Resorufin Enters the Photodynamic Therapy Arena: A Monoamine Oxidase Activatable Agent for Selective Cytotoxicity

A red-absorbing, water-soluble, and iodinated resorufin derivative (R1) that can be selectively activated with a monoamine oxidase (MAO) enzyme was synthesized, and its potential as a photodynamic therapy (PDT) agent was evaluated. R1 showed high ¹O₂ generation yields in aqueous solutions upon addition of MAO isoforms, and it was further tested in cell culture studies. R1 induced photocytotoxicity after being triggered by endogenous MAO enzyme in cancer cells with a much higher efficiency in SH-SY5Y neuroblastoma cells with high MAO-A expression. Additionally, R1 displayed differential cytotoxicity between cancer and normal cells, without any considerable dark toxicity. To the best of our knowledge, R1 marks the first example of a resorufin-based photosensitizer (PS) as well as the first anticancer drug that is activated by a MAO enzyme. Remarkably, the target PDT agent was obtained only in three steps as a result of versatile resorufin chemistry.     

Spindle cell melanoma coexisting with chronic lymphocytic leukemia/small lymphocytic lymphoma: a rare collision tumor in multiple sites

A strong association has been reported between chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) and malignant melanoma (MM). In rare cases of MM, lymphoid malignancies may be detected incidentally during sentinel lymph node biopsies. In this case, we found a unique collision of MM and CLL infiltration in the skin. An 88-year-old male patient presented with a mass on the nasal root. Histopathological examination of the skin biopsy specimen revealed a deeply infiltrative, atypical spindle cell proliferation in the background of a collagenous stroma. Accompanying this lesion, there were foci of monotonous lymphoid cell populations involving skin appendages. In the immunohistochemical studies, the spindle cells were diffusely positive for S100, and focally positive for Melan-A and HMB45; the lymphoid cells were positive for CD20, CD5, and Bcl-2 and negative for CD3, Bcl-6, CD10, and Cyclin D1. Histopathological and immunohistochemical findings were consistent with diagnoses of spindle cell melanoma and CLL. Interestingly, these two tumors together in their same morphological appearance were confirmed in a subsequent liver biopsy. Active skin surveillance of patients with CLL may be important to detect MM at an early stage that correlates with a better prognosis.     

The effect of mineral trioxide aggregate on the contractility of the rat thoracic aorta

Mineral trioxide aggregate (MTA) is being advocated for vital pulp therapy. In the case of direct pulp capping, hemorrhage control is an important step on success, but little is known about the effect of MTA on pulpal bleeding. In addition, there has been a lack of information on the effect of MTA on smooth muscle contraction, such as can occur in the blood vessels of dental pulp. The present study assessed the vascular effects of MTA, using the rat aortic ring preparations as a tissue model. MTA (100-500 mg) induced dose-dependent contraction in rat thoracic aorta. The contractile effect of MTA was blocked by calcium channel blocker nifedipine (1 muM). These data suggest that the vasoconstrictor property of MTA is related to calcium influx and it may allow proper control of hemorrhage which is critical for the success of any pulp-capping treatment.     

Effects of mesiodistal inclination of implants on stress distribution in implant-supported fixed prostheses

PURPOSE: Patterns of von Mises stress values surrounding implants supporting fixed prostheses in the posterior edentulous maxilla were evaluated using 3-dimensional finite element analysis. MATERIALS AND METHODS: Implants were placed in maxillary bone in 2 different configurations. In the first configuration, implants were placed in the first premolar, second premolar, and second molar regions; in the second configuration, implants were placed in the second premolar and second molar regions, and a mesial cantilever was extended to the space of the first premolar tooth on the superstructure. On the implant placed in the socket of the second molar, 3 different inclinations were used (0, 15, and 30 degrees). Loading was applied in the vertical, oblique, and horizontal axes. RESULTS: Inclination of the implant in the molar region was found to result in increased stress. Significant increase in stress on the implant embedded in the premolar region was also seen in the design with the cantilever as compared to the conventional prosthesis design. Discussion: The stress concentrations observed at the neck of the implant were similar to results reported in the literature. CONCLUSION: The highest stress value obtained in the study was 194.2 MPa with oblique loading. This value did not exceed the endurance limit of pure titanium, which is 259.9 MPa.     

