Journal of Pharmacology & Pharmaceutical Research最新文献

{"title":"Cruzain Inhibitors as Prominent Molecules with The Potential to become Drug Candidates against Chagas Disease","authors":"L. Y. Vargas-Méndez, V. Kouznetsov","doi":"10.31038/jppr.2019233","DOIUrl":"https://doi.org/10.31038/jppr.2019233","url":null,"abstract":"Chagas disease, a parasitic, endemic infection affects about 10–15 million of people all over Latin America. In addition, Chagas disease has an increased global impact in nonendemic areas due to immigration patterns. More than 10, 000 deaths are caused by this disease each year, and nearly 70 million people are susceptible to infection. Although Chagas disease was identified more than 100 years ago, current therapeutic options for this condition are limited mainly to two ineffective drugs, benznidazole and nifurtimox. These two drugs are not optimal as currently applied because they show substantial toxicity, require long courses of administration and have inconsistent efficacy. In light of these problems, safer and more effective therapeutic options for patients with Chagas disease are clearly needed. Many candidate drugs are currently being tested. Among them, cruzapain inhibitors are considered promising agents that have been shown to have potential for more effective treatment of the chronic form of Chagas disease. In this work we review briefly the most significant advance in the design of new molecules able to kill Trypanosoma cruzi via an inhibition of the enzyme cruzain (also referred to as cruzipain, the full-length native enzyme).","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115597710","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":"Determination of Biuret Content in Fertilizers by High Performance Liquid Chromatography: Single-Laboratory Validation and Collaborative Ring Test Study","authors":"D. Chu, M. Hojjatie, Gang Liu","doi":"10.31038/jppr.2019236","DOIUrl":"https://doi.org/10.31038/jppr.2019236","url":null,"abstract":"Urea or urea-based fertilizers has become the leading form of nitrogen fertilizers around the world. Biuret, as one of major by-products formed during the manufacturing of urea, was proved to be harmful to plant growth. A Single-Laboratory Validation (SLV) study for a newly proposed High Performance Liquid Chromatography (HPLC) method was conducted. A total of six samples were tested in the SLV study: two urea samples, and four compound fertilizers with various compositions from different sources. In addition, one biuret standard from Aldrich® and one biuret reference from Alfa Aesar® were used as standard materials. The system was linear over a concentration range of 0~200 ppm biuret, with a correlation coefficient≥0.999. Recoveries were determined by spiking three of the validation samples with known amounts of biuret standard solutions and measuring the biuret level according to the method. The recovery rates lies between 98.14% and 107.24%. Method precision was determined by analyzing of six validation samples under five replicate analyses, the RSDs ranged from 0.69% to 1.85%. Further study by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) has revealed that the biuret was well-separated from urea and other N-containing compounds in the system by this method. Moreover, the proposed method is verified in the international Collaborative Ring Test (CRT) study organized by ISO/TC 134 “Fertilizers and Soil Conditioners”. Systematically statistical analysis on the data obtained has proven that this method is capable of effectively monitoring biuret content in a wide range of fertilizers.","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133665932","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":"JAK Inhibitors: New Treatments for RA and beyond","authors":"P. Ruminski, J. Dipersio","doi":"10.31038/jppr.2019212","DOIUrl":"https://doi.org/10.31038/jppr.2019212","url":null,"abstract":"Janus kinases are a family of intra-cellular tyrosine kinases that are activated after stimulation of several cell surface receptors by their specific growth factors, growth hormones, chemokines and cytokines. After activation, they phosphorylate STAT transcription factors, resulting in the transportation of these STATs to the nucleus and affecting expression of specific genes. These transduced cytokinemediated signals via the JAK-STAT pathway are pivotal for the downstream signaling of inflammatory responses and their desired, as well as pathologic affects. As such, JAK kinases are a critical conduit for translating information from a cell’s extracellular environment to its nucleus, resulting in gene expression profiles corresponding to these extracellular cues.","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117069216","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":"Comparison of Various Selection Strategies Used for Isolation of Human Monoclonal scFv Antibody Specific to GPCRs Heteromers","authors":"S. Łukasiewicz, A. Stachowicz, Monika Bzowska, M. Dziedzicka-Wasylewska","doi":"10.31038/jppr.2019224","DOIUrl":"https://doi.org/10.31038/jppr.2019224","url":null,"abstract":"Currently, novel drug design focused on the searching pharmacological compounds acting via influence on GPCRs heteromers. The strategy allows obtaining highly selective effects since these heteromers appear only on specific cells and tissues. Therefore, human monoclonal scFv antibodies able to recognizing GPCRs heteromers may constitute a valuable tool in modern therapies. Antibody