Significant Increase In Blood Levels Research Articles

BLOOD LEVELS OF INTERLEUKIN-17A IN PATIENTS WITH ARTERIAL HYPERTENSION AND ITS RELATIONSHIP WITH THE CHARACTERISTICS OF THE COURSE OF DISEASE

Objective: One of the most important links in the pathogenesis of arterial hypertension (AH) is currently considered to be the activation of subclinical inflammation. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 lymphocytes. The objective of the study was to evaluate the changes in blood levels of IL-17A in patients with AH and its relationship with the characteristics of the course of the disease. Design and method: The study involved 65 patients with grade 2-3 AH (34 men and 31 women aged 37 to 59 years) and 22 practically healthy individuals in the control group (12 men and 10 women aged 19 to 47 years). Patients were examined using standard clinical, laboratory and instrumental methods. The scope of the study also included the determination of blood levels of IL-17A and highly sensitive C-reactive protein (hsCRP) by the enzyme immunoassay. Examination of all patients and persons of the control group was carried out before the start of the war in Ukraine. Results: A significant increase in blood levels of IL-17A was established in general in the group of patients with 2-3 degree AH ((7.12 [4.74;10.67]) pg/mL, P <0.05) in comparison with practically healthy individuals ((3.24 [0,96;4,59]) pg/mL). The highest blood levels of IL-17A were found in patients with AH with a more pronounced increase in blood pressure (BP) up to the 3rd degree of AH ((9.87 [5.98;13.56]) pg/mL, P<0.05) compared with the levels of this factor in patients with 2nd degree of AH ((5.85 [3,66;8,12]) pg/mL). Significant positive correlations were found between blood levels of IL-17A and hsCRP (P = 0,023), left ventricular mass index (P = 0,027) and systolic BP (P = 0,036). Conclusions: In patients with grade 2-3 AH, a significant increase in blood levels of proinflammatory cytokine IL-17A and its relationship with indicators of activation of subclinical inflammation, the severity of hypertrophic remodeling of the heart, and the severity of hypertension were found.

Blood metabolites in preterm infants with retinopathy of prematurity based on tandem mass spectrometry: a preliminary study

To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics. Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers. There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP. Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.

Plasma Levels of Fetuin B and Fibrinogen in Chronic Obstructive Pulmonary Disease: A Preliminary Cross-sectional Study

Introduction: Recent exploratory proteomics study reported increased blood levels of Fetuin B (FETUB) in Chronic Obstructive Pulmonary Disease (COPD). Growing body of evidence demonstrates fibrinogen not only as acute phase reactant but also possesses features advocating as biomarker of COPD. Aim: To determine the blood levels of FETUB and fibrinogen independently as well as in combination COPD and among severity of COPD. Materials and Methods: A single-centred cross-sectional study of eight months duration was conducted during May to December 2017. A total of 76 blood samples (38 COPD patients and 38 controls) were recruited. Based on distribution, parametric and non parametric statistical tools were used. Analysis of co-variance and multiple multivariate linear regression models were utilised to assess the influence of clinical data on FETUB. Steel-Dwass-Critchlow- Fligner method was employed for multiple pairwise comparisons. Receiver Operating Characteristic (ROC) curve were generated to compute cut-off of FETUB, fibrinogen and their combination. Results: The median age of subjects were 57 years with an IQR of 50-66 years for controls whereas 58 years (IQR 50-65 years) for COPD subjects. In comparison to controls, a significant increase in blood levels of both FETUB and fibrinogen in COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages of COPD was prominent. Among COPD grades, differences of FETUB levels were significant in GOLD I vs II and GOLD IV vs I, II and III whereas fibrinogen levels in GOLD III from GOLD IV. FETUB showed independent correlation with Forced Expiratory Volume (FEV) 1% pred and severity of COPD. A moderate improvement in combined (FETUB+fibrinogen) analysis of control vs COPD was noticed. Conclusion: The present study demonstrates significant increase in blood levels of FETUB in COPD and among the severity of COPD in comparison to fibrinogen. Hence, FETUB can be a more promising probable inflammatory biomarker in COPD.

