Synthesis of Chitosan Beads Incorporating Graphene Oxide/Titanium Dioxide Nanoparticles for In Vivo Studies.

Scaffold development for cell regeneration has increased in recent years due to the high demand for more efficient and biocompatible materials. Nanomaterials have become a critical alternative for mechanical, thermal, and antimicrobial property reinforcement in several biopolymers. In this work, four different chitosan (CS) bead formulations crosslinked with glutaraldehyde (GLA), including titanium dioxide nanoparticles (TiO2), and graphene oxide (GO) nanosheets, were prepared with potential biomedical applications in mind. The characterization of by FTIR spectroscopy, X-ray photoelectron spectroscopy (XRD), thermogravimetric analysis (TGA), energy-dispersive spectroscopy (EDS) and scanning electron microscopy (SEM), demonstrated an efficient preparation of nanocomposites, with nanoparticles well-dispersed in the polymer matrix. In vivo, subdermal implantation of the beads in Wistar rat's tissue for 90 days showed a proper and complete healing process without any allergenic response to any of the formulations. Masson's trichrome staining of the histological implanted tissues demonstrated the presence of a group of macrophage/histiocyte compatible cells, which indicates a high degree of biocompatibility of the beads. The materials were very stable under body conditions as the morphometry studies showed, but with low resorption percentages. These high stability beads could be used as biocompatible, resistant materials for long-term applications. The results presented in this study show the enormous potential of these chitosan nanocomposites in cell regeneration and biomedical applications.

Bilateral ptosis as first presentation of cytophagic histiocytic panniculitis: a case report.

BACKGROUND: Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis that may progress to panniculitis-like T-cell lymphoma. We report a case of CHP that first manifested as bilateral ptosis, which is the first reported case of this presentation. CASE PRESENTATION: A 25-year-old woman without medical history was referred to the neurology department of our hospital for evaluation of bilateral ptosis. Three months previously, she suddenly complained of bilateral ptosis without apparent cause. Simultaneously, non-painful tender subcutaneous nodules and eschar-like skin lesions were observed on her extremities and trunk. A diagnosis of CHP was made based on skin biopsy from the left thigh showing lobular panniculitis, vasculitis, and adiponecrosis, with infiltration of inflammatory cells, including lymphocytes, histiocytes, and phagocytic histiocytes. Her condition continued to worsen with corticosteroid and immunosuppressive agent (thalidomide) treatment. Significant improvement was noticed after three cycles of chemotherapy of THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone). CONCLUSIONS: CHP is a rare condition whose clinical presentation may include bilateral ptosis and biopsy is required for diagnosis of CHP.

Elastophagocytosis and Elastolysis in Leprosy.

Elastophagocytosis is the engulfment of the elastic fibres by the histiocytes, multinucleated giant cells, or both. The cutaneous lesions showing elastophagocytosis are annular elastolytic giant cell granuloma, actinic keratoses, persistent insect-bite reactions, elastosis perforans serpiginosa, foreign body granuloma. Occasionally, it may occur in infectious diseases like leprosy, granulomatous syphilis, North-American blastomycosis, bacterial folliculitis, and cutaneous leishmaniasis. We report a case of lepromatous leprosy with necrotic erythema nodosum leprosum with secondary anetoderma. Histopathology from the atrophic macule of anetoderma revealed periappendageal, perineural infiltration, elastophagocytosis and reduction in elastic fibres.

BRAFV600E-mutation is invariably present and associated to oncogene-induced senescence in Erdheim-Chester disease.

OBJECTIVES: Erdheim-Chester disease (ECD) is a rare form of histiocytosis characterised by uncontrolled chronic inflammation. The oncogenic BRAF(V600E) mutation has been reported in biopsies in 19 out of 37 patients with ECD from the largest published cohort, but never found in the patients' peripheral blood. Also, the role of the mutation in the pathogenesis of the disease has not been elucidated yet. BRAF(V600E) has been associated with oncogene-induced senescence (OIS), a protective mechanism against oncogenic events, characterised by the induction of proinflammatory pathways. METHODS: We verified the BRAF status in biopsies and peripheral blood from 18 patients with ECD from our cohort and matched controls by means of immunohistochemistry and of an ultrasensitive assay, based on the combination of a locked nucleic acid PCR and pyrosequencing. Droplet digital PCR was used to confirm the findings. We also evaluated the presence of senescence markers in ECD histiocytes. RESULTS: BRAF(V600E) mutation was present in all the biopsy and peripheral blood samples from patients with ECD and in none of the controls. ECD histiocytes and a fraction of circulating monocytes from patients with ECD showed signs of a constitutive activation of the MAPK pathway. Moreover, BRAF-mutated histiocytes expressed markers of OIS. CONCLUSIONS: The oncogenic BRAF(V600E) mutation is present in biopsies and in the peripheral blood from all patients with ECD who were evaluated and is associated with OIS. These findings have significant implications for the pathogenesis, diagnosis and treatment of ECD.

