Vitamin D in Type 2 Diabetes and Its Correlation With Heat Shock Protein 70, Ferric Reducing Ability of Plasma, Advanced Oxidation Protein Products and Advanced Glycation End Products.

AIM: To investigate the association between vitamin D3 level and oxidative stress biomarkers such as Heat Shock Protein 70 (HSP70), ferric reducing ability of plasma (FRAP), advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) in patients with Type 2 diabetes. METHOD: In this cross-sectional study, 54 patients including 32 females and 22 males with a mean age of 54.92 ± 11.37 years with T2D attending the diabetes clinic from 2021 to 2022 were included. According to the average level of vitamin D in this population (14.91), they were divided into two groups with vitamin D ≤15 ng/mL and vitamin D >15 ng/mL. Multivariate regression analysis was conducted to evaluate the relationship between vitamin D and AOPP, HSP and FRAP parameters. The correlation between vitamin D and other variables was evaluated via the Pearson correlation test. RESULT: Vitamin D level had a positive relation with FRAP (ß = 0.32, p = 0.017) and HSP (ß = 0.39, p = 0.003), but had a negative relation with AOPP (ß = -0.30, p = 0.02). The level of 2hPP also had a negative relation with the level of vitamin D (ß = -0.33, p = 0.03). There was not any relationship between the level of vitamin D and AGEs or other variables. After adjusting for multiple confounders for the multivariate regression model, HSP remained significant. CONCLUSION: This research indicates the relationship between vitamin D levels and oxidative stress biomarkers in patients with Type 2 diabetes.

Vitamin C supplementation lowers advanced glycation end products (AGEs) and malondialdehyde (MDA) in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial.

This study evaluated how daily vitamin C administration impacts systemic oxidative stress and inflammation and its safety in T2D patients. This randomized, double-blinded, placebo-controlled, parallel-arm clinical trial included 70 patients with T2D. They were allocated to receive either 500 mg/day of vitamin C or a matching placebo for 8 weeks. Of the 70 subjects assigned to the trial, 57 were included in the statistical analysis (vitamin C: n = 32, placebo: n = 25). Inflammatory and oxidative markers, including advanced glycation end products (AGEs), malondialdehyde (MDA), advanced oxidation protein products (AOPP), oxidized low-density lipoprotein (ox-LDL), highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and ferric reducing ability of plasma (FRAP) were measured at baseline and the end of the trial. In addition, vitamin C tolerance was evaluated. A nutritionist visited all participants for a standard diabetic regimen. Following vitamin C supplementation, the serum levels of MDA (p-value < .001) and AGEs (p-value = .002) demonstrated a significant decrease after controlling for multiple confounders, including age, blood pressure, waist circumference, HbA1C, TG, and LDL-C, while no significant changes were observed for AOPP (p-value = .234) and ox-LDL (p-value = .480). The FRAP showed an increasing trend as an antioxidant marker but was not statistically significant (p-value = .312). The hs-CRP and TNF-α had no significant changes (p-value: .899 and .454, respectively). Also, no major adverse events were observed. Vitamin C supplementation may be beneficial in reducing AGEs and MDA in patients with T2D.

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma.

Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p < 0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49 ± 4.7 vs. 67.93 ± 8.8, p < 0.001), AOPP (137.64 ± 21.9 vs. 119.08 ± 33.1, p < 0.001), MDA (3.56 ± 0.30 vs. 3.05 ± 0.33, p < 0.001), and ox-LDL (19.78 ± 0.97 vs. 16.94 ± 1.02, p < 0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d = -2.853, 95% CI 2.50-3.19) and MDA (d = -1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5 ± 156.7 vs. 1239.3 ± 290, p < 0.001) and CAT (2.34 ± 0.34 vs. 2.63 ± 0.38, p < 0.001), GPx (102.37 ± 6.58 vs. 108.03 ± 6.95, p < 0.001), and SOD (5.13 ± 0.39 vs. 5.53 ± 0.31, p < 0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d = 1.135, 95% CI 0.46-0.34) and GPx (d = 0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.

Advanced glycation end products, advanced oxidation protein products, and ferric reducing ability of plasma in patients with rheumatoid arthritis: a focus on activity scores.

