Influence of 1 Alpha, 25-Dihydroxyvitamin D3 on