) in Japan. This cross-sectional study was conducted at a hospital in Toyota, Japan, from January 2015 to June 2016. Pregnant women who visited the hospital and were diagnosed with GDM in the second trimester were enrolled. We analyzed depression symptoms using the Centers for Epidemiological Studies Depression Scale (CES-D) and considered related factors of depression symptoms, such as dietary intake and daily walking. Dietary intake during the past month was assessed using a brief self-administered diet history questionnaire, and daily walking was assessed using an accelerometer. The prevalence rate for GDM was 8.8%, and 25 pregnant women with GDM were analyzed. The CES-D was not significantly correlated with pre-pregnancy BMI, postprandial plasma glucose, hemoglobin A1c, and the number of steps walked. In contrast, a significant negative correlation was observed between the CES-D score and intake of fish with bones, simmered fish, pickles, green leaves, mushrooms, and green tea. Furthermore, a significant positive correlation was found between Coke® and CES-D scores. For nutrient intake, a significant negative correlation was found between the CES-D score and vitamin K, folate, and β-carotene levels. The present study suggests that depression symptoms among pregnant women with GDM in the second trimester may be associated with diet.

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Brief Report
  • Maryam Mohsenikia, Shima Rafiee, Laya Seyede Rozei, Alireza Ebrahimi, ...
    Article type: brief-report
    2020 Volume 14 Issue 5 Pages 239-242
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    Althaea officinalis (AO) is reported to have the ability to activate fibroblasts as well as anti-inflammatory and antioxidative properties. Herein, we investigated the effects of this herbal medicine on wound healing in rat models by using stereological methods. In this experiment, 48 male Wistar rats were divided into four groups randomly (n = 12): the control group with no treatment, the gel-base treated group, 5% and 10% AO-gel treated groups. The treatments were administered every 24 hours. Wound closure rate, volume densities of collagen bundles, hair follicles, and vessels, vessel's length density and mean diameter, and fibroblast populations were estimated. Fibroblast populations, hair follicles, and mean diameter of vessels in the dermis of AO-treated groups were noticeably higher than those of control and base groups. Also, collagen bundles synthesis was significantly higher in the AO10%-treated group compared to the control and base groups. According to our research and previous studies, AO has the potential to be considered as an alternative medicine in wound healing treatment; however, further clinical investigations are suggested.

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  • Yan Liu, Dongdong Zhang, Rongrong Gao, Xiaochun Zhang, Xuefei Yang, Ch ...
    Article type: brief-report
    2020 Volume 14 Issue 5 Pages 243-248
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    The bark of Cinnamomum bejolghota (Buch.-Ham.) Sweet (C. bejolghota) is widely used as medicine to treat bacterial diarrhea in Myanmar. We previously reported that the bark extract of C. bejolghota significantly inhibited secretion effector proteins of the type three secretion system (T3SS) in Salmonella. This study is designed to investigate the anti-virulence potential of the C. bejolghota bark extract against Salmonella Typhimuriumin in in vivo and in vitro experiments. The results suggested that the polar fraction Fr.M1 inhibited the secretion of effector proteins SipA, SipB, SipC and SipD without affecting bacteria growth and the translocation of SipC into MDA-MB-231 cells. In addition, Fr.M1 alleviated inflammatory symptoms of mice in Salmonella-infected mouse model. Overall, the results provide evidence for medicinal usage of C. bejolghota bark to treat diarrhea in Myanmar.

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Case Report
  • Sagnik Biswas, Sujay Halkur Shankar, Animesh Ray, Prashant Ramteke
    Article type: case-report
    2020 Volume 14 Issue 5 Pages 249-251
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    T-cell acute lymphoblastic lymphoma is a common hematological malignancy of childhood. It can involve the bone marrow, blood, or tissues like the thymus, lymph nodes as well as extra-nodal sites. Two aspects of the disease make early diagnosis critical - the clinically aggressive nature of the neoplasm, and availability of effective chemotherapy against the disease. Diagnosis is largely based on clinical suspicion and confirmation by histopathological examination of the affected tissue. However, biopsy results may not always be helpful in establishing the diagnosis. We describe the case of an 18-year old patient presenting with fever and an anterior mediastinal mass suspected to have a T-cell lymphoma where an initial biopsy from the mass had features of a thymoma. The patient was kept in close follow up for 2 months when there was a recurrence of symptoms and a repeat bone marrow evaluation revealed a T-cell lymphoma.

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  • Chan Hum Park, Tsutomu Kitazawa, Akihiro Futamura, Hiroshi Hirana, Mas ...
    Article type: case-report
    2020 Volume 14 Issue 5 Pages 252-255
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    We report a case of a 65-year-old patient with hypertension, dyslipidemia, type 2 diabetes, chronic kidney disease, and hyperuricemia, who showed an improvement in lifestyle-induced metabolic syndrome on the administration of 7.5 g of Kangen-karyu extract per day for 6 months. The levels of serum total cholesterol, low-density lipoprotein-cholesterol, and triglycerides were decreased. The systolic/diastolic blood pressure was decreased following administration. Other parameters such as estimated glomerular filtration rate, creatinine, uric acid, aspartate transaminase, alanine aminotransferase, γ-glutamyl transpeptidase, and creatine phosphokinase were improved by the administration of Kangen-karyu extract. At that time, the physical and subjective symptoms had partially disappeared. We present evidence supporting the use of Kangen-karyu extract against metabolic syndrome.

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Communication
  • Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
    2020 Volume 14 Issue 5 Pages 256-258
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    In the ongoing coronavirus diseases-2019 (COVID-19) crisis that caused immense suffering and deaths, the choice of therapy for the prevention and life-saving conditions must be based on sound scientific evidence. Uncertainty and apprehension are exacerbated in people using angiotensin-converting enzyme (ACE) inhibitors to control their comorbidities such as hypertension and diabetes. These drugs are reported to result in unfavorable outcome as they tend to increase the levels of ACE2 which mediates the entry of SARS-CoV-2. Amiloride, a prototypic inhibitor of epithelial sodium channels (ENaC) can be an ideal candidate for COVID-19 patients, given its ACE reducing and cytosolic pH increasing effects. Moreover, its potassium-sparing and anti-epileptic activities make it a promising alternative or a combinatorial agent.

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  • Itsuro Kazama
    2020 Volume 14 Issue 5 Pages 259-261
    Published: October 31, 2020
    Released on J-STAGE: November 04, 2020
    Advance online publication: October 29, 2020
    JOURNAL FREE ACCESS

    Regardless of the severity of coronavirus disease 2019 (COVID-19), a high proportion of patients struggle with persistent respiratory or systemic symptoms after recovery. This is called "postCOVID syndrome", for which pulmonary fibrosis is one of the pathogenesis. Besides T-lymphocytes and macrophages, mast cells also contribute to the development of cytokine storm and thus stimulate the activity of fibroblasts. Additionally, by the exocytotic release of fibroblast-activating factors, mast cells directly facilitate the progression of pulmonary fibrosis. In our previous basic studies, anti-allergic drugs (olopatadine, ketotifen), antibiotics (clarithromycin) and corticosteroids (hydrocortisone, dexamethasone) inhibited the process of exocytosis and showed their potency as highly effective mast cell stabilizers. Given such pharmacological properties of these commonly used drugs, they may be useful in the treatment of post-COVID-19 pulmonary fibrosis and in relieving the symptoms of post-COVID syndrome.

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