H. Bas, Z. Takçı, A. Arici, Sercan Sezgin, Cigdem kunt Lsler
{"title":"A Clinical Experience: A Cutaneous Leishmaniasis Case with Spontan AbortusFollowing To Meglumine Antimoniate Therapy","authors":"H. Bas, Z. Takçı, A. Arici, Sercan Sezgin, Cigdem kunt Lsler","doi":"10.4172/2157-7609.1000183","DOIUrl":"https://doi.org/10.4172/2157-7609.1000183","url":null,"abstract":"A 27 years old female patient was diagnosed with cutaneous leishmaniasis histopathologically and received intramuscular meglumine antimoniate therapy at a dose of 20 mg/kg/day for consecutive 20 days. The base-line pretreatment complete blood count, hepatic transaminases, lipase, amylase, beta-hCG level and electrocardiogram were within normal limits. Following to the treatment-free two weeks at the control visit, the patient stated that she was 4 weeks pregnant. Gynecological follow-up was recommended to the patient but it is learned that she had spontaneous abortion one day later. We presented our experience on this case regarding possible toxicity of meglumine antimoniate treatment on fetus.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"174 1","pages":"0-0"},"PeriodicalIF":0.0,"publicationDate":"2015-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78028487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Review of the Biochemical, Hematological and Histological Modulations in Acetaminophen Induced Hepatoxicity and the Potential of Urtica Dioica in the Regeneration of the Liver","authors":"K. Juma, N. J. Joseph, Mburu N David","doi":"10.4172/2157-7609.1000182","DOIUrl":"https://doi.org/10.4172/2157-7609.1000182","url":null,"abstract":"Acetaminophen is a common antipyretic/analgesic drug available as an over the counter prescription. It is an acetilide and phenacetic derivatives. Extensive studies on the safety of acetaminophen have been performed and evidence of hepatoxicity remains to be established. It has also been used in the management of fever and pain. In addition, it has been compounded with many other drugs raising concerns over the safety and efficacy of the use of acetaminophen. The toxicity effect of acetaminophen have also been sustained in all routes of administration; intravenous, intramuscular, rectal and oral with similar biochemical, hematological and histological profiles. The liver is the main organ responsible for metabolic biotransformation of acetaminophen. The hematological, biochemical and pathological effect of the acetaminophen hepatotoxicity will provide a better understanding of the mechanism of action in acetaminophen toxicity. This study therefore reviews previous studies assessing hepatoxicity by examining the biochemical, hematological and histological findings as determined after acetaminophen administration. The potential for Urtica dioica in protecting the liver and its ability in regenerating the hematological, liver enzymes and tissues has been demonstrated in many other studies as shown in this study. Hence, there is great potential for Urtica dioica in the protection of the liver against acetaminophen induced hepatotoxicity. Statistical analysis is also very important for the interpretation of toxicity data. This study has also reviewed the relevant statistical methods as they have been used in various toxicological studies.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"130 4 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2015-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76595955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Chinnasamy, himathi, Neo Xuan Hao Edwin, P. Jayaraman, J. Venugopal, S. Ramakrishna, Dinesh Kumar Srinivasan
{"title":"Controlled Release of Dexamethasone in PCL/Silk Fibroin/Ascorbic Acid Nanoparticles for the Initiation of Adipose Derived Stem Cells into Osteogenesis","authors":"G. Chinnasamy, himathi, Neo Xuan Hao Edwin, P. Jayaraman, J. Venugopal, S. Ramakrishna, Dinesh Kumar Srinivasan","doi":"10.4172/2157-7609.1000177","DOIUrl":"https://doi.org/10.4172/2157-7609.1000177","url":null,"abstract":"Mimicking hybrid extracellular matrix is one of the major challenges in bone tissue engineering. Biocomposite micro/nanoparticle of polycaprolactone (PCL), silk fibroin (SF), ascorbic acid (AA) and dexamethasone (DM) were fabricated by the electrospraying methods in order to generate an