Concentrations Of Metalloproteinase Research Articles

Вплив імунокорекції на запальний процес урогенітального тракту у чоловіків з безпліддям

We studied the concentration of metalloproteinases, pro-and anti-inflammatory cytokines, lymphocyte activation markers in seminal plasma of men with oligosymptomatic forms of chronic inflammation of the urogenital tract complicated with infertility. It was shown that chronic inflammation of the urogenital tract shifts the levels of cytokine profile, reduces the concentration of metalloproteinase-2 (576.4 +/- 89.3 ng/ml, P < 0.001), chemokines - fractalkine (16.3 +/- 1.3 pg/ml, P < 0.001) and chemmmokine regulated by activation, expression and secretion of normal T-cells (RANTES (12.7 +/- 1.0 pg/ ml, P < 0.001). Additionally, we observed a sharp increase in IL-8 (215.5 +/- 7.8 pg/ml, P < 0.01), MCP-1 (926.4 +/- 30.2 pg/ml, P < 0.001) and elevation of the CD25 + / CD95 + ratio. These observations point for alterations in apoptotic mechanisms in pathological forms of the generative cells and their accumulation in the sperm. Prolonged inflammation of the genital area is accompanied by depletion of the local immune system resulting in the development of infertility. The multidirectional shifts in IL-10/IL-12 index have been established: an increase in the group of patients with elevated level of hypercapitated spermatozoa and its reduction in microsomatic morphotype of spermatozoa. These data emphasize the importance of the microenvironment in maturation of gametes. It was shown that an inclusion of alfagin and gepatomax in immunorehabilitation of men with oligosymptomatic forms of urogenital infections improves leukocyte subpopulation content of sperm and concentrations of pro-and anti-inflammatory cytokines, and therefore, results in an increase in fertilizing potential.

Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial

BackgroundNeurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomized, double-blind, placebo-controlled trial, 42 patients undergoing glial tumor surgery randomly received 40 mg atorvastatin or placebo twice daily from seven days prior to operation and continued for a 3 weeks period. Plasma MMP-9 concentration measured 4 times, immediately before starting atorvastatin or placebo, immediately before surgery, 24 hours and two weeks after the surgery. Karnofsky performance score was assessed before first dose of atorvastatin as a baseline and 2 months after the surgery.ResultsKarnofsky performance scale after surgery raised significantly more in Atorvastatin group (11.43 +/- 10.62 vs. 4.00 +/- 8.21) (p = 0.03). Atorvastatin did not significantly reduce MMP-9 plasma concentration 24 hours after surgery in comparison to placebo. No statistical significance detected regarding length of hospital stay among the groups. Significant reduction in MMP-9 plasma concentration was recorded in atorvastatin group two weeks after surgery (p = 0.048).ConclusionsSignificant statistical differences detected with atorvastatin group regarding MMP-9 plasma concentration, clinical outcome and Karnofsky performance score. Consequently, atorvastatin use may lead to better outcome after neurosurgical procedures.

Elastase and metalloproteinase-9 concentrations in saliva in patients with chronic periodontitis.

Elastase and metalloproteinase-9 (MMP-9) are two of numerous proteolytic enzymes released by neutrophilic granulocytes in the course of periodontitis. The aim of the study was to determine the concentrations of elastase and MMP-9 in saliva in patients with chronic periodontitis compared to healthy individuals.The enzyme-linked immunosorbent assay method was employed to determine the concentrations of elastase and MMP-9 in saliva in patients with chronic periodontitis and with pocket depth (PD) ≥ 6 mm and PD < 6 mm, as well as in saliva of healthy individuals. Significantly higher concentrations of elastase and MMP-9 were observed in patients with periodontitis compared to healthy individuals (p < 0.01). Also a significant difference in elastase concentration in saliva was observed between the PD ≥ 4 mm and PD < 6 mm groups and between the PD ≥ 6 mm and control groups, and statistically significant differences in MMP-9 concentrations between the PD ≥ 6 mm and control groups. No statistically significant differences were observed between the PD < 6 mm and control groups for elastase concentrations in saliva as well as between the PD ≥ 6 mm and PD < 6 mm groups, and also between the PD < 6 mm and control groups for MMP-9 concentrations in saliva. Elastase and MMP-9 concentrations in saliva can be considered as biochemical indicators of severity of periodontitis.