Mitral Valve Prolapse in Young and Middle-aged Patients with Hypertension

One of the risk factors that plays an important role in the pathogenesis but is insufficiently studied in the development and progression of hypertension (AH) is the presence of connective tissue dysplasia (СTD). CTD are genetically determined conditions characterized by defects in fibrous structures and the main substance of connective tissue (CT), which lead to disruption of the formation of organs and systems, have a progressive course and determine the features of the associated pathology.The objective: study of the frequency and severity of mitral valve prolapse in patients with hypertension.Materials and methods. We examined 153 patients with primary hypertension I–II stage 1 – 3 degrees (90 men and 63 women) aged 22 to 45 years.Results. Mitral valve prolapse (MVP) was detected in 32 % of patients with hypertension (grade 1 MVP – in 21 % of patients and grade 2 – in 11 %, respectively. The frequency of MVP in stage I hypertension was established than in stage II. MVP with mitral regurgitation of 1–2 degrees was higher in hypertension of stage II in comparison with AH of stage I. MVP of 1 degree was most often associated with increased variability of systolic blood pressure (SBP), and MVP of 2 degree – with increased SBP load and type of daily profile «non-dipper» BP was characterized by a higher incidence of left ventricular hypertrophy (LVH) and supraventricular arrhythmias than in patients without MVP, with an increase in the concentration of free oxyproline in the blood in patients with grade 1 hypertension and total oxyproline – in patients with hypertension with MVP 2 degree.Conclusions. It was found that 32 % of patients with hypertension of young and middle age have MVP 1–2 degrees. An increase in the frequency of MVP in general (1 and 2 degrees) in patients with stage I hypertension, compared with patients with stage II hypertension, as well as the frequency of stage 1 MVP in patients with stage I hypertension compared with patients with stage II hypertension. At the same time, the frequency of MVP 2 degree and MVP with MR 1–2 degree was higher in patients with stage II hypertension compared with stage I hypertension. Patients with hypertension with MVP were characterized by a higher frequency of LVH and the occurrence of supraventricular arrhythmias than for patients without MVP. There was a significant increase in blood levels of free oxyproline in the group of patients with hypertension with MVP 1 degree compared with patients with MVP 2 degree and a significant increase in blood levels of total oxyproline in patients with MVP 2 degree compared with patients with MVP 1 degree.

Systematic review and meta-analysis of randomized controlled trials on the effects of obeticholic acid on the blood lipid profile: Insights into liver disorders and liver cancer

AimTreatment with obeticholic acid (OCA) affects the blood lipid profile. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to investigate the effects of OCA on blood lipids and lipoproteins. Methods and resultsThe electronic databases of PubMed, Web of Science, SCOPUS, and Google Scholar were searched. The mean differences were meta-analyzed to obtain a pooled weighted mean difference (WMD) and the 95% CI across the trials using the Der Simonian and Laird random-effects method. Six (6) articles with 10 trials for low-density lipoprotein cholesterol (LDL-C), and 8 trials for high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) levels were included in the meta-analysis. . Most studies were conducted in patients with liver dysregulation (fatty liver, liver cancer). The pooled results showed that the levels of TC (WMD: 6.357 mg/dl) and LDL-C (WMD: 6.067 mg/dl) increased while TG (WMD: -22.417 mg/dl) decreased after treatment with OCA. A slight but significant decrease was also observed for HDL-C levels (WMD: -1.492 mg/dl). A significant non-linear response was observed only between the TG levels and the length of intervention. Larger reductions in TG levels were observed over intervention durations of less than 3 weeks, but regarding interventions for more than 3 weeks, the impact on TG was modest. ConclusionOCA administration causes significant increases in blood levels of TC and LDL-C while decreasing HDL-C and TG in humans. More study needed on liver cancer.