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory disorder causing functional disabilities. Oxidative stress can cause inflammation and can also be induced by inflammation. Measuring oxidative stress markers could help better understand the pathophysiology of RA and may be used to define the disease severity. MATERIAL AND METHOD: In this case-control study, 75 RA patients were selected among those referred to the rheumatology clinic. Patients were further categorized into two groups, with active and inactive disease according to the Disease Activity Score (DAS) 28. Forty healthy volunteered persons were selected as the control group. Blood samples were obtained, and advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), and ferric reducing ability of plasma (FRAP) were measured. The results were compared via student t-test and Chi-square. RESULTS: Mean ± SD values for AGEs, AOPP, and FRAP in cases and controls were 53.29 ± 6.82 vs. 44.43 ± 7.13 (p = 0.001), 146.08 ± 19.56 vs. 135.79 ± 14.23 (p = 0.004), and 967.13 ± 226.66 vs. 1012.87 ± 215.94 (p = 0.2), respectively. Mean ± SD values for AGEs, AOPP, and FRAP in patients with active disease and inactive disease were 53.32 ± 7.2 vs. 53.26 ± 6.48 (p = 0.9), 146.97 ± 17.56 vs. 145.06 ± 21.84 (p = 0.6), and 953.17 ± 217.09 vs. 983.09 ± 239.31 (p = 0.5), respectively. CONCLUSION: AGEs and AOPP but not FRAP were significantly increased in RA patients compared to healthy controls. There was no significant difference between AGEs, AOPP, and FRAP in RA patients with active and inactive disease. Key points • AGEs and AOPP but not FRAP were significantly increased in RA patients compared to healthy controls. • There was no significant difference between AGEs, AOPP, and FRAP in RA patients with active and inactive disease.

Barriers to initiation of insulin therapy in poorly controlled type 2 diabetes based on self-determination theory.

BACKGROUND: Proper glycaemic control can slow progression of diabetes complications. One of the main causes of poor glycaemic control is delayed initiation of insulin therapy. AIMS: To explain the reasons for delayed insulin initiation based on a behavioural model using patients' innate psychological needs. METHODS: We enrolled 151 patients with type 2 diabetes who had indications for insulin therapy. Thirty general practitioners (GPs) were included as care providers. Patients were studied by questionnaires evaluating components of self determination theory, such as competency, relatedness and autonomy. We also evaluated patients' attitudes towards insulin therapy using the Insulin Treatment Appraisal Scale questionnaire. GPs' attitudes towards insulin therapy were assessed with a different questionnaire. RESULTS: Competency of patients was scored as acceptable (14.44/20). Relatedness score was low at around 15.63/30. The findings suggested that the patients' intrinsic motivation was less than their extrinsic motivation (8.41/15 vs 15.03/20). The main barrier to insulin therapy on the patients' side was rejection of severity of illness (67.5%). According to GPs, low compliance (96.7%) was the main cause of delayed insulin prescription. CONCLUSIONS: We observed that patients do not have a proper understanding about their illness. Due to the low score of relatedness as a representative of patients and care providers' relationship, we highlight the importance of educating both about insulin therapy and how they can have the most effective relationship in this process.

Effects of probiotic, cinnamon, and synbiotic supplementation on glycemic control and antioxidant status in people with type 2 diabetes; a randomized, double-blind, placebo-controlled study.

PURPOSE: The aim of this study was to investigate the effect of probiotic bacteria of Lactobacillus acidophilus, cinnamon powder and their combinations on the glycemic and antioxidant indices in patients with type 2 diabetes. METHODS: A total of 136 patients randomized with type 2 diabetes entered the study and were randomly divided into four groups who were matched for age and gender. Thereafter, alongside their routine pharmacotherapy, each group followed one of the following diets: Group A: Lactobacillus acidophilus 108 cfu and 0.5 g of powdered cinnamon (synbiotic). Group B: Lactobacillus acidophilus (probiotic), Group C: powdered cinnamon. Group D: rice flour powder as placebo. At the beginning and end of the intervention, fasting blood sugar (FBS), HbA1c, advance glycation end products (AGE), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and antioxidant enzymes of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured. RESULTS: Following 3 months of treatment, the mean FBS level was decreased significantly in probiotic, cinnamon, and synbiotic supplementation groups compared with control (P < 0.01). FBS levels in probiotic, cinnamon, and synbiotic groups were significantly decreased compared with the control group (P = 0.001, P = 0.063 and P = 0.001, respectively). The mean HbA1C in probiotic, cinnamon, and synbiotic groups were also decreased (P = 0.001, P = 0.001 and P = 0.04, respectively). The mean AGE in synbiotic group was significantly decreased (P = 0.037). Probiotic, cinnamon and synbiotic all could improve antioxidant enzyme activity modestly. However, the most significant effect was seen in probiotic group. CONCLUSIONS: According to the current results, the use of probiotic supplements (individually or in combination with cinnamon) leads to a reduction in blood glucose and an increase in antioxidant enzymes in people with type 2 diabetes.