Resistance Exercise Increases Endothelial Progenitor Cells and Angiogenic Factors

Bone marrow-derived endothelial progenitor cells (EPC) are involved in vascular growth and repair. They increase in the circulation after a single bout of aerobic exercise, potentially related to muscle ischemia. Muscular endurance resistance exercise (MERE) bouts also have the potential to induce muscle ischemia if appropriately structured. The objective of this study is to determine the influence of a single bout of MERE on circulating EPC and related angiogenic factors. Thirteen trained men age 22.4 ± 0.5 yr (mean ± SEM) performed a bout of MERE consisting of three sets of six exercises at participants' 15-repetition maximum without resting between repetitions or exercises. The MERE bout duration was 12.1 ± 0.6 min. Blood lactate and HR were 11.9 ± 0.9 mmol·L and 142 ± 5 bpm, respectively, at the end of MERE. Blood was sampled preexercise and at 10 min, 2 h, and 24 h postexercise. Circulating EPC and serum concentrations of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D), granulocyte colony stimulating factor, soluble Tie-2, soluble fms-like tyrosine kinase-1, and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-9) were higher (P < 0.05) in the postexercise period. Circulating EPC levels were unchanged at 10 min postexercise but higher at 2 h postexercise (P < 0.05). The concentration of most angiogenic factors and metalloproteinases were higher at 10 min postexercise (VEGF-A, +38%; VEGF-C, +40%; VEGF-D, +9%; soluble Tie-2, +15%; soluble fms-like tyrosine kinase-1, +24%; MMP-1, +62%; MMP-2, +3%; MMP-3, +54%; and MMP-9, +45%; all P < 0.05). Soluble E-selectin was lower (P < 0.05) at 2 and 24 h postexercise, with endothelial microparticles and thrombomodulin unchanged. Short intense bouts of MERE can trigger increases in circulating EPC and related angiogenic factors, potentially contributing to vascular adaptation and vasculoprotection.

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis, based on measurements of plaque and intima–media thickness

PurposeTo examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima–media thickness (IMT). MethodsThis cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1–2, ≥3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8–1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors. ResultsMMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01–24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1–78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7–64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5–65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5–132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14–245.66, p = 0.01). ConclusionsElevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.

Serum SPARC and Matrix Metalloproteinase-2 and Metalloproteinase-9 Concentrations after Bariatric Surgery in Obese Adults

Remodeling of the extracellular matrix (ECM) of adipose tissue is regarded as part of the pathophysiology of obesity. Secreted protein acidic and rich in cysteine (SPARC) was the first ECM protein described in adipose tissue. Matrix metalloproteinases (MMPs) also play a role in ECM remodeling, and MMP-2 and MMP-9 may be associated with abnormal ECM metabolism. Here, we investigated changes in serum SPARC, MMP-2, and MMP-9 concentrations after bariatric surgery in obese adults. We recruited 34 obese patients who were scheduled to undergo bariatric surgery for weight loss. We analyzed changes in serum SPARC, MMP-2, and MMP-9 concentrations before and 9 months after bariatric surgery and any associations between changes in SPARC, MMP-2, and MMP-9 concentrations and obesity-related parameters. Serum leptin levels significantly decreased, and the serum adiponectin level significantly increased after bariatric surgery. The serum SPARC concentration decreased significantly from 165.0 ± 18.2 to 68.7 ± 6.7 ng/mL (p < 0.001), and the MMP-2 concentration also decreased significantly from 262.2 ± 15.2 to 235.9 ± 10.5 ng/mL (p < 0.001). Changes in the serum SPARC concentration were significantly correlated with HOMA-IR changes, and changes in the serum MMP-9 concentration were found to inversely correlate with serum adiponectin changes. These findings show that significant decreases in serum SPARC and MMP-2 concentrations occur after bariatric surgery. Our results thus suggest that weight loss via bariatric surgery could alter the ECM environment, and that these changes are related to certain metabolic changes.

