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Publication Open Access Cyclooxygenase enzymes expression in the kidney(2014) Namphung Suemanotham; Mahidol University. Faculty of Veterinary Science. Department of Clinical Science and Public Healthdisease. In human medicine, renal cyclooxygenase (COX) enzymes (especially COX-2) have been involved in the progression of CKD as one of the biological mechanism that modulates hypertension and/or proteinuria via their products, prostanoids. Furthermore...โรคไตเรื้อรังเป็นหนึ่งในสาเหตุหลักของการเสียชีวิตทั้งในมนุษย์และสัตว์ การพบภาวะโปรตีนในปัสสาวะเรื้อรังที่มีต้นกำเนิดมาจากไต และภาวะความดันโลหิตสูงถือเป็นสองปัจจัยที่มีความเกี่ยวข้องกับการพัฒนาของโรค การศึกษาในมนุษย์พบว่า เอนไซม์ cyclooxygenase (COXPublication Open Access Preliminary evaluation of the analgesic and anti-inflammatory effects of Tacca integrifolia in rodents(2015) Thatree Autsavakitipong; Parirat Khonsung; Ampai Panthong; Natthakarn Chiranthanut; Puongtip Kunanusorn; Narong Nuntasaen; Thaworn Jaipetch; Samreang Bunteang; Vichai Reutrakul; Mahidol University. Kanchanaburi Campus. Center for Innovation ChemistrySummary. This is a preliminary investigation of the ethyl acetate extract of the leaf of Tacca integrifolia (TIE) for the analgesic activity using writhing response in mice, tail flick test in rats and for anti-inflammatory activity using ethyl phenyl propiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid-induced hind paw edema, as well as cotton pellet-induced granuloma formation in rats. The results showed that TIE (200 mg/kg, PO) significantly inhibited pain caused by acetic acid injection (65.9%) but did not exhibit effect in tail flick test in rats. These findings suggest that analgesic mechanism of TIE may act via peripherally pathway. The study of anti-inflammatory effect showed that TIE significantly inhibited ear edema induced by EPP. TIE (200 mg/kg, PO) inhibited paw edema induced by carrageenan (55.5%) and arachidonic acid (48.6%) but had no effect on cotton-induced granuloma formation in rats. In conclusion, the ethyl acetate extract of leaf of T. integrifolia possessed anti-inflammatory activity in acute inflammation and analgesic activity. Industrial relevant. Plants of the genus Tacca have been reported to possess many activities such as analgesic, anti-inflammatory and, antipyretic activities. Many species have been used to treat high blood pressure, burn, gastric ulcer, and hepatitis. The scientific studies supporting the traditional uses of Tacca integrifolia for some of the alleged activities are still lacking. The screening test for analgesic and anti-inflammatory effect of the ethyl acetate extract of the leaf of Tacca integrifolia provides scientific data to confirm the potentials of T. integrifolia as an analgesic and anti-inflammatory anti-inflammatory drug in the future.Publication Open Access Identification of clinical factors associated with severe dengue among Thai adults: a prospective study(2015) Vipa Thanachartwet; Nittha Oer-areemitr; Supat Chamnanchanunt; Duangjai Sahassananda; Akanitt Jittmittraphap; Plengsakoon Suwannakudt; Varunee Desakorn; Anan Wattanathum; Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical MedicineBackground: Dengue is the most common mosquito-borne viral disease in humans. Recently, there has been an epidemic shift of dengue from mainly affecting children to affecting more adults with increased severity. However, clinical factors associated with severe dengue in adults have varied widely between studies. We aimed to identify the clinical factors associated with the development of severe dengue according to the World Health Organization (WHO)’s 2009 definition. Methods: We conducted a prospective study of adults with dengue admitted to the Hospital for Tropical Diseases in Bangkok, Thailand, from October 2012 to December 2014. Univariate and stepwise multivariate logistic regression analyses were performed. Results: Of the 153 hospitalized patients with confirmed dengue viral infections, 132 (86.3 %) patients had non-severe dengue including dengue without warning