Transient Inflammatory Reaction Research Articles

A preliminary investigation of the subcutaneous tissue reaction to a 3D printed polydioxanone device in horses

BackgroundA 3D printed self-locking device made of polydioxanone (PDO) was developed to facilitate a standardized ligation technique. The subcutaneous tissue reaction to the device was evaluated after implantation in ten horses of mixed age, sex and breed and compared to loops of poly(lactic-co-glycolic acid) (PLGA). In two of the horses, the implants were removed before closing the skin. The appearance of the implants and surrounding tissue was followed over time using ultrasonography. Implants were removed after 10 and 27 (± 1) days for histologic examination.ResultsOn macroscopic inspection at day 10, the PDO-device was fragmented and the surrounding tissue was oedematous. On ultrasonographic examination, the device was seen as a hyperechoic structure with strong acoustic shadowing that could be detected 4 months post-implantation, but not at 7 months. Histology revealed a transient granulomatous inflammation, i.e., a foreign body reaction, which surrounded both PDO and PLGA implants. The type and intensity of the inflammation varied between individuals and tissue category.ConclusionsThe 3D printed PDO-device caused a transient inflammatory reaction in the subcutaneous tissue and complete resorption occurred between 4 and 7 months. Considering the intended use as a ligation device the early fragmentation warrants further adjustments of both material and the 3D printing process before the device can be used in a clinical setting.

A Transient Inflammatory Reaction with a B-Cell Lymphoid Infiltrate and Dysplastic Bone Marrow Changes Associated with the BNT162b2 COVID-19 Vaccine

COVID-19 vaccines were introduced soon after the COVID-19 pandemic emerged in 2020. Various side effects were reported worldwide, including several types of common systemic side effects such as fever and general fatigue. Reports of other rare manifestations also emerged. We report the case of an adult male with a rare systemic syndrome mimicking lymphoma after he had received the first dose of an mRNA-based COVID-19 vaccine. After nearly 6 months of investigation with suspicion for an infection or malignancy, all symptoms resolved, laboratory tests normalized, and imaging showed no sign of active disease.LEARNING POINTSA lymphoma-like reaction is a possible side effect of COVID-19 vaccination.It is important to rule out other causes of systemic symptoms before diagnosing a reaction to a COVID-19 vaccine.A lymphoma-like reaction following administration of a COVID-19 vaccine has a good prognosis.

Verrucous epidermal nevus: diagnostic difficulties.

Along Blachko’s lines are distributed diseases with Mendelian inheritance such as incontinentia pigmenti, polygenic hereditary diseases such as psoriasis or atopic dermatitis (3), nevi such as verrucous epidermal nevus (VEN) and its inflammatory variant (1), and acquired diseases such as lichen striatus (LS). All these diseases share a condition of mosaicism, that is, they presuppose the existence of a gene mutation, often post-zygotic, that gives rise to a clone of cells different from all the others. The type of mutated gene is responsible for the different morphology of these diseases, but the distribution on the skin of the mutated clone is always the same; therefore, it does not depend on the gene, but on the time in which the mutation occurred and on the stereotyped movements of the migrations that skin cells undergo during fetal life. If the nevus is very extensive and therefore secondary to an early mutation, other organs may be involved such as the nervous system, the eye, the skeletal system, as happening in epidermal nevus syndrome (4) or even some gonadal cells with the risk that the mutation is transmitted to the zygote of the offspring thus giving rise to a generalized inherited disease (5). VEN is usually present at birth; when it is localized in hidden locations or when it initially manifests with just hyperpigmented lesions it may become evident later. However, it is exceptional that it manifests itself at 8 years as in the present case. Its earliness and its morphology are able in most cases to easily differentiate it from an acquired inflammatory condition such as LS. LS is a self-healing inflammatory skin disease, usually asymptomatic, which affects the first years of age, usually between 5 and 15 years, and is distributed linearly along Blaschko’s lines, suggesting that on the line in which it occurs there is a clone of mutated cells as a result of a post-zygotic mutation: this mutation would give the cells involved a particular susceptibility towards an exogenous agent that, upon its arrival, would cause the transient inflammatory reaction (2). There are various hypotheses on the pathogenetic mechanisms that lead to the inflammatory reaction and its spontaneous regression. The present case has posed problems of differential diagnosis between VEN and LS. The histological findings were not able to eliminate the clinical doubt, indeed they added another possible differential diagnosis, i.e. inflammatory linear verrucous epidermal nevus. The latter diagnosis was discarded due to the lack of itching and obvious clinical signs of inflammation. Only prolonged clinical observation over time resolved the diagnostic doubt thanks to the persistence of the lesions and the greater evidence of papillomatous and warty structures.

Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints

There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals.

Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers.

AimsWhereas intravenous administration of Toll‐like receptor 4 ligand lipopolysaccharide (LPS) to human volunteers is frequently used in clinical pharmacology studies, systemic use of LPS has practical limitations. We aimed to characterize the intradermal LPS response in healthy volunteers, and as such qualify the method as local inflammation model for clinical pharmacology studies.MethodsEighteen healthy male volunteers received 2 or 4 intradermal 5 ng LPS injections and 1 saline injection on the forearms. The LPS response was evaluated by noninvasive (perfusion, skin temperature and erythema) and invasive assessments (cellular and cytokine responses) in skin biopsy and blister exudate.ResultsLPS elicited a visible response and returned to baseline at 48 hours. Erythema, perfusion and temperature were statistically significant (P < .0001) over a 24‐hour time course compared to saline. The protein response was dominated by an acute interleukin (IL)‐6, IL‐8 and tumour necrosis factor response followed by IL‐1β, IL‐10 and interferon‐γ. The cellular response consisted of an acute neutrophil influx followed by different monocyte subsets and dendritic cells.DiscussionIntradermal LPS administration in humans causes an acute, localized and transient inflammatory reaction that is well‐tolerated by healthy volunteers. This may be a valuable inflammation model for evaluating the pharmacological activity of anti‐inflammatory investigational compounds in proof of pharmacology studies.

Outcomes of implanting porcine small intestinal submucosa mesh in rabbit vesicovaginal space

Objective: To assess surgical outcomes of implanted porcine small intestinal submucosa (SIS) mesh in the rabbit vesicovaginal space (VVS) and explore its application value in pelvic floor reconstruction surgery. Methods: Sixteen male rabbits were randomly divided into four groups, and each group had four rabbits. All groups of rabbits were implanted with SIS mesh in the vesicovaginal space. They were humanely killed after a postoperative period of 7, 30, 90 and 180 days by group. The grafted area was removed with the surrounding bladder and vaginal tissues. The specimens were embedded in paraffin and then stained with HE and Masson's trichrome stains for visual observations, cells counts, and assessment of tissues and collagen fibers. Results: (1) After HE staining, a large number of inflammatory response cells mainly eosinophils and lymphocytes infiltrated around the SIS mesh in 7 days group, and neovascularization was observed, the infiltration area of inflammatory response cells further increased in 30 days group, the infiltration area of inflammatory response cells significantly reduced in 90 days group, while the inflammatory response basically subsided in 180 days group. (2) After Masson's trichromestaining, the collagen structure of SIS mesh in 7 days group was clear and intact. While, the collagen structure of SIS mesh was partially degraded in 30 days group, the SIS meshes of 4 rabbits were completely degraded, but the collagen fragments of SIS remained in 90 days group. In 180 days group, the SIS mesh of all rabbits was degraded, and one of them had the formation of new collagen fibers. Conclusions: SIS mesh implanted into the VVS of rabbits can lead to a transient non infective inflammatory reaction, which could be completely degraded and a small amount of new collagen fibers could be produced after 180 days of implantation. Which shown that SIS mesh should be used cautiously in pelvic floor reconstruction surgery.

The role of bacterial stimuli in inflammation-driven bone formation.

