An efficient sample preparation method based on dispersive liquid�liquid microextraction associated with back extraction for trace determination of acidic pharmaceuticals

Reduction of matrix effect seems to be a great challenge for the development of a practical method in bioanalysis. In this regard, a simple and efficient DLLME procedure along with a back-extraction step (DLLME-BE) was developed for the preconcentration of four common non-steroidal anti-inflammatory drugs (NSAIDs) in various biological fluid samples. Briefly, the analytes of interest were initially transferred into the extraction solvent followed by the back-extraction into an immiscible basic methanol (as an acceptor phase) for further preconcentration and clean-up. The main purpose of the work is reducing the matrix effect and sensitive determination of target molecules in the complex matrices. Following on, the separation and determination of the analytes were carried out using GC�MS (in-port derivatization) and HPLC-DAD instrument. The influential parameters affecting the DLLME-BE method were evaluated in detail and the best extraction conditions were established. Under the optimum conditions, low method detection limits in the range of 0.1�1.0 and 0.1�6.0 µg L�1 were obtained for GC�MS and HPLC-DAD analysis, respectively. Additionally, fair intra-day precisions of 2.7�14.5 and 2.8�7.8 as well as inter-day precisions of 3.9�14.5 and 3.5�8.1 were achieved for the GC�MS and HPLC-DAD analysis, respectively. Finally, the method was successfully applied for the determination of four common NSAIDs in different biological fluid samples. © 2018 King Saud Universit

An efficient sample preparation method based on dispersive liquid�liquid microextraction associated with back extraction for trace determination of acidic pharmaceuticals

Reduction of matrix effect seems to be a great challenge for the development of a practical method in bioanalysis. In this regard, a simple and efficient DLLME procedure along with a back-extraction step (DLLME-BE) was developed for the preconcentration of four common non-steroidal anti-inflammatory drugs (NSAIDs) in various biological fluid samples. Briefly, the analytes of interest were initially transferred into the extraction solvent followed by the back-extraction into an immiscible basic methanol (as an acceptor phase) for further preconcentration and clean-up. The main purpose of the work is reducing the matrix effect and sensitive determination of target molecules in the complex matrices. Following on, the separation and determination of the analytes were carried out using GC�MS (in-port derivatization) and HPLC-DAD instrument. The influential parameters affecting the DLLME-BE method were evaluated in detail and the best extraction conditions were established. Under the optimum conditions, low method detection limits in the range of 0.1�1.0 and 0.1�6.0 µg L�1 were obtained for GC�MS and HPLC-DAD analysis, respectively. Additionally, fair intra-day precisions of 2.7�14.5 and 2.8�7.8 as well as inter-day precisions of 3.9�14.5 and 3.5�8.1 were achieved for the GC�MS and HPLC-DAD analysis, respectively. Finally, the method was successfully applied for the determination of four common NSAIDs in different biological fluid samples. © 2018 King Saud Universit

The Effects of Synbiotic Supplementation on Carotid Intima-Media Thickness, Biomarkers of Inflammation, and Oxidative Stress in People with Overweight, Diabetes, and Coronary Heart Disease: a Randomized, Double-Blind, Placebo-Controlled Trial

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidant actions. The aim of this study was to evaluate the effects of synbiotic supplementation on carotid intima-media thickness (CIMT), biomarkers of inflammation, and oxidative stress in people with overweight, diabetes, and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was conducted and involved 60 people with overweight, diabetes, and CHD, aged 50�85 years old. Participants were randomly allocated into two groups to take either synbiotic supplements containing three probiotic bacteria spices Lactobacillus acidophilus strain T16 (IBRC-M10785), Lactobacillus casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 � 10 9  CFU/g each) plus 800 mg inulin or placebo (n = 30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention period to determine metabolic variables. After the 12-week intervention, compared with the placebo, synbiotic supplementation significantly reduced serum high-sensitivity C-reactive protein (hs-CRP) (� 3101.7 ± 5109.1 vs. � 6.2 ± 3163.6 ng/mL, P = 0.02), plasma malondialdehyde (MDA) (� 0.6 ± 1.0 vs. � 0.1 ± 0.3 μmol/L, P = 0.01), and significantly increased nitric oxide (NO) levels (+ 7.8 ± 10.3 vs. � 3.6 ± 6.9 μmol/L, P < 0.001). We did not observe any significant changes of synbiotic supplementation on other biomarkers of oxidative stress and CIMT levels. Overall, synbiotic supplementation for 12 weeks among people with overweight, diabetes, and CHD had beneficial effects on serum hs-CRP, plasma NO, and MDA levels; however, it did not have any effect on other biomarkers of oxidative stress and CIMT levels. © 2017, Springer Science+Business Media, LLC

