Glaucoma is a major global cause of blindness, but the molecular mechanisms responsible for the neurodegenerative damage are not clear. Undoubtedly, the high intraocular pressure (IOP) and the secondary ischemic and mechanical damage of the optic nerve have a crucial role in retinal ganglion cell (RGC) death. Several studies specifically analyzed the events that lead to nerve fiber layer thinning, showing the importance of both intra- and extracellular factors. In parallel, many neuroprotective substances have been tested for their efficacy and safety in hindering the negative effects that lead to RGC death. New formulations of these compounds, also suitable for chronic oral administration, are likely to be used in clinical practice in the future along with conventional therapies, in order to control the progression of the visual impairment due to primary open-angle glaucoma (POAG). This review illustrates some of these old and new promising agents for the adjuvant treatment of POAG, with particular emphasis on forskolin and melatonin.
{"title":"Neuroprotection in Glaucoma: Old and New Promising Treatments.","authors":"Dario Rusciano, Salvatore Pezzino, Maria Giulia Mutolo, Rossella Giannotti, Aloisa Librando, Nicola Pescosolido","doi":"10.1155/2017/4320408","DOIUrl":"https://doi.org/10.1155/2017/4320408","url":null,"abstract":"<p><p>Glaucoma is a major global cause of blindness, but the molecular mechanisms responsible for the neurodegenerative damage are not clear. Undoubtedly, the high intraocular pressure (IOP) and the secondary ischemic and mechanical damage of the optic nerve have a crucial role in retinal ganglion cell (RGC) death. Several studies specifically analyzed the events that lead to nerve fiber layer thinning, showing the importance of both intra- and extracellular factors. In parallel, many neuroprotective substances have been tested for their efficacy and safety in hindering the negative effects that lead to RGC death. New formulations of these compounds, also suitable for chronic oral administration, are likely to be used in clinical practice in the future along with conventional therapies, in order to control the progression of the visual impairment due to primary open-angle glaucoma (POAG). This review illustrates some of these old and new promising agents for the adjuvant treatment of POAG, with particular emphasis on forskolin and melatonin.</p>","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2017 ","pages":"4320408"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/4320408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36921683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-01-01Epub Date: 2017-07-09DOI: 10.1155/2017/6507048
Yaping Zhang, Man Mi, Yan-Hua Xie, Si-Wang Wang, Lars Edvinsson, Cang-Bao Xu
Thromboxane A2 (TXA2) acts on TXA2 receptors (TP) to regulate renal artery blood flow and subsequently contributes to the pathogenesis of renal ischemia. The present study was designed to examine if nuclear factor-kappaB (NF-κB) signaling pathway is involved in the downregulation of TP receptors in rat renal artery. Rat renal artery segments were organ cultured for 6 or 24 h. Downregulation of TP receptors was monitored using myograph (contractile function), real-time PCR (receptor mRNA), and immunohistochemistry (receptor protein). Specific inhibitors (MG-132 and BMS345541) for NF-κB signaling pathway were used to dissect the underlying molecular mechanisms involved. Compared to fresh (noncultured) segments, organ culture of the renal artery segments for 24 h induced a significant rightward shift of U46619 (TP receptor agonist) contractile response curves (pEC50: 6.89 ± 0.06 versus 6.48 ± 0.04, P < 0.001). This decreased contractile response to U46619 was paralleled with decreased TP receptor mRNA and protein expressions in the renal artery smooth muscle cells. Specific inhibitors (MG-132 and BMS345541) for NF-κB signaling pathway significantly abolished the decreased TP protein expression and receptor-mediated contractions. In conclusion, downregulation of TP receptors in the renal artery smooth muscle cells occurs mainly via the NF-κB signaling pathway.
