Терапія післяопераційних ран армованими пов’язками на основі пекти-ну та їх протимікробна дія

A reinforced pectin-based dressing with a reinforcing element containing the antimicrobial agent chlorhexidine bigluconate has been developed. In vitro studies have shown that the hydrogel pectin dressing containing 0.03 ÷ 1.5 % chlorhexidine bigluconate inhibits the growth of both gram-positive (S. aureus) and gram-negative (P. aeruginosa) bacteria. The dressing can be used in the complex treatment of postoperative wounds with infectious-inflammatory process. The efficacy of different doses of chlorhexidine bigluconate was characterized by growth inhibition and increase of microorganism-free areas on the culture medium around the site of dressing localization, and regardless of the type of bacteria. Bacterial growth inhibition radius size depends on the dose of chlorhexidine in the hydrogel pectin dressing. The inhibition of growth of S. aureus and P. aeruginosa is directly proportional to chlorhexidine bigluconate content. The increase of dressing saturation with chlorhexidine to 1.0 and 1.5 % recorded the maximum inhibition of the growth of microorganisms. A veterinary clinical trial has shown a good therapeutic effect in the wound healing, in particular in the complex treatment of postoperative and accidental wounds both in the presence of infectious-inflammatory process and in its absence. The reinforced pectin-based dressing with cotton (or polypropylene) reinforcement element containing chlorhexidine bigluconate reduces the cost of dressings and bandaging frequency during wound healing. It protects the wound surface from contamination, mechanical irritation, bacterial contamination and the development of secondary infection. The dressing promotes good water, air and heat exchange between the wound and the environment, adsorbs excess exudate, maintains a moist environment and does not cause hyperosmotic damage and drying of the wound. Surgical wound healing occurred under the initial tension for 7 days. Considering the method of its application, this dressing is suitable for use on different parts of the animal's body (neck, withers, chest and abdomen, lower back, buttocks, thighs, shoulders, etc.).Розроблено армовану пов’язку на основі пектину з елементом армування, що містить антимікробний засіб хлоргексидин біглюконат. Проведені дослідження in vitro показали, що гідрогелева пектинова пов’язка з вмістом 0,03 ÷ 1,5 % хлоргексидину біглюконату пригнічує ріст як грампозитивних (S. aureus), так і грамнегативних (P. aeruginosa) бактерій. Завдяки цьому пов’язка може бути використана і за комплексного лікування післяопераційних ран з інфекційно-запальним процесом. Ефективність дії різних доз хлоргексидину біглюконату характеризувалася пригніченням росту та збільшенням вільного від мікроорганізмів зон середовища культивування навколо місця локалізації пов’язки з діючою речовиною, незалежно від виду бактерій. Однак величина діаметру зони пригнічення росту бактерій залежить від дози хлоргексидину в гідрогелевій пектиновій пов’язці. За пропорційного підвищення вмісту хлоргексидину біглюконату інгібування росту S. aureus і P. aeruginosa посилюється. Так, коли збільшували насичення пов’язки хлоргексидином до 1,0 і 1,5 %, реєстрували максимальне інгібування росту мікроорганізмів. Клінічне дослідження показало добрий лікувальний ефект у ветеринарній практиці за терапії ран, зокрема за комплексного лікування післяопераційних і випадкових ран як за наявності інфекційно-запального процесу, так і за його відсутності. Застосування армованої пов’язки на основі пектину з бавовняним (чи поліпропіленовим) елементом армування з вмістом хлоргексидину біглюконату скорочує витрати перев'язувального матеріалу і частоту перев’язок впродовж часу загоєння ран. Вона забезпечує захист ранової поверхні від забруднення, механічного подразнення, бактеріальної контамінації та розвитку вторинної інфекції. Пов’язка сприяє доброму водо-, повітро- та теплообміну між раною та зовнішнім середовищем, адсорбує надлишок ексудату, підтримує вологе середовище і не викликає гіперосмотичного ушкодження й висихання рани. Загоювання післяопераційної рани відбулося за первинним натягом впродовж 7 діб. Зважаючи на спосіб накладання, дана пов’язка може бути придатна для застосування у різних ділянках тіла тварини (шиї, холки, грудної й черевної стінок, попереку, крижів, стегна, плеча тощо)

Resistance to Elsinoë Ampelina and Expression of Related Resistant Genes in Vitis Rotundifolia Michx. Grapes

Muscadine grapes (Vitis rotundifolia Michx) are considered as excellent genetic resources for grape breeding programs as they are known for their hardiness and resistance to pests and diseases. However, contrary to popular belief, our study indicated that not all muscadine cultivars are resistant to anthracnose disease. In order to identify a source of genetic tolerance towards anthracnose among muscadine cultivars, a series of in-situ and ex-situ experiments were conducted through strict and sensitive screening processes. Two consecutive years of field evaluation of 54 grape cultivars showed various levels of anthracnose incidence among the cultivars between a scale of 0 (tolerant) to 5 (highly-susceptible). Resistance bioassay by inoculation of different spore densities of Elsinoë ampelina on 40 cultivars presented similar results and was consistent with those obtained from the field test. A real-time PCR analysis was conducted to investigate differences of gene expression between susceptible and tolerant cultivars and to confirm results by phenotypic identification. Expression of genes encoding chalcone synthase, stilbene synthase, polygalacturonase-inhibiting protein, chitinase and lipid transfer-protein was only detected in tolerant cultivars. Resistant muscadine cultivars identified in this study could be excellent candidates for grape disease resistance breeding programs

Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.

6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI(+)] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI(+)]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI(+)] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases

Differential overexpression of SERPINA3 in human prion diseases

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans

Protease-Resistant Prions Selectively Decrease Shadoo Protein

The central event in prion diseases is the conformational conversion of the cellular prion protein (PrPC) into PrPSc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrPSc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho), a protein that resembles the flexibly disordered N-terminal domain of PrPC, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrPSc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrPSc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrPSc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrPSc during prion disease