The Unwounded Skin Remodeling in Animal Models of Diabetes Types 1 and 2

Diabetes mellitus types 1 and 2 are chronic diseases that cause serious health complications, including dermatologic problems. The diabetic skin is characterized by disturbances in collagen metabolism. A tissue remodeling depends on the degradation of extracellular matrix through the matrix metalloproteinases, which are regulated by e.g. the tissue inhibitors of metalloproteinases. The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is essential to maintain homeostasis in the skin. The aim of this study was to determine the concentration of metalloproteinase 2, tissue inhibitor of metalloproteinase 3 and the concentration of collagen type 1 in unwounded skin of diabetes type 1 and 2 and healthy controls. The treatment of diabetes resulted in a significant decrease of MMP2, increase of TIMP3 and COL1 concentrations in the skin as compared to the untreated diabetic skin. The concentrations of MMP2 in the skin of treated rats did not show significant differences from the healthy control group. TIMP3 concentrations in the skin of treated rats are not returned to the level observed in the control group. Disturbances of the extracellular matrix of the skin are similar in diabetes type 1 and 2. Application of insulin in diabetes therapy more preferably affects the extracellular matrix homeostasis of the skin.

Serum endothelin-1 and NT-proBNP, but not ADMA, endoglin and TIMP-1 levels, reflect impaired right ventricular function in patients with systemic sclerosis

BackgroundHeart and pulmonary involvement is a leading cause of systemic sclerosis (SSc)-related deaths.ObjectivesThe aim of our study was to assess if biochemical markers of right ventricular (RV) overload, endothelial function and collagen metabolism can predict RV dysfunction assessed by Doppler echocardiography in SSc patients.MethodsWe prospectively studied 111 consecutive patients (101 F, 10 M, age 54.2 ± 13.8 years) with diagnosed SSc (mean disease duration 9.4 ± 11.4 years) and a group of 21 age-matched subjects (18 F, 3 M, age 49.3 + 10.5 years). We performed transthoracic echocardiography (Phillips iE 33) and measured serum endothelin-1 (ET-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), asymmetric dimethylarginine (ADMA), endoglin and human tissue inhibitor of matrix metalloproteinase (TIMP-1) concentration.ResultsMedian serum NT-proBNP level in SSc patients was 133.5 (range 21.86–17,670 pg/ml) and was significantly higher than in controls (p = 0.0002). Moreover, the median serum ET-1 level of 1.49 (range 0.26–8.75 pg/ml) was higher in SSc patients (p = 0.002). However, no significant differences in ADMA, TIMP-1 and endoglin serum concentration between SSc patients and controls were observed. Serum NT-proBNP concentration correlated positively with echocardiographic signs of RV overload: tricuspid regurgitation pressure gradient (r = 0.38, p = 0.0004) and RV Tei index (r = 0.25, p = 0.01). ET-1 serum level correlated negatively with tricuspid annular plane systolic excursion (r = −0.4, p = 0.01) and positively with inferior vena cava diameter measured at expiration (r = 0.38, p = 0.0002). The echocardiographic signs of RV overload were significantly more pronounced in the highest NT-proBNP tertile (>195 pg/ml) group than in the lowest one (<88 pg/ml).ConclusionsSerum ET-1 and NT-proBNP, but not endoglin, ADMA and TIMP-1 levels correlating with the echocardiographic parameters of RV overload, can be considered as noninvasive indicators of RV dysfunction in SSc patients.

Increased Plasma Tissue Inhibitors of Metalloproteinase Concentrations as Negative Predictors Associated With Deterioration of Kidney Allograft Function Upon Long-Term Observation

