Role of MMP-2, MMP-9, TIMP-1, and TIMP-2 in children with ventricular septal defect.

Ventricular septal defect (VSD) is the second most common congenital heart anomaly. In most cases, it closes spontaneously in the first year of life, but it sometimes requires surgical closure due to the risk of serious complications. This is why it is important to identify markers that could help predict its course.

The Relevance of β-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience.

(1) Background: Thalassemia syndromes are common monogenic disorders that represent a significant global health issue. No systematic epidemiological or molecular investigations on thalassemias in the Croatian population have been reported to date. (2) Methods: This prospective study included 70 children with a presumptive diagnosis of thalassemia and their 42 first-degree relatives.

Metabolic and Hepatic Effects of Energy-Reduced Anti-Inflammatory Diet in Younger Adults with Obesity.

Background: Associated with epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease worldwide. The cornerstone of therapy for NAFLD is lifestyle intervention, mainly focused on weight loss. Significant weight loss results from energy-restricted diets, regardless of macronutrient distribution.

The Efficacy of an Energy-Restricted Anti-Inflammatory Diet for the Management of Obesity in Younger Adults.

There is growing evidence of the dietary impact on obesity-induced low-grade chronic inflammation and the associated chronic non-communicable diseases modification. We determined changes in body composition and cardiometabolic and inflammatory status of participants with obesity after 24 weeks of a dietary intervention based on an energy-reduced anti-inflammatory diet and examined the relationship of these changes with changes in the inflammatory potential of the diet. The anthropometric and body composition parameters of 81 participants (average age of 43 years, 74 women) were assessed.

Enhanced Antioxidative Defense by Vitamins C and E Consumption Prevents 7-Day High-Salt Diet-Induced Microvascular Endothelial Function Impairment in Young Healthy Individuals.

This study aimed to examine whether the oral supplementation of vitamins C and E during a seven-day high salt diet (HS; ~14 g salt/day) prevents microvascular endothelial function impairment and changes oxidative status caused by HS diet in 51 (26 women and 25 men) young healthy individuals. Laser Doppler flowmetry measurements demonstrated that skin post-occlusive reactive hyperemia (PORH), and acetylcholine-induced dilation (AChID) were significantly impaired in the HS group, but not in HS+C+E group, while sodium nitroprusside-induced dilation remained unaffected by treatments. Serum oxidative stress markers: Thiobarbituric acid reactive substances (TBARS), 8-iso prostaglandin-F2α, and leukocytes' intracellular hydrogen peroxide (HO) production were significantly increased, while ferric-reducing ability of plasma (FRAP) and catalase concentrations were decreased in the HS group.

Thymic alterations induced by partial hepatectomy: Upregulation of glycoprotein 96, CD91 and TLR2 and generation of regulatory T cells.

Glycoprotein 96 (gp96) is an endoplasmic reticulum (ER)-resident heat shock protein. It controls the folding of nascent membrane-spanning and secretory proteins, participates in stress-induced unfolded protein response (UPR) and in pathways leading to proteolysis of damaged proteins through ER-associated degradation pathways and chaperone-mediated autophagy. In addition, gp96 controls the steroid biosynthesis and Ca²⁺ homeostasis and participates in insulin-IGF/signaling pathways.

Metallothionein I+II expression as an early sign of chronic relapsing experimental autoimmune encephalomyelitis in rats.

Metallothioneins (MTs) are small, cysteine-rich proteins which have been implicated in various forms of stress providing cytoprotective action against oxidative injury, DNA damage and apoptosis. Owing to their high affinity for physiological metals, such as zinc and copper MTs are also critical components of regulatory proteins involved in cell growth and multiplication, as well as in the maintenance of immune homeostasis. To elucidate the role of MTs in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MT I+II proteins and the content of free Zn ions in the brain, spinal cord and in the liver early in the course of chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) pathogenesis, i.

Endoplasmic reticulum resident heat shock protein-gp96 as morphogenetic and immunoregulatory factor in syngeneic pregnancy.

The severe remodeling of endometrial stroma during blastocyst adhesion and trophoblast invasion initiates at maternal-fetal interface the reaction of evolutionary old heat shock response, in which heat shock proteins, as molecular chaperons, monitor the configurations of newly synthesized proteins and prevent the formation of functionless aggregates of misfolded proteins, targeting them to degradation by a the ubiquitin-proteasome system. In addition, the endoplasmic reticulum (ER)-resident HSPs, such as gp96/GRP94 may, after binding to CD91 and TLRs, elicit antigen-specific and antigen-unspecific immune responses, owing to its peptide-chaperoning capacity and ability to activate APCs. Considering these properties, we examined tissue expression of gp96 at the maternal-fetal interface and in the maternal liver and spleen on the 16th day of undisturbed syngeneic pregnancy and after the treatment with peptidoglycan monomer linked with zinc (PGM-Zn).