Nitric oxide and TNF-α are correlates of diabetic retinopathy independent of hs-CRP and HbA1c.

PURPOSE: Regarding the role of inflammation in progression of diabetes this study was conducted to investigate the association between inflammatory biomarkers such as nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) with the chance of existence of diabetic retinopathy and its progression in patients with diabetes. METHODS: A total of 83 patients with T2DM (Type 2 diabetes mellitus) were divided into three groups of patients with proliferative diabetic retinopathy (PDR), patients with non-proliferative diabetic retinopathy (NPDR) and patients without diabetic retinopathy (NDR) based on ophthalmologic funduscopic examination. Twenty six healthy controls were also enrolled. Blood samples were taken after 12 h of overnight fasting, NO, TNF-α, and hs-CRP were measured. Association of the level of these biomarkers with retinopathy was analyzed. RESULTS: The levels of TNF-α, NO and hs-CRP were higher among patients with diabetic retinopathy. Multinomial Logistic Regression model showed that TNF-α and NO could predict the presence of retinopathy among patients with diabetes when adjusted for hs-CRP, HbA1c, FBS, gender, total cholesterol, triglyceride, HDL, LDL, BMI, and age (respectively OR = 1.76, CI 95% = 1.01-3.02, p = 0.046 and OR = 1.12, CI 95% = 1.05-1.18, p < 0.001); however they could not predict the severity of retinopathy. In ROC analysis AUC for TNFα was 0.849 (p < 0.001) and for NO was 0.907 (p < 0.001). Serum TNF-α level of 7.10 pmol/L could be suggestive of the presence of retinopathy (sensitivity = 92.2% and specificity = 66.0%), also serum NO level of 45.96 µmol/L could be suggestive of the presence of retinopathy (sensitivity = 96.1% and specificity = 86%). CONCLUSIONS: Our results suggest elevated levels of NO and TNF-α can be suggestive of diabetic retinopathy.

Intravenous laser wavelength radiation effect on LCAT, PON1, catalase, and FRAP in diabetic rats.

The main purpose of this study is to evaluate the effect of intravenous irradiation of different low-level laser wavelengths on the activity of lecithin-cholesterol acyltransferase (LCAT), paraoxonase (PON1), catalase, and ferric reducing ability of plasma (FRAP) in diabetic rats. First, diabetes was induced in rats using streptozotocin (STZ). Enzymes' activity was measured in the blood samples and compared before and after intravenous laser blood irradiation. We used four continuous-wave lasers-IR (λ = 808 nm), Red (λ = 638 nm), Green (λ = 532 nm), and Blue (λ = 450 nm)-to compare the wavelength's effect on different enzymes' activity. Laser power was fixed at 0.01 mW and laser energy was changed by 2-, 4-, 6-, and 8-min time of radiations.The enzymes' activity of blood samples was measured 2, 6, and 24 h after radiation. The results show an increase in the activity of different enzymes when compare with diabetic non-radiated samples. More importantly, with a constant laser energy, the enzymes' activity increased with decreasing laser wavelength. It is important to note that with a constant laser energy, as the wavelength decreases, the photon energy increases and the number of photons decrease, while the enzyme's activity elevation increases. As a result, we can conclude that in intravenous low-level laser therapy, photon energy is more important than the number of photons even if their product, energy, is kept constant.

Serum HSP70 level in patients with endometrial cancer with and without diabetes.

