Between the illicit use of opioids and attendant overdoses, and accidental overdoses with prescribed drugs, overuse of opioids has become a serious problem. At the same time, finding that fine balance between minimizing the risk of opioid misuse and abuse while at the same time providing access to treatment for patients who need pain control presents an ongoing challenge. Efforts to discover and develop better agents have led to what we term “new-look” opioids. We summarize here one such approach—known as biased ligands. By targeting a subset of GPCR signal transduction, this approach attempts to increase the separation between therapeutic and adverse effects.
{"title":"“New-Look” Opioids: Biased Ligands","authors":"J. Pergolizzi, M. Ossipov, R. Taylor, R. Raffa","doi":"10.4236/pp.2018.97018","DOIUrl":"https://doi.org/10.4236/pp.2018.97018","url":null,"abstract":"Between the illicit use of opioids and attendant overdoses, and accidental overdoses with prescribed drugs, overuse of opioids has become a serious problem. At the same time, finding that fine balance between minimizing the risk of opioid misuse and abuse while at the same time providing access to treatment for patients who need pain control presents an ongoing challenge. Efforts to discover and develop better agents have led to what we term “new-look” opioids. We summarize here one such approach—known as biased ligands. By targeting a subset of GPCR signal transduction, this approach attempts to increase the separation between therapeutic and adverse effects.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83959924","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}
When any type of product has been ordered to be removed from the marketplace by a governmental regulatory body, that action is a powerful indicator that the product has been determined to be unsafe for further use, thereby branding the product as defective and opening up the possibility of product liability litigation. When the product is a drug or medical device, it is especially serious since the possibility of personal injury (acute and/or chronic) or death may occur. Needless to say, in these situations, product injury litigation will almost surely follow. We review the definition and requisite claims needed to establish drug product liability, and the role that the medical literature, clinical trial data, and even experimental research data can play in product (drug)-injury litigation. We show how each of these resources played a significant role in two well-known cases: Fen-Phen and thimerosal. The ultimate goal of such knowledge is to make better informed decisions about drug safety.
{"title":"The Role of Medical Literature, Clinical Trials and Experimental Research in Drug Product-Injury Litigation: A Primer with Two Examples","authors":"J. Kitzen, J. Pergolizzi, R. Taylor, R. Raffa","doi":"10.4236/PP.2018.96016","DOIUrl":"https://doi.org/10.4236/PP.2018.96016","url":null,"abstract":"When any type of product has been ordered to be removed from the marketplace by a governmental regulatory body, that action is a powerful indicator that the product has been determined to be unsafe for further use, thereby branding the product as defective and opening up the possibility of product liability litigation. When the product is a drug or medical device, it is especially serious since the possibility of personal injury (acute and/or chronic) or death may occur. Needless to say, in these situations, product injury litigation will almost surely follow. We review the definition and requisite claims needed to establish drug product liability, and the role that the medical literature, clinical trial data, and even experimental research data can play in product (drug)-injury litigation. We show how each of these resources played a significant role in two well-known cases: Fen-Phen and thimerosal. The ultimate goal of such knowledge is to make better informed decisions about drug safety.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79608968","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}
Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed soft extract (active ingredients of GRANUFINK? Prosta forte 500 mg), seed oil and isolated Δ7-sterols could inhibit the conversion of [1,2,6,7-3H(N)]-testosterone to DHT by 5α-reductases. Also, we tested competition with [3H]-DHT for binding to the androgen receptor (AR). Pumpkin seed oil and pumpkin seed soft extract were identified as moderately active inhibitors of 5α-R1 and 5α-R2, with almost similar inhibitory capacities (IC50 < 5 mg/ml for 5α-R1 and about IC50 = 6 mg/ml for 5α-R2). The isolated Δ7-sterols were more active inhibitors (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 mg/ml for 5α-R2). All three test compounds bound to the AR dose-dependently, with strong binding by Δ7-sterols (IC50 = 0.2 mg/ml) and weaker binding by pumpkin seed oil (IC50 = 0.4 mg/ml) and pumpkin seed soft extract (IC50 = 1.1 mg/ml). We propose that inhibition of 5α-reductases and competitive binding to the AR are mechanisms of action, by which the Uromedic? pumpkin seed derived test compounds, most specifically Δ7-sterols, counteract DHT and thereby exert clinically positive effects on the prostate, as well as bladder-strengthening effects.
