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Purpose: To determine the increases in SSB and DSB yields after post gamma-irradiation incubation of plasmid DNA with the Escherichia coli base excision repair endonucleases formamidopyrimidineDNA N-glycosylase (FPG) and endonuclease III (endo III). Materials and methods: Aqueous solutions of plasmid DNA were irradiated with [sup 137]Cs gamma-rays in the presence of 10[sup -4]-10[sup -1] mol dm[sup -3] formate. After irradiation, aliquots were treated with FPG and/or endo III. SSB and DSB yields were then determined using gel electrophoresis. Results: Both SSB and DSB yields were found to increase after enzyme incubation, with the increase in the DSB yield being approximately equal to the square of the increase in the SSB yield. The correlation between the increases in the SSB and DSB yields was unaffected by the scavenger concentration during irradiation. Conclusion: Under the conditions used, the majority of DSB appear to be formed from two hydroxyl radical attacks. [ABSTRACT FROM AUTHOR]

Purpose: It was previously shown that γ-irradiation of aqueous solutions of plasmid DNA in the presence of millimolar concentrations of thiocyanate ions leads to the formation in very high yields of sites recognized by the base excision repair endonuclease formamido-pyrimidine-DNA N-glycosylase (FPG). The authors wished to characterize the mechanism responsible for the production of these FPG-sensitive sites. Materials and methods: An aqueous solution of plasmid DNA containing thiocyanate ions was irradiated with [sup 137]Cs γ-rays. After irradiation, aliquots were treated with FPG. Break yields were determined using neutral agarose gel electrophoresis. Results: The yield of FPG-sensitive sites decreased with decreasing enzyme activity, increasing thiocyanate concentration, increasing dose-rate, increasing ionic strength, increasing nitrite or iodide concentration, and decreasing oxygen concentration. Conclusions: The observations suggest that the monomeric thiocyanate radical SCN• is an intermediate in the reaction, and that the yields of FPG-sensitive sites are determined by competition between the disproportionation of the dimeric radical anion (SCN)[sub 2]• - and the fate of a one-electron oxidized guanine species in DNA. The latter can react with oxygen to produce an FPGsensitive site or can be reduced without producing an FPGsensitive site. The results help to clarify the mechanisms responsible for DNA damage by the direct eÚect of ionizing radiation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine whether a single-use negative pressure wound therapy (NPWT) system achieves individualized goals of therapy when used to treat patients with a variety of wound types., Design: Multiple case series., Subjects and Setting: The same comprised 25 participants; their mean age was 51.2 years (SD: 18.2; range: 19-79 years); 14 were male (56%) and 11 were female (44%). Seven study participants withdrew from study participation. Wound etiologies vary; 4 had diabetic foot ulcers; 1 had a full-thickness pressure injury; 7 were treated for management of an abscess or cyst; 4 had necrotizing fasciitis, 5 had nonhealing postsurgical wounds, and 4 had wounds of other etiologies. Data were collected at 2 ambulatory wound care clinics located in the Southeastern United States (Augusta and Austell, Georgia)., Methods: A single-outcome measure was selected for each participant by his or her attending physician at a baseline visit. Selected end points were (1) decrease in wound volume, (2) decrease in size of the tunneling area, (3) decrease in size of the undermining, (4) decrease in the amount of slough, (5) increase in granulation tissue formation, (6) decrease in periwound swelling, and (7) wound bed progression toward transition to another treatment modality (such as standard dressing, surgical closure, flap, or graft). Progress toward the individualized goal was monitored until the goal was achieved (study end point) or a maximum of 4 weeks following initiation of treatment., Results: The most common primary treatment goal was to achieve a decrease in wound volume (22 of 25 study participants), and the goal to increase granulation tissue was chosen for the remaining 3 study participants. A majority of participants (18 of 23, 78.3%) reached their individualized treatment outcome. The remaining 5 participants (21.7%) were withdrawn during the study (for reasons not related to the therapy). The median (interquartile range [IQR]) duration of NPWT therapy was 19 days (IQR: 14-21 days). Between baseline and the final assessment, median reductions in wound area and volume were 42.7% (IQR: 25.7-71.5) and 87.5% (IQR: 30.7-94.6)., Conclusions: The single-use NPWT system achieved multiple individualized treatment objectives in a variety of wound types. Individually selected goals of therapy were met by all study participants who completed the study., Competing Interests: Funding for writing of the manuscript and performance of this clinical study was provided by Medela AG. Rey Paglinawan and Karin Lussi are employees of Medela AG (Switzerland). For the remaining authors, no conflicts of interest were declared., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Wound, Ostomy, and Continence Nurses Society.)

