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Introduction: The number of heart transplantations has decreased in recent years and the number of implantable left ventricular assist devices (LVADs) has increased significantly. In addition, due to the current condition of these patients, the duration of stay in intensive care and mechanical ventilation increases. Percutaneous dilatational tracheostomy (PDT) is applied to these patients due to the need for prolonged mechanical ventilation. Complications may be seen during this period due to the use of anticoagulant therapy. Case presentation: Our 2 patients with hemorrhagic CVO were receiving anticoagulant and antiplatelet therapy, and prolonged mechanical ventilation support due to LVAD, this condition leads to the necessity of tracheostomy. Conclusions: Bleeding complications cannot be overlooked in these patients who have to take anticoagulant therapy. [ABSTRACT FROM AUTHOR]

Extravasation may occur due to medications, modes of infusion and diverse patientrelated etiologies Therefore, it is necessary to be careful in the infusion of the acidic vasopressors. A long-term bedridden patient was taking norepinephrine due to hemodynamic impairment. We have attempted to present the extravasation injury caused as a result of peripheral infusion of a vasopressor for a short time upon development of catheter infection. [ABSTRACT FROM AUTHOR]

In this study we investigated the effects of antibiotic and intraperitoneal ozone administration on proinflammatory cytokine, antioxidant levels and tissue damage in the treatment of experimentally infectious peritonitis. Thirty-three adult male New Zealand White Rabbits were used. The study consisted of four groups including the non-treatment group (G1), antibiotic group (G2), ozone group (G3) and ozone + antibiotic group (G4). Trimethoprim sulfadimethylprymidine was administered at a dose of 50 mg/kg subcutaneously (s.c.) and amoxicillin sodium at a dose of 15 mg/kg intramuscularly (i.m.). Medical ozone was administered intraperitoneally (i.p.) at a concentration of 30 µg O3/ml and dose of 80 ml/kg. Once peritonitis was produced, blood samples were taken from the animals before treatment and at regular intervals following treatment. Blood samples were used for haemograms and to measure levels of antioxidant and oxidative enzymes and pro-inflammatory cytokine levels. Tissue samples were examined histopathologically. There was no statistically significant difference between groups with respect to levels of pro-inflammatory cytokines. Antioxidant enzymes were found to be higher in groups G2 and G3. The granulocyte and lymphocyte values in group G3 were determined to increase earlier than in the other groups. The peritonitis scores were similar in G1 and G3, which is higher compared to G2 and G4 groups. Minimal tissue damage was observed in the group G2. It was concluded that antibiotic use for preventing peritoneum damage in experimental acute peritonitis was more effective than ozone therapy alone. [ABSTRACT FROM AUTHOR]

Ocean acidification (OA) and crude oil pollution have been highlighted as some of the most pervasive anthropogenic influences on the ocean.In marine teleosts, early life-history stages are particularly vulnerable to disturbance by CO2-driven acidification as they lack pH-mediated intracellular regulation. Embryos exposed to trace levels of crude oil constituents dissolved in water exhibit a common syndrome of developmental abnormalities. So far, little is known about the combined effects of OA and crude oil on the early life history of marine fish. Eggs and larvae of the marine medaka (Oryzias melastigma) were treated with CO2 (1080 μatm atmospheric CO2), the water-soluble fraction (WSF) of crude oil (500 μg/L) and a CO2 (1080 μatm atmospheric CO2)/WSF (500 μg/L) mixture within 4 h after oviposition. Isolated and combined OA/WSF had no detectable effect on embryonic duration, egg survival rate and size at hatching. Histopathological anomalies of tissue and lipid metabolic disorder were significant when CO2 or WSF was given alone at 30 days of age. Combination of CO2 and WSF enhanced their toxicity compared to their separate administration. Since the early life-history stage of marine fish is thought to be impacted more heavily by increasing CO2 partial pressure (pCO2) levels and crude oil pollution, OA and crude oil pollution have the potential to act as an additional source of natural mortality. [ABSTRACT FROM AUTHOR]

