Role of phospholipase A(2) and tyrosine kinase in Clostridium difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Clostridium difficile-associated disease causes diarrhea to fulminant colitis and death. We investigated the role of phospholipase A(2) (PLA(2)) inhibitors, aristolochic acid (AA), bromophenacyl bromide BPB and quinacrine (QUIN) on the C. difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion. Toxin A caused severe hemorrhagic and inflammatory fluid secretion at 6-8 h in rabbit ileal segments, an effect that was significantly inhibited by QUIN (71%, P < 0.01), AA (87%, P < 0.0001) or by BPB (51%, P < 0.01). The secretory effect of toxin A was also inhibited in segments adjacent to those with AA (89%, P < 0.01). Furthermore, QUIN or AA substantially reduced the histologic damage seen after 6-8 h in rabbit ileal segments. The cyclooxygenase inhibitor, indomethacin, also significantly inhibited (96%; n = 6) the secretory effects of toxin A in ligated rabbit intestinal segments. The destruction by toxin A of F-actin at the light junctions of T-84 cell monolayers was not inhibited by AA or BPB. AA or QUIN had no effect on the T-84 cell tissue resistance reduction over 8-24 h after toxin A exposure. All the inhibitors were shown to be effective in the doses administered direct in ileal loops to inhibit PLA(2) activity. The data suggest that PLA(2) is involved in the major pathway of toxin A-induced histologic inflammatory damage and hemorrhagic fluid secretion. Cop. right (C) 2008 John Wiley & Sons, Ltd.

Protective effect of (-)-epigallocatechin gallate on ultraviolet b-induced skin damage in hairless mice

Purpose: To investigate the protective effect of green tea (-)-epigallocatechin gallate (EGCg) on ultraviolet B (UV-B)-induced skin damages in hairless mice in order to develop a natural sunscreen compound for use in skin care products and cosmetics. Methods: EGCg was dissolved in acetone at concentrations of 1.0, 10.0 and 50.0 mg/mL, and topically applied to the skin of hairless mice at doses of 0.2 mL/cm2, with acetone as control. The mice were then irradiatd m2 UV-B for 30 min daily. EGCg treatment and UV-B irradiation were carried out daily for 28 consecutive days. The mice were then sacrificed and their dorsal skin examined by transmission electron microscopy (TEM) on the 28th day. Results: UV-B irradiation induced severe macroscopic skin damage including chapping, cracking and abnormal desquamation in the treated hairless mice. EGCg showed dose-dependent protective effects against UV-B induced damage on the skin. Treatments with 10.0 and 50.0 mg/mL EGCg alleviated UVB-induced skin damage by suppressing both keratinocyte apoptosis and mitochondrial dysfunction, along with inhibiting the production of melanin pigment. Conclusion: Topical application of green tea EGCg shows dose-dependent protective effect against UV-B-induced damage on hairless mouse skin. Thus, the plant compound can potentially be used as an alternative agent for photoprotection against UV-B exposure.

Mitigating effects of Jambul against lead induced toxicity in epididymis and vas deferens of mice

Background: Precious fruits like jambul are neglected and wasted while environmental pollutants like lead intake remain overlooked. Objective: The aim of this study was to investigate the effects of the Jambul pulp extract on lead detrimental effects in pseudostratified epithelium and the stereocilia of mice epididymis and vas deferens. Materials and Methods: Thirty young males mice (Mus musculus) were distributed randomly in 3 groups (n= 10) called control, Pb (Lead) and Pb-J (Lead-Jambul). The Pb and Pb-J were provided 50ppm Pb in drinking water ad libitum for 15 days and Pb free water for the next 5 days. The Pb-J group received 0.2ml jambul pulp extract on 12 hourly bases. Control group was not given any treatment. Organs (epididymis and vas deference) were recovered on 21st day after euthanasia. The organs were finally processed for histological and micrometric studies. Results: Marked histologic and micrometric changes in both organs were noted in Pb group. These include significant (P ≤ 0.05) decrease in cross sectional area of caput and cauda epididymis folding tubing along with evident alterations of their endothelial thickness. Prominent signs of apoptosis (vacuolations) in the corpus pseudostratified endothelium and the destruction of stereocilia of the epididymis and vas deferens in Pb compared to control group were observed. Evident signs of recovery, in both organs, such as proliferation and rearrangements in pseudostratified endothelium and the stereocilia along with convincing recovery in micrometric parameters were observed in Pb-J group. Conclusion: The results indicate that epididymis and vas deferens are highly sensitive to Pb exposure while Jambul pulp extract has shown rich mitigating potentials against such histopathologies.

