Indicators of stress hematopoiesis in the blood predict COVID-19 progression in patients over 65 years old.

OBJECTIVES: Advanced age is a well-established risk factor for severe coronavirus disease 2019 (COVID-19). Exacerbated inflammation affects multiple organs, among which hematopoiesis responds by increased output of various cells. We aimed to determine the association between COVID-19 progression and large immature cell (LIC) counts, changes in erythrocyte and platelet distribution widths (RDW, PDW) with reference to patients' age. METHODS: A total of 755 patients with complete blood cell (CBC) analysis in the first 24 h of hospitalization were enrolled. Patients were divided into two groups: under and above 65 years of age. RESULTS: The LIC counts were different in both groups (p < 0.003). However, only the senior patients had markedly different values of RDW and PDW (p < 0.001). The receiver operating characteristic (ROC) curve analysis provided increased LIC (AUC = 0.600), RDW (AUC = 0.609), PDW (AUC = 0.556), and platelet to LIC ratio (AUC = 0.634) as significant in discriminating outcome in the older group. Importantly, these results were not repeated in the younger patients. In the elderly, the progression was predicted with LIC cut-off at ≥ 0.305 × 109/L (OR = 3.166) and RDW over 12.15% (OR = 2.081). DISCUSSION: Aging is characterized by a decline in immunological competence with a compromised control of inflammation leading to a proinflammatory state. This background together with the actions of pathogens may lead to emergency myelopoiesis. CONCLUSION: Our results point to the important differences between age groups regarding CBC-related parameters of stress hematopoiesis during severe infection. Higher LIC, RDW and PDW levels were reliable in the early identification of COVID-19 progression only in the elderly.

Platelet-derived immuno-inflammatory indices show best performance in early prediction of COVID-19 progression.

BACKGROUND: Coronavirus disease 2019 (COVID-19) profoundly affects the immune and hematopoietic systems with various degrees of reactive changes in the blood cell counts. Immuno-inflammatory indices are considered a simple and effective tool in the prediction of COVID-19 outcomes. We aimed to evaluate and compare the usefulness of leukocyte and platelet counts-based immuno-inflammatory indices on admission to hospital in predicting COVID-19 progression and mortality. METHODS: A total of 945 patients were enrolled. In addition to blood cell counts, we assessed hemogram-derived immuno-inflammatory indices in relation to COVID-19 progression and death. The indices were tested by analysis of variance, receiver operating characteristic curve analysis, and binomial logistic regressions. RESULTS: Patients with severe COVID-19 had significantly higher counts of neutrophils, eosinophils, and large immature cells (LIC), while decreased counts of platelets and monocytes. Lymphopenia was found in all of the patients, but without significant association with the outcomes. Patients with a LIC count ≥0.265 x 09 /L had 54.7% more odds of having COVID-19 progression. In multivariable analyses, platelets/neutrophil-to-lymphocyte ratio (P/NLR) and platelets-to-neutrophil radio (P/N) were significant independent predictors of COVID-19 progression and mortality. The odds of a poor outcome were two times higher in cases with P/NLR < 43 x 109 /L and P/N < 29 x 109 /L. CONCLUSION: Indices that include platelet count in combination with neutrophil and/or lymphocyte counts displayed the best discriminatory ability and prognostic value of COVID-19 outcomes. Additionally, LIC showed promising results in the early identification of severe COVID-19.

Vitamins, microelements and the immune system: current standpoint in the fight against coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease associated with severe systemic inflammation. The optimal status of vitamins and microelements is considered crucial for the proper functioning of the immune system and necessary for successful recovery. Most patients with respiratory distress in COVID-19 are vitamin and microelement deficient, with vitamin D and Se deficiency being the most common. Anyway, various micronutrient supplements are widely and arbitrarily used for prevention or in the treatment of COVID-19. We aimed to summarise current knowledge about molecular and physiological mechanisms of vitamins (D, A, C, B6, B9 and B12) and microelements (Se, Zn, Cu and Fe) involved in the immune system regulation in consideration with COVID-19 pathogenesis, as well as recent findings related to their usage and effects in the prevention and treatment of COVID-19. In the early course of the pandemic, several, mainly observational, studies reported an association of some micronutrients, such as vitamin C, D and Zn, with severity reduction and survival improvement. Still, emerging randomised controlled trials showed no effect of vitamin D on hospitalisation length and no effect of vitamin C and Zn on symptom reduction. Up to date, there is evidence neither for nor against the use of micronutrients in the treatment of COVID-19. The doses that exceed the recommended for the general population and age group should not be used, except in clinical trials. Benefits of supplementation are primarily expected in populations prone to micronutrient deficiencies, who are, as well, at a higher risk of worse outcomes in COVID-19.