血栓素A2 (TXA2)作用于TXA2受体(TP)调节肾动脉血流，从而参与肾缺血的发病机制。本研究旨在探讨核因子κ b (NF-κB)信号通路是否参与大鼠肾动脉TP受体的下调。大鼠肾动脉段器官培养6、24 h。采用肌图(收缩功能)、实时PCR(受体mRNA)和免疫组化(受体蛋白)监测TP受体的下调。利用NF-κB信号通路特异性抑制剂(MG-132和BMS345541)来剖析其潜在的分子机制。与新鲜(未培养)肾动脉段相比，器官培养24小时可诱导U46619 (TP受体激动剂)收缩反应曲线显著右移(pEC50: 6.89±0.06 vs 6.48±0.04,P < 0.001)。U46619的收缩反应降低与肾动脉平滑肌细胞中TP受体mRNA和蛋白表达的降低是一致的。NF-κB信号通路特异性抑制剂MG-132和BMS345541显著消除TP蛋白表达下降和受体介导的收缩。综上所述，肾动脉平滑肌细胞中TP受体的下调主要通过NF-κB信号通路发生。
{"title":"Downregulation of Thromboxane A<sub>2</sub> Receptor Occurs Mainly via Nuclear Factor-KappaB Signaling Pathway in Rat Renal Artery.","authors":"Yaping Zhang, Man Mi, Yan-Hua Xie, Si-Wang Wang, Lars Edvinsson, Cang-Bao Xu","doi":"10.1155/2017/6507048","DOIUrl":"https://doi.org/10.1155/2017/6507048","url":null,"abstract":"<p><p>Thromboxane A<sub>2</sub> (TXA<sub>2</sub>) acts on TXA<sub>2</sub> receptors (TP) to regulate renal artery blood flow and subsequently contributes to the pathogenesis of renal ischemia. The present study was designed to examine if nuclear factor-kappaB (NF-<i>κ</i>B) signaling pathway is involved in the downregulation of TP receptors in rat renal artery. Rat renal artery segments were organ cultured for 6 or 24 h. Downregulation of TP receptors was monitored using myograph (contractile function), real-time PCR (receptor mRNA), and immunohistochemistry (receptor protein). Specific inhibitors (MG-132 and BMS345541) for NF-<i>κ</i>B signaling pathway were used to dissect the underlying molecular mechanisms involved. Compared to fresh (noncultured) segments, organ culture of the renal artery segments for 24 h induced a significant rightward shift of U46619 (TP receptor agonist) contractile response curves (pEC<sub>50</sub>: 6.89 ± 0.06 versus 6.48 ± 0.04, <i>P</i> < 0.001). This decreased contractile response to U46619 was paralleled with decreased TP receptor mRNA and protein expressions in the renal artery smooth muscle cells. Specific inhibitors (MG-132 and BMS345541) for NF-<i>κ</i>B signaling pathway significantly abolished the decreased TP protein expression and receptor-mediated contractions. In conclusion, downregulation of TP receptors in the renal artery smooth muscle cells occurs mainly via the NF-<i>κ</i>B signaling pathway.</p>","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2017 ","pages":"6507048"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/6507048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35292644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ethnopharmacological relevance: Cryptolepis sanguinolenta is a scrambling thin-stemmed shrub found in Africa. Traditionally in West Africa, it is employed in the treatment of malaria, diarrhea, and respiratory conditions. This review discusses the traditional importance as well as the phytochemical, ethnomedical, pharmacological, and toxicological importance of this plant.
Materials and methods: Excerpta Medica Database, Google Scholar, Springer, and PubMed Central were the electronic databases used to search for and filter primary studies on Cryptolepis sanguinolenta.
Results: The detailed review of various studies conducted on C. sanguinolenta and some of its constituents gives an important body of proof of its potential therapeutic benefits and also of its use as a source of lead compounds with therapeutic potentials.
Conclusion: The review on C. sanguinolenta is important in identifying grey areas in the research on this medicinal plant and also provides comprehensive data thus far to continue research on this plant.