Chronic sustained hypoxia-induced redox remodeling causes contractile dysfunction in mouse sternohyoid muscle

Chronic sustained hypoxia (CH) induces structural and functional adaptations in respiratory muscles of animal models, however the underlying molecular mechanisms are unclear. This study explores the putative role of CH-induced redox remodeling in a translational mouse model, with a focus on the sternohyoid—a representative upper airway dilator muscle involved in the control of pharyngeal airway caliber. We hypothesized that exposure to CH induces redox disturbance in mouse sternohyoid muscle in a time-dependent manner affecting metabolic capacity and contractile performance. C57Bl6/J mice were exposed to normoxia or normobaric CH (FiO2 = 0.1) for 1, 3, or 6 weeks. A second cohort of animals was exposed to CH for 6 weeks with and without antioxidant supplementation (tempol or N-acetyl cysteine in the drinking water). Following CH exposure, we performed 2D redox proteomics with mass spectrometry, metabolic enzyme activity assays, and cell-signaling assays. Additionally, we assessed isotonic contractile and endurance properties ex vivo. Temporal changes in protein oxidation and glycolytic enzyme activities were observed. Redox modulation of sternohyoid muscle proteins key to contraction, metabolism and cellular homeostasis was identified. There was no change in redox-sensitive proteasome activity or HIF-1α content, but CH decreased phospho-JNK content independent of antioxidant supplementation. CH was detrimental to sternohyoid force- and power-generating capacity and this was prevented by chronic antioxidant supplementation. We conclude that CH causes upper airway dilator muscle dysfunction due to redox modulation of proteins key to function and homeostasis. Such changes could serve to further disrupt respiratory homeostasis in diseases characterized by CH such as chronic obstructive pulmonary disease. Antioxidants may have potential use as an adjunctive therapy in hypoxic respiratory disease.

THERMOGRAVIMETRIC ALTERATIONS OF CASSAVA STARCH GRANULES INDUCED BY HYDROGEN PEROXIDE, UV RAYS AND MICROWAVE

Starches are applied in several fields of industry. Amylose and amylopectin (natural polymers) constitute the starch in vegetable cells. In some processes native starches cannot support high stress conditions (high temperatures/acidity). Then, modification methods are developed aiming the improving of starch technological utilization. Oxidative modification with H2O2 has been the subject of many researches. UV rays as well microwave irradiation can be used. The aim was to confirm possible thermogravimetric alterations in native cassava starch (A) granules due to a double starch modification: 1st step) H2O2 standard solutions 0.1 mol L-1 (B), 0.2 mol L-1 (C) and 0.3 mol L-1 (D) and UV rays exposure for 1h; 2nd step) microwave irradiation for 5 min. The results of thermogravimetric curves (TG-DTA) show that the behaviors of the starch proprieties were modified. Highlighting, the modified samples C and D showed a decrease on the thermal stability step. This alteration turned them suitable to many field of industry like the paper one.

The mechanical strength of phosphates under friction-induced cross-linking

Purpose: In the present study, we consider mechanical properties of phosphate glasses under high temperatureinduced and under friction-induced cross-linking, which enhance the modulus of elasticity. Design/methodology/approach: Two nanomechanical properties are evaluated, the first parameter is the modulus of elasticity (E) (or Young's modulus) and the second parameter is the hardness (H). Zinc meta-, pyro - and orthophosphates were recognized as amorphous-colloidal nanoparticles were synthesized under laboratory conditions and showed antiwear properties in engine oil. Findings: Young's modulus of the phosphate glasses formed under high temperature was in the 60-89 GPa range. For phosphate tribofilm formed under friction hardness and the Young's modulus were in the range of 2-10 GPa and 40-215 GPa, respectively. The degree of cross-linking during friction is provided by internal pressure of about 600 MPa and temperature close to 1000°C enhancing mechanical properties by factor of 3 (see Fig 1). Research limitations/implications: The addition of iron or aluminum ions to phosphate glasses under high temperature - and friction-induced amorphization of zinc metaphosphate and pyrophosphate tends to provide more cross-linking and mechanically stronger structures. Iron and aluminum (FeO4 or AlO4 units), incorporated into phosphate structure as network formers, contribute to the anion network bonding by converting the P=O bonds into bridging oxygen. Future work should consider on development of new of materials prepared by solgel processes, eg., zinc (II)-silicic acid. Originality/value: This paper analyses the friction pressure-induced and temperature–induced the two factors lead phosphate tribofilm glasses to chemically advanced glass structures, which may enhance the wear inhibition. Adding the coordinating ions alters the pressure at which cross-linking occurs and increases the antiwear properties of the surface material significantly.

Exposure to pesticides, ill health and averting behaviour : costs and determining the relationship

Farmers' exposure to pesticides is high in developing countries. As a result many farmers suffer from ill-health, both short and long term. Deaths are not uncommon. This paper addresses this issue. Field survey data from Sri Lanka are used to estimate farmers' expenditure on defensive behavior (DE) and to determine factors that influence DE. The avertive behavior approach is used to estimate costs. Tobit regression analysis is used to determine factors that influence DE. Field survey data show that farmers' expenditures on DE are low. This is inversely related to high incidence of ill health among farmers using pesticides.