Pub Date : 2016-04-23DOI: 10.3844/AJPTSP.2016.8.19
M. Canavese
Understanding the inflammasome biology is one of the most exciting challenges in immuno-pharmacology. The role of the inflammasomes has been recognized in the host defense mechanism against invading pathogens and in the development of several conditions, such as cancer, auto-inflammatory, autoimmune, metabolic and neurodegenerative disorders. DNA recognition by the cells is a crucial immunological step leading to the initiation of an innate immune response. Absent in Melanoma 2 (AIM2) is a cytoplasmic sensor that perceives double-stranded DNA of microbial or host origin. Once the DNA is bound, AIM2 assembles a multiprotein complex named inflammasome, which drives pyroptosis and proteolytic cleavage of pro-IL-1I² and pro-IL-18 pro-inflammatory cytokines, leading to a protective inflammasome-mediated host response. However, improper recognition of self-DNA by AIM2 triggers deleterious inflammatory responses, leading to systemic inflammation and several pathological conditions. Therefore, understanding the mechanisms of AIM2-inflammasome-mediated inflammation will provide an essential knowledge base to develop new successful therapeutic strategies to cure the outlined pathologies in which AIM2- inflammasome activation plays a key role, as well as to guide clinical practice. This mini-review provides an overview on the latest research findings on AIM2 inflammasome, with particular focus on its role in autoimmunity and skin disorders. An update on its therapeutic implications has also been documented.
{"title":"The Duality of AIM2 Inflammasome: A Focus on its Role in Autoimmunity and Skin Diseases","authors":"M. Canavese","doi":"10.3844/AJPTSP.2016.8.19","DOIUrl":"https://doi.org/10.3844/AJPTSP.2016.8.19","url":null,"abstract":"Understanding the inflammasome biology is one of the most exciting challenges in immuno-pharmacology. The role of the inflammasomes has been recognized in the host defense mechanism against invading pathogens and in the development of several conditions, such as cancer, auto-inflammatory, autoimmune, metabolic and neurodegenerative disorders. DNA recognition by the cells is a crucial immunological step leading to the initiation of an innate immune response. Absent in Melanoma 2 (AIM2) is a cytoplasmic sensor that perceives double-stranded DNA of microbial or host origin. Once the DNA is bound, AIM2 assembles a multiprotein complex named inflammasome, which drives pyroptosis and proteolytic cleavage of pro-IL-1I² and pro-IL-18 pro-inflammatory cytokines, leading to a protective inflammasome-mediated host response. However, improper recognition of self-DNA by AIM2 triggers deleterious inflammatory responses, leading to systemic inflammation and several pathological conditions. Therefore, understanding the mechanisms of AIM2-inflammasome-mediated inflammation will provide an essential knowledge base to develop new successful therapeutic strategies to cure the outlined pathologies in which AIM2- inflammasome activation plays a key role, as well as to guide clinical practice. This mini-review provides an overview on the latest research findings on AIM2 inflammasome, with particular focus on its role in autoimmunity and skin disorders. An update on its therapeutic implications has also been documented.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"33 1","pages":"8-19"},"PeriodicalIF":0.0,"publicationDate":"2016-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91384678","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}
Pub Date : 2016-02-01DOI: 10.3844/AJPTSP.2016.26.31
A. Mankwe, J. Aprioku, A. Obianime
Artemisinin-based Combination Therapies (ACTs) are employed as first-line agents in malaria chemotherapy. In many malaria endemic areas, ACTs are frequently abused partly due to resistance, poor drug control and inadequate health facilities. This study investigated the effects of prolong administration of Artesunate-Sulfadoxine-Pyrimethamine (ATS-SP), Artesunate-Amodiaquine (ATS-Amod) and Artemether-Lumefantrine (ATM-Lum) on plasma levels of biochemical parameters (AST, ALT, ALP, urea and creatinine) and lipids in guinea pigs. Adult guinea pigs were administered standard (NTD) or Double Therapeutic Dose (DTD) equivalents of ATS-SP, ATS-Amod or ATM-Lum for 14 days. Some other animals received similar drug treatments but were allowed to recover for 14 days. Control group was given vehicle. ATS-Amod caused significant (p<0.05) elevations in AST, ALT, urea and creatinine levels without altering ALP compared to control. The elevations were all reversed except the DTD-induced creatinine elevation. ATS-SP reversibly elevated (p<0.05) AST and creatinine levels. ATM-Lum caused no effect on urea, creatinine and ALT, but increased AST and ALP levels. Lipids were unaffected, except triglyceride level that was reversibly elevated (p<0.05) by ATS-SP (DTD). The results demonstrate that standard doses of the ACTs may have no harmful effects, but prolong overdose treatment with artesunate-amodiaquine or artesunate-SP may elevate creatinine and triglyceride levels, respectively.
