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International Journal of Pharmacology
eISSN: 1812-5700
pISSN: 1811-7775

Editor-in-Chief:  Majid Y. Moridani
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Review Article
Bayesian Meta-Analysis: The Effect of Statins on the Treatment of Hypercholesterolemia
Qingzan Kong, Qing Zhu and Liqi Wang
Statins inhibit cholesterol synthesis by blocking 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver, thereby ameliorating hypercholesterolemia. Thus, to determine statins with the best efficacy, a meta-analysis was performed to compare the effects of statins against hypercholesterolemia. Comprehensive literature searches were established, from Cochrane library, Pubmed, Embase. The studies were performed to randomize controlled trials (RCTs), cohort studies or case-control studies about efficacy of different statin drugs and dose against hypercholesterolemia published between 1997 and 20 February, 2017. Study qualities were assessed according to Cochrane collaboration recommendations. The non-programming software Aggregate Data Drug Information System (ADDIS) (version 1.16.5) was used to perform Bayesian network meta-analysis and compare treatments using the Markov Chain Monte Carlo (MCMC) method. Overall, 28 RCTs studies, including 12855 patients, met the inclusion criteria. Total cholesterol (TC) levels significantly reduced (p<0.05) using 2 mg Pitavastatin (Pit) than those using 20 mg Pravastatin (Pra), 10 mg Simvastatin (Sim) or 10 mg Atorvastatin (Ato). Similarly, triglyceride (TG) levels reduced using 2 mg Pit than those using 20 mg Pra (p<0.05), 10 mg Sim (p<0.05) or 20 mg Sim (p<0.05) and reduced apolipoprotein B (Apo B) levels were observed than those using 10 mg Ato or 20 mg Pra (p<0.05). Rosuvastatin (Ros) significantly reduced TC and TG levels (p<0.05) when administered at 20 and 10 mg Ros treatments ameliorated percentage changes in low-density lipoprotein cholesterol more than the other drugs (p<0.05) and increased high-density lipoprotein cholesterol levels more effectively than 10 mg Ato (p<0.05), 20 mg Pra (p<0.05) or 10 mg Sim (p<0.05). Increases in Apo A1 levels did not differ between treatments (p>0.05). Among the present statin drug regimens, 2 mg Pit and 10 or 20 mg Ros had the highest efficacy against hypercholesterolemia.
Research Article
Electroacupuncture Rescued the Impairment of Hippocampal Neurons in Perimenopausal Depression Rats via Activating the CREB/BDNF Pathway
Shao- Heng Li, Li-Tong Wang, Xue Deng, Ya- NanJiao, Liang Kong, Martin Fu, Lian-Qun Jia, Jing-Xian Yang and Lu Ren
Background and Objective: Perimenopausal depression is caused by the impaired function of the ovarium prior to menopause and characterized by a persistent feeling of sadness and loss of interest. Electroacupuncture (EA) therapy has been demonstrated to be effective in patients with depression. The effects of EA in perimenopausal depression as well as the underlying mechanisms remain unclear. This study aimed to elucidate the therapeutic effect of EA on perimenopausal depression and its correlation with the CREB/BNDF signaling pathway to understand the mechanisms underlying the EA effect. Materials and Methods: Chronic Unpredictable Mild Stress (CUMS) combined with bilateral ovariectomy (OVX) were used to establish a rat model of perimenopausal depression. The Open Field Test (OFT) and sucrose preference tests were used to examine the anxiety level and anhedonia effect of OVX+CUMS rat model and the effects of EA. The MTT assay and flow cytometry were used to detect the cell viability and apoptosis of hippocampal neurons. The immunohistochemistry and ELISA assay were utilized for measuring the proteins expressions and RT-PCR for mRNA expressions, respectively. Comparisons among more than two groups were made using one-way analysis of variance (ANOVA) followed by the Least Significant Difference (LSD) test. Results: The EA at the "Shenshu", "Baihui" and "Sanyinjiao" points could reverse the increased and reduced sucrose preference induced by CUMS and OVX. Meanwhile, the reduced cell viability, increased cell apoptosis and impaired function of hippocampal neurons in the perimenopausal depression model rats were prevented by EA treatment. Moreover, EA increased p-CREB and BDNF expression in the hippocampal neurons and this effect was found to be suppressed by the CREB antagonist KG-501. Conclusion: The EA treatment could rescue the impairment induced by OVX+CUMS via CREB/BDNF pathway activation. Taken together, the results suggest that EA could be a potential therapy for perimenopausal depression.
