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1.
J Mater Chem B ; 5(3): 485-495, 2017 Jan 21.
Article in English | MEDLINE | ID: mdl-28652917

ABSTRACT

Photocrosslinked, biodegradable hydrogels have been extensively investigated for biomedical applications, including drug delivery and tissue engineering. Here, dextran (DEX) was chemically modified with mono(2-acryloyloxyethyl) succinate (MAES) via an esterification reaction, resulting in macromers that could be photocrosslinked to form hydrolytically degradable hydrogels. Hydrogel swelling ratio and degradation rate were controlled by varying the degree of MAES modification. Thiolated cell adhesion peptides (GRGDSPC) were conjugated to acrylated dextran via thiol-acrylate reaction to regulate the interactions of human mesenchymal stem cells (hMSCs) with the photocrosslinkable hydrogels. The hydrogels permitted sustained release of short interfering RNA (siRNA) over 7 weeks and were cytocompatible with hMSCs. Sustained presentation of siRNA from these photocrosslinked DEX hydrogels enhanced the osteogenic differentiation of encapsulated hMSCs. These DEX hydrogels with tunable siRNA delivery and cell adhesive properties may provide an excellent platform for bioactive molecule delivery and tissue regeneration applications.

3.
J Mater Chem B ; 5(18): 3418-3419, 2017 May 14.
Article in English | MEDLINE | ID: mdl-32264407

ABSTRACT

Correction for 'Photocrosslinkable, biodegradable hydrogels with controlled cell adhesivity for prolonged siRNA delivery to hMSCs to enhance their osteogenic differentiation' by Minh Khanh Nguyen et al., J. Mater. Chem. B, 2017, 5, 485-495.

4.
Biomaterials ; 35(24): 6278-6286, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24831973

ABSTRACT

To date, RNA interfering molecules have been used to differentiate stem cells on two-dimensional (2D) substrates that do not mimic three-dimensional (3D) microenvironments in the body. Here, in situ forming poly(ethylene glycol) (PEG) hydrogels were engineered for controlled, localized and sustained delivery of RNA interfering molecules to differentiate stem cells encapsulated within the 3D polymer network. RNA interfering molecules were released from the hydrogels in a sustained and controlled manner over the course of 3-6 weeks, and exhibited high bioactivity. Importantly, it was demonstrated that the delivery of siRNA and/or miRNA from the hydrogel constructs enhanced the osteogenic differentiation of encapsulated stem cells. Prolonged delivery of siRNA and/or miRNA from this polymeric scaffold permitted extended regulation of cell behavior, unlike traditional siRNA experiments performed in vitro. This approach presents a powerful new methodology for controlling cell fate, and is promising for multiple applications in tissue engineering and regenerative medicine.


Subject(s)
Cell Differentiation , Hydrogels/chemistry , Mesenchymal Stem Cells/cytology , Osteogenesis , RNA Interference , Alkaline Phosphatase/metabolism , Calcium/metabolism , Humans , Hydrogels/chemical synthesis , Kinetics , Magnetic Resonance Spectroscopy , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , RNA, Small Interfering/metabolism , Rheology , Time Factors
5.
Med Sci Monit ; 17(1): CS1-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21169912

ABSTRACT

BACKGROUND: Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. CASE REPORT: Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU's with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU's due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU's healed. CONCLUSIONS: LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases.


Subject(s)
Autoimmune Diseases/pathology , Leg Ulcer/etiology , Leg Ulcer/pathology , Vasculitis/complications , Animals , Antibodies, Monoclonal/therapeutic use , Azathioprine/therapeutic use , Ciprofloxacin/therapeutic use , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Female , Humans , Hydroxychloroquine/therapeutic use , Hyperbaric Oxygenation/methods , Infliximab , Larva , Leg Ulcer/drug therapy , Leg Ulcer/therapy , Male , Methylprednisolone/therapeutic use , Middle Aged , Prednisolone/therapeutic use , Skin Transplantation/methods , Treatment Outcome , Vancomycin/therapeutic use , Young Adult
6.
Am J Med Sci ; 335(3): 242-5, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18344702

ABSTRACT

BACKGROUND: Fascia and soft tissues, rich in collagen, receptors of pain and capable of significant distention, may be targets of autoimmune inflammatory diseases. We observed fasciitis due to the protein supplement Pure Whey, which has not been reported previously. METHODS: Sonography (Sonosite-Titan, 5 to 10 MHz, L-38) was performed on a patient (age, 26 years; body mass index, 38 kg/m2) with protein fasciitis. He had developed compact swelling of his forearms, hands, and legs, with skin irregularity and severe disability (without peripheral eosinophilia, normal Ig and ESR 18/hr) after taking Pure Whey, containing L-tryptophan (1.4 g per 100 g of protein). A deep skin biopsy was performed. The thickness of the brachioradial fascia (BRF) was measured and compared with 10 healthy control subjects (men ages 36.7 +/- 8.3 years; body mass index, 26.4 +/- 6.5 kg/m2). RESULTS: The deep skin biopsy showed severe fat interlobular and fascial thickening with mononuclear (noneosinophilic) infiltrate and fibrosis associated with fasciitis. BRF of the 10 healthy men had a thickness of 0.75 +/- 0.19 mm, compared with the patient's 2.4 mm thickened and cleaved BRF. After 2.5 months of corticosteroid therapy (30 mg/d with tapering) and discontinuation of the protein supplement, the patient's BRF returned to a monolayer appearance. Its thickness reduced to normal (0.8 mm), with significant clinical improvement. CONCLUSIONS: This case of noneosinophilic fasciitis associated with ingestion of L-tryptophan-containing protein supplement responded favorably to corticosteroid therapy. Sonography proved to be an effective method to visualize and confirm the fasciitis and to follow the course and therapy.