Background: NPWT is widely used to manage hard-to-heal wounds, and many different devices are available. Personal-use NPWT systems are becoming more popular, although current options have limited functionality., Purpose: The primary objective was to determine acceptable progress of wounds towards a predefined goal of therapy for a variety of open wounds being treated with a novel NPWT personal-use system with enhanced functionality., Methods: In this prospective, nonrandomized, interventional study, patients were treated with a personal-use NPWT system over 4 weeks, initially in a wound care clinic setting, and were discharged home with the device. Clinician satisfaction with the device was also evaluated., Results: Ten patients were evaluated. Acceptable progress towards all predetermined goals was reached for all patients; a median reduction in wound volume of 84.6% and improved granulation was achieved within the 4-week treatment period. No device-related deficiencies were reported. In general, clinicians were satisfied with the device's ease of use and mobility., Conclusion: Personal-use NPWT is easy to use, has positive effects on healing on a variety of wound types, and is well accepted by clinicians.

In acute experimental autoimmune encephalomyelitis (EAE), demyelination is induced by myelin-specific CD4(+) T lymphocytes and myelin-specific antibodies. Recovery from the disease is initiated by cytokines which suppress T cell expansion and the production of myelin-toxic molecules by macrophages. Th2/3 cell-derived signals may also be involved in central nervous system (CNS) repair. Remyelination is thought to be initiated by the recruitment and differentiation of oligodendrocyte precursor cells (OPC) in demyelinated CNS lesions. Here, we report that unlike Th1 cytokines (TNF-alpha, IFN-gamma), the Th2/3 cytokine TGF-beta induces primary microglia from C57BL/6 mice to secrete a chemotactic factor for primary OPC. We identified this factor to be the hepatocyte growth factor (HGF). Our studies show that TGF-beta-1-2-3 as well as IFN-beta induce HGF secretion by microglia and that antibodies to the HGF receptor c-Met abrogate OPC chemotaxis induced by TGF-beta2-treated microglia. In addition we show spinal cord lesions in EAE induced in SJL/J mice to contain both OPC and HGF producing macrophages in the recovery phase, but not in the acute stage of disease. Taken these findings, TGF-beta may play a pivotal role in remyelination by inducing microglia to release HGF which is both a chemotactic and differentiation factor for OPC.

In experimental autoimmune encephalomyelitis, the acute phase of the disease is produced by T-helper lymphocyte type 1 (TH1), which produces mainly TNFalpha and IFNgamma. Recovery from the disease is mediated by T-helper lymphocyte types 2 and 3 (TH2/TH3), which, among other cytokines, produce transforming growth factor beta (TGFbeta). To address the influence of TGFbeta on TH1-induced gene expression, microarray technology was used on murine primary microglial cells stimulated with IFNgamma and TNFalpha in the absence or presence of TGFbeta. The resulting data from an investigation of up to 5,500 genes provided the notion that TGFbeta prevents the induction of a proinflammatory gene program within microglia exposed to a TH1 milieu. TH1 cytokines upregulated 175 genes comprising cytokine, chemokine, and genes involved in host response to infection and the TNFalpha/IFNgamma intracellular signaling pathway. It is observed that TGFbeta inhibits expression of 25% of the TNFalpha/IFNgamma-induced genes and a further 66 TNFalpha/IFNgamma-independent genes. The focus of TGFbeta inhibition is observed to be directed in genes involved in chemotaxis (IL-15, CXCL1, CXCL2, CCL3, CCL4, CCL5, CCL9), chemokine receptors (CCR5, CCR9), LIF receptor, and FPR2, and on genes mediating cell migration (MMP9, MMP13, MacMARCKS, endothelin receptor B, Ena/VASP, Gas7), apoptosis (FAS, TNF, TNF receptor, caspase-1 and -11), and host response to infection (toll-like receptor 6, Mx-1, and MARCO). Taken collectively, the data strongly suggest that one of the main effects of TGFbeta is to impair cell entry into the CNS and to hinder migration of microglia in the CNS parenchyma., (Copyright 2003 Wiley-Liss, Inc.)