signs (7 patients, 5.3 %) and dengue with warning signs (125, 94.7 %). The rest (21, 13.7 %) had severe dengue including severe plasma leakage (16, 76.2 %), severe organ involvement (16, 76.2 %), and severe clinical bleeding (8, 38.1 %). Using stepwise multivariate logistic regression, clinical factors identified as independently associated with the development of severe dengue were: (1) being >40 years old (odds ratio [OR]: 5.215, 95 % confidence interval [CI]: 1.538–17.689), (2) having persistent vomiting (OR: 4.817, CI: 1.375–16.873), (3) having >300 cells per μL of absolute atypical lymphocytes (OR: 3.163, CI: 1.017–9.834), and (4) having lactate levels ≥2.0 mmol/L (OR: 7.340, CI: 2.334–23.087). In addition, increases in lactate and absolute atypical lymphocyte levels corresponded with severe dengue (p < 0.05). Conclusions: Our study identified several clinical factors independently associated with the development of severe dengue among hospitalized adults with dengue. This can aid in the early recognition and prompt management of at-risk patients to reduce morbidity and mortality.Publication Open Access Possible involvement of glucocorticoids in mycotoxin-induced neuroinflammation(2015) Boonrat Chantong; Punnee Nusuetrong; Mahidol University. Faculty of Veterinary Science. Department of Preclinical Science and Applied Animal Science; Srinakharinwirot University. Faculty of Medicine. Department of PhysiologyThe mycotoxins are commonly encountered in human cereal foods and animal feed throughout the world as a result of infestation of grains in the field and in storage by the fungi including genus Aspergillus, Penicillum and Fusarium. Modulation of the inflammatory responses in the central nervous system (CNS) appears particularly critical role of some relevance mycotoxins such as T-2 toxin, fumonisin B1 and ochratoxin A. Specifically, mentioned mycotoxins disturbed mitogen-activated protein kinases (MAPKs) as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) which mediate robust induction of proinflammatory gene expression in both in vitro and in vivo. In CNS, glucocorticoids are powerful endogenous and therapeutic modulators of inflammation though both MAPKs and NF-κB signaling. In addition, toxicity of mycotoxins also was altered with glucocorticoid. Taken together, glucocorticoids may possibly involve in the action of mycotoxins on neuroinflammatory responses. Therefore, factors disturbing glucocorticoid regulation in CNS such as stress, infection, and xenobiotics may enhance response to mycotoxin toxicity. It is anticipated that these investigations will be applicable to identify the therapeutic intervention or prevention.Publication Open Access Effect of simvastatin on monocyte chemoattractant protein-1 expression in endometriosis patients: a randomized controlled trial(2017) Wanwisa Waiyaput; Somphoch Pumipichet; Sawaek Weerakiet; Sasivimol Rattanasiri; Areepan Sophonsritsuk; Mahidol University. Department of Obstetrics & Gynecology, Ramathibodi Hospital . Reproductive Endocrinology and Infertility UnitBackground: Simvastatin is a promising new drug for the treatment of endometriosis. It is a cholesterol-lowering drug that acts by inhibiting HMG-CoA reductase, resulting in a decrease in mevalonate, a precursor of cholesterol and monocyte chemoattractant protein-1 (MCP-1). This study investigated the effect of pre-operative oral simvastatin administration on MCP-1 gene expression and serum MCP-1 protein levels in patients with endometriosis. Methods: A prospective, randomized, controlled study was conducted at the Reproductive Endocrinology Unit of the Department of Obstetrics and Gynecology at the Faculty of Medicine Ramathibodi Hospital. Forty women (mean age: 18–45 years) scheduled for laparoscopic surgery who had been diagnosed with endometriosis were recruited and randomly assigned to either a treatment group (20 mg/d of orally administered simvastatin for 2 weeks before surgery) or an untreated control group. Serum was collected before and after treatment and protein levels of MCP-1 were determined. MCP-1 and CD68 transcript levels