Deposition Of Inflammatory Cells Research Articles

Beyond the Cardiovascular Effects of Glucagon-like Peptide-1 Receptor Agonists: Body Slimming and Plaque Stabilization. Are New Statins Born?

Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.

Dual red and near-infrared light-emitting diode irradiation ameliorates LPS-induced otitis media in a rat model.

Objective: Otitis media (OM) is an infectious and inflammatory disease of the middle ear (ME) that often recurs and requires long-term antibiotic treatment. Light emitting diode (LED)-based devices have shown therapeutic efficacy in reducing inflammation. This study aimed to investigate the anti-inflammatory effects of red and near-infrared (NIR) LED irradiation on lipopolysaccharide (LPS)-induced OM in rats, human middle ear epithelial cells (HMEECs), and murine macrophage cells (RAW 264.7). Methods: An animal model was established by LPS injection (2.0mg/mL) into the ME of rats via the tympanic membrane. A red/NIR LED system was used to irradiate the rats (655/842nm, intensity: 102mW/m2, time: 30min/day for 3 days and cells (653/842nm, intensity: 49.4mW/m2, time: 3h) after LPS exposure. Hematoxylin and eosin staining was performed to examine pathomorphological changes in the tympanic cavity of the ME of the rats. Enzyme-linked immunosorbent assay, immunoblotting, and RT-qPCR analyses were used to determine the mRNA and protein expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mitogen-activated protein kinases (MAPKs) signaling was examined to elucidate the molecular mechanism underlying the reduction of LPS-induced pro-inflammatory cytokines following LED irradiation. Results: The ME mucosal thickness and inflammatory cell deposits were increased by LPS injection, which were reduced by LED irradiation. The protein expression levels of IL-1β, IL-6, and TNF-α were significantly reduced in the LED-irradiated OM group. LED irradiation strongly inhibited the production of LPS-stimulated IL-1β, IL-6, and TNF-α in HMEECs and RAW 264.7 cells without cytotoxicity in vitro. Furthermore, the phosphorylation of ERK, p38, and JNK was inhibited by LED irradiation. Conclusion: This study demonstrated that red/NIR LED irradiation effectively suppressed inflammation caused by OM. Moreover, red/NIR LED irradiation reduced pro-inflammatory cytokine production in HMEECs and RAW 264.7 cells through the blockade of MAPK signaling.

Dental follicle mesenchymal stem cells ameliorated glandular dysfunction in Sjögren's syndrome murine model.

Dental mesenchymal stem cells (MSCs) are potential for use in tissue regeneration in inflammatory diseases due to their rapid proliferating, multilineage differentiation, and strong anti-inflammatory features. In the present study, immunoregulatory and glandular tissue regeneration effects of the dental follicle (DF)MSCs in Sjögren's Syndrome (SS) were investigated. Dental follicle (DF) tissues were obtained from healthy individuals during tooth extraction, tissues were digested enzymatically and DFMSCs were cultured until the third passage. DFMSCs were labeled with Quantum dot 655 for cell tracking analysis. The induction of the SS mouse model was performed by the injection of Ro60-273-289 peptide intraperitoneally. DFMSCs were injected intraperitoneally, or into submandibular, or lacrimal glands. Splenocytes were analyzed for intracellular cytokine (IFN-γ, IL-17, IL-10) secretion in T helper cells, lymphocyte proliferation, and B lymphocyte subsets. Histologic analysis was done for submandibular and lacrimal glands with hematoxylin-eosin staining for morphologic examination. The systemic injection of DFMSCs significantly reduced intracellular IFN-γ and IL-17 secreting CD4+ T cells in splenocytes (p<0.05), and decreased inflammatory cell deposits and fibrosis in the glandular tissues. DFMSCs differentiated to glandular epithelial cells in submandibular and lacrimal injections with a significant reduction in lymphocytic foci. The results showed that few amounts of DFMSCs were deposited in glandular tissues when applied intraperitoneally, while high amounts of DFMSCs were located in glandular tissues and differentiated to glandular epithelial cells when applied locally in SS murine model. DFMSCs have the potential for the regulation of Th1, Th17, and Treg balance in SS, and ameliorate glandular dysfunction. DFMSCs can be a beneficial therapeutic application for SS.