Physiological effects of incidental capture and seasonality on juvenile green sea turtles (Chelonia mydas)

Fishery is one of the main threats faced by sea turtles. However, literature relating to the physiological effects of incidental capture by fishing gears is scarce. The aim of this study is to establish blood reference values for a juvenile population of Chelonia mydas, from Ubatuba- Brazil, and compare them with incidental captured animals by fisheries in the same area, considering seasonal variation. Animals were captured during summer and winter, from direct capture (diving) and incidental capture (pound net and gillnet). Blood samples were collected from 96 healthy green sea turtles and, were analyzed for determining levels of glucose, lactate, total protein, uric acid, albumin, total lipids, triglycerides, VLDL cholesterol, total cholesterol, corticosterone concentrations, total antioxidant capacity, and lipid peroxidation. Corticosterone concentrations were significantly lower in animals captured by diving than in those captured by pound net and gillnet and were thought tso more closely represent baseline levels. Thus, the values found in animals captured by diving were used to establish reference values for this population. Turtles captured in summer had a significant increase in blood levels of glucose, total protein, uric acid, albumin, TBARS, and TEAC; and a decrease in total lipids compared with turtles captured in winter. Although pound nets are considered a low impact fishery to the turtles due to the low mortality rates, seven out of twelve parameters differed significantly from baseline values established for the species. Entanglement in gillnets caused greater perturbations than pound net and all parameters analyzed were significantly different from the reference values. These data indicate that incidental capture causes substantial alterations in health parameters of sea turtles. The results obtained in this study would help in future rehabilitation programs of sea turtles that are captured by fisheries. Additionally, reference values can be used for future comparisons with populations of the same species and with unhealthy and stressed individuals.

The Usefulness of Diagnostic Panels Based on Circulating Adipocytokines/Regulatory Peptides, Renal Function Tests, Insulin Resistance Indicators and Lipid-Carbohydrate Metabolism Parameters in Diagnosis and Prognosis of Type 2 Diabetes Mellitus with Obesity.

The quantitative analysis of selected regulatory molecules, i.e., adropin, irisin, and vaspin in the plasma of obese patients with newly diagnosed, untreated type 2 diabetes mellitus, and in the same patients after six months of using metformin, in relation to adropinemia, irisinemia and vaspinemia in obese individuals, was performed. The relationship between plasma concentration of the adipocytokines/regulatory peptides and parameters of renal function (albumin/creatinine ratio—ACR, estimated glomerular filtration rate—eGFR), values of insulin resistance indicators (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR2), Homeostatic Model Assessment of Insulin Sensitivity (HOMA-S), Homeostatic Model Assessment of β-cell function (HOMA-B), quantitative insulin sensitivity check index (QUICKI), insulin), and parameters of carbohydrate-lipid metabolism (fasting plasma glucose—FPG, glycated hemoglobin—HbA1C, estimated glucose disposal rate—eGDR, fasting lipid profile, TG/HDL ratio) in obese type 2 diabetic patients was also investigated. Circulating irisin and vaspin were found significantly different in subjects with metabolically healthy obesity and in type 2 diabetic patients. Significant increases in blood levels of both analyzed adipokines/regulatory peptides were observed in diabetic patients after six months of metformin treatment, as compared to pre-treatment levels. The change in plasma vaspin level in response to metformin therapy was parallel with the improving of insulin resistance/sensitivity parameters. An attempt was made to identify a set of biochemical tests that would vary greatly in obese non-diabetic subjects and obese patients with type 2 diabetes, as well as a set of parameters that are changing in patients with type 2 diabetes under the influence of six months metformin therapy, and thus differentiating patients′ metabolic state before and after treatment. For these data analyses, both statistical measures of strength of the relationships of individual parameters, as well as multidimensional methods, including discriminant analysis and multifactorial analysis derived from machine learning methods, were used. Adropin, irisin, and vaspin were found as promising regulatory molecules, which may turn out to be useful indicators in the early detection of T2DM and differentiating the obesity phenotype with normal metabolic profile from T2DM obese patients. Multifactorial discriminant analysis revealed that irisin and vaspin plasma levels contribute clinically relevant information concerning the effectiveness of metformin treatment in T2D patients. Among the sets of variables differentiating with the highest accuracy the metabolic state of patients before and after six-month metformin treatment, were: (1) vaspin, HbA1c, HDL, LDL, TG, insulin, and HOMA-B (ACC = 88 [%]); (2) vaspin, irisin, QUICKI, and eGDR (ACC = 86 [%]); as well as, (3) vaspin, irisin, LDL, HOMA-S, ACR, and eGFR (ACC = 86 [%]).