Immune cells and their soluble factors regulate skeletal cells during normal bone regeneration and pathological bone formation. Bacterial infections can trigger immune responses that activate pro-osteogenic pathways, but these are usually overshadowed by osteolysis and concerns of systemic inflammation. The aim of this study was to determine whether the transient local inflammatory reaction to non-viable bacterial immune agonists could lead to favourable new bone formation. In a series of rabbit studies, as proof-of-concept, how tibial intramedullary injection of viable or killed bacterial species affected bone remodelling and new bone formation was determined. Application of killed bacteria led to considerable new bone formation after 4 weeks, without the prolonged systemic inflammation and exaggerated bone lysis seen with active infection. The osteo-immunomodulatory effects of various species of killed bacteria and the dose response relationship were subsequently screened in ectopically-implanted ceramic scaffolds. Histomorphometry after 8 weeks showed that a relatively low dose of killed bacteria enhanced ectopic bone induction. Moreover, lipoteichoic acid - the bacterial cell-wall derived toll-like-receptor (TLR)-2 activator - was identified as an osteo-stimulatory factor. Collectively, the data indicated that bacterial stimuli could be harnessed to stimulate osteogenesis, which occurs through a synergy with osteoinductive signals. This finding holds promise for the use of non-viable bacteria, bacterial antigens, or their simplified analogues as immuno-modulatory bone regenerating tools in bone biomaterials.

Insufficient IL-10 Production as a Mechanism Underlying the Pathogenesis of Systemic Juvenile Idiopathic Arthritis.

Systemic juvenile idiopathic arthritis (sJIA) is a childhood-onset immune disorder of unknown cause. One of the concepts is that the disease results from an inappropriate control of immune responses to an initially harmless trigger. In the current study, we investigated whether sJIA may be caused by defects in IL-10, a key cytokine in controlling inflammation. We used a translational approach, with an sJIA-like mouse model and sJIA patient samples. The sJIA mouse model relies on injection of CFA in IFN-γ-deficient BALB/c mice; corresponding wild type (WT) mice only develop a subtle and transient inflammatory reaction. Diseased IFN-γ-deficient mice showed a defective IL-10 production in CD4+ regulatory T cells, CD19+ B cells, and CD3-CD122+CD49b+ NK cells, with B cells as the major source of IL-10. In addition, neutralization of IL-10 in WT mice resulted in a chronic immune inflammatory disorder clinically and hematologically reminiscent of sJIA. In sJIA patients, IL-10 plasma levels were strikingly low as compared with proinflammatory mediators. Furthermore, CD19+ B cells from sJIA patients showed a decreased IL-10 production, both ex vivo and after in vitro stimulation. In conclusion, IL-10 neutralization in CFA-challenged WT mice converts a transient inflammatory reaction into a chronic disease and represents an alternative model for sJIA in IFN-γ-competent mice. Cell-specific IL-10 defects were observed in sJIA mice and patients, together with an insufficient IL-10 production to counterbalance their proinflammatory cytokines. Our data indicate that a defective IL-10 production contributes to the pathogenesis of sJIA.

Surgical treatment of severe congenital ptosis using deep temporal fascia

ABSTRACTPurpose: To evaluate the surgical outcome of a frontalis sling using deep temporal fascia in the treatment of severe congenital ptosis (SCP).Methods: A retrospective, interventional case series was performed. The study involved 25 patients with SCP (>4 mm). All patients underwent frontalis sling surgery with deep temporal fascia between 2004 and 2012 with a follow-up period of 12 months at a minimum. Data regarding eyelid position, eyelid symmetry, cosmetic outcomes, and postoperative complications were evaluated.Results: The mean age at surgery was 7.68 years (range 4–17 years) with an average follow-up of 60 months (range is 12–108 months). The functional success rate was 88% (22/25). Ptosis recurred in 8% (2/25) of patients, overcorrection was present in 4% (1/25) of patients. The patients with ptosis recurrence underwent reoperation.The preoperative margin-to-reflex distance (MRD1) was −0.85±0.87 mm (range, −2.5 to + 0.5 mm), while the postoperative MRD1 was + 2.1 ± 1.05 mm (range, −1.5 to + 4 mm) (p < .0001). Lid symmetry (asymmetry < of 1 mm of MRD1 between the two eyes) was present in all the successful cases.Postoperative complications included transient exposure keratopathy (32%) and inflammatory brow reaction (8%).Conclusions: Frontalis sling operation with deep fascia temporalis is very effective in the treatment of SCP with excellent long-term functional and cosmetic successes.

