Metabolic syndrome and its association with the Dietary Inflammatory Index (DII)® in a Croatian working population.

BACKGROUND: Metabolic syndrome (MetS) is a global public health concern, although its association with the inflammatory potential of the diet is still indefinite. The main objective of the present study was to investigate the association of MetS and its components with the inflammatory potential of the diet in a Croatian working population with sedentary occupations. METHODS: In a cross-sectional study, Croatian workers (n = 366) self-administrated questionnaires for sociodemographic and health-related data. Their anthropometric measurements and fasting blood samples were collected for evaluation of MetS. The inflammatory potential of the diet was assessed with a Dietary Inflammatory Index (DII)® , scored using dietary data collected from a food frequency questionnaire. Multivariable logistic regression analysis, adjusted for sex, age, body mass index, education, smoking, physical activity and energy intake, was used to establish the association between DII and MetS. RESULTS: MetS prevalence was 25% and was significantly associated with a pro-inflammatory diet [mean (SD) 3.28 (1.45); P < 0.01]. The pro-inflammatory diet was statistically associated with women, university degree, moderate physical activity, snacking between meals, central obesity, hypertriglyceridaemia, hypertension, low high-density lipoprotein-cholesterol, MetS prevalence and lower adherence to a Mediterranean diet. Multivariable logistic regression analysis showed a statistically positive association for a one-unit increase in the DII and MetS prevalence (odds ratio = 2.31; 95% confidence interval = 1.61-3.31; P < 0.01) and hypertension (odds ratio = 1.28; 95% confidence interval = 1.01-1.64; P = 0.04). CONCLUSIONS: Further longitudinal studies in different parts of Croatia, including inflammation biomarkers, are needed to enable a more defined view of the inflammatory potential of a diet and its association with various inflammatory-based health conditions. The results obtained in the present study indicate the need for the development of anti-inflammatory dietary interventions for population health protection.

Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell Immunity in the Global Burden of Atherosclerosis.

Changes in immune and inflammatory responses may play a crucial role in the development and progression of atherosclerosis, as an autoimmune, chronic and progressive inflammatory disease. Immunological activity and vascular inflammation during atherosclerosis can be modulated by autoimmune responses against self-antigens, according to changeable risk factors (cholesterol, oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids, etc.), and accompanied by accumulation of leucocytes and proinflammatory cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs), whose concentration are increased in foam cell-rich regions. Regulatory T cells (Tregs) represent a unique subpopulation of T cells specialized in the regulation of immune response and in the suppression of proatherogenic T cells. The aim of our study was to examine the interactions between the concentration of enzyme matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of Tregs in peripheral blood of two groups of patients: with carotid artery stenosis (CAS), undergoing surgery and with mild atherosclerosis (A) from general practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme MMP expression, and Tregs was examined by flow cytometric analysis. Our data have showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A patients in comparison with healthy controls and indicated this method as an easy marker for the monitoring of the development of atherosclerosis. Simultaneously, the diminished number of Tregs in the same patients pointed the importance of these regulatory mechanisms in the etiopathogenesis of atherosclerosis and possible Tregs-mediated therapy.

[DIET CHARACTERISTICS IN PATIENTS WITH CHRONIC KIDNEY DISEASE].

Because of the increasing number of patients, chronic kidney disease (CKD) has become a significant public health problem. As kidney function decreases, it is necessary to introduce certain dietary modifications. The aim was to investigate what is the appropriate approach to diet of CKD patients, which could contribute to slowing down progression of the disease. Dietary recommendations are individual for each patient, but also vary in the same patient depending on the stage of disease progression because special attention must be paid to appropriate intake of macronutrients (protein, carbohydrates and fats), micronutrients (sodium, potassium, calcium, phosphorus, zinc, selenium, various vitamins), and water. In newly diagnosed patients, it is necessary to assess their nutritional status and energy requirements. It has been shown that protein-energy malnutrition, muscle loss and cachexia are strong predictors of mortality in CKD. Comparing different dietary approaches in everyday life of patients suffering from CKD, it was found that the most effective diet is Mediterranean food style. Studies confirm that Mediterranean diet has a preventive effect on renal function and reduces progression of the disease. Preventive measures, correct identification and early intervention can increase survival of patients and improve their quality of life. Mediterranean diet tailored to individual stages of CKD has been confirmed as the best choice in CKD patients.

[NEPHROTOXIC DRUGS].

Renal tissue is sensitive to the effect of potentially nephrotoxic drugs and other substances that are available over-the-counter or can be purchased at healthy food stores or elsewhere, and harmful substances from the environment. The harmful effects of these substances lead to the development of recognizable clinical syndromes, including acute or chronic renal failure, tubulopathy, and proteinuria. Risk factors that influence the development of kidney disease induced by drugs are divided into those related to patient characteristics, drug characteristics, and renal function. Drugs that commonly exhibit nephrotoxic effects are analgesics, antimicrobials, chemotherapeutics, contrast agents, immunosuppressants, herbal preparations and substances containing heavy metals. Family physician must carefully observe their patients, nurturing individual approach to drug selection and determining the dose. Renal function can quickly return to normal if the damage is recognized on time. Recent research yields insights into the identification of new biomarkers that will contribute to early detection of drug induced kidney damage.