{"title":"Effects of Artemisinin-Based Combination Therapies on Lipids and Hepatorenal Circulating Indices in Guinea Pigs","authors":"A. Mankwe, J. Aprioku, A. Obianime","doi":"10.3844/AJPTSP.2016.26.31","DOIUrl":"https://doi.org/10.3844/AJPTSP.2016.26.31","url":null,"abstract":"Artemisinin-based Combination Therapies (ACTs) are employed as first-line agents in malaria chemotherapy. In many malaria endemic areas, ACTs are frequently abused partly due to resistance, poor drug control and inadequate health facilities. This study investigated the effects of prolong administration of Artesunate-Sulfadoxine-Pyrimethamine (ATS-SP), Artesunate-Amodiaquine (ATS-Amod) and Artemether-Lumefantrine (ATM-Lum) on plasma levels of biochemical parameters (AST, ALT, ALP, urea and creatinine) and lipids in guinea pigs. Adult guinea pigs were administered standard (NTD) or Double Therapeutic Dose (DTD) equivalents of ATS-SP, ATS-Amod or ATM-Lum for 14 days. Some other animals received similar drug treatments but were allowed to recover for 14 days. Control group was given vehicle. ATS-Amod caused significant (p<0.05) elevations in AST, ALT, urea and creatinine levels without altering ALP compared to control. The elevations were all reversed except the DTD-induced creatinine elevation. ATS-SP reversibly elevated (p<0.05) AST and creatinine levels. ATM-Lum caused no effect on urea, creatinine and ALT, but increased AST and ALP levels. Lipids were unaffected, except triglyceride level that was reversibly elevated (p<0.05) by ATS-SP (DTD). The results demonstrate that standard doses of the ACTs may have no harmful effects, but prolong overdose treatment with artesunate-amodiaquine or artesunate-SP may elevate creatinine and triglyceride levels, respectively.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"42 1","pages":"26-31"},"PeriodicalIF":0.0,"publicationDate":"2016-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91525844","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}
E. N. Sholikhah, M. A. Wijayanti, R. A. Susidarti, Indah Purwantini, Rani Afifah Nur Hestiyani, H. Yusuf, Mustofa
Eurycomanone is the most active compounds in the roots of Eurycoma longifolia and shown to have in vitro antiplasmodial activity. However, the stage of Plasmodium falciparum cycles which are sensitive to eurycomanone have not been investigated. This study was conducted to investigate stage specificity of eurycomanone at various stages of P. falciparum life cycles. Stage specificity of eurycomanone at various stages of P. falciparum was performed on P. falciparum culture in vitro. A total of 100 µL of solution containing P. falciparum at ring stage after synchronized with 1-2% parasitemia (hematocrit 3%) were included in 96 wells microcultures and then added 100 µL of solution containing eurycomanone with 6 various concentrations. The specificity of eurycomanone was evaluated microscopically by counting the percentage of each stage of P. falciparum after for 8, 16, 24, 32, 40, 48, 56, 64 and 72 h incubation time, compared with control without any compound. The results showed that eurycomanone can kill ring stage of P. falciparum and may inhibit the development of young schizont to mature schizont in vitro. However, it needs further investigations for the mechanism.
