Autologous Lipofilling Improves Clinical Outcome in Patients With Symptomatic Dermal Scars Through Induction of a Pro-Regenerative Immune Response

Author(s):  
Maroesjka Spiekman ◽  
Delia L Francia ◽  
Dieuwertje M Mossel ◽  
Linda A Brouwer ◽  
Gilles F H Diercks ◽  
...  

Abstract Background Autologous lipofilling is emerging procedure to augment and possibly reverse dermal scars and to reduce scar-related pain, but its efficacy and mechanisms are poorly understood. Objectives To test the hypothesis that repeated lipografts reverse dermal scars by re-initiation of wound healing. Methods In a prospective, non-placebo controlled clinical study, 27 adult patients with symptomatic scars were given two lipofilling treatments at 3-month intervals. As primary outcome, clinical effects were measured using the patient and observer scar assessment scale (POSAS). Scar biopsies were taken before and after treatments to assess scar remodeling at a cellular level. Results Twenty patients completed the study. Patients’ scars improved after lipofilling. The total POSAS scores (combined patient and observer scores) decreased from 73.2±14.7 points pre-treatment to 46.1±14.0 and 32.3±13.2 after the first and second treatment, respectively. Patient POSAS scores decreased from 37.3±8.8 points to 27.2±11.3 and 21.1±11.4 points, whereas Observer POSAS scores decreased from 35.9±9.5 points, which decreased to 18.9±6.0 and 11.3±4.5 points after the first and second lipofilling treatment, respectively. After each lipofilling treatment, T-lymphocytes, mast cells and M2 macrophages had invaded scar tissue and associated was increased vascularization. In addition, the scar-associated epidermis showed increase in epidermal cell proliferation which was akin to normal skin. Moreover, lipofilling treatment caused normalization of the extracellular matrix (ECM) organization towards that of normal skin. Conclusions Autologous lipofilling improves clinical outcome of dermal scars through the induction of a pro-regenerative immune response, increased vascularization, and epidermal proliferation and remodeling of scar tissue ECM.

2021 ◽  
Author(s):  
Seishi Ogawa ◽  
Magnus Tobiasson ◽  
Shinya Sato ◽  
Elsa Bernard ◽  
Shigeki Ohtake ◽  
...  

Abstract Azacitidine is a mainstay of therapy for high-risk MDS and other myeloid neoplasms. A significant correlation between azacitidine response and clinical outcome suggests a potential role of mutational profiling based on next-generation sequencing (NGS) before and after therapy in evaluating response and predicting overall survival (OS), which however has not fully elucidated. Here through NGS-based mutational profiling of large cohorts (n=451) of azacitidine-treated patients with high-risk MDS and other myeloid neoplasms, we show significant roles of multi-hit TP53 and germline DDX41 mutations in pre-treatment samples and post-treatment clone size in the evaluation/prediction of azacitidine response and OS after azacitidine therapy, which outperformed the prediction based only on clinical response and IPSS-R score. Post-treatment clone size strongly correlated with clinical response with exception of large persistent mutations frequently affecting TET2 after achieving complete remission and those with DDX41 mutations, which poorly correlated with clinical response. Our results highlight the importance of evaluating mutations in both pre- and post-treatment samples in the assessment of response and the prediction of OS after azacitidine therapy.


2014 ◽  
Vol 84 (3-4) ◽  
pp. 0140-0151 ◽  
Author(s):  
Thilaga Rati Selvaraju ◽  
Huzwah Khaza’ai ◽  
Sharmili Vidyadaran ◽  
Mohd Sokhini Abd Mutalib ◽  
Vasudevan Ramachandran ◽  
...  

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.


2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.


Author(s):  
Ashish Kumar Agarwal ◽  
Daulat Singh Meena ◽  
Vijay Pathak ◽  
Anoop Jain ◽  
Rakesh Kumar Ola

Background: The aim of the present study was to study the effect of percutaneous balloon mitral  valvuloplasty (PBMV) on P wave dispersion and to test the correlation between P-maximum and  P-dispersion to right ventricular function and pulmonary artery pressure before and after PMBV. Also to study the impact of P-maximum and P-wave dispersion on the short term clinical outcome after successful PBMV in patients with mitral stenosis (MS) and sinus rhythm. Methods: 75 patients undergoing PMBV were enrolled in this study. We evaluated P-maximum, P-minimum and P-wave dispersion before and one month and one year after PBMV . We studied the changes in pulmonary arterial pressure (PAP), left atrial (LA) dimension, mitral diastolic gradient, and mitral valve area, in addition to the changes in right ventricular function utilizing tissue Doppler assessment both before and after PMBV, in addition the role of the P-wave dispersion in prediction of late cardiac events. Results: There were significant decrease in mean diastolic gradient, PAP, and LA size and significant improvement in right ventricular tissue Doppler indices after PMBV. Accompany these hemodynamic changes after PMBV. P-maximum and P-wave dispersion were found to be decreased (P < 0.001). Conclusion: Successful PBMV was associated with a decrease in Pmax and PWD. These simple electrocardiographic indices may predict the success of the procedure immediately after PBMV.  The P-maximum and P-wave dispersion changes were correlated with significant impairment of right dysfunction and the degree of pulmonary artery pressure. Keywords: PBMV.PAP,LA


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan H. Trager ◽  
Emanuelle Rizk ◽  
Sharon Rose ◽  
Kuixi Zhu ◽  
Branden Lau ◽  
...  