Research Article
Efficacy and Safety of Intraocular Pressure-Lowering Agents Bimatoprost and Timolol Maleate in Glaucoma
Lin Chen, Xiaoli Zeng and Xuewen Huang
Background and Objective: Intraocular pressure (IOP) elevation is a major risk associated with glaucoma. Timolol is the most frequently used drug in the management of open-angle glaucoma (OG). The objective of this study was to compare the IOP-lowering effects of bimatoprost (BM) with timolol in a Chinese population with OG. Methodology: A total of 480 eyes of indoor patients suffering from OG (study group) and 50 normal eyes of indoor patients not suffering from OG (non-study group) were included in the study. The eyes of the treatment, control and non-study groups were treated with one drop of 0.03% w/v BM once daily, 0.5% w/v timolol maleate (TM) twice daily and water injection twice daily for 3 months, respectively. The IOP was measured at baseline and at 2, 6 weeks and 3 months of treatment. Conjunctival hyperemia, eye irritation, ocular hyperemia, foreign body sensation in eyes, corneal staining, heart rate and systolic and diastolic blood pressures were determined for the study group between baseline and 3 months of treatment. SPSS was use to analyze the data. Analysis of covariance was used to show better efficacy of BM compared with TM. One-way analysis of variance (ANOVA) and the Wilcoxon test were used for insignificant differences of ocular and systematic adverse effects. Results: There was a significant difference in IOP at baseline compared with the end of 3 months of BM (p = 0.00041) and TM (p = 0.0091) treatments. There was no significant difference between conjunctival hyperemia, eye irritation, ocular hyperemia, foreign body sensations in eyes, corneal staining, heart rate and systolic and diastolic blood pressures between baseline and at the end of 3 months of patients treated with BM. There was a significant difference for eyes reaching and maintaining an IOP<18 mmHg between the control group and the treatment group (p = 0.0478). Conclusion: The BM was more effective than timolol in lowering IOP over 3 months of treatment in open-angle glaucoma patients.
Research Article
Inhibitory Effect of Sulforaphane on Secretory Group IIA Phospholipase A2
Yuri Lee, Wonhwa Lee, Jaehong Kim and Jong-Sup Bae
Background and Objective: The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) has been shown to be elevated in various inflammatory diseases and Lipopolysaccharide (LPS) up-regulates the expression of sPLA2-IIA in Human umbilical vein endothelial cells (HUVECs). Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes and inflammatory responses. Here, SFN was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and in mouse models of sepsis. Materials and Methods: After HUVECs were activated with LPS, cells were post-treated with SFN. In vivo, LPS-injected or Cecal ligation and puncture (CLP) operated mice were administrated SFN. Then, the effects of SFN on the activity and expression of sPLA2-IIA were determined by Enzyme-linked immunosorbent assay (ELISA). The effects of SFN on the activities of cytosolic phospholipase A2 (cPLA2) and Extracellular signal-regulated kinase (ERK)1/2 were monitored. Statistical relevance was determined by one-way analysis of variance (ANOVA). p<0.05 were considered to indicate significance Results: Post-treatment of cells or mice with SFN inhibited LPS- or CLP-induced expression and activity of sPLA2-IIA. SFN also suppressed the activation of cPLA2 and ERK1/2 by LPS. Conclusion: It is concluded that, SFN inhibited LPS-mediated expression of sPLA2-IIA by suppression of cPLA2 and ERK1/2.