Dynamics of homeostasis in patients with acute pancreatitis, depending on the use of parenteral nutrition

The data of patients with severe acute pancreatitis (AP) who were treated for the period from 2014 to 2018 were analyzed. Patients who on the second day of intensive therapy experienced intestinal failure syndrome, which made it impossible to conduct early enteral nutrition, nutritional support began with a total parenteral nutrition (TPN). Depending on the type of mixture that was used as nutritional support, the patients were divided into subgroups: subgroup 1 (n = 22) - patients who received three-component mixtures in special TPN bags. Subgroup 2 (n = 20) - patients who received three-component mixtures with a high content of ω-3 fatty acids for TPN. Subgroup 3 (control) - patients (n = 25), in which the TPN consisted of separate modules of carbohydrates, amino acids and fats. It is shown that during severe AP accompanied by increased levels of cortisol in patients subgroups 1, 2 and 3 is 1.8, 1.7 and 1.9 times higher than normal, stress-induced hyperglycemia and hypoalbuminemia from the first day of the disease. Conducting modular TPN did not provide a protein-saving effect against the background of hypercatabolism caused by the course of severe acute pancreatitis. The addition of ω-3 FA in the composition of TPN by three-chamber bags contributed to a more rapid recovery of the level of total blood protein and albumin against the background of the course of severe AP. On the background of the nutritional support by TPN using the three-chambered bags of enriched ω-3 fatty acids, it has been registered normalization of neutrophil-leukocyte index at 7 days by reducing leukocytosis and a significant increase in blood levels of lymphocytes, a faster and more pronounced decrease in blood levels of CRP. It determined that in patients with severe AP 1 and 2 subgroups that received TPN using a three-chambered bags, the total period of hospital treatment (27,5 ± 2,7 days and 22.1 ± 0.8 days, respectively) was significantly less than in patients who underwent TPN using modular systems (35.5 ± 7.7 days) (p 1, 2 = 0.001, p1, 3 <0.001, p2, 3 <0.001).

Tomato Nutrient Complex Effect on Blood Pressure (P06-112-19)

ObjectivesExamine the effect of a carotenoid-rich Tomato Nutrient Complex on blood pressure and perform a dose-response analysis and uncover the optimal effective supplementation dose in maintaining blood pressure within normal range among individuals with systolic blood pressure between 130–140 mmHg, otherwise healthy subjects. MethodsIn this double-blind, randomized, placebo-controlled study, different doses of the Tomato Nutrient Complex were examined, corresponding to 5 mg, 15 mg, and 30 mg lycopene. The effect of the tomato-derived treatment was compared with 15 mg of synthetic Lycopene and placebo over 8 weeks of treatment. In addition, we analyzed the bioavailability of the carotenoids following treatment with different doses of the Tomato Nutrient Complex in a group of 25 healthy volunteers. Volunteers were treated for four weeks with Tomato Nutrient Complex providing 2, 5 and 15 mg lycopene. ResultsResults indicate that treatment for 8 weeks with Tomato Nutrient Complex standardized to contain 15 mg or 30 mg of lycopene was associated with statistically significant reductions in mean SBP of 9.7 mmHg and 7 mmHg compared to baseline values respectively. Treatment with the lower dose Tomato Nutrient Complex standardized for 5 mg of lycopene, or treatment with 15 mg of synthetic lycopene as a standalone did not show a significant effect.In parallel, we analyzed the bioavailability of the carotenoids in healthy subjects. In a group of 25 healthy volunteers treated for 4 weeks with different doses of the Tomato Nutrient Complex. we identified a dose dependent and significant increase in blood level of lycopene, phytoene, and phytofluene. ConclusionsOverall, the results suggest that the carotenoids in the Tomato Nutrient Complex are well absorbed in a dose dependent manner and that only the carotenoid levels achieved by the dose corresponding to 15 mg lycopene or more, is correlated to a beneficial effect on systolic blood pressure while lower doses and standalone lycopene are not enough to drive the effect. Funding SourcesLycored.