{"title":"Stage Specificity of Eurycomanone Isolated from Eurycoma longifolia on Plasmodium falciparum Cycles","authors":"E. N. Sholikhah, M. A. Wijayanti, R. A. Susidarti, Indah Purwantini, Rani Afifah Nur Hestiyani, H. Yusuf, Mustofa","doi":"10.3844/AJPTSP.2016.1.7","DOIUrl":"https://doi.org/10.3844/AJPTSP.2016.1.7","url":null,"abstract":"Eurycomanone is the most active compounds in the roots of Eurycoma longifolia and shown to have in vitro antiplasmodial activity. However, the stage of Plasmodium falciparum cycles which are sensitive to eurycomanone have not been investigated. This study was conducted to investigate stage specificity of eurycomanone at various stages of P. falciparum life cycles. Stage specificity of eurycomanone at various stages of P. falciparum was performed on P. falciparum culture in vitro. A total of 100 µL of solution containing P. falciparum at ring stage after synchronized with 1-2% parasitemia (hematocrit 3%) were included in 96 wells microcultures and then added 100 µL of solution containing eurycomanone with 6 various concentrations. The specificity of eurycomanone was evaluated microscopically by counting the percentage of each stage of P. falciparum after for 8, 16, 24, 32, 40, 48, 56, 64 and 72 h incubation time, compared with control without any compound. The results showed that eurycomanone can kill ring stage of P. falciparum and may inhibit the development of young schizont to mature schizont in vitro. However, it needs further investigations for the mechanism.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"1 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2016-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87791114","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}
Pub Date : 2015-10-22DOI: 10.3844/AJPTSP.2015.37.39
G. Nocentini, G. Migliorati, C. Riccardi
{"title":"Are we Able to Harness the Immunomodulatory Power of Cytokines for Novel Autoimmune Disease Treatments","authors":"G. Nocentini, G. Migliorati, C. Riccardi","doi":"10.3844/AJPTSP.2015.37.39","DOIUrl":"https://doi.org/10.3844/AJPTSP.2015.37.39","url":null,"abstract":"","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"1 1","pages":"37-39"},"PeriodicalIF":0.0,"publicationDate":"2015-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82195430","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}
Pub Date : 2015-09-13DOI: 10.3844/AJPTSP.2015.40.45
R. Ganesan, Rajalakshmi Ettiyan
Abrus Precatorius commonly known as Rosary bead or Kundumani (Arena, 1986) is an irritant poison affecting almost all major systems of the body with more damage to the gastrointestinal system. The mortality rate is 10 to 15% for a lethal dose of just 1-2 crushed seeds. Following is the case report of hemorrhagic colitis due to the ingestion of a toxic dose of ABRUS seeds (Reedman et al., 2008). Sigmoidoscopy was done to document the hemorrhagic colitis. Client was treated as severe colitis with intra venous antibiotics, intravenous steroids; Oral Mesalamine, Intra venous Pantaprazole and IV fluids. Despite consuming a large amount of the toxin, our client survived.
Abrus Precatorius通常被称为Rosary珠或Kundumani (Arena, 1986)是一种刺激性毒药，几乎影响身体的所有主要系统，对胃肠道系统的损害更大。1-2粒碾碎的种子致死剂量，死亡率为10% - 15%。以下是因摄入有毒剂量的ABRUS种子而导致出血性结肠炎的病例报告(Reedman et al.， 2008)。乙状结肠镜检查记录出血性结肠炎。病人被诊断为严重结肠炎，静脉注射抗生素、类固醇;口服美沙拉明，静脉注射泮他拉唑和静脉输液。尽管摄入了大量毒素，我们的委托人还是活了下来。
{"title":"Abrus Precatorius Induced Hemorrhagic Colitis","authors":"R. Ganesan, Rajalakshmi Ettiyan","doi":"10.3844/AJPTSP.2015.40.45","DOIUrl":"https://doi.org/10.3844/AJPTSP.2015.40.45","url":null,"abstract":"Abrus Precatorius commonly known as Rosary bead or Kundumani (Arena, 1986) is an irritant poison affecting almost all major systems of the body with more damage to the gastrointestinal system. The mortality rate is 10 to 15% for a lethal dose of just 1-2 crushed seeds. Following is the case report of hemorrhagic colitis due to the ingestion of a toxic dose of ABRUS seeds (Reedman et al., 2008). Sigmoidoscopy was done to document the hemorrhagic colitis. Client was treated as severe colitis with intra venous antibiotics, intravenous steroids; Oral Mesalamine, Intra venous Pantaprazole and IV fluids. Despite consuming a large amount of the toxin, our client survived.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"31 1","pages":"40-45"},"PeriodicalIF":0.0,"publicationDate":"2015-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84172343","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}
