International Journal of Biological Macromolecules, Jul 1, 2015
An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was invest... more An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression. Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency of the system by inhibition of topoisomerase 1. CysTMC was synthetized and characterized by 1 H NMR and FTIR. Nanoparticles were prepared through complexation of CMD and cysTMC. Particle size and surface charge was 100-150 nm and 17-21 mV respectively with drug content of around 2.6%. Gel electrophoresis assay proved the stability of antisense in simulated gastric and intestinal fluids. Nanoparticles showed high mucoadhesion and glutathione responsive release. Cellular uptake was observed by confocal microscopy and quantified by flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore, present system could be considered an effective combination therapy of highly hydrophobic SN38 and hSET1.
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several fin... more Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several findings suggest that correcting the dysregulated signaling pathways may offer a potential therapeutic approach in this disease. Extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase family, plays a major role in regulation of cell proliferation, autophagy process, and protein synthesis. The available literature suggests dysregulated ERK1/2 in AD patients with potential implications in the multifaceted underlying pathologies of AD, including amyloid-β plaque formation, tau phosphorylation, and neuroinflammation. In this regard, in the current review, we aim to summarize the reports on the potential roles of ERK1/2 in AD pathophysiology.
Objective: Chronic obstructive pulmonary disease (COPD) is associated with many health complicati... more Objective: Chronic obstructive pulmonary disease (COPD) is associated with many health complications, including pulmonary hypertension (PH). Although oral calcium channel blockers have shown promising results in managing COPD-induced PH, significant systemic side effects may limit their use in this population. Administering verapamil through nebulization can be an alternative approach. We aim to assess the possible therapeutic effects of verapamil inhalation in outpatients with pulmonary hypertension (PH) secondary to COPD. Methods: A double-blind, randomized placebo-controlled clinical trial was conducted. Patients with PH were randomly assigned to two groups of 15 participants. The intervention group received a short-term single dose of 10 mg nebulized verapamil (4 ampoules of 2.5 mg/ml verapamil solutions). The control group received nebulized distilled water as a placebo in addition to their standard treatment throughout the study. Results: Systolic pulmonary artery pressure (sPAP) did not improve as a primary outcome significantly in patients receiving nebulized verapamil compared with those on placebo (p = 0.89). Spirometry results showed a significant improvement in FVC in the intervention group from 1.72 AE 0.63 to 1.85 AE 0.58 L (p = 0.00), and FEV1/FVC ratio decreased significantly after verapamil administration (p = 0.027).
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several fin... more Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several findings suggest that correcting the dysregulated signaling pathways may offer a potential therapeutic approach in this disease. Extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase family, plays a major role in regulation of cell proliferation, autophagy process, and protein synthesis. The available literature suggests dysregulated ERK1/2 in AD patients with potential implications in the multifaceted underlying pathologies of AD, including amyloid-β plaque formation, tau phosphorylation, and neuroinflammation. In this regard, in the current review, we aim to summarize the reports on the potential roles of ERK1/2 in AD pathophysiology.
Background: The recent studies emphasized on the correlation of vancomycin antibacterial effect w... more Background: The recent studies emphasized on the correlation of vancomycin antibacterial effect with pharmacokinetics properties such as the area under the curve/minimum inhibitory concentration (AUC24/MIC) ≥400 and serum trough level 15-20 mg /L in the patients with severe infection with methicillin-resistant Staphylococcus aureus (MRSA). The purpose is to assay the vancomycin pharmacokinetic properties in our population and evaluates the correlation between AUC24/MIC and trough serum level of vancomycin in given patients. Methods: The patients with a positive MRSA culture, treated with vancomycin, were enrolled in this cross-sectional study. Three plasma samples were obtained during the study including 30 min before fourth and the fifth dose as trough levels and 1 hour after the fourth dose as peak level to determine AUC24. E-TEST determined the MIC of vancomycin. Results: Thirty-eight patients with an average age of 48.33±16.44 were enrolled in this study. The mean ± SD of MIC wa...
