TRACP Influences Th1 pathways by affecting dendritic cell function.

TRACP, a marker of osteoclasts, is also expressed by cells of the immune system. We identified a novel function for TRACP in the dendritic cell. DCs from TRACP knockout mice have impaired maturation and trigger reduced Th1 responses in vivo. We postulate that TRACP has an important role in the presentation of antigens to T cells. INTRODUCTION: TRACP is highly expressed by osteoclasts, activated macrophages, and dendritic cells (DCs). Knockout mice lacking TRACP have an intrinsic defect in osteoclastic resorption and macrophages that display abnormal immunomodulatory responses and cytokine secretion profiles. Our aim in this study was to investigate the significance of TRACP in the inductive phase of the immune response by examining dendritic cells from TRACP(-/-) mice. MATERIALS AND METHODS: Maturational state and function of leukocyte subsets in mice was assessed by flow cytometry. The ability of the immune system to respond to nonspecific activation and to specific antigen was assessed by delayed type hypersensitivity and the presence of isotype-specific serum antibody in vivo and T-cell proliferation and cytokine production in vitro. RESULTS: The ability of lipopolysaccharide (LPS) to upregulate MHC II and CD80 in DCs from TRACP(-/-) mice was reduced compared with wildtype mice, although production of IL-10 by DCs from TRACP-deficient animals was increased. T- and B-cell responses not involving antigen presentation (anti-CD3, TNP-ficoll) were normal in TRACP(-/-) mice, but responses to T-dependent antigens were impaired. Specifically, TRACP(-/-) mice had defective delayed hypersensitivity responses to picryl chloride and reduced proliferative responses to ovalbumin compared with wildtype mice. In response to ovalbumin, but not anti-CD3, T cells from TRACP(-/-) mice produced less interferon-gamma (IFN-gamma), but there was no difference in IL-4 production: TRACP(-/-) mice also produced less ovalbumin (OVA)-specific IgG2a after immunization. CONCLUSIONS: The finding that DCs from TRACP(-/-) mice have impaired maturation and defective Th1 responses shows that TRACP is important for polarizing responses in na?ve T cells to antigen-presented dendritic cells.     

The effects of fenugreek seed extract supplementation in patients with Alzheimer's disease: A randomized,double-blind,placebo-controlled trial

The aim of the current randomized control trial (RCT) study was to investigate the effects of fenugreek seed extract on memory, depression, quality of life, blood pressure, and serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels in adult AD patients. This randomized clinical trial was conducted in geriatric homes in Iran. The study participants included 82 AD patients with mild-to-moderate memory deficit. Patients in the intervention group received 5 cc of fenugreek seed extract for 4 months and subjects in the control group received a placebo. Memory, depression, quality of life, and BP levels, as well as serum MDA and TAC, were assessed before and after the intervention. There was a significant increase in serum levels of TAC (p < 0.001) and a reduction in serum MDA status (p < 0.001) after 4 months of fenugreek seed extract supplementation. In addition, increasing levels of memory (p < 0.001) and quality of life (p < 0.001), as well as reduction of depression (p = 0.002), systolic BP (p < 0.001), and diastolic BP (p < 0.001) levels were detected in the intervention group compared with baseline. Fenugreek seed extract supplementation in AD patients shows promising positive effects on memory, quality of life, BP, and selective oxidative indices levels.     

Novel Evolutionary Models and Periodic Charts in p- and q-Individual Chromosomes of Auxiliary Lymph Node and Buccal Cells

Signal copy number (SCN) and signal intensity (SI) of subtelomeres (ST) are investigated in auxiliary lymph node (ALN) and buccal (BUC) cells by fluorescence in situ hybridization. The extracted total cell of 38256 and 2309 was, respectively, analyzed from the benign ALN- and BUC-cells of an affected breast cancer patient. The Periodic model was based on ST behavior including normal-, down-, and upregulated clones with diverse SCN. The arm-p/q ratio based signature, as a subtelomeric array, reflects discordance and concordance of ST-behavior within individual chromosomes as a concept of “Individualization of Cells” rather than “Global Insight of Cells”. The Periodic charts could be considered as a reliable and refreshable platform through which the cellular evolution could be patterned and characterized. Signature of ST-profile in the BUC and ALN cells and the nature of diverse SCN and SI as quantitative and qualitative value led to modeling the real personalized perspective of cellular evolution. Protein expression of Ki67, Cyclin D1, and Cyclin E was assayed, as a complementary panel. These targets could be applied as the predictive and preventive markers for an early detection at BUC and ALN levels to plan the required managements in the breast cancer patients.     

