Complication rates after DBS surgery remain low, proving that DBS is not only effective but also safe. Certain strategies do exist in order to minimize complications.
A significant increase in the induction of inducible nitric-oxide synthase (iNOS) protein expression and in the levels of nitrite plus nitrate was observed in rat aortic smooth muscle cells (RASMCs) stably transfected with catalase (RASMC-2C2) as compared with empty vector-transfected RASMC-V4 cells after exposure to cytokines and lipopolysaccharide. The increased expression of iNOS protein in the RASMC-2C2 cells was associated with a significant activation of nuclear transcription factor B, one of the transcriptional regulators of iNOS expression. The induction of iNOS was also accompanied by increased protein tyrosine nitration in both cell types as revealed by immunocytochemical staining and high pressure liquid chromatography with on-line electrospray ionization tandem mass spectrometry. Nitrotyrosine formation was inhibited by 1400W, an iNOS inhibitor, by 4-(2-aminoethyl) benzenesulfonyl fluoride, an inhibitor of NADPH oxidase, and by the superoxide dismutase mimetic M40403, but not by the peroxidase inhibitor 4-aminobenzoic hydrazide. Electron microscopy using affinity-purified anti-nitrotyrosine antibodies revealed labeling at the cytosolic side of the rough endoplasmic reticulum membranes, in the nucleus, occasionally in mitochondria, and consistently within the fibrillar layer underneath the plasma membrane. Collectively, the data in this model system indicate that hydrogen peroxide, by inhibiting the activation of nuclear transcription factor B, prevents iNOS expression, whereas superoxide contributes in a precise pattern of intracellular protein tyrosine nitration.
Glioblastoma, (grade IV astrocytoma), is characterized by rapid growth and resistance to treatment. Identification of markers of aggressiveness in this tumor could represent new therapeutic targets. Interleukins (IL)-6 and IL-10 may be considered as possible candidates, regulating cell growth, resistance to chemotherapy and angiogenesis. ELISPOT method provides a useful tool for the determination of the exact cell number of peripheral lymphocytes secreting a specific cytokine. IL-6 and IL-10 secretion levels were determined using ELISPOT methodology in peripheral blood mononuclear cells of 18 patients with astrocytic neoplasms (3 grade II and 15 grade IV), in parallel with 18 healthy controls. Additionally, immunohistochemical expression of these two cytokines was performed in paraffin-embedded neoplastic tissue in 12 of these patients. The secretion of IL-6 from peripheral monocytes was significantly higher in glioma patients compared to controls (P = 0.0003). In addition, IL-10 secretion from peripheral mononuclear and tumor cells of glioma patients was also higher as compared to healthy controls (P = 0.0002). Based on immunohistochemical staining, IL-6 expression was localized in tumor cells and macrophages as well as in areas of large ischemic necrosis, while the major source of IL-10 expression in glioblastomas was the microglia/macrophage cells. It is suggested that IL-10 contributes to the progression of astrocytomas by suppressing the patient's immune response, whereas IL-6 provides an additional growth advantage. This study demonstrates for the first time the usefulness of ELISPOT in estimating the secretion of IL-6 and IL-10 from peripheral blood and the correlation of their expression in neoplastic cells.
AimTo evaluate the clinical efficacy and safety of an intra-articular injection of bone marrow aspirate concentrate (BMAC) as a treatment option for osteoarthritis (OA) of the knee.Materials and methodsBetween June 2014 and February 2017, data from 233 patients with knee osteoarthritis treated with BMAC injection at a single center, were retrospectively evaluated. Only patients with idiopathic osteoarthritis were included. Exclusion criteria were post-traumatic osteoarthritis, previous knee surgery, age less than 50 years old or more than 85 years old, active infection, uncontrolled diabetes mellitus, rheumatological or other systemic disease, malignancy, or treatment with immunosuppressive drugs. Bone marrow from the iliac crest was aspirated/concentrated with a standardized technique using a single-spin manual method. Patients were evaluated before and after the procedure, using the numeric pain scale (NPS) and Oxford knee score (OKS). Mean follow-up period was 11 months, range (6–30 months).ResultsA total of 121 of 233 patients had completed data as previously defined and were included in the statistical analysis. There were 85 females and 36 males, with mean age 70 years (range 50–85). Compared to baseline, the mean NPS decreased from 8.33 to 4.49 (p < 0.001) and the mean OKS increased from 20.20 to 32.29 (P < 0.001) at final follow-up. There were no complications.ConclusionA single intra-articular injection of BMAC is a safe and reliable procedure that results in clinical improvement of knee OA.
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