INTRODUCTION Uremic pruritus (UP) is one of the major complaints in hemodialysis patients without... more INTRODUCTION Uremic pruritus (UP) is one of the major complaints in hemodialysis patients without specific treatment. Considering the antipruritic effect of melatonin in atopic dermatitis (AD) and similarities in mechanism between pruritus in AD and UP, this randomized clinical trial designed to evaluate the antipruritic effect of melatonin on hemodialysis patients with UP. METHODS This multicenter double-blind randomized clinical trial was conducted among the hemodialysis patients with UP. Adult patients were randomly assigned to receive two capsules of melatonin 5 mg /d for a 2 weeks period, undergoing a 1 week washout period, and then two capsules of placebo for another 2 weeks period, or the reverse sequence. Visual Analogue Scale (VAS), % affected Body Surface Area (%BSA) and 12-Pruritus Severity Scale questionnaire (12-PSS) were measured before and after each of the three periods. A crossover analysis of variance adjusted by treatment, period and carryover effect was performed...
Iranian Journal of Pharmaceutical Research : IJPR, 2021
Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a... more Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a negative impact on patient quality of life and potentially resulting in early liver transplants. Given the main role of the autotaxin enzyme in pruritus induced by CLD and the suppressive effects of melatonin on the expression of the autotaxin gene, this study was designed to evaluate the antipruritic effect of melatonin in patients with CLD. A double-blind, cross-over, randomized, placebo-controlled pilot trial was conducted on patients with CLD -induced pruritis. Patients were randomly assigned to two groups where they received melatonin 10-mg at night or placebo for 2 weeks. After a 2-week washout period, patients were then crossed over to the other group. The Visual Analog Scale (VAS) and the 12-Item Pruritus Severity Score (12-PSS) were used to assess patient response to therapy as the co-primary outcomes, while liver function tests were assayed too. Forty patients completed the st...
BACKGROUND Currently, there is no published questionnaire translated in the Persian language for ... more BACKGROUND Currently, there is no published questionnaire translated in the Persian language for pruritus evaluation in patients with chronic liver disease. Therefore, it would be well worth having a valid and reliable Persian questionnaire for assessing pruritus with its different aspects. This study was designed to evaluate the validity and reliability of the translated version of the 12-Item Pruritus Severity Score (12-PSS) METHODS The patients with pruritus due to chronic liver disease, who referred to the liver clinic affiliated to Tehran University of Medical Sciences, were enrolled in this cross-sectional study. Following the forward-backward translation of 12-PSS into Persian, the content validity index (CVI) and its reliability were assessed. The patients were asked to respond to the visual analog scale (VAS) along with 12-PSS on their visits to evaluate the correlation between them. RESULTS 160 eligible patients were entered in the present study. The mean age was 46.03 (±1...
Gastroenterology and Hepatology From Bed to Bench, 2021
Aim: A positive effect of melatonin on platelet count in patients with chronic liver disease is r... more Aim: A positive effect of melatonin on platelet count in patients with chronic liver disease is reported in the current study. Background: Thrombocytopenia occurs when the severity of liver disease is exacerbated. Reduction in the secretion of thrombopoetin, as an intrinsic hormone produced mainly by the liver, plays an important role in this complication induced by liver disease. Methods: This research was a double-blind, cross-over, placebo-controlled pilot study. Patients with liver disease were given two 5-mg pearls of melatonin or a placebo for two weeks, and after a 2-week washout period, their groups were switched. Liver function tests and platelet counts were assessed once at the beginning and once at the end of each phase of the study. Results In the current study, 40 patients meeting the eligibility criteria were included. The average platelet count was significantly increased by melatonin in comparison with the placebo (from 175.67±92.84 to 191.10±98.82 vs. from 185.22±98...