Research Article
Neuroprotective Efficacy of Cadambine Against Cadmium in Primary Brain Neonatal Rat Cells
Shan-Wu Dong, Yong Chen, Guang-Hua Liu, Lin Chen, Xue-Hua Zhao and Zhenyu Wang
Background and Objective: Cadmium is a heavy metal that accumulates with time in different tissues of the body like central nervous system, kidney, liver etc. causing toxic effects especially to the brain and has a very long biological half-life. The objective of this study was to explore the neuroprotective effect of cadambine an indole alkaloid against cadmium-induced toxicity. Materials and Methods: Three cell lines namely N2A, SH-SY5Y and primary brain neonatal rat cells were used in this study. Cell viability and neuroprotection assays were assessed by MTT assay to determine the effect of cadmium and cadambine. Changes in the intracellular calcium levels, ROS and mitochondrial membrane potential were determined by flow cytometer. Western blotting was done to analyse the effects of cadmium and cadambine on pro-apoptotic and anti-apoptotic genes. Student’s t-test was used to compare the data. Results: In this study, it was confirmed that cadmium induced toxicity was reversed by cadambine. Cadambine increased the viability of cells treated with of cadmium induced toxicity. Furthermore, cadmium treatment led to generation of ROS, increased calcium levels, loss of MMP and increase in the expression of pro-apoptotic proteins. Interestingly, these effects was reversed by cadambine in primary brain neonatal rat cells. Conclusion: These findings led us to the conclusion that exposure to cadmium induces neurotoxic effects in brain and cadambine not only reversed the toxic effects of cadmium but also led to inhibition of cadmium-induced apoptosis. Based on this data, cadambine can further be investigated as potent neuroprotective agent.
Research Article
Bactericidal Activity, Isolation and Identification of Most Active Compound from 20 Plants used in Traditional Mexican Medicine Against Multidrug-Resistant Bacteria
C. Rivas-Morales, V.M. Rivas-Galindo, J. Rodriguez-Rodriguez, S.A. Galindo-Rodriguez, C. Leos-Rivas and D.G. Garcia-Hernandez
Background and Objective: Plants are used in Mexico as traditional medicine for the treatment of diverse illnesses such as stomach pain, fever, diarrhea, insomnia, flu and other respiratory diseases. Twenty were selected to determine their bactericidal activity. The aim of this study was the isolation of molecules from plants used in Mexican traditional medicine. Materials and Methods: Using chromatographic procedures, the responsible bactericidal molecules from rosemary was extracted and then identified by spectroscopic analysis IR, 1H NMR, 13C NMR, DEPT, HSQC and GC-MS. Measures of central tendency were determined by statistical analysis. Results: Ten of these plants showed bactericidal activity against multidrug-resistant bacteria. This biological activity was reported for Carya illinoensis against Pseudomonas aeruginosa, also for Equisetum robustum, Stevia rebaudiana and Castela texana against Methicillin resistant Staphylococcus aureus (MRSA). The methanolic extract of Rosmarinus officinalis (rosemary) showed important bactericidal activity against MRSA (ATCC BAA-44) and clinically isolated MRSA. Conclusion: Rosemary’s bactericidal molecules were isolated and then identified as a mixture of betulinic, oleanolic and ursolic acid (MIC = 725 μg mL–1).
