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Mohammed Sherif - One of the best experts on this subject based on the ideXlab platform.
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Calcium Channel Blockers for preventing acute tubular necrosis in kidney transplant recipients
Cochrane Database of Systematic Reviews, 2007Co-Authors: Ilona Shilliday, Mohammed SherifAbstract:BACKGROUND: The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium Channel Blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. OBJECTIVES: To evaluate the benefits and harms of using Calcium Channel Blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966) and EMBASE (from 1980). The Trials Search Coordinator was contacted to develop the search strategy. Date of last database and register search: January 2005 SELECTION CRITERIA: Randomised controlled trials comparing Calcium Channel Blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Ten trials were suitable for inclusion. Treatment with Calcium Channel Blockers in the peri-transplant period was associated with a significant decrease in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed graft function (RR 0.51, 95% CI 0.36 to 0.72). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. AUTHORS' CONCLUSIONS: These results suggest that Calcium Channel Blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.
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Calcium Channel Blockers for preventing acute tubular necrosis in kidney transplant recipients
Cochrane Database of Systematic Reviews, 2007Co-Authors: Ilona Shilliday, Mohammed SherifAbstract:Background The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium Channel Blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. Objectives To evaluate the benefits and harms of using Calcium Channel Blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. Search strategy We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966) and EMBASE (from 1980). The Trials Search Coordinator was contacted to develop the search strategy. Date of last search: January 2007 Selection criteria Randomised controlled trials comparing Calcium Channel Blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. Data collection and analysis Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as mean differences (WMD) with 95% confidence intervals (CI). Main results Thirteen trials (724 participants) were suitable for inclusion. Treatment with Calcium Channel Blockers in the peri-transplant period was associated with a significant decrease in the incidence of post-transplant ATN (RR 0.62, 95% CI 0.46 to 0.85) and delayed graft function (RR 0.55, 95% CI 0.42 to 0.73). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. Authors' conclusions These results suggest that Calcium Channel Blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.
Ilona Shilliday - One of the best experts on this subject based on the ideXlab platform.
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Calcium Channel Blockers for preventing acute tubular necrosis in kidney transplant recipients
Cochrane Database of Systematic Reviews, 2007Co-Authors: Ilona Shilliday, Mohammed SherifAbstract:BACKGROUND: The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium Channel Blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. OBJECTIVES: To evaluate the benefits and harms of using Calcium Channel Blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966) and EMBASE (from 1980). The Trials Search Coordinator was contacted to develop the search strategy. Date of last database and register search: January 2005 SELECTION CRITERIA: Randomised controlled trials comparing Calcium Channel Blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Ten trials were suitable for inclusion. Treatment with Calcium Channel Blockers in the peri-transplant period was associated with a significant decrease in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed graft function (RR 0.51, 95% CI 0.36 to 0.72). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. AUTHORS' CONCLUSIONS: These results suggest that Calcium Channel Blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.
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Calcium Channel Blockers for preventing acute tubular necrosis in kidney transplant recipients
Cochrane Database of Systematic Reviews, 2007Co-Authors: Ilona Shilliday, Mohammed SherifAbstract:Background The incidence of delayed graft function in cadaveric grafts has increased over the last few years due in part to the large demand for cadaveric kidneys necessitating the use of kidneys from marginal donors. Calcium Channel Blockers have the potential to reduce the incidence of post-transplant acute tubular necrosis (ATN) if given in the peri-operative period. However, there is controversy surrounding their use in this situation with no consensus as to their efficacy. Objectives To evaluate the benefits and harms of using Calcium Channel Blockers in the peri-transplant period in patients at risk of ATN following cadaveric kidney transplantation. Search strategy We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966) and EMBASE (from 1980). The Trials Search Coordinator was contacted to develop the search strategy. Date of last search: January 2007 Selection criteria Randomised controlled trials comparing Calcium Channel Blockers given in the peri-transplant period with controls were included. Quasi-randomised trials were excluded. Data collection and analysis Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as mean differences (WMD) with 95% confidence intervals (CI). Main results Thirteen trials (724 participants) were suitable for inclusion. Treatment with Calcium Channel Blockers in the peri-transplant period was associated with a significant decrease in the incidence of post-transplant ATN (RR 0.62, 95% CI 0.46 to 0.85) and delayed graft function (RR 0.55, 95% CI 0.42 to 0.73). There was no difference between control and treatment groups in graft loss, mortality, requirement for haemodialysis. There was insufficient information to comment on adverse events. Authors' conclusions These results suggest that Calcium Channel Blockers given in the peri-operative period may reduce the incidence of ATN post-transplantation. The result should be treated with caution due to the heterogeneity of the trials which made comparison of studies and pooling of data difficult.