International Journal of Biological Macromolecules, Jul 1, 2015
An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was invest... more An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression. Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency of the system by inhibition of topoisomerase 1. CysTMC was synthetized and characterized by 1 H NMR and FTIR. Nanoparticles were prepared through complexation of CMD and cysTMC. Particle size and surface charge was 100-150 nm and 17-21 mV respectively with drug content of around 2.6%. Gel electrophoresis assay proved the stability of antisense in simulated gastric and intestinal fluids. Nanoparticles showed high mucoadhesion and glutathione responsive release. Cellular uptake was observed by confocal microscopy and quantified by flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore, present system could be considered an effective combination therapy of highly hydrophobic SN38 and hSET1.
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several fin... more Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several findings suggest that correcting the dysregulated signaling pathways may offer a potential therapeutic approach in this disease. Extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase family, plays a major role in regulation of cell proliferation, autophagy process, and protein synthesis. The available literature suggests dysregulated ERK1/2 in AD patients with potential implications in the multifaceted underlying pathologies of AD, including amyloid-β plaque formation, tau phosphorylation, and neuroinflammation. In this regard, in the current review, we aim to summarize the reports on the potential roles of ERK1/2 in AD pathophysiology.
Objective: Chronic obstructive pulmonary disease (COPD) is associated with many health complicati... more Objective: Chronic obstructive pulmonary disease (COPD) is associated with many health complications, including pulmonary hypertension (PH). Although oral calcium channel blockers have shown promising results in managing COPD-induced PH, significant systemic side effects may limit their use in this population. Administering verapamil through nebulization can be an alternative approach. We aim to assess the possible therapeutic effects of verapamil inhalation in outpatients with pulmonary hypertension (PH) secondary to COPD. Methods: A double-blind, randomized placebo-controlled clinical trial was conducted. Patients with PH were randomly assigned to two groups of 15 participants. The intervention group received a short-term single dose of 10 mg nebulized verapamil (4 ampoules of 2.5 mg/ml verapamil solutions). The control group received nebulized distilled water as a placebo in addition to their standard treatment throughout the study. Results: Systolic pulmonary artery pressure (sPAP) did not improve as a primary outcome significantly in patients receiving nebulized verapamil compared with those on placebo (p = 0.89). Spirometry results showed a significant improvement in FVC in the intervention group from 1.72 AE 0.63 to 1.85 AE 0.58 L (p = 0.00), and FEV1/FVC ratio decreased significantly after verapamil administration (p = 0.027).
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several fin... more Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Several findings suggest that correcting the dysregulated signaling pathways may offer a potential therapeutic approach in this disease. Extracellular signal-regulated kinase 1/2 (ERK1/2), a member of the mitogen-activated protein kinase family, plays a major role in regulation of cell proliferation, autophagy process, and protein synthesis. The available literature suggests dysregulated ERK1/2 in AD patients with potential implications in the multifaceted underlying pathologies of AD, including amyloid-β plaque formation, tau phosphorylation, and neuroinflammation. In this regard, in the current review, we aim to summarize the reports on the potential roles of ERK1/2 in AD pathophysiology.
Background: The recent studies emphasized on the correlation of vancomycin antibacterial effect w... more Background: The recent studies emphasized on the correlation of vancomycin antibacterial effect with pharmacokinetics properties such as the area under the curve/minimum inhibitory concentration (AUC24/MIC) ≥400 and serum trough level 15-20 mg /L in the patients with severe infection with methicillin-resistant Staphylococcus aureus (MRSA). The purpose is to assay the vancomycin pharmacokinetic properties in our population and evaluates the correlation between AUC24/MIC and trough serum level of vancomycin in given patients. Methods: The patients with a positive MRSA culture, treated with vancomycin, were enrolled in this cross-sectional study. Three plasma samples were obtained during the study including 30 min before fourth and the fifth dose as trough levels and 1 hour after the fourth dose as peak level to determine AUC24. E-TEST determined the MIC of vancomycin. Results: Thirty-eight patients with an average age of 48.33±16.44 were enrolled in this study. The mean ± SD of MIC wa...