Low-dose radiations derived from cone-beam CT induce transient DNA damage and persistent inflammatory reactions in stem cells from deciduous teeth.

Cone-beam CT (CBCT), a radiographic tool for diagnosis, treatment, and follow-up in dental practice, was introduced also in pediatric radiology, especially orthodontics. Such patients subjected to repetitive X-rays examinations may receive substantial levels of radiation doses. Ionizing radiation (IR), a recognized carcinogenic factor causing DNA double-strand breaks (DSBs) could be harmful to undifferentiated cells such as dental pulp stem cells (DPSCs) since inaccurately repaired or unrepaired DSBs may lead to malignant transformation. The H2AX and MRE11 proteins generated following DSBs formation and pro-inflammatory cytokines (CKs) secreted after irradiation are relevant candidates to monitor the cellular responses induced by CBCT. DPSCs were extracted from human exfoliated deciduous teeth and their phenotype was assessed by immunocytochemistry and flow-cytometry. Cells were exposed to IR doses: 5.4-107.7 mGy, corresponding to 0.5-8 consecutive skull exposures, respectively. H2AX and MRE11 were detected in whole cells, while IL-1α, IL-6, IL-8, TNFα in supernatants, using enzyme-linked immunosorbent assay(ELISA)at different time points after exposure. The phosphorylationlevel of H2AX in DPSCs increased considerably at 0.5 h after exposure (p<0.001 for 3, 5, 8 skullexposuresandp<0.05 for 1 skull exposure, respectively). MRE11 response could only be detected for thehighest IR dose (p<0.001) in the same interval. CKs secretion increased upon CBCT exposureaccording to doses and time. The DPSCs exposure to CBCT induces transient DNA damage and persistent inflammatory reaction in DPSCs drawing the attention on the potential risks of IR exposures and on the importance of dose monitoring in pediatric population.

Degradation, Intra-Articular Biocompatibility, Drug Release, and Bioactivity of Tacrolimus-Loaded Poly(d-l-lactide-PEG)-b-poly(l-lactide) Multiblock Copolymer-Based Monospheres

The aim of this study was to develop a formulation with a sustained intra-articular release of the anti-inflammatory drug tacrolimus. Drug release kinetics from the prepared tacrolimus loaded monodisperse biodegradable microspheres based on poly(d-l-lactide-PEG)-b-poly(l-lactide) multiblock copolymers were tunable by changing polymer composition, particularly hydrophobic-hydrophilic block ratio. The monospheres were 30 μm and released the drug, depending on the formulation, in 7 to >42 days. The formulation exhibiting sustained release for 1 month was selected for further in vivo evaluation. Rat knees were injected with three different doses of tacrolimus (10 wt %) loaded monospheres (2.5, 5.0, and 10 mg), contralateral control knees with saline. Micro-CT and histology showed no negative changes on cartilage, indicating good biocompatibility. Minor osteophyte formation was seen in a dose dependent fashion, suggesting local drug release and therapeutic action thereof. To investigate in vivo drug release, tacrolimus monospheres were injected into horse joints, after which multiple blood and synovial fluid samples were taken. Sustained intra-articular release was seen during the entire four-week follow-up, with negligible systemic drug concentrations (<1 ng/mL), confirming the feasibility of local intra-articular drug delivery without provoking systemic effects. Intra-articular injection of unloaded monospheres led to a transient inflammatory reaction, measured by total synovial leucocyte count (72 h). This reaction was significantly lower in joints injected with tacrolimus loaded monospheres, showing not only the successful local tacrolimus delivery but also local anti-inflammatory action. This local anti-inflammatory potential without systemic side-effects can be beneficial in the treatment of inflammatory joint diseases, among which is osteoarthritis.

Hypersensitive Reaction to Tattoos: A Growing Menace in Rural India.