phage display technique together with high throughput screening play a key role in the development of clinically useful immunomolecules. Therefore in the present work we focused on the comparison of various strategies used for biopanning process during phage display procedure, dedicated to isolation scFv antibodies specifically recognizing GPCRs heteromers. Experiments were conducted in two different cell lines (CHO-K1 and HEK 293) and six various selection procedures were described. Elimination of nonspecific bindings constitutes a key point during the process. Results obtained duing selection conducted in the conditions promoting internalization process were the most satisfactory.","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131087384","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":"Pediatric COVID-19","authors":"N. A. Jabir, Al Awwadi, Makarim M. Ali Hassan","doi":"10.31038/jppr.2021423","DOIUrl":"https://doi.org/10.31038/jppr.2021423","url":null,"abstract":"Corona is a common viral disease that can be transmitted between humans and different types of animals, meaning it can be transmitted between different races and types of living organisms. It is characterized as having broad-spectrum disease symptoms that differ from one patient to another in their severity and type. In the last months of 2019, a storm of infection with the Corona virus appeared in the Chinese city of Wuhan, with symptoms that were almost different in severity and led to deaths in some infections. The virus was characterized by its rapid spread among people, which surprised researchers, doctors and people in that city and in China in general. Which challenged Chinese researchers and scientists to investigate the type and nature of the causative agent, so they were able to diagnose Corona virus (Cove 2).","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115684451","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":"Microemulsions and Nanoparticles as Carriers for Dermal and Transdermal Drug Delivery","authors":"C. Velasco-Aguirre, A. Sintov","doi":"10.31038/jppr.2019241","DOIUrl":"https://doi.org/10.31038/jppr.2019241","url":null,"abstract":"The major obstacle of dermal and transdermal therapeutics is the low penetration rate of xenobiotics through the skin due to the diffusional barrier of its upper layer, the stratum corneum. A wide array of techniques has been proposed thus far, however, recent developments in the application of nanosystems for topical drug administration have gained much interest and optimism. In this review, we provide a comprehensive overview of the main types of nanocarriers that have been studied and developed up-to-date. We conclude that the nanosystems may become a useful dosage form for a variety of dermally active principals by modulating drug transfer and serving as nontoxic penetration enhancers.","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126788282","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":"L-Ornithine L-Aspartate: Multimodal Therapeutic Agent for Hyperammonemia and Hepatic Encephalopathy in Cirrhosis","authors":"R. Butterworth","doi":"10.31038/jppr.2019234","DOIUrl":"https://doi.org/10.31038/jppr.2019234","url":null,"abstract":"L-ornithine L-aspartate (LOLA) is a 1:1 stable salt of naturally-occurring amino acids L-ornithine and L-aspartic acid. Following oral administration, LOLA is rapidly absorbed dependent on the Na+ ion gradient. The elimination half-life is estimated to be in the 30–45 min range with bioavailability of 82.2%. LOLA has the proven capacity to cause lowering of blood ammonia and it does so as a result of multiple established mechanisms. Being a urea cycle intermediate and, more specifically, an activator of carbomyl phosphate synthetase, L-ornithine stimulates ammonia removal as urea by periportal hepatocytes. Both L-ornithine and L-aspartate are substrates for transamination reactions resulting in formation of glutamate, the obligate substrate for glutamine synthetase located in perivenous hepatocytes, skeletal muscle and brain. Increases of brain glutamine correlate with severity of Hepatic Encephalopathy (HE) in patients with cirrhosis. In cirrhosis, the normal pattern of inter-organ trafficking is modified and skeletal muscle replaces the liver as the major ammonia-removing organ. Muscle wasting (sarcopenia) occurs in cirrhosis as a result of exposure to ammonia and this seriously limits its ammonia-lowering capacity leading to a vicious cycle and worsening of hyperammonemia. Trials demonstrate that treatment with LOLA improves muscle function in patients with cirrhosis. There is evidence to suggest that LOLA also has direct hepatoprotective actions in these patients via mechanisms related to the production of antioxidants and the synthesis of nitric oxide leading to improved hepatic microcirculation. Over 20 randomized controlled trials together with systematic reviews and meta-analyses have demonstrated that LOLA is effective for the prevention and treatment of HE in cirrhosis where improvements in mental state occurred as a consequence of the lowering of circulating ammonia.","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129836015","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":"Experimental Studies and First Retrospective Clinical Data Suggest a Possible Benefit of CBD in COVID-19","authors":"R. Likar, M. Köstenberger, Stefan Neuwersch-Sommeregger, G. Nahler","doi":"10.31038/jppr.2021412","DOIUrl":"https://doi.org/10.31038/jppr.2021412","url":null,"abstract":"SARS-CoV-2 