Research Article
Determination of Tamoxifen and 4-Hydroxytamoxifen Levels in Rat Plasma after Administration of the Ethyl Acetate Fraction of Myrmecodia erinaceae Becc. using Liquid Chromatography Tandem Mass-Spectrometry
Sri Teguh Rahayu, Yahdiana Harahap, Abdul Mun`im and Noorwati Sutandyo
Background and Objective: The effects of anti-oestrogen and the side effects of tamoxifen and its metabolite 4-Hydroxytamoxifen (4-OHTAM) depend on their levels in plasma. The ethyl acetate fraction of Myrmecodia erinaceae Becc. was observed to effect the plasma levels of tamoxifen and 4-OHTAM. A sensitive, selective and valid method is needed to quantitatively determine the concentration of tamoxifen and 4-OHTAM in plasma. Methodology: Tamoxifen and 4-OHTAM were simultaneously extracted from plasma by protein precipitation using acetonitrile-0.2% formic acid. It was then analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS) with a C18 ACQUITY® column (100 mm×2.1 mm x 1.7 μm) and a column temperature of 40°C. The mobile phase consisted of acetonitrile-0.2% formic acid, 0.2% formic acid (70:30 v/v) and a flow rate of 0.2 mL min–1. A total of 30 female white rats (Sprague-Dawley) were divided into 6 groups (KKN, KP, KN, D100, D200 and D400). With the exception of the KKN group, all the groups were given tamoxifen 20 mg kg–1 b.wt. Then, 30 min later the D100, D200 and D400 groups were given an ethyl acetate fraction equivalent to quercetin 100, 200 and 400 mg kg–1 b.wt., respectively, once a day for 20 days. Blood was collected and analyzed every day. Results: The analytical method was linear (r>0.99) in the range concentration of 2-200 ng mL–1 for tamoxifen and 4-OHTAM. All the validation parameters met the criteria of the 2011 European Medicines Agency (EMA) guidelines. The concentrations of tamoxifen and 4-OHTAM decreased after administration of the ethyl acetate fraction for 20 days and tamoxifen metabolism was inhibited. Conclusion: The proposed method simultaneously measured the concentrations of tamoxifen and 4-OHTAM in plasma in female rats.
Research Article
Cellular Defense Enzyme Profile for Non-cytotoxic and Phenol Enriched Extracts of Heliotropium europaeum, Carlina oligocephala and Echinops ritro
Belgin S. Isgor, Yasemin G. Isgor and Fatmagul Geven
Background and Objective: The discovery of traditional plants with some medicinal properties, verifying their biological targets and the bioassay guided standardization of their active components are the particular interest of diverse research groups recently. These efforts may help to revise the therapy modalities with natural product supplements. In this context, the possible biological targets of plants, namely Heliotropium europaeum, Carlina oligocephala and Echinops ritro, with no known medicinal value but recognized for their region specific traditional use, were evaluated. Here, the biological targets were enzymes of the antioxidant and xenobiotic defense mechanisms, with roles on inflammatory response. Materials and Methods: Cytotoxicity analyses were performed by using human promyelocytic (HL60) and chronic myelogenous leukemia (K562) cells for circulating models and breast adenocarcinoma (MCF7) cells for epithelial model to evaluate the non-toxic dose range of extracts by virtue of XTT and trypan blue. The target aimed effectiveness of these plants were determined with dose response profiles and IC50 values against glutathione peroxidase (GPX), glutathione transferase (GST), catalase (CAT) and superoxide dismutase (SOD) targets, as well as their capacity to reduce free radicals (DPPH) and non-radical hydrogen peroxide (H2O2). For standardization purposes, all extract concentrations were brought to 23.81 mg L–1 GAE and dilutions were made from these stocks. The IC50 values were determined by nonlinear regression analysis, with sigmoidal dose-response 4-parameter logistic equation. Results: The results showed that the best DPPH and H2O2 scavenging was observed with E. ritro extracts. On the contrary, the best enzyme inhibition profile was observed with H. europaeum against CAT, SOD, GPX and GST targets. Among the enzymes evaluated, all plants with different fractions also exerted strong GPX and CAT inhibition. Conclusion: The enzyme profiling of extracts may reveal the medicinal value of herbal remedies, by identifying their effects on cellular targets. In addition to define how reasonable the use of plants in traditional and complementary medicine (TCM) practices, these efforts may help to improve the standardized supplement preparations to benefit therapeutics with reduced efficiency due to inference with cellular defense and drug resistance enzymes, or both.