民族药理学意义：Cryptolepis sanguinolenta 是一种生长在非洲的蔓生细茎灌木。在西非的传统中，它被用于治疗疟疾、腹泻和呼吸道疾病。这篇综述讨论了这种植物的传统重要性以及植物化学、民族医学、药理学和毒理学方面的重要性：Excerpta Medica Database、Google Scholar、Springer 和 PubMed Central 是用于搜索和筛选 Cryptolepis sanguinolenta 主要研究的电子数据库：结果：对 C. sanguinolenta 及其部分成分进行的各种研究的详细综述为其潜在的治疗功效提供了重要的证据，也为其作为具有治疗潜力的先导化合物的来源提供了重要的证据：关于 C. sanguinolenta 的综述对于确定这种药用植物研究中的灰色地带非常重要，同时也为继续研究这种植物提供了全面的数据。
{"title":"Phytochemical and Pharmacological Review of <i>Cryptolepis sanguinolenta</i> (Lindl.) Schlechter.","authors":"Newman Osafo, Kwesi Boadu Mensah, Oduro Kofi Yeboah","doi":"10.1155/2017/3026370","DOIUrl":"10.1155/2017/3026370","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong><i>Cryptolepis sanguinolenta</i> is a scrambling thin-stemmed shrub found in Africa. Traditionally in West Africa, it is employed in the treatment of malaria, diarrhea, and respiratory conditions. This review discusses the traditional importance as well as the phytochemical, ethnomedical, pharmacological, and toxicological importance of this plant.</p><p><strong>Materials and methods: </strong>Excerpta Medica Database, Google Scholar, Springer, and PubMed Central were the electronic databases used to search for and filter primary studies on <i>Cryptolepis sanguinolenta</i>.</p><p><strong>Results: </strong>The detailed review of various studies conducted on <i>C. sanguinolenta</i> and some of its constituents gives an important body of proof of its potential therapeutic benefits and also of its use as a source of lead compounds with therapeutic potentials.</p><p><strong>Conclusion: </strong>The review on <i>C. sanguinolenta</i> is important in identifying grey areas in the research on this medicinal plant and also provides comprehensive data thus far to continue research on this plant.</p>","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2017 ","pages":"3026370"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36090015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim of this study was to illustrate the initial subclinical drug-induced liver injury and the associated adaptive immune response by monitoring for the changes in plasma IL-2, IL-10, and some cytochrome P450 activity during chronic administration of nevirapine (NVP), isoniazid (INH), and paracetamol (PAR) in rats without clinical hepatotoxicity. Male Sprague-Dawley (SD) rats were divided into four groups (saline (S), NVP, INH, and PAR) of 25 animals each. The drugs were administered daily for 42 days at therapeutic doses (NVP 200 mg/kg, PAR 500 mg/kg, and INH 20 mg/kg) to the respective groups by oral gavage and five rats per group were sacrificed weekly. All the three drugs induced a subclinical liver injury in the first 2-3 weeks followed by healing, indicating adaption. The liver injury was pathologically similar and was associated with immune stimulation and increased cytochrome P450 activity. NVP- and PAR-induced liver injury lasted up to 14 days while that for INH lasted for 28 days. NVP-induced liver injury was associated with increased IL-2, CD4 count, and CYP3A2 activity, followed by increased IL-10 during the healing phase. In conclusion, the initial drug-induced subclinical liver injury, its spontaneous healing, and the associated adaptive immune response have been demonstrated.