Chronic allograft injury (CAI) is the most frequent cause of progressive kidney allograft impairment and eventual loss, which is due to interstitial fibrosis and tubular atrophy (IF/TA). Mechanisms of CAI are not fully understood. Chemokines, cytokines, metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) play roles in fibrosis development. The aims of this study were to evaluate plasma and urine TIMPs (TIMP-1 and TIMP-2), MMPs (MMP-2 and MMP-9), proinflammatory interleukin-6 (IL-6), chemokine (C-C motif) ligand 2 (CCL2 chemokines previously known as monocyte chemoattractant protein-1 [MCP-1]) among 150 recipients beyond 1 year post–renal transplantations and to explore the usefulness of these potential biomarkers of ongoing allograft injury. Renal transplant recipients compared with healthy volunteers (control group) showed significantly increased plasma and urine IL-6, MMP-9, TIMP-1, and TIMP-2, as well as lower plasma MMP-2 and urine CCL2 concentrations. Compared with recipients showing good function those with impairments displayed higher plasma TIMP-1 (P < .001) and TIMP-2 (P = .003) concentrations. The recipient estimated glomerular filtration rate (eGFR) values negatively correlated with plasma TIMP-1 and TIMP-2 levels (r = −0.43; P < .0001 and rs = −0.42; P < .0001, respectively) and with urine IL-6 excretion (rs = −0.33; P < .0001). Multivariate and receiver operating characteristic (ROC) analyses showed TIMP-1 plasma level assessments to be useful estimates of allograft injury.

Randomized controlled trial on collagen/oxidized regenerated cellulose/silver treatment

Collagen/oxidized regenerated cellulose (ORC)/silver therapy has been designed to facilitate wound healing by normalizing the microenvironment and correcting biochemical imbalances in chronic wounds. The aim of this study was to compare collagen/ORC/silver therapy to control (standard treatment). Patients with diabetic foot ulcers were randomized to either collagen/ORC/silver (24) or control treatment (15). Wound area measurements and wound fluid samples were taken weekly. Protease levels were measured in wound fluid samples to investigate differences between responders (≥50% reduction in wound area by week 4) and nonresponders (<50% reduction in wound area by week 4). There were significantly more responders in the collagen/ORC/silver group compared with the control group (79% vs. 43%, p = 0.035). There were significantly fewer withdrawals from the study because of infection in the collagen/ORC/silver group compared with the control group (0% vs. 31%, p = 0.012). The sum of matrix metalloproteinase-9 and elastase concentration was higher in nonresponders compared with responders at baseline (p = 0.0705) and week 4 (p = 0.012). The results suggest that collagen/ORC/silver normalizes the wound microenvironment and protects against infection, resulting in improved wound healing. It was also demonstrated that measuring a combination of proteases may be a more relevant prognostic healing marker than any individual protease alone.

Serum concentrations of metalloproteinase 2, metalloproteinase 9 and granzyme B in contact eczema patients

IntroductionContact eczema is a common skin condition with complex etiology, variable clinical presentation and lengthy therapy duration. The mechanism of contact eczema is complex, since it is affected by multiple inflammatory mediators.AimTo assess concentrations of metalloproteinase 2 (MMP-2), metalloproteinase 9 (MMP-9) and granzyme B (GzmB) in patients with contact eczema.Material and methodsSeventy patients with contact eczema and 30 healthy persons as controls were included in the study. In all subjects, MMP-2, MMP-9 and GzmB were determined using ELISA immunoassay. In study group patients, concentrations were assayed in periods of disease exacerbation and remission. Obtained results were analyzed statistically.ResultsMean MMP-2 and GzmB concentrations were found to be significantly higher in the study group than in the control group. Mean MMP-2, MMP-9 and GzmB levels were also statistically significantly higher during skin lesion relapse compared to contact eczema remission periods.ConclusionsThe presented paper demonstrates that MMP-2, MMP-9 and GzmB are good markers of contact eczema exacerbations.