{"title":"Uromedic® Pumpkin Seed Derived Δ7-Sterols, Extract and Oil Inhibit 5α-Reductases and Bind to Androgen Receptor in Vitro","authors":"Stefan Heim, Stephanie Seibt, H. Stier, M. Moré","doi":"10.4236/PP.2018.96015","DOIUrl":"https://doi.org/10.4236/PP.2018.96015","url":null,"abstract":"Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed soft extract (active ingredients of GRANUFINK? Prosta forte 500 mg), seed oil and isolated Δ7-sterols could inhibit the conversion of [1,2,6,7-3H(N)]-testosterone to DHT by 5α-reductases. Also, we tested competition with [3H]-DHT for binding to the androgen receptor (AR). Pumpkin seed oil and pumpkin seed soft extract were identified as moderately active inhibitors of 5α-R1 and 5α-R2, with almost similar inhibitory capacities (IC50 < 5 mg/ml for 5α-R1 and about IC50 = 6 mg/ml for 5α-R2). The isolated Δ7-sterols were more active inhibitors (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 mg/ml for 5α-R2). All three test compounds bound to the AR dose-dependently, with strong binding by Δ7-sterols (IC50 = 0.2 mg/ml) and weaker binding by pumpkin seed oil (IC50 = 0.4 mg/ml) and pumpkin seed soft extract (IC50 = 1.1 mg/ml). We propose that inhibition of 5α-reductases and competitive binding to the AR are mechanisms of action, by which the Uromedic? pumpkin seed derived test compounds, most specifically Δ7-sterols, counteract DHT and thereby exert clinically positive effects on the prostate, as well as bladder-strengthening effects.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83025335","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}
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most common forms of dementia. Clinical studies and preclinical data in the last decade proved that AD and Diabetes mellitus share a pathophysiological pathway, indicating that insulin resistance, oxidative stress and inflammatory response would increase the risks of developing AD in diabetic patients. This review presents briefly the etiology of AD and Diabetes, discusses the possible theories about the interplaying risk factors and the mechanism of action of anti-diabetic medications recommended for the treatment of AD. It is concluded that antidiabetics have good potential to improve dementia, especially in earlier AD stages. However, many of the underlying intricate molecular pathways are still unclear and thus thorough future research is required.
{"title":"The Use of Anti-Diabetic Drugs in Alzheimer’s Disease, New Therapeutic Options and Future Perspective","authors":"O. M. Ibrahim, M. Hassan","doi":"10.4236/PP.2018.96013","DOIUrl":"https://doi.org/10.4236/PP.2018.96013","url":null,"abstract":"Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most common forms of dementia. Clinical studies and preclinical data in the last decade proved that AD and Diabetes mellitus share a pathophysiological pathway, indicating that insulin resistance, oxidative stress and inflammatory response would increase the risks of developing AD in diabetic patients. This review presents briefly the etiology of AD and Diabetes, discusses the possible theories about the interplaying risk factors and the mechanism of action of anti-diabetic medications recommended for the treatment of AD. It is concluded that antidiabetics have good potential to improve dementia, especially in earlier AD stages. However, many of the underlying intricate molecular pathways are still unclear and thus thorough future research is required.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88679306","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}
O. M. Ibrahim, M. Rashrash, R. Albasha, R. Alani, Sama Khadhum, Sameh S. M. Soliman
Background: Proton pump inhibitors (PPIs) are drugs that reduce the production of acid in the stomach. Recently, the use of PPI has been increasing among communities, whether with or without prescription. As a part of the healthcare team, the pharmacist should not only dispense medications but also ensure the appropriate use of these medications. Studies conducted within 16 countries showed substantial variation in the appropriateness of the use of PPI drugs. Aim: To evaluate the appropriateness of PPIs use in Sharjah, UAE based on surveys answered by pharmacists, physicians, and patients. Methods: A cross-sectional survey study was conducted on December 2017 at Sharjah, UAE as an example of information obtained from the Middle East. Two different surveys were conducted on physicians and pharmacists. Both Physicians and Pharmacists were chosen randomly from Yellow Pages. The results obtained from both studies were used to develop a patient’s survey, which was distributed among University of Sharjah students, their families and random people at Shopping Malls and Clinics. Results: The results obtained from the patients’ survey showed that ~39% of PPI users from the region of Sharjah are 25 - 44 years old. Approximately 79% are using PPI according to physicians’ prescriptions. Prescriptions’ duration is varied between 1 month (39%) and 6 months (22%), where 52% of PPI users ask their physicians to prescribe PPIs when needed. Suggested reasons for the use of PPI included inappropriate food habits (52%), use of other medications (16%) or bacterial infection (13%). Around 52% of the patients did not receive any recommendations regarding the deprescribing of PPIs. According to the pharmacists’ surveys, an average sale of 5 - 10 PPI packages is reported per day, and around 50% are sold without a prescription. Most pharmacists were not fully aware of the health conditions and side effects of PPI drugs. On the other hand, physicians’ surveys showed that PPIs were mainly prescribed in the case of GERD and ulcer and for a maximum of 2 - 4 weeks. Approximately 75% of physicians recommend changing regimen by reducing the dose and stopping in case of chronic use of PPIs. Conclusion: The results from this survey study indicated that even though most PPI consumers at Sharjah, UAE are well aware of the use of PPI drugs and they follow the instructions given by the Physicians’, there is some discrepancy in the information obtained by the physicians, pharmacists, and patients. The reason for this discrepancy may be attributed to the missing role of the pharmacists which is currently just dispensing the medications without appropriate counseling. Thus the appropriate role of the pharmacists should be implemented according to the known international guidelines.