Background:Increased enthusiasm toward newer fashion trends among rural India along with the lack of government regulation has led to increased tattoo reactions.Objective:The objective of this study is to describe various clinical manifestations of hypersensitive reactions to tattoo ink reported at a tertiary care hospital in Mandya district.Materials and Methods:An observational study was carried out over a period of 1 year from June 2014 to May 2015 at Mandya Institute of Medical Sciences, Mandya. All the patients reporting with allergic reaction due to tattooing were included in the present study after obtaining informed consent. Transient acute inflammatory reaction, infections, and skin diseases localized on tattooed area were excluded from this study. A detailed history regarding the onset, duration and color used for tattooing were collected. Cutaneous examination and biopsy was to done to know the type of reaction.Results:Fifty cutaneous allergic reactions were diagnosed among 39 patients. Mean age of subjects was 22 years and mean duration before the appearance of lesion was 7 months. Common colors associated with reactions were red (53.9%), black (33.3%), green (5.1%), and multicolor (7.7%). Itching was the predominant symptom. Skin lesions mainly consisted of lichenoid papules and plaques, eczematous lesions, and verrucous lesions. Lichenoid histopathology reaction was the most common tissue allergic reaction.Conclusion:Increasing popularity of tattooing among young people has predisposed to parallel increase in adverse reactions. Red pigment is most common cause of allergic reaction in the present study, and lichenoid reaction is the most common reaction.

CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis.

Osteoclasts are bone tissue macrophages critical to maintain bone homeostasis. However, whether osteoclasts are susceptible to flaviviral infections and involved in dengue virus (DV)-induced disease pathogenesis is still unknown. In this study, we found that osteoclasts were preferentially susceptible to DV infection and produced similar amounts of cytokines and infectious virions as macrophages. Interestingly, DV-induced cytokine secretion and nuclear translocation of the transcription factor NFATc1 in osteoclast via the Syk-coupled myeloid C-type lectin member 5A (CLEC5A). Moreover, DV caused transient inflammatory reaction in bone tissue and upregulated osteolytic activity to release C-telopeptide of type I collagen (CTX-1) from bone tissue. Furthermore, DV-induced osteolytic activity was attenuated in CLEC5A-deficient mice, and administration of antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic activity and reduced CTX-1 serum level in vivo. This observation suggests that osteoclasts serve as a novel target for DV, and transient upregulation of osteolytic activity may contribute to the clinical symptoms in dengue patients.Key messagesCultured osteoclasts were susceptible to DV infection.Osteoclasts produced similar amounts of cytokines and infectious virions as macrophages.DV induced nuclear translocation of NFATc1 in osteoclast via CLEC5A.DV caused transient inflammatory reaction in bone tissue and upregulated osteolytic activity.Antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic activity in vivo.Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-016-1409-0) contains supplementary material, which is available to authorized users.

Dynamics of spinal microglia repopulation following an acute depletion.

Our understanding on the function of microglia has been revolutionized in the recent 20 years. However, the process of maintaining microglia homeostasis has not been fully understood. In this study, we dissected the features of spinal microglia repopulation following an acute partial depletion. By injecting intrathecally Mac-1-saporin, a microglia selective immunotoxin, we ablated 50% microglia in the spinal cord of naive mice. Spinal microglia repopulated rapidly and local homeostasis was re-established within 14 days post-depletion. Mac-1-saporin treatment resulted in microglia cell proliferation and circulating monocyte infiltration. The latter is indeed part of an acute, transient inflammatory reaction that follows cell depletion, and was characterized by an increase in the expression of inflammatory molecules and by the breakdown of the blood spinal cord barrier. During this period, microglia formed cell clusters and exhibited a M1-like phenotype. MCP-1/CCR2 signaling was essential in promoting this depletion associated spinal inflammatory reaction. Interestingly, ruling out MCP-1-mediated secondary inflammation, including blocking recruitment of monocyte-derived microglia, did not affect depletion-triggered microglia repopulation. Our results also demonstrated that newly generated microglia kept their responsiveness to peripheral nerve injury and their contribution to injury-associated neuropathic pain was not significantly altered.

