Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
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Original Articles
  • Mostafa R. Fayed, Reem N. El-Naga, El-Sayed Akool, Ebtehal El-Demerdas ...
    Volume 12 (2018) Issue 2 Pages 58-67
    Released: May 13, 2018
    JOURNALS FREE ACCESS

    Liver fibrosis results from chronic inflammation that precipitates excessive accumulation of extracellular matrix. Oxidative stress is involved in its pathogenesis. This study aimed to elucidate the potential antifibrotic effect of the NADPH oxidase (NOX) inhibitor, apocynin against concanavalin A (ConA)-induced immunological model of liver fibrosis, and to investigate the ability of the antioxidant, alpha-lipoic acid (α-LA) to potentiate this effect. Rats were treated with apocynin and/or α-LA for six weeks. Hepatotoxicity indices, oxidative stress, insulin, NOXs, inflammatory and liver fibrosis markers were assessed. Treatment of animals with apocynin and α-LA significantly ameliorated the changes in liver functions and histopathological architecture induced by ConA. Liver fibrosis induced by ConA was evident where alpha-smooth muscle actin and transforming growth factor- beta1 were elevated, which was further confirmed by Masson's trichrome stain and increased hydroxyproline. Co-treatment with apocynin and α-LA significantly reduced their expression. Besides, apocynin and α-LA significantly ameliorated oxidative stress injury evoked by ConA, as evidenced by enhancing reduced glutathione content, antioxidant enzymes activities and decreasing lipid peroxides. ConA induced a significant elevation in serum insulin level and inflammatory markers; tumor necrosis factor-alpha, interleukin-6 and nuclear factor kappa b. Furthermore, the mRNA tissue expression of NOXs 1 and 4 was found to be elevated in the ConA group. All these elevations were significantly reduced by apocynin and α-LA co-treatment. These findings indicate that using apocynin and α-LA in combination possess marked antifibrotic effects, and that NOX enzymes are partially involved in the pathogenesis of ConA-induced liver fibrosis.

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  • Abdelhak Elkhazraji, El Arbi Bouaiti, Hassan Boulahyaoui, Christiana p ...
    Volume 12 (2018) Issue 2 Pages 68-76
    Released: May 13, 2018
    JOURNALS FREE ACCESS

    We investigated the impact of non-genetics factors, and single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, CYP4F2, and GGCX on acenocoumarol dosage in Moroccan adult's patients, in order to develop an algorithm to predict acenocoumarol dose for Moroccan patients. Our study consisted of 217 Moroccan patients taking a maintenance dose of acenocoumarol for various indications. The patients were genotyped for VKORC1 –1639 G>A, VKORC1 1173 C>T, CYP2C9*2, CYP2C9*3, CYP4F2 1347 G>A and GGCX 12970 C>G SNPs. The statistical analysis was performed using the SPSS software. The age and SNPs in VKORC1 and CYP2C9 were significantly associated with the weekly acenocoumarol dose requirement (p = 0.023, p = 0.0001 and p = 0.001 respectively). There was no association found between the weekly acenocoumarol dose and the CYP4F2 or GGCX variants (p-value > 0.05). Non-parametric analysis confirmed the accumulate effect of variant alleles at VKORC1 –1639 G>A, VKORC1 1173 C>T and CYP2C9 SNPs on the acenocoumarol dose requirement. With 90.24% less dose required for one patient carrying homozygote variant at VKORC1 –1173 (TT) and CYP2C9 *x/*x haplotype. The multiple linear regression analysis showed that mutation in VKORC1 –1639, VKORC1 1173 SNPs, or in CYP2C9 haplotype reduces the mean acenocoumarol weekly dose to 25.4%, 23.4% and 6.2%, respectively. The R2 for multiple regression analysis final model was found to be 35.9%. In this work we were able to establish the factors influencing interindividual sensitivity to the anticoagulant therapy that can help physicians to predict optimal dose requirement for long term therapy.

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  • Jue Wang, Shuna Gao, Yejing Wang, Jianjun Zhou, Jing Lin, Ling Wang, Y ...
    Volume 12 (2018) Issue 2 Pages 77-87
    Released: May 13, 2018
    [Advance publication] Released: April 22, 2018
    JOURNALS FREE ACCESS