Heat shock protein Gp96 as potential regulator of morphostasis after partial hepatectomy in mice.

Gp96 (also known as glucose-regulated protein 94, endoplasmin) is the endoplasmic reticulum (ER)-resident protein, which belongs to the heat shock protein HSP90 family. It is upregulated in response to glucose starvation and other stressful stimuli that disrupt protein synthesis in the ER. There, it is acting as a molecular chaperon involved in the correction of unfolded proteins, in the activation of proteasome-dependent ER-associated degradation of the misfolded proteins, and in activation of protein translations that modulate the polypeptide traffic into the ER.

Determination of enzyme matrix metalloproteinases-9 and immune status as indicators of development of the environmental diseases.

The majority of environmental diseases are multifactorial airway illnesses, including genetic background and exposure to different kind of airborne irritants and allergens. Altered lifestyle and changes in environmental exposures contribute to the occurring of these diseases. The term of environmental illnesses includes the disease primarily caused by pollution of air and water, chemical and physical agents, radiation, contaminated food and direct contact with the toxins we are exposed to natural and/or working environment.

Cross-talk between NKT and regulatory T cells (Tregs) in modulation of immune response in patients with colorectal cancer following different pain management techniques.

Natural killer T (NKT) and regulatory T cells (Tregs) play an important role in innate immune response. Natural killer (NK) and NKT cells are indispensable factors in the body's ongoing defense against tumor development, as well as viral infection. NKT cells are a subset of T cells that shares properties of natural killer cells and conventional T cells.

Comparative study of frequency of different lymphocytes subpopulation in peripheral blood of patients with prostate cancer and benign prostatic hyperplasia.

Purpose: Benign prostatic hyperplasia (BPH) and prostate cancer (PC) are the most common urologic diseases among men over fifty and, until recently, they were considered to be caused by the impaired immune response. Despite many studies designed to investigate T-cell-based antitumor immunity, the role of innate immune cells in BPH and PC is still poorly understood. In this study the frequency of different leukocytes subpopulation in peripheral blood of BPH, PC patients and in healthy volunteers was analysed and compared.

Prognostic value of venoarterial carbon dioxide gradient in patients with severe sepsis and septic shock.

Aim: To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco(2)) and its prognostic value for survival of patients with severe sepsis and septic shock.

Methods: The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated.

Time-course expression of metallothioneins and tissue metals in chronic relapsing form of experimental autoimmune encephalomyelitis.

To elucidate the role of metallothioneins (MTs) in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MTs I+II and the tissue concentrations of Zn²+ and Cu²+ in the brain, spinal cord (SC) and in the liver during the periods of attacks and remissions in chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE). Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control rats were treated with CFA.

Expression of cytolytic protein-perforin in peripheral blood lymphocytes in severe traumatic brain injured patients.

Purpose: The purpose of this study was to investigate the changes of cytotoxic protein-perforin in peripheral blood lymphocytes in severe TBI patients and possible correlation between severity of TBI and perforin expression.

Methods: Flow cytometry was used for simultaneous detection of intracellular perforin and cell surface antigens of peripheral blood lymphocytes of 20 severe TBI patients on day 1, 4 and 7 after the onset of injury. Peripheral blood mononuclear cells from 20 healthy volunteers were used as control.

Regulatory T cells (Tregs) monitoring in environmental diseases.

The prevalence of environmental diseases is increasing worldwide and these diseases are an onerous burden both to the individual and to the public health. Urban air pollution is a grave problem in majority of metropolises, which contain high levels of traffic congestion generating great amounts of genotoxic substances. The contribution of such environmental exposure to increase prevalence of many allergic, environmental diseases and multiple chemical sensitivity or other related syndromes, as a result of an abnormal immune response based on environmental damage of lymphocyte subsets, is marked.

Perforin expression in peripheral blood lymphatic cells of patients subjected to laparoscopic or open cholecystectomy.