{"title":"Evaluation of Appropriateness of Proton Pump Inhibitors (PPIs) Use in the Region of Sharjah, United Arab Emirates (UAE)","authors":"O. M. Ibrahim, M. Rashrash, R. Albasha, R. Alani, Sama Khadhum, Sameh S. M. Soliman","doi":"10.4236/pp.2018.96012","DOIUrl":"https://doi.org/10.4236/pp.2018.96012","url":null,"abstract":"Background: Proton pump inhibitors (PPIs) are drugs that reduce the production of acid in the stomach. Recently, the use of PPI has been increasing among communities, whether with or without prescription. As a part of the healthcare team, the pharmacist should not only dispense medications but also ensure the appropriate use of these medications. Studies conducted within 16 countries showed substantial variation in the appropriateness of the use of PPI drugs. Aim: To evaluate the appropriateness of PPIs use in Sharjah, UAE based on surveys answered by pharmacists, physicians, and patients. Methods: A cross-sectional survey study was conducted on December 2017 at Sharjah, UAE as an example of information obtained from the Middle East. Two different surveys were conducted on physicians and pharmacists. Both Physicians and Pharmacists were chosen randomly from Yellow Pages. The results obtained from both studies were used to develop a patient’s survey, which was distributed among University of Sharjah students, their families and random people at Shopping Malls and Clinics. Results: The results obtained from the patients’ survey showed that ~39% of PPI users from the region of Sharjah are 25 - 44 years old. Approximately 79% are using PPI according to physicians’ prescriptions. Prescriptions’ duration is varied between 1 month (39%) and 6 months (22%), where 52% of PPI users ask their physicians to prescribe PPIs when needed. Suggested reasons for the use of PPI included inappropriate food habits (52%), use of other medications (16%) or bacterial infection (13%). Around 52% of the patients did not receive any recommendations regarding the deprescribing of PPIs. According to the pharmacists’ surveys, an average sale of 5 - 10 PPI packages is reported per day, and around 50% are sold without a prescription. Most pharmacists were not fully aware of the health conditions and side effects of PPI drugs. On the other hand, physicians’ surveys showed that PPIs were mainly prescribed in the case of GERD and ulcer and for a maximum of 2 - 4 weeks. Approximately 75% of physicians recommend changing regimen by reducing the dose and stopping in case of chronic use of PPIs. Conclusion: The results from this survey study indicated that even though most PPI consumers at Sharjah, UAE are well aware of the use of PPI drugs and they follow the instructions given by the Physicians’, there is some discrepancy in the information obtained by the physicians, pharmacists, and patients. The reason for this discrepancy may be attributed to the missing role of the pharmacists which is currently just dispensing the medications without appropriate counseling. Thus the appropriate role of the pharmacists should be implemented according to the known international guidelines.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85887955","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}
J. Ezeonwumelu, M. Ntale, S. Ogbonnia, Ezera Agwu, J. Tanayen, A. Adedeji, C. Okonkwo, Ambrose Amamchukwu Akunne, Jennifer Chibuogwu Ebosie, F. Byarugaba
Oral lesions, diarrhoea, Pneumocystis carinii pneumonia, tuberculosis and urinary tract infections are some of the opportunistic infections (OIs) which arise when the CD4 cells of the HIV/AIDS patient fall below 200 cells/mm3. HIV/AIDS infection complications include tissue damage from oral lesions accompanied with pains. Pain is a disagreeable sensory and sensitive experience associated with actual or potential tissue damage. This condition requires immediate treatment with analgesics and antibiotics. However, the inability of rural dwellers to afford readily available drugs is a consequence for using herbs like Bidens pilosa whose local usefulness in the management of oral lesions of HIV/AIDS has not been proven scientifically. Therefore, the objective of this study was to provide the scientific basis in rats for the traditional healers’ use of Bidens pilosa leaves’ extracts in managing pain associated with oral lesions of HIV/AIDS patients in South Western Uganda. Assessment of the analgesic effects of Bidens pilosa was conducted using acetic acid in mice, formalin-induced pain and tail flick methods in rats. Both aqueous and ethanolic extracts of the leaves of Bidens pilosa produced statistically significant dose dependent inhibition of acetic acid induced pain, non dose dependent pain reduction in formalin induced pain, (p < 0.05; student t-test) and non dose dependent tail withdrawal pattern (p < 0.05, Multivariate ANOVA test). Hence, we conclude that extracts of Bidens pilosa have an analgesic basis for their local use in treatment of oral lesions associated pain in HIV/AIDS patients in South-Western Uganda.