[CHOLESTASIS AND INFLAMMATION OF THE PANCREAS IN FAMILY MEDICINE].

Cholestasis indicates stagnation of bile, a disorder in the synthesis, secretion and/or outflow of bile. Cholestasis is classified as intrahepatic or extrahepatic. Intrahepatic cholestasis may occur as a result of hepatocellular disorders or due to obstruction of the intrahepatic bile ducts. Extrahepatic cholestasis is caused by obstruction of the bile ducts outside the liver. Cholestasis manifests as acute or chronic (>6 months). Early biochemical markers of cholestasis include increased alkaline phosphatase, γ-glutamyltransferase, and conjugated hyperbilirubinemia. Clinically, the most common presenting symptoms are jaundice, itchy skin and fatigue. A key element in diagnosis is visual presentation of the biliary system. New insights into the pathophysiological mechanisms of cholestasis at the molecular level will contribute to the development of new treatments. Pancreatitis is an inflammatory process in the tissue of the pancreas caused by prematurely activated pancreatic enzymes. The course of acute pancreatitis is in most cases mild, with minimal organ dysfunction and full recovery, while the severe form of the disease is characterized by complications and high mortality. Chronic pancreatitis is characterized by persistent inflammation of the pancreas with permanent damage to glandular tissue in the presence of fibrosis and narrowed pancreatic ducts. Treatment of pancreatitis is supportive and directed to maintaining the basic physiological functions. The role of family physicians is very important in early detection of liver diseases, which can significantly affect the success of treatment and improve the quality of life in these patients.

Different perforin expression in peripheral blood and prostate tissue in patients with benign prostatic hyperplasia and prostate cancer.

Perforin (P) is a prototypical cytotoxic molecule involved in cell-mediated immunity against various pathogens, alloantigens and particularly different tumours. The purpose of this study was to determine P expression in different lymphocyte subpopulations isolated from peripheral blood and prostate tissue of patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa) and compare it with the P expression found in the control group. Twenty subjects were recruited in each of the groups. Prostate mononuclear cells of the BPH and PCa tissues were isolated by enzymatic digestion and gradient density centrifugation, whereas peripheral blood mononuclear cells were isolated by gradient density centrifugation alone. Cells and tissue samples were labelled using monoclonal antibodies against P and different surface antigens (CD3, CD4, CD8 and CD56) and analysed by immunofluorescence and flow cytometry. Total P expression in peripheral blood lymphocytes did not differ significantly between BPH/PCa patients and control group, although the BPH and PCa tissue showed lower P expression level. A negative correlation between prostate-specific antigen levels and the overall percentage of P(+), CD3(+) CD56(-) P(+) , and CD3(-) CD56(+) P(+) cells in the prostate tissue was observed only in patients with PCa. Our findings indicate that the low frequency of P(+) lymphocytes, including T, NKT and NK cells, in the prostate tissue of patients with BPH and, particularly, PCa could be the consequence of local tissue microenvironment and one of the mechanisms involved in the pathogenesis of prostate hyperplasia following malignant alteration.

The proposed mechanism of action during different pain management techniques on expression of cytolytic molecule perforin in patients after colorectal cancer surgery.

The postoperative period is accompanied with neuroendocrine, metabolic and immune alteration which is caused by tissue damage, anesthesia, postoperative pain and psychological stress. Postoperative pain contributes to dysfunction of immune response as a result of interaction between central nervous and immune system. The postoperatively activated hypotalamo-pituitary-adrenocortical axis, sympathic and parasympathic nerve systems are important modulators of immune response. According to bidirectional communication of immune and nervous system, appropriate postoperative pain management could affect immune response in postoperative period. Although the postoperative suppression of immune response has been reported, a very little are known about the influences of different pain management techniques on cytotoxic function of immune cells in patients with colorectal cancer in early postoperative period. Perforin is a cytotoxic molecule expressed by activated lymphocytes which has a crucial role in elimination of tumor cells and virus-infected cells, mostly during the effector's phase of immune response. Immune compromise during the postoperative period could affect the healing processes, incidence of postoperative infections and rate and size of tumor metastases disseminated during operation. The pharmacological management of postoperative pain in patients with malignancies uses very different analgesic techniques whose possible influence on cytotoxic functions of immune cells are still understood poor. For decades the most common way of treating postoperative pain after colorectal cancer surgery was intravenous analgesia with opiods. In the last decade many investigations pointed out that opiods can also contribute to postoperative suppression of immune response. Epidural analgesia is a regional anesthesia technique that acts directly on the origin of pain impulses and pain relief can be achieved with small doses of opiods combined with local anesthetics. Local anesthetics potentate analgesic properties of opiods but per se are also acting as antiinflammatory drugs. Afferent neural blockade by epidural analgesia attenuates neuroendocrine stress response. We propose that epidural analgesia could be more convenient that intravenous analgesia in maintenance of immunological homeostasis that is altered by surgical stress, tumor growth and pain.