Black chokeberry Aronia melanocarpa extract reduces blood pressure, glycemia and lipid profile in patients with metabolic syndrome: a prospective controlled trial.

The aim of the study was to examine the effect of 4-week supplementation of Alixir 400 PROTECT® (Standardized Aronia L. Melanocarpa Extract Extract-SAE) on clinical and biochemical parameters in patients with confirmed metabolic syndrome (MetS). This study was designed as a prospective open-label clinical case-series study with 28 days of follow-up with cases selected and followed during the period from February 1, 2018 to November 2019. The study included 143 male and female patients with MetS who were subjected to SAE. SAE supplementation significantly altered SP, BP as well as HR values. After 2 weeks, CHOL levels significantly decreased in the fMetS-DM group compared to the baseline values in this group, while the LDL levels significantly decreased in the fMetS group. Triglycerides significantly decreased only after 4 weeks of SAE treatment in diabetic groups of patients (fMetS-DM and mMetS-DM) compared to the baseline, while in non-diabetic groups this marker was not significantly altered. Increased polyphenols or SAE consumption is correlated with a positive effect on body weight, total cholesterol, low and high-density lipoproteins, blood pressure and glycemia. Increasing consumption of polyphenol-rich foods could be a promising strategy to reduce cardiovascular risk.

Effects of silica-rich water on systemic and peritoneal inflammation in rats exposed to chronic low-level (900-MHz) microwave radiation.

Immunomodulating effect of silica-rich water represents a novel field for research, especially regarding its features toward environmental pollutants. The aim of our study was to evaluate the effects of silica-rich water intake on systemic and peritoneal inflammation in rats that were chronically exposed to the low-level microwave (MW) radiation from mobile phones. Wistar Albino rats were exposed to 900 MHz MW radiation for 3 months. The four-treatment model involved rats with standard water (SW) or experimental silica-rich water intake (EW). Peritoneal macrophages (PMs) were harvested using peritoneal lavage and divided into non-stimulated and lipopolysaccharide (LPS) stimulated subgroups. The MW-exposed rats with silica-rich water (MW+EW) had lower serum tumor necrosis factor α (TNF-α) and interleukin 2 (IL-2) levels, but higher IL-10 levels, than MW+SW rats (p < 0.05). The higher TNF-α production by non-stimulated MW exposed PMs was ameliorated by the silica-rich water (p < 0.01). The MW exposition suppressed LPS potential for TNF-α synthesis in both water type groups, with greater suppression in animals that took standard water. Our results show the modulating effect of silica-rich water toward MW-induced systemic and peritoneal inflammation, which reflects the water ability to shape monocyte plasticity, thereby altering the balance between their proinflammatory and anti-inflammatory properties.

Improvements in long standing cardiac pathologies by individualized homeopathic remedies: A case series.

We present three cases of cardiac arrest at different stages of pathology. Acute myocardial infarction and resulting heart failure is emerging as the leading cause of mortality. In the long run, acute episodes and cardiac remodelling can cause considerable damage and result in heart failure. In these cases, individualized homeopathic therapy was instituted along with the conventional medicines and the results were encouraging. The changes in the laboratory diagnostic parameters (single-photon emission computed tomography, electrocardiograph, echocardiography and ejection fraction as the case may be) are demonstrated over time. The key result seen in all three cases was the preservation of general well-being while the haemodynamic states also improved. While the three cases provide evidence of positive outcomes for homeopathic therapy, more extensive studies are required in a hospital setting to establish the real extent to which this therapy may be employed.

Effect of silicon-rich water intake on the systemic and peritoneal inflammation of rats with chronic low levels of aluminum ingestion.