Elastophagocytosis: underlying mechanisms and associated cutaneous entities.

Elastophagocytosis is the phagocytosis of elastic fibers that can microscopically be seen in the cytoplasm of histiocytes, multinucleated giant cells, or both. Generally believed to be a characteristic feature of certain granulomatous disorders such as annular elastolytic giant cell granuloma or elastolytic disorders such as mid-dermal elastolysis, this feature has also been described in other cutaneous inflammatory conditions, cutaneous malignancies, infectious entities, and secondary to certain medications. The list of diseases that can exhibit this peculiar finding on histopathology is long. In this review we attempt to shed light on the available literature concerning the pathogenesis of this phenomenon and the plethora of skin conditions that exhibit elastophagocytosis.

Characteristic effects of methylglyoxal and its degraded product formate on viability of human histiocytes: a possible detoxification pathway of methylglyoxal.

Methylglyoxal (MGO) is a toxic and highly reactive alpha-oxoaldehyde, elevated in the states of various diseases underlying enhanced oxidative stress. Furthermore, MGO has been reported to generate another aldehyde, formic acid (FA). In this sense, investigating the biological property of FA is crucially important. The present study examined the effects of MGO and FA on cell viability using the U937 human histiocytic cell line. FA showed a dose-dependent increase in cell viability at the concentrations of MGO in which cell viability decreased. The mechanism of the increase by FA involved the presence of endogenous hydrogen peroxide (H2O2) and tetrahydrofolate in the folate pathway, whereas that of the decrease in cell viability by MGO involved interaction with H2O2 and oxidative damage. These findings suggest that FA production by MGO degradation may play a role in attenuation of oxidative cellular injury caused by MGO. We hypothesize that FA generation pathway constitutes a detoxification system for MGO.

[Comparative estimation of proliferation of histiocytes of the liver, spleen and kidney wounds after their gastroplasty in the experiment].

In experiment on 78 rabbits comparative morphometrycal research of proliferation of hystiocytes wounds of liver, spleen and kidney has been carried out after their plastics by a seromuscular flap of the stomach on a vascular pedicle, hepatorrhaphy, omentolienoplasty and omentonephroplasty in terms from 1 till 360 day. It is established, that plastic properties of the used autotransplants influence intensity of proliferation of hystiocytes in them. Application of a seromuscular flap of the stomach on a vascular pedicle for covering the wounds of liver, spleen and kidney promotes decrease in them to intensity proliferation of hystiocytes on all extent of the experiment in comparison with hepatorrhaphy and omentoplasty. Tissues of donor wound area of stomach do not undergo serious morphological changes after taking autotransplant.

Inflammatory cells in renal allografts.

Renal transplants are injured by a variety of diseases and pathways. One important cause for acute and chronic graft failure is rejection. Since the advent of kidney transplantation, it has become apparent that rejection is a cellular and/or antibody mediated inflammatory process with different histologic phenotypes, and clinical degrees of severity. In recent years, the immunohistochemical detection of the complement degradation product C4d has further helped to unravel mechanisms of graft injury. Our brief review of 'renal allograft inflammation' focuses on basic morphologic aspects of rejection. Our goal is to foster the close correlation between 'histologic variants of rejection/inflammation' and molecular signaling cascades including chemokine induced effects.

Reactive histiocytic proliferation in the pleural fluid mimicking metastatic signet ring adenocarcinoma.

Reactive nodular and diffuse histiocytic proliferations of mesothelial and non-mesothelial lined sites have been sporadically reported in the literature. However, there is no cytologic literature describing this process. We report a case of reactive histiocytic proliferation mimicking a metastatic signet ring adenocarcinoma in pleural fluid from a 33-year-old white male. Ancillary studies such as immunohistochemistry should be used to elucidate the cell of origin and avoid diagnostic errors.

Leukemic Transdifferentiation of Follicular Lymphoma Into an Acute Histiocytic Leukemia in a 52-Year-Old Caucasian Woman.

