Manuka Honey/2-Hydroxyethyl Methacrylate/Gelatin Hybrid Hydrogel Scaffolds for Potential Tissue Regeneration.

Scaffolding biomaterials are gaining great importance due to their beneficial properties for medical purposes. Targeted biomaterial engineering strategies through the synergy of different material types can be applied to design hybrid scaffolding biomaterials with advantageous properties for biomedical applications. In our research, a novel combination of the bioactive agent Manuka honey (MHo) with 2-hydroxyethyl methacrylate/gelatin (HG) hydrogel scaffolds was created as an efficient bioactive platform for biomedical applications. The effects of Manuka honey content on structural characteristics, porosity, swelling performance, in vitro degradation, and in vitro biocompatibility (fibroblast and keratinocyte cell lines) of hybrid hydrogel scaffolds were studied using Fourier transform infrared spectroscopy, the gravimetric method, and in vitro MTT biocompatibility assays. The engineered hybrid hydrogel scaffolds show advantageous properties, including porosity in the range of 71.25% to 90.09%, specific pH- and temperature-dependent swelling performance, and convenient absorption capacity. In vitro degradation studies showed scaffold degradability ranging from 6.27% to 27.18% for four weeks. In vitro biocompatibility assays on healthy human fibroblast (MRC5 cells) and keratinocyte (HaCaT cells) cell lines by MTT tests showed that cell viability depends on the Manuka honey content loaded in the HG hydrogel scaffolds. A sample containing the highest Manuka honey content (30%) exhibited the best biocompatible properties. The obtained results reveal that the synergy of the bioactive agent, Manuka honey, with 2-hydroxyethyl methacrylate/gelatin as hybrid hydrogel scaffolds has potential for biomedical purposes. By tuning the Manuka honey content in HG hydrogel scaffolds advantageous properties of hybrid scaffolds can be achieved for biomedical applications.

Pregnancy-Induced Sweet's Syndrome Treated with Infliximab.

OBJECTIVE: To present a case of relapsing and resistant Sweet's syndrome that developed during pregnancy together with an onset of Crohn's disease, showing complete resolution with the use of infliximab. CLINICAL PRESENTATION AND INTERVENTION: A 30-year-old pregnant woman presented with fever, skin lesions, and diarrhea. Skin biopsy confirmed neutrophilic dermatosis and she was diagnosed with Crohn's disease after endoscopy. There was no recurrence of Sweet's syndrome outside of her pregnancy. During a previous pregnancy, while corticosteroids were ineffective, complete regression of skin lesions was achieved using infliximab. CONCLUSION: The "off-label" use of infliximab is beneficial for relapsing and resistant Sweet's syndrome.

Antimicrobial synergism and cytotoxic properties of Citrus limon L., Piper nigrum L. and Melaleuca alternifolia (Maiden and Betche) Cheel essential oils.

OBJECTIVES: The chemical composition, antimicrobial and synergistic effect, and cytotoxic activity of Citrus limon (lemon), Piper nigrum (green pepper) and Melaleuca alternifoila (tea tree) essential oils (EOs) were investigated. METHODS: Chemical analyses of essential oils were tested by GC-FID and GC-MS spectroscopy. The antimicrobial activity assay was conducted using microdilution method against several oral bacteria and Candida spp. originating from the humans with oral disorders. The synergistic antimicrobial activity was evaluated using checkerboard method. The cytotoxicity evaluation of EOs was assessed using MTT test. KEY FINDINGS: Limonene (37.5%) and ß-pinene (17.9%) were the major compounds in C. limon oil, ß-pinene (34.4%), δ-3-carene (19.7%), limonene (18.7%) and α-pinene (10.4%) in P. nigrum oil and terpinen-4-ol (38.6%) and γ-terpinene (21.7%) in M. alternifolia oil. The broad-spectrum antimicrobial activity was achieved by tested three EOs, with C. limon oil being the strongest against bacteria and M. alternifolia oil strongest against fungi. The EOs demonstrated synergism; their combined application revealed an increase in antimicrobial activity. All tested essential oils showed lower cytotoxic activity in comparison with the positive control, and the obtained results confirmed a dose-dependent activity. CONCLUSIONS: The results of this study encourage use of tested EOs in development of a novel agent intended for prevention or therapy of corresponding oral disorders.

Dexamethasone-cyclophosphamide pulse therapy in pemphigus: a review of 72 cases.

