Aim: The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatm... more Aim: The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contrac-tile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. Methods: Male Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hyper-tensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose-response curves to phenylephrine (Phe) (10-9-10-5 M) and clonidine (Clo) (10-9-10-5 M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 µM) and/or losartan (10 µM). Results: Pioglitazone and losartan caused a shift to the right in contractile response to phenylephrine in all groups. The sensitivity of the aortic rings to phenylephrine was decreased in the presence of pioglitazone and/or losartan in all groups. The contractile response of clonidine decreased in the presence of pioglitazone and/or losartan in the control, HT and DM groups. Conclusion: The sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. Concomitant use of PPAR-gamma agonists, thiazolidine-diones, and angiotensin receptor blockers may be effective treatment for diabetes and hypertension. Hypertension and diabetes mellitus are both common diseases worldwide and they co-exist frequently, resulting in significant rates of morbidity and mortality. Diabetes mellitus and hypertension have been identified as risk factors for cardiovascular disease and cause altered vascular responsiveness to several vasoconstrictors and vasodilators. 1-3 Endothelium-dependent vasodilation is reduced in diabetes, largely due to excessive oxidative stress and the bio-availability of nitric oxide. Endothelium-derived nitric oxide (NO) is a potent endogenous nitrovasodilator and plays a major role in modulation of vascular tone. 4 NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension has been one of the most frequently used models of experimental hypertension since 1990. 5 Thiazolidinediones (TZDs) such as pioglitazone are a class of oral antidiabetic agent that act primarily by decreasing insulin resistance. Drugs in this class act as potent and highly selective agonists for peroxisome proliferator-activated receptor gamma (PPARg). 6 Pioglitazone repairs blunted endothelium-dependent vasodilatation, protects against oxidative stress and lowers blood pressure. 7-11 The vascular endothelium mediates relaxant responses to a wide range of vasodilators and modulates the constrictor responses to alpha agonists such as phenylephrine and clonidine. The streptozotocin (STZ)-induced diabetic rat model has been widely used to study changes in vascular reactivity to alpha adrenoceptor agonists. 12 Hyperglycaemia is likely to modulate physiological responses to angiotensin II and may contribute to the pathogenesis of vascular dysfunction in diabetes. 13 Angiotensin type 1 receptor (AT 1 R) blockers (ARBs) such as losartan are widely used in the treatment of hypertension. 14,15 It is not clear how concomitant use of medication in the treatment of hypertension and diabetes has effects on vascular contractility. Hence the aim of this study was to investigate the effect of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine (Phe), and the alpha-2 agonist, clonidine (Clo), in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. methods Male Wistar rats (250-300 g) were obtained from the experimental animal centre of Adnan Menderes University and all experiments were performed according to the principles and guidelines of the Adnan Menderes University animal ethics committee. Male Wistar rats were randomly allocated to four groups: a control group (Cont) (n = 15), a diabetic group (DM) (n = 20), a hypertensive group (HT) (n = 20), and a hypertensive diabetic group (HT + DM) (n = 20). All rats were housed at 22-24°C on a 12-hour dark-light cycle and received food and water (or L-NAME solution in department of medical pharmacology, Faculty of medicine, adnan menderes university, aydin, turkey Ibrahim Tugrul, MD, [email protected] Turhan Dost, MD
Context: Different Hypericum species such as Hypericum perforatum (HP) L. and Hypericum triquetri... more Context: Different Hypericum species such as Hypericum perforatum (HP) L. and Hypericum triquetrifolium Turra are well known and widely used traditional medicine in Turkey. Objectives: We investigated the effect of standardized HP extract on endothelium and vascular function. Materials and methods: After suspending the aortas with endothelium in organ baths containing Krebs solution, contractile and relaxant responses were assessed in the absence and presence of HP (0.05 mg/ml). Results: Although there were significant reductions in the contractile responses to phenylephrine (1113.73 ± 164.11; 477.40 ± 39.94; p < 0.05) and potassium chloride (745.58 ± 66.73; 112.58 ± 26.58; p < 0.05), no differences in the relaxant responses to acetylcholine (94.61 ± 2.65; 87.79 ± 9.40) and sodium nitroprusside (108.82 ± 5.06; 106.43 ± 7.45) were observed. Discussion and conclusion: These data suggest that even the high dose of HP intervention does not bring any harmful effect on endothelium and smooth muscle function; meanwhile it might be beneficial on some of diseases accompanied with increased vascular contraction.