BACKGROUND AND OBJECTIVES: Study evaluated effect of silicon-rich water intake on systemic inflammation and functional characteristics of peritoneal macrophages (PMs) of rats that were chronically exposed to dietary aluminum. METHODS: One month-old female Wistar Albino rats were administered aluminum chloride dissolved in distilled water (1.6mg/kg body weight in 0.5mL) by gavage for 90days. The rats were then given standard (6mg/L) or silicon-rich water (19mg/L silicon) (n=7/group). Control rats underwent sham gavage and received standard or silicon-rich water (n=7/group). Blood was assessed for cytokine levels. Unstimulated and lipopolysaccharide (LPS)-stimulated PMs were assessed in terms of phagocytic activity and cytokine secretion in vitro. RESULTS: Chronic exposition to dietary aluminum and silicon-rich drinking water did not change serum TNF-α levels. Aluminum increased serum IL-2 and this was reversed by silicon-rich water. The aluminum-exposed rats had higher serum sICAM-1 than sham-gavaged, unrelated to type of water. LPS-stimulated PMs from aluminum-intoxicated animals exhibited low phagocytic activity and release of TNF-α, this was significantly improved by silicon-rich water intake. In the presence of silicon-rich water, LPS-stimulated and unstimulated PMs from aluminum-exposed rats produced significantly more IL-10. CONCLUSIONS: Chronic ingestion of aluminum, increases systemic and peritoneal inflammation and PM dysfunction. The presence of high levels of the natural aluminum antagonist silicon in the drinking water restored IL-10 and TNF-α PM secretion, preventing prolonged inflammation. Thus, silicon intake can decrease the immunotoxicity of aluminum.

Mechanisms of plasminogen activator inhibitor 1 action in stromal remodeling and related diseases.

Plasminogen activator inhibitor type 1 (PAI-1) is the main physiologic inhibitor of fibrinolysis. However, it is also involved in many physiological processes such as extracellular matrix (ECM) proteolysis and remodeling, cell adhesion, motility, and apoptosis, angiogenesis, etc. The aim of the study was to summarize current knowledge and gain insights into the mechanisms of PAI-1 action in the processes of stromal remodeling and diseases with considerable matrix pathologies (atherosclerosis, tissue fibrosis, cancer metastasis, pregnancy related complications, etc). As a component of an early cellular response to injury, PAI-1 reacts with membrane surface proteins and participates in the initiation of intracellular signaling, specifically cytoskeletal reorganization and motility. Complexity of ECM homeostasis resides in varying relation of the plasminogen system components and other matrix constituents. Inflammatory mediators (transforming growth factor-ß and interferon-γ) and hormones (angiotensin II) are in the close interdependent relation with PAI-1. Also, special attention is devoted to the role of increased PAI-1 concentrations due to the common 4G/5G polymorphism. Some of the novel mechanisms of ECM modification consider PAI-1 dependent stabilization of urokinase mediated cell adhesion, control of the vascular endothelial cadherin trafficking and interaction with endothelial cells proteasome, its relation to matrix metalloproteinase 2 and osteopontin, and oxidative inhibition by myeloperoxidase. Targeting and/or alteration of PAI-1 functions might bring benefit to the future therapeutic approaches in diseases where ECM undergoes substantial remodeling.

Nitric oxide synthesis modulation - a possible diagnostic and therapeutic target in colorectal cancer.

PURPOSE: Considering the contradictory literature data about the role of nitric oxide (NO) in colon carcinogenesis, the purpose of this study was to examine the changes of L-arginine metabolites in colon cancer and surrounding tissue as possible molecular markers of tumor behavior after surgery and the possibility of NO synthesis modulation in new individualized therapeutic strategies. METHODS: The study encompassed 50 patients who underwent surgery for colorectal cancer (CRC). The three tissue specimens were taken by surgery (tumor, adjacent and healthy tissue) and the concentrations of NO2+NO3, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in the tissue specimens. RESULTS: The results proved higher NO2+NO3 concentrations in adjacent tissue compared to the tumor, implicating high angiogenic potential of the tumor-surrounding tissue, which could have clinical importance in the assessment of the probability of tumor local recurrence and metastasis. Increased ADMA concentrations in tumor tissue associated with low NO levels, could lead to new therapeutic strategies directed to the use of inhibitors of NO synthesis as ideal candidates for molecular therapy of CRC. ADMA concentration in adjacent tissue was an independent predictor of distant metastasis. CONCLUSIONS: The obtained results suggest that determination of the examined biomarkers in CRC and adjacent tissue samples could give useful information about tumor proliferative and angiogenic potential, which in turn could enable individualization of therapy and the choice of proper adjuvant therapy in patients with CRC.