Development of Complete Thoracic Spinal Cord Transection Model in Rats for Delayed Transplantation of Stem Cells

In vivo study of a rat spinal cord injury model. To develop complete transection model of thoracic spinal cord using a polymer sheet and a microtube relevant for delayed transplantation of stem cells. Stem cell transplantation for the regeneration of spinal cord injuries has used animal models. However, current models suffer from inflammation and leakage, which lessens their usefulness in studying delayed stem cell transplantation. Thoracic spinal cord at T9 level of adult Sprague-Dawley rats was exposed and a 50:50 sheet of poly(D,L-lactic-coglycolic acid) was inserted, exposed spinal cord was completely transected, and collagen was filled between the gap between the proximal and distal stumps of transected spinal cord. A microtube was placed and fixed between the polymer surfaces facing each other. Behavior testing, magnetic resonance imaging, and myelography were performed to characterize the new complete transection with a gap formation and polymer insertion (GAP) model and to compare the GAP model with the control models. Human mesenchymal stem cells (hMSCs) were transplanted into 3 models and immunohistochemistry and western blot were performed. The inserted poly(D,L-lactic-coglycolic acid) sheet was completely disappeared 10 weeks after operation, but the inserted microtube remained firmly fixed in its original position. Myelography of the GAP model showed no leakage of contrast medium around the injured spinal cord, whereas magnetic resonance imaging of the severe contusion and simple transection models showed some leakage of contrast medium. Immunohistochemistry and western blot after hMSCs transplantation indicated that transplanted hMSCs survived and migrated well in the GAP model, and the deposition of inflammatory cells in GAP model was less than a simple transection model or severe contusion model. The developed GAP model is more relevant for delayed transplantation of stem cells for the study of regeneration of spinal cord injury of rats.

Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto

Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.

Human Amniotic Fluid Mesenchymal Stem Cells in Combination with Hyperbaric Oxygen Augment Peripheral Nerve Regeneration

Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.

Cryopreservation alters antigenicity of allografts in a porcine model of transplant vasculopathy

The need for arterial grafts in coronary surgery to complement autologous vessels has generated interest in cryopreservation of small diameter allografts. We evaluated functional and histologic changes occurring in cryopreserved allografts 3 months after porcine femoral artery transplants. Methods Twenty recipient and 15 donor pigs included a control group of 16 fresh and 12 cryopreserved nonimplant arteries were used. Fresh ( n = 5) and cryopreserved ( n = 5) autografts were implanted to assess cryopreservation effects in the absence of rejection. Fresh allografts with or without treatment with cyclosporine (CsA) ( n = 6 of 8) and cryopreserved allografts with or without treatment with CsA ( n = 6 of 10) were performed to study the antigenicity of cryopreserved allografts. Arteries were stained with hematoxylin and eosin, Masson's trichrome, and orcein for morphometric analyses and immunostained to identify endothelial cells, smooth muscle cells, T lymphocytes, and macrophages. Results Among nonimplant arteries, cryopreservation reduced α-actin expression and increased the luminal area. All implanted autografts were patent. Cryopreserved autografts showed reduced α-actin expression and developed intimal hyperplasia compared to fresh autografts. Treatment with CsA improved the patency of fresh allografts from 0% to 83% ( P < .01) and of cryopreserved allografts from 40% to 100% ( P < .05). Cryopreserved allografts showed substantial intimal hyperplasia, and fresh allografts had more T lymphocyte infiltration in the intimal layer with aneurysmal dilatation. Conclusions Cryopreservation reduces the deposition of inflammatory cells and prevents the thrombosis or aneurysmal lesions observed in fresh allografts. Therefore, cryopreservation modifies the antigenicity of vascular allografts.

Intraocular lens explantation in uveitis.

Visual rehabilitation after cataract surgery has been improved with the development of IOLs. These lenses are well tolerated in many uveitis patients when complete control of preoperative inflammation is achieved. However, in some patients, IOL placement after cataract extraction results in chronic inflammation, deposition of inflammatory cells and debris on the IOL surface, and inflammatory membrane formation despite antiinflammatory coverage. Patients with systemic diseases characterized by chronic inflammation, such as sarcoidosis and JRA, and those with chronic ocular inflammatory conditions or inflammation involving the intermediate segment of the eye may be at high risk for these complications. In patients in whom antiinflammatory therapy fails, adequate control of inflammation may be achieved after lens explantation.