Aim: This short communication aims to evaluate the relation in between drug exposure time and ear... more Aim: This short communication aims to evaluate the relation in between drug exposure time and early pregnancy regarding gestational weeks. Methods: The study covers the referrals made to the Department of Pharmacology for a teratogenic consultation in a 3-year period. From the recordings of pregnant women, the last menstrual period and the starting date of medication were used to determine the time of prescription with regard to gestational weeks. Results: In all of the three years, potentially teratogenic medication was prescribed more frequently in the 3rd, 4th and 5th gestational weeks (in between 15-35 days of pregnancy). Approximately 75% of the pregnant women in the study were prescribed with drugs, most frequently with analgesics, antibiotics, gastrointestinal drugs and antidepressants, in these gestational weeks. Conclusions: The timing of prescriptions in early pregnancy frequently coincides with the increased levels of maternal progesterone in implantation period. Progesterone may lead to negative mood symptoms of an increased pain perception, anxiety, irritability and aggression in some of the pregnant women and therefore causes an increased stress condition which in turn may result in pain, infection and inflammation in the individual. Taking the frequently used medications into consideration, the reason for prescriptions in this period might be related to the symptoms originating from the effects of progesterone. Future studies are needed to better demonstrate this association of drug exposure and effects of maternal progesterone in early pregnancy.
Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/ reperfusion (I/R... more Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/ reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N o-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24 h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.4870.2 mg/l serum) than in the control group (2.6970.2 mg/l serum). L-NAME (40 mg kg À1 for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.
Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies... more Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies have investigated the relationship and risks between diet lifestyle, carbohydrate intake, and diabetes. It is not known exactly how diets, along with medication, affect medication during the treatment of diabetes mellitus. The purpose of this review is to summarize studies investigating the interaction of low-carbohydrate diets (LCD) and diabetes mellitus medication.
Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies... more Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies have investigated the relationship and risks between diet lifestyle, carbohydrate intake, and diabetes. It is not known exactly how diets, along with medication, affect medication during the treatment of diabetes mellitus. The purpose of this review is to summarize studies investigating the interaction of low-carbohydrate diets (LCD) and diabetes mellitus medication.
Asploro Journal of Biomedical and Clinical Case Reports, 2019
Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies... more Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies have investigated the relationship and risks between diet lifestyle, carbohydrate intake, and diabetes. It is not known exactly how diets, along with medication, affect medication during the treatment of diabetes mellitus. The purpose of this review is to summarize studies investigating the interaction of low-carbohydrate diets (LCD) and diabetes mellitus medication.
Aim: The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatm... more Aim: The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contrac-tile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. Methods: Male Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hyper-tensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose-response curves to phenylephrine (Phe) (10-9-10-5 M) and clonidine (Clo) (10-9-10-5 M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 µM) and/or losartan (10 µM). Results: Pioglitazone and losartan caused a shift to the right in contractile response to phenylephrine in all groups. The sensitivity of the aortic rings to phenylephrine was decreased in the presence of pioglitazone and/or losartan in all groups. The contractile response of clonidine decreased in the presence of pioglitazone and/or losartan in the control, HT and DM groups. Conclusion: The sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. Concomitant use of PPAR-gamma agonists, thiazolidine-diones, and angiotensin receptor blockers may be effective treatment for diabetes and hypertension. Hypertension and diabetes mellitus are both common diseases worldwide and they co-exist frequently, resulting in significant rates of morbidity and mortality. Diabetes mellitus and hypertension have been identified as risk factors for cardiovascular disease and cause altered vascular responsiveness to several vasoconstrictors and vasodilators. 1-3 Endothelium-dependent vasodilation is reduced in diabetes, largely due to excessive oxidative stress and the bio-availability of nitric oxide. Endothelium-derived nitric oxide (NO) is a potent endogenous nitrovasodilator and plays a major role in modulation of vascular tone. 4 NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension has been one of the most frequently used models of experimental hypertension since 1990. 5 Thiazolidinediones (TZDs) such as pioglitazone are a class of oral antidiabetic agent that act primarily by decreasing insulin resistance. Drugs in this class act as potent and highly selective agonists for peroxisome proliferator-activated receptor gamma (PPARg). 6 Pioglitazone repairs blunted endothelium-dependent vasodilatation, protects against oxidative stress and lowers blood pressure. 7-11 The vascular endothelium mediates relaxant responses to a wide range of vasodilators and modulates the constrictor responses to alpha agonists such as phenylephrine and clonidine. The streptozotocin (STZ)-induced diabetic rat model has been widely used to study changes in vascular reactivity to alpha adrenoceptor agonists. 