INTRODUCTION Uremic pruritus (UP) is one of the major complaints in hemodialysis patients without... more INTRODUCTION Uremic pruritus (UP) is one of the major complaints in hemodialysis patients without specific treatment. Considering the antipruritic effect of melatonin in atopic dermatitis (AD) and similarities in mechanism between pruritus in AD and UP, this randomized clinical trial designed to evaluate the antipruritic effect of melatonin on hemodialysis patients with UP. METHODS This multicenter double-blind randomized clinical trial was conducted among the hemodialysis patients with UP. Adult patients were randomly assigned to receive two capsules of melatonin 5 mg /d for a 2 weeks period, undergoing a 1 week washout period, and then two capsules of placebo for another 2 weeks period, or the reverse sequence. Visual Analogue Scale (VAS), % affected Body Surface Area (%BSA) and 12-Pruritus Severity Scale questionnaire (12-PSS) were measured before and after each of the three periods. A crossover analysis of variance adjusted by treatment, period and carryover effect was performed...
Iranian Journal of Pharmaceutical Research : IJPR, 2021
Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a... more Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a negative impact on patient quality of life and potentially resulting in early liver transplants. Given the main role of the autotaxin enzyme in pruritus induced by CLD and the suppressive effects of melatonin on the expression of the autotaxin gene, this study was designed to evaluate the antipruritic effect of melatonin in patients with CLD. A double-blind, cross-over, randomized, placebo-controlled pilot trial was conducted on patients with CLD -induced pruritis. Patients were randomly assigned to two groups where they received melatonin 10-mg at night or placebo for 2 weeks. After a 2-week washout period, patients were then crossed over to the other group. The Visual Analog Scale (VAS) and the 12-Item Pruritus Severity Score (12-PSS) were used to assess patient response to therapy as the co-primary outcomes, while liver function tests were assayed too. Forty patients completed the st...
BACKGROUND Currently, there is no published questionnaire translated in the Persian language for ... more BACKGROUND Currently, there is no published questionnaire translated in the Persian language for pruritus evaluation in patients with chronic liver disease. Therefore, it would be well worth having a valid and reliable Persian questionnaire for assessing pruritus with its different aspects. This study was designed to evaluate the validity and reliability of the translated version of the 12-Item Pruritus Severity Score (12-PSS) METHODS The patients with pruritus due to chronic liver disease, who referred to the liver clinic affiliated to Tehran University of Medical Sciences, were enrolled in this cross-sectional study. Following the forward-backward translation of 12-PSS into Persian, the content validity index (CVI) and its reliability were assessed. The patients were asked to respond to the visual analog scale (VAS) along with 12-PSS on their visits to evaluate the correlation between them. RESULTS 160 eligible patients were entered in the present study. The mean age was 46.03 (±1...
Gastroenterology and Hepatology From Bed to Bench, 2021
Aim: A positive effect of melatonin on platelet count in patients with chronic liver disease is r... more Aim: A positive effect of melatonin on platelet count in patients with chronic liver disease is reported in the current study. Background: Thrombocytopenia occurs when the severity of liver disease is exacerbated. Reduction in the secretion of thrombopoetin, as an intrinsic hormone produced mainly by the liver, plays an important role in this complication induced by liver disease. Methods: This research was a double-blind, cross-over, placebo-controlled pilot study. Patients with liver disease were given two 5-mg pearls of melatonin or a placebo for two weeks, and after a 2-week washout period, their groups were switched. Liver function tests and platelet counts were assessed once at the beginning and once at the end of each phase of the study. Results In the current study, 40 patients meeting the eligibility criteria were included. The average platelet count was significantly increased by melatonin in comparison with the placebo (from 175.67±92.84 to 191.10±98.82 vs. from 185.22±98...
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