Colorimetric assay of matrix metalloproteinase activity based on metal-induced self-assembly of carboxy gold nanoparticles

Among proteases, matrix metalloproteinases (MMPs) have been of significant interest because they are considered as one of the promising biomarkers in association with cancer metastasis, inflammation and other degenerative diseases. Many attempts based on the optical sensing have been made to analyze the activity of MMPs, but most of them require an expensive fluorescence readout and a labor-intensive process. To circumvent this issue, we demonstrated a simple colorimetric detection of protease activity by using carboxy gold nanoparticles (AuNPs) and histidine-containing peptides via metal-affinity coordination. Due to their higher surface-to-volume ratio, the nanometer size of AuNPs enables the surface ligands to function like a chelator, providing greater affinity with metal ions, even in the absence of chelators. With no additional modification by multidentate ligands, the carboxy AuNPs were easily aggregated and changed in color (from reddish-brown to violet) after adding peptide substrates with hexahistidine at both ends and metal ions, whereas the presence of proteases in solution prevented NP aggregation by cleaving the peptides, thereby retaining the original color of the AuNPs. When the extinction ratio (E520/E700) of the AuNP solution was measured as a function of matrix metalloproteinase concentration in a single reaction, there was good linearity from as low as 3nM to 52nM. This approach is anticipated to be useful in designing other diagnostic nanosensors.

Vitamin A deficiency disturbs collagen IV and laminin composition and decreases matrix metalloproteinase concentrations in rat lung. Partial reversibility by retinoic acid

Vitamin A is essential for lung development and pulmonary cell differentiation. Its deficiency leads to altered lung structure and function and to basement membrane architecture and composition disturbances. Previously, we showed that lack of retinoids thickens the alveolar basement membrane and increases collagen IV, which are reversed by retinoic acid, the main biologically active vitamin A form. This study analyzed how vitamin A deficiency affects the subunit composition of collagen IV and laminin of lung basement membranes and pulmonary matrix metalloproteinase content, plus the recovering effect of all-trans-retinoic acid. Male weanling pups were fed a retinol-adequate/-deficient diet until 60 days old. A subgroup of vitamin-A-deficient pups received daily intraperitoneal all-trans-retinoic acid injections for 10 days. Collagen IV and laminin chain composition were modified in vitamin-A-deficient rats. The protein and mRNA contents of chains α1(IV), α3(IV) and α4(IV) increased; those of chains α2(IV) and α5(IV) remained unchanged; and the protein and mRNA contents of laminin chains α5, β1 and γ1 decreased. The mRNA of laminin chains α2 and α4 also decreased. Matrix metalloproteinases 2 and 9 decreased, but the tissue inhibitors of metalloproteinases 1 and 2 did not change. Treating vitamin-A-deficient rats with retinoic acid reversed all alterations, but laminin chains α2, α4 and α5 and matrix metalloproteinase 2 remained low. In conclusion, vitamin A deficiency alters the subunit composition of collagen IV and laminin and the lung's proteolytic potential, which are partly reverted by retinoic acid. These alterations could contribute to impaired lung function and predispose to pulmonary disease.

Targeted nanoparticles in imaging: paving the way for personalized medicine in the battle against cancer

The way we view cancer has advanced greatly in the past few decades from simplistic approaches to finely honed systems. This transition has been made possible because of advancements on two fronts: the first is the rapidly expanding knowledge base of the mechanisms and characteristics of cancer; the second is innovation in imaging agent design. Rapid advancements in imaging and therapeutic agents are being made through the evolution from one-dimensional molecules to multi-functional nanoparticles. Powerful new agents that have high specificity and minimal toxicity are being developed for in vivo imaging. Here we detail the unique characteristics of cancer that allow differentiation from normal tissue and how they are exploited in nanoparticle imaging development. Firstly, genetic alterations, either endogenous or induced through gene therapy, are one such class of characteristics. Proteomic differences such as overexpressed surface receptors is another targetable feature used for enhanced nanoparticle retention. Increased need for nutrients and specific growth signals to sustain proliferation and angiogenesis are further examples of how cancer can be targeted. Lastly, migration and invasion through a unique microenvironment are two additional traits that are exploitable, due to differences in metalloproteinase concentrations and other factors. These differences are guiding current nanoparticle design to better target, image and treat cancer.

Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachnoid hemorrhage

Objectives: The pathogenesis of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) is multi-factorial and not completely elucidated. Matrix metalloproteinase-9 (MMP-9) might participate in wall remodeling leading to luminal narrowing. The authors investigated MMP-9 concentration in brain extracellular fluid of aSAH patients and assessed whether this enzyme could have a predictive value for the risk of DCI.Methods: Patients were classified according to the grading of the World Federation of Neurological Surgeons (WFNS) in low- and high-grade patients (WFNS = 1–3, n = 9 and WFNS = 4–5, n = 12, respectively). Cerebral microdialysis probes were placed in brain parenchyma of the respective vascular territory of the aneurysm in 21 consecutive aSAH patients, enrolled in a prospective study on inflammation. Microdialysis samples, collected daily from day 0 until day 8 after aSAH, were retrospectively analyzed for MMP-9 by zymography.Results: Initial concentration of the MMP-9 proform (pro-MMP-9) was significantly higher in high-grade patients as compared to low-grade patients. Furthermore, initial pro-MMP-9 concentration in patients with DCI was seven-fold higher than in asymptomatic patients. Pro-MMP-9 values greater than or equal to 0·27 pg/μl showed 83% sensitivity and 63% specificity in predicting vasospasm. The mature form of the MMP-9 could be preferentially detected in patients with DCI but was usually low.Discussion: The pro and mature forms of MMP-9 were released locally in the brain after aSAH. Pro-MMP-9 release was related to WFNS grade severity. This protease, considered as playing a critical role in endothelial basal membrane damage, may contribute to the inflammatory processes leading to arterial narrowing.

Alteration of immunologic responses on peripheral blood in the acute phase of ischemic stroke: Blood genomic profiling study

ObjectivePeripheral blood cells and inflammatory mediators have a detrimental effect on brain during cerebral ischemia. We investigated the immunologic changes on peripheral blood in the acute phase of ischemic stroke using RNA microarray. MethodsmRNA microarray and real time-polymerase chain reaction (RT-PCR) for genes of interest in microarray data were analyzed in 12 stroke patients and 12 controls. Plasma matrix metalloproteinase-9 (MMP-9) concentrations were measured in 120 stroke patients and 82 controls. ResultsIn microarray analysis, a total of 11 genes of interest showed different expression in patients with ischemic stroke. The three most highly expressed genes were C19orf59 (chromosome 19 open reading frame 59), MMP9 and IL18RAP (interleukin-18 receptor accessory protein), whereas gene with the lowest expression was GNLY (granulysin). The expression patterns of three selected genes (MMP9, IL18RAP and GNLY) were validated by RT-PCR. The plasma concentration of MMP-9 was significantly elevated in the stroke patients, and showed a weakly positive correlation with infarct volume. Gene set enrichment analysis (GSEA) showed that gene sets related to immunity and defense, signal transduction, transport and cell adhesion were significant in acute ischemic stroke. ConclusionsIn the peripheral blood, numerous genes of inflammatory mediators, including MMP9, IL18RAP and GNLY, are altered in the acute phase of ischemic stroke. This stroke-specific gene expression profiling provides valuable information about the role of peripheral inflammation to the pathophysiological mechanism of ischemic stroke.

Magnesium Reduces Matrix Metalloproteinase-9, But Not Glial Fibrillary Acidic Protein, In Cardiac Surgery Patients

Magnesium (Mg) is one of the most important ions in the brain. Its supplementation decreases intracellular disorders and improves final outcomes following traumatic brain injury. Aim: The aim of the study was to analyze the effects of magnesium supplementation on arteriovenous differences in plasma magnesium concentration in brain circulation (a–vMg), plasma matrix metalloproteinase-9 (MMP-9) and glial fibrillary acidic protein (GFAP) concentrations in cardiac surgery patients. Methods: A total of 92 adult patients were enrolled. Patients were allocated into three groups: A, receiving 6.66 mg of MgSO4 per min intravenously; B, receiving 10 mg of MgSO4; and C, receiving 13.33 mg of MgSO4. Results: In all groups, GFAP and MMP-9 increased after extracorporeal circulation and immediately after surgery. Sequentially higher concentrations of MMP-9 and a–vMg were noted in groups A, B and C. Plasma GFAP concentrations were similar in all groups. Conclusion: Magnesium supplementation reduces plasma MMP-9 and a-vMg in brain circulation but does not affect plasma GFAP.