Research Article
Toxicological Evaluation of Aqueous Extract of Lauridia tetragona (L.F.) R.H. Archer Leaf in Wistar Rats
Olubunmi Abosede Wintola and Anthony Jide Afolayan
Background and Objective: Medicinal plants are used in the treatment and management of various diseases. The usage of herbs and their formulations have witnessed progressive increase among the populace especially in the rural areas because of the notion that these products are safe and free from undesirable side effects. This study was aimed at evaluating the toxicological potential of aqueous extract of Lauridia tetragona leaf in Wistar rats. Methodology: The acute toxicity test was performed with single oral administration of 5000 mg kg–1 b.wt., of L. tetragona extract to rats and the animals were observed for 14 days for signs of toxicity. This was followed by subacute toxicity experiment conducted by oral administration of graded doses (50, 100 and 200 mg kg–1) of L. tetragona extract daily for 28 days. Behavioural changes as well as haematological, biochemical and histological parameters were then evaluated. Data were analysed using two-way ANOVA with the aid of GraphPad Prism software. Results: Results revealed significant reduction (p<0.05) in the feed intake, serum glucose, lymphocytes and platelet levels of extract treated rats compared to the control. There were also some alterations in the liver and kidney function parameters. However, there were no treatment related differences in the histopathological evaluations. Conclusion: It can be concluded that administration of aqueous extract of L. tetragona may be safe at the dosages tested in this study but its continuous usage can cause anorexia.
Research Article
Phytochemical and Biological Studies of Tribulus terrestris L. Growing in Egypt
Nagwa Mohammed Ammar, Seham Salah El-Din El-Hawary, Doha Abdou Mohamed, Manal Shafik Afifi, Dina Magdy Ghanem and Gamal Awad
Background and Objective: The genus Tribulus of the Zygophyllaceae family comprises several species which grow as shrubs or herbs in subtropical areas around the world. Phytochemical and biological studies of the different successive extracts of the aerial parts of Tribulus terrestris L. (Family Zygophyllaceae), growing in Egypt as well as the isolation and identification of the biologically active natural fractions or compounds were carried out. Methodology: The volatile constituents were prepared and analyzed by GC/MS. The lipoidal matter was prepared and analyzed by GLC. The carbohydrate and the amino acid contents were prepared and analyzed by HPLC. Saponin fraction was prepared. The activities of polar, non-polar extracts and saponin fraction as aphrodisiac, antimicrobial, cytotoxic and antioxidant were evaluated. Results: GC/MS of volatile constituents revealed the presence of thirty two compounds. The major compound was methyl linolenate (18.56%). The major fatty acid in the lipoidal matter is heptadecanoic acid (33.56%). HPLC analysis of carbohydrate and amino acid revealed the presence of inulin (5.61%) and glutamic acid (2.85%), respectively. Saponin yield was 7.38%. The results of the biological investigation of the polar and non-polar extracts revealed their aphrodisiac, antimicrobial, cytotoxic and antioxidant activities with different percentages. Phytochemical examination of the aqueous methanolic biologically active extract by HPLC revealed the presence of phenolic and flavonoid contents (11.16 and 6.076%) respectively as well as saponin. Isolation and identification of rutin, quercetin and diosgenin were carried out using several chromatographic and spectroscopic analysis. Conclusion: The herb under investigation revealed potent and remarkable biological activities due to the presence of different active constituents.