12 Hyperglycaemia is likely to modulate physiological responses to angiotensin II and may contribute to the pathogenesis of vascular dysfunction in diabetes. 13 Angiotensin type 1 receptor (AT 1 R) blockers (ARBs) such as losartan are widely used in the treatment of hypertension. 14,15 It is not clear how concomitant use of medication in the treatment of hypertension and diabetes has effects on vascular contractility. Hence the aim of this study was to investigate the effect of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine (Phe), and the alpha-2 agonist, clonidine (Clo), in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. methods Male Wistar rats (250-300 g) were obtained from the experimental animal centre of Adnan Menderes University and all experiments were performed according to the principles and guidelines of the Adnan Menderes University animal ethics committee. Male Wistar rats were randomly allocated to four groups: a control group (Cont) (n = 15), a diabetic group (DM) (n = 20), a hypertensive group (HT) (n = 20), and a hypertensive diabetic group (HT + DM) (n = 20). All rats were housed at 22-24°C on a 12-hour dark-light cycle and received food and water (or L-NAME solution in department of medical pharmacology, Faculty of medicine, adnan menderes university, aydin, turkey Ibrahim Tugrul, MD, [email protected] Turhan Dost, MD
Context: Different Hypericum species such as Hypericum perforatum (HP) L. and Hypericum triquetri... more Context: Different Hypericum species such as Hypericum perforatum (HP) L. and Hypericum triquetrifolium Turra are well known and widely used traditional medicine in Turkey. Objectives: We investigated the effect of standardized HP extract on endothelium and vascular function. Materials and methods: After suspending the aortas with endothelium in organ baths containing Krebs solution, contractile and relaxant responses were assessed in the absence and presence of HP (0.05 mg/ml). Results: Although there were significant reductions in the contractile responses to phenylephrine (1113.73 ± 164.11; 477.40 ± 39.94; p < 0.05) and potassium chloride (745.58 ± 66.73; 112.58 ± 26.58; p < 0.05), no differences in the relaxant responses to acetylcholine (94.61 ± 2.65; 87.79 ± 9.40) and sodium nitroprusside (108.82 ± 5.06; 106.43 ± 7.45) were observed. Discussion and conclusion: These data suggest that even the high dose of HP intervention does not bring any harmful effect on endothelium and smooth muscle function; meanwhile it might be beneficial on some of diseases accompanied with increased vascular contraction.
Aim: This short communication aims to evaluate the relation in between drug exposure time and ear... more Aim: This short communication aims to evaluate the relation in between drug exposure time and early pregnancy regarding gestational weeks. Methods: The study covers the referrals made to the Department of Pharmacology for a teratogenic consultation in a 3-year period. From the recordings of pregnant women, the last menstrual period and the starting date of medication were used to determine the time of prescription with regard to gestational weeks. Results: In all of the three years, potentially teratogenic medication was prescribed more frequently in the 3rd, 4th and 5th gestational weeks (in between 15-35 days of pregnancy). Approximately 75% of the pregnant women in the study were prescribed with drugs, most frequently with analgesics, antibiotics, gastrointestinal drugs and antidepressants, in these gestational weeks. Conclusions: The timing of prescriptions in early pregnancy frequently coincides with the increased levels of maternal progesterone in implantation period. Progesterone may lead to negative mood symptoms of an increased pain perception, anxiety, irritability and aggression in some of the pregnant women and therefore causes an increased stress condition which in turn may result in pain, infection and inflammation in the individual. Taking the frequently used medications into consideration, the reason for prescriptions in this period might be related to the symptoms originating from the effects of progesterone. Future studies are needed to better demonstrate this association of drug exposure and effects of maternal progesterone in early pregnancy.
Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/ reperfusion (I/R... more Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/ reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N o-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24 h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.4870.2 mg/l serum) than in the control group (2.6970.2 mg/l serum). L-NAME (40 mg kg À1 for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.
Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies... more Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies have investigated the relationship and risks between diet lifestyle, carbohydrate intake, and diabetes. It is not known exactly how diets, along with medication, affect medication during the treatment of diabetes mellitus. The purpose of this review is to summarize studies investigating the interaction of low-carbohydrate diets (LCD) and diabetes mellitus medication.
Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies... more Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies have investigated the relationship and risks between diet lifestyle, carbohydrate intake, and diabetes. It is not known exactly how diets, along with medication, affect medication during the treatment of diabetes mellitus. The purpose of this review is to summarize studies investigating the interaction of low-carbohydrate diets (LCD) and diabetes mellitus medication.
Asploro Journal of Biomedical and Clinical Case Reports, 2019
Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies... more Diet is one of the main therapies for patients with type 2 diabetes mellitus (T2DM). Many studies have investigated the relationship and risks between diet lifestyle, carbohydrate intake, and diabetes. It is not known exactly how diets, along with medication, affect medication during the treatment of diabetes mellitus. The purpose of this review is to summarize studies investigating the interaction of low-carbohydrate diets (LCD) and diabetes mellitus medication.
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