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Intraperitoneal clodronate liposomes remodel the local macrophage niche and potentiate biomaterial-induced osteoinduction.

BACKGROUND: Osteoinductive biomaterials hold promise for repairing critical-size bone defects, yet the mechanisms underlying materials-instructed osteoinduction (MIOI) remain unclear. Macrophages are central, and local liposomal clodronate (LipClod) typically suppresses osteogenesis. Whether systemic LipClod modulates MIOI is unknown. We investigated the effect of intraperitoneal (i.p.) LipClod on ectopic osteoinduction. METHODS: Male FVB mice received subcutaneous β-tricalcium phosphate (TCPs) scaffolds and a single i.p. LipClod dose 1 day after implantation; vehicle liposomes served as contr

Lung disease in relation to unique monocyte-macrophage subpopulations induced by combined inhalant endotoxin and collagen-induced arthritis.

BACKGROUND: Lung disease is the most overrepresented cause of death in rheumatoid arthritis (RA). Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung disease with a combination of airborne exposures and collagen-induced arthritis (CIA), a model that recapitulates features of RA-associated interstitial lung disease (RA-ILD). As patients with RA-ILD demonstrate unique circulating monocyte subpopulations, this study aims to characterize lung infiltrating monocytes/macrophages in a mouse model of RA-ILD and determine whether reducing these cells

Osteonecrosis of the jaw induced by clodronate, an alkylbiphosphonate: case report and literature review.

PURPOSE: To report on a case of osteonecrosis of the jaw (ONJ) in a patient treated with clodronate, an alkylbiphosphonate, and to draw attention to the risk of ONJ following treatment with all biphosphonates, whether they are alkyl- or amino-biphosphonates. CASE REPORT: Beginning at age 58 years, a female patient took clodronate for almost 13 years for a metastatic bone cancer. She also underwent chemotherapy and radiotherapy. Three months after the end of biphosphonate therapy, she suffered from toothache, and tooth 27 (left maxillary second molar) was extracted. A maxillary focus of osteit

Efficacy of intramuscular clodronate in Complex Regional Pain Syndrome type I: description of a case located in the astragalus in a patient with psoriatic arthritis.

Reflex sympathetic dystrophy or Complex Regional Pain Syndrome type I (CRPS I) is a painful regional disease with non-metameric topography, which shows extreme pathomorphological variability, from forms in which pain is the only clinical manifestation, to "pseudo-purulent" forms characterized by impressive local manifestations. The use of high doses of bisphosphonates in the treatment of CRPS I is confirmed in different publications which associate their efficacy with their specific biological properties and multiple actions at local level. This case report describes a case of CRPS I in the as

Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (op/op) mice after macrophage depletion.

We previously reported that macrophage colony-stimulating factor (M-CSF, CSF-1) played important roles in the process of the repopulation of Kupffer cells after their elimination by administration of liposome-entrapped dichloromethylene diphosphonate (lipo-MDP). In this study, we examined the repopulation of Kupffer cells and splenic red pulp macrophages in osteopetrotic (op/op) mice defective in the production of functional M-CSF and their littermate mice by using the lipo-MDP model. In untreated op/op mice, numbers of F4/80-positive Kupffer cells in the liver and F4/80-positive splenic red p

The use of a model of in vivo macrophage depletion to study the role of macrophages during infection with Bacillus anthracis spores.

The pathogenesis of infection by Bacillus anthracis has been the subject of many investigations, but remains incompletely understood. It has been shown that B. anthracis spores germinate in macrophages and perhaps require this intracellular niche to germinate in vivo before outgrowth of the vegetative organism. However, it has also been reported that macrophages are sporicidal in vitro. In our in vivo model, macrophages were depleted from mice by either silica treatment or treatment with liposome-encapsulated dichloromethylene disphosphonate (Cl(2)MDP), and the animals were infected parenteral

Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization.