improved osteogenic environment for the proliferation and differentiation of adipose derived stem cells (ADSCs) into osteogenesis. Fabricated electrosprayed micro/nanoparticle was characterized for particle morphology, hydrophilicity, porosity and FTIR analysis for bone tissue regeneration. FESEM micrographs of the nanoparticles revealed porous, fibreless, uniform particles with particle diameter in the range of 720 ± 1.8 nm - 3.5 ± 4.2 μm. The drug release profile indicates that the sustained release of dexamethasone up to 10 days and degradation of nanoparticles around 13-20% after 60 days. ADSCs were cultured on these nanoparticles and were induced to undergo osteogenic differentiation in the presence of AA/DM. The cells morphology, proliferation and interaction were analysed by CMFDA dye extraction method, MTS assay and FESEM analysis respectively.ADSCs differentiation into osteogenesis was confirmed using alkaline phosphatase activity and mineralisation by Alizarin Red staining. The significance of AA and DM biomolecules initiates particular biological functions for the proliferation of ADSCs and differentiation into osteogenic lineages. The obtained results proved that the biocomposite PCL/SF/AA/DM micro/nanoparticle stimulated osteogenic differentiation and mineralisation of ADSCs for bone tissue regeneration.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"19 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2015-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82901831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haoping Huang, Guoguang Liu, Wenying Lv, Kun Yao, Yapu Kang, Fuhua Li, Longli Lin
{"title":"Ozone-Oxidation Products of Ibuprofen and Toxicity Analysis in Simulated Drinking Water","authors":"Haoping Huang, Guoguang Liu, Wenying Lv, Kun Yao, Yapu Kang, Fuhua Li, Longli Lin","doi":"10.4172/2157-7609.1000181","DOIUrl":"https://doi.org/10.4172/2157-7609.1000181","url":null,"abstract":"In this study, we report the simulation of the ozone disinfection of drinking water in the presence of ibuprofen, its oxidative degradation products, and the acute toxicity analysis by luminescent bacteria bioassay. The results showed that the ibuprofen oxidation followed first-order kinetics. The ultra-performance liquid chromatography quadrupole time-of-flight mass (UPLC/Q-TOF-MS) analysis showed that the major oxidation products of ibuprofen were as follows: (i) 4-ethylbenzaldehyde, (ii) 2-[4-(1,2-dihydroxypropyl)-2-hydroxy carboxylic acid, (iii) 1-(4-ethylphenyl)-2-methylpropanol, (iv) 1-(4-ethylphenyl)-2-methylpropanone, (v) 2-[4-(1-hydroxy-2-methylpropyl)phenyl]isobutyl propionate, and (vi) 4-ethylbutyl benzene. A reaction mechanism for the ibuprofen oxidation was proposed based on the oxidative degradation products. The photobacterium phosphoreum toxicity tests showed that the toxicity of the ibuprofen oxidation products is higher than ibuprofen. Thus, the ozone-oxidation products of ibuprofen generate a higher risk of acute toxicity.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"56 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2015-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88429582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Charfi, M. Bensassi, E. Gaïes, H. Eljebari, N. Jebabli, M. Lakhal, A. Klouz, I. Salouage, S. Trabelsi
{"title":"PRES Induced by Cyclosporin with Normal Blood Concentrations in a Bone Marrow Recipient","authors":"R. Charfi, M. Bensassi, E. Gaïes, H. Eljebari, N. Jebabli, M. Lakhal, A. Klouz, I. Salouage, S. Trabelsi","doi":"10.4172/2157-7609.1000178","DOIUrl":"https://doi.org/10.4172/2157-7609.1000178","url":null,"abstract":"Introduction: Posterior reversible encephalopathy syndrome (PRES) is a clinic neuroradiological entity. This syndrome occurs in complex conditions as allogenic bone marrow transplantation, organ transplantation and immunosuppressant therapy such as cyclosporin (CsA). The occurrence of PRES is favored by a high concentration of CsA. Therefore, therapeutic monitoring of CsA is necessary to effects due to overdose. The therapeutic range of CsA is between 150-300 ng/mL. We aimed to present a case PRES induced by CsA in bone marrow transplantation with normal cyclosporine blood concentrations. Case: A 26 years old man received an allogenic bone marrow for bone marrow