{"title":"Changes in IL-2 and IL-10 during Chronic Administration of Isoniazid, Nevirapine, and Paracetamol in Rats","authors":"Zanelle Bekker, A. Walubo, J. D. du Plessis","doi":"10.1155/2016/3094783","DOIUrl":"https://doi.org/10.1155/2016/3094783","url":null,"abstract":"The aim of this study was to illustrate the initial subclinical drug-induced liver injury and the associated adaptive immune response by monitoring for the changes in plasma IL-2, IL-10, and some cytochrome P450 activity during chronic administration of nevirapine (NVP), isoniazid (INH), and paracetamol (PAR) in rats without clinical hepatotoxicity. Male Sprague-Dawley (SD) rats were divided into four groups (saline (S), NVP, INH, and PAR) of 25 animals each. The drugs were administered daily for 42 days at therapeutic doses (NVP 200 mg/kg, PAR 500 mg/kg, and INH 20 mg/kg) to the respective groups by oral gavage and five rats per group were sacrificed weekly. All the three drugs induced a subclinical liver injury in the first 2-3 weeks followed by healing, indicating adaption. The liver injury was pathologically similar and was associated with immune stimulation and increased cytochrome P450 activity. NVP- and PAR-induced liver injury lasted up to 14 days while that for INH lasted for 28 days. NVP-induced liver injury was associated with increased IL-2, CD4 count, and CYP3A2 activity, followed by increased IL-10 during the healing phase. In conclusion, the initial drug-induced subclinical liver injury, its spontaneous healing, and the associated adaptive immune response have been demonstrated.","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/3094783","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64318222","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}
Nushrat Sharmin Ani, Sudip Chakraborty, M. Moniruzzaman
Murraya koenigii L. is a perennial shrub, belonging to the family Rutaceae. Traditionally, the leaves of this plant are extensively used in treatment of a wide range of diseases and disorders including pain and inflammation. Although researchers have revealed the antinociceptive effects of this plant's leaves during past few years, the mechanisms underlying these effects are still unknown. Therefore, the present study evaluated some antinociceptive mechanisms of the methanolic extract of M. koenigii (MEMK) leaves along with its antinociceptive potential using several animal models. The antinociceptive effects of MEMK were evaluated using formalin-induced licking and acetic acid-induced writhing tests at the doses of 50, 100, and 200 mg/kg. In addition, we also justified the possible participations of glutamatergic system and ATP-sensitive potassium channels in the observed activities. Our results demonstrated that MEMK significantly (p < 0.01) inhibited the pain thresholds induced by formalin and acetic acid in a dose-dependent manner. MEMK also significantly (p < 0.01) suppressed glutamate-induced pain. Moreover, pretreatment with glibenclamide (an ATP-sensitive potassium channel blocker) at 10 mg/kg significantly (p < 0.05) reversed the MEMK-mediated antinociception. These revealed that MEMK might have the potential to interact with glutamatergic system and the ATP-sensitive potassium channels to exhibit its antinociceptive activities. Therefore, our results strongly support the antinociceptive effects of M. koenigii leaves and provide scientific basis of their analgesic uses in the traditional medicine.
{"title":"The Methanolic Extract from Murraya koenigii L. Inhibits Glutamate-Induced Pain and Involves ATP-Sensitive K+ Channel as Antinociceptive Mechanism","authors":"Nushrat Sharmin Ani, Sudip Chakraborty, M. Moniruzzaman","doi":"10.1155/2016/3790860","DOIUrl":"https://doi.org/10.1155/2016/3790860","url":null,"abstract":"Murraya koenigii L. is a perennial shrub, belonging to the family Rutaceae. Traditionally, the leaves of this plant are extensively used in treatment of a wide range of diseases and disorders including pain and inflammation. Although researchers have revealed the antinociceptive effects of this plant's leaves during past few years, the mechanisms underlying these effects are still unknown. Therefore, the present study evaluated some antinociceptive mechanisms of the methanolic extract of M. koenigii (MEMK) leaves along with its antinociceptive potential using several animal models. The antinociceptive effects of MEMK were evaluated using formalin-induced licking and acetic acid-induced writhing tests at the doses of 50, 100, and 200 mg/kg. In addition, we also justified the possible participations of glutamatergic system and ATP-sensitive potassium channels in the observed activities. Our results demonstrated that MEMK significantly (p < 0.01) inhibited the pain thresholds induced by formalin and acetic acid in a dose-dependent manner. MEMK also significantly (p < 0.01) suppressed glutamate-induced pain. Moreover, pretreatment with glibenclamide (an ATP-sensitive potassium channel blocker) at 10 mg/kg significantly (p < 0.05) reversed the MEMK-mediated antinociception. These revealed that MEMK might have the potential to interact with glutamatergic system and the ATP-sensitive potassium channels to exhibit its antinociceptive activities. Therefore, our results strongly support the antinociceptive effects of M. koenigii leaves and provide scientific basis of their analgesic uses in the traditional medicine.","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/3790860","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64348064","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}
Objective. To evaluate thrombus degrading effect of a fibrinolytic enzyme from food origin Stenotrophomonas sp. of Indonesia. Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. For in vivo studies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg. Blood clot in the tail was induced by kappa carrageenan injection at 1 mg/kg BW. Results. Experiment with cell culture confirmed the enzyme safety at the concentration used and increased expression of tPA. Decreasing of thrombus was observed in the positive group down to 70.35 ± 23.11% of the negative control animals (100%). The thrombus observed in the crude enzyme treatment was down to 56.99 ± 15.95% and 71.5 ± 15.7% for semipurified enzyme. Scanning electron microscopy showed clearly that bood clots were found in the animals injected with kappa carrageenan; however, in the treatment and positive groups, the clot was much reduced. Conclusions. Oral treatment of enzyme from Stenotrophomonas sp. of Indonesian fermented food was capable of degrading thrombus induced in Wistar rats.