Impact of Conversion From Advagraf to Twice-Daily Generic Tacrolimus in Kidney Transplant Recipients: A Single-Center Study

BackgroundThe conversion of twice-daily (Prograf) to once-daily tacrolimus (Advagraf) as well as from Prograf to a generic tacrolimus preparation was proved to be safe in kidney transplant patients. There are no published studies comparing the clinical outcomes of patients who were receiving Advagraf and were switched to generic preparations of tacrolimus. ObjectivesTo evaluate the impact, safety profile, side effects, and renal graft function after the conversion of Advagraf to a generic preparation of tacrolimus. Population and MethodsThis prospective study was conducted over a 9-month period. The conversion to twice-daily generic tacrolimus was performed on a 1 mg:1 mg basis, total daily dose. We included 123 kidney transplant recipients (55% male). The mean (± SD) age was 49.9 ± 12 years. There were 100 (81%) Caucasian patients; the mean (± SD) time from transplantation to conversion was 4.6 ± 4.4 years. ResultsA significant increase in blood levels (18%; P = .000) was reported. There was a necessary tacrolimus dose reduction of 17% (P = .000) and ≥3 blood trough levels to adjust the initial tacrolimus blood levels. The mean serum creatinine remained stable before conversion, at months 1 and 6 (1.40, 1.43, and 1.46 mg/dL, respectively). Significant adverse effects were reported in 9% of our patients. There were no episodes of acute rejection or graft loss during the study. ConclusionsThe conversion proved to be safe. A drug reduction was necessary to ensure stable renal function and good tolerability.

Antagonism of substance P and perception of breathlessness in patients with chronic obstructive pulmonary disease

The objective of this study was to investigate whether substance P, an excitatory neuropeptide, modulates the perception of breathlessness by administering aprepitant, a selective antagonist that blocks neurokinin (NK)-1 receptor signaling.Individual targeted resistive load breathing (RLB) was used to provoke breathlessness.In Study 1, sixteen patients (age, 70±6 years) with chronic obstructive pulmonary disease (COPD) reported similar ratings of breathlessness during RLB between oral aprepitant (125mg) and placebo. After aprepitant, but not with placebo, there were significant increases in blood levels of substance P (+54±39%) and beta-endorphin (+27±17%). A similar design was used in Study 2 except that naloxone (10mg) was administered intravenously prior to RLB to block any effect of endogenous opioids. Nine patients with COPD reported comparable breathlessness ratings during RLB between aprepitant and placebo.Our results do not support a role for the substance P-NK-1 pathway in the perception of breathlessness in patients with COPD. With selective antagonism of NK-1 signaling, there was co-transmission of substance P and beta-endorphin neuropeptides.

Urban air pollution and effects on biomarkers of systemic inflammation and coagulation: a panel study in healthy adults

Context: Urban particulate air pollution is associated with cardiovascular diseases and mortality, possibly mediated through systemic inflammation and increased blood viscosity.Objectives: To examine short-term effects of exposure to urban air pollution on blood biomarkers for systemic inflammation and coagulation in a panel of healthy adults living in Gothenburg, Sweden.Materials and methods: The 16 volunteers, all non-smokers, median age 35 years, were called for blood sampling the morning after a day with high levels of urban particulate matter (PM10 > 30 µg/m3) or a day with low levels (PM10 < 15 µg/m3 and NO2 < 35 µg/m3). Associations between exposure to air pollution and each biomarker (C-reactive protein, fibrinogen, serum amyloid A, coagulation factor VIII, plasminogen activator inhibitor-1, p-selectin, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, Clara cell protein 16 and surfactant protein D) were examined using a linear mixed-effects model.Results: In total, 12 sampling sessions were performed, six after high-pollution and six after low-pollution days, over 21 months. The ratio of air pollution levels between high- and low-pollution days was five for PM10 (median: 49 and 10 µg/m3) and two for NO2 (median: 47 and 24 µg/m3). No significant increase in blood levels of any of the biomarkers were seen after days with high air pollution levels compared with low levels.Conclusion: Biomarkers of inflammation and coagulation were not found to be significantly increased in the mornings after days with elevated levels of urban air pollution compared with low levels when performing repeated blood samplings in healthy volunteers.

