Use of bacteria- and fungus-binding mesh in negative pressure wound therapy provides significant granulation tissue without tissue ingrowth.

Objective: Bacteria- and fungus-binding mesh traps and inactivates bacteria and fungus, which makes it interesting, alternative, and wound filler for negative pressure wound therapy (NPWT). The aim of this study was to compare pathogen-binding mesh, black foam, and gauze in NPWT with regard to granulation tissue formation and ingrowth of wound bed tissue in the wound filler. Methods: Wounds on the backs of 8 pigs underwent 72 hours of NPWT using pathogen-binding mesh, foam, or gauze. Microdeformation of the wound bed and granulation tissue formation and the force required to remove the wound fillers was studied. Results: Pathogen-binding mesh produced more granulation tissue, leukocyte infiltration, and tissue disorganization in the wound bed than gauze, but less than foam. All 3 wound fillers caused microdeformation of the wound bed surface. Little force was required to remove pathogen-binding mesh and gauze, while considerable force was needed to remove foam. This is the result of tissue growth into the foam, but not into pathogen-binding mesh or gauze, as shown by examination of biopsy sections from the wound bed. Conclusions: This study shows that using pathogen-binding mesh as a wound filler for NPWT leads to a significant amount of granulation tissue in the wound bed, more than that with gauze, but eliminates the problems of ingrowth of the wound bed into the wound filler. Pathogen-binding mesh is thus an interesting wound filler in NPWT

The Effects of Variable, Intermittent, and Continuous Negative Pressure Wound Therapy, Using Foam or Gauze, on Wound Contraction, Granulation Tissue Formation, and Ingrowth Into the Wound Filler

Objective: Negative pressure wound therapy (NPWT) is commonly used in the continuous mode. Intermittent pressure therapy (IPT) results in faster wound healing, but it often causes pain. Variable pressure therapy (VPT) has therefore been introduced to provide a smooth transition between 2 different pressure environments, thereby maintaining the negative pressure environment throughout the therapy. The aim of the present study was to examine the effects of IPT and VPT on granulation tissue formation. Method: A peripheral wound in a porcine model was treated for 72 hours with continuous NPWT (-80 mm Hg), IPT (0 to -80 mm Hg), or VPT (-10 to -80 mm Hg), using foam or gauze as wound filler. Wound contraction and force to remove the wound filler were measured. Biopsies from the wound bed were examined histologically for granulation tissue formation. Results: Intermittent pressure therapy and VPT produced similar results. Wound contraction was more pronounced following IPT and VPT than continuous NPWT. Intermittent pressure therapy and VPT resulted in the formation of more granulation tissue than continuous NPWT. Leukocyte infiltration and tissue disorganization were more prominent after IPT and VPT than after continuous NPWT. Granulation tissue grew into foam but not into gauze, regardless of the mode of negative pressure application, and less force was needed to remove gauze than foam. Conclusions: Wound contraction and granulation tissue formation is more pronounced following IPT and VPT than continuous NPWT. Granulation tissue grows into foam but not into gauze. The choice of negative pressure mode and wound filler is crucial in clinical practice to optimize healing while minimizing pain

Tumor necrosis factor and its receptors in the neuroretina and retinal vasculature after ischemia-reperfusion injury in the pig retina

Numerous studies have been performed aimed at limiting the extent of retinal injury after ischemia, but there is still no effective pharmacological treatment available. The aim of the present study was to examine the role of tumor necrosis factor (TNF)α and its receptors (TNF-R1 and TNF-R2), especially considering the neuroretina and the retinal vasculature since the retinal blood vessels are key organs in circulatory failure

The Effects of Variable, Intermittent, and Continuous Negative Pressure Wound Therapy, Using Foam or Gauze, on Wound Contraction, Granulation Tissue Formation, and Ingrowth Into the Wound Filler