Perforin-(P-) related characteristics of cytotoxic T lymphocytes and natural killer cells were investigated in peripheral blood of patients subjected to open (OC; n = 23) or laparoscopic cholecystectomy (LC; n = 21) and healthy controls (n = 20). Blood samples were obtained preoperatively and 24 hours after the surgeries, and the data were correlated with the intensity of cholestasis and concomitant inflammation, determined by functional hepatic tests. Postoperative differences were found to be minimal: OC decreased only the percentage of CD56(+) cells, while LC decreased the fraction of CD8(+)P(+) cells and augmented the mean fluorescence intensity of P in CD56 cells.

Heat shock protein-GP96 as an innate sensor of damage and activator of autoreactive NKT and regulatory T cells during liver regeneration.

Tissue disintegration after injury leads, in the endoplasmic reticulum (ER), to activation of adaptive pathways known as the ER stress response. It is directed to the correction of unfolded proteins and to the activation of proteasome-dependent ER-associated degradation of the misfolded proteins, but induces also a rapid activation of natural and adaptive immunity, since a ER resident heat shock protein-gp96 acts not only as a molecular chaperone, but also as a strong adjuvant, able to cross-present the antigenic peptides onto MHC class I or MHC class II pathways. Analyzing its potential role in processes of normal growth, in mice subjected to 1/3 partial hepatectomy (pHx) we determined the tissue expression of gp96 protein and mRNA in regenerating liver, thymus and spleen, determining simultaneously the phenotypic profile and spontaneous cytotoxic activity of intrahepatic and splenic mononuclear lymphatic cells (MNLC) against NKT- and NK-cells sensitive targets (syngeneic thymocytes and YAC-1) in wild, perforin and FasL deficient mice.

Metallothionein expression and tissue metal kinetics after partial hepatectomy in mice.

To better elucidate previous results showing that partial hepatectomy noticeably changes the tissue content of zinc, calcium, magnesium, and iron(II) ions in regenerating the liver, thymus, and spleen, we report on the correlation of these metal tissue kinetics in these organs with the expression of metallothionein-I+II (MT-I+II) proteins and MT-I mRNA in early postoperative period (1, 2, 6, 12, and 24 h) after one-third hepatectomy (pHx). The results showed that 2 h after pHx the regenerating liver accumulated Zn2+, Ca2+, Mg2+, and Fe2+ ions while decreasing the concentration of all these metals in the spleen and of Zn2+ in the thymus. On the 24th h, a new high accumulation of Zn2+ and Ca2+ was seen in the regenerating liver and of Zn2+, Ca2+, and Fe2+ in the spleen.

Metal tissue kinetics in regenerating liver, thymus, spleen, and submandibular gland after partial hepatectomy in mice.

Liver regeneration after partial hepatectomy (pHx) is a well-defined process, which involves the concerted action of extra- and intracellular factors resulting in induction of cell replication and its inhibition at the time when the entire liver mass is restored. Concomitantly, the breakdown of previously maintained tolerance and the exposure of self-antigens lead to the activation of preimmune and immune repertoires, which participate in surveillance against aberrant cells and the re-establishment of previous morphostasis. Because, in these events, important biological function might have tissue minerals that are affecting the structural integrity and enzyme activities, transduction signals, transcription and replication factors during cell proliferation and apoptosis, as well as the development and maintenance of immune functions and cytokine production, in this study we analyzed tissue dynamics of zinc, iron, magnesium, and calcium in the liver, thymus, spleen, and submandibular gland in intact and pHx mice on the 1st, 2nd, 7th, and 15th d after one-third pHx, using microwave digestion and inductivity coupled plasma spectrometry.

Metatarsal metastasis from transitional cell cancer of the urinary bladder.

Urinary bladder cancers can be grouped into three general categories: superficial, invasive and metastatic. Approximately 90% of malignant tumors of the urinary bladder are of epithelial origin and the majority of them are transitional cell carcinomas (TCC). Metastatic spread of urinary bladder cancers usually includes regional lymph nodes, the lung, the liver and the bones.

Augmentation of NKT and NK cell-mediated cytotoxicity by peptidoglycan monomer linked with zinc.

Background: Peptidoglycan monomer (PGM), which was originally prepared by biosynthesis from culture fluids of penicillin-treated Brevibacterium divaricatum, is an immunostimulator, the activities of which might be improved by addition of zinc (Zn) to the basic molecule.

Methods: To test the possible cytotoxic effects of this new analogue, we analyzed the ability of PGM-Zn and PGM to change the phenotypic profile of hepatic and splenic mononuclear lymphatic cells and to affect the growth of malignant T-cell line YAC-1 and syngeneic thymocytes.

Results: Pretreatment of C57BL/6 mice primarily with PGM-Zn over 6 days (10/mg/kg intraperitoneally) significantly enhanced the proportions of NK1.