Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) predisposes to cardiovascular complications. Increased concentrations of pro-inflammatory mediators and imbalanced concentrations of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may reflect the pathophysiology of MetS. We compared the circulating levels of MMPs, TIMPs, and inflammatory mediators in MetS patients with those found in healthy controls. Methods: We studied 25 healthy subjects and 25 MetS patients. The plasma levels of pro-MMP-2 and pro-MMP-9 were determined by gelatin zymography. The plasma concentrations of MMP-8, MMP-3, TIMP-1, TIMP-2, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1), and sP-selectin were measured by ELISA kits. Results: We found higher sP-selectin, sICAM-1, MCP-1, and IL-6 (all P<0.05) concentrations in MetS patients compared with healthy controls. No differences in pro-MMP-2, MMP-3, and TIMP-2 levels were found (all P>0.05). However, we found higher pro-MMP-9, MMP-8. and TIMP-1 levels in MetS patients compared with healthy controls (all P<0.05). Conclusions: Patients with MetS have increased circulating concentrations of pro-MMP-9, MMP-8, and TIMP-1 that are associated with increased concentrations of pro-inflammatory mediators and adhesion molecules. These findings suggest that MMPs may have a role in the increased cardiovascular risk of MetS patients. Pharmacological interventions targeting MMPs, especially MMP-9 and MMP-8 deserve further investigation in MetS patients. (C) 2009 Elsevier B.V. All rights reserved.

Inverse relationship between markers of nitric oxide formation and plasma matrix metalloproteinase-9 levels in healthy volunteers

Background: Nitric oxide (NO) is a major regulator of cardiovascular homeostasis and has anti-atherogenic properties. Reduced NO formation is associated with endothelial dysfunction and with cardiovascular risk factors. Although NO downregulates the expression and activity of the pro-atherogenic enzyme matrix metalloproteinase-9 (MMP-9), no previous clinical study has examined whether endogenous NO formation is inversely associated with the circulating levels of pro-MMP-9, which are associated with cardiovascular events. We examined this hypothesis in 175 healthy male subjects who were non-smokers. Methods: To assess NO bioavailability, the plasma concentrations of nitrite, nitrate, and cGMP were determined using an ozone-based chemiluminescence assay and an enzyme immunoassay. Pro-MMP-9 and pro-MMP-2 levels were measured in plasma samples by gelatin zymography. Results: We found significant negative correlations between pro-MMP-9 levels and plasma nitrite (P=0.035, rs=-0.159), nitrate (P=0.040, rs=-0.158), and cGMP (P=0.011, rs=-0.189) concentrations. However, no significant correlations were found between pro-MMP-2 levels and the plasma concentrations of markers of NO bioavailability (all P>0.05). Conclusions: There is an inverse relationship between markers of NO formation and plasma MMP-9 levels. This finding may shed some light on the possible mechanisms involved in the increased cardiovascular risk of apparently healthy subjects with low NO bioavailability or high circulating levels of pro-MMP-9. (C) 2008 Elsevier B.V. All rights reserved.

Smallest weak and smallest totally weak critical sets in the latin squares of order at most seven

A critical set in a latin square of order n is a set of entries in a latin square which can be embedded in precisely one latin square of order n. Also, if any element of the critical set is deleted, the remaining set can be embedded in more than one latin square of order n. In this paper we find smallest weak and smallest totally weak critical sets for all the latin squares of orders six and seven. Moreover, we computationally prove that there is no (totally) weak critical set in the back circulant latin square of order five and we find a totally weak critical set of size seven in the other main class of latin squares of order five.

Arachidonic acid stimulates glucose uptake in 3T3-L1 adipocytes by increasing GLUT1 and GLUT4 levels at the plasma membrane: Evidence for involvement of lipoxygenase metabolites and peroxisome proliferator-activated receptor