Diabetes mellitus (DM) is associated with an increased risk of endometrial carcinoma (EC). Heat shock proteins have a role in the modulation of both diseases. The aim of this study was to investigate extracellular HSP70 (eHSP70) level alternations in patients with two different types of EC (endometrioid and non-endometrioid) with and without type 2 diabetes. In a case-control study, 88 participants were enrolled in four groups including: 18 EC patients with DM, 19 EC patients without DM, 29 patients with DM, and 22 healthy individuals. Blood samples were taken before surgery in cancer patients. Estradiol, eHSP70, sex hormone-binding globulin (SHBG), FBS, and HbA1c were assessed. Serum HSP70 level was higher in patients with diabetes (52.24 ± 14.2 ng/ml) compared to healthy controls (39.04 ± 6.96) (p < .05). It was lower in EC (26.05 ± 12.28) compared to healthy controls (39.04 ± 6.96) (p < .05). eHSP70 was also lower in endometrioid-type carcinoma (22.57 ± 11) compared to non-endometrioid type (31.55 ± 12.38) (p < .05). Further analysis showed increased levels of eHSP70 in patients having both endometrioid-type carcinoma and diabetes (27.23 ± 11.41) compared to the same patients without DM (17.08 ± 7.78) (p < .05). Presence of diabetes in patients with endometrioid type carcinoma resulted in an increase in eHSP70 approaching the level of eHSP70 in patients with non-endometrioid histology.

The effect of cold atmospheric plasma on diabetes-induced enzyme glycation, oxidative stress, and inflammation; in vitro and in vivo.

Cold atmospheric plasma (CAP) is known as the versatile tool in different biological, and medical applications. In this study, we investigated the effect of cold plasma on diabetes via in vitro and in vivo assessments. We performed the in vitro assay to evaluate the impact of CAP on glycated glutathione peroxidase (GPx) through enzyme activity measurement as a function index and far- and near-UV circular dichroism (CD) and fluorescence analysis as structure indices. The result of in vitro assessment showed that the exposure of glycated GPx to plasma causes a considerable increase in enzyme activity up to 30%. Also, the evaluation of far- and near-UV CD and fluorescence analysis indicated a modification in the protein structure. According to obtained result from in vitro assessment, in vivo assay evaluated the effect of CAP on diabetic mice through analyzing of blood glucose level (BGL), advanced glycation end products (AGEs), antioxidant activity, oxidative stress biomarkers such as malondialdehyde (MDA), advanced oxidation protein products (AOPP), and oxidized low-density lipoprotein (oxLDL), and inflammation factors including tumor necrosis factor (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). The result of in vivo experiment also showed a 20% increase in antioxidant activity. Also, the reduction in AGEs, oxidative stress biomarkers, and inflammatory cytokines concentrations was observed. The result of this study revealed that CAP could be useful in diabetes treatment and can be utilized as a complementary method for diabetes therapy.

Loss of Inverse Association between Framingham Risk Score and Estimated Glomerular Filtration Rate in Moderate to Severe Diabetic Kidney Disease.

BACKGROUND: We investigated the association of estimated glomerular filtration rate (eGFR) with Framingham risk score (FRS), and actual cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). We also assessed improvement in FRS for prediction of CVD after inclusion of eGFR and albuminuria. METHODS: A total of 571 patients with T2DM and mean age 55 were divided into 2 groups based on the presence of CVD. Participants without CVD were then divided into three groups according to FRS. CVD is defined as an episode of CCU admission, Myocardial infarction, history of coronary artery bypass graft surgery or percutaneous intervention. FRS is calculated using the Wilson 1998 Circulation equation, which includes age, sex, high blood pressure, smoking, high-density lipoprotein (HDL), total cholesterol and diabetes as components to assess CVD risk in 10 years. RESULTS: An inverse adjusted association between eGFR and prevalent CVD was confirmed by multiple logistic regression analysis (OR = 0.84, 95% CI: 0.74, 0.94, P = 0.03). We observed every 10 mL/min/1.73 m2 decrease in eGFR is related to 3% increase in FRS in patients without chronic kidney disease (CKD) (coefficient = -0.03, P < 0.001). The association between FRS and GFR and also CVD and eGFR were not significant in patients with CKD (P = 0.12; P = 0.17, respectively). Predictive values for FRS components with and without considering eGFR and albuminuria were calculated (0.74 and 0.75, respectively). CONCLUSION: Inclusion of eGFR and albuminuria in the FRS formula did not improve the predictive value of the model. We showed an inverse association between eGFR and FRS in early stages of diabetic kidney disease, which was lost in patients with CKD.

