Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
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Review
  • Yasuhiko Matsumoto, Saki Azami, Haruka Shiga, Tae Nagamachi, Hikari Mo ...
    Type: review-article
    2019 Volume 13 Issue 4 Pages 177-182
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    Cryptococcus neoformans, a human pathogenic fungus, infects immunocompromised humans and causes serious diseases such as cerebral meningitis. C. neoformans controls the expression of virulence factors in response to the host environment via various signal transduction pathways. Understanding the molecular mechanisms involved in C. neoformans infection will contribute to the development of methods to prevent and treat C. neoformans-related diseases. C. neoformans produces virulence factors, such as a polysaccharide capsule and melanin, to escape host immunity. Several proteins of C. neoformans are reported to regulate production of the virulence factors. In this review, on the basis of studies using gene-deficient mutants of C. neoformans and animal infection models, we outline the signal transduction pathways involved in the regulation of virulence factors.

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Original Articles
  • Kei Kikuchi, Akiko Miki, Hiroki Satoh, Noriko Iba, Rika Sato-Sakuma, H ...
    Type: research-article
    2019 Volume 13 Issue 4 Pages 183-188
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    Patient narratives of adverse drug events (ADEs) often differ from the symptoms listed on the package inserts of pharmaceutical products using common ADE terminology and could be a source of great comfort to patients with the same disease. To explore this idea, we analyzed written narratives obtained from 48 patients with breast cancer using the NPO Corporation Database of Individual Patients' Experiences, Japan (DIPEx-Japan). Our analysis aimed to determine the utility of an "Adverse Drug Event Database" for use in clinical settings as a novel source of disease information in patients' own words. An analysis of transcripts from 29 patients, in which they recounted their treatment drugs and the time of onset and duration of ADEs in great detail, revealed several discrepancies between the language they used to describe various side effects and the standard ADE terminology on package inserts. We conclude that the language used to describe ADEs on package inserts is insufficient for helping patients as they struggle to recognize, internalize, and overcome ADEs, and argue the need for available, detailed information in the words of real patients about the nature of the ADEs predicted, as well as their clinical course and duration. Such information would be invaluable in supplementing the standardized language used on package inserts. Databases of patients' narrative accounts of ADEs are needed as information sources that can be reliably disseminated among patients.

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  • Krishna A. Lad, Anurag Maheshwari, Bhagawati Saxena
    Type: research-article
    2019 Volume 13 Issue 4 Pages 189-197
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    Traumatic brain injury (TBI) leads to the disruption of blood-brain barrier integrity and therefore results in increased brain water content (brain edema). Brain edema is a significant factor for increased intracranial pressure (ICP), which ultimately causes functional disability and death. The decompressive craniotomy (DC) is a surgical procedure widely used for treating increased ICP following TBI. The life-saving craniotomy itself results in brain injury. The objective of this study is to investigate the effect of agomelatine against craniotomy induced brain injury. The craniotomy was performed by a variable speed micro-motor dental driller of 0.8 mm drill bit. The present study, in addition to blood-brain permeability, brain water content (edema) and histological examination of the brain, also estimated locomotor activity, oxidant, and antioxidant parameters. Results show that the craniotomy induced increase in the blood-brain barrier permeability, brain water content (edema), oxidative stress (lipid peroxide and nitric oxide) and impaired antioxidant mechanisms (superoxide dismutase, catalase, and reduced glutathione) in rats. The craniotomy was also found to increase neuronal cell death indicated by augmented chromatolysis and impaired locomotor activity. Administration of agomelatine after the craniotomy ameliorated histopathological, neurochemical and behavioral consequences of craniotomy. Thus agomelatine is effective against brain injury caused by craniotomy.

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  • Bo-Kyoung Kim, Sung-A Kim, Sun-Mi Baek, Eun Young Lee, Eun Soo Lee, Ch ...
    2019 Volume 13 Issue 4 Pages 198-206
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    Curcumin, a compound found in Indian yellow curry, is known to possess various biological activities, including anti-oxidant, anti-inflammatory, and anti-cancer activities. Cur2004-8 is a synthetic curcumin derivative having symmetrical bis-alkynyl pyridines that shows a strong anti-angiogenic activity. In the present study, we examined the effect of dietary supplementation with Cur2004-8 on response to environmental stresses and aging using Caenorhabditis elegans as a model system. Dietary intervention with Cur2004-8 significantly increased resistance of C. elegans to oxidative stress. Its anti-oxidative-stress effect was greater than curcumin. However, response of C. elegans to heat stress or ultraviolet irradiation was not significantly affected by Cur2004-8. Next, we examined the effect of Cur2004-8 on aging. Cur2004-8 significantly extended both mean and maximum lifespan, accompanying a shift in time-course distribution of progeny production. Age-related decline in motility was also delayed by supplementation with Cur2004-8. In addition, Cur2004-8 prevented amyloid-beta-induced toxicity in Alzheimer's disease model animals which required a forkhead box (FOXO) transcription factor DAF-16. Dietary supplementation with Cur2004-8 also reversed the increase of mortality observed in worms treated with high-glucose-diet. These results suggest that Cur2004-8 has higher anti-oxidant and anti-aging activities than curcumin. It can be used for the development of novel anti-aging product.

