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.

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.

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.

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.

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.

Progressive glomerulonephritis and histiocytic sarcoma associated with macrophage functional defects in CYP1B1-deficient mice.

The cytochrome P450 CYP1B1 enzyme metabolically activates polycyclic aromatic hydrocarbons and is a major P450 isoenzyme in human monocytes and macrophages. We have shown previously that mice deficient in CYP1B1 were resistant to induced tumors after 7,12-dimethylbenz[a]anthracene exposure. The pathology of aging CYP1B1 null mice on a B6; 129 background was studied in groups of 29 males and 30 females. By 12 months, 50% of the female mice had developed a unusual progressive glomerulonephritis while males had similar renal lesions later in life. This disease followed a sequence of proliferative, membranoproliferative and sclerotic glomerulonephritis. Anti-DNA antibodies were found in the blood of the mice along with immune deposits containing immunoglobulins in subepithelial locations of the glomerular basement membrane. The lesions were unlike those found in aging wild-type B6;129 mice or mice of other strains. We found that macrophages from CYP1B1-null mice were impaired in the phagocytosis of apoptotic, necrotic, and opsonized cells. This suggests a generalized defect in the phagocytic activity of CYP1B1-null mouse macrophages. Male mice also developed a high incidence (62-64%) of histiocytic sarcomas. Our study provides evidence that deficiency of CYP1B1 can play a role in the development of glomerular disease, normal processing of catabolic DNA and tumors of the mononuclear phagocyte system. The function of CYP1B1 in histiocytes and macrophages may involve both self-tolerance and tumor suppression.

Interstitial heparan sulfate in granulomatous inflammatory skin diseases.

BACKGROUND: Heparan sulfate (HS) is a glycosaminoglycan that is anchored to the outside of cell membranes. Under ordinary circumstances, it is not present in the interstitium, but under certain circumstances, mainly in the setting of inflammation and tissue repair, HS can be shed from the cell surface into the interstitium in a regulated fashion. Under these circumstances, interstitial HS seems to have an immunomodulatory function because of its binding of many cytokines. However, it is not known which cell types present at an inflammatory site are responsible for this shedding. OBJECTIVE: We have investigated the presence of interstitial HS by immunohistochemistry in various inflammatory skin diseases characterized by different compositions of the inflammatory infiltrate. RESULTS: Strong interstitial HS immunoreactivity was present only in diseases with a predominantly histiocytic infiltrate but not in diseases with a predominantly lymphocytic or neutrophilic infiltrate. CONCLUSIONS: This indicates that histiocytes have a direct or indirect role in the HS shedding process. In the well-formed granulomas of sarcoidosis, interstitial HS immunoreactivity was spatially associated with the fibrotic ring at the periphery of the granulomas, but not with the center harboring the histiocytes. This suggests that histiocytes can stimulate fibroblasts to shed HS into the interstitium.

[Langerhans and non-Langerhans histiocytosis]. / Histiocytoses langerhansiennes et non langerhansiennes.

Although Langerhans cell histiocytosis (LCH) was described a century ago, its cause and pathogenesis are still unknown. A wide spectrum of disease and variable clinical behavior are characteristic. The clinical varieties of this enigmatic disease range from a lethal leukemia-like disorder that primarily affects infants to a curable solitary lytic lesion of bone. LCH is a clonal proliferative disorder of histiocytes that resembles in morphology and phenotype the dendritic antigen-presenting Langerhans' cells of the skin and other organs. Despite gaps in understanding, significant improvements in the therapies for this disease have been made. Careful risk stratification is critical for the appropriate administration of therapy. Patients with good prognostic factors may need only observation as their disease spontaneously regresses, or minimal intervention. The active search for more effective treatments for patients with poor prognostic features is a major future challenge for the Histiocyte Society.

The gingival inflammatory infiltrate in cardiac patients treated with calcium antagonists.

