Evaluation of MMP1 and MMP3 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma

Purpose: To investigate possible genetic associations of matrix metalloproteinase-1 (MMP1) and MMP3 gene polymorphisms with exfoliation syndrome (XFS) with (XFS/+G) and without (XFS/-G) glaucoma in a cohort of Greek patients. Methods: A total of 182 unrelated Greek patients with XFS, including 92 patients with XFS/+G, and 214 unrelated age- and gender-matched controls were enrolled in the study. MMP1-1607 1G/2G (rs1799750) and MMP3-1171 5A/6A (rs3025058) polymorphisms were determined using standard PCR/restriction fragment length polymorphism methods. Differences in allele and genotype distributions were analyzed using logistic regression. Results: The distribution of genotypes and alleles in MMP1 and MMP3 polymorphisms was not significantly different between cases with exfoliation syndrome, with or without glaucoma, and controls. However, the allele contrast for the MMP1 variant showed a trend for a significant association with XFS/-G (Odds Ratio=1.47 [1.03-2.10]), since after correction for multiple comparisons, this association was no longer statistically significant. Conclusions: Our study provided some evidence of a possible role of the MMP1 variant in the development of exfoliation syndrome in Greek patients

Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation

open access articleEncapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials

Increased Diacylglycerols Characterize Hepatic Lipid Changes in Progression of Human Nonalcoholic Fatty Liver Disease; Comparison to a Murine Model

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD.Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts.Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts.Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD

Deoxynivalenol and its toxicity

Deoxynivalenol (DON) is one of several mycotoxins produced by certain Fusarium species that frequently infect corn, wheat, oats, barley, rice, and other grains in the field or during storage. The exposure risk to human is directly through foods of plant origin (cereal grains) or indirectly through foods of animal origin (kidney, liver, milk, eggs). It has been detected in buckwheat, popcorn, sorgum, triticale, and other food products including flour, bread, breakfast cereals, noodles, infant foods, pancakes, malt and beer. DON affects animal and human health causing acute temporary nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and fever. This review briefly summarizes toxicities of this mycotoxin as well as effects on reproduction and their antagonistic and synergic actions

Subjective rating of fatigue

lspitivalo se kako varira osjećaj umora u funkciji trajanja statičnog napora. Ispitanici su nakon statičnog napora različitog trajanja (30, 60, 90, 120, 150 i 180 sek) procjenjivali svoj stupanj umora na neograničenoj skali bez zadanog standarda. Na završetku ispitivanja na istim ispitanicima izvršeno je snimanje sumiranog EMG-a četiri aktivne mišićne skupine u toku od 180 sek jednakog statičnog napora. Dobiveni rezultati pokazuju da subjektivne procjene umora u funkciji trajanja statičnog napora variraju u obliku blage sigmoidalne krivulje. Izgleda, kao da u početku statičnog napora ispitanici još ne osjećaju umor, dok kod najdužih statičnih napora do usporenja porasta osjećaja umora u funkciji trajanja statičnog napora dolazi zbog svojevrsnog artefakta. Čini se kao da ispitanici u toku pokusa i nehotice fiksiraju gornju granicu svojih procjena, što dovodi do nužnog smanjenja procjena što se više toj granici približuju. Zbog toga se može samo srednji dio prosječne krivulje izraziti potencijalnom funkcijom Ψ =0,0048 (φ - 30")1, 54, gdje je Ψ subjektivna veličina umora, trajanje statičnog napora, a 30" predstavlja zamišljenu liminalnu vrijednost osjećaja umora. Krivulja prosječnog sumiranog EMG-a ima sličan tok kao i prosječna procjena osjećaja umora u funkciji trajanja statičnog napora i može se izraziti analognom formulom EMG = 0,0051 (φ - 30")1, 51. Naprotiv, među individualnim krivuljama pojedinih ispitanika nema nekog jasnog. slaganja. Individualne krivulje sumiranog EMG-a pojedinih ispitanika jednako se toliko međusobno razlikuju koliko krivulje subjektivnih procjena umora.After static efforts of various duration (30, 60, 90, 120, 150 and 180 sec.) subjects rated the degree of their feeling of fatigue on an unlimited scale without a given standard. On the same subjects were recorded, during static effort, the summed EMG of four active muscle groups. The results obtained showed that subjective ratings of fatigue in the function of duration of the static effort vary in the form of a mild sigmoid curve. The medium section of the average curve can be expressed by a potential function Ψ = 0,0048 (φ - 30")1, 54 where Ψ stands for the subjective degree of fatigue, φ for duration of the static effort and 30" represents presumed liminal value of the feeling of fatigue. The curve of the average summed EMG is very similar to that of the average rating of the feeling of fatigue in the function of duration of the static effort and can be expressed as EMG = 0,0051 (φ - 30")1, 51. Individual curves of the summed EMG differ to the same extent as the individual curves of subjective ratings of fatigue