Terrance P. Snutch - One of the best experts on this subject based on the ideXlab platform.
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Recent advances in the development of T‐type Calcium Channel Blockers for pain intervention
British journal of pharmacology, 2017Co-Authors: Terrance P. Snutch, Gerald W. ZamponiAbstract:Cav3.2 T-type Calcium Channels are important regulators of pain signals in afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore it stands to reason that inhibiting T-type Calcium Channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T-type Channel Blockers such as ethosuximide, and by analgesic effects of siRNA depletion of Cav3.2 Channels. In the past five years, considerable effort has been applied towards identifying novel classes of T-type Calcium Channel Blockers. Here we review recent developments in the discovery of novel classes of T-type Calcium Channel Blockers, and their analgesics effects in animal models of pain and in clinical trials.
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Scaffold-based design and synthesis of potent N-type Calcium Channel Blockers.
Bioorganic & medicinal chemistry letters, 2009Co-Authors: Gerald W. Zamponi, Hassan Pajouhesh, Zhong Ping Feng, Lingyun Zhang, Yanbing Ding, Francesco Belardetti, David Dolphin, Lester A. Mitscher, Terrance P. SnutchAbstract:The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion Channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type Calcium Channel Blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type Calcium Channel Blockers which have good selectivity over L-type Calcium Channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium Channel.
Gerald W. Zamponi - One of the best experts on this subject based on the ideXlab platform.
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Recent advances in the development of T‐type Calcium Channel Blockers for pain intervention
British journal of pharmacology, 2017Co-Authors: Terrance P. Snutch, Gerald W. ZamponiAbstract:Cav3.2 T-type Calcium Channels are important regulators of pain signals in afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore it stands to reason that inhibiting T-type Calcium Channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T-type Channel Blockers such as ethosuximide, and by analgesic effects of siRNA depletion of Cav3.2 Channels. In the past five years, considerable effort has been applied towards identifying novel classes of T-type Calcium Channel Blockers. Here we review recent developments in the discovery of novel classes of T-type Calcium Channel Blockers, and their analgesics effects in animal models of pain and in clinical trials.
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Scaffold-based design and synthesis of potent N-type Calcium Channel Blockers.
Bioorganic & medicinal chemistry letters, 2009Co-Authors: Gerald W. Zamponi, Hassan Pajouhesh, Zhong Ping Feng, Lingyun Zhang, Yanbing Ding, Francesco Belardetti, David Dolphin, Lester A. Mitscher, Terrance P. SnutchAbstract:The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion Channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type Calcium Channel Blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type Calcium Channel Blockers which have good selectivity over L-type Calcium Channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium Channel.
şukru Beydemir - One of the best experts on this subject based on the ideXlab platform.
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anti diabetic properties of Calcium Channel Blockers inhibition effects on aldose reductase enzyme activity
Applied Biochemistry and Biotechnology, 2019Co-Authors: Cuneyt Turkes, Yeliz Demir, şukru BeydemirAbstract:Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some Calcium Channel Blockers and the enzyme. It was found that Calcium Channel Blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87–8.77 μM and Ki constants in the range of 2.07 ± 0.72–5.62 ± 1.53 μM. The Calcium Channel Blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (Ki: 2.07 ± 0.72 μM). They may be useful in the treatment and/or prevention of diabetic complications.
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effect of Calcium Channel Blockers on paraoxonase 1 pon1 activity and oxidative stress
Pharmacological Reports, 2014Co-Authors: Cuneyt Turkes, Hakan Soyut, şukru BeydemirAbstract:Abstract Background In this study, we investigated the in vitro effects of Calcium Channel Blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate) on the activity of paraoxonase-1 (PON1). Methods PON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion-exchange and Sephadex G-200 gel filtration chromatography. Results The Calcium Channel Blockers decreased the in vitro PON1 activity. The inhibition mechanism of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and isradipine were competitive inhibitors. Conclusions Our results showed that Calcium Channel Blockers exhibit inhibitory effects on PON1 at low concentrations. The IC 50 values for nifedipine, nitrendipine, isradipine, and amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304 mM, respectively, and the K i constants were calculated to be 0.222 ± 0.049 mM, 0.151 ± 0.067 mM, 0.286 ± 0.137 mM, and 0.321 ± 0.002 mM, respectively.