Association of extracellular heat shock protein 70 and insulin resistance in type 2 diabetes; independent of obesity and C-reactive protein.

Despite few studies on intracellular heat shock protein70, the clinical association between insulin resistance and extracellular heat shock protein70 (eHSP70) is not well studied. In the current study, we examined the association between homeostatic model assessment-insulin resistance (HOMA-IR) and eHSP70 in patients with type 2 diabetes (T2DM) and healthy controls. A total of 145 patients with T2DM and 41 matched healthy controls were selected. Patients and controls were divided based on waist circumference (WC) to two groups, and eHSP70 was compared between them. The association between HOMA-IR and eHSP70 was examined using regression models adjusted for age, high-sensitive C-reactive protein (hs-CRP), and central obesity as confounding factors. While eHSP70 and hs-CRP were significantly correlated with HOMA-IR in patients with T2DM (p = 0.032, 0.025, respectively), there was no correlation between eHSP70 and HOMA-IR in the control group. Extracellular HSP70 and hs-CRP were not correlated in healthy controls. But a significant association appeared between eHSP70 and hs-CRP in patients with T2DM (p = 0.05). Both BMI and WC were not correlated with eHSP70 in both groups. Extracellular HSP70 was positively associated with HOMA-IR in patients with T2DM, independent from hs-CRP and obesity. We also showed eHSP70 levels remained unchanged through increase in BMI or WC in patients with T2D and in healthy controls. Our findings suggest that eHSP70 may contribute to the pathogenesis of T2DM by increasing insulin resistance.

Investigating the effect of visfatin on ERalpha phosphorylation (Ser118 and Ser167) and ERE-dependent transcriptional activity.

Obesity is associated with higher postmenopausal breast cancer incidence. Visfatin level alteration is one of the mechanisms by which obesity promotes cancer. Ligand-independent activation of estrogen receptor alpha (ERα) is also associated with carcinogenesis. The activity of ERα is modulated through phosphorylation on multiple sites by a number of protein kinases. Here we investigated the effect of visfatin as a novel adipocytokine on the phosphorylation and activity of ERα in MCF-7 breast cancer cells. We showed that exogenous administration of visfatin significantly increased the phosphorylation of ERα at serine 118 (Ser118) and 167 (Ser167) residues. Visfatin-induced Ser118 phosphorylation was diminished after treatment of cells with U0126 (MEK1/2 inhibitor). Furthermore, our results showed that visfatin-induced Ser167 phosphorylation is mediated through both MAPK and PI3K/Akt signaling pathways. Inhibition of the enzymatic activity of visfatin by FK866 had no effect on phosphorylation of ERα. We also showed that visfatin enhanced the estrogen response element (ERE)-dependent activity of ER in the presence of 17-ß estradiol (E2). Additional study on T47D cells showed that visfatin also increased Ser118 and Ser167 phosphorylation of ERα and enhanced ERE-dependent activity in the presence of E2 in these cells.

Pulse pressure and diabetes treatments: Blood pressure and pulse pressure difference among glucose lowering modality groups in type 2 diabetes.

Type 2 diabetes is associated with higher pulse pressure. In this study, we assessed and compared effects of classic diabetes treatments on pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in patients with type 2 diabetes.In a retrospective cohort study, 718 non-hypertensive patients with type 2 diabetes were selected and divided into 4 groups including metformin, insulin, glibenclamide+metformin, and metformin+insulin. They were followed for 4 consecutive visits lasting about 45.5 months. Effects of drug regimens on pulse and blood pressure over time were assessed separately and compared in regression models with generalized estimating equation method and were adjusted for age, duration of diabetes, sex, smoking, and body mass index (BMI).Studied groups had no significant change in PP, SBP, and DBP over time. No significant difference in PP and DBP among studied groups was observed (PP:P = 0.090; DBP:P = 0.063). Pairwise comparisons of PP, SBP, and DBP showed no statistically significant contrast between any 2 studied groups. Interactions of time and treatment were not different among groups.Our results demonstrate patients using metformin got higher PP and SBP over time. Averagely, pulse and blood pressure among groups were not different. Trends of variation in pulse and blood pressure were not different among studied diabetes treatments.