    Cancer has become the leading cause of death and a major burden to public health in China. The current study analyzed the composition, incidence, mortality, and temporal trends for some major cancer types among permanent residents in Luwan district of Shanghai from 2002 to 2011, so as to provide data for cancer research. Data were collected from the database of cancer registration and management system in Shanghai. Number of new cases, number of deaths, incidence, and mortality of each cancer type were calculated. The incidence and mortality rates were standardized. Temporal trends in the incidence and mortality were assessed using average annual percent change. There were 12,843 new cancer cases and 8,331 deaths from cancer in Luwan from January 2002 to December 2011. Age-standardized incidence rates by Segi's standard were 229.46 and 205.05 per 100,000 population for males and females, respectively. For males, the most commonly diagnosed cancers were lung, colorectal, stomach, liver, prostate, bladder, pancreas, kidney, lymphoma, and esophageal cancers; for females, they were breast, colorectal, lung, stomach, thyroid, liver, ovary, pancreas, uterus, and brain cancers. The incidence rates for all cancers combined increased significantly for both males and females from 2002 to 2011 (p < 0.05 for both). Age-standardized mortality rates were 147.04 and 90.62 per 100,000 population for males and females, respectively. The mortality rates have stayed stable during the 10-year period for both males and females (p > 0.05 for both). Our results suggest that cancer incidence and mortality rates in Luwan district of Shanghai vary by age, sex, tumor type. The increasing trends in cancer incidence call for effective prevention and control measures in the district. The significance of cancer registration for disease surveillance and management needs to be further advocated.

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Brief Reports
  • Masaki Ishii, Yasuhiko Matsumoto, Kazuhisa Sekimizu
    Volume 12 (2018) Issue 2 Pages 88-91
    Released: May 13, 2018
    JOURNALS FREE ACCESS

    Lactic acid bacteria are provided by fermented foods, beverages, medicines, and supplements. Because the beneficial effects of medicines and supplements containing functional lactic acid bacteria are related to the bacterial cell number, it is important to establish a simple method for estimating the total number of lactic acid bacterial cells in the products for quality control. Almost all of the lactic acid bacteria in the products are dead, however, making it difficult to estimate the total number of lactic acid bacterial cells in the products using a standard colony-counting method. Here we estimated the total lactic acid bacterial cell number in samples containing dead bacteria by quantifying the DNA. The number of viable Enterococcus faecalis 0831-07 cells decreased to less than 1 × 10-8 by 15 min of heat treatment at 80°C. The amount of extracted DNA from heat-treated cells was 78% that of non-heated cells. The number of viable Lactobacillus paraplantarum 11-1 cells decreased to 1 × 10-4 after 4 days culture. The amount of extracted DNA of the long-cultured cells, however, was maintained at 97%. These results suggest that cell number of lactic acid bacteria killed by heat-treatment or long-term culture can be estimated by DNA quantification.

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  • Binh C. Nguyen, Sung-A Kim, Seong-Min Won, Sang-Kyu Park, Yoshihiro Ut ...
    Volume 12 (2018) Issue 2 Pages 92-96
    Released: May 13, 2018
    JOURNALS FREE ACCESS

    PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic/ageing kinase, and its dysfunction extends the healthy lifespan of C. elegans by activating HSP16 gene. 15K is a highly cell-permeable 1,2,3-triazolyl ester of ketorolac that down-regulates both PAK1 and its down-stream COX-2 in R- and S-forms, respectively. 15K is 500-5,000 times more potent than ketorolac, an old pain-killer, inhibiting the growth of cancer cell lines with IC50 ranging 5-24 nM. Scores of natural and synthetic PAK1-blockers have been shown to extend the lifespan of small animals such as C. elegans, but none of them has been effective at nM levels. Thus, we examined in vivo effect of 15K at nM levels on the survival rate of C. elegans with or without heat-shock. Like the PAK1-deficient mutant, 15K (at 50 nM)-treated worm significantly lives longer, is far more heat-resistant and less productive (fertile) than the non-treated counterpart, with an increased expression of HSP16 gene. 15K has been proven to be among the most potent anti-cancerous and longevity-promoting PAK1-blockers, and therefore has a potential to treat a variety of solid tumours without severe side effect.

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  • Nitin Gupta, Manish Soneja, Yogiraj Ray, Monalisa Sahu, Kutty Sharada ...
    Volume 12 (2018) Issue 2 Pages 97-100
    Released: May 13, 2018
    [Advance publication] Released: April 17, 2018
    JOURNALS FREE ACCESS