aplasia in January 2013. He was treated by CsA. Mean CsA dose was 2.57 mg/kg/day. CsA mean blood concentration was 295 ng/mL. After 20 days, our patient presented a complex partial seizure and cortical abnormal. He had no history of head injury, epilepsy or hypertension and there was no family history of neurological or psychiatric disorders. Patient’s blood pressure wasn’t measured. CsA was stopped. He received mycophenolate acid and clonazepam. Seizure and abnormal vision vanished 10 days later. Whereas, the patient developed graft-versus-host disease (GVHD). Then, mycophenolate acid was stopped 1.5 month later and CsA taken back. CsA mean dose was 1.1 mg/kg/day. Mean CsA blood concentration was 167.71 ng/mL. After two months, the patient developed general seizures and in Magnetic Resonance Imaging (MRI) there was a low-density in the subcortical white matter areas. So, CsA was stopped once and for all and the seizures vanished few days later. Conclusion: PRES is responsible for various and no specific neurological symptoms. These symptoms are usually reversible but sometimes fatal. Therapeutic monitoring of CsA was necessary to avoid neurotoxicity depending of concentration but we must remain cautious even if patients have CsA blood concentrations in the therapeutic range.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"16 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2015-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79138821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanostructures for Drug Delivery","authors":"Vinit Kumar, F. Rizzolio, G. Toffoli","doi":"10.4172/2157-7609.1000E125","DOIUrl":"https://doi.org/10.4172/2157-7609.1000E125","url":null,"abstract":"","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72773986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Shindoh, R. Shishido, Natsu Narumi, H. Takano, M. Miura
{"title":"Effects of Long-Acting ò2-Agonist and Corticosteroid Inhalation on Diaphragm Muscle in Mice","authors":"C. Shindoh, R. Shishido, Natsu Narumi, H. Takano, M. Miura","doi":"10.4172/2157-7609.1000176","DOIUrl":"https://doi.org/10.4172/2157-7609.1000176","url":null,"abstract":"Background and Objective: Although a combination of inhaled corticosteroid (ICS) and inhaled long-acting β2- agonist (LABA) reduces exacerbation of asthma, whether these affect diaphragm muscle contraction is still unclear. Methods: We investigated the effects of ICS and LABA inhalation separately, endotoxin injection-only, and ICS or LABA inhalation plus endotoxin injection on diaphragm contractile properties and nitric oxide (NO) production during 4 h, using BALB/c mice (n=84). In this study, budesonide was used as the ICS, and formoterol fumarate dehydrate was used as the LABA. After administrations of these drugs, the diaphragm muscles were dissected, and their contractile properties, including force/frequency (F/f) curves and twitch contraction, were measured by electrical pulse stimulation in an isometric condition. A reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry was performed to assess NO production, which induces cellular damages in diaphragm muscle fibers. Results: The ICS inhalation did not significantly shift the F/f curves; but the LABA inhalation significantly shifted them upward compared with shams at 1 h (p < 0.01), 2 h (p < 0.01), and 4 h (p < 0.05) after inhalation, that is, it showed an inotropic effect. Although endotoxin injection resulted in a downward shift in F/f curves at 4 h (p < 0.01) and induced NO production, the endotoxin plus either ICS or LABA inhalation prevented downward shifts of the F/f curves and inhibited NO production. Conclusions: These results indicate that the inhalation of LABA potentiates diaphragm muscle contractility more than ICS inhalation and that both ICS and LABA inhalation inhibit NO production induced by endotoxin injection.