Subjective rating of fatigue

lspitivalo se kako varira osjećaj umora u funkciji trajanja statičnog napora. Ispitanici su nakon statičnog napora različitog trajanja (30, 60, 90, 120, 150 i 180 sek) procjenjivali svoj stupanj umora na neograničenoj skali bez zadanog standarda. Na završetku ispitivanja na istim ispitanicima izvršeno je snimanje sumiranog EMG-a četiri aktivne mišićne skupine u toku od 180 sek jednakog statičnog napora. Dobiveni rezultati pokazuju da subjektivne procjene umora u funkciji trajanja statičnog napora variraju u obliku blage sigmoidalne krivulje. Izgleda, kao da u početku statičnog napora ispitanici još ne osjećaju umor, dok kod najdužih statičnih napora do usporenja porasta osjećaja umora u funkciji trajanja statičnog napora dolazi zbog svojevrsnog artefakta. Čini se kao da ispitanici u toku pokusa i nehotice fiksiraju gornju granicu svojih procjena, što dovodi do nužnog smanjenja procjena što se više toj granici približuju. Zbog toga se može samo srednji dio prosječne krivulje izraziti potencijalnom funkcijom Ψ =0,0048 (φ - 30")1, 54, gdje je Ψ subjektivna veličina umora, trajanje statičnog napora, a 30" predstavlja zamišljenu liminalnu vrijednost osjećaja umora. Krivulja prosječnog sumiranog EMG-a ima sličan tok kao i prosječna procjena osjećaja umora u funkciji trajanja statičnog napora i može se izraziti analognom formulom EMG = 0,0051 (φ - 30")1, 51. Naprotiv, među individualnim krivuljama pojedinih ispitanika nema nekog jasnog. slaganja. Individualne krivulje sumiranog EMG-a pojedinih ispitanika jednako se toliko međusobno razlikuju koliko krivulje subjektivnih procjena umora.After static efforts of various duration (30, 60, 90, 120, 150 and 180 sec.) subjects rated the degree of their feeling of fatigue on an unlimited scale without a given standard. On the same subjects were recorded, during static effort, the summed EMG of four active muscle groups. The results obtained showed that subjective ratings of fatigue in the function of duration of the static effort vary in the form of a mild sigmoid curve. The medium section of the average curve can be expressed by a potential function Ψ = 0,0048 (φ - 30")1, 54 where Ψ stands for the subjective degree of fatigue, φ for duration of the static effort and 30" represents presumed liminal value of the feeling of fatigue. The curve of the average summed EMG is very similar to that of the average rating of the feeling of fatigue in the function of duration of the static effort and can be expressed as EMG = 0,0051 (φ - 30")1, 51. Individual curves of the summed EMG differ to the same extent as the individual curves of subjective ratings of fatigue

On ecosystems dynamics

International audienceWe show how a dynamical system given by a t-score function for some class of monotonic data transformations generates consistent extreme value estimators. The variation of their values increases the uncertainty of proper assessment of climate change. Two important examples illustrate the methodology: mass balance measurements on Guanaco glacier, Chile, and extreme snow loads in Slovakia. We experience singular learning of the transitions in ecosystems