The effect of two fibre impregnation methods on the cytotoxicity of a glass and carbon fibre-reinforced acrylic resin denture base material on oral epithelial cells and fibroblasts

Acrylic resin dentures may have cytotoxic effects on oral soft tissues. However, there is sparse data about the cytotoxic effect of fibre-reinforced acrylic resin denture base materials. The purpose of this in vitro study was to determine the effect of two fibre impregnation methods on the cytotoxicity of a glass and carbon fibre-reinforced heat-polymerized acrylic resin denture base material on oral epithelial cells and fibroblasts. One hundred acrylic resin discs were assigned to five experimental groups (n = 20). One of the groups did not include any fibre. Two groups consisted of silane and monomer treated glass fibres (Vetrolex) impregnated into acrylic resin (QC-20) discs. The other two groups consisted of silane and monomer treated carbon fibres (Type Tenox J, HTA). Untreated cell culture was used as positive control. The human oral epithelial cell line and buccal fibroblast cultures were exposed to test specimens. The cytotoxicity of the test materials was determined by succinic dehydrogenase activity (MTT method) after 24 and 72 h exposures. Data were analysed with a statistical software program (SPSSFW, 9.0). A one-way analysis of variance (anova) test and Bonferroni test were used for the comparisons between the groups. All statistical tests were performed at the 0.95 confidence level (P < 0.05). After 24 and 72 h incubation, cell viability percentages of all experimental groups showed significant decrease according to the positive control cell culture. Fibroblastic cell viability percentages of silane and monomer treated fibre-reinforced groups were lower than the unreinforced group. Cell viability of monomer-treated groups displayed the lowest percentages. Elapsed incubation time decreased epithelial cell viability in silane-treated groups. Fibroblastic cell viability was not influenced by elapsed time except the unreinforced group.     

Combined use of platelet-rich plasma and bone grafting with or without guided tissue regeneration in the treatment of anterior interproximal defects

BACKGROUND: The aim of periodontal therapy is to prevent tissue destruction while achieving the regeneration of damaged tissues. Platelet-rich plasma (PRP) is used to generate new bone, periodontal ligament, and new attachment with a strategy based on the modulation and enhancement of wound healing through an autologous source for growth factors obtained from the patient's own blood. The purpose of the present study was to evaluate the efficacy of PRP when used in combination with beta-tricalcium phosphate (beta-TCP) alloplastic graft material and collagen barrier membrane in the treatment of anterior interproximal intrabony defects. METHODS: Thirty interproximal intrabony defects in 25 systemically healthy patients were selected for the study. Defects were distributed randomly and equally into three groups: graft alone (beta-TCP), graft + PRP, and graft + PRP + membrane. The plaque index, gingival index, periodontal probing depth, relative attachment level, transgingival probing measurement, and radiographic analyses were performed at baseline and repeated after 6, 9, and 12 months. RESULTS: At the end of 12 months, relative attachment gain was 2.4, 2.1, and 2.5 mm in the three treatment groups, respectively. No statistically significant differences in clinical and radiographic measurements were observed among the groups. CONCLUSIONS: All options were effective in the treatment of anterior interproximal intrabony defects. The results also suggested that PRP added no clinical benefit to beta-TCP alloplastic graft material used alone or in combination with GTR.     

Primary antibody deficiencies in Turkey: molecular and clinical aspects

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n?=?4), CD40L (n?=?1), ICOS (n?=?1), IGHM (n?=?1), and TCF3 (n?=?1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2–10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.

     

Correction to: Primary antibody deficiencies in Turkey: molecular and clinical aspects

Immunologic Research -     

Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency

Journal of Clinical Immunology - NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are...