Association of MMP-3 5A/6A gene polymorphism with susceptibility to carotid atherosclerosis

ObjectivesStromelysin-1 (MMP-3) as a key member of metalloproteinase family could have an important role in atherogenesis. The 5A/6A polymorphism in the promoter of MMP-3 gene affects the level of MMP-3 gene expression. We assessed whether the MMP-3 promoter low- and high-activity genotypes are related to susceptibility for carotid atherosclerosis (CA) in Serbian population.Design and methodsThe study group of case-control design consisted of 515 participants. The 265 patients with ultrasonographic evidence of carotid plaque presence were recruited for the study. The 5A/6A polymorphism was typed by RFLP-PCR.ResultsThere was significantly higher prevalence of genotypes containing 6A allele in the patients with CA compared to controls (p < 0.05). The model of inheritance with the dominant effect of 6A allele gave elevated and significant OR for carotid atherosclerosis (adjusted OR 2.35, CI = 1.0–5.5, p = 0.048).ConclusionsSubjects carrying genotypes with 6A allele had significantly higher susceptibility to carotid atherosclerosis.     

Change in transferrin sialylation is a potential prognostic marker for severity of acute pancreatitis

ObjectivesEarly prediction of severe acute pancreatitis is one of the problems in clinical practice. Since many diseases are associated with alteration in glycosylation, in this work we studied sialylation of transferrin and serum proteins in acute pancreatitis.Design and methodsSialylation was analyzed during first eight days of hospitalization of 30 patients and compared to 28 healthy controls. Transferrin sialylation was measured using enzyme linked lectin assay, while sialic acid on proteins was measured using resorcinol method.ResultsBoth analyzed parameters changed during studied period. The change in transferrin sialylation between Day1 and Day2 of hospitalization was shown to be an early prognostic marker of acute pancreatitis, with better sensitivity (88.9%) and specificity (90.5%) than other markers tested.ConclusionsSialylation of transferrin and total serum proteins reflects the intensity of inflammatory response during acute pancreatitis and could be used as prognostic parameter for disease severity.     

Aging, aluminium and basal forebrain lesions modify substrate kinetics of erythrocyte membrane Na,K-ATPase in the rat

Several studies suggested that the activity of erythrocyte Na,K-ATPase declines with aging. Here, it is postulated that alterations in the substrate kinetics of the erythrocyte membrane Na,K-ATPase could be more aggravated in conditions of brain cholinergic dysfunction seen in Alzheimer's disease than in normal aging. To test this hypothesis, we compared the Na,K-ATPase activity (Vmax/Km parameters) in aged rats with those in young rats with brain cholinergic dysfunction induced by electrolytic-, kainic acid-lesioned nucleus basalis magnocellularis (NBM) or by intracerebroventricular AlCl_{3} administration. In the above mentioned groups, Vmax values were significantly lower in comparison to the control animals. Furthermore, Km values were significantly higher in animals with electrolytic-induced NBM lesions, AlCl_{3} treated rats and aged animals. However, Km was significantly lower in kainic acid-induced NBM lesions compared to the control group. The Na,K-ATPase catalytic efficiency, estimated by the ratio Vm/Km, decreased as followed: young animals > aged animals > kainic acid lesion > electrolityc lesion > AlCl_{3}. Our data suggest that neurodegenerative processes similar to those seen in Alzheimer's disease affect the sodium/potassium pump functionality which might be detected in peripheral blood erythrocyte membranes.     

Spiritual well-being, intrinsic religiosity, and suicidal behavior in predominantly Catholic Croatian war veterans with chronic posttraumatic stress disorder: a case control study

We investigated relationships between spiritual well-being (SWB), intrinsic religiosity (IR), and suicidal behavior in 45 Croatian war veterans with chronic posttraumatic stress disorder and 32 healthy volunteers. Compared with the volunteers, the veterans had significantly lower SWB scores (p = 0.000) and existential well-being (EWB) scores (p = 0.000). Scores on the religious well-being (RWB) subscale (p = 0.108) and the IR scale did not differ significantly between the groups (p = 0.803). Veterans' suicidality inversely correlated with SWB (p = 0.000), EWB (p = 0.000), RWB (p = 0.026), and IR (p = 0.041), with the association being stronger for the EWB subscale than for the RWB subscale. Veterans who had attempted suicide at least once in their lifetime had significantly higher Suicidal Assessment Scale scores and lower EWB scores than veterans who never attempted suicide. Low EWB scores may imply an increased risk of suicidality. Some religious activities were more frequent among the veterans than among the healthy volunteers, possibly reflecting the veterans' increased help-seeking behavior due to poor EWB.     