We report an instructive case of acute myeloid leukemia with histiocytic differentiation (acute histiocytic leukemia) arising in a patient, a 52-year-old woman with a history of follicular lymphoma. The results of genetic studies proved a clonal relationship between the lymphoma and the leukemic cells. To our knowledge, this is the first report of leukemic transdifferentiation of follicular lymphoma into modified base 5-methylcytosine (M(5)c)-like acute histiocytic leukemia and the first reported karyotype on a transdifferentiated neoplasm.

Lifespan of rabbit erythrocytes and activity of the reticulohistiocyte system.

The survival rate was measured of differently aged rabbit erythrocytes that had been taken from young and old animals, tagged with 51Cr and injected into young and old animals. The survival rate of the donor erythrocytes depends mostly on the age of the recipient animals. The life span of the injected cells found in old animals was much lower than that found in young animals. On the other hand, the age of the donor animal also has an influence, although only a small one, on the life span of the red blood cells. The cells from young animals live rather longer than those from old animals.

Phagocytic activity of the reticulohistiocyte system in rabbits after splenectomy and activation with ink.

The survival rate was measured of differently aged rabbit erythrocytes that had been taken from young animals, tagged with 51Cr and injected into young and old animals. The recipient animals had either been splenectomized, or had an ink-activated reticulohistiocyte system, or both. In young as well as in old ink-treated animals the injected cells lived for a much shorter time than in the non-treated animals. In splenectomized animals the red blood cells lived a little longer than those in the control group. In animals which had been both splenectomized and ink-treated the 51Cr-tagged cells again lived for a shorter time than those in the control group, but longer than in the ink-treated animals.

Age dependent phagocytosis of red cell membranes by the reticulohistiocytary system of the isolated perfused rat liver.

Isolated rat livers were perfused with a medium free of immune globulins, protein and hemoglobin to investigate age-dependent differences in the phagocytosis of erythrocyte membranes. Membranes of young erythrocytes were phagocyted significantly more than those of old ones. The control parameters of the liver function also were significantly higher during the increased phagocytosis of the young cells than for the old cells and the control group. In the aged animals the characteristic of the elimination curve is changing. The old livers eliminated less ghosts than the young ones. These results are significant.

Generation and characterization of mouse microglial cell lines.

A murine cell line (MMGT1) has been established after transfection of primary microglial cell cultures with a v-myc-containing plasmid. This cell line was comparable with primary microglial cells with respect to morphology, presence of acetylated low density lipoprotein receptor, non-specific esterase, CD63, major histocompatibility complex antigens and CD11, and binding for Ricinus communis agglutinin. Primary microglia as well as MMGT1 cells were negative for glial fibrillary acidic protein. Different MMGT1 strains were obtained after subcloning, two of which resembled histiocytes (F4/80 and BM-8). These cell strains, MMGT12 and 16, were able to opsonize latex beads, and could be induced by endotoxins (LPS) to secrete TNF-alpha, IL-1, IL-6, TGF-beta, and EGF. The other subclones had intermediate (MCA519, ER-MP20) or mixed macrophage characteristics and did not react to endotoxin by an increase in TNF-alpha, IL-1, and TGF-beta. Our newly established murine microglial lines may prove to be useful models to study inflammation and repair in the brain.

Evidence for vascular tone regulation by resident or infiltrating leukocytes.

The normal vascular wall contains resident leukocytes, notably tissue macrophages (histiocytes) and mast cells, that confer a rapid, eicosanoid-dependent vasoconstrictor response to agonists typical of leukocytes, such as the complement-derived anaphylatoxin C5a or the formylated peptide f-Met-Leu-Phe (isolated organ methodology). The eicosanoid-dependent vasomotor response is even more intense in pathologies that involve leukocyte infiltration of the blood vessel wall, such as atherosclerosis and serum sickness in the rabbit. The leukocyte compartment of the blood vessel is the likely source of vasoactive mediators (eicosanoids, radicals, cytokines) of physiopathological importance, with possible application in cardiac ischemia, lupus nephritis, vasculitides, and graft rejection. This line of investigation may be compared to the discovery and characterization of endothelium-dependent vasomotor responses. However, the problem is experimentally more demanding: histological correlations, experiments based on leukocyte depletion, reconstitution, and enrichment are useful approaches to document this form of circulatory control.

Reactive histiocytic hyperplasia with hemophagocytosis in hematopoietic organs: a reevaluation of the benign hemophagocytic proliferations.