Influence of Metronomic Cyclophosphamide and Interleukine-2 alone or Combined on Blood Regulatory T Cells in Patients with Advanced Malignant Melanoma Treated with Dendritic Cell Vaccines

Background: Interleukine-2 and Cyclophosphamide are known to influence the circulating T cells and are used for immune manipulation in cancer patients. We analyzed the influence on the Treg population in three different dendritic cell (DC) vaccine trials including either concurrent interleukine-2 (IL-2), combined IL-2 and metronomic Cyclophosphamide (MCy), or only MCy.Methods: Melanoma patients received treatment with autologous DCs. IL-2 was applied in trial I and II and MCy was applied in trial I and III. Flowcytometry analysis was performed on fresh drawn blood-samples measuring CD4, CD25 and CD127.Results: In the trials where IL-2 was applied a marked increase in the proportion of CD4+CD25+CD127- Tregs from baseline to the 4th vaccine was observed. This was followed by a decrease, although not to baseline values. Additional analysis showed that the inhibitory function was predominant in the CD49d- subpopulation of Tregs which only increased slightly during treatment. The absolute lymphocyte count (ALC) and the number of CD4+ T cells also increased in these trials. In the trial where only MC was applied the Tregs remained stable throughout the trial whereas decrease in the ALC and CD4+ T cells were observed.Conclusion: We found that adjuvant treatment with low doses of IL-2 during DC vaccination therapy causes a significant increase in blood level of classically defined, CD4+CD25+CD127-, Tregs but far less in the CD49d- subpopulation and that the use of MC was unable to reduce Treg blood level and unable to counteract IL-2 dependent increase in the CD4+CD25+CD127- T cells.These findings have implications for the clinical use of IL-2 as well as MCy as immune modulators.

Bioavailability of a Co-formulated Combination of Amodiaquine and Artesunate under Fed and Fasted Conditions

To assess the effect of food on the pharmacokinetics of the anti-malarial amodiaquine (AQ, CAS 6398-98-7) and artesunate (AS, CAS 182824-33-5) and their active metabolites [desethylamodiaquine (DSA, CAS 81496-81-3) and dihydroartemisinin (DHA, CAS79352-78-6), respectively] in healthy volunteers. In an open, two-way crossover study, 22 healthy male volunteers fasted overnight and were randomised to receive a single oral administration of 4 tablets of a fixed-dose combination containing 135 mg AQ and 50 mg AS in the absence or presence of a standardised high-fat breakfast, administered 30 min before drug administration. Blood samples were collected up to Day 10 and AQ, DSA, AS and DHA were assayed by an LC/MS/MS method. Relative to the fasting state, the administration of the fixed-dose combination after a high-fat breakfast resulted in delayed median Tmax values for AQ (15 min and for DSA (2.3 h). The geometric mean ratios (GMR) of fed to fasting conditions indicated increased Cmax values for AQ (GMR 1.22) (90% CI: 1.07-1.39) and DSA (GMR 1.21) (90% CI: 1.05-1.39) and increased AUC0-t values for AQ (GMR 1.59) (90% CI: 1.39-1.83) and for DSA (GMR 1.13) (90% CI: 1.04-1.24). The median Tmax values were not delayed for AS as opposed to DHA (approximately 1 h delay). The Cmax values were decreased for AS (GMR 0.36) (90% CI: 0.30-0.47) and for DHA (GMR 0.51) (90% CI: 0.44-0.60). The AUC0-t values were slightly decreased for AS (GMR 0.89) (90% CI: 0.74-1.06) and for DHA (GMR 0.93) (90% CI: 0.84-1.02). Intake of AQ and AS with a high fat meal resulted in (1) a statistically significant increase in blood levels of AQ and DSA which may affect the safety and tolerability of the study drugs and (2) a decrease in AS and DHA blood levels which may affect efficacy. These results suggest that the fixed-dose combination should not be administered with a high-fat meal.

The Role of Cadmium as a Causative Agent of Recurrent Abortion in Egyptian Women

ABSTRACT Environmental pollution is one of the ever surging problems receiving careful attention in Egypt, as well as in the world. It has been evidenced that environmental pollutants play an important role in the manifestations of severe reproductive-associated disorders. Among them, an environmental pollutant, Cd, has contributed to several deleterious effects. Maternal exposure to Cd is associated with low birthweight and an increase in spontaneous abortion. Spontaneous abortion is highly frustrating for both patients and physicians. The data from the present study reveal that there was a significant increase in blood level of Cd in the aborter groups as compared to the control group of healthy women. Also there was a significant decrease in serum ferritin, which correlated positively with abortion. Also, plasma levels of malondialdehyde were significantly elevated in aborter groups. There was also a highly significant increase in plasma 8-hydroxyl-2-deoxyguanosine in the aborter groups as compared to the control group, accompanied by a significant decrease in plasma carnosine in aborter groups as compared with the control group. In the same manner there was a reduction in the progesterone hormone in aborter groups. Our results suggest that exposure to Cd is associated with an increased risk of recurrent spontaneous abortion in Egyptian women.