were also quantified using real-time PCR on endometriotic cyst tissues. Results: MCP-1 gene expression on endometriotic cyst was not significantly different between the simvastatin-treated and untreated groups (P = 0.99). CD68 expression was higher in the treatment group compared to the control group, but this was not statistically significant (P = 0.055). Serum MCP-1 levels following simvastatin treatment were higher than in samples obtained before treatment (297.89 ± 70.77 and 255.51 ± 63.79 pg/ml, respectively) (P = 0.01). Conclusions: Treatment with 20 mg/d of simvastatin for 2 weeks did not reduce the expression of either the chemokine MCP-1 gene or macrophage-specific genes. Cumulatively, this suggests that simvastatin is not ideal for treating endometriosis because a higher dose of simvastatin (40–100 mg/d) would be needed to achieve the target outcome, which would significantly increase the risk of myopathy in patients. Trial registration: Thai Clinical Trials Registry TCTR20130627003 Registered: June 27, 2013.Publication Open Access Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke.(2013-09) Salunya Tancharoen; ศรัณยา ตันเจริญ; Kikuchi, Kiyoshi; Ito, Takashi; Morimoto-Yamashita, Yoko; Miura, Naoki; Kawahara, Ko-ichi; Maruyama, Ikuro; Murai, Yoshinaka; Tanaka, Eiichiro; Tanaka, Eiichiro; Mahidol University. Faculty of Dentistry. Department of PharmacologyStroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.Publication Open Access Lupinifolin, a bioactive flavanone from Myriopteron extensum (Wight) K. Schum. stem(2004-12) Noppamas Soonthornchareonnon; Lersak Ubonopas; Songsri Kaewsuwan; Mansong Wuttiudomlert; Mahidol University. Faculty of Pharmacy. Department of Pharmacognosy; Mahidol University. Faculty of Pharmacy. Department of MicrobiologyLupinifolin was isolated from the crude hexane extract of Myriopteron extensum stem. Structural identification was carried on by spectroscopic methods and the comparison of its mp,[α]27 D, 1H and 13C NMR spectroscopic data with published values and biological activities (anti-herpes simplex virus type 1, antimycobacterial, antibacterial, antifungal, antiplasmodial, anti-inflammatory, antioxidative and cytotoxicity) of ethanolic extract and lupinifolin were tested. Lupinifolin and the ethanolic extract exhibited strongly active anti-HSV-1 with IC50 values of 0.3 and 0.1 μg/ml, respectively. Lupinifolin showed selective cytotoxicity towards breast cancer (BC) with IC50values of 3.3 μg/ml and expressed weakly cytotoxic activity towards KB and NCI-H187. Lupinifolin also expressed moderate antimycobacterial activity with MIC at 12.5 μg/ml. Lupinifolin was inactive against Candida albicans and dermatophytes while the ethanolic extract inhibited all tested dermatophytes with the concentration of 6.73 mg/disc. Both of them showed moderate active to Gram-positive bacteria and no activity against Gram-negative bacteria. Lupinifolin and the ethanolic extract showed inactive in the DPPH radical scavenging, antiplasmodial and anti-inflammatory assay at concentration 200, 10 and 50 μg/ml, respectively.Publication Open Access Antibacterial activity of Ocimum sanctum oil against Streptococcus mutans : in vitro.(2015-09) Rattiporn Kaypetch; รัตติพร กายเพชร; Thaniya Muadcheingka; ธนิยา หมวดเชียงคะ; Pairin Tonput; Rattiporn Kaypetch; รัตติพร กายเพชร; Mahidol University. Faculty of Dentistry. Research Office; Mahidol University. Faculty of Dentistry. Department of Oral MicrobiologyObjectives: This study aimed to investigate the antibacterial effect of essential oil extracted from Ocimum sanctum against caries-related bacteria, Streptococcus mutans. Materials and methods: Essential oil extracted from leaves of Ocimum sanctum by steam distillation (Botanicessence, Bangkok, Thailand) were used in this study. The antibacterial effect was determined against Streptococcus mutans ATCC 25175 and Streptococcus mutans KPSK2 using disc diffusion and micro broth dilution technique. Results: Ocimum sanctum essential oil had antibacterial effects against both strains of Streptococcus mutans with the zone of inhibition ranging