Objective: Negative pressure wound therapy (NPWT) is commonly used in the continuous mode. Intermittent pressure therapy (IPT) results in faster wound healing, but it often causes pain. Variable pressure therapy (VPT) has therefore been introduced to provide a smooth transition between 2 different pressure environments, thereby maintaining the negative pressure environment throughout the therapy. The aim of the present study was to examine the effects of IPT and VPT on granulation tissue formation. Method: A peripheral wound in a porcine model was treated for 72 hours with continuous NPWT (-80 mm Hg), IPT (0 to -80 mm Hg), or VPT (-10 to -80 mm Hg), using foam or gauze as wound filler. Wound contraction and force to remove the wound filler were measured. Biopsies from the wound bed were examined histologically for granulation tissue formation. Results: Intermittent pressure therapy and VPT produced similar results. Wound contraction was more pronounced following IPT and VPT than continuous NPWT. Intermittent pressure therapy and VPT resulted in the formation of more granulation tissue than continuous NPWT. Leukocyte infiltration and tissue disorganization were more prominent after IPT and VPT than after continuous NPWT. Granulation tissue grew into foam but not into gauze, regardless of the mode of negative pressure application, and less force was needed to remove gauze than foam. Conclusions: Wound contraction and granulation tissue formation is more pronounced following IPT and VPT than continuous NPWT. Granulation tissue grows into foam but not into gauze. The choice of negative pressure mode and wound filler is crucial in clinical practice to optimize healing while minimizing pain

Protein kinase C in porcine retinal arteries and neuroretina following retinal ischemia-reperfusion

PURPOSE: Identification of the intracellular signal-transduction pathways activated in retinal ischemia may be important in revealing novel pharmacological targets. To date, most studies have focused on identifying neuroprotective agents. The retinal blood vessels are key organs in circulatory failure, and this study was therefore designed to examine the retinal vasculature separately from the neuroretina. METHODS: Retinal ischemia was induced by elevating the intraocular pressure in porcine eyes, followed by 5, 12, or 20 h of reperfusion. Protein kinase C (PKC)alpha, PKCbeta1, and PKCbeta2 mRNA levels, and protein expression were determined using real-time PCR, western blot, and immunofluorescence staining techniques. RESULTS: The retinal arteries could easily be dissected free and studied separately from the neuroretina in this porcine model. The PKCalpha, PKCbeta1, and PKCbeta2 mRNA levels tended to be lower in ischemia-reperfused than in sham-operated eyes in both the retinal arteries and the neuroretina. This was most prominent after 5 h, and less pronounced after 12 h and 20 h of reperfusion. Likewise, the protein levels of PKCalpha, PKCbeta1, and PKCbeta2 were slightly lower following ischemia-reperfusion when compared to sham-operated eyes. PKCalpha, PKCbeta1, and PKCbeta2 immunostaining were observed in bipolar cells of the neuroretina and in endothelial cells, and to a low extent in the smooth muscle layer, of the retinal arteries. CONCLUSIONS: Retinal ischemia followed by reperfusion results in lower levels of PKC in both the neuroretina and retinal arteries. New targets for pharmacological treatment may be found by studying the retinal vasculature so as to identify the intracellular signal-transduction pathways involved in the development of injury following retinal circulatory failure

Mitogen-activated protein kinases in the porcine retinal arteries and neuroretina following retinal ischemia-reperfusion

PURPOSE: The aim of the present study was to examine changes in the expression of intracellular signal-transduction pathways, specifically mitogen-activated protein kinases, following retinal ischemia-reperfusion. METHODS: Retinal ischemia was induced by elevating the intraocular pressure in porcine eyes, followed by 5, 12, or 20 h of reperfusion. The results were compared to those of the sham- operated fellow eye. The retinal arteries and neuroretina were isolated separately and examined. Tissue morphology and DNA fragmentation were studied using histology. Extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, c-junNH(2)-terminal kinases (JNK), and c-jun protein and mRNA expression were examined using immunofluorescence staining, western blot, and real-time PCR techniques. RESULTS: Pyknotic cell nuclei, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, and glial fibrillary acidic protein mRNA expression were increased in ischemia, suggesting injury. Phosphorylated ERK1/2 protein levels were increased in the neuroretina following ischemia, while mRNA levels were unaltered. p38 protein and mRNA levels were not affected by ischemia. Immunofluorescence staining for phosphorylated p38 was especially intense in the retinal blood vessels, while only weak in the neuroretina. Phosphorylated JNK protein and mRNA were slightly decreased in ischemia. Phosphorylated c-jun protein and mRNA levels were higher in the neuroretina after ischemia-reperfusion. CONCLUSIONS: Retinal ischemia-reperfusion alters expression of mitogen-activated protein kinases, particularly ERK1/2, in the neuroretina and retinal arteries. The development of pharmacological treatment targeting these intracellular transduction pathways may prevent injury to the eye following retinal circulatory failure