Exposure of insulin-sensitive tissues to free fatty acids can impair glucose disposal through inhibition of carbohydrate oxidation and glucose transport. However, certain fatty acids and their derivatives can also act as endogenous ligands for peroxisome proliferator-activated receptor gamma (PPARgamma ), a nuclear receptor that positively modulates insulin sensitivity. To clarify the effects of externally delivered fatty acids on glucose uptake in an insulin-responsive cell type, we systematically examined the effects of a range of fatty acids on glucose uptake in 3T3-L1 adipocytes. Of the fatty acids examined, arachidonic acid (AA) had the greatest positive effects, significantly increasing basal and insulin-stimulated glucose uptake by 1.8- and 2-fold, respectively, with effects being maximal at 4 h at which time membrane phospholipid content of AA was markedly increased. The effects of AA were sensitive to the inhibition of protein synthesis but were unrelated to changes in membrane fluidity. AA had no effect on total cellular levels of glucose transporters, but significantly increased levels of GLUT1 and GLUT4 at the plasma membrane. While the effects of AA were insensitive to cyclooxygenase inhibition, the lipoxygenase inhibitor, nordihydroguaiaretic acid, substantially blocked the AA effect on basal glucose uptake. Furthermore, adenoviral expression of a dominant-negative PPARgamma mutant attenuated the AA potentiation of basal glucose uptake. Thus, AA potentiates basal and insulin-stimulated glucose uptake in 3T3-L1 adipocytes by a cyclooxygenase-independent mechanism that increases the levels of both GLUT1 and GLUT4 at the plasma membrane. These effects are at least partly dependent on de novo protein synthesis, an intact lipoxygenase pathway and the activation of PPARgamma with these pathways having a greater role in the absence than in the presence of insulin.

Critical cyber pedagogy: Doing multiliteracies in the Singapore classrooms

The Ministry of Education in Singapore has embarked on the ambitious project of introducing IT in schools. The IT Masterplan, budgeted at a cost of $2 billion, aims to wire up all schools by the year 2002. While the well-funded IT Masterplan is seeing the project in its final phase of implementation, this paper argues for a "critical cyber pedagogy" along with the acquisition of the functional and operational skills of technology. Drawing on theories of critical multiliteracies (Burbules & Callister, 2000; Luke, 2000b; New London Group, 1996), this paper explores and suggests how an instructional design of two classroom activities can be utilized as new forms of cyber and technoliteracies. Through the critical evaluation of websites and hypertext construction, students will be equipped with a new literacy that extends reading and writing by incorporating new blended forms of hybrid textualities. This technology-assisted pedagogy can achieve the desired outcome of self-directed learning, teamwork, critical thinking and problem solving strategies necessary for a knowledge-based society.

Critical review of acid in situ leach uranium mining: 1. USA and Australia

The technique of in situ leach (ISL) uranium mining is well established in the USA, as well as being used extensively in Eastern Europe and the former Soviet Union. The method is being proposed and tested on uranium deposits in Australia, with sulfuric acid chemistry and no restoration of groundwater following mining. Test sites in the USA were required to restore groundwater to ascertain the extent of impacts and compare costs to alkaline ISL mines. The problems encountered include expensive and difficult restoration, gypsum precipitation, higher salinity and some heavy metals and radionuclides after restoration. One of the most critical issues is whether natural attenuation is capable of restoring groundwater quality and geochemical conditions in an acid leached aquifer zone. The history of acid ISL sites in the USA and Australia are presented in this study, with a particular focus on the demonstration of restoration of groundwater impacts.

Critical review of acid in situ leach uranium mining: 2. Soviet Block and Asia

The technique of in situ leach (ISL) uranium mining is well established in the USA, as well as being used extensively in Eastern Europe and the former Soviet Union. The method is being proposed and tested on uranium deposits in Australia, with sulphuric acid chemistry and no restoration of groundwater following mining. ISL mines in the former Soviet Union generally used acid reagents and were operated without due consideration given to environmental protection. At many former mine sites, the extent of groundwater contamination is significant because of high salinity, heavy metal and radionuclide concentrations compared with pre-mining and changes in the hydrogeological regime caused by mining. After the political collapse of the Soviet Union by the early 1990s, most uranium mines were shut down or ordered to be phased out by government policy. Programmes of restoration are now being undertaken but are proving technically difficult and hampered by a lack of adequate financial resources. The history and problems of acid ISL sites in countries of the former Soviet Union and Asia are presented in this study.

Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load

Primary infection with the human herpesvirus, Epstein-Barr virus (EBV), may result in subclinical seroconversion or may appear as infectious mononucleosis (IM), a lymphoproliferative disease of variable severity. Why primary infection manifests differently between patients is unknown, and, given the difficulties in identifying donors undergoing silent seroconversion, little information has been reported. However, a longstanding assumption has been held that IM represents an exaggerated form of the virologic and immunologic events of asymptomatic infection. T-cell receptor (TCR) repertoires of a unique cohort of subclinically infected patients undergoing silent infection were studied, and the results highlight a fundamental difference between the 2 forms of infection. In contrast to the massive T-cell expansions mobilized during the acute symptomatic phase of IM, asymptomatic donors largely maintain homeostatic T-cell control and peripheral blood repertoire diversity. This disparity cannot simply be linked to severity or spread of the infection because high levels of EBV DNA were found in the blood from both types of acute infection. The results suggest that large expansions of T cells within the blood during IM may not always be associated with the control of primary EBV infection and that they may represent an overreaction that exacerbates disease. (C) 2001 by The American Society of Hematology.