Pub Date : 2015-08-27DOI: 10.3844/AJPTSP.2015.46.55
B. Das, S. Alam, Rajib Bhattacharjee, B. Das
Euphorbia antiquorum (L.) is used as traditional medicine for various ailments in Bangladesh. But the scientific basis for its use especially in pain and inflammation remains largely unknown. Therefore, the present study was designed to evaluate analgesic and anti-inflammatory effect of the aqueous ethanolic extract of the whole plant. The analgesic activity was evaluated by hot plate, acetic acid induced writhing and formalin induced writhing methods in Swiss Albino mice at the doses of 250 and 500 mg kg-1 body weight. The extract was also investigated for the anti-inflammatory effect on Long Evans rats at above mentioned doses using carrageenan induced rat paw edema method. Phytochemical analysis of the extract revealed the presence of tannins, alkaloids, flavonoids, saponins and terpenoids. The extract elicited a significant (p
{"title":"Analgesic and Anti-inflammatory Activity of Euphorbia antiquorum Linn","authors":"B. Das, S. Alam, Rajib Bhattacharjee, B. Das","doi":"10.3844/AJPTSP.2015.46.55","DOIUrl":"https://doi.org/10.3844/AJPTSP.2015.46.55","url":null,"abstract":"Euphorbia antiquorum (L.) is used as traditional medicine for various ailments in Bangladesh. But the scientific basis for its use especially in pain and inflammation remains largely unknown. Therefore, the present study was designed to evaluate analgesic and anti-inflammatory effect of the aqueous ethanolic extract of the whole plant. The analgesic activity was evaluated by hot plate, acetic acid induced writhing and formalin induced writhing methods in Swiss Albino mice at the doses of 250 and 500 mg kg-1 body weight. The extract was also investigated for the anti-inflammatory effect on Long Evans rats at above mentioned doses using carrageenan induced rat paw edema method. Phytochemical analysis of the extract revealed the presence of tannins, alkaloids, flavonoids, saponins and terpenoids. The extract elicited a significant (p","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"1 1","pages":"46-55"},"PeriodicalIF":0.0,"publicationDate":"2015-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83010204","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}
Pub Date : 2015-06-02DOI: 10.3844/AJPTSP.2015.27.31
K. Murti, M. Khan, A. Dey, M. Sethi, P. Das, K. Pandey
The main objective of the present study to investigate the utilization pattern of antihypertensive drugs in hypertensive patients and to find out whether the prescription pattern is in adherence with the JNC7 guidelines for the management of hypertension. A prospective study was conducted and drug utilization data were collected from 137 hypertensive patients who were attended as Out Patient Department (OPD) of Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Patna, Bihar, India. The data was retrieved from patientâs medical records as well as from the interview of patients and their legally acceptable representatives. The following classes of antihypertensive drugs were analyzed; Angiotensin Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARBs), Beta Blockers (BBs), Calcium Channel Blockers (CCBs) and Diuretics. The inclusion criteria for the recruitment of study subjects were the patients suffering from hypertension with or without other co-morbid conditions. The analysis of the prescription frequency, proportion of the different antihypertensive classes of drugs as monotherapy as well as combination therapy was done. The most frequently prescribed classes of antihypertensive medications were Diuretics (mainly thiazides followed by Loop category) followed by CCBs, BBs, ACEIs and ARBs. Antihypertensive drug combination therapy was given to 72.26% of the total population while monotherapy was received by 27.73% of the total hypertensive population, representing more utilization of combination therapy as compared to monotherapy. The prescription pattern of these classes of drugs was found to be considerately in adherence to JNC7 guidelines for the management of hypertension. It was evident from the study that hypertension is more pronounced in males with increasing age as compared to females. The diuretics were the first choice alone or in combination and pattern of prescription was adhered to JNC-7 Guidelines.