The contributions of fasting and postprandial blood glucose increments to oxidative stress and inflammation in dyslipidemic type 2 diabetic patients with stable ischemic heart disease.

BACKGROUND/OBJECTIVES: Contributions of fasting and postprandial blood glucose increments on level of inflammation and oxidative stress biomarkers in patients with stable ischemic heart disease (IHD) and diabetes mellitus type 2 (T2DM) was evaluated. METHODOLOGY: Ninety T2DM patients (60 with IHD and 30 without IHD) treated with metformin and/or sulphonylurea were enrolled in cross-sectional nested case-control clinical study. The areas under the six-point daily glucose curve above the fasting glucose concentrations (AUCpp) and over 5.5mmol/L (AUCbg) were calculated to determine postprandial (AUCpp) and fasting (AUCbg-AUCpp) glucose increments. Malondialdehyde (MDA), protein carbonyl group (PCO), fibrinogen, C-reactive protein (hsCRP), leukocyte count and adhesion molecules ICAM-1 and VCAM-1 were determined. RESULTS: AUCbg-AUCpp 58.2 (95%CI 40.6-75.8) was higher in IHD group compared to non-IHD 36.9 (95%CI 23.5-50.2) mmol*h/L. They had significantly higher ICAM-1 (mean±SD) 72.70±30.6 vs. 60.22±22.6ng/mL and MDA 16.47±4.5 vs. 13.42±4.01µmol/g plasma proteins, but similar PCO, VCAM-1, fibrinogen, hsCRP concentration and leukocyte count. AUCpp positively correlated with MDA (r=0.45) and ICAM-1 (r=0.32) in the presence of IHD, and VCAM-1 (r=0.44) in the absence of IHD. AUCbg-AUCpp positively correlated with PCO (r=0.45) in the absence of IHD. The analysis revealed that AUCpp over turning point of 0mmol*h/L was associated with high MDA and ICAM-1 expression in diabetics with IHD. AUCbg-AUCpp over 30mmol*h/L leads to high oxidative protein modification in diabetics without IHD. CONCLUSION: In T2DM patients with stable IHD, AUCpp at any point, significantly contributes to increasing of MDA and ICAM-1 expression. Fasting blood glucose increment showed significant correlation with carbonyl content in diabetics without IHD.

Experimental closure of gunshot wounds by fibrin glue with antibiotics in pigs.

BACKGROUND/AIM: Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, after the primary surgical management, were closed with delayed primary suture during the next four to seven days. This period coincides with the fibroblastic phase of wound healing. Fibrin glue is used as a local hemostatic and as a matrix for the local dosed release of antibiotics. Antibiotics addition to fibrin glue resulted in continuous diffusion into the surrounding next 4 to 7 days. The aim of this study was to create the preconditions for gunshot wounds closing without complications by the application of fibrin glue with antibiotics 24 h after primary surgical treatment. METHODS: A total of 14 pigs were wounded in the gluteofemoral region by the bullet M67, initial velocity of 720 m/s. All wounded animals were surgically treated according to the principles of the war-surgery doctrine. Seven wounds were closed with primary delayed suture four days after the primary surgical treatment (traditional approach). Fibrin glue with antibiotics was introduced in seven wounds during the primary surgical treatment and primary delayed suture was done after 24 h. The macroscopic appearance and the clinical assessment of the wound were done during the primary surgical treatment and during its revision after 24 h, as well as histopathological findings at the days 4 and 7 after wounding. RESULTS: Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, and treated with fibrin glue with antibiotics after primary surgical management, were closed with primary delayed suture after 24 h. In further wound evolution there were no complications. CONCLUSION: Uncomplicated soft-tissue wounds caused by an automatic M70AB2 rifle may be closed primarily with delayed suture without the risk of developing complications if on revision, 24 h after primary surgery, there were no present necrotic tissues, hematoma, and any signs of infection when fibrin glue with antibiotics (ceftriaxone and clindamycin) was applied. The use of this method should be limited to individual and strictly controlled cases in civil practice for now.