    The clinical practice guidelines on nosocomial pneumonia recommends an empirical regimen that would work in 95% of the patients based on the local antibiogram. The aim of the study was development of an antibiogram for guiding empiric therapy in settings with high prevalence of multi-drug resistant organisms. A retrospective review of electronic health records (e-hospital portal) was done to analyze all respiratory isolates from patients admitted in medical wards and intensive care unit between May 2016 and May 2017. The samples included brocho-alveolar lavage (BAL), mini broncho-alveolar lavage (mini-BAL) and endotracheal aspirate. The sensitivity pattern (combined and individual) of all bacterial isolates were analysed for commonly used antibiotics and their combinations. Out of the 269 isolates, the most common organisms were Pseudomonas aeruginosa (125, 46%), Acinetobacter baumanni (74, 27%) and Klebsiella pneumoniae (50, 19%). Cefoperazone-sulbactam (43%) had the best sensitivity pattern overall. Cefoperazone-sulbactam plus amikacin (56%) was the combination with the best combined sensitivity overall. There is a high prevalence of resistance in the commonly implicated organisms to the available antibiotics. There is an urgent need for implementation of effective anti-microbial stewardship programmes and development of newer antimicrobials.

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Case Reports
  • Masashi Ohe, Haruki Shida, Tetsuya Horita, Ken Furuya, Satoshi Hashino
    Volume 12 (2018) Issue 2 Pages 101-103
    Released: May 13, 2018
    [Advance publication] Released: April 23, 2018
    JOURNALS FREE ACCESS

    Macrolides have immunomodulatory effects including anti-inflammatory effects as well as antibacterial activity. In consideration of these immunomodulatory effects, we report a patient with primary immune thrombocytopenia (ITP) treated using clarithromycin (CAM), a macrolide, followed by prednisolone (PSL). A 78-year-old man with thrombocytopenia was admitted to our hospital for further examination. Initial laboratory data showed reduced platelet counts (1.7 × 104/μL). Finally, we diagnosed the patient as having primary ITP. Because the patient was suffering from diabetes mellitus (DM), he was treated with CAM as an alternative to PSL. The platelet count increased to 6.1 × 104/μL. The CAM treatment was terminated owing to gradual nausea and palpitation. During the CAM treatment, the DM was under control. We reinitiated treatment for ITP. The patient was successfully treated using PSL without severe hyperglycemia. This case shows that CAM treatment may represent a useful option for ITP patients who cannot receive PSL due to DM.

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  • Rabih Tabet, Youssef Shammaa, Boutros Karam, Harout Yacoub, James Laff ...
    Volume 12 (2018) Issue 2 Pages 104-107
    Released: May 13, 2018
    [Advance publication] Released: April 23, 2018
    JOURNALS FREE ACCESS

    Thromboembolic events such as deep vein thrombosis and pulmonary embolism are well-known complications that can occur after prothrombin complex concentrate therapy. However, acute myocardial infarction is a very rare but potentially life-threatening complication that was exclusively described in patients with bleeding disorders who received chronic and recurrent concentrate infusions. We report the case of a 70 year-old male patient with cholangiocarcinoma who was admitted to our hospital with worsening fatigue and weakness. His stay was complicated by uncontrolled bleeding secondary to rivaroxaban use and advanced liver disease. By the end of the prothrombin complex concentrate infusion used to reverse his coagulopathy, patient developed ST-segment elevation myocardial infarction with cardiogenic shock and passed away. This is the first reported case of acute myocardial infarction that occurs in a patient without hemophilia and after the first prothrombin complex concentrate infusion.

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  • Seyda Ignak, Ozlem Unay Demirel, Sevda Soydan, Erkan Esen
    Volume 12 (2018) Issue 2 Pages 108-110
    Released: May 13, 2018
    [Advance publication] Released: April 23, 2018
    JOURNALS FREE ACCESS

    We present Shewanella algea infection in a chronic suppurative otitis media (CSOM) patient with cholesteatoma in terms of clinical course and treatment. This is the first time S. algea is found as solely pathogen in a CSOM patient without history of contact with seawater in Turkey. The patient admitted to the hospital several times with complaints of otorrhoea, was diagnosed as otitis media and treated. He was hospitalized to the otorhinolaryngology department for further evaluation of recurrent infections. The patient was diagnosed as cholesteatoma according to computed tomography scan findings and was operated for cholesteatoma. As a result of surgical and medical treatment he was discharged with full recovery. Physicians must be aware of rarely seen pathogens and their unexpected ways of transmission and underlying causes such as cholesteatoma when treating patients for CSOM.

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  • Ankita Baidya, Vanishri Ganakumar, Ranveer S Jadon, Piyush Ranjan, Smi ...
    Volume 12 (2018) Issue 2 Pages 111-113
    Released: May 13, 2018
    JOURNALS FREE ACCESS

    Septic pulmonary emboli can occur as a complication of many diseases, most common being right sided infective endocarditis. Septic emboli through a peripheral venous cannula are rarely reported in literature though central venous catheter is commonly implicated. We describe a case of widespread cellulitis and septic pulmonary emboli as a complication of peripheral venous cannulation.

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