damages human cells and organs by multiple mechanisms. Intriguingly, preclinical studies have demonstrated that cannabidiol (CBD) may interact in many ways with virus entry and cell stress on one hand, and with inflammatory mechanisms affecting the lung and other organs on the other. A number of very recent in vitro and in silico studies demonstrate that CBD may be able to affect a high number of different proteins that are involved in the infection process, among them the Glucose Regulated Protein 78, heme oxygenase 1 (HO1), the virus-specific protease SARS-CoV-2 Mpro and apelin. Furthermore, a number of animal studies confirmed independently the anti-inflammatory and organ protective properties of CBD. As there is still no optimal treatment known, highly purified magisterial phyto-CBD has been included to a standard therapy for COVID-19 as an adjunct anti-inflammatory drug. A retrospective analysis of data of 30 patients hospitalised for COVID-19 and who received adjuvant low dose CBD (up to 300 mg/day), show a more pronounced reduction of virus load, normalisation of lymphocyte counts and of other abnormal laboratory parameters when compared to a non-matched group of patients who did not receive CBD.","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114067953","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":"Review on Divalent Atom and Group in Bioisosterism","authors":"Hawi M. Daka","doi":"10.31038/jppr.2021421","DOIUrl":"https://doi.org/10.31038/jppr.2021421","url":null,"abstract":"Bioisosterism in rational drug design approach specifically the divalent atom and group in their modification and optimization to improve the pharmacokinetic and pharmacodynamics properties of compound have been studied.","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"195 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133684131","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":"Nootropic, Neuroprotective and Anti-oxidant Role of Apocynin in Scopolamine Induced Memory Deficit in a Zebrafish Model","authors":"Sneha Bagle, Suraj Muke, V. Peshattiwar, A. Kaikini, S. Sathaye, Prof. Sadhana Sathaye","doi":"10.31038/jppr.2021414","DOIUrl":"https://doi.org/10.31038/jppr.2021414","url":null,"abstract":"Four decades of search in quest of an effective therapeutic option for Alzheimer’s disease (AD) has led to a complete clinical failure, putting pre-clinical models, their evaluation in spotlight. The pre-clinical stage if lead with a systemic approach, than jumping straight into clinical trials, will reduce financial burden opening avenues for effective AD therapeutics. Preliminary screening therefore shall be fast, ensuring use of efficient, easy, and less time consuming pre-clinical models for screening new entities. Aim of present research was therefore development of a quick, effective, and easy zebrafish model for preliminary screening of probable AD therapeutics. The present research used total of 72 zebrafish divided into six groups, control, negative control, vehicle control, and 3 groups for apocynin (10 mg/kg, 30 mg/kg, and 70 mg/kg). We investigated memory retention, long term memory retention using passive avoidance paradigm, free radical generation using DCFDA assay, and glial cell proliferation using H and E histological staining. Intraperitoneally administered scopolamine (0.025 mg/kg) induced memory deficits hindering memory formation. Apocynin at all doses prevented scopolamine-induced amnesia. Apocynin was found to be capable of reducing free radical load and curbing the inflammation due to scopolamine administration. Moreover; long term memory retention was observed with 10 mg/kg apocynin. Our revelations designate the fact that passive avoidance model in zebrafish could be used as an acute model in order to screen potential entities for treatment of AD. Our findings highlight that a single dose of apocynin could reverse memory deficits induced by single scopolamine injection by acting on cholinergic transmission pathway. Apocynin being an anti-oxidant reduced the free radical generation, thus engaging one of the crucial pathways toward AD pathophysiology. In addition it offered neuroprotection by reducing glial cell proliferation. In conclusion apocynin exhibited multifaceted pharmacological activities like being nootropic, neuroprotective, and anti-oxidant in preclinical AD model. of the neuronal environment. Administration of single dose of SCP demonstrates the highest score for glial cell proliferation and hence the severe neuronal damage. The damage was totally reversed by apocynin 10 mg/kg and 30 mg/kg as evident with nil glial cell proliferation. The other dose of apocynin 70 mg/kg was effective compared to the negative control group, but could not completely reverse the damage. Apocynin thus bestowed neuroprotection by mitigating the neuronal damage, ultimately maintaining the neuronal homeostasis against the mulct of scopolamine administration. Our study reveals and advocates that passive avoidance test in zebrafish can be used as an acute preliminary in-vivo model to screen potential anti-Alzheimer entities. Our findings emphasize that the phytoactive apocynin reversed the memory deficits and retained the memory hampe","PeriodicalId":285318,"journal":{"name":"Journal of Pharmacology & Pharmaceutical Research","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133096805","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}