{"title":"Thrombus Degradation by Fibrinolytic Enzyme of Stenotrophomonas sp. Originated from Indonesian Soybean-Based Fermented Food on Wistar Rats","authors":"F. Nailufar, R. Tjandrawinata, M. Suhartono","doi":"10.1155/2016/4206908","DOIUrl":"https://doi.org/10.1155/2016/4206908","url":null,"abstract":"Objective. To evaluate thrombus degrading effect of a fibrinolytic enzyme from food origin Stenotrophomonas sp. of Indonesia. Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. For in vivo studies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg. Blood clot in the tail was induced by kappa carrageenan injection at 1 mg/kg BW. Results. Experiment with cell culture confirmed the enzyme safety at the concentration used and increased expression of tPA. Decreasing of thrombus was observed in the positive group down to 70.35 ± 23.11% of the negative control animals (100%). The thrombus observed in the crude enzyme treatment was down to 56.99 ± 15.95% and 71.5 ± 15.7% for semipurified enzyme. Scanning electron microscopy showed clearly that bood clots were found in the animals injected with kappa carrageenan; however, in the treatment and positive groups, the clot was much reduced. Conclusions. Oral treatment of enzyme from Stenotrophomonas sp. of Indonesian fermented food was capable of degrading thrombus induced in Wistar rats.","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/4206908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64371269","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}
V. Kreil, L. Ambros, A. Prados, L. Tarragona, A. Monfrinotti, G. Bramuglia, M. Rebuelto
We investigate the pharmacokinetics of two different cephalexin formulations administered to llamas by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of cephalexin against some Escherichia coli and staphylococci isolated from llamas, and we apply the PK/PD modelling approach, so that effective dosage recommendations for this species could be made. Six llamas received immediate (10 mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin. Pharmacokinetic parameters were calculated by noncompartmental approach. Immediate release SC administration produced a significantly longer elimination half-life as compared with the IV and IM administration (1.3 ± 0.2 versus 0.6 ± 0.1 and 0.6 ± 0.1 h, resp.) and higher mean absorption time as compared with the IM administration (1.7 ± 0.5 versus 0.6 ± 0.4 h). Absolute bioavailability was in the range of 72–89% for both formulations and routes of administration. Cephalexin MIC90 values against staphylococci and E. coli were 1.0 and 8.0 μg/mL, respectively. Our results show that the immediate release formulation (10 mg/kg) would be effective for treating staphylococcal infections administered every 8 h (IM) or 12 h (SC), whereas the sustained release formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h, respectively.