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  • Sanae A. Ishijima, Masataro Hiruma, Kazuhisa Sekimizu, Shigeru Abe
    Type: research-article
    2019 Volume 13 Issue 4 Pages 207-211
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    The prevalence of tinea pedis (also known as athlete's foot) in Japanese workers as well as contamination of their footwear by pathogenic filamentous fungi were investigated. Health checks by a dermatologist at a factory located in the Kanto region (Japan) led to a clinical and morphologic diagnosis of tinea pedis in 9 of 19 workers. Scales obtained from the feet and dust obtained from the protective footwear (safety shoes) worn daily in the factory were obtained from these nine subjects and tested using a mycological culture technique. Scales obtained from six of the nine subjects indicated pathogenic filamentous fungi, not only Trichophyton spp., but also Acremonium, which causes symptoms similar to tinea pedis or onychomycosis. Similarly, culture of the dust obtained from the safety shoes yielded pathogenic filamentous fungi in six of the nine subjects, and in four samples Trichophyton spp. was also identified. These findings suggest that cultivable Trichophyton spp. can be detected in approximately 40% of the safety shoes of workers with tinea pedis. The risk of reinfection by pathogenic filamentous fungi is likely increased by wearing dermatophyte-contaminated shoes.

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  • Nurul Hannim Zaidun, Zar Chi Thent Sahema, Abdul Aziz Mardiana, Raj L ...
    2019 Volume 13 Issue 4 Pages 212-221
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    Chronic uncontrolled hyperglycaemia leads to increased oxidative stress and lipid peroxidation resulting in vascular complications and accelerates the progression of diabetic atherosclerosis. Though varieties of modern drugs used in the treatment of diabetes, the complications of diabetes are increasing. Naringenin (NG), has been reported to have potent antioxidant and anti-atherosclerotic properties. However, the effects of NG as vasculoprotective agent in prolonged hyperglycaemia are not well documented. Thus, this study was aimed to determine the effect of NG against vascular changes after prolonged hyperglycaemia in a diabetic rat model. Thirty adult male Sprague-Dawley rats were induced with fructose and streptozotocin to develop the diabetic rat model. After 4 weeks, the rats were randomly divided into 5 groups each group consisting of 6 animals: control, control treated with NG, non-treated diabetes mellitus (DM), DM treated with NG and metformin-treated DM. The treatment with NG (50 mg/kg) and metformin were continued for 5 weeks. The results showed that consumption of NG at 4 weeks post diabetic did not improved blood sugar, blood pressure and serum lipid profile. However, NG did significantly improve oxidative stress parameters in the aortic tissue like malondialdehyde (MDA). Analysis through light microscopy and transmission electron microscope (TEM) reverted the histological changes caused by prolonged hyperglycaemia. The findings thus demonstrated that introduction of NG after prolonged exposure to hyperglycaemia improved the vascular deterioration in diabetic group by decreasing oxidative stress evident by the reduced in the lipid peroxidation activity. Thus, this study showed the potential use of NG as adjunct in managing the diabetic condition during late presentation.

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Brief Report
  • Xiaochun Zhang, Rongrong Gao, Yan Liu, Yuhe Cong, Dongdong Zhang, Yu Z ...
    Type: research-article
    2019 Volume 13 Issue 4 Pages 222-227
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    Based on the anti-virulence activity on Salmonella, the ethyl acetate extract (EAE) of Mesua ferrea flower was investigated for its chemical constituents. Ten purified compounds were identified and assayed for their inhibitory activity against Type III secretion system (T3SS) by polyacrylamide gel electrophoresis (SDS-PAGE) and Western blots experiments. We found the biflavonoids, rhusflavanone and mesuaferrone B, exhibited inhibitory effects on the secretion of Salmonella pathogenicity island 1 (SPI-1) effector proteins (SipA, B, C and D) without effecting the bacterial growth. In addition, 5, 6, 6'-trihydroxy-[1,1'-biphenyl]-3,3'-dicarboxylic acid (6) is a new natural product from M. ferrea flower.