{"title":"Analgesic Appraisal of Bidens pilosa (Asteraceae) Leaf Extracts Used in Management of Oral Lesion Pain in HIV/AIDS Patients in Rodents","authors":"J. Ezeonwumelu, M. Ntale, S. Ogbonnia, Ezera Agwu, J. Tanayen, A. Adedeji, C. Okonkwo, Ambrose Amamchukwu Akunne, Jennifer Chibuogwu Ebosie, F. Byarugaba","doi":"10.4236/PP.2018.96014","DOIUrl":"https://doi.org/10.4236/PP.2018.96014","url":null,"abstract":"Oral lesions, diarrhoea, Pneumocystis carinii pneumonia, tuberculosis and urinary tract infections are some of the opportunistic infections (OIs) which arise when the CD4 cells of the HIV/AIDS patient fall below 200 cells/mm3. HIV/AIDS infection complications include tissue damage from oral lesions accompanied with pains. Pain is a disagreeable sensory and sensitive experience associated with actual or potential tissue damage. This condition requires immediate treatment with analgesics and antibiotics. However, the inability of rural dwellers to afford readily available drugs is a consequence for using herbs like Bidens pilosa whose local usefulness in the management of oral lesions of HIV/AIDS has not been proven scientifically. Therefore, the objective of this study was to provide the scientific basis in rats for the traditional healers’ use of Bidens pilosa leaves’ extracts in managing pain associated with oral lesions of HIV/AIDS patients in South Western Uganda. Assessment of the analgesic effects of Bidens pilosa was conducted using acetic acid in mice, formalin-induced pain and tail flick methods in rats. Both aqueous and ethanolic extracts of the leaves of Bidens pilosa produced statistically significant dose dependent inhibition of acetic acid induced pain, non dose dependent pain reduction in formalin induced pain, (p < 0.05; student t-test) and non dose dependent tail withdrawal pattern (p < 0.05, Multivariate ANOVA test). Hence, we conclude that extracts of Bidens pilosa have an analgesic basis for their local use in treatment of oral lesions associated pain in HIV/AIDS patients in South-Western Uganda.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77891806","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}
Identification of novel specialized metabolites or bioactive compounds represents the main objective in the research field of natural product leads and drug discovery. Mass spectrometry (MS) provides a central tool to expedite and make more efficient the discovery and isolation phases, while minimizing the waste of resources on rediscovery of known compounds. MS contributes acutely to elucidation and identification of numerous species because it allows molecular mass and structural features determination. In particular, identification of the elemental composition of a precursor ion of interest by accurate mass measurement and investigation of dissociative processes undergone by the molecule, represent a worthy methodology to access the structure assignment. The aim of this study was to discover and identify novel antibacterial drugs from microbial source in a jungle of already known compounds. The focus of this paper is on the analytical strategy that permitted the disclosure of a new compound, otherwise confused with other substances. Emphasis is placed on the interpretation of the ESI-MS/MS fragmentation pattern that combined with high resolution mass determination, allowed step by step to properly deduce the exact molecular formula of an unknown component with a molecular weight higher than 1500 Daltons.
