Matrix metalloproteinase secretion by gastric epithelial cells is regulated by E prostaglandins and MAPKs

Because matrix metalloproteinases (MMPs) play roles in inflammatory tissue injury, we asked whether MMP secretion by gastric epithelial cells may contribute to gastric injury in response to signals involved in Helicobacter pylori-induced inflammation and/or cyclooxygenase inhibition. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and epidermal growth factor (EGF) stimulated gastric cell MMP-1 secretion, indicating that MMP-1 secretion occurs in inflammatory as well as non-inflammatory situations. MMP-1 secretion required activation of the MAPK Erk and subsequent protein synthesis but was down-regulated by the alternate MAPK, p38. In contrast, secretion of MMP-13 was stimulated by TNF-alpha/IL-1beta but not EGF and was Erk-independent and mediated by p38. MMP-13 secretion was more rapid (peak, 6 h) than MMP-1 (peak > or =30 h) and only partly depended on protein synthesis, suggesting initial release of a pre-existing MMP-13 pool. Therefore, MMP-1 and MMP-13 secretion are differentially regulated by MAPKs. MMP-1 secretion was regulated by E prostaglandins (PGEs) in an Erk-dependent manner. PGEs enhanced Erk activation and MMP-1 secretion in response to EGF but inhibited Erk and MMP-1 when TNF-alpha and IL-1beta were the stimuli, indicating that the effects of PGEs on gastric cell responses are context-dependent. These data show that secretion of MMPs is differentially regulated by MAPKs and suggest mechanisms through which H. pylori infection and/or cyclooxygenase inhibition may induce epithelial cell signaling to contribute to gastric ulcerogenesis.     

Structural aspects of RecA-dependent homologous strand exchange involving human telomeric DNA

Telomeric DNA sequences in human cells and those of other vertebrates consist of long d(TTAGGG) repeats. In somatic cells, telomeres shorten every cell division with shortening serving as a mitotic clock that counts cell divisions and ultimately results in cellular senescence. Telomere length is principally maintained by a ribonucleoprotein, telomerase. However, a non-negligible proportion of human cells use a recombination-based mechanism for telomere maintenance, termed alternative maintenance of telomeres (ALT). Although the molecular mechanism of ALT is not known, GT-rich sequences in prokaryotes and eukaryotes display high levels of recombination relative to those of non-GT-rich DNA. We show that human telomeric strand-exchange complexes mediated by Escherichia coli RecA protein differ from those formed with nontelomeric sequences. Moreover, telomeric strand-exchange intermediates, unlike those involving nontelomeric sequences, exhibit a tendency to form higher-order nucleoprotein structures. We propose that the strong DNA unwinding activity inherent in the assembly of the RecA strand-exchange complex promotes the formation of alternative DNA structures at human telomeric loci. Organization of these noncanonical structures into higher-order complexes involving multiple DNA duplexes could facilitate the search for homology on different DNA molecules and provide a framework for understanding recombination-dependent mechanisms of telomere maintenance.     

Phagocytic functions of microglial cells in the central nervous system and their importance in two neurodegenerative diseases: multiple sclerosis and Alzheimer’s disease

Microglial cells are the resident phagocytic cells of the central nervous system (CNS). They possess a wide range of receptors allowing them to identify and internalize numerous pathogens. We will discuss here the role of the most important receptors of microglia involved in non-opsonin-dependent phagocytosis (mannose receptor, β-glucan receptor, scavenger receptor) and that of receptors involved in the opsonin-dependent phagocytosis, namely the complement 3 (CR3) and the Fcγ receptors (FcγR). First, the molecular and cellular mechanisms induced when these receptors are conducting a phagocytic event are presented. In the second part, we will discuss the role these receptors may play in multiple sclerosis and Alzheimer’s disease, in the elimination by phagocytosis of myelin and beta amyloid peptide respectively. The first two authors contributed equally to this work.     

Functional ability of the elderly in institutional and non-institutional care in Croatia

Gerontology-public health indicators of functional ability of the elderly in institutional and non-institutional health care in Croatia were determined by use of expert methodology developed at Department of Gerontology, Dr. Andrija Stampar Institute of Public Health in Zagreb, with the aim to upgrade the Program of Health Care Measures and Procedures in Health Care of the Elderly. Comparison of functional ability between the users of selected Old People's Homes (institutional care; N = 5030) and Gerontology Centers (non-institutional care; N = 2112) yielded highest between-group difference in the proportion of "fully movable" and "fully independent" categories in favor of the latter, thus steering the program of health care for the elderly accordingly. In addition, study results showed greater difference in the proportion of categories describing mental status of institutional and non-institutional care users as compared with the categories describing their physical status, suggesting that mental status plays a more important role than physical status in the geriatric user's stay in non-institutional care versus institutional care. This issue requires additional studies. The results obtained by this indicator analysis pointed to the preventive and geroprophylactic measures to ensure efficient health care for the elderly and to develop the program of mental health promotion and preservation. According to 2007 estimate, there were 759,318 (16.9%) persons aged > or = 65 in Croatia. Data collected at gerontology database kept at Department of Gerontology, Dr. Andrija Stampar Institute of Public Health (September 2008) showed 2% of the elderly (N = 14807) to be accommodated at Old People's Homes, which is below the European average of 4%.     