Histiocytic hyperplasia with hemophagocytosis (HHH) is a relatively rare condition that has often been mistaken for a neoplastic disorder, but which most frequently represents a secondary reactive phenomenon whose associated risk factors have not yet been clearly defined. Histologic sections of hematopoietic organs (bone marrow, lymph nodes, and spleen) from 230 consecutive adults autopsies were reviewed to identify cases of HHH and to correlate them with clinical and autopsy findings. Moderate to severe HHH was present in the bone marrow in 102 and 230 cases, in the lymph nodes in 79 of 191 cases, and in the spleens of 16 of 209 cases. Recent blood transfusions, bacterial sepsis, major surgery, underlying disseminated malignancy, Candida sepsis, and viral infection were studied as potential risk factors. Both crude and adjusted analyses indicated a strong association between recent blood transfusions and the development of HHH in the bone marrow (P less than .0001). There was a marked dose-response relationship between number of units and the risk of HHH, with an adjusted risk ratio of 59.9 for five or more units compared with no transfusions. Bacterial sepsis was also associated with a significantly increased risk of HHH in the bone marrow in both the crude and adjusted analyses (adjusted risk ratio, 4.10; P = .0002). Major surgery and viral infection were only marginally associated with an increased risk for HHH (P = .03 and P = 0.06, respectively), and underlying disseminated malignancy and Candida sepsis did not appear to contribute any risk. Analyses for HHH in lymph nodes and spleen were similar to analysis for the bone marrow, but were somewhat less marked. The results of this study suggest that reactive HHH in hematopoietic organs may be far more common than has previously been acknowledged, and is most often multifactorial rather than related to a single underlying condition, with transfusions and bacterial sepsis constituting the most significant risk factors. Therefore, reactive HHH may represent a frequent secondary phenomenon in critically ill patients undergoing transfusions and should not be mistaken for an ominous sign or for the development of a superimposed malignancy.

Common reactive erythrophagocytosis in axillary lymph nodes.

Erythrophagocytosis by histiocytes in the sinuses of axillary lymph nodes is a common yet little-known phenomenon. The axillary lymph node dissections of 23 patients were studied by light microscopy and graded for the amount of erythrophagocytosis. None of the patients had evidence of a systemic hemolytic process. Nineteen of them exhibited some degree of erythrophagocytosis, and this was present even in four of the six patients who never had a prior breast biopsy. Breast biopsy was associated with massive degrees of erythrophagocytosis in 8 of 17 patients, and after a postbiopsy interval of two weeks 11 of 13 patients had hemosiderin deposition in the lymph nodes, evidence of red blood cell breakdown. This study serves to substantiate statements, made by others without confirmatory data, that large degrees of erythrophagocytosis may be seen in axillary lymph nodes after breast biopsies and that small amounts of erythrophagocytosis may be identified in lymph nodes of patients with no prior trauma history.

True histiocytic lymphoma of the thymus. Report of a case and a study of the distribution of histiocytic cells in the fetal and adult thymus.

The thymus was the site of a true histiocytic lymphoma. Immunohistochemical demonstration of lysozyme and alpha-1-antitrypsin in the tumor cells indicated the histiocytic nature of the tumor. Five fetal and five adult thymus glands were studied for the presence and distribution of true histiocytic cells. Histiocytes were demonstrated predominantly in the connective tissue septa and constituted approximately 2% of cells in these thymuses. Histiocytes are therefore a normal constituent of the thymus, which may become the primary site of true histiocytic lymphoma.

Migration of mesothelioma cells correlates with histotype-specific synthesis of extracellular matrix.

Three human pleural malignant mesothelioma cell cultures (MM) of epithelioid (E1), fibrous (F1) and byphasic (B1) histotype were studied in their synthesis of the extracellular matrix (ECM) components laminin (LM), fibronectin (FN), type IV collagen (cIV), and in their chemotactic and haptotactic migration towards the ECM produced proteins. MM-B1 showed the highest FN synthesis and release; MM-E1 produced the highest quantity of basement membrane constituents LM and cIV; MM-F1 weakly produced and released FN, LM and cIV. MM-B1 had the highest chemotactic and haptotactic motility, MM-F1 migrated toward the lowest concentration of LM while had reduced chemotactic activity toward FN and cIV; MM-E1 had the lowest migratory activity toward each ECM substrate. We demonstrated that three MM of different histotype are characterized by different ECM production and that these differences determine a variable ability of each MM to spread and migrate towards ECM substrates.