{"title":"High Resolution Mass Spectrometry for the Recognition and Structural Characterization of a New Antimicrobial Compound","authors":"L. Carrano, A. Naggi, Elena Urso","doi":"10.4236/PP.2018.95011","DOIUrl":"https://doi.org/10.4236/PP.2018.95011","url":null,"abstract":"Identification of novel specialized metabolites or bioactive compounds represents the main objective in the research field of natural product leads and drug discovery. Mass spectrometry (MS) provides a central tool to expedite and make more efficient the discovery and isolation phases, while minimizing the waste of resources on rediscovery of known compounds. MS contributes acutely to elucidation and identification of numerous species because it allows molecular mass and structural features determination. In particular, identification of the elemental composition of a precursor ion of interest by accurate mass measurement and investigation of dissociative processes undergone by the molecule, represent a worthy methodology to access the structure assignment. The aim of this study was to discover and identify novel antibacterial drugs from microbial source in a jungle of already known compounds. The focus of this paper is on the analytical strategy that permitted the disclosure of a new compound, otherwise confused with other substances. Emphasis is placed on the interpretation of the ESI-MS/MS fragmentation pattern that combined with high resolution mass determination, allowed step by step to properly deduce the exact molecular formula of an unknown component with a molecular weight higher than 1500 Daltons.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75109687","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}
Injectable drugs manufactured in E. coli must be tested for host residual DNA (hr DNA) impurity in ensuring drug purity and safety. Because of low allowable hr DNA as impurity, highly sensitive methods are needed. Droplet digital PCR (ddPCR) is a new method where the reaction is partitioned into about 20,000 nanoliter-sized droplets and each droplet acts as individual PCR reaction. After completion of end-point PCR, droplets are analyzed for fluorescence and categorized as positive or negative and DNA quantified using Poisson statistics. Here we describe development of a direct E. coli hr DNA dd PCR method where the drug is directly added to the ddPCR reaction. We show that the ddPCR method has acceptable precision and high accuracy, works with different biologic drugs, and compared to qPCR shows higher tolerance of drug matrices. The method does not require DNA extraction or standard curves for quantification of hr DNA in unknown samples.
用大肠杆菌生产的注射用药物必须进行宿主残留DNA (hr DNA)杂质检测，以保证药物的纯度和安全性。由于允许的hr较低，因此需要高灵敏度的方法。液滴数字PCR (ddPCR)是一种新方法，它将反应分割成约20,000纳米升大小的液滴，每个液滴作为单个PCR反应。终点PCR完成后，对液滴进行荧光分析，并将其分为阳性或阴性，并使用泊松统计量对DNA进行定量。在这里，我们描述了直接大肠杆菌hr DNA ddPCR方法的发展，其中药物直接添加到ddPCR反应中。我们发现，ddPCR方法具有可接受的精密度和较高的准确度，适用于不同的生物药物，与qPCR相比，对药物基质具有更高的耐受性。该方法不需要DNA提取或标准曲线来定量未知样品中的hr DNA。
{"title":"A Direct Droplet Digital PCR Method for E. coli Host Residual DNA Quantification","authors":"Jeremy Anderson, M. Hussain","doi":"10.4236/pp.2018.94009","DOIUrl":"https://doi.org/10.4236/pp.2018.94009","url":null,"abstract":"Injectable drugs manufactured in E. coli must be tested for host residual DNA (hr DNA) impurity in ensuring drug purity and safety. Because of low allowable hr DNA as impurity, highly sensitive methods are needed. Droplet digital PCR (ddPCR) is a new method where the reaction is partitioned into about 20,000 nanoliter-sized droplets and each droplet acts as individual PCR reaction. After completion of end-point PCR, droplets are analyzed for fluorescence and categorized as positive or negative and DNA quantified using Poisson statistics. Here we describe development of a direct E. coli hr DNA dd PCR method where the drug is directly added to the ddPCR reaction. We show that the ddPCR method has acceptable precision and high accuracy, works with different biologic drugs, and compared to qPCR shows higher tolerance of drug matrices. The method does not require DNA extraction or standard curves for quantification of hr DNA in unknown samples.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89903216","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}
In this study, antioxidant, cytotoxic, larvicidal, antimicrobial and anthelmintic effects and phenolic contents of ethanol, methanol and acetone extracts of leaf and tuber parts of Cyclamen alpinum were investigated. DPPH, ABTS, β-carotene assays were carried out in antioxidant activity and total phenolic and flavonoid contents were tested in determination assay. 9 phenolic contents were determined by HPLC. Artemia salina was used in the cytotoxic effect. Larvicidal effect was investigated against Culex pipiens. Disc diffusion method was used in antimicrobial effect. The tuber part was found to be more toxic than the leaf part in the anthelmintic activity assay. The highest value obtained from the antioxidant activity experiment was observed with value of 86.73 ± 0.16 (%) in DPPH assay. The lowest LC50 value in larvicidal effect was determined 0.151 mg/mL after 72 hours. Consequently, there is need for further studies on the Cyclamen alpinum, which has the ability to fight against diseases such as cancer, cardiovascular diseases, etc.