Effect of Low-Level Laser Irradiation on the Function of Glycated Catalase.

Introduction: The aim of this work is to evaluate the effect of low-level laser irradiation (LLLI), by lasers with different wavelengths, on glycated catalase enzyme in vitro experimentally. Methods: This is done by measuring the activity and structure properties of glycated catalase enzyme. The structure properties were evaluated with circular dichroism (CD) and fluoroscopy methods. Three continuous wave (CW) lasers in the visible spectrum (λ =450, 530, 638 nm) and a 100-ns pulsed laser in the infrared spectrum (λ =905 nm) were chosen for comparison. For the infrared laser, same effects have been investigated for different energy doses. The effect of photon energy (hυ) at different wavelengths was measured on activity, CD, and fluoroscopy properties of catalase, and compared with the control group (samples without irradiation). The energy intensity of laser should not exceed 0.1 J/cm2 . Experiments were performed on glycated catalase between 2 to 16 weeks after glycation of catalase. The LLLI effect was also investigated on the samples, by comparing the catalase activity, CD and fluoroscopy for different wavelengths. Results: Our results indicated, the decrease in catalase activity as a function of glycation time (weeks) for all samples, and a slight increase on its activity by different laser wavelengths irradiation for any fixed period of glycation time. Finally, the catalase activity has been increased as the laser's photon energy (hυ) intensified. More specifically, the blue laser (λ =450 nm) had the most and the red laser (λ =638 nm) had the least effect, and the green laser (λ =530 nm) had the medium effect on catalase activity as well. Furthermore, pulsed laser had an additional effect by increasing energy dosage. Conclusion: As we expected in all experiments, an increase in the catalase activity was coincident with a decrease in the catalase fluoroscopy and CD parameters.

The Association between Modulating Inflammatory Cytokines and Constipation of Geriatrics in Iran.

BACKGROUND The effect of changes in intestinal microbiota on constipation is contraversial. Constipation is more prevalent in elderly. Therefore, the current study was designed to assess the role of modulating inflammatory cytokines in old age patients with constipation by evaluating the serum levels of tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-l), and interleukin 6 (IL-6). METHODS This case-control study was done on 100 participants, aged 65 years or higher, with and without functional constipation according to ROME III criteria (50 participants in each group). Baseline demographic, clinical characteristics, and serum levels of TNF-α, IL-1, and IL-6 were compared between the case and control groups. Independent t test and Chi-square test were used for analysis of data. RESULTS Mean levels of TNF-α, IL-1, and IL-6 were (666.80 ± 101.40 pg/mL vs. 489.20 ± 53.68 pg/mL, p < 0.001), (435.96 ± 52.31 pg/mL vs. 296.44 ± 45.50 pg/mL, p < 0.001) and (438.18 ± 59.57 pg/mL vs. 290.14 ± 36.39 pg/mL, p < 0.001) in the case and control groups, respectively. A reverse correlation was found between the aging process and TNF-α (r = -0.26; p = 0.04), as well as IL-1 level (r = -0.41; p = 0.003) in the control group. A direct correlation was observed between the aging process and TNF-α (r = 0.40; p = 0.004) and IL-6 (r = 0.44; p = 0.002) levels in the case group. CONCLUSION This study showed a significant association between the serum level of modulating inflammatory cytokines and age-related constipation in Iranian subjects. It seems that the serum level of modulating inflammatory cytokines can be affected by diversity and abundance in the gut microbiota. The role of diversity in microbial population and their abundance in gut must be evaluated in further studies.

Effect of hemodialysis on oxidants and antioxidant factors in chronic renal failure.