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Case Report
  • Yusuke Morinaga, Kouhei Nii, Kimiya Sakamoto, Ritsurou Inoue, Takafumi ...
    Type: case-report
    2019 Volume 13 Issue 4 Pages 228-231
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    We describe a rare case of neurovascular compression syndrome (NVCS) of the brain stem and opsoclonus-myoclonus syndrome (OMS) complicated with vestibular paroxysmia (VP) and autonomic symptoms. Moreover, we discuss the case with respect to the available information in medical literature. A 36-year-old man with vertigo and nausea had difficulty standing, and was transported by an ambulance to our hospital. He had VP, opsoclonus, cervical myoclonus, anxiety, and restless legs syndrome. Magnetic resonance imaging at hospitalization showed that the dolichoectatic vertebral artery was in contact with the postero-lateral side of the pontomedullary junction. He was diagnosed with NVCS of the brain stem (most likely of the input to the vestibular nucleus) associated with contact with the dolichoectatic vertebral artery. Combination therapy using multiple antiepileptic drugs, such as low-dose carbamazepine, clonazepam, and lacosamide, improved his clinical symptoms. He was finally able to walk and was discharged on day 42 after admission. He is being routinely followed-up since then. Further research is needed to confirm the validity of the combination therapy.

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  • Yusuke Morinaga, Ichiro Abe, Tomohiro Minamikawa, Yusuke Ueda, Kouhei ...
    Type: case-report
    2019 Volume 13 Issue 4 Pages 232-238
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    We present a case of a patient with drug-induced hypersensitivity syndrome (DIHS) caused by salazosulfapyridine combined with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by interstitial pneumonia (IP). A 67-year-old man with a past history of rheumatism (RA) presented with right hemiparalysis and aphasia as the chief complaints. A diagnosis of left embolic cerebral infarction following trial therapy for RA based on computed tomography findings was made, and external decompression was performed. Salazosulfapyridine was newly started on day 7. Dabigatran was started on day 37. On day 41, the patient developed fever. On day 42, edema and erythema appeared on his face, and erythema and rash appeared on his trunk and extremities, with gradual transition to erythroderma. The drug eruption was initially attributed to the dabigatran. Various symptoms of organ dysfunction (enteritis, myocarditis, interstitial pneumonia, hepatic disorder, stomatitis, and others) then appeared and persisted; hence, a diagnosis of DIHS associated with human herpes virus 6 and cytomegalovirus infection induced by salazosulfapyridine was suggested, and the oral administration of salazosulfapyridine was discontinued on day 53. Hyponatremia was observed in association with exacerbation of IP. Due to low serum osmotic pressure and prompt improvement of the serum sodium level by fluid restriction, the SIADH was attributed to IP. In this case, steroid pulse therapy followed by gradual decrease therapy prevented worsening of the condition.

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  • Yusuke Morinaga, Kouhei Nii, Kimiya Sakamoto, Ritsurou Inoue, Takafumi ...
    Type: case-report
    2019 Volume 13 Issue 4 Pages 239-243
    Published: August 31, 2019
    Released: September 18, 2019
    JOURNALS FREE ACCESS

    Barré-Lièou syndrome is a manifestation of various autonomic and secondary symptoms, such as muscle stiffness, tinnitus, dizziness, and pain in the head, neck, eyes, throat, ears, chest, and back. While thought to be caused by hyperactivation of the autonomic nervous system due to trauma, there is currently no firmly established etiology. This, and the nonspecific nature of many of its symptoms, presents a challenge both for clinicians, who must provide a correct diagnosis and patients, who are often misdiagnosed or faced with undue scrutiny from insurance companies. Here, we present two cases of Barré-Lièou syndrome, focusing on the processes leading to diagnosis, treatment, and problems encountered. Case 1 involves a 68-year-old woman whose head computed tomography (CT) scan revealed no abnormalities following a car accident. Approximately 10 months after her initial injury, Barré-Lièou syndrome was suspected because of autonomic symptoms that developed over time. She was prescribed an α-blocker, and 9 months later, her symptoms subsided. Case 2 was a 69-year-old woman who presented with bruising to the right chest and right knee after colliding with a car while riding her bicycle. One month later, Barré-Lièou syndrome was suspected because of her autonomic symptoms. She was prescribed an α-blocker, and 17 months later, her symptoms subsided. Because of the characteristic autonomic and secondary symptoms described above and a positive response to α-blockers, Barré-Lièou syndrome was suspected in both cases. We believe reporting cases will aid in the understanding of this disease and help patients obtain positive outcomes.

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