The effects of probiotic supplementation on metabolic status in type 2 diabetic patients with coronary heart disease IRCT2017082733941N5 IRCT

Background This study was conducted to evaluate the effects of probiotic supplementation on metabolic profiles in diabetic patients with coronary heart disease (CHD). Methods This randomized, double-blind, placebo-controlled trial was performed among 60 diabetic patients with CHD, aged 40–85 years at a cardiology clinic in Kashan, Iran, from October 2017 through January 2018. Patients were randomly divided into two groups to take either probiotic supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at the beginning of the study and after the 12-week intervention to determine related markers. Results After 12-week intervention, probiotic supplementation significantly decreased fasting plasma glucose (β − 20.02 mg/dL; 95% CI − 33.86, − 6.17; P = 0.005), insulin (β − 2.09 µIU/mL; 95% CI − 3.77, − 0.41; P = 0.01), insulin resistance (β − 0.50; 95% CI − 0.96, − 0.03; P = 0.03) and total-/HDL-cholesterol ratio (β − 0.27; 95% CI − 0.52, − 0.03; P = 0.02), and significantly increased insulin sensitivity (β 0.008; 95% CI 0.001, 0.01; P = 0.02) and HDL-cholesterol levels (β 2.52 mg/dL; 95% CI 0.04, 5.00; P = 0.04) compared with the placebo. Moreover, probiotic supplementation led to a significant reduction in serum high sensitivity C-reactive protein (β − 0.88 mg/L; 95% CI − 1.39, − 0.38; P = 0.001), and a significant elevation in total antioxidant capacity (β 108.44 mmol/L; 95% CI 47.61, 169.27; P = 0.001) and total glutathione levels (β 45.15 µmol/L; 95% CI 5.82, 84.47; P = 0.02) compared with the placebo. Probiotic supplementation did not affect other metabolic profiles. Conclusions Overall, we found that probiotic supplementation for 12 weeks had beneficial effects on glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, biomarkers of inflammation and oxidative stress in diabetic patients with CHD. Keywords Probiotic Coronary heart disease Metabolic status Type 2 diabetes mellitu

Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: A randomized, double-blind, controlled trial

Background and aims: Combined probiotic and selenium supplementation may improve Alzheimer's disease (AD) by correcting metabolic abnormalities, and attenuating inflammation and oxidative stress. This study aimed to determine the effects of probiotic and selenium co-supplementation on cognitive function and metabolic status among patients with AD. Methods: This randomized, double-blind, controlled clinical trial was conducted among 79 patients with AD. Patients were randomly assigned to receive either selenium (200 μg/day) plus probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (2 � 109 CFU/day each) (n = 27), selenium (200 μg/day) (n = 26) or placebo (n = 26) for 12 weeks. Results: Selenium supplementation, compared with the placebo, significantly reduced serum high sensitivity C-reactive protein (hs-CRP) (P < 0.001), insulin (P = 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (P = 0.002), LDL-cholesterol (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.004), and significantly increased total glutathione (GSH) (P = 0.001) and the quantitative insulin sensitivity check index (QUICKI) (P = 0.01). Compared with only selenium and placebo, probiotic and selenium co-supplementation resulted in a significant increase in mini-mental state examination score (+1.5 ± 1.3 vs. +0.5 ± 1.2 and �0.2 ± 1.1, respectively, P < 0.001). Probiotic plus selenium intake resulted in a significant reduction in hs-CRP (�1.6 ± 1.4 vs. �0.8 ± 1.0 and +0.1 ± 0.5 mg/L, respectively, P < 0.001), and a significant increase in total antioxidant capacity (+89.4 ± 129.6 vs. +20.0 ± 62.5 and �0.7 ± 27.2 mmol/L, respectively, P = 0.001) and GSH (+122.8 ± 136.5 vs. +102.2 ± 135.2 and +1.5 ± 53.2 μmol/L, respectively, P = 0.001) compared with only selenium and placebo. In addition, subjects who received probiotic plus selenium supplements had significantly lower insulin levels (�2.1 ± 2.5 vs. �1.0 ± 1.3 and +0.7 ± 2.0 μIU/mL, respectively, P < 0.001), HOMA-IR (�0.5 ± 0.6 vs. �0.2 ± 0.3 and +0.1 ± 0.4, respectively, P < 0.001), and higher QUICKI (+0.01 ± 0.01 vs. +0.005 ± 0.007 and �0.002 ± 0.01, respectively, P < 0.006) compared with only selenium and placebo. Additionally, probiotic and selenium co-supplementation resulted in a significant reduction in serum triglycerides (�17.9 ± 26.1 vs. �3.5 ± 33.9 and +0.3 ± 9.3 mg/dL, respectively, P = 0.02), VLDL- (�3.6 ± 5.2 vs. �0.7 ± 6.8 and +0.05 ± 1.8 mg/dL, respectively, P = 0.02), LDL- (�8.8 ± 17.8 vs. �8.1 ± 19.2 and +2.7 ± 19.0 mg/dL, respectively, P = 0.04) and total-/HDL-cholesterol (�0.3 ± 0.7 vs. �0.4 ± 0.9 and +0.3 ± 0.6, respectively, P = 0.005) compared with only selenium and placebo. Conclusions: Overall, we found that probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170612034497N5). © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis

The Effects of Synbiotic Supplementation on Pregnancy Outcomes in Gestational Diabetes

Synbiotics are known to exert multiple beneficial effects, including anti-inflammatory and antioxidative actions. This study was designed to evaluate the effects of synbiotic administration on biomarkers of inflammation, oxidative stress, and pregnancy outcomes among gestational diabetic (GDM) women. This randomized, double-blind, placebo-controlled clinical trial was carried out among 60 subjects with GDM who were not on oral hypoglycemic agents. Patients were randomly assigned to consume either one synbiotic capsule containing Lactobacillus acidophilus strain T16 (IBRC-M10785), L. casei strain T2 (IBRC-M10783), and Bifidobacterium bifidum strain T1 (IBRC-M10771) (2 � 10 9  CFU/g each) plus 800 mg inulin (HPX) (n = 30) or placebo (n = 30) for 6 weeks. Compared with the placebo, synbiotic supplementation significantly decreased serum high-sensitivity C-reactive protein (hs-CRP) (� 1.9 ± 4.2 vs. +1.1 ± 3.5 mg/L, P = 0.004), plasma malondialdehyde (MDA) (� 0.1 ± 0.6 vs. + 0.3 ± 0.7 μmol/L, P = 0.02), and significantly increased total antioxidant capacity (TAC) (+ 70.1 ± 130.9 vs. � 19.7 ± 124.6 mmol/L, P = 0.009) and total glutathione (GSH) levels (+ 28.7 ± 61.5 vs. � 14.9 ± 85.3 μmol/L, P = 0.02). Supplementation with synbiotic had a significant decrease in cesarean section rate (16.7 vs. 40.0, P = 0.04), lower incidence of hyperbilirubinemic newborns (3.3 vs. 30.0, P = 0.006), and newborns� hospitalization (3.3 vs. 30.0, P = 0.006) compared with the placebo. Synbiotic supplementation did not affect plasma nitric oxide (NO) levels and other pregnancy outcomes. Overall, synbiotic supplementation among GDM women for 6 weeks had beneficial effects on serum hs-CRP, plasma TAC, GSH, and MDA; cesarean section; incidence of newborn�s hyperbilirubinemia; and newborns� hospitalization but did not affect plasma NO levels and other pregnancy outcomes. http://www.irct.ir: www.irct.ir: IRCT201704205623N108. © 2017, Springer Science+Business Media, LLC

Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: A randomized, double-blind, controlled trial