The current study was conducted to assess the effect of hemodialysis (HD) on the status of plasma oxidants and antioxidants among patients with end-stage renal disease (ESRD). These parameters can have an influence on the HD process and can also be useful for follow-up of these patients. The participants of this cross-sectional study comprised 91 patients with a mean age of 51.1 ± 8.2 years on chronic HD with kt/v between 1.2 and 1.4. The etiology of ESRD in these patients was as follows: diabetes mellitus in 39, hypertension in 35, and glomerulonephritis in 17 patients. All patients were on maintenance treatment with phosphate binder, 1,25 Vitamin D, iron, and erythropoietin therapy as per the K/DOQI guidelines. They were selected by random method from Shahid Bahonar Hospital, Karaj, Iran. The height, weight, waist circumference (WC), and blood pressure were measured according to standardized protocols, and blood samples were obtained before and after HD. Blood samples were checked for advanced glycation end products, advanced oxidation protein product, malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), and ferritin reducing ability of plasma, catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD), and blood urea nitrogen (BUN). The means of MDA, BUN, advanced glycation end product (AGE), and ox-LDL plasma level postdialysis significantly decreased compared to the predialysis level. The mean of plasma catalase, GPx, and SOD increased significantly postdialysis compared to the predia- lysis level in these patients. Factors including age, body mass index, WC, and diastolic blood pressure affected changes in levels of oxidants and antioxidants after HD. Our study results revealed that the status of antioxidants and oxidants tends to improve after HD.

Inhibitory effect of curcumin on angiogenesis in a streptozotocin-induced diabetic rat model: An aortic ring assay.

BACKGROUND: Curcumin (diferuloylmethane) has been associated with the inhibition of angiogenesis, as well as the prevention of cancers and inflammatory processes. The aim of this study was to assess the efficacy of curcumin in suppressing angiogenesis in the cultured endothelial cells of rat aortic rings. METHODS: Eight-week-old male Wistar rats were randomized into five groups each with a different treatment and cell culturing paradigm: controls cultured in the absence of VEGF (vascular endothelial growth factor) (C), controls cultured in the presence of VEGF (C-V), controls treated with curcumin and then cultured in media lacking VEGF (C-TC), diabetics cultured in media supplemented with VEGF (D-V) and diabetics treated with curcumin and then cultured in media supplemented with VEGF (D-V-TC). Each group consisted of 8 animals. Diabetes was induced in by streptozotocin (STZ; 60 mg/kg body weight, IV). After 8 weeks, animals were sacrificed and their aortas were excised. Ring-shaped explants were embedded in a 96-well culture plate. Angiogenesis response was measured by counting the number of primary microtubules in each well. RESULTS: Optic microscopy revealed that the D-V group had the highest number of microvessels, while angiogenesis was not observed in the C or C-TC groups. The number of primary microtubules was significantly lower in the D-V-TC group compared to the D-V group (P < 0.05). The D-V-TC group had a significantly higher number of microvessels compared to the C-TC group (P < 0.05). CONCLUSION: Curcumin attenuates angiogenesis response in stertozotocin-induced diabetic rats.

The Preventive Effect of L-Lysine on Lysozyme Glycation in Type 2 Diabetes.

Lysozyme is a bactericidal enzyme whose structure and functions change in diabetes. Chemical chaperones are small molecules including polyamines (e.g. spermine), amino acids (e.g. L-lysine) and polyols (e.g. glycerol). They can improve protein conformation in several stressful conditions such as glycation. In this study, the authors aimed to observe the effect of L-lysine as a chemical chaperone on structure and function of glycated lysozyme. In this study, in vitro and in vivo effects of L-lysine on lysozyme glycation were investigated. Lysozyme was incubated with glucose and/or L-lysine, followed by an investigation of its structure by electrophoresis, fluorescence spectroscopy, and circular dichroism spectroscopy and also assessment of its bactericidal activity against M. lysodeikticus. In the clinical trial, patients with type 2 diabetes mellitus (T2DM) were randomly divided into two groups of 25 (test and control). All patients received metformin and glibenclamide for a three months period. The test group was supplemented with 3 g/day of L-lysine. The quantity and activity of lysozyme and other parameters were then measured. Among the test group, L-lysine was found to reduce the advanced glycation end products (AGEs) in the sera of patients with T2DM and in vitro condition. This chemical chaperone reversed the alteration in lysozyme structure and function due to glycation and resulted in increased lysozyme activity. Structure and function of glycated lysozyme are significantly improved by l-lysine; therefore it can be considered an effective therapeutic supplementation in T2DM, decreasing the risk of infection in these patients.