Generality and Mechanism of Intracellular pH Effect on Vascular Tone

Both the net effects and the mechanisms of action of intracellular pH (pHi) perturbations upon vascular tone have been investigated. pHi was modified using two procedures; NH4Cl application and withdrawal (NH4Cl pulse) and organic salt application. NH4Cl application and its subsequent withdrawal have been found to produce intracellular alkalinity and acidity, respectively, in various non-vascular (Roos and Boron, 1981; Thomas, 1984) as well as vascular tissues (Spurway and Wray, 1987). Application of weak organic salts has been found to decrease pHi in various tissues (Roos and Boron, 1981). Most experiments concerned with mechanism were carried out on one or both of two preparations: the rabbit ear vascular bed perfused through its central artery and the isolated perfused rat tail artery, each activated with NA, at about 2

Nigella sativa Improves Glycemic Control and Ameliorates Oxidative Stress in Patients with Type 2 Diabetes Mellitus: Placebo Controlled Participant Blinded Clinical Trial

<div><p>Background and Objective</p><p>Oxidative stress plays an important role in pathogenesis of diabetes mellitus and its complications. Our previous study has shown glucose lowering effect produced by 3 months supplementation of Nigella sativa (NS) in combination with oral hypoglycemic drugs among type 2 diabetics. This study explored the long term glucose lowering effect (over one year) of NS in patients with type 2 diabetes mellitus on oral hypoglycemic drugs and to study its effect on redox status of such patients.</p><p>Methods</p><p>114 type 2 diabetic patients on standard oral hypoglycemic drugs were assigned into 2 groups by convenience. The control group (n = 57) received activated charcoal as placebo and NS group (n = 57) received 2g NS, daily, for one year in addition to their standard medications. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA_1c), C- peptide, total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), glutathione and thiobarbituric acid reactive substances (TBARS) at the baseline, and every 3 months thereafter were determined. Insulin resistance and β-cell activity were calculated using HOMA 2 calculator.</p><p>Results</p><p>Comparison between the two groups showed a significant drop in FBG (from 180±5.75 to 180±5.59 in control Vs from 195±6.57 to 172 ±5.83 in NS group), HbA1c (from 8.2±0.12 to 8.5±0.14 in control VS from 8.6±0.13 to 8.2±0.14 in NS group), and TBARS (from 48.3±6.89 to 52.9 ±5.82 in control VS from 54.1±4.64 to 41.9 ±3.16 in NS group), in addition to a significant elevation in TAC, SOD and glutathione in NS patients compared to controls. In NS group, insulin resistance was significantly lower, while β-cell activity was significantly higher than the baseline values during the whole treatment period.</p><p>Conclusion</p><p>Long term supplementation with Nigella sativa improves glucose homeostasis and enhances antioxidant defense system in type 2 diabetic patients treated with oral hypoglycemic drugs.</p><p>Trial Registration</p><p>Clinical Trials Registry-India (CTRI) <a href="https://clinicaltrials.gov/ct2/show/CTRI/2013/06/003781" target="_blank">CTRI/2013/06/003781</a></p></div

Comparison of glycemic variables; fasting blood glucose (FBG), hemoglobinA_1c (HbA_1c), C- peptide, insulin resistance, and β-cell activity between the control (placebo) group and N. sativa group at different treatment durations.

<p>Number of patients in parenthesis ()</p><p>*Differences are significant at P ≤ 0.05</p><p>Comparison of glycemic variables; fasting blood glucose (FBG), hemoglobinA_1c (HbA_1c), C- peptide, insulin resistance, and β-cell activity between the control (placebo) group and N. sativa group at different treatment durations.</p

Changes in Fasting blood glucose (FBG), Hemoglobin A_1c (HbA_1c), C- peptide (C-pept), Insulin resistance (IR) and β-cell activity at different treatment durations, compared to their corresponding baseline values, in the control (placebo) and N. sativa groups.

<p>n = number of patients B = baseline values m = months</p><p>Analysis was carried out using Linear Mixed Model in SPSS.</p><p>*Difference is significant at P ≤ 0.05.</p><p>Changes in Fasting blood glucose (FBG), Hemoglobin A_1c (HbA_1c), C- peptide (C-pept), Insulin resistance (IR) and β-cell activity at different treatment durations, compared to their corresponding baseline values, in the control (placebo) and N. sativa groups.</p

Flow of Patients from enrollment to the end of study.

<p>Flow of Patients from enrollment to the end of study.</p

Changes in Total antioxidants capacity (TAC), Superoxide dismutase (SOD) activity, Catalase (CAT) activity, Glutathione and Thiobarbituric acid reactive substances (TBARS) at different treatment durations, in control (placebo) group and N. sativa group, compared to their corresponding baseline values.

<p>n = number of patients B = baseline values m = months</p><p>Analysis was carried out using Linear Mixed Model in SPSS.</p><p>*Difference is significant at P ≤ 0.05.</p><p>Changes in Total antioxidants capacity (TAC), Superoxide dismutase (SOD) activity, Catalase (CAT) activity, Glutathione and Thiobarbituric acid reactive substances (TBARS) at different treatment durations, in control (placebo) group and N. sativa group, compared to their corresponding baseline values.</p

Changes in Random blood glucose (Mean±SEM) measured by self- monitoring glucometers, in the control (placebo) group and N. sativa group, compared to the corresponding baseline values using linear mixed model.

<p>Difference is significant at * P < 0.05, ** P <0.01 and *** P < 0.001.</p

Comparison of Total antioxidant (TAC) capacity, antioxidant enzymes; super oxide dismutase activity (SOD), catalase (CAT) activity, glutathione level and lipid peroxidation index (thiobarbituric acid reactive substances TBARS) between the control (placebo) group and N. sativa group at different treatment durations.

<p>Number of patients is given in parenthesis ().</p><p>*Differences are significant at P ≤ 0.05</p><p>Comparison of Total antioxidant (TAC) capacity, antioxidant enzymes; super oxide dismutase activity (SOD), catalase (CAT) activity, glutathione level and lipid peroxidation index (thiobarbituric acid reactive substances TBARS) between the control (placebo) group and N. sativa group at different treatment durations.</p