Research Article
Metallocenes-induced Apoptosis in Human Hepatic Cancer HepG2 Cells: The Prodigy of Zamzam Water
Ahmed Abd-Rabou Abd-Rabou, Eman Abdul-Rahman Assirey, Ramiz Saad and Hanan Sayed Ibrahim
Background and Objective: Hepatocellular carcinoma (HCC) is a public health problem and one of the common causes of mortality around the world. Zamzam water (ZW) contains metallocenes that were reported as promising anticancer agents by blocking DNA replication. The purpose of the current study was to explore the antiproliferative effect of ZW against HCC in vitro. Materials and Methods: To achieve this goal, elemental analysis by inductively coupled plasma mass spectrometry (ICP-MS) was used for metal testing in ZW and tap water (TW), as well as metal-free water sources, deionized water (DW) and double deionized water (DDW). Water was applied in vitro on hepatic cancer HepG2 cells to test their cytotoxic effects and the underlining apoptotic mechanism. One-way ANOVA was used as a statistical method to compare between treated and untreated groups. Results: It was found that ZW is explicitly rich in Na, Ca and Mg ions which are essential for biological homeostasis in human beings. Moreover, it was reported that ZW has an oncolytic property, owing to the presence of V, Fe and Se, where it produces the highest killing effect with about 35% of cell death associated with mitochondrial impairment with a dose dependent decrease in cell viability of HepG2 cells upon treatment. To test the underlining mechanism of the anti-cancer effect of ZW, apoptosis was performed to investigate the apoptotic signals. It was found that ZW killed the HepG2 cells through apoptosis. Mechanistically, 0.84% of the pro-apoptotic cells increased significantly to be 38% post-treatment with 50% ZW v/v. Conclusion: The balanced nutritional composition of ZW could be of great interest, synergizing with other anti-cancer components to thwart cancer progression.
Research Article
Antimicrobial Profile of Premna pubescens. Blume and Centella asiatica Extracts Against Bacteria and Fungi Pathogens
Martina Restuati and Diky Setya Diningrat
Background and Objective: North Sumatera Indonesia has a rich heritage of knowledge on medicinal plants used for preventive and curative medicine Premna pubescens. Blume (Buasbuas) has been used to increase the body immunity and endurance. Centella asiatica (Pegagan) is used for medicinal purposes. This study is important to find out the antimicrobial capabilities of Premna pubescens (P. pubescens) and Centella asiatica (C. asiatica) methanol extracts. This study is expected to provide the scientific foundation for the development of plants that are traditionally believed to be efficacious drug. The aim of the study was to investigate in vitro antimicrobial activity of North Sumatera medicinal plants P. pubescens and C. asiatica against the main pathogens. Materials and Methods: The organic solvent plant extracts are tested on the various microorganisms including bacteria and fungi by using agar diffusion technique. The data was analyzed with ANOVA statistics by using SPSS software. Results: The length of the inhibition zone was measured in mm from the edge of the well to the inhibition zone. P. pubescens showed significant moderate activity against (14 mm) Pseudomonas marginalis and (21 mm) Streptococcus mutans with 100 mg mL–1 DMSO plant drug concentration. The results of lowest (MICs) values are at 66 and highest ones are at 152 mg mL–1 for P. pubescens meanwhile those of (MICs) values are 0-155 mg mL–1 for C. asiatica. Conclusion: In general, based on the result of this research, it can be said that P. pubescens and C. asiatica plants can be used as antibacterial and antifungal compounds.
Research Article
Population Pharmacokinetic Modeling and Simulation of Afloqualone to Predict Steady-state Exposure Levels
Hyun-moon Back, Sudeep Pradhan, Young-ran Yoon, Wonku Kang, Jung-woo Chae, Nayoung Han, Nakajima Miki, Kwang-il Kwon, Sang-kyum Kim and Hwi-yeol Yun
Background and Objective: Afloqualone (AFQ) is a quinazoline family GABAergic drug used as muscle relaxant. After oral administration of AFQ, greatly elevated exposure in some individuals were observed which might cause severe side effects. The aim of this study was to develop a population pharmacokinetic model of AFQ and search possible reason of high inter-individual variability (IIV) in the clinical study and further demonstrate its impact on exposure on AFQ through simulation. Methodology: To evaluate the exposure of AFQ and confirm the high difference between subjects, non-compartmental analysis was assessed. A Population PK model of AFQ was developed using healthy human AFQ PK data and simulation study was performed with final PK model. Results: A two-compartment model with first order absorption and elimination was used to explain the pharmacokinetics of AFQ. The high level of HIV in AFQ exposure was explained through assumption two subject group with high exposure group (HEG) or normal exposure group (NEG). Through simulations, it was proved that big difference of AFQ exposure between subjects could be observed in some individual and dose of AFQ needs to be reduced for such subjects in HEG. Conclusion: Population PK model of AFQ for explaining high IIV was successfully developed and exposure of AFQ between subjects was simulated. Finally, suggesting an appropriate dose of AFQ in HEG which could be had possibility of genetic polymorphism.