Subject(s)
Dietary Supplements , Fasciitis/diagnostic imaging , Tryptophan/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Fasciitis/chemically induced , Fasciitis/drug therapy , Humans , Male , Treatment Outcome , Tryptophan/administration & dosage , Ultrasonography
7.
Clin Rheumatol ; 26(9): 1517-21, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17401513

ABSTRACT

Oxidative stress is involved in pathogenesis of Raynaud's phenomenon (RP), a hallmark of systemic sclerosis (SSc). Frequent episodes of ischemia-reperfusion may lead to release of free radicals and enhanced lipid peroxidation reflected by elevated levels of malondialdehyde (MDA). The failure of native antioxidants (Catalase [CAT], Superoxide dismutase [SOD], and Ceruloplasmin [CP]) might be crucial in endothelial cells damage in RP. Iloprost (IL) synthetic prostacyclin analogue is currently used in the treatment of SSc patients with RP. The objectives of this study were to compare the serum levels of MDA and CP, CAT and SOD activity in red blood cells hemolysate in SSc patients compared to healthy controls; and to study the effect of 5-days IL infusions on MDA and CP levels, and CAT and SOD activity in SSc patients with RP. Twelve SSc patients were treated with 50 mug IL for 5 days. Blood samples were taken before and after day 1st and after day 5th of IL infusions. Levels of CAT were measured according to the Aebi's method; SOD, according to the Misra and Fridovich method; MDA, according to Slater's method; and CP, according to Ravin's method. Activities of CAT (p < 0.001) and SOD (p < 0.04) were significantly reduced; levels of CP (p < 0.006) and MDA (p < 0.06) were raised in SSc compared to controls. IL infusions caused reduction in MDA (p < 0.0001) levels and enhanced production of SOD (p < 0.006) and CAT (p < 0.003). The levels of CP did not change (p = 0.48). Oxidant status in SSc patients with RP is impaired. Therapy with IL led to normalization of antioxidant activity. We suggest that CAT may be a sensitive and reliable laboratory marker of oxidative stress severity in RP. We found that IL, in addition to its vasoactive properties, has a potential to activate inner antioxidant system. Activation of inner antioxidant activity may explain long-term effect of IL instead of its very short half-life time.


Subject(s)
Iloprost/pharmacology , Oxidative Stress/drug effects , Platelet Aggregation Inhibitors/pharmacology , Raynaud Disease/drug therapy , Scleroderma, Systemic/complications , Adult , Antioxidants , Catalase/blood , Catalase/drug effects , Ceruloplasmin/analysis , Ceruloplasmin/drug effects , Female , Humans , Malondialdehyde/blood , Malondialdehyde/metabolism , Middle Aged , Raynaud Disease/etiology , Scleroderma, Systemic/drug therapy , Superoxide Dismutase/blood , Superoxide Dismutase/drug effects
8.
J Clin Rheumatol ; 12(6): 298-300, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17149062

ABSTRACT

We report 3 patients with acute calcific tendinitis and bursitis of the rectus femoris muscle masquerading hip joint pain. Typically, there is tenderness and warmth lateral to the hip just below the anterior inferior iliac spine. Calcification can be seen on x-rays and may resolve as pain resolves with local injections and antiinflammatory drugs.


Subject(s)
Calcinosis/diagnostic imaging , Quadriceps Muscle/diagnostic imaging , Tendinopathy/diagnostic imaging , Female , Humans , Male , Middle Aged , Radiography
9.
J Rheumatol ; 33(3): 497-500, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16511906

ABSTRACT

OBJECTIVE: . The treatment of rheumatoid arthritis (RA) has changed dramatically with the introduction of anti-tumor necrosis factor (TNF) agents. Unfortunately, a subset of patients have partial or no response. No measurements were found to predict the efficacy of this therapy. Anti-cyclic citrullinated protein antibodies (anti-CCP) are highly specific and sensitive for RA, and their titer correlates with erosive disease. We investigated the correlation between the efficacy of infliximab therapy and the titer of anti-CCP. METHODS: Thirty consecutive seropositive patients with RA were treated with infusion of 3 mg/kg infliximab on Weeks 0, 2, 6, and 14. Clinical assessment and blood withdrawal were done before each treatment, i.e., at the minimal concentration of the drug. Disease activity was assessed by DAS28 score and by interleukin 6 (IL-6) level. Anti-CCP titer was measured by a commercial ELISA at Week 0 and Week 14. RESULTS: At baseline, 24 patients were positive for anti-CCP antibodies. In most patients there was a significant correlation between clinical response to therapy and anti-CCP titer. The results were especially noteworthy in those patients who showed a sustained and significant decrease in IL-6 levels through the entire period. CONCLUSION: Anti-CCP titer and IL-6 levels might be early predictors of the efficacy of anti-TNF therapy in patients with RA.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Peptides, Cyclic/immunology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Female , Health Status , Humans , Infliximab , Interleukin-6/blood , Male , Middle Aged , Predictive Value of Tests , Severity of Illness Index , Treatment Outcome
11.
Am J Med Sci ; 325(6): 363-4, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12811232