The Effects of Transition from Bedtime to Morning Glargine Administration in Patients with Poorly Regulated Type 1 Diabetes Mellitus: Croatian Pilot Study.

INTRODUCTION: The objective of this study was to compare differences in glucoregulation, frequency of hypoglycemic episodes, glucose variability and lipid profiles of inpatients with poorly regulated type 1 diabetes mellitus (T1DM) after evening versus morning glargine application. METHODS: Eighteen patients with poorly regulated T1DM, glycated hemoglobin (Hba1c) levels ≥7% and frequent nocturnal and/or morning hypoglycemic episodes were included in this study. There was a 12-week screening phase where patients continued their usual insulin regimen and were encouraged to achieve optimal glycemic control; however, all patients maintained HbA1c values ≥7% and continued to have frequent nocturnal and/or morning hypoglycemic events and were therefore transitioned to morning application of insulin glargine for 12 weeks. The primary outcome was to investigate changes in HbA1c values 12 weeks after the transition. The secondary outcome was to evaluate the effect of transition on glucose variability, incidence of hypoglycemic episodes, insulin doses, lipid profile and weight. Data were analyzed using paired Student's t test and Pearson correlation. RESULTS: After the transition, there was no significant change in total daily dose of basal insulin (p 0.114) and the average body weight remained unchanged, while significant reduction of HbA1c was present (8.02 ± 0.5 vs. 7.4 ± 0.3%) (p < 0.01) resulting in a decrease in nocturnal and daytime hypoglycemic episodes per month per person (p < 0.01). Parameters of glucose variability (glycemic standard deviations and J-index) were also improved after transition period (p < 0.01). As for the lipid profile, increase of high-density lipoprotein cholesterol and decrease of triglycerides (p < 0.01) were noticed, while other lipid parameters remained unaffected. Furthermore, insignificant association of basal insulin dose with HbA1c values regardless of the time of administration was observed. CONCLUSION: In patients with poorly regulated T1DM, transition to morning application of glargine improved glucoregulation (including a decrease in HbA1c, glucose variability and number of nocturnal hypoglycemic episodes), followed by favorable changes in lipid profile without affecting body weight. These effects were associated with the time of application, but not with the insulin dose.

Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease.

Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p<0.001), while ADP and AMP were significantly increased in both groups of patients compared with control healthy individuals (p<0.001), together with their final degradation product, uric acid (p<0.001). The index of ATP/ADP and ATP/uric acid showed gradual significant fall in both the groups, compared with the control value (p<0.001), near five times in a group on dialysis. Total XOD was up-regulated significantly in a group with essential hypertension, more than in a group on dialysis. The activity of XO, which dominantly contributes reactive oxygen species (ROS) production, significantly increased in dialysis group, more than in a group with essential hypertension. In conclusion, the examination of the role of circulating purine nucleotides and uric acid in pathogenesis of hypertension and possible development of renal disease, together with XO role in ROS production, may help in modulating their liberation and ROS production in slowing progression from hypertension to renal failure.

Work stress related lipid disorders and arterial hypertension in professional drivers - a cross-sectional study.

BACKGROUND/AIM: Occupational stress is a term used to define ongoing stress that is related to the workplace. The study was conducted to determine association of occupational stress index (OSI) and its aspects with arterial hypertension and lipid disorders using data from a cross-sectional survey of male professional drivers. METHODS: The cross-sectional study was performed in 439 professional drivers divided into groups (city- and intercity bus drivers, truck and taxi drivers). The OSI and OSI aspects (high demands, strictness, underload, extrinsic time pressure, noxious exposure, avoidance and conflict) were calculated using the standardized questionnaire. Determination of serum lipids, blood pressure (BP) and cardiovascular risk factors were done. RESULTS: A significant difference in prevalence of diagnosed hypertension and dyslipidemia was found along with a difference in total OSI and OSI aspects among examined subgroups of drivers. A total OSI was highest in city, high in intercity bus drivers, and the lowest one in truck and taxi drivers (82.79 +/- 3.5, 81.28 +/- 3.7, 73.75 +/- 3.5, 71.61 +/- 4.4, respectively; p < 0.01). Similar pattern showed triglycerides (TG), total cholesterol (TC) and LDL cholesterol and BP, while HDL-cholesterol showed reverse order (p < 0.01). Logistic regression analyses with multiple OSI aspects adjusted for age and years of exposure showed associations of total OSI with arterial hypertension [OR 5.5; 95% CI (2.24-7.95)] and dyslipidemia [OR 1.43 95% CI (1.09-2.80)]. Underload was the most important OSI aspect associated with the arterial hypertension [OR 1.18; 95% CI (1.04-2.58)] and elevated LDL cholesterol [1.26; 95 CI (1.19-2.1)]. A total OSI had a significant association with elevated LDL cholesterol [2.64; 95% CI (1.19-7.7)], triglycerides [OR 3.27; 95% CI (1.20-5.1)] and low HDL cholesterol [OR 3.29; 95% CI (1.8-5.8)] (p < 0.01). CONCLUSION: The study provides the evidence for the significant association of total OSI and underload with lipid disorders and elevated blood pressure in professional drivers, which could be a possible link between job stress and coronary heart disease. Regular periodical examinations and workplace interventions aimed to decrease total OSI and underload are important aspects in primary prevention and additional reduction of cardiovascular risk.