{"title":"Pharmacokinetics of Immediate and Sustained Release Cephalexin Administered by Different Routes to Llamas (Lama glama)","authors":"V. Kreil, L. Ambros, A. Prados, L. Tarragona, A. Monfrinotti, G. Bramuglia, M. Rebuelto","doi":"10.1155/2016/4621039","DOIUrl":"https://doi.org/10.1155/2016/4621039","url":null,"abstract":"We investigate the pharmacokinetics of two different cephalexin formulations administered to llamas by the intravenous (IV), intramuscular (IM), and subcutaneous (SC) routes, the minimum inhibitory concentration (MIC) of cephalexin against some Escherichia coli and staphylococci isolated from llamas, and we apply the PK/PD modelling approach, so that effective dosage recommendations for this species could be made. Six llamas received immediate (10 mg/kg, IV, IM, and SC) and sustained (8 mg/kg IM, SC) release cephalexin. Pharmacokinetic parameters were calculated by noncompartmental approach. Immediate release SC administration produced a significantly longer elimination half-life as compared with the IV and IM administration (1.3 ± 0.2 versus 0.6 ± 0.1 and 0.6 ± 0.1 h, resp.) and higher mean absorption time as compared with the IM administration (1.7 ± 0.5 versus 0.6 ± 0.4 h). Absolute bioavailability was in the range of 72–89% for both formulations and routes of administration. Cephalexin MIC90 values against staphylococci and E. coli were 1.0 and 8.0 μg/mL, respectively. Our results show that the immediate release formulation (10 mg/kg) would be effective for treating staphylococcal infections administered every 8 h (IM) or 12 h (SC), whereas the sustained release formulation (8 mg/kg) would require the IM or SC administration every 12 or 24 h, respectively.","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/4621039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64389398","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}
M. S. T. Sheik Uduman, Rajitha Reddy, Priyanka Punuru, G. Chakka, G. Karunakaran
The present study was designed to investigate the role of combined administration of Ramipril and Candesartan against in vitro myocardial ischemic reperfusion injury in rat. Male Wistar albino rats were divided into five groups (n = 6) and treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of global ischemia (5 min of stabilization, 9 min of global ischemia, and 12 min of reflow). Combination of Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of superoxide dismutase, reduced glutathione, catalase, and nitric oxide and decreased the levels of thiobarbituric acid reactive substances. In addition, the superior protective role of combination of Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well preserved myocardial tissue architecture in light microscopy and transmission electron microscopy analysis studies. The combination was proved to be effective in salvaging the myocardial tissue against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels are needed.
{"title":"Protective Role of Ramipril and Candesartan against Myocardial Ischemic Reperfusion Injury: A Biochemical and Transmission Electron Microscopical Study","authors":"M. S. T. Sheik Uduman, Rajitha Reddy, Priyanka Punuru, G. Chakka, G. Karunakaran","doi":"10.1155/2016/4608979","DOIUrl":"https://doi.org/10.1155/2016/4608979","url":null,"abstract":"The present study was designed to investigate the role of combined administration of Ramipril and Candesartan against in vitro myocardial ischemic reperfusion injury in rat. Male Wistar albino rats were divided into five groups (n = 6) and treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of global ischemia (5 min of stabilization, 9 min of global ischemia, and 12 min of reflow). Combination of Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of superoxide dismutase, reduced glutathione, catalase, and nitric oxide and decreased the levels of thiobarbituric acid reactive substances. In addition, the superior protective role of combination of Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well preserved myocardial tissue architecture in light microscopy and transmission electron microscopy analysis studies. The combination was proved to be effective in salvaging the myocardial tissue against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels are needed.","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/4608979","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64388349","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}
S. Khademvatan, Alborz Eskandari, J. Saki, M. Foroutan-Rad
Leishmaniasis is a tropical parasitic infection. The resistance and toxicity issues are the major complications and remain significant consequences related to the treatment of leishmaniasis with the recent and classical drugs. Thus there is an immediate requirement to develop new compounds for the treatment of this protozoan disease. Sea cucumbers or holothurians are potentially presented as the marine sources of antimicrobial and cytotoxic compounds. The aim of this study was investigation of in vitro antileishmanial activity of methanol extract of body wall, coelomic fluid, and cuvierian organs of Holothuria leucospilota obtained from coastal parts of Persian Gulf against Leishmania infantum promastigotes and axenic amastigotes. The colorimetric MTT assay was used to determine L. infantum promastigotes and axenic amastigotes viability at different concentrations of the extracts and drug control (Glucantime®) at time dependent manner and the results are represented as IC50 (50% of inhibitory concentration). Coelomic fluid was the most active extract among the three different extracts of H. leucospilota against L. infantum promastigotes and axenic amastigotes with IC50s of 62.33 μg/mL and 22.4 μg/mL and 73 μg/mL and 46 μg/mL at 48 and 72 hours after treatment, respectively. Cuvierian organs extract showed less toxicity with IC50s more than 1000 μg/mL for both Leishmania infantum axenic amastigotes and promastigotes forms after 48 and 72 hours of exposure. Results acquired from the present study propose that the sea cucumber H. leucospilota may be a provoking source of antileishmanial compounds and could be a lead source in the development of the potent antileishmanial and cytotoxic drugs.