Differential effect of high dietary fat intakes on haemorheological parameters in rats

High dietary intake of fats has been thought to be one of the major risk factors for the development of CVD. Less is known about the possible influence of fats from various sources on haemorheological abnormalities, which are considered an important factor in the pathogenesis of these diseases. The goal of the present study was to investigate effects of high-fat diets enriched in unsaturated fatty acids (USFA), SFA or trans-fatty acids (TFA), respectively, on haemorheological parameters in rats. Wistar female rats were divided into four groups and fed diets based on the AIN-93M formulation containing approximately 10 % energy from soyabean oil (control group) or 40 % energy from soyabean oil (USFA), palm oil (SFA) and vegetable shortening (TFA) for 8 weeks. The results showed that rats fed high-fat diets exhibited significant increases in serum TAG levels (P < 0.01), plasma viscosity (P < 0.01), whole blood viscosity (P < 0.01) and internal viscosity (P < 0.01) compared to the controls. The TFA group showed a significant decrease in erythrocyte deformability (P < 0.01) and increase in internal viscosity (P < 0.01) compared with the other groups. In addition, a significant increase in blood levels of free radicals (P < 0.01) was found in the TFA group, suggesting that the attack of oxygen-free radicals could be responsible for the impaired erythrocyte deformability. These impairments could be partly responsible for the development of various circulatory disorders. The present haemorheological study provides additional insights into the potential adverse effects of trans-fat and high-fat diets on haemorheological parameters.

Effects of ascorbate on monosodium glutamate-associated toxicities that may impact upon immunocompetence

Excitotoxic food additives react with specialized receptors in the brain and other tissues. Unfortunately, in many instances, these reactions lead to free radical generation (resulting in oxidative stress/lipid peroxidation) and altered membrane fluidity. Ultimately, damage induced by these agents was shown to give rise to endocrine disorders and altered cell-mediated immune responses in general, and dysfunction of lymphocytes and macrophages in particular. The effects of ascorbate against some basic toxicities (that ultimately evolve into endocrine and immune system dysfunctions) induced by monosodium glutamate (MSG) was studied in rats. For 21 days, control rats received a daily placebo (4 mL distilled water) via gastric intubation; other rats were treated daily with 100 mg MSG kg−1 body weight or 100 mg MSG + 100 mg ascorbate kg−1 in 4 mL vehicle. A day after the final exposure, rats were euthanized. Serum was isolated to examine several lipid and electrolyte parameters, i.e. cholesterol, triglycerides, VLDL LDL, HDL, Na+, K+, Cl−, and . Rat spleen and thymus were also harvested for analysis. Results showed that, compared to effects from MSG alone, co-ingestion of ascorbate led to reductions in serum cholesterol, LDL, Na+, and K+. Only with serum HDL, ascorbate leads to increases compared to MSG alone. The co-treatment was also seen to block/mitigate the near three-fold rise in thymic and splenic absolute weights (and respective organ indices) produced by exposure to MSG alone. Similarly, MSG treatment also induced significant increases in blood levels of both monocytes/macrophages and eosinophils; these outcomes were again reversed by co-treatment. Data suggest that co-ingestion of ascorbate may help reduce the risk from some toxicities attributable to selective dietary constituents/additives.