AbstractThe presence of actinic keratoses (AKs) increases a patient’s risk of developing squamous cell carcinoma by greater than six-fold. We evaluated the effect of topical treatment with imiquimod on the tumor microenvironment by measuring transcriptomic differences in AKs before and after treatment with imiquimod 3.75%. Biopsies were collected prospectively from 21 patients and examined histologically. RNA was extracted and transcriptomic analyses of 788 genes were performed using the nanoString assay. Imiquimod decreased number of AKs by study endpoint at week 14 (p < 0.0001). Post-imiquimod therapy, levels of CDK1, CXCL13, IL1B, GADPH, TTK, ILF3, EWSR1, BIRC5, PLAUR, ISG20, and C1QBP were significantly lower (adjusted p < 0.05). Complete responders (CR) exhibited a distinct pattern of inflammatory gene expression pre-treatment relative to incomplete responders (IR), with alterations in 15 inflammatory pathways (p < 0.05) reflecting differential expression of 103 genes (p < 0.05). Presence of adverse effects was associated with improved treatment response. Differences in gene expression were found between pre-treatment samples in CR versus IR, suggesting that higher levels of inflammation pre-treament may play a part in regression of AKs. Further characterization of the immune micro-environment in AKs may help develop biomarkers predictive of response to topical immune modulators and may guide therapy.


2021 ◽  
Vol 70 (4) ◽  
pp. 429-444
Author(s):  
Franz Nürnberger ◽  
Stephan Leisengang ◽  
Daniela Ott ◽  
Jolanta Murgott ◽  
Rüdiger Gerstberger ◽  
...  

Abstract Objective Bacterial lipopolysaccharide (LPS) may contribute to the manifestation of inflammatory pain within structures of the afferent somatosensory system. LPS can induce a state of refractoriness to its own effects termed LPS tolerance. We employed primary neuro-glial cultures from rat dorsal root ganglia (DRG) and the superficial dorsal horn (SDH) of the spinal cord, mainly including the substantia gelatinosa to establish and characterize a model of LPS tolerance within these structures. Methods Tolerance was induced by pre-treatment of both cultures with 1 µg/ml LPS for 18 h, followed by a short-term stimulation with a higher LPS dose (10 µg/ml for 2 h). Cultures treated with solvent were used as controls. Cells from DRG or SDH were investigated by means of RT-PCR (expression of inflammatory genes) and immunocytochemistry (translocation of inflammatory transcription factors into nuclei of cells from both cultures). Supernatants from both cultures were assayed for tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by highly sensitive bioassays. Results At the mRNA-level, pre-treatment with 1 µg/ml LPS caused reduced expression of TNF-α and enhanced IL-10/TNF-α expression ratios in both cultures upon subsequent stimulation with 10 µg/ml LPS, i.e. LPS tolerance. SDH cultures further showed reduced release of TNF-α into the supernatants and attenuated TNF-α immunoreactivity in microglial cells. In the state of LPS tolerance macrophages from DRG and microglial cells from SDH showed reduced LPS-induced nuclear translocation of the inflammatory transcription factors NFκB and NF-IL6. Nuclear immunoreactivity of the IL-6-activated transcription factor STAT3 was further reduced in neurons from DRG and astrocytes from SDH in LPS tolerant cultures. Conclusion A state of LPS tolerance can be induced in primary cultures from the afferent somatosensory system, which is characterized by a down-regulation of pro-inflammatory mediators. Thus, this model can be applied to study the effects of LPS tolerance at the cellular level, for example possible modifications of neuronal reactivity patterns upon inflammatory stimulation.


2014 ◽  
Vol 804 ◽  
pp. 149-152 ◽  
Author(s):  
Ji Sun Kim ◽  
Jae Ho Baek ◽  
Myung Hwan Kim ◽  
Seong Soo Hong ◽  
Man Sig Lee

In this study, we confirmed effect of carbon pre-treatment on Pd dispersion in synthesis of Pd/C catalyst. Physical characteristics on the surface of before and after pre-treated carbon were analyzed by nitrogen adsorption-desorption analysis. The dispersion and size of Pd particles were analyzed by XRD, FE-TEM and CO-chemisorption. After pre-treatment, surface area of carbon were decreased. And mesopore area ratio were increased with decreasing micropore area ratio. In the case of pre-treated carbon, we confirmed high dispersion of Pd particles.


Author(s):  
Avinash V Borgaonkar ◽  
Ismail Syed ◽  
Shirish H Sonawane

Molybdenum disulphide (MoS2) is a popularly used solid lubricant in various applications due to its superior tribological behaviour. However, it possesses poor wear resistance which requires further improvement. In the present study efforts have been made to enhance the tribological properties of pure MoS2 coating film by doping TiO2 nanoparticles as a reinforcement material. The Manganese phosphating is selected as a pre-treatment method to improve the bond strength between coating and substrate. The coating is bonded with the substrate material employing sodium silicate as a binder. The effects of wt. % of TiO2 onto the mechanical properties of composite MoS2-TiO2 coating such as hardness and bond strength have been studied. In addition coating microstructure before and after experimental test was studied using optical microscope and scanning electron microscope. It was also found that with increase in wt. % addition of TiO2 upto 15% into MoS2 base matrix, the hardness of coating increases proportionally. Beyond 15 wt. % addition of TiO2, the coating becomes brittle in nature. This leads to reduction in the scratch resistance.


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