{"title":"Cytotoxic Activity of Holothuria leucospilota Extract against Leishmania infantum In Vitro","authors":"S. Khademvatan, Alborz Eskandari, J. Saki, M. Foroutan-Rad","doi":"10.1155/2016/8195381","DOIUrl":"https://doi.org/10.1155/2016/8195381","url":null,"abstract":"Leishmaniasis is a tropical parasitic infection. The resistance and toxicity issues are the major complications and remain significant consequences related to the treatment of leishmaniasis with the recent and classical drugs. Thus there is an immediate requirement to develop new compounds for the treatment of this protozoan disease. Sea cucumbers or holothurians are potentially presented as the marine sources of antimicrobial and cytotoxic compounds. The aim of this study was investigation of in vitro antileishmanial activity of methanol extract of body wall, coelomic fluid, and cuvierian organs of Holothuria leucospilota obtained from coastal parts of Persian Gulf against Leishmania infantum promastigotes and axenic amastigotes. The colorimetric MTT assay was used to determine L. infantum promastigotes and axenic amastigotes viability at different concentrations of the extracts and drug control (Glucantime®) at time dependent manner and the results are represented as IC50 (50% of inhibitory concentration). Coelomic fluid was the most active extract among the three different extracts of H. leucospilota against L. infantum promastigotes and axenic amastigotes with IC50s of 62.33 μg/mL and 22.4 μg/mL and 73 μg/mL and 46 μg/mL at 48 and 72 hours after treatment, respectively. Cuvierian organs extract showed less toxicity with IC50s more than 1000 μg/mL for both Leishmania infantum axenic amastigotes and promastigotes forms after 48 and 72 hours of exposure. Results acquired from the present study propose that the sea cucumber H. leucospilota may be a provoking source of antileishmanial compounds and could be a lead source in the development of the potent antileishmanial and cytotoxic drugs.","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/8195381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64553968","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}
Hadi Darvishi Khezri, E. Salehifar, M. Kosaryan, Aily Aliasgharian, H. Jalali, A. Hadian Amree
Major β-thalassemia (β-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of β-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with β-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.
重度β-地中海贫血(β-TM)是一种最常见的遗传性溶血性贫血，是由于血红蛋白中β-珠蛋白链的缺失或合成减少而引起的。这种缺陷导致红细胞溶解和慢性贫血，可通过多次输血和铁螯合治疗。如果不进行铁螯合治疗，铁超载会给患者带来许多并发症。抗氧化成分在疾病的治疗中起着重要作用。水飞蓟素是从水飞蓟植物中分离得到的抗氧化类黄酮。在本研究中，我们通过PubMed、ISI Web of Knowledge、Science Direct、Scopus、Ovid和Cochrane图书馆数据库，回顾了2015年9月1日之前关于水飞蓟素使用的临床和实验研究，并评估了水飞蓟素对控制β-TM患者铁超载并发症的潜在作用。基于本研究的结果，我们可以得出结论，水飞蓟素可能是一种有用的辅助治疗多器官功能障碍。
{"title":"Potential Effects of Silymarin and Its Flavonolignan Components in Patients with β-Thalassemia Major: A Comprehensive Review in 2015","authors":"Hadi Darvishi Khezri, E. Salehifar, M. Kosaryan, Aily Aliasgharian, H. Jalali, A. Hadian Amree","doi":"10.1155/2016/3046373","DOIUrl":"https://doi.org/10.1155/2016/3046373","url":null,"abstract":"Major β-thalassemia (β-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of β-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with β-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.","PeriodicalId":7389,"journal":{"name":"Advances in Pharmacological Sciences","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2016/3046373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64312459","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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