ABSTRACT

We report a rare case of a patient with long-standing familial Mediterranean fever who presented with sudden onset of dyspnea, abdominal pain, and cutaneous manifestations. Chest CT and histologic preparations disclosed pulmonary hemorrhage and signs of systemic vasculitis. Cyclophosphamide and steroid therapy were initiated, with marked improvement. Based on this and 1 other case, we propose that systemic vasculitis should be included as a clinical manifestation of FMF.


Subject(s)
Familial Mediterranean Fever/diagnosis , Multiple Organ Failure/diagnosis , Vasculitis/diagnosis , Acute Disease , Adult , Familial Mediterranean Fever/complications , Female , Humans , Multiple Organ Failure/complications , Vasculitis/complications
12.
J Rheumatol ; 29(7): 1556-8, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12136920

ABSTRACT

Spinal cord involvement is uncommon in giant cell arteritis (GCA) and spinal cord infarction is extremely rare. We describe an 80-year-old man with active GCA who developed sudden paraplegia and dissociated sensory loss while receiving steroid treatment. Magnetic resonance imaging showed high signal abnormality consistent with spinal cord infarction in the anterior spinal artery territory at the level of D10. The case illustrates the elusive nature of GCA and the diagnostic and therapeutic dilemmas faced by the physician caring for these patients.


Subject(s)
Giant Cell Arteritis/complications , Infarction/drug therapy , Infarction/etiology , Methotrexate/administration & dosage , Methylprednisolone/administration & dosage , Prednisone/administration & dosage , Spinal Cord/blood supply , Aged , Aged, 80 and over , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Follow-Up Studies , Giant Cell Arteritis/diagnosis , Humans , Infarction/pathology , Infusions, Intravenous , Magnetic Resonance Imaging , Male , Risk Assessment , Spinal Cord Ischemia/drug therapy , Spinal Cord Ischemia/etiology , Spinal Cord Ischemia/pathology , Treatment Outcome
13.
Harefuah ; 141(1): 20-5, 127, 2002 Jan.
Article in Hebrew | MEDLINE | ID: mdl-11851101

ABSTRACT

This is a case report of a 21 year old young man who suffers from severe early bilateral hip joint osteoarthrosis. Due to this surprising finding we discuss the differential diagnosis between Kashin-Beck disease, an endemic disease of the patients prior living area (east Siberia) and severe hip joint damage secondary to juvenile rheumatoid arthritis and other diseases.


Subject(s)
Arthritis, Rheumatoid/etiology , Selenium/deficiency , Adult , Female , Humans
14.
Semin Arthritis Rheum ; 32(3): 157-62, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12528080

ABSTRACT

OBJECTIVE: To review the clinical features, diagnosis, treatment, and outcome of interferon-induced Raynaud's phenomenon. METHODS: The medical literature was reviewed from 1967 to November 2001 with the assistance of a MEDLINE search using the key words: Raynaud, Interferon, ischemia, thrombosis and necrosis. A qualitative review was performed after the articles were abstracted and the relevant information was summarized. RESULTS: Twenty-four cases of interferon-induced Raynaud's phenomenon (including our patient) are described. Interpheron-alpha was the most common causative agent (14 cases). The symptoms appeared weeks to years after beginning treatment and varied from mild vasospasm to occlusion of digital arteries and tissue necrosis (14 cases), sometimes necessitating finger amputation (6 patients). Digital plethysmography, arteriography and capillaroscopy were valuable diagnostic tools. In 4 cases, cardiac, ophthalmic, or central nervous system drug-induced ischemia accompanied the peripheral Raynaud's phenomenon. Of the 15 cases with a documented outcome, withdrawal of the drug alone resulted in complete (6 patients) or partial (1 patient) recovery. In the others, supportive therapy was needed. The recovery period lasted from 2 weeks to 3 months. In 2 patients, continuation of treatment was possible. CONCLUSIONS: Raynaud's phenomenon and related complications must be recognized as possible side effects of interferon therapy. Early diagnosis and withdrawal of the drug may prevent unnecessary morbidity and disability.


Subject(s)
Interferon-alpha/adverse effects , Raynaud Disease/chemically induced , Humans , Male , Middle Aged , Raynaud Disease/pathology , Raynaud Disease/therapy , Remission, Spontaneous , Seasons , Treatment Outcome
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