{"title":"Prescription Pattern of Anti-Hypertensive Drugs in Adherence to JNC- 7 Guidelines","authors":"K. Murti, M. Khan, A. Dey, M. Sethi, P. Das, K. Pandey","doi":"10.3844/AJPTSP.2015.27.31","DOIUrl":"https://doi.org/10.3844/AJPTSP.2015.27.31","url":null,"abstract":"The main objective of the present study to investigate the utilization pattern of antihypertensive drugs in hypertensive patients and to find out whether the prescription pattern is in adherence with the JNC7 guidelines for the management of hypertension. A prospective study was conducted and drug utilization data were collected from 137 hypertensive patients who were attended as Out Patient Department (OPD) of Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Patna, Bihar, India. The data was retrieved from patientâs medical records as well as from the interview of patients and their legally acceptable representatives. The following classes of antihypertensive drugs were analyzed; Angiotensin Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARBs), Beta Blockers (BBs), Calcium Channel Blockers (CCBs) and Diuretics. The inclusion criteria for the recruitment of study subjects were the patients suffering from hypertension with or without other co-morbid conditions. The analysis of the prescription frequency, proportion of the different antihypertensive classes of drugs as monotherapy as well as combination therapy was done. The most frequently prescribed classes of antihypertensive medications were Diuretics (mainly thiazides followed by Loop category) followed by CCBs, BBs, ACEIs and ARBs. Antihypertensive drug combination therapy was given to 72.26% of the total population while monotherapy was received by 27.73% of the total hypertensive population, representing more utilization of combination therapy as compared to monotherapy. The prescription pattern of these classes of drugs was found to be considerately in adherence to JNC7 guidelines for the management of hypertension. It was evident from the study that hypertension is more pronounced in males with increasing age as compared to females. The diuretics were the first choice alone or in combination and pattern of prescription was adhered to JNC-7 Guidelines.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"24 7","pages":"27-31"},"PeriodicalIF":0.0,"publicationDate":"2015-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91401602","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}
Pub Date : 2015-06-02DOI: 10.3844/AJPTSP.2015.32.36
J. V. Peixoto, F. Dias, C. Damiani, I. K. Silva, S. S. Veiga, J. C. Francisco, R. Fogaça
Loxoceles spiders gender are worldwide spread and its bites can cause dermonecrosis or even a systemic effect (hemolysis, kidney and liver injury). It is believed that phospholipase D, the main component present in the venom, could be responsible for the injury. In this study, we used a recombinant form of phospholipase D (rLiD1) and evaluated its direct and systemic effects on the contractility of papillary muscles and in the left intra ventricular pressure of isolated perfused hearts, respectively. In papillary muscle directly exposed to rLiD1 no effects on force, maximum speed of contraction (df/dtmax) or relaxation (df/dtmin) were observed. In isolated perfused heart, the peak of systolic pressure and the rate of relaxation (dP/dtmin) were reduced in animals treated with rLiD1. However, the maximum speed of pressure developed during contraction (dP/dtmax) was unaffected. These data suggest that rLiD1 did not affect directly the excitation contraction coupling or the contractility of the myocardium but its systemic effect can induce reduction in the cardiac performance.
{"title":"Effects of Recombinant Toxin Phospholipase D in Cardiac Muscle of Rats","authors":"J. V. Peixoto, F. Dias, C. Damiani, I. K. Silva, S. S. Veiga, J. C. Francisco, R. Fogaça","doi":"10.3844/AJPTSP.2015.32.36","DOIUrl":"https://doi.org/10.3844/AJPTSP.2015.32.36","url":null,"abstract":"Loxoceles spiders gender are worldwide spread and its bites can cause dermonecrosis or even a systemic effect (hemolysis, kidney and liver injury). It is believed that phospholipase D, the main component present in the venom, could be responsible for the injury. In this study, we used a recombinant form of phospholipase D (rLiD1) and evaluated its direct and systemic effects on the contractility of papillary muscles and in the left intra ventricular pressure of isolated perfused hearts, respectively. In papillary muscle directly exposed to rLiD1 no effects on force, maximum speed of contraction (df/dtmax) or relaxation (df/dtmin) were observed. In isolated perfused heart, the peak of systolic pressure and the rate of relaxation (dP/dtmin) were reduced in animals treated with rLiD1. However, the maximum speed of pressure developed during contraction (dP/dtmax) was unaffected. These data suggest that rLiD1 did not affect directly the excitation contraction coupling or the contractility of the myocardium but its systemic effect can induce reduction in the cardiac performance.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"10 1","pages":"32-36"},"PeriodicalIF":0.0,"publicationDate":"2015-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89480800","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}
Pub Date : 2015-05-27DOI: 10.3844/AJPTSP.2015.13.26
M. Ullah
Water For Injections (WFI) which is the main vehicle of Large Volume Parenterals (LVPs) should be free from trace amount of genotoxic impurities. This review gives emphasis on quantification of genotoxic trace metals during qualification of WFI in LVPs manufacturing unit. According to ICH guidelines, impurities related to drug substances are classified into three main categories: Organic impurities, inorganic (elemental) impurities and residual solvents. Within these categories, genotoxic impurities form a special case that poses a significant safety risk, even at low concentrations, because they may be mutagenic and are therefore potentially damaging to DNA. As a result they can lead to mutations or cause cancer. Chemical carcinogens most often directly or after xenobiotic metabolism, act as genotoxic causes to induce DNA damage. The roles of trace metals (some of which are either genotoxic or non-genotoxic) in cancer development and inhibition have a complex character and have raised many questions because of their essential and toxic effects on people's health. Trace metals such as cadmium, nickel, arsenic, beryllium and chromium (VI) have been recognized as human or animal carcinogens by International Agency for Research on Cancer (IARC). There are several genotoxic chemicals like residual solvent, impurities and trace metals present in Pharmaceuticals to form carcinogens. Regulatory body like FDA and EMEA has fixed up specific limits for these elemental impurities. The toxicity of an elemental impurity is related to its extent of exposure (bioavailability). In that sense, parenteral dosage forms has its most possibility to be bioavailable than the other dosage forms, the limit of genotoxic impurities are 10 times lower than that of oral dosage forms by United States Pharmacopoeia (USP). The present article is for the importance of identification and quantification of the trace amount of the metal genotoxic impurities in Water For Injection (WFI) during qualification (IQ, OQ, PQ) as a preventive measure to control the production and distribution of WFI for Large Volume Parenteral (LVP) production.