BACKGROUND: Autoimmune pemphigus is a group of severe blistering diseases. Although corticosteroids have dramatically altered the prognosis of pemphigus, morbidity and mortality resulting from the adverse effects of systemic corticosteroids remain high. Dexamethasone-cyclophosphamide pulse (DCP) therapy was introduced to diminish the adverse effects of prolonged conventional daily dose regimens. OBJECTIVE: To report our experience with the use of the DCP regimen in patients with autoimmune pemphigus. METHODS: In the period 1998-2002, 72 patients with various forms of autoimmune pemphigus treated with DCP therapy were included, of whom 36 patients were previously treated with conventional corticosteroid therapy, and 36 were newly diagnosed patients. RESULTS: Of the 72 patients, 43 completed treatment, while 13 patients did not respond adequately to the treatment and continued with the conventional daily regimen, nine patients were lost to follow-up, and seven patients died. Two of these deaths were probably a consequence of DCP therapy. CONCLUSION: DCP regimen is a beneficial treatment for patients with pemphigus, sparing the adverse effects of conventional regimens.

Serological and clinical comparison of children and adults with anti-endomysial antibodies.

We compared serological and clinical presentation of 38 adults (5 males, 33 females) and 37 children (15 boys, 22 girls) with anti-endomysial antibodies (AEA).AEA, antinuclear (ANA), anti-parietal (APA), anti-thyroid microsomal (ATMA), anti-thyreoglobulin (ATGA), anti-smooth muscle (SMA) and anti-mitochondrial (AMA) antibodies were detected by IIF. Anti-tissue transglutaminase (tTG), anti-extractable nuclear antigens (ENA) and anti-actin (AAA) antibodies were studied by ELISA. There were no differences in frequency of ANA, APA, ATGA, SMA, AMA and AAA in children and adults. ATMA (p < 0.001) and anti-ENA (p < 0.05) positivity were more frequently found in adults. Anti-Ro/SSA had 7/38 adults and 1/37 children (p < 0.05). Adults had more frequently silent form of celiac disease associated with autoimmune diseases (p < 0.001). We are the first to demonstrate that in spite of no difference in ANA positivity in adults and children, ANA in adults more frequently target ENA, especially Ro/SSA antigen. The reason for this ANA specificity could be the longer gluten exposure in adults.

Regressing anaplastic CD30-positive large-cell lymphoma of the skin.

Originally believed to be of histiocytic origin, regressing primary cutaneous anaplastic large-cell lymphoma is a CD30 (Ki 1) positive T-cell lymphoma with histologic high grade malignancy, but with an often favorable clinical course with regression of individual lesions. We present a case of a 69-year-old white woman with an 8-month history of noduloulcerative lesions on her right lower leg, otherwise in good general health. The clinical, histologic, and immunohistochemical findings pointed to CD30 positive primary cutaneous anaplastic large-cell lymphoma. There were no signs of generalization, lymph node or internal organ involvement. After 2 years of activity, the disease regressed. During the 10-year follow-up period, no signs of disease reactivation were noted. Accurate recognition of this lymphoma is important to avoid unnecessary aggressive treatments.

Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides.

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.

[Rare forms of panniculitis: subcutaneous sarcoidosis and panniculitis associated with dermatomyositis]. / Retke forme panikulitisa: supkutana sarkoidoza i panikulitis u sklopu dermatomiozitisa.

Panniculitides represent heterogenous group of disorders involving subcutaneous fat tissue, and are etiologically related to different causes, including systemic diseases. Two female patients having subcutaneous sarcoidosis and panniculitis associated with dermatomyositis are presented in this paper. The first patient, (38 years of age), was with the nodes on forearms and lower legs, which occurred one month after hypophysectomy for adrenocorticoscopic (ACTH)-secreting pituitary adenoma, and showed histopathologically confirmed epithelioid, noncaseating granulomas in the subcutaneous fat tissue. Laboratory and radiographic findings were normal, with the exception of positive rheumatoid factor and incompletely developed cysts in proximal phalanges of the hand. The second patient (56 years of age), was with subcutaneous nodes on the upper arm and the lateral chest wall, which were noticed several months after the diagnosis of dermatomyositis. Histopathological examination showed lobular pannicilitis with hyaline fibrosis and plasmocytic-lymphocytic infiltrate.

Intracardiac thrombosis and fever possibly triggered by ovulation induction in a patient with antiphospholipid antibodies.

We report on a 28-year old patient with polycystic ovary syndrome (PCOS) who presented with fever and laboratory markers of inflammation. Her medical history was relevant for multiple ovulation inductions (OI) and ovarian hyperstimulation syndrome (OHSS). She had two miscarriages and one preterm delivery. Intracardiac thrombosis was diagnosed in the presence of antiphospholipid antibodies. We suggest that primary antiphospholipid syndrome (APS) was possibly triggered by OI.