Biocompatibility of poly(d,l-lactic-co-hydroxymethyl glycolic acid) microspheres after subcutaneous and subcapsular renal injection

Poly(d,l-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) is a biodegradable copolymer with potential as a novel carrier in polymeric drug delivery systems. In this study, the biocompatibility of PLHMGA microspheres (PLHMGA-ms) was investigated both in vitro in three different cell types (PK-84, HK-2 and PTECs) and in vivo at two implantation sites (by subcutaneous and subcapsular renal injection) in rats. Both monodisperse (narrow size distribution) and polydisperse PLHMGA-ms were prepared with volume weight mean diameter of 34 and 17μm, respectively. Mono and polydisperse PLHMGA-ms showed good cytocompatibility properties upon 72h incubation with the cells (100μg microspheres/600μL/cell line). A mild foreign body reaction was seen shortly after subcutaneous injection (20mg per pocket) of both mono and polydisperse PLHMGA-ms with the presence of mainly macrophages, few foreign body giant cells and myofibroblasts. This transient inflammatory reaction diminished within 28 days after injection, the time-point at which the microspheres were degraded. The degradation profile is comparable to the in vitro degradation time of the microspheres (i.e., within 35 days) when incubated at 37°C in phosphate buffered saline. Subcapsular renal injection of monodisperse PLHMGA-ms (10mg) in rats was characterized with similar inflammatory patterns compared to the subcutaneous injection. No cortical damage was observed in the injected kidneys. In conclusion, this study demonstrates that PLHMGA-ms are well tolerated after in vivo injection in rats. This makes them a good candidate for controlled delivery systems of low-molecular weight drugs as well as protein biopharmaceuticals.

Inflammatory markers, oxidative stress, and antioxidant capacity in healthy allo-HSCT donors during hematopoietic stem cell mobilization.

The aim of this study is to investigate the impact of mobilization with granulocyte colony stimulating factor (G-CSF) and apheresis procedure on inflammatory and oxidative stress markers, and antioxidant capacity in healthy allo-HSCT donors. The study was conducted in the Stem Cell Transplantation Unit of Gazi University Hospital between October 2010 and March 2011, and 25 consecutive allo-HSCT donors were included. The alteration in the serum levels of iron, iron binding capacity, albumin, ferritin, IL-6, hs-CRP, TAC, MDA, and AOPP were determined at five different time points. (1) Prior to the first dose of G-CSF (T0), (2) preapheresis (on the fourth day of G-CSF before the apeheresis procedure) (T1), (3) immediately postapheresis (T2), (4) 24 h postapheresis (T3), and (5) a week after apheresis (T4). Serum ferritin levels increased steadily after administration of G-CSF and remained high up toT4. Both serum IL-6 and hs-CRP levels began to increase in the T1 sampling and reached to a maximum level at T3 and decreased even below the basal levels at T4. Serum AOPP levels decreased at preapheresis and postapheresis time points, while they increased at T3 and T4 samples. Serum MDA levels decreased at T1, T2, T3, and T4 samples. Serum TAC increased significantly and steadily at all time points post G-CSF. In conclusion; mobilization with G-CSF and apheresis caused a transient inflammatory reaction and a protein limited oxidative stress in healthy allo-HCT donors.

Effect of muscle weakness and joint inflammation on the onset and progression of osteoarthritis in the rabbit knee

Interactions between mechanical and non-mechanical independent risk factors for the onset and progression of Osteoarthritis (OA) are poorly understood. Therefore, the goal of the present study was to investigate the invivo effects of muscle weakness, joint inflammation and the combination on the onset and progression of OA in a rabbit knee joint model. Thirty 1-year-old female New Zealand White rabbits (average 5.7kg, range 4.8-6.6kg) were divided into four groups with one limb randomly assigned to be the experimental side: (1) surgical denervation of the vastus lateralis (VL) muscle; (2) muscle weakness induced by intramuscular injection of Botulinum toxin A (BTX-A); (3) intraarticular injection with Carrageenan to induce a transient inflammatory reaction; (4) combination of Carrageenan and BTX-A injection. After 90days, cartilage histology of the articular surfaces were microscopically analyzed using the Osteoarthritis Research Society International (OARSI) histology scoring system. VL denervation resulted in significantly higher OARSI scores in the patellofemoral joint (group 1). BTX-A administration resulted in significant cartilage damage in all four compartments of the knee (group 2). Carrageenan did not cause significant cartilage damage. BTX-A combined with Carrageenan lead to severe cartilage damage in all four compartments. Muscle weakness lead to significant OA in the rabbit knee. A transient local inflammatory stimulus did not promote cartilage degradation nor did it enhance OA progression when combined with muscle weakness. These results are surprising and add to the literature the conclusion that acute inflammation is probably not an independent risk factor for OA in this rabbit model.

Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts.

Saliva has been implicated to support oral wound healing, a process that requires a transient inflammatory reaction. However, definitive proof that saliva can provoke an inflammatory response remained elusive. We investigated the ability of freshly harvested and sterile-filtered saliva to cause an inflammatory response of oral fibroblasts and epithelial cells. The expression of cytokines and chemokines was assessed by microarray, RT-PCR, immunoassays, and Luminex technology. The involvement of signaling pathways was determined by Western blot analysis and pharmacologic inhibitors. We report that sterile-filtered whole saliva was a potent inducer of IL-6 and IL-8 in fibroblasts from the gingiva, the palate, and the periodontal ligament, but not of oral epithelial cells. This strong inflammatory response requires nuclear factor-kappa B and mitogen-activated protein kinase signaling. The pro-inflammatory capacity is heat stable and has a molecular weight of <40kDa. Genome-wide microarrays and Luminex technology further revealed that saliva substantially increased expression of other inflammatory genes and various chemokines. To preclude that the observed pro-inflammatory activity is the result of oral bacteria, sterile-filtered parotid saliva, collected under almost aseptic conditions, was used and also increased IL-6 and IL-8 expression in gingiva fibroblasts. The inflammatory response was, furthermore, independent of MYD88, an adapter protein of the Toll-like receptor signaling pathway. We conclude that saliva can provoke a robust inflammatory response in oral fibroblasts involving the classical nuclear factor-kappa B and mitogen-activated protein kinase signaling pathway. Since fibroblasts but not epithelial cells show a strong inflammatory response, saliva may support the innate immunity of defect sites exposing the oral connective tissue.

Tattoo-associated skin reaction: the importance of an early diagnosis and proper treatment.

Tattoo is going to be a very common practice especially among young people and we are witnessing a gradual increase of numerous potential complications to tattoo placement which are often seen by physicians, but generally unknown to the public. The most common skin reactions to tattoo include a transient acute inflammatory reaction due to trauma of the skin with needles and medical complications such as superficial and deep local infections, systemic infections, allergic contact dermatitis, photodermatitis, granulomatous and lichenoid reactions, and skin diseases localized on tattooed area (eczema, psoriasis, lichen, and morphea). Next to these inflammatory skin reactions we have to consider also the possibility of the development of cutaneous conditions such as pseudolymphomatous reactions and pseudoepitheliomatous hyperplasia. The aim of this study is to underline the importance of an early diagnosis by performing a histological examination especially when we are in front of suspected papulonodular lesions arising from a tattoo, followed by a proper treatment, since cutaneous neoplastic evolution is known to be a rare but possible complication.

Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization

Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)–poly(ethylene glycol) (PEG)–PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres. All synthesized microspheres were spherical in shape, calibrated in the 300–500μm range, swelled in phosphate-buffered saline (PBS) and easily injectable through a microcatheter. Hydrolytic degradation experiments performed in PBS at 37°C showed that all of the formulations tested were totally degraded in less than 2days. The resulting degradation products were a mixture of low-molecular-weight compounds (PEG, lactic and glycolic acids) and water-soluble polymethacrylate chains having molecular weights below the threshold for renal filtration of 50kgmol−1 for the microspheres containing MDO. Both the microspheres and the degradation products were determined to exhibit minimal cytotoxicity against L929 fibroblasts. Additionally, in vivo implantation in a subcutaneous rabbit model supported the in vitro results of a rapid degradation rate of microspheres and provided only a mild and transient inflammatory reaction comparable to that of the control group.