{"title":"Selected Genotoxic Impurities Profiling During WFI Qualification to Control Carcinogenesis in Large Volume Parenterals","authors":"M. Ullah","doi":"10.3844/AJPTSP.2015.13.26","DOIUrl":"https://doi.org/10.3844/AJPTSP.2015.13.26","url":null,"abstract":"Water For Injections (WFI) which is the main vehicle of Large Volume Parenterals (LVPs) should be free from trace amount of genotoxic impurities. This review gives emphasis on quantification of genotoxic trace metals during qualification of WFI in LVPs manufacturing unit. According to ICH guidelines, impurities related to drug substances are classified into three main categories: Organic impurities, inorganic (elemental) impurities and residual solvents. Within these categories, genotoxic impurities form a special case that poses a significant safety risk, even at low concentrations, because they may be mutagenic and are therefore potentially damaging to DNA. As a result they can lead to mutations or cause cancer. Chemical carcinogens most often directly or after xenobiotic metabolism, act as genotoxic causes to induce DNA damage. The roles of trace metals (some of which are either genotoxic or non-genotoxic) in cancer development and inhibition have a complex character and have raised many questions because of their essential and toxic effects on people's health. Trace metals such as cadmium, nickel, arsenic, beryllium and chromium (VI) have been recognized as human or animal carcinogens by International Agency for Research on Cancer (IARC). There are several genotoxic chemicals like residual solvent, impurities and trace metals present in Pharmaceuticals to form carcinogens. Regulatory body like FDA and EMEA has fixed up specific limits for these elemental impurities. The toxicity of an elemental impurity is related to its extent of exposure (bioavailability). In that sense, parenteral dosage forms has its most possibility to be bioavailable than the other dosage forms, the limit of genotoxic impurities are 10 times lower than that of oral dosage forms by United States Pharmacopoeia (USP). The present article is for the importance of identification and quantification of the trace amount of the metal genotoxic impurities in Water For Injection (WFI) during qualification (IQ, OQ, PQ) as a preventive measure to control the production and distribution of WFI for Large Volume Parenteral (LVP) production.","PeriodicalId":7769,"journal":{"name":"American Journal of Pharmacology and Toxicology","volume":"350 1","pages":"13-26"},"PeriodicalIF":0.0,"publicationDate":"2015-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77323063","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}
Pub Date : 2015-05-06DOI: 10.3844/AJPTSP.2015.1.12
M. Canavese
Vascular Endothelial Growth Factor (VEGF) is the major player in the regulation of physiological angiogenesis as well as it has also been implicated in pathological angiogenesis, associated with cancers and other conditions, among which psoriasis, autoimmune diseases and visual loss in macular degeneration. Interestingly, three regulatory Single Nucleotide Polymorphisms (rSNPs) in the promoter region of VEGF-A gene have been significantly associated with different human diseases and it is possible that, in the near future, the cumulative effect of several high-risk Single Nucleotide Polymorphisms (SNPs) may prove useful in a clinical setting. Currently, new VEGF inhibitors are undergoing clinical testing in various disease conditions, given that VEGF inhibition has also been contemplated as a possible strategy for prevention of angiogenesis and vascular leakage to decrease inflammation. This review focuses mainly on the role of Vascular Endothelial Growth Factor in several pathological contexts, highlighting the emerging association of the most common VEGF polymorphisms with disease risk. An update on the therapeutic implications of VEGF has also been documented.
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