Background and aims: Combined probiotic and selenium supplementation may improve Alzheimer's disease (AD) by correcting metabolic abnormalities, and attenuating inflammation and oxidative stress. This study aimed to determine the effects of probiotic and selenium co-supplementation on cognitive function and metabolic status among patients with AD. Methods: This randomized, double-blind, controlled clinical trial was conducted among 79 patients with AD. Patients were randomly assigned to receive either selenium (200 μg/day) plus probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (2 × 109 CFU/day each) (n = 27), selenium (200 μg/day) (n = 26) or placebo (n = 26) for 12 weeks. Results: Selenium supplementation, compared with the placebo, significantly reduced serum high sensitivity C-reactive protein (hs-CRP) (P < 0.001), insulin (P = 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (P = 0.002), LDL-cholesterol (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.004), and significantly increased total glutathione (GSH) (P = 0.001) and the quantitative insulin sensitivity check index (QUICKI) (P = 0.01). Compared with only selenium and placebo, probiotic and selenium co-supplementation resulted in a significant increase in mini-mental state examination score (+1.5 ± 1.3 vs. +0.5 ± 1.2 and −0.2 ± 1.1, respectively, P < 0.001). Probiotic plus selenium intake resulted in a significant reduction in hs-CRP (−1.6 ± 1.4 vs. −0.8 ± 1.0 and +0.1 ± 0.5 mg/L, respectively, P < 0.001), and a significant increase in total antioxidant capacity (+89.4 ± 129.6 vs. +20.0 ± 62.5 and −0.7 ± 27.2 mmol/L, respectively, P = 0.001) and GSH (+122.8 ± 136.5 vs. +102.2 ± 135.2 and +1.5 ± 53.2 μmol/L, respectively, P = 0.001) compared with only selenium and placebo. In addition, subjects who received probiotic plus selenium supplements had significantly lower insulin levels (−2.1 ± 2.5 vs. −1.0 ± 1.3 and +0.7 ± 2.0 μIU/mL, respectively, P < 0.001), HOMA-IR (−0.5 ± 0.6 vs. −0.2 ± 0.3 and +0.1 ± 0.4, respectively, P < 0.001), and higher QUICKI (+0.01 ± 0.01 vs. +0.005 ± 0.007 and −0.002 ± 0.01, respectively, P < 0.006) compared with only selenium and placebo. Additionally, probiotic and selenium co-supplementation resulted in a significant reduction in serum triglycerides (−17.9 ± 26.1 vs. −3.5 ± 33.9 and +0.3 ± 9.3 mg/dL, respectively, P = 0.02), VLDL- (−3.6 ± 5.2 vs. −0.7 ± 6.8 and +0.05 ± 1.8 mg/dL, respectively, P = 0.02), LDL- (−8.8 ± 17.8 vs. −8.1 ± 19.2 and +2.7 ± 19.0 mg/dL, respectively, P = 0.04) and total-/HDL-cholesterol (−0.3 ± 0.7 vs. −0.4 ± 0.9 and +0.3 ± 0.6, respectively, P = 0.005) compared with only selenium and placebo. Conclusions: Overall, we found that probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trial

Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: A randomized, double-blind, controlled trial

Background and aims: Combined probiotic and selenium supplementation may improve Alzheimer's disease (AD) by correcting metabolic abnormalities, and attenuating inflammation and oxidative stress. This study aimed to determine the effects of probiotic and selenium co-supplementation on cognitive function and metabolic status among patients with AD. Methods: This randomized, double-blind, controlled clinical trial was conducted among 79 patients with AD. Patients were randomly assigned to receive either selenium (200 μg/day) plus probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (2 � 109 CFU/day each) (n = 27), selenium (200 μg/day) (n = 26) or placebo (n = 26) for 12 weeks. Results: Selenium supplementation, compared with the placebo, significantly reduced serum high sensitivity C-reactive protein (hs-CRP) (P &lt; 0.001), insulin (P = 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (P = 0.002), LDL-cholesterol (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.004), and significantly increased total glutathione (GSH) (P = 0.001) and the quantitative insulin sensitivity check index (QUICKI) (P = 0.01). Compared with only selenium and placebo, probiotic and selenium co-supplementation resulted in a significant increase in mini-mental state examination score (+1.5 ± 1.3 vs. +0.5 ± 1.2 and �0.2 ± 1.1, respectively, P &lt; 0.001). Probiotic plus selenium intake resulted in a significant reduction in hs-CRP (�1.6 ± 1.4 vs. �0.8 ± 1.0 and +0.1 ± 0.5 mg/L, respectively, P &lt; 0.001), and a significant increase in total antioxidant capacity (+89.4 ± 129.6 vs. +20.0 ± 62.5 and �0.7 ± 27.2 mmol/L, respectively, P = 0.001) and GSH (+122.8 ± 136.5 vs. +102.2 ± 135.2 and +1.5 ± 53.2 μmol/L, respectively, P = 0.001) compared with only selenium and placebo. In addition, subjects who received probiotic plus selenium supplements had significantly lower insulin levels (�2.1 ± 2.5 vs. �1.0 ± 1.3 and +0.7 ± 2.0 μIU/mL, respectively, P &lt; 0.001), HOMA-IR (�0.5 ± 0.6 vs. �0.2 ± 0.3 and +0.1 ± 0.4, respectively, P &lt; 0.001), and higher QUICKI (+0.01 ± 0.01 vs. +0.005 ± 0.007 and �0.002 ± 0.01, respectively, P &lt; 0.006) compared with only selenium and placebo. Additionally, probiotic and selenium co-supplementation resulted in a significant reduction in serum triglycerides (�17.9 ± 26.1 vs. �3.5 ± 33.9 and +0.3 ± 9.3 mg/dL, respectively, P = 0.02), VLDL- (�3.6 ± 5.2 vs. �0.7 ± 6.8 and +0.05 ± 1.8 mg/dL, respectively, P = 0.02), LDL- (�8.8 ± 17.8 vs. �8.1 ± 19.2 and +2.7 ± 19.0 mg/dL, respectively, P = 0.04) and total-/HDL-cholesterol (�0.3 ± 0.7 vs. �0.4 ± 0.9 and +0.3 ± 0.6, respectively, P = 0.005) compared with only selenium and placebo. Conclusions: Overall, we found that probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170612034497N5). © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis

Effects of probiotic supplementation on hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial

Background: To the best of our knowledge, data on effects of probiotic administration on hormonal profiles, biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome (PCOS) are scarce. This investigation was conducted to assess the effects of probiotic supplementation on hormonal profiles, biomarkers of inflammation and oxidative stress in women with PCOS. Methods: This randomized, double-blind, placebo-controlled trial was conducted on 60 women with PCOS, aged 18-40 years old. Subjects were randomly assigned into 2 groups to receive either probiotics or placebo (n = 30 each group) for 12 weeks. Metabolic profiles were quantified at baseline and after a 12-week intervention. Results: After the 12-week intervention, compared with placebo, probiotic supplementation significantly increased serum sex hormone-binding globulin (SHBG) (+25.9 ± 32.5 vs. +0.5 ± 15.6 nmol/L, P < 0.001) and plasma total antioxidant capacity (TAC) (+8.8 ± 120.5 vs. -98.3 ± 246.4 mmol/L, P = 0.04), and significantly decreased serum total testosterone (-0.2 ± 0.7 vs. +0.2 ± 0.6 ng/mL, P = 0.03), modified Ferriman-Gallwey (mF-G) scores (-1.7 ± 1.5 vs. -0.2 ± 1.0, P < 0.001), serum high-sensitivity C-reactive protein (hs-CRP) (-1150.0 ± 1295.2 vs. +202.5 ± 1426.3 ng/mL, P < 0.001) and plasma malondialdehyde (MDA) concentrations (-0.2 ± 0.6 vs. +0.9 ± 1.3 µmol/L, P < 0.001). We did not observe any detrimental effect of probiotic supplementation on other metabolic profiles. Conclusion: Overall, probiotic supplementation of PCOS women for 12 weeks had beneficial effects on total testosterone, SHBG, mFG scores, hs-CRP, TAC and MDA levels but did not affect other metabolic profiles. © 2018 The Author(s)

The Effects of Synbiotic Supplementation on Metabolic Status in Diabetic Patients Undergoing Hemodialysis: a Randomized, Double-Blinded, Placebo-Controlled Trial

This study was conducted to evaluate the effects of synbiotic supplementation on metabolic profiles in diabetic patients undergoing hemodialysis (HD). This randomized, double-blinded, placebo-controlled clinical trial was performed in 60 diabetic HD patients. Participants were randomly assigned into two groups to receive either synbiotic capsule, containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum (2 � 109 CFU/g each), plus 0.8 g/day of inulin (n = 30) or placebo (n = 30) for 12 weeks. Synbiotic supplementation significantly decreased fasting plasma glucose (β � 13.56 mg/dL; 95 CI, � 23.82, � 3.30; P = 0.01), insulin levels (β � 5.49 μIU/mL; 95 CI, � 6.92, � 4.05; P &lt; 0.001), and insulin resistance (β � 2.25; 95 CI, � 3.02, � 1.48; P &lt; 0.001), while increased the quantitative insulin sensitivity check index (β 0.02; 95 CI, 0.01, 0.02; P &lt; 0.001) compared with the placebo. Additionally, synbiotic intake resulted in a significant reduction in high-sensitivity C-reactive protein (β � 2930.48 ng/mL; 95 CI, � 3741.15, � 2119.80; P &lt; 0.001) and malondialdehyde levels (β � 0.60 μmol/L; 95 CI, � 0.99, � 0.20; P = 0.003). Moreover, we found a significant increase in total antioxidant capacity (β 142.99 mmol/L; 95 CI, 61.72, 224.25; P = 0.001) and total glutathione levels (β 131.11 μmol/L; 95 CI, 89.35, 172.87; P &lt; 0.001) in the synbiotic group compared with the placebo group. Overall, synbiotic supplementation for 12 weeks had beneficial effects on glycemic control, biomarkers of inflammation, and oxidative stress in diabetic patients under HD. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT2017090133941N17). http://www.irct.ir: IRCT2017090133941N17. © 2018, Springer Science+Business Media, LLC, part of Springer Nature