Concentrated Ambient Ultrafine Particle Exposure Induces Cardiac Changes in Young Healthy Volunteers

Exposure to ambient ultrafine particles has been associated with cardiopulmonary toxicity and mortality. Adverse effects specifically linked to ultrafine particles include loss of sympathovagal balance and altered hemostasis. To characterize the effects of acute exposure to ambient ultrafine particles in young healthy humans. Nineteen healthy nonsmoking male and female subjects between the ages of 18 and 35 were exposed to filtered air or to an atmosphere in which captured ultrafine (<0.16 microm) particles were concentrated by a factor of up to 20-fold over ambient levels with the use of particle concentrators fitted with size-selective outlets (ultrafine concentrated ambient particles [UFCAPs]). Subjects underwent bronchoalveolar lavage 18 hours after each exposure. Cardiovascular endpoints measured included pulmonary function, clinical chemistry, and hematological parameters, as well as heart rate variability and repolarization indices. Exposure to UFCAPs was statistically associated with an increase in frequency domain markers of heart rate variability, specifically indicative of elevated vagal input to the heart. Consistent with this finding were increases in the variance associated with the duration of the QT interval. In addition, UFCAP exposure resulted in a significant increase in blood levels of the fibrin degradation product D-dimer as well as a modest elevation in the inflammatory chemokine IL-8 recovered in the lavage fluid. These findings show mild inflammatory and prothrombic responses and are suggestive of alterations in cardiac repolarization induced by UFCAP inhalation.

Curcumin Supplementation Lowers TNF-α, IL-6, IL-8, and MCP-1 Secretion in High Glucose-Treated Cultured Monocytes and Blood Levels of TNF-α, IL-6, MCP-1, Glucose, and Glycosylated Hemoglobin in Diabetic Rats

This study examined the hypothesis that curcumin supplementation decreases blood levels of IL-6, MCP-1, TNF-alpha, hyperglycemia, and oxidative stress by using a cell-culture model and a diabetic rat model. U937 monocytes were cultured with control (7 mM) and high glucose (35 mM) in the absence or presence of curcumin (0.01-1 microM) at 37 degrees C for 24 h. Diabetes was induced in Sprague-Dawley rats by injection of streptozotocin (STZ) (i.p., 65 mg/kg BW). Control buffer, olive oil, or curcumin (100 mg/kg BW) supplementation was administered by gavage daily for 7 weeks. Blood was collected by heart puncture with light anesthesia. Results show that the effect of high glucose on lipid peroxidation, IL-6, IL-8, MCP-1, and TNF-alpha secretion was inhibited by curcumin in cultured monocytes. In the rat model, diabetes caused a significant increase in blood levels of IL-6, MCP-1, TNF-alpha, glucose, HbA(1), and oxidative stress, which was significantly decreased in curcumin-supplemented rats. Thus, curcumin can decrease markers of vascular inflammation and oxidative stress levels in both a cell-culture model and in the blood of diabetic rats. This suggests that curcumin supplementation can reduce glycemia and the risk of vascular inflammation in diabetes.

Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study

BackgroundThe purpose of the present investigation was to determine the effects of EPA/DHA supplementation on resting and exercise-induced inflammation and oxidative stress in exercise-trained men. Fourteen men supplemented with 2224 mg EPA+2208 mg DHA and a placebo for 6 weeks in a random order, double blind cross-over design (with an 8 week washout) prior to performing a 60 minute treadmill climb using a weighted pack. Blood was collected pre and post exercise and analyzed for a variety of oxidative stress and inflammatory biomarkers. Blood lactate, muscle soreness, and creatine kinase activity were also measured.ResultsTreatment with EPA/DHA resulted in a significant increase in blood levels of both EPA (18 ± 2 μmol·L-1 vs. 143 ± 23 μmol·L-1; p < 0.0001) and DHA (67 ± 4 μmol·L-1 vs. 157 ± 13 μmol·L-1; p < 0.0001), while no differences were noted for placebo. Resting levels of CRP and TNF-α were lower with EPA/DHA compared to placebo (p < 0.05). Resting oxidative stress markers were not different (p > 0.05). There was a mild increase in oxidative stress in response to exercise (XO and H2O2) (p < 0.05). No interaction effects were noted. However, a condition effect was noted for CRP and TNF-α, with lower values with the EPA/DHA condition.ConclusionEPA/DHA supplementation increases blood levels of these fatty acids and results in decreased resting levels of inflammatory biomarkers in exercise-trained men, but does not appear necessary for exercise-induced attenuation in either inflammation or oxidative stress. This may be due to the finding that trained men exhibit a minimal increase in both inflammation and oxidative stress in response to moderate duration (60 minute) aerobic exercise.