Concepts for critical appraisal of an original research paper.

With the ever-growing evidence base it is more difficult to keep abreast of relevant issues in health care. Studies are also becoming more complex in order to address specific research and clinical questions. Appropriate interpretation of these studies is paramount to a progressive practice in health care. This article presents an intellectual framework for the critical appraisal of an original research article. (author abstract)

Development of a real-time RT-PCR assay for plasma membrane calcium ATPase isoform 1 (PMCA1) mRNA levels in a human breast epithelial cell line.

The plasma membrane Ca2+ pump is a key regulator of cytosolic free Ca2+. Recent studies have demonstrated the dynamic expression of the plasma membrane Ca2+ pump in a variety of cell types. Furthermore, alterations in plasma membrane calcium pump activity have now been implicated in human disease. In this study, the development of a technique to quantitatively assess mRNA expression of the human plasma membrane Ca2+ ATPase (PMCA1) isoform of the plasma membrane Ca2+ pump, using a real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) assay in a human breast epithelial cell line (MCF-7) is described. The sequences of the PMCA1 primers and probe for real-time RT-PCR are presented. The results also indicate that PMCA1 mRNA can be normalized to both 18S ribosomal RNA (18S rRNA) and human glyceraldehyde-3-phosphate dehydrogenase (hGAPDH) in MCF-7 cells. Real-time RT-PCR will be most useful in assessing PMCA1 mRNA expression in cases where only low amounts of RNA are available and/or when numerous samples must be assessed simultaneously. (C) 2001 Elsevier Science Inc. All rights reserved.

A critical comparison of the external and internal boron requirements for contrasting species in boron-buffered solution culture

Despite reports that boron (B) requirements differ among plant species there is a shortage of critical evidence to demonstrate unequivocally whether species differ in internal or external B requirements or both. The present research was conducted to establish the external and internal B requirements of three contrasting species, a woody dicot (marri), an herbaceous dicot (sunflower) and a monocot (wheat) using B-buffered solution culture. Boron-buffered solution culture provided satisfactory control of external B concentrations ranging from 0.04 to 30 muM throughout the 20- (sunflower and wheat) or 40-day (marri) growth period. At low external B concentrations (less than or equal to 0.13 muM), the growth of marri and sunflower was severely depressed but by contrast the vegetative growth of wheat plants was satisfactory and free of B deficiency symptoms. Marri and sunflower plants achieved total maximum shoot growth at greater than or equal to1.2 muM B in solutions while wheat plants did so at greater than or equal to 0.6 muM B. The critical B concentrations (mg kg(-1) dry matter) in the youngest open leaf blades of marri, sunflower and wheat plants were 17.9, 19.7 and 1.2 on 20, 10 and 10 days after transplanting (DAT), respectively. Lower internal and external B requirements of wheat were matched by a lower uptake rate of B compared to marri and sunflower.

Responses of sugarcane, maize, and soybean to phosphorus and vesicular-arbuscular mycorrhizal fungi

The presence of vesicular-arbuscular mycorrhizal (VAM) fungi in long-term cane-growing fields associated with yield decline led to the supposition that VAM fungi may be responsible for the poor yields. A glasshouse trial was established to test the effectiveness of a species of VAM fungi, Glomus clarum, extracted from one of these North Queensland fields on the growth of sugarcane (Saccharum interspecific hybrid), maize (Zea mays), and soybean (Glycine max) for 6 phosphorus (P) rates (0, 2.7, 8.2, 25, 74, 222 mg/kg). For maize and soybean plants that received VAM (+ VAM), root colonisation was associated with enhanced P uptake, improved dry weight (DW) production, and higher index tissue-P concentrations than those without VAM (-VAM). By comparing DW responses of maize and soybean for different P rates, savings in fertiliser P of up to 160 and 213 kg/ha, respectively, were realised. Sugarcane plants were generally less responsive. Apart from a 30% DW increase with VAM when 2.7 mg P/kg was added, DW of +VAM plants was equivalent to, or worse than in the case of 222 mg P/kg, DW of -VAM plants. For all 3 host species, colonisation was least at the highest P application, presumably from excessive P within the plant tissue. Critical P concentrations for the 3 host species were below those reported elsewhere, and for soybean and sugarcane, the critical concentration for +VAM plants was lower than that of -VAM plants. There are 3 implications that arise from this study. First, VAM fungi present in cane-growing soils can promote the growth of maize and soybean, which are potential rotation crops, over a range of P levels. Second, the mycorrhizal strain taken from this site did not generally contribute to a yield decline in sugarcane plants. Third, application of P fertiliser is not necessary for sugarcane when acid-extractable P is