from 7 to 25.95 mm. The antibacterial effect against Streptococcus mutans KPSK2 was more potent than that on Streptococcus mutans ATCC 25175. Minimum inhibitory concentration of Streptococcus mutans ATCC 25175 and Streptococcus mutans KPSK2 equal to 0.188 and 0.047 mg/ml, respectively. Minimum bactericidal concentration against Streptococcus mutans ATCC 25175 and Streptococcus mutans KPSK2 equal to 0.377 and 0.095 mg/ml. Conclusion: Essential oils from Ocimum sanctum showed moderate antibacterial effect against both strains of Streptococcus mutans. It can be beneficial to use as an agent to prevent or aid the treatment of dental caries.Publication Open Access Gastric acid inhibition of Capsicum extract in isolated mouse whole stomach(2006-06) Utaipat A; Chareonsuk S; Thongyen A; Thirawarapan SS; Suvitayavat W; Mahidol University. Faculty of Pharmacy. Department of Pharmacology; Mahidol University. Faculty of Pharmacy. Department of PhysiologyThe purpose of this study was to determine the effect of capsicum extract on gastric acid secretion induced by histamine and bethanechol using the isolated mouse stomach model. Gastric acid secretions were collected every 10 minutes. After collecting the first sample, capsicum extract was applied to the serosal solution in the organ bath. 20 minutes after applying capsicum extract, 5 μM histamine or 100 μM bethanechol was applied. This study has found that capsicum extract could reduce gastric acid secretion induced by histamine. Capsicum extract at concentrations of 8 and 16 μg/ ml significantly reduced gastric acid secretion, 8 μg/ml producing the greatest effect on reduction of cumulative acid secretion. The inhibitory effect of capsicum extract (8 μg/ml) on acid secretion induced by histamine was reduced in the presence of indomethacin (0.1 μM), suggesting a role of prostaglandins in the capsicum response. In contrast to histamine-induced secretion, 8 μg/ml capsicum extract did not decrease gastric acid secretion induced by bethanechol. In summary, capsicum extract at a concentration of 8 μg/ml reduced gastric acid secretion induced by histamine, partially reduced this secretion through prostaglandins but had no effect on induction of gastric secretion by bethanechol.Publication Open Access Elucidating the structure-activity relationships of the vasorelaxation and antioxidation properties of thionicotinic acid derivatives(2010) Supaluk Prachayasittikul; Orapin Wongsawatkul; Apilak Worachartcheewan; Chanin Nantasenamat; Somsak Ruchirawat; Virapong PrachayasittikulNicotinic acid, known as vitamin B3, is an effective lipid lowering drug and intense cutaneous vasodilator. This study reports the effect of 2-(1-adamantylthio)nicotinic acid (6) and its amide 7 and nitrile analog 8 on phenylephrine-induced contraction of rat thoracic aorta as well as antioxidative activity. It was found that the tested thionicotinic acid analogs 6-8 exerted maximal vasorelaxation in a dose-dependent manner, but their effects were less than acetylcholine (ACh)-induced nitric oxide (NO) vasorelaxation. The vasorelaxations were reduced, apparently, in both NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin (INDO). Synergistic effects were observed in the presence of L-NAME plus INDO, leading to loss of vasorelaxation of both the ACh and the tested nicotinic acids. Complete loss of the vasorelaxation was noted under removal of endothelial cells. This infers that the vasorelaxations are mediated partially by endothelium-induced NO and prostacyclin. The thionicotinic acid analogs all exhibited antioxidant properties in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays. Significantly, the thionicotinic acid 6 is the most potent vasorelaxant with ED50 of 21.3 nM and is the most potent antioxidant (as discerned from DPPH assay). Molecular modeling was also used to provide mechanistic insights into the vasorelaxant and antioxidative activities. The findings reveal that the thionicotinic acid analogs are a novel class of vasorelaxant and antioxidant compounds which have potential to be further developed as promising therapeutics.