PURPOSE: Macrophage recruitment to the choroid has been proposed to contribute to the pathogenesis of choroidal neovascularization (CNV) in AMD. The study was conducted to determine whether treatment with clodronate liposomes (CL(2)MDP-lip), which cause depletion of blood monocytes and lymph node macrophages, diminishes the severity of neovascularization in a mouse model of laser-induced CNV. METHODS: Laser-induced CNV was performed in female 16-month-old C57BL/6 mice. Macrophages were depleted by use of CL(2)MDP-lip intraperitoneally and subcutaneously 72 and 24 hours before and every 2 to 3

[Macrophage depletion inhibits leukocyte recruitment in experimental melanin-induced uveitis (EMIU)].

BACKGROUND: To study the role of macrophages in experimental melanin-induced uveitis (EMIU), we used the method of intravital microscopy to analyse changes in leukocyte adhesion to iris venules of live rats with EMIU after pretreatment with liposomal clodronate. MATERIALS AND METHODS: EMIU was induced in Lewis rats (n = 48) by intraperitoneal immunisation with bovine crude melanosomes emulsified in complete Freund's adjuvant (CFA) and pertussis toxin (PTX). Control animals received CFA and PTX only (n = 12) or no injection (n = 6). Animals were treated with liposomal clodronate (DMDP-lip) or

A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults.

In patients with multiple myeloma, despite a major reduction of bone pain achieved with chemotherapy, skeletal disease continues to progress. The effects of clodronate, an inhibitor of osteoclastic bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed multiple myeloma. Within the framework of the VIth MRC Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed multiple myeloma were randomized to receive either clodronate 1600 mg daily (n=264) or an outwardly identical placebo (n=272) in addition to chemotherapy. Tre

Severe osteoporosis due to systemic mast cell disease: successful treatment with interferon alpha-2B.

We describe a 33-year old man suffering from severe vertebral osteoporosis and urticaria pigmentosa due to systemic mast cell disease (SMCD). Because i.v. clodronate therapy could not prevent further vertebral fractures, an additional treatment with interferon alpha-2b was initiated. During 24 months of treatment, our patient had no further pain episodes, no new vertebral fractures were discovered, trabecular bone mineral density (BMD) increased significantly and urticarial symptoms improved. Nevertheless, the extent of skin lesions remained unchanged. On histological examination, a remarkable

The effect of clodronate on bone in metastatic prostate cancer. Histomorphometric report of a double-blind randomised placebo-controlled study.

57 patients with advanced prostate cancer and a failure of prior hormonal treatment were selected for a double-blind placebo-controlled trial, in which they were randomly allocated to receive either clodronate (C) or placebo concomitantly with the basic cancer treatment, estramustine phosphate (E) (560 mg daily). The treatment was started intravenously with 300 mg of C or placebo in 5 consecutive days, and thereafter maintained orally with 1600 mg of C or identical placebo daily for 3 months. Bone biopsies were taken at admission and at 3 months. Measurements of serum calcium, phosphate, alkal

Prophylactic treatment of skeletal metastases, tumor-induced osteolysis, and hypercalcemia in rats with the bisphosphonate Cl2MBP.

BACKGROUND: The purpose of this study was to investigate the influence of a prophylactic bone protective treatment with the bisphosphonate dichloromethane/diphosphonic acid (Cl2MBP) in an experimental model of osteolysis with intraosseous implantation of the Walker carcinosarcoma 256 B. METHODS: The biphosphonate was given as a high-dose, short-term treatment (30 mg/5 days sc) followed by a treatment-free interval (1-7 weeks) or as a low-dose, long-term prophylactic treatment (2.5 or 5.0 mg/day/3 weeks sc). Osteolysis was measured with a radiographic and histologic grading system. RESULTS: T

Squaric Acid Dibutylester Promotes Innate Immune-Driven Hair Growth with CD206+ Macrophage Accumulation in the Dermis.

Alopecia areata (AA) is an autoimmune skin disorder that causes hair loss. Squaric acid dibutylester (SADBE) is used for AA treatment as a topical immunotherapy that promotes hair growth by inducing allergic contact dermatitis in skin lesions. However, the mechanism of action remains unclear. C3H/HeJ mice spontaneously develop AA, and SADBE application induces hair growth at the lesion on day 28. In healthy young mice treated with SADBE, hair growth was observed after day 14. Fluorescent immunostaining of SADBE-treated skin tissues revealed a remarkable accumulation of macrophages in the dermi

A systematic review and meta-analysis of interventional studies of bisphosphonates and denosumab in multiple myeloma and future perspectives.

Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodr

Совпадение в полном тексте источника
… First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX):a randomised controlled trial. Lancet. 2010;376(9757):1989–1999. doi: 10.1016/S0140-6736(10)62051-X. 54. D'Arena G, Gobbi PG, Broglia C, et al. … Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX):secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12(8):743–752. doi: 10.1016/S1470-2045(11)70157-7. 71. …

Treatment with Histone Deacetylase Inhibitor Attenuates Peripheral Inflammation-Induced Cognitive Dysfunction and Microglial Activation: The Effect of SAHA as a Peripheral HDAC Inhibitor.

It has been demonstrated that peripheral inflammation induces cognitive dysfunction. Several histone deacetylase (HDAC) inhibitors ameliorate cognitive dysfunction in animal models of not only peripheral inflammation but also Alzheimer's disease. However, it is not clear which HDAC expressed in the central nervous system or peripheral tissues is involved in the therapeutic effect of HDAC inhibition on cognitive dysfunction. Hence, the present study investigated the effect of peripheral HDAC inhibition on peripheral inflammation-induced cognitive dysfunction. Suberoylanilide hydroxamic acid (SA

Acute Lymphoblastic Leukemia with Malignant Hypercalcemia: A Case Report.

BACKGROUND Malignant hypercalcemia is a rare finding in the pediatric population, even more rare in hematological malignancies, such as leukemia. CASE REPORT We present a case of a 6-year-old female patient who was diagnosed with acute lymphoblastic leukemia, with secondary hypercalcemia. She started chemotherapy following the IC-BFM ALL2002 protocol with simultaneous calcitonin, diuretics and aggressive hydration for hypercalcemia, and went into complete remission after the induction therapy. After 4 months of chemotherapy, she was diagnosed with relapse associated again with malignant hyperc

Endocrine manifestations of systemic mastocytosis in bone.

Systemic Mastocytosis (SM) is characterized by accumulation of clonal, neoplastic proliferations of abnormal mast cells (MC) in one or more organ system other than skin. Presence of these multifocal clusters of abnormal mast cells is an essential feature of SM. Frequently associated with D816V (KIT) mutation, the presence of this mutation and elevated serum tryptase are minor criteria for diagnosis. SM manifestations depend on the degree of mast cell proliferation, activation and degranulation. SM has a variable prognosis and presentation, from indolent to "smoldering" to life-threatening dise

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results.

Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long-term follow-up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21-28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5.9-year median follow-up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5.2% vs. CLO 5.8% at 2 years; incidence platea

Bisphosphonates for malignancy-related bone disease: current status, future developments.

This review relates to the efficacy and safety of bisphosphonates in metastatic bone disease. It discusses practical recommendations and possible future indications for bisphosphonate therapy. The current aims of bisphosphonates for metastatic bone disease are to prevent skeletal-related events (SREs), reduce bone pain and improve quality of life. Phase III clinical trials of clodronate and pamidronate have established their efficacy against bone complications in patients with breast cancer and multiple myeloma, while randomized trials have shown SRE reductions with zoledronic acid in patients

Maresin1 Improves Angiogenesis and Cognitive Function by Regulating Perivascular Macrophages in Rats with Chronic Cerebral Hypoperfusion.

Population aging imposes a substantial dementia burden. Chronic cerebral hypoperfusion (CCH) serves as a crucial early pathological basis for Alzheimer's disease (AD) and Vascular Dementia (VaD). Our previous studies have demonstrated that macrophage-derived docosahexaenoic acid metabolite Maresin1 can ameliorate CCH-induced cognitive impairment, though the underlying angiogenesis-related mechanisms remain to be elucidated. We developed a rat model of chronic cerebral hypoperfusion using the bilateral common carotid artery occlusion surgical approach. Cognitive improvements and angiogenic mech