Heparin-surface-modified intraocular lenses in pediatric cataract surgery: Prospective randomized study

Purpose To evaluate the performance of heparin-surface-modified (HSM) intraocular lenses (IOLs) in pediatric eyes after cataract surgery. Setting L.V. Prasad Eye Institute, Hyderabad, India. Methods This prospective, randomized, double-masked, controlled clinical trial comprised 90 children aged 2 to 14 years with cataract. The patients were consecutively randomized to receive an HSM (Group 1) or an unmodified (Group 2) poly(methyl methacrylate) (PMMA) IOL. Extracapsular cataract extraction (ECCE) with IOL implantation was performed in children 8 years and older and ECCE with primary posterior capsulotomy, anterior vitrectomy, and IOL implantation in children younger than 8 years. Outcome parameters were inflammatory cell deposits on the IOL surface, posterior synechias, and anterior chamber reaction. Results Follow-up data were available for 73, 70, 60, and 68 patients at 1 week, 1 month, 3 months, and 6 months, respectively. Significantly fewer cell deposits were noted in Group 1 at 1, 3, and 6 months ( P < .001). Synechia formation and anterior chamber reaction were comparable in the 2 groups. Conclusion The lower incidence of inflammatory cell deposit formation in eyes with HSM PMMA IOLs indicates that these IOLs have greater bicompatibility than unmodified IOLs in pediatric cataract surgery.

Effect of heparin-surface-modified poly(methyl methacrylate) intraocular lenses on the postoperative inflammation in an Asian population

Purpose: To compare the efficacy of heparin-surface-modified (HSM), poly(methyl methacrylate) (PMMA) posterior chamber intraocular lenses (IOLs) with that of unmodified PMMA IOLs in reducing postoperative complications caused by inflammatory reactions after extracapsular cataract extraction in an Asian population.Setting: Departments of Ophthalmology, University of Malaya, Kuala Lumpur, Malaysia, and Tan Tock Seng Hospital, Singapore.Methods: In a randomized, double-blind study performed at two centers, 51 patients received an HSM PMMA lens and 48, an unmodified PMMA IOL. Cell and pigment deposits were evaluated by slitlamp at 1 to 6 days, 2 to 3 weeks, and 3 to 6 months postoperatively.Results: Significantly more eyes with unmodified IOLs had inflammatory cell deposits than those with HSM IOLs at 3 to 6 months (P < .001) and 12 to 14 months (P = .018) postoperatively. The HSM group also had significantly fewer cell deposits per patient at these two follow-ups. Significantly more eyes in the non-HSM group had pigment deposits 3 to 6 months after surgery (P = .049). One year postoperatively, about 85% of patients in both groups had a best corrected visual acuity of 0.5 or better.Conclusion: Heparin surface modification significantly reduced the inflammatory response to PMMA IOLs in an Asian population for at least 12 to 14 months.

Oberflächenqualität faltbarer Intraokularlinsen aus Silikon - Eine rasterelektronenmikroskopische Studie

Soft intraocular lenses (IOLs) have been developed to be folded during insertion to allow implantation through a small incision. The surface of the IOL is of great importance in postoperative inflammation and long-term acceptance of the implant. Rough and sharp edges can damage delicate intraocular tissues. The purpose of this study was to analyze new, foldable silicone IOLs for surface quality prior to and following folding. Eleven silicone IOLs of different types were included in this study (four one-piece plate-haptic silicone IOLs and seven three-piece silicone IOLs with polypropylene, PMMA or polyimid haptics). We performed scanning electron microscopy on brand-new IOLs prior to and following folding either with forceps or inserter. Special attention was given to the silicone optic surface, optic edges, haptic-optic junctions and the haptic itself. Photographs were taken at 5-350 times magnification. All IOLS demonstrated a smooth and homogeneous optic surface at low magnification. At high-power magnification (X 350), distinctive surface patterns were evident in some IOLs, which turned out to be artefacts. The edge finish showed surplus silicone material and molding flash in six of 11 IOLs. Positioning holes of the 4 plate-haptic IOLs were, except in one IOL, rounded and not rough. Photographs of the haptic-optic junctions revealed surplus material or clefts between the haptic and optic in six of the 7 three-piece IOLs; the loop ends of two IOLs showed a roughened or irregular surface. We did not detect any IOL changes produced by folding. The silicone IOLs tested demonstrated generally acceptable surface properties, but most IOLs had regional surface irregularities of varying magnitude. The clinical impact of these remains to be established, but surplus material or surface defects might result in deposition of inflammatory cells, protein or microorganisms and synechia formation. Folding of the IOLs did not produce superficial defects.