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"12 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2015-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85255626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plasma Exosomes and Drug Metabolic Cytochrome P450 Enzymes","authors":"Santosh Kumar","doi":"10.4172/2157-7609.1000E124","DOIUrl":"https://doi.org/10.4172/2157-7609.1000E124","url":null,"abstract":"The major drug metabolic enzymes, Cytochromes P450 (CYP), are abundantly present in hepatocytes, and to some extent in other extrahepatic cells such as monocytes. Since these enzymes metabolize the majority of xenobiotics leading to formation of Reactive Oxygen Species (ROS) and some toxic metabolites, hepatocytes and monocytes could produce extracellular vesicles such as exosomes. The exosomes produced by the liver and blood cells eventually secrete into the plasma, which may contain high levels of exosomes containing CYP enzymes. The level of plasma exosomal CYP enzymes may also be induced under certain conditions. Therefore, plasma exosomal CYP may be used as biological markers, as well as biocatalysts for various purposes in medicine, bioremediation, and industrial synthesis. This editorial briefly describes this novel and exciting area of research in the field of exosomes, and their potential as biomarkers and in therapy.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"3 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2015-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85984190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrochemical Detection of p-Chloroaniline at Clay Modified Carbon Paste Electrode: Application in Tap Water","authors":"T. E. Ouafy, A. Chtaini, H. Oulfajrite, R. Najih","doi":"10.4172/2157-7609.1000174","DOIUrl":"https://doi.org/10.4172/2157-7609.1000174","url":null,"abstract":"We report a sensitive electrochemical voltammetric method for analyzing p-Chloroaniline using a carbon paste electrochemical (CPE) modified by porous material, such Clay (C). P-Chloroaniline strongly adsorbed on a C-CPE surface and provides facile electrochemical quantitative methods for electroactive p-Chloroaniline (p-CA). Operational parameters have been optimized, and the stripping voltammetric performance has been studied using square wave voltammetry. The peaks current intensity are highly linear, with a good sensitivity of C-CPE. These findings can lead to a widespread use of electrochemical sensors to detect chloroaniline contaminates.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"16 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2015-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73289424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"17-Hydroexemestane: A Potent Inhibitor of CYP19 (Aromatase) and Substrate of CYP3A","authors":"ry Kk, David Fa, D. Zeruesenay","doi":"10.4172/2157-7609.1000171","DOIUrl":"https://doi.org/10.4172/2157-7609.1000171","url":null,"abstract":"17-hydroexemestane is the major metabolite of exemestane in vivo. Previous studies have shown that 17-hydroexemestane is androgenic and bone protective. Due to structure similarities, we hypothesized that, like exemestane, 17-hydroexemestane is an inhibitor of aromatase (CYP19). Our aim was to assess the potency (IC50) of 17-hydroexemestane toward CYP19 inhibition, and to determine the specific CYPs responsible for 17-hydroexemestane metabolism. Using recombinant human CYP19, we investigated the ability of exemestane and 17-hydroexemestane to block the formation of estradiol from testosterone. We found that 17-hydroexemestane potently inhibited aromatase. IC 50 values for the inhibition of CYP19 by exemestane and 17-hydroexemestane were 1.5 μM and 3 μM, respectively. Furthermore, using recombinant human P450s, human liver microsomes, and HPLC analytical techniques, we identified one major metabolite (MIII) of 17-hydroexemestane in the human liver microsomal incubate. In a bank of 15 well-characterized HLMs, MIII formation rate was significantly correlated with the activity of CYP3A (rs= 0.78, p=0.001).In a panel of baculovirus-expressed CYP enzymes, only CYP3A4 and CYP3A5 catalyzed MIII formation at the highest rate. In sum, these in vitro data suggest that 17-hydroexemestane is a potent inhibitor of CYP19 and that CYP3A plays a major role in its metabolism. Whether genetic polymorphisms and drug interactions involving these enzymes may contribute to the disposition and action of 17-hydroexemestane in breast cancer patients remains to be elucidated.","PeriodicalId":15537,"journal":{"name":"Journal of Drug Metabolism and Toxicology","volume":"6 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86621687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}