Early changes in frequency of peripheral blood lymphocyte subpopulations in severe traumatic brain-injured patients.

Infections are leading causes of increased morbidity and mortality of severe traumatic brain-injured (STBI) patients. The mechanism underlying the susceptibility to the infections is still unexplained. The purpose of the study was to investigate changes in frequency of leucocytes subpopulations in peripheral blood of patients with STBI during the course of intensive care treatment. Twenty patients with STBI were included in the study. Healthy age- and sex- volunteers served as control. Peripheral blood samples were taken from these patients at day 1, 4 and 7, and peripheral blood mononuclear cells (PBMC) were isolated. The percentage of T, B lymphocyte, NK and NKT cells as well as monocytes was analysed by simultaneous detection of surface antigens using fluorochrome-conjugated monoclonal antibodies. The two major subsets of T lymphocytes (CD3(+)CD56(-)CD4(+) and CD3(+)CD56(-)CD8(+)) and NK cells (CD3(-)CD56(+dim) and CD3(-)CD56(+bright)) were also analysed by flow cytometry. Extracranial infections were presented in 55% patients with STBI. At day 4, the percentage of T lymphocytes with cytotoxic phenotype significantly diminished and their numbers restored at day 7. The frequency of NKT cells showed the identical time-dependent pattern, whereas the percentage of NK cells diminished on day 4 but did not restore after 7 days. The frequency of B lymphocytes did not change significantly during the time investigated, whereas the percentage of monocytes increased immediately after the injury and gradually diminished. The decrease in cells with cytotoxic phenotype might explain high incidence of susceptibility to infection of patients with STBI.

Short-term exposure of mice to gasoline vapor increases the metallothionein expression in the brain, lungs and kidney.

Environmental airborne pollution has been repeatedly shown to affect multiple aspects of brain and cardiopulmonary function, leading to cognitive and behavioral changes and to the pronounced inflammatory response in the respiratory airways. Since in the cellular defense system the important role might have stress proteins-metallothionein (MT)-I and MT-II, which are involved in sequestration and dispersal of metal ions, regulation of the biosynthesis and activities of zinc-dependent transcription factors, as well as in cellular protection from reactive oxygen species, genotoxicity and apoptosis, in this study we investigated their expression in the brain, lungs and kidney, following intermittent exposure of mice to gasoline vapor. Control groups consisted of intact mice and of those closed in the metabolic chamber and ventilated with fresh air. The data obtained by immunohistochemistry showed that gasoline inhalation markedly upregulated the MTs expression in tissues which were directly or indirectly exposed to toxic components, significantly increasing the number of MT I+II positive cells in CNS (the entorhinal cortex, ependymal cells, astroglial cells in subventricular zone and inside the brain parenchyma, subgranular and CA1-CA3 zone of the dentate gyrus in hippocampus and macrophages-like cells in perivascular spaces), in the lungs (pneumocytes type I and type II) and in the kidneys (parietal wall of Bowman capsule, proximal and distal tubules). The data point to the protective and growth-regulatory effects of MT I + II on places of injuries, induced by inhalation of gasoline vapor.

Syngeneic pregnancy induces overexpression of natural killer T cells in maternal liver.

Conditions such as stress, infection, autoimmune disease, etc. elevate the number and function of extrathymic T cells that are generated mainly in the liver. As primitive, self-reactive clones of T cells that coexpress receptors of the natural killer (NK) lineage, they mediate cytotoxicity against altered self, malignant and infected cells and have the unique potential to rapidly secrete large amount of T helper 1 (Th1) or Th2 cytokines. To elucidate whether some of these changes occur even during the syngeneic pregnancy, we made phenotypic and functional characterization of mononuclear lymphatic cells (MNLCs) isolated from the liver and spleen of pregnant C57BL/6 mice, testing their cytotoxicity against syngeneic thymocytes as well as against NK- and lymphokine-activated killer (LAK)-sensitive targets. The data have shown that on the sixteenth day of syngeneic pregnancy TCRint, NK1.1+ and IL-2Rbeta+ cells were accumulated in the liver, while the quantities of CD4+ and CD8+ T cells and total number classical NK (NK1.1+CD3- or IL-2Rbeta+CD3-) cells were increased in the spleen. Pregnancy-activated hepatic and splenic MNLCs were more cytotoxic against syngeneic thymocytes, YAC-1 and P815 targets, suggesting that the maternal liver is a main producer of autoreactive NKT clones, which subsequently augment NK- and LAK cell-mediated cytotoxicity in the liver and spleen.