Diagnostic significance of nitrates and nitrites and L-arginine, in development of hepatorenal syndrome in patients with end stage alcoholic liver cirrhosis.

Hepatorenal syndrome (HRS) represents a complication of the end-stage liver cirrhosis. The aim of the present study was to analyze concentrations of nitrates and nitrites (NO2 + NO3) and L-arginine in patients with liver cirrhosis and HRS as a possible predictive marker for the development of HRS. The research was performed in a group of 28 patients with cirrhosis and HRS, a group of 22 patients suffering from cirrhosis without HRS and a control group comprised of 42 healthy voluntary blood donors. In patients with end-stage alcoholic liver cirrhosis, with HRS, the concentrations of NO2 + NO3 increased and correlated with the degree of cirrhosis progression, compared to patients without HRS and significantly higher compared to the control group. The level of NO2 + NO3 was in a positive correlation with the degree of liver damage de Ritis coefficient (HRS = 0.72; cirrhosis: = 0.55; control = -0.10). Significant positive correlation was found between NO2 + NO3 concentration and inflammatory marker C-reactive protein (HRSC = 0.75; cirrhosis = 0.70, control = -0.25). The correlation between NO2 + NO3 concentration and creatinine concentration in patients with HRS was significantly higher compared to patients without HRS (HRS = 0.82; cirrhosis = 0.32; control = -0.25). By using binary regression analysis, on the basis of clinical criteria of HRS diagnosis, the strongest independent positive predictor for HRS development was NO2 + NO3, associated with 45.02 times higher incidence of HRS, compared to arginine (12.7 times higher incidence), creatinine (13.1 times higher incidence), and AST/ALT ratio (10.55 higher incidence of HRS). Since the determination of NO2 + NO3 represents a reliable and easily applicable method, it may be used as an early predictive marker for HRS development.

Correlation of inflammation parameters and biochemical markers of cholestasis with the intensity of lipid peroxidation in patients with choledocholithiasis.