Changes in Proteasome Structure and Function Caused by HAMLET in Tumor Cells

BACKGROUND: Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. METHODOLOGY/PRINCIPAL FINDINGS: HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. CONCLUSIONS/SIGNIFICANCE: The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells

Up-regulation of endothelin type B receptors in the human internal mammary artery in culture is dependent on protein kinase C and mitogen-activated kinase signaling pathways

<p>Abstract</p> <p>Background</p> <p>Up-regulation of vascular endothelin type B (ET_B) receptors is implicated in the pathogenesis of cardiovascular disease. Culture of intact arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for, <it>ex vivo</it>, in detail delineation of the regulation of endothelin receptors. We hypothesize that mitogen-activated kinases (MAPK) and protein kinase C (PKC) are involved in the regulation of endothelin ET_Breceptors in human internal mammary arteries.</p> <p>Methods</p> <p>Human internal mammary arteries were obtained during coronary artery bypass graft surgery and were studied before and after 24 hours of organ culture, using <it>in vitro </it>pharmacology, real time PCR and Western blot techniques. Sarafotoxin 6c and endothelin-1 were used to examine the endothelin ET_Aand ET_Breceptor effects, respectively. The involvement of PKC and MAPK in the endothelin receptor regulation was examined by culture in the presence of antagonists.</p> <p>Results</p> <p>The endohtelin-1-induced contraction (after endothelin ET_Breceptor desensitization) and the endothelin ET_Areceptor mRNA expression levels were not altered by culture. The sarafotoxin 6c contraction, endothelin ET_Breceptor protein and mRNA expression levels were increased after organ culture. This increase was antagonized by; (1) PKC inhibitors (10 μM bisindolylmaleimide I and 10 μM Ro-32-0432), and (2) inhibitors of the p38, extracellular signal related kinases 1 and 2 (ERK1/2) and C-jun terminal kinase (JNK) MAPK pathways (10 μM SB203580, 10 μM PD98059 and 10 μM SP600125, respectively).</p> <p>Conclusion</p> <p>In conclusion, PKC and MAPK seem to be involved in the up-regulation of endothelin ET_Breceptor expression in human internal mammary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin ET_Breceptor changes in cardiovascular disease.</p

Perceived connections between information and communication technology use and mental symptoms among young adults - a qualitative study

<p>Abstract</p> <p>Background</p> <p>Prospective associations have been found between high use of information and communication technology (ICT) and reported mental symptoms among young adult university students, but the causal mechanisms are unclear. Our aim was to explore possible explanations for associations between high ICT use and symptoms of depression, sleep disorders, and stress among young adults in order to propose a model of possible pathways to mental health effects that can be tested epidemiologically.</p> <p>Methods</p> <p>We conducted a qualitative interview study with 16 women and 16 men (21-28 years), recruited from a cohort of university students on the basis of reporting high computer (n = 28) or mobile phone (n = 20) use at baseline and reporting mental symptoms at the one-year follow-up. Semi-structured interviews were performed, with open-ended questions about possible connections between the use of computers and mobile phones, and stress, depression, and sleep disturbances. The interview data were analyzed with qualitative content analysis and summarized in a model.</p> <p>Results</p> <p>Central factors appearing to explain high quantitative ICT use were personal dependency, and demands for achievement and availability originating from the domains of work, study, social life, and individual aspirations. Consequences included mental overload, neglect of other activities and personal needs, time pressure, role conflicts, guilt feelings, social isolation, physical symptoms, worry about electromagnetic radiation, and economic problems. Qualitative aspects (destructive communication and information) were also reported, with consequences including vulnerability, misunderstandings, altered values, and feelings of inadequacy. User problems were a source of frustration. Altered ICT use as an effect of mental symptoms was reported, as well as possible positive effects of ICT on mental health.</p> <p>Conclusions</p> <p>The concepts and ideas of the young adults with high ICT use and mental symptoms generated a model of possible paths for associations between ICT exposure and mental symptoms. Demands for achievement and availability as well as personal dependency were major causes of high ICT exposure but also direct sources of stress and mental symptoms. The proposed model shows that factors in different domains may have an impact and should be considered in epidemiological and intervention studies.</p