Natural history of cellular deposits on the anterior intraocular lens surface

Previous cytopathological studies have demonstrated the presence of cellular deposits on the poly(methyl methacrylate) (PMMA) intraocular lens (IOL) surface. In this prospective study, IOL surface specular microscopy was used to document the natural history of these deposits in the first year following PMMA IOL implantation. Intraocular lens surface specular microscopy was performed 1, 3, 6, and 12 months after endocapsular cataract surgery in 27 otherwise normal eyes. Postoperatively, IOLs were assessed for the presence of inflammatory cells, with the number of cells graded from 0 (none) to 4 (many). Two inflammatory cell types were visualized: small and giant cells. Small cells were found on 81.5% of IOLs at 1 month, 73.1 % at 3 months, and 30.4% at 12 months. Small cells were found in only small numbers (peak mean cell score of 1.26 ± 0.94 at 1 month). Giant cells were found on 59.3% of lenses at 1 month, 73.1 % at 3 months, and 39.1 % at 12 months. The number of giant cells on each lens peaked at 3 months (mean cell score 2.0 ± 1.55), when 50% of lenses achieved a giant cell score of 3 or 4. Inflammatory cell deposits are, therefore, a normal occurrence on the PMMA IOL surface for up to 1 year after surgery. This cellular response consists of two distinct processes: a small cell response, which peaks by 1 month, and a later giant cell response, which peaks at 3 months.

Pathologie des Hornhaut-Endothels bei der bullösen Keratopathie nach Iris-Cliplinsen-Implantation

12 patients developed pseudophakic bullous keratopathy 2 to 7 years following i.c. cataract-extraction with implantation of 4-loop iris clip lenses necessitating perforating keratoplasty. To study the pathogenesis of pseudophakic bullous keratopathy the corneal endothelium of the excised button was investigated light-microscopically after vital staining of the endothelium. Additionally the surface of the explanted intraocular lenses were examined by the method of Wolter. The result is a central cell density of the excised corneal buttons between 179 and 867 cells/mm2. Large cell-free areas were always found indicating that a disturbance of the endothelial barrier function is the major reason for corneal decompensation. A relation between inflammatory cell deposits on the IOL-surfaces and the endothelial decompensation was not apparent. As the main reason for endothelial decompensation a chronical mechanically induced endothelial cell loss is supposed leading to disturbances of the endothelial barrier function. To prevent a repeated corneal decompensation it is recommended to remove iris-clip-lenses during the procedure of perforating keratoplasty.

Cutaneous hemorrhages and gangrenes localized to the lower limbs in patients with collagen diseases and in diabetics.

The appearance and development of cutaneous hemorrhages and gangrenes localized to the lower limbs in patients with certain systemic collagen diseases and in patients with purpura hyperglobulinemica Waldenstrom were compared to similar lesions in diabetics. There were characteristic differences, clinically as well as microscopically. The diabetic gangrene was clinically characterized by a surrounding zone of erythema. Such erythema was never seen in the patients with collagen diseases and gangrene. Especially in elderly diabetics, purpura was common and was localized to the erythematous areas of gangrenes as well as to non-erythematous areas. The cutaneous hemorrhages of the patients with collagen diseases were of varying size and were most often raised and palpable, in contrast to those in the diabetics. Large cutaneous hemorrhages in patients with collagen diseases often transformed into gangrenes. In diabetics, gangrene as well as purpura were generally precipitated by factors such as cardiac decompensation with edema of the legs. Such precipitating factors were not seen in the patients with collagen diseases. In diabetics, the erythema adjacent to a cutaneous necrosis corresponded microscopically to dilated small blood vessels surrounded by only a small number of inflammatory cells. No thrombotic vessels were seen. In the patients with collagen diseases, thrombotic vessels were observed in the cutaneous areas adjacent to the necrosis. In and around the walls of the small blood vessels there was a pronounced deposition of inflammatory cells.