BACKGROUND/AIM: During choledocholitiasis inflammatory oxidant stress involves the promotion of mitochondrial dysfunction through an intracellular oxidant stress in hepatocytes leading mainly to necrosis and less to apoptosis. The product of oxidative stress, malondialdehyde (MDA), is extremely cytotoxic and damages cell membranes and intracellular macromolecules. The toxicity of MDA is based on its ability to act as a mutagenic agent in a cell. Therefore, the aim of this prospective study was to establish correlation of the parameters of inflammation and biochemical markers of cholestasis with the intensity of oxidative stress in pathogenesis of liver function disorders. METHODS: Seventy adult subjects of either sex included in the study were devided into two groups: I--40 patients with obstructive icterus caused by choledocholithiasis, and II--30 healthy individuals. All the participants were subjected to a clinical, laboratory and ultrasonic check-up at the Internal Department of the Military Hospital in Nis. The parameters of oxidative stress: MDA, a measure of lipid peroxidation, and inflammation parameters: C-reactive protein (CRP), fibrinogen, albumins, number of leukocytes (Leu), granulocytes (Gr), lymphocytes (Ly) and monocytes (Mo) and biochemical markers of cholestasis: activity of gamma-glutamyltransferase (gamma-GT) and alkaline phosphatase (AP) enzymes, the level of total, direct and indirect bilirubin were determined by standard biochemical methods. RESULTS: Lower values of albumin (p < 0.001), and significantly higher values of fibrinogen (p < 0.05) and CRP (p < 0.001) were found in the blood of the patients with cholestasis due to choledocholithiasis in relation to the controls. Significantly higher values of Leu (p < 0.01) and Gr (p < 0.001) with decreasing number of Ly (p < 0.001) and Mo (p < 0.001) were found in blood of the patients with cholestasis due to choledocholithiasis in relation to the control. Similarly, higher values of gamma-GT, and AP (p < 0.001), as well as the level of total, direct and indirect bilirubin (p < 0.001) were found in blood of the patients with cholestasis due to choledocholithiasis in relation to the controls. The concentration of MDA (p < 0.001) was increased in the patients with choledocholithiasis in relation to the controls. There was a significant positive linear correlation of the number of leukocytes (r = 0.51, p < 0.05) and the concentration of total (r = 0.87, p < 0.01), direct (r = 0.85, p < 0.01) and indirect (r = 0.88, p < 0.01) bilirubin with the concentration of MDA in the group of patients with choledocholithiasis. CONCLUSION: Neutrophils and the levels of total, direct and indirect bilirubin have a significant positive linear correlation with the level of lipid peroxidation in patients with choledocholithiasis. Neutrophilia and hiperbilirubinemia observed in this way represent important parameters in estimating the level of liver tissue damage in choledocholithiasis.

Relationship of adipokine to insulin sensitivity and glycemic regulation in obese women--the effect of body weight reduction by caloric restriction.

BACKGROUND/AIM: Visceral fat is highly active metabolic and endocrine tissue which secretes many adipokines that act both on local and systemic level. It is believed that adipokines and "low-grade inflammatory state" represent a potential link between obesity, metabolic syndrome, insulin resistance and cardiovascular disease. Leptin and adiponectin are considered to be the most important adipokines with the potential metabolic and cardiovascular effects. Body weight loss improves insulin sensitivity and decreases risk for most complications associated with obesity. The aim of this study was to determine the effects of moderate loss of body weight on the level of leptin and adiponectin, insulin sensitivity and abnormalities of glycoregulation in obese women, to determine whether and to what extent the secretory products of adipose tissue, leptin and adiponectin contribute to insulin sensitivity, as well as to assess their relationship and influence on glycemia and insulinemia during the period of losing body weight using a calorie restricted diet. METHODS: The study involved 90 obese female subjects (BMI > or = 30 kg/m2) of different age with weight loss no less than 5% during a six-month period by application of restricted dietary regime. The calorie range was between 1,100-1,350 kcal. Serum levels of leptin and adiponectin, fasting glucose, fasting insulinemia, and Homeostasis Model Assessment of Insulin Resistance (HOMA-R) index were determined in all the subjects initially and after weight reduction. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test--OGTT. RESULTS: Applying a 6-month restrictive dietary regime the subjects achieved an average weight loss of 8.73 +/- 1.98 kg and 8.64 +/- 1.96%, which led to the reduction of fasting glycemia, fasting insulinemia and HOMA-R index at the maximum level of statistical significance (p < 0.001). The achieved reduction led to a statistically significant decrease of leptin level and increase of adiponectin level (p < 0.001). The correction of the established pre-diabetic disorders of glycoregulation was not statistically significant. There was a statistically significant correlation between the anthropometric parameters, leptin, adiponectin, fasting glycemia, fasting insulinemia and HOMA-R index. There was a positive correlation between leptin, fasting insulinemia and HOMA-R, as well as a statistically significant negative correlation between adiponectin, fasting insulinemia and HOMA-R index (p < 0.01). CONCLUSION: Body weight increase and central fat accumulation lead to changes in serum levels of leptin and adiponectin, reduction of insulin sensitivity and development of glycemic dysregulation. Secretory products of adipose tissue, leptin and adiponectin contribute to the genesis of these disorders. The obtained results show that the effect of adiponectin on insulin sensitivity is more significant. The analysis of the effects of weight loss on the investigated parameters shows that moderate weight reduction by restrictive dietary regime lead to changes of investigated parameters at the maximum level of statistical significance. Such results emphasize the importance of weight reduction in obese persons, as well as the need for consistent implementation of restricted dietary regime in the process of treatment of obesity.