Quality of life of patients after stroke in county Osijek-Baranya

The purpose of this prospective study was to determine quality of life of patients after stroke in Osijek-Baranya County. The research included 161 patients (82 men and 79 women) who had their first acute stroke and were treated at Department of Neurology, Osijek University Hospital Center The Barthel Index (BI) was used to assess functional deficiency and SS-QOL (Stroke-Specific Quality of Life) questionnaire was used for self-evaluation of patients' physical and mental health. The first assessment was carried out in the acute phase of the disease, and control assessments 30, 90 and 180 days after the stroke. Mean Barthel Index score was higher at every successive measurement (55, 80, 95, 95). All BI items were statistically significant (Friedman, p < 0.001) apart from dressing and bowel control. BI score indicated greater dependence in women in all assessments except for those taken 90 days after onset of symptoms (chi2-test, p = 0.111). Mean values of SS-QOL for physical health were: 105.2, 98.3, 105.7, 117.5 and for mental health: 64.24, 57.9, 64.3, 68.1. Statistically significant difference was present in men, both for physical health (Friedman p = 0.009) and total SS-QOL (Friedman p = 0.014), while in women there was no statistically significant difference between the measurements (Friedman p = 0.719). The research showed that stroke has significant influence on basic and specific daily life activities and interferes with the quality of life of stroke patients. Women have lower level of independence. Patients who live with their families make better evaluation of their physical and mental health.     

Splenic hematoma as a first manifestation of cytomegalovirus infection

Splenic rupture is rare but life threatening complication of mononucleosis syndrome. It has been suggested that subcapsular splenic hematoma formation precedes rupture. The case of 44-year-old, previously healthy, male with splenic hematoma occurring after rising of heavy cargo is reported. Mononucleosis syndrome was suggested based on routine laboratory tests (elevated white blood cell count with predominance of lymphocytes and raised serum transaminases) and CMV infection was confirmed by serological test. Nonoperative management was used since the patient was hemodynamically stable with no further signs of splenic rupture. The same approach has been used in growing number of cases of patients with spontaneous splenic rupture in mononucleosis syndrome. Importance of considering splenic hematoma and/or rupture if abdominal pain occurs in the course of mononucleosis syndrome is outlined as well as importance of routine laboratory tests in suspecting mononucleosis syndrome in otherwise clinically silent patient.     

Synthesis,anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives

The action of the coumarin-type drugs and related compounds is reviewed to their VKOR antagonistic effects. In our study, twenty 3-pyridinyl, pyrimidinyl and pyrazolyl-4-hydroxycoumarin derivatives were synthesized. A comparative in vivo (CT, PT determination) and in vitro (measurement of PIVKA-II levels) anticoagulant study with respect to warfarin showed that the synthesized compounds have different anticoagulant activities, the most prospective compounds were the 3-pyrazolyl-4-hydroxycoumarin derivatives.     

Chronic 1alpha,25-(OH)2 vitamin D3 treatment reduces Ca2+ -mediated hippocampal biomarkers of aging

Aging in the hippocampus of several species is characterized by alterations in multiple Ca(2+)-mediated processes, including an increase in L-type voltage-gated Ca(2+) channel (L-VGCC) current, an enhanced Ca(2+)-dependent slow afterhyperpolarization (AHP), impaired synaptic plasticity and elevated Ca(2+) transients. Previously, we found that 1alpha,25-dihydoxyvitamin D(3) (1,25VitD), a major Ca(2+) regulating hormone, down-regulates L-VGCC expression in cultured hippocampal neurons. Here, we tested whether in vivo treatment of aged F344 rats with 1,25VitD would reverse some of the Ca(2+) -mediated biomarkers of aging seen in hippocampal CA1 neurons. As previously reported, L-VGCC currents and the AHP were larger in aged than in young neurons. Treatment with 1,25VitD over 7 days decreased L-VGCC activity in aged rats, as well as the age-related increase in AHP amplitude and duration. In addition, reduced L-VGCC activity was correlated with reduced AHPs in the same animals. These data provide direct evidence that 1,25VitD can regulate multiple Ca(2+)-dependent processes in neurons, with particular impact on reducing age-related changes associated with Ca(2+) dysregulation. Thus, these results may have therapeutic implications and suggest that 1,25VitD, often taken to maintain bone health, may also retard some consequences of brain aging.