Research Article
Anticoagulation Therapy: For Patients Attitude, Knowledge and Concerns Regarding their Effects on International Normalized Ratios in Saudi Arabia
Fahad Ibrahim Al-Saikhan, Mohamed Abd-Elghany Abd-Elaziz, Rehab Hamdy Ashour and Taimour Langaee
Background and Objective: Thoughtful evaluation of patients’ knowledge, satisfaction and concerns in anticoagulation clinics helps to understand areas of improvement. This study aimed to examine patients’ drug knowledge, satisfaction and concerns with provided anticoagulation services. Materials and Methods: This study was designed as a cross-sectional survey that was developed and conducted in a regional anticoagulation clinic with good number of patients. Two hundred sixty eight were recruited in the survey. Patients’ warfarin refill records and time within the therapeutic INR range were retrieved from hospital databases. All statistical assessment and analysis were carried out with SPSS. Results: Adequate knowledge of warfarin-food and warfarin-drug interactions was lacking in about 50% of patients. Satisfaction with provided service was not optimal. Concerns associated with warfarin was bothersome to many patients due to possible drug-drug interactions (41.42%), missed doses impact (29.10%), adverse drug reactions (29.85%). All of which might lead to unfavorable consequences. Higher satisfaction was associated with better knowledge (r = 0.27, p = 0.001) and fewer concerns (rs = - 0.26, p = 0.002). Improved drug-related knowledge and higher satisfaction were positively reflected in these patients’ attitude toward drug use compliance in knowledge (rs = 0.23, p = 0.01) and satisfaction (rs = 0.19, p = 0.041). Eventually, good INR control was shown more with better knowledge, higher satisfaction and better warfarin adherence (p = 0.004, 0.03, 0.04 and 0.004, respectively). Conclusion: There is a deficit in patients’ knowledge and satisfaction with warfarin therapy. Such deficits lifted the threshold of concerns with warfarin use and negatively affected INR control.
Research Article
Orally Administered Chitooligosaccharides Modulate Colon Microbiota in Normal and Colitis Mice
Ting Long, Zhi-Jun Yu, Jun Wang, Jia Liu and Bing-Shu He
Background and Objective: The alterations in the gut microbiota composition are gaining increasing attention in view of their influence on the development of ulcerative colitis. The anti colitis effect of orally administered chitooligosaccharides (COS) had been reported in the animal models of ulcerative colitis but the mechanism is still uncertain. Interestingly, COS have long been proposed as potential natural prebiotics based on in vitro experiments. The aim of this study is to confirm the prebiotic property of COS in vivo and further clarify the mechanisms of their anti colitis effect. Materials and Methods: The COS at the dose of 500 mg kg–1 were orally given normal mice and colitis mice treated by 3.5% dextran sulfate sodium (DSS). The colon microbial composition in mice was evaluated by qualitative analysis of 16S ribosomal DNA in colonic content samples using real-time PCR. Results: The COS could function as prebiotics by increasing the levels of Bacteroidetes and Actinobacteria phyla, the relative ratio of Bacteroidetes to Firmicutes, as well as common probiotics such as Lactobacillus and Bifidobacterium and inhibiting the growth of Firmicutes and Proteobacteria phyla, as well as potential pathogens such as Enterococcus, in both normal and colitis mice. In addition, oral intake of COS were found to enhance the colonic concentrations of short-chain fatty acids (SCFAs), the dominating fermentation end-products of bacteria in the large bowel having abilities to support the transport processes, energy metabolism, cellular growth and differentiation of colonocytes. Conclusion: The data suggested that COS administration might had beneficial effects on the health of the intestinal tract and more importantly, tended to protect mice from dysbiosis of native gut microbiome and against the suppression of SCFA production, which might be a potential mechanism for their anti colitis effect.

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