Association of the MMP-3 5A/6A gene polymorphism with multiple sclerosis in patients from Serbia

Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in remodeling of the extracellular matrix. MMPs are suggested to play a role in the influx of inflammatory cells into the CNS, disruption of the blood brain barrier, and to degrade myelin in vitro. In this study, we have investigated the possible association of MMP-3 5A/6A gene polymorphism with MS susceptibility and/or severity in patients from Serbia. A total of 184 MS patients (150 RR, 34 SP) and 236 controls have been studied. Results show that the distribution of MMP-3 5A/6A genotype frequencies between MS patients and controls were not significantly different. In bout onset patients, carriers of MMP-3 6A/6A genotype had significantly higher mean MSSS values compared to the carriers of 5A allele (6.29+/-1.89 vs. 5.29+/-2.62, respectively, ANCOVA, p=0.01 Scheffe post-hoc test). In conclusion, our results indicate association of MMP-3 6A/6A genotype with significantly higher mean MSSS values. Thus, the obtained results suggest that it should be carefully considered during follow up of patients with MS. Further genetic and functional studies are needed to resolve the complex role of MMPs and their tissue inhibitors in MS pathology and/or regeneration.     

Temporal patterns of motor behavioural improvements by MK-801 in Mongolian gerbils submitted to different duration of global cerebral ischemia

The purpose of this study was to investigate the temporal pattern of NMDA receptors antagonist-MK-801 on motor behaviour parameters in gerbils submitted to different duration of global cerebral ischemia. The common carotid arteries of gerbils were occluded for 5, 10 or 15min. Gerbils were given MK-801 (3mg/kg i.p.) or saline immediately after the occlusion in normothermic conditions prior to testing. Motor activity was registered 1, 2, 4, 7, 14, 21 and 28 days after reperfusion during 60min by open field test. At the same time, the effect of NMDA receptor blockade was followed in vivo by monitoring the neurological status of whole animals or at the cellular level by standard light and confocal microscopy on brain slices. Post-ischemic gerbils quickly developed hypermotor response with the most intensity in animals submitted to 15min ischemia. MK-801 administrated immediately after ischemia significantly decreased this hyperactivity. In all ischemic-treated animals, behavioural suppression by MK-801 was observed already 1 day after occlusion and was lasting as far as observed ischemia-dependent hypermotor responses. Beneficial effect of MK-801 was also confirmed by morphological and neurological status data. These findings suggest that sustained ischemia-induced hyperactivity is related to abnormalities in NMDA glutamatergic function, as well as its manifestation could be completely abolished by NMDA receptor blockade immediately after ischemic insult.     

Diabetic nephropathy in children and adolescents

Type 1 diabetes mellitus (T1DM) commonly occurs in childhood or adolescence, although the rising prevalence of type 2 diabetes mellitus (T2DM) in these age groups is now being seen worldwide. Diabetic nephropathy (DN) develops in 15–20% of subjects with T1DM and in similar or higher percentage of T2DM patients, causing increased morbidity and premature mortality. Although overt DN or kidney failure caused by either type of diabetes are very uncommon during childhood or adolescence, diabetic kidney disease in susceptible patients almost certainly begins soon after disease onset and may accelerate during adolescence, leading to microalbuminuria or incipient DN. Therefore, all diabetics warrant ongoing assessment of kidney function and screening for the earliest manifestations of renal injury. Pediatric health care professionals ought to understand about risk factors, strategy for prevention, method for screening, and treatment of early DN. This review considers each form of diabetes separately, including natural history, risk factors for development, screening for early manifestations, and strategy recommended for prevention and treatment of DN in children and adolescents.     

Activated cells in urine and monocyte chemotactic peptide-1 (MCP-1)--sensitive rejection markers in renal graft recipients

Chemokines induced during an acute immune alloresponse cause cellular infiltration of the allograft. These chemokines and cells are excreted with urine. The aim of the study was to assess the diagnostic utility of urinary excretion of monocyte chemotactic peptide-1 and certain cells involved in infiltration i.e. CD3+, CD64+ and HLA-DR+ cells. The study entailed 35 patients with acute renal rejection and 65 with a stable graft function. Urinary sediments were prepared by means of cytospin and stained with anti-CD3, anti-CD64, anti-HLA-DR labeled monoclonal antibodies. Urinary expression of MCP-1 was assayed by ELISA. In the patients with acute rejection MCP-1 level was ten-fold higher than in the patients with a stable graft function (6.1+/-3.4 vs 0.6+/-0.4 ng/mg creatinine). The number of CD3+ cells was over 5 times higher than in the non-rejection patients (13.4+/-4.6 vs 2.5+/-2.2). The number of HLA-DR+ cells was 6 times higher in the acute rejection patients (15.7+/-5.9 vs 2.5+/-2.7). The number of CD64+ cells was significantly increased in the patients during an acute rejection episode (p<0.0001). CD3+, HLA-DR+ and CD64+ cell counts strongly correlated with urine excretion of MCP-1. The counts of CD3+ and HLA-DR+ cells correlated with Banff score. The assessment of MCP-1 as well as CD3+, CD64+ and HLA-DR+ cells can provide a useful non-invasive device for the diagnosis of acute rejection. A sole assay of HLA-DR+ cell excretion provides enough specificity and sensitivity for the routine monitoring of patients after kidney transplantation, saving costs and time.