A Preclinical Assessment of Neural Stem Cells as Delivery Vehicles for Anti-Amyloid Therapeutics

Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated Aβ peptides that are the major constituents of the senile plaques. Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered. We found that our injection methods led to cells largely distributing to white matter tracts, which are anisotropic conduits for fluids that facilitate rapid distribution within the CNS. Third, with regard to MMP9 as a therapeutic to remove senile plaques, we observed high concentrations of endogenous metalloproteinases around amyloid plaques in the mouse models used for these preclinical tests with no evidence that the NSC-delivered enzymes elevated these activities or had any impact. Interestingly, MMP9-expressing NSCs formed substantially larger grafts. Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.

The role of selected metalloproteinases in cheiroarthropathy in children with type 1 diabetes - a pilotage study

Metalloproteinases of the external matrix play an important role in ethiopatogenesis of diabetic complications especially in microangiopathy and also in fibrosing processes with occurrence the cheiroarthropathy, but clinical data are insufficient. The aim of the study was to assess the influence of metalloproteinases such as gelatinase A (MMP2) and gelatinase B (MMP9), and their tissue inhibitors (TIMP2, TIMP9) in ethiopathogenesis of cheiroatrhopathy in children with diabetes type 1. Forty one children were observed in average age of 14.98 years (±3.03 years), with the average duration of diabetes 6.78 years (±3.21 years), and with average HbA1c within all diabetes duration time 7.1% (6.47-7.5%). In all patients, the occurrence of cheiroarthropathy was checked, and concentration of metalloproteinase's and their inhibitors in serum were measured using ELISA method. Probe was divided into two groups because of presence of cheiroarthropathy. The comparing analysis of these two groups was conducted, and the correlation between metalloproteinase's concentration and their tissue inhibitors with selected parameters was done. When comparing group with cheiroarthropathy (n = 19) with the group without cheiroarthropathy (n = 22), the statistically significant elevated levels of metalloproteinase's were proved such as: MMP2 - 202 ng/ml (193-207) vs. 138 ng/ml (130-158), p < 0.001; MMP9 - 462 ng/ml (426-505) vs. 288 ng/ml (251-313), 0.001; TIMP2 - 182 ng/ml (177-190) vs. 104 ng/ml (88-165), p < 0.001); TIMP9 - 85 ng/ml (68-95) vs. 55 ng/ml (50-60), p < 0.001. There was no correlation between occurrence of cheiroarthropathy and age of the diabetes onset, duration of diabetes, grade of metabolic compensation, insulin dosages, weight and height. In children with long-term diabetes, although relatively metabolic compensation, the cheiroarthropathy has been occurred accompanying by elevated concentrations of metalloproteinase's and their tissue inhibitors. The presence of cheiroarthropathy could be treated as a simple test to identification the patients endangered to develop chronic vascular complication.

Effect of Helicobacter pylori Eradication According to the IL-8-251 Polymorphism in Koreans

Previous studies suggested that polymorphisms of proinflammatory cytokine genes are important host genetic factors in Helicobacter pylori infection. The present study evaluated whether IL-8-251 polymorphism affected H. pylori eradication rate and to investigate the effect of H. pylori eradication on angiogenesis and the inflammatory process according to the IL-8-251 polymorphism. A total of 250 H. pylori-positive patients treated by endoscopic resection of the gastric neoplasm were classified into 3 groups (134 H. pylori-eradicated group, 19 H. pylori-eradication failure group, and 97 H. pylori-infected group). H. pylori status, histology, and angiogenic factor levels were evaluated at baseline, 6 months, and 18 months. H. pylori eradication rate was 92.9% in AA genotype, 85.7% in AT genotype and 88.4% in TT genotype (P value = 0.731). Elevated IL-8 and matrix metalloproteinase-9 concentrations in H. pylori-infected gastric mucosa were reversible by successful eradication of H. pylori, independent of the IL-8-251 polymorphism. It is suggested that elevated IL-8 and MMP-9 concentrations in H. pylori-infected gastric mucosa are altered significantly after successful eradication and these conditions continue for 18 months. However, IL-8-251 polymorphism does not affect H. pylori eradication rate and the sequential changes of related angiogenic factors after H. pylori eradication in Koreans.