OBJECTIVES: To analyse the periodontal inflammatory infiltrates in patients with cardiac disease, some of these patients were treated with calcium antagonists (nifedipine and diltiazem) and some were not, to compare them with a healthy control group, and to evaluate the changes in the inflammatory infiltrate after periodontal treatment. MATERIAL AND METHODS: A "healthy group" (HG, n=12), a "cardiac group" (CG, n=12) without treatment with calcium antagonists, a "nifedipine group" (NG, n=18) and a "diltiazem group" (DG, n=13) were analysed. Biopsies were taken from a zone 2-3 mm below the upper part of the interproximal papillae 12-13 and 33-32 before causal periodontal treatment and after 1 year. Using haematoxylin-eosin staining, the plasma cells (P), lymphocytes (L), histiocytes (H) and polymorphonuclear cells (PMN) were counted. T and B lymphocytes were evaluated using the monoclonal antibodies anti-CD20 and anti-CD45RO. Statistical tests used: chi2 for study of the sample composition; ANOVA for comparison between groups; Student t-test and Wilcoxon test for comparison between visits; post-hoc test Bonferroni. RESULTS: When the cells were compared statistically, differences were established for L at the first visit (p<0.00001) and at the last visit (p<0.02), for the B lymphocytes (first visit p<0.0021, last visit p<0.022) and for the T lymphocytes (first visit p<0.0042, last visit p<0.0021). Between the 2 visits, HG showed significant reductions for P (p<0.01), L (p<0.045) and H (p<0.033); and the NG for L (p<0.0001). Lymphocytes showed differences in the NG with respect to the B lymphocytes (p<0.008). CONCLUSIONS: Nifedipine affects the inflammatory infiltrate with a greater number of lymphocytes (especially B) and these cells fell significantly in number after periodontal treatment.

[The cells of accessory immune system]. / Las células del sistema inmune accesorio.

In the Reticulo-Endothelial System (RES), named at present Accessory Immune System (AIS), two chief groups of cells can be recognized: 1--Antigen-presenting cells: Dendritic cells 2--Antigen-processing cells: Macrophages (or Histiocytic cell) True malignant Langerhans cell neoplasm has not been yet clearly demonstrated. Finally, it is important to note that marcrophages and dentritic cells are commonly observed as relative cells in numerous malignant tumors (carcinomas, sarcomas, lymphomas, etc) However, their precise role has yet to be determined.

Las células del sistema inmune accesorio / The cells of accessory immune system

El Sistema Retículo Endotelial (SRE), actualmente denominado Sistema Inmune Accesorio (SIA), está integrado por dos grupos celulares principales: 1- Células presentadoras de antígenos: Células Dendríticas; 2- Células procesadoras de antígenos: Macrófagos (o Histiocitos). Estas células están distribuidas por todo el organismo en órganos linfáticos, sangre, hígado, glándulas endocrinas, pulmón, piel, vasos sanguíneos, sistema nervioso central y periféricos (SNC y P), placenta, riñón y partes blandas. Las células dendríticas y los macrófagos se pueden visualizar en los tejidos con la técnica de impregnación argéntica de Del Río Hortega- Polak, y con numerosas técnicas inmunohistoquímicas específicas. Los macrófagos/monocitos se originan en la médula ósea a partir de una célula precursora común. El linaje del macrófago/monocito es: Célula precursora común que se diferencia en Unidades Formadoras de Colonias (CFU-S), luego en Unidades Formadoras de Colonias de Granulocitos/Macrófagos (CFF-G/M), posteriormente en Unidades Formadoras de Colonias de macrófagos(CFU-M), y finalmente en Monoblastos y Macrófagos/Monocitos. El origen de las células dendríticas es heterogéneo. Provienen de las mismas células precursoras mieloides que originan a los macrófagos, pero también tendrían un origen linfoide. Los macrófagos participan en diferentes funciones: 1-Fagocitosis. 2-Inmunidad natural. 3- Secreción de citocinas. 4-Presentación de antígenos. Las células dendríticas son principalmente presentadoras de antígenos y activadoras de las células T. Las proliferaciones reactivas no neoplásicas y las neoplasias malignas de las células del SIA, actualmente están siendo revisadas. Las principales entidades son entre otras: 1- Procesos Reactivos No Neoplásicos de los macrófagos: Síndomes Hemofagocíticos. Histiocitosis Sinusal con Linfadenopatía Masiva (Enfermedad de Rosai-Dorfman). Y Procesos Reactivos No Neoplásicos de las células de Langerhans: Histocitosis de células de Langerhans (Histiocitosis X). 2- Neoplasias Malignas de Células Histiocíticas: Histiocitosarcoma (antes Retículosarcoma). Histiocitosis Maligna. Microglioma del SNC. 3- Neoplasias Malignas de Células Dendríticas: Sarcoma de Células Dendríticas Foliculares y Sarcoma de Células Dendríticas Interdigitadas. Las verdaderas neoplasias malignas de células de Langerhans no han sido aún claramente demostradas. Finalmente, cabe destacar que los macrófagos y células dendríticas se encuentran... (Au)