Effect of different frequencies of repetitive transcranial magnetic stimulation on acquisition of chemical kindled seizures in rats

In the current study we investigated the effect of repetitive transcranial magnetic stimulation (rTMS) at different frequencies on chemical kindling in rats. Chemical kindling was induced by injection of pentylenetetrazol (PTZ; 45 mg/kg) at the intervals of 48 h between the injections. In the first experiment, effect of 0.25, 1 and 5 Hz rTMS (four trains of 4 s at motor threshold intensity) on kindling acquisition was investigated. In the second experiment, the stability of rTMS effects was checked in animals of the first experiment during a follow-up period of 2 weeks. Animals received a single dose of PTZ at 7th and 14th day after the last PTZ injection (12th injection) and their seizure parameters were recorded. Obtained results showed that application of rTMS at the frequencies of 0.25 and 1 Hz had anticonvulsant effect and decreased the PTZ kindling acquisition. However, when applied at the frequency of 5 Hz, it had an increasing effect on PTZ kindling rate. During the follow-up study, the seizure severity increased in animals treated with 0.25 Hz rTMS (and somehow in animals treated with 1 Hz rTMS), but did not change in animals treated with 5 Hz rTMS compared to the 12th PTZ injection. Our results showed that rTMS application may have an anticonvulsant effect during chemical kindling acquisition at very low frequency (0.25 Hz) and can increase the seizure severity at high frequency (5 Hz). However, during follow-up, the anticonvulsant effects of rTMS may be converted to proconvulsive effects.     

In-vitro and in-vivo cytotoxicity and efficacy evaluation of novel glycyl-glycine and alanyl-alanine conjugates of chitosan and trimethyl chitosan nano-particles as carriers for oral insulin delivery

Purpose

The aim of this research work was to explore the possibility of providing multifunctional oral insulin delivery system by conjugating several types of dipeptides on chitosan and trimethyl chitosan to be used as drug carriers.

The incidence of humeral bone resorption in uncemented reverse shoulder arthroplasty and the impact on functional outcomes

BackgroundFull-thickness bone resorption around the humeral stem in shoulder arthroplasty is an increasingly recognized phenomenon, but the impact on outcomes remains unclear. This study aims to investigate prevalence of bone resorption in patients with the Zimmer-Biomet Comprehensive reverse shoulder arthroplasty and the impact on the functional outcomes.MethodsA retrospective analysis was carried out on 65 consecutive patients with primary reverse total shoulder arthroplasty using the Comprehensive Shoulder System from 2014 to 2020, with a minimum of 12-month follow-up. The prevalence of humeral bone resorption was graded from 0 to 4, and risk factors for these changes and their impact on functional outcomes were further investigated.ResultsThe majority of patients (75%) were female with an average age of 75 years (53-93), with an overall average follow-up of 26 months (12-60). Bone resorption occurred in 53 patients (82%), and full-thickness bone resorption occurred in only 8 patients (12%). Metaphyseal bone (zones 1 and 7) is mostly at the risk of high-grade resorption. There was no difference in the final Oxford Shoulder Score between patients who had differential resorption grades from 0 to 4 (P = .5742). None of the risk factors from the previous literature including age, sex, indication for surgery, rotator cuff tear and repair, and intramedullary occupation ratio of the implant showed any impact on the rate of resorption.ConclusionFull-thickness humeral bone resorption occurred in approximately 12% of patients when using the Comprehensive reverse shoulder arthroplasty, but it has no impact on the functional outcomes or revision rate in the short-to-medium term.     

The effect of systemic erythropoietin and oral prednisolone on recent-onset non-arteritic anterior ischemic optic neuropathy: a randomized clinical trial

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent-onset non-arteritic...