Melatonin protects rat thymus against oxidative stress caused by exposure to microwaves and modulates proliferation/apoptosis of thymocytes.

The aim of the study was to evaluate the effect of melatonin on oxidative stress, DNA fragmentation, apoptsis and proliferation in thymus tissue of rats exposed to microwaves. Wistar rats were divided in four groups: I - treated with saline; II - treated with melatonin; III - microwaves exposed; IV - microwaves exposed and melatonin treated. Melatonin (2 mg/kg i.p.) was administered daily. Animals were sacrificed after 20, 40 and 60 days. A significant increase in malondialdehyde and carbonyl group content, as well as decrease in catalase and increase in xanthine oxidase activity were registered under microwave exposure. Melatonin prevented the increase in malondialdehyde and carbonyl group content, and reversed the effect on catalase and xanthine oxidase activity. Both, alkaline and acid DNase activity were increased due to microwave exposure. Furthermore, microwaves caused increase in apoptosis rate (detected using Annexin V-FITC/PI kit) and reduced proliferative capacity of thymocytes (induced by ConA). However, melatonin caused decrease in alkaline and acid DNase activity, decrease in apoptotic rate and increase in proliferation rate of thymocytes. Melatonin exerts protective effects on rat thymocytes by modulating processes of apoptosis and proliferation, and causes decrease in DNA fragmentation and oxidative stress intensity under exposure to microwaves.

Associations between the occupational stress index and hypertension, type 2 diabetes mellitus, and lipid disorders in middle-aged men and women.

INTRODUCTION: Retrospective and prospective studies show that stress at work is linked to an increased risk of hypertension, diabetes mellitus, and coronary heart disease. However, the nature of the contributory job stressors and biological mechanisms need further elucidation. OBJECTIVES: The study is aimed to determine the associations between aspects of the occupational stress index (OSI) and arterial hypertension, diabetes mellitus (DM) type 2, and lipid disorders in working middle-aged men and women. METHODS: The cross-sectional study involved 989 middle-aged men and women in different occupations. The OSI was calculated by using standardized questionnaires. The total participation rate was 93%. Occupational stressors were divided into seven groups: High Demands, Strictness, Underload, Extrinsic Time Pressure, Noxious Exposure, Avoidance, and Conflict/Uncertainty. Serum lipid levels, glucoregulation, blood pressure, and cardiovascular risk factors were measured. RESULTS: For both women and men, the total OSI score associated significantly with DM (women: odds ratio [OR] 2.4, 95% confidence intervals [CI] 1.67-3.45; men: 1.21, 1.15-1.45), any type of dyslipidemia (women: 1.54, 1.17-2.03; men: 1.31, 1.24-1.39), and arterial hypertension (women: 1.15, 1.10-1.21; men: 1.58, 1.49-1.68). The group as a whole showed associations between total OSI and low high-density lipoprotein (HDL) cholesterol, high total cholesterol, and high triglyceride levels. Of the OSI aspects, Underload associated significantly in both men and women with arterial hypertension (women: 3.48, 1.91-6.31; men: 2.71, 1.96-3.75) and dyslipidemia (women: 3.26, 2.13-4.99; men: 2.11, 1.76-2.52). Underload was also associated with several lipid abnormalities in the group as a whole. It associated with DM in women only (4.7, 2.84-7.81). All remaining OSI aspects also associated significantly and positively with DM in women only. Conversely, in male workers, but not female workers, High Demand, Conflict/Uncertainty, and Extrinsic Time Pressure associated significantly with arterial hypertension. Strictness and Conflict/Uncertainty associated positively with dyslipidemia in women only. Noxious Exposures associated positively with DM and arterial hypertension in women only. CONCLUSIONS: The study provides evidence for the association of work stress with metabolic disorders and hypertension. Total OSI associated significantly with DM type 2, arterial hypertension, and dyslipidemia in both genders. Different OSI aspects associated with these health issues in gender- and occupational-specific patterns. Underload, which represents lack of social communication, simple task preparation, and underestimation of working results, associated most strongly of all OSI aspects with disease in both the sexes.