{"title":"Antioxidant, Antimicrobial, Cytotoxic, Larvicidal and Anthelmintic Activities and Phenolic Contents of Cyclamen alpinum","authors":"M. Turan, R. Mammadov","doi":"10.4236/PP.2018.94008","DOIUrl":"https://doi.org/10.4236/PP.2018.94008","url":null,"abstract":"In this study, antioxidant, cytotoxic, larvicidal, antimicrobial and anthelmintic effects and phenolic contents of ethanol, methanol and acetone extracts of leaf and tuber parts of Cyclamen alpinum were investigated. DPPH, ABTS, β-carotene assays were carried out in antioxidant activity and total phenolic and flavonoid contents were tested in determination assay. 9 phenolic contents were determined by HPLC. Artemia salina was used in the cytotoxic effect. Larvicidal effect was investigated against Culex pipiens. Disc diffusion method was used in antimicrobial effect. The tuber part was found to be more toxic than the leaf part in the anthelmintic activity assay. The highest value obtained from the antioxidant activity experiment was observed with value of 86.73 ± 0.16 (%) in DPPH assay. The lowest LC50 value in larvicidal effect was determined 0.151 mg/mL after 72 hours. Consequently, there is need for further studies on the Cyclamen alpinum, which has the ability to fight against diseases such as cancer, cardiovascular diseases, etc.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73327852","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}
Hiccups commonly occur in patients undergoing chemotherapy for lung cancer and may diminish their motivation for treatment. Therefore, it is important to characterize the hiccups and their risk factors. We examined the medical records of 120 patients with lung cancer during their initial chemotherapy and extracted data on the patients’ profiles and the onset, duration, and severity of their hiccup episodes. We found the incidence of hiccups to be 19.2% among the patients. Hiccups appeared within 3 days of beginning the chemotherapy and disappeared within 4 days. Hiccups hindered sleep in two patients. The characteristics of the hiccups episodes in our study were not different from those of previous studies. We also investigated distinctive features of the patients who developed hiccups. The occurrence of hiccups was associated with gender, age, and the treatment with platinum agents. Antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists, also showed significant effects on hiccup episodes. Although the dose-responsive effect of dexamethasone on hiccups was insignificant and the effects of two neurokinin-1 receptor antagonists, aprepitant and fosaprepitant, on hiccups appeared identical. From these results, we suggest that a high incidence of hiccups may be anticipated with a prophylactic use of antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists.
{"title":"Effect of Antiemetic Agents on Hiccups during Chemotherapy in Patients with Lung Cancer","authors":"Shinya Toriumi, K. Nakazawa, M. Shoji","doi":"10.4236/pp.2018.94010","DOIUrl":"https://doi.org/10.4236/pp.2018.94010","url":null,"abstract":"Hiccups commonly occur in patients undergoing chemotherapy for lung cancer and may diminish their motivation for treatment. Therefore, it is important to characterize the hiccups and their risk factors. We examined the medical records of 120 patients with lung cancer during their initial chemotherapy and extracted data on the patients’ profiles and the onset, duration, and severity of their hiccup episodes. We found the incidence of hiccups to be 19.2% among the patients. Hiccups appeared within 3 days of beginning the chemotherapy and disappeared within 4 days. Hiccups hindered sleep in two patients. The characteristics of the hiccups episodes in our study were not different from those of previous studies. We also investigated distinctive features of the patients who developed hiccups. The occurrence of hiccups was associated with gender, age, and the treatment with platinum agents. Antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists, also showed significant effects on hiccup episodes. Although the dose-responsive effect of dexamethasone on hiccups was insignificant and the effects of two neurokinin-1 receptor antagonists, aprepitant and fosaprepitant, on hiccups appeared identical. From these results, we suggest that a high incidence of hiccups may be anticipated with a prophylactic use of antiemetic agents, dexamethasone and neurokinin-1 receptor antagonists.","PeriodicalId":19875,"journal":{"name":"Pharmacology & Pharmacy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85819182","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}
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