Background: Posterior decompression has been the most common surgical procedure for lumbar spinal stenosis. Endoscopic decompression is a new surgical technique for spinal stenosis decompression. Subjective outcomes after the procedure, VAS and functional scores, were very satisfying but there were no reports published on the amount of tissue damage for this procedure. Objective: To evaluate the paravertebral muscles and soft tissue destruction between two methods of spinal decompression by muscle enzyme, CRP and size of muscle destruction. Materials and Methods: Study design. A cohort series of two groups of the patients, open decompression and BPED, who underwent spinal stenosis decompression were compared in postoperative outcomes such as modified Macnab criteria, VAS, CPK, and CRP. Results: The CRP and CPK level were significantly lower in BPED group than in open decompression group at 24 and 72 hours after surgery (p<0.05). Size of soft tissue destructions after BPED were 35+18 milliliters. Conclusion: Postoperative CPK and CRP level of BPED were statistically significant lower than conventional laminectomy. [ABSTRACT FROM AUTHOR]

Patients scheduled for cochlear implantation often retain residual hearing in the low frequencies. Unfortunately, some patients lose their residual hearing following implantation and the reasons for this are not well understood. Evidence suggests that electrotoxicity could be one of the factors responsible for this late adverse effect. Therefore, the aim of this study was to investigate the survival of spiral ganglion neurons (SGN) subjected to in vitro electrical stimulation (ES). A stimulation setup was developed to provide defined electrical fields at given points of the chamber. SGN isolated from Sprague Dawley rats (P3–4) were dissociated and cultured in the chamber for 24 h prior to biphasic, pulsed electrical field exposure for another 24 h. The current varied in the range of 0 to 2 mA and the pulse width from 10 to 400 μs. Neurite growth and survival were evaluated with respect to the charge density at the position of the cells. Non-exposed SGN cultures served as control. Charge densities below 2.2 μC·cm−2·phase−1 appeared to have no effect on SGN survival and neurite outgrowth. Charge densities above 4.9 μC·cm−2·phase−1 were detrimental to almost all cells in culture. After fitting results to a sigmoidal dose response curve, a LD50 of 2.9 μC·cm−2·phase−1 was calculated. This screening regarding survival and outgrowth of SGN provides parameters that could be used to further investigate the effect of ES on SGN and to develop possible protection strategies, which could potentially rescue residual hearing in the implanted patients. [ABSTRACT FROM AUTHOR]

The study evaluated the effects of intramuscular injection of butaphosphan and cyanocobalamin combination (BPC) on the plasma levels of cortisol, cytokines, and the activities of selected enzymes in Oliveflounder exposed to crowding stress. Three groups of fish (n = 12 per group) were kept in different glass tanks with stocking densities of 46 kg/m3(group BP and SCH) and 15 kg/m3 (group SCL). Group BP was treated with 0.5 ml of BPC. While groupSCH and SCL were treated with 0.5 ml of saline. Blood was collected a day after injection (T1), and weekly for two consecutive weeks (T2 and T3). The plasma levels of interleukin (IL) ‐1β, IL‐6, cortisol, lysozyme, and the activities of aspartate aminotransferase (AST) and alanine transaminase (ALT)were determined using an ELISA kit. The statistical significance of differences was assessed using ANOVAfollowed by Tukey‐HSD test (P < 0.05 considered significant).A significantbody weight gain was measured in the BP and SCL groupscompared with SCH at T3. The activities of AST (at T1, T2, and T3) and ALT (at T1 and T2) were declined significantly (P < 0.05) following treatment of overcrowded fish with BPC than saline. Similarly, BPCcaused a significant reduction in the levels of cortisol and IL‐1β at T2 and T3.This is the first report of the effect of the combination of butaphosphan and cyanocobalamin on plasma immune and biochemical parametersin fish. Therefore, the combination could be beneficial in preventing overcrowding‐induced immune suppression and tissue damage in Olive flounder. [ABSTRACT FROM AUTHOR]

The human respiratory syncytial virus (hRSV) remains one of the leading pathogens causing acute respiratory tract infections (ARTIs) in children younger than 2 years old, worldwide. Hospitalizations during the winter season due to hRSV-induced bronchiolitis and pneumonia increase every year. Despite this, there are no available vaccines to mitigate the health and economic burden caused by hRSV infection. The pathology caused by hRSV induces significant damage to the pulmonary epithelium, due to an excessive inflammatory response at the airways. Cytokines are considered essential players for the establishment and modulation of the immune and inflammatory responses, which can either be beneficial or harmful for the host. The deleterious effect observed upon hRSV infection is mainly due to tissue damage caused by immune cells recruited to the site of infection. This cellular recruitment takes place due to an altered profile of cytokines secreted by epithelial cells. As a result of inflammatory cell recruitment, the amounts of cytokines, such as IL-1, IL-6, IL-10, and CCL5 are further increased, while IL-10 and IFN-γ are decreased. However, additional studies are required to elicit the mediators directly associated with hRSV damage entirely. In addition to the detrimental induction of inflammatory mediators in the respiratory tract caused by hRSV, reports indicating alterations in the central nervous system (CNS) have been published. Indeed, elevated levels of IL-6, IL-8 (CXCL8), CCL2, and CCL4 have been reported in cerebrospinal fluid from patients with severe bronchiolitis and hRSV-associated encephalopathy. In this review article, we provide an in-depth analysis of the role of cytokines secreted upon hRSV infection and their potentially harmful contribution to tissue damage of the respiratory tract and the CNS. [ABSTRACT FROM AUTHOR]

Abstract Inflammation is a complex mechanism that plays a key role during diseases. Dynamic features of the extracellular matrix (ECM), in particular, during phases of tissue inflammation, have long been appreciated, and a great deal of several investigations has focused on the effects of ECM derivatives on cell function. It has been well defined that during inflammatory and tissue injury, ECM components were degraded. ECM degradation direct consequence is the loss of cell homeostasis, while a further consequence is the generation of fragments from larger precursor molecules. These bio-functional ECM shred defined matrikines as capable of playing different actions, especially when they function as powerful initiators, able to prime the inflammatory mechanism. Non-sulphated glycosaminoglycan hyaluronan (HA) is the major component of the ECM that undergoes specific modulation during tissue damage and inflammation. HA fragments at very low molecular weight are produced as a result of HA depolymerization. Several evidence has considered the plausibility that HA breakdown products play a modulatory action in the sequential stages of inflammation, although the effective mechanism of these HA derivative compounds act is not completely defined. This review will focus on the pro-inflammatory effects of HA fragments in recent years obtained by in vitro investigations. [ABSTRACT FROM AUTHOR]

The rotational motion has been utilized in several medical needle technologies to enhance the capability of cutting tissue. The needle rotation helps significantly reduce the tissue cutting force, which improves procedure outcome and pain. However, the needle rotation can also incur tissue winding that intensifies tissue damage, which results in complications of bleeding and hematoma. Some histological observations showed that bidirectional needle rotation could reduce the tissue damage caused by tissue winding. In this study, we established a cohesive surface based finite element model to evaluate the cutting force in needle insertion with unidirectional and bidirectional rotation. The simulation results suggested that the frequency of switching direction of needle rotation insignificantly influences the cutting force. The Latin Hypercube method was used to generate a response surface of cutting force and locate the minimum at the insertion speed of 1 mm/s combined with the slice/push ratio of 1.9. In clinical use, we suggested that the needle speeds can be first selected to optimize the cutting force according to the type of target tissue. If the desired needle rotation is high, a proper switching frequency can be applied to reduce the tissue winding damage without increasing the cutting force. [ABSTRACT FROM AUTHOR]

Abstract Cadmium (Cd) is one of the most ubiquitous toxic heavy metal in the environment. The present study was conducted to evaluate the protective role of aqueous bark extract of Terminalia arjuna (TA) against Cd induced oxidative damage in hepatic and cardiac tissues as the TA bark extract has folkloric medicinal use in the treatment of various hepatic and cardiac disorders. Male Wistar rats were divided into 4 groups. The control group was treated with normal saline as the vehicle; the second group orally administered with TA (20 mg/kg bw) daily for 15 days; the third group injected with Cd-acetate (0.44 mg/kg bw, s.c.) every alternate day for a period of 15 days; and the fourth group was administered with TA, 60 min prior to Cd treatment. The biomarkers of organ damage were significantly increased in the Cd treated groups. Besides, a significant alteration in the tissue levels of biomarkers of oxidative stress, the activities and the levels of antioxidant enzymes was observed following treatment with Cd. Additionally, some of the enzymes were found to be inhibited uncompetitively by Cd when tested in an in vitro system. Furthermore, evidence gathered from studies on the histological parameters and mitochondrial membrane potential in both the tissues argue in favour of the possible protective role of TA against Cd induced damage. Finally, gas chromatography–mass spectrometry revealed the presence of eight major bioactive phytochemicals in aqueous bark extract of TA having potent free radical scavenging property. The results indicate that the extract could protect hepatic and cardiac tissues against Cd-induced oxidative stress mediated damages through antioxidant mechanism(s). Graphical abstract Schematic diagram representing the probable protective mechanism of aqueous bark extract of Terminalia arjuna against cadmium-induced oxidative stress mediated hepatic and cardiac injury. Being a deleterious environmental pollutant, cadmium induces oxidative stress in the liver and heart tissues. After Cd enters into the body by ingestion or inhalation, it modulates either the first line of antioxidant defense system or, its individual enzymes. This causes depletion of endogenous antioxidants [reduced glutathione (GSH) and total thiol (TSH) content)] following the oxidation of different bio-molecules, such as lipids, proteins and nucleic acids. This eventually develops oxidative stress in the liver and heart tissues. On the other hand, Cd induces intra-cellular level of oxidative stress by the generation of singlet oxygen which further produces various harmful free radicals, such as superoxide anion radical (O 2 .-), hydrogen peroxide (H 2 O 2), hydroxyl radical (•OH), etc. through a number of chain reactions. Such reactive oxygen species causes alterations in the activities of different intra-cellular antioxidant enzymes [Mn-superoxide dismutase (Mn-SOD), Catalase (CAT), Glutathione peroxide (GPx), Glutathione reductase (GR)]- both present in mitochondrial as well as cytosolic fractions; thereby modulating mitochondrial membrane potential, thus ultimately resulting in tissue injury. However, aqueous bark extract of Terminalia arjuna protects against all these Cd-induced oxidative stress mediated tissue injuries in both the liver and heart tissues by restoring their normal cellular levels or, activities. Image 1 Highlights • Aqueous extract of T. arjuna bark is widely consumed as ayurvedic medicine in rural India. • This aqueous bark extract has been found to possess antioxidant properties. • Cadmium acetate causes oxidative stress mediated damages to rat liver and heart. • This extract provided protection against these damages. • Antioxidant mechanism(s) are suggested to be responsible for such protection. [ABSTRACT FROM AUTHOR]

Abstract Leukocyte populations quickly respond to tissue damage, but most leukocyte kinetic studies are not based on multiparameter flow cytometry. We systematically investigated several blood leukocyte populations after controlled tissue damage. 48 patients were assigned to either an anterior or posterolateral total hip arthroplasty. Peripheral blood was collected pre-operatively and at 2 h, 24 h, 48 h, 2 and 6 weeks postoperatively and assessed by flow cytometry for absolute counts of multiple leukocyte populations using standardized EuroFlow protocols. Absolute counts of leukocyte subsets differed significantly between consecutive time points. Neutrophils increased instantly after surgery, while most leukocyte subsets initially decreased, followed by increasing cell counts until 48 h. At two weeks all leukocyte counts were restored to pre-operative counts. Immune cell kinetics upon acute tissue damage exhibit reproducible patterns, which differ between the leukocyte subsets and with "opposite kinetics" among monocyte subsets. Flow cytometric leukocyte monitoring can be used to minimally invasively monitor tissue damage. Highlights • Tissue damage leads to fast and significant changes in leukocyte subset counts. • Leukocyte populations have distinct kinetic patterns in response to acute tissue damage. • Neutrophil counts massively increase within 2 h after tissue damage onset. • Blood monocyte subsets show opposite kinetics/dynamics with sequential return to normal counts after tissue damage. [ABSTRACT FROM AUTHOR]

Abstract The use of synchrotron radiation micro-computed tomography (SR-microCT) is becoming increasingly popular for studying the relationship between microstructure and bone mechanics subjected to in situ mechanical testing. However, it is well known that the effect of SR X-ray radiation can considerably alter the mechanical properties of bone tissue. Digital volume correlation (DVC) has been extensively used to compute full-field strain distributions in bone specimens subjected to step-wise mechanical loading, but tissue damage from sequential SR-microCT scans has not been previously addressed. Therefore, the aim of this study is to examine the influence of SR irradiation-induced microdamage on the apparent elastic properties of trabecular bone using DVC applied to in situ SR-microCT tomograms obtained with different exposure times. Results showed how DVC was able to identify high local strain levels (> 10,000 µε) corresponding to visible microcracks at high irradiation doses (~ 230 kGy), despite the apparent elastic properties remained unaltered. Microcracks were not detected and bone plasticity was preserved for low irradiation doses (~ 33 kGy), although image quality and consequently, DVC performance were reduced. DVC results suggested some local deterioration of tissue that might have resulted from mechanical strain concentration further enhanced by some level of local irradiation even for low accumulated dose. Graphical abstract fx1 Highlights •.High irradiation doses do not always alter apparent mechanics of trabecular bone. • High local strain levels were identified after long SR X-ray exposures. • Local deterioration of trabecular bone tissue may also occur at low X-ray doses. • X-ray damage minimised for in situ tests, but SR-microCT image quality compromised. [ABSTRACT FROM AUTHOR]

L. (viannia) braziliensis infection causes American Tegumentary Leishmaniasis (ATL), with prolonged time to healing lesions. The potent inflammatory response developed by the host is important to control the parasite burden and infection however an unbalanced immunity may cooperate to the tissue damage observed. The range of mechanisms underlying the pathological responses associated with ATL still needs to be better understood. That includes epigenetic regulation by non-coding MicroRNAs (miRNAs), non-coding sequences around 22 nucleotides that act as post-transcriptional regulators of RNAs encoding proteins. The miRNAs have been associated with diverse parasitic diseases, including leishmaniasis. Here we evaluated miRNAs that targeted genes expressed in cutaneous leishmaniasis lesions (CL) by comparing its expression in both CL and normal skin obtained from the same individual. In addition, we evaluated if the miRNAs expression would be correlated with clinical parameters such as therapeutic failure, healing time as well as lesion size. The miR-361-3p and miR-140-3p were significantly more expressed in CL lesions compared to normal skin samples (p = 0.0001 and p < 0.0001, respectively). In addition, the miR-361-3p was correlated with both, therapeutic failure and healing time of disease (r = 0.6, p = 0.003 and r = 0.5, p = 0.007, respectively). In addition, complementary analysis shown that miR-361-3p is able to identify with good sensitivity (81.2%) and specificity (100%) patients who tend to fail initial treatment with pentavalent antimonial (Sbv). Finally, the survival analysis considering "cure" as the endpoint showed that the higher the expression of miR-361-3p, the longer the healing time of CL. Overall, our data suggest the potential of miR-361-3p as a prognostic biomarker in CL caused by L. braziliensis. [ABSTRACT FROM AUTHOR]

This paper postulates that overuse injury in sport is a biomechanical event resulting from the mechanical fatigue of biological tissue. A theoretical foundation and operational framework necessary to model overuse injury as a mechanical fatigue phenomenon is introduced. Adopting this framework may provide a more mechanistic understanding of overuse injury and inform training and preventive strategies to reduce their occurrence. [ABSTRACT FROM AUTHOR]

Progressive white matter degeneration in periventricular and deep white matter regions appears as white matter hyperintensities (WMH) on MRI scans. To date, periventricular WMHs are often associated with vascular dysfunction. Here, we demonstrate that ventricular inflation resulting from cerebral atrophy and hemodynamic pulsation with every heartbeat leads to a mechanical loading state of periventricular tissues that significantly affects the ventricular wall. Specifically, we present a physics-based modeling approach that provides a rationale for ependymal cell involvement in periventricular WMH formation. Building on eight previously created 2D finite element brain models, we introduce novel mechanomarkers for ependymal cell loading and geometric measures that characterize lateral ventricular shape. We show that our novel mechanomarkers, such as maximum ependymal cell deformations and maximum curvature of the ventricular wall, spatially overlap with periventricular WMH locations and are sensitive predictors for WMH formation. We also explore the role of the septum pellucidum in mitigating mechanical loading of the ventricular wall by constraining the radial expansion of the lateral ventricles during loading. Our models consistently show that ependymal cells are stretched thin only in the horns of the ventricles irrespective of ventricular shape. We therefore pose that periventricular WMH etiology is strongly linked to the deterioration of the over-stretched ventricular wall resulting in CSF leakage into periventricular white matter. Subsequent secondary damage mechanisms, including vascular degeneration, exacerbate lesion formation and lead to progressive growth into deep white matter regions. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are being extensively investigated for their potential in tissue engineering and regenerative medicine. However, recent evidence suggests that the beneficial effects of MSCs may be manifest by their released extracellular vesicles (EVs); typically not requiring the administration of MSCs. This evidence, predominantly from pre-clinical in vitro and in vivo studies, suggests that MSC-EVs may exhibit substantial therapeutic properties in many pathophysiological conditions, potentially restoring an extensive range of damaged or diseased tissues and organs. These benefits of MSC EVs are apparently found, regardless of the anatomical or body fluid origin of the MSCs (and include e.g., bone marrow, adipose tissue, umbilical cord, urine, etc). Furthermore, early indications suggest that the favourable effects of MSC-EVs could be further enhanced by modifying the way in which the donor MSCs are cultured (for example, in hypoxic compared to normoxic conditions, in 3D compared to 2D culture formats) and/or if the EVs are subsequently bio-engineered (for example, loaded with specific cargo). So far, few human clinical trials of MSC-EVs have been conducted and questions remain unanswered on whether the heterogeneous population of EVs is beneficial or some specific sub-populations, how best we can culture and scale-up MSC-EV production and isolation for clinical utility, and in what format they should be administered. However, as reviewed here, there is now substantial evidence supporting the use of MSC-EVs in tissue engineering and regenerative medicine and further research to establish how best to exploit this approach for societal and economic benefit is warranted.

Extracellular vesicles (EVs), which are the main paracrine components of stem cells, mimic the regenerative capacity of these cells. Stem cell-derived EVs (SC-EVs) have been used for the treatment of various forms of tissue injury in preclinical trials through maintenance of their stemness, induction of regenerative phenotypes, apoptosis inhibition, and immune regulation. The efficiency of SC-EVs may be enhanced by selecting the appropriate EV-producing cells and cell phenotypes, optimizing cell culture conditions for the production of optimal EVs, and further engineering the EVs produced to transport therapeutic and targeting molecules.

Alcohol abuse is a major public health crisis. Relative evidences supported that the gut microbiota (GM) played an important role in central nervous system (CNS) function, and the composition of them had changed after alcohol drinking. We sought to explore the changes of GM in alcohol dependence. In our study, the GM of mice with alcohol administration was detected through analyzed 16S rRNA gene sequencing and the fecal metabolites were analyzed by LC-MS. The microbial diversity was significantly higher in the alcohol administration group, the abundance of phylum Firmicutes and its class Clostridiales were elevated, meanwhile the abundance of Lachnospiraceae, Alistipes, and Odoribacter showed significant differences among the three groups. Based on LC-MS results, bile acid, secondary bile acid, serotonin and taurine level had varying degrees of changes in alcohol model. From paraffin sections, tissue damage was observed in liver and colon. These findings provide direct evidence that alcohol intake affects the composition of GM, enable a better understanding of the function of GM in the microbiota-gut-brain (MGB) axis, and give a new thought for alcohol addiction treatment.

IntroductionConditioning regimens preceding allogeneic stem cell transplantation (alloSCT) can cause tissue damage and acceleration of the development of graft-versus-host disease (GVHD). T-cell-depleted alloSCT with postponed donor lymphocyte infusion (DLI) may reduce GVHD, because tissue injury can be restored at the time of DLI. In this study, we investigated the presence of tissue injury and inflammation in skin during the period of hematologic recovery and immune reconstitution after alloSCT.MethodsSkin biopsies were immunohistochemically stained for HLA class II, CD1a, CD11c, CD40, CD54, CD68, CD86, CD206, CD3, and CD8. HLA class II-expressing cells were characterized as activated T-cells, antigen-presenting cells (APCs), or tissue repairing macrophages. In sex-mismatched patient and donor couples, origin of cells was determined by multiplex analysis combining XY-FISH and fluorescent immunohistochemistry.ResultsNo inflammatory environment due to pretransplant conditioning was detected at the time of alloSCT, irrespective of the conditioning regimen. An increase in HLA class II-positive macrophages and CD3 T-cells was observed 12–24 weeks after myeloablative alloSCT, but these macrophages did not show signs of interaction with the co-localized T-cells. In contrast, during GVHD, an increase in HLA class II-expressing cells coinciding with T-cell interaction was observed, resulting in an overt inflammatory reaction with the presence of activated APC, activated donor T-cells, and localized upregulation of HLA class II expression on epidermal cells. In the absence of GVHD, patient derived macrophages were gradually replaced by donor-derived macrophages although patient-derived macrophages were detectable even 24 weeks after alloSCT.ConclusionConditioning regimens cause tissue damage in the skin, but this does not result in a local increase of activated APC. In contrast to the inflamed situation in GVHD, when interaction takes place between activated APC and donor T-cells, the tissue damage caused by myeloablative alloSCT results in dermal recruitment of HLA class II-positive tissue repairing macrophages co-existing with increased numbers of patient- and donor-derived T-cells, but without signs of specific interaction and initiation of an immune response. Thus, the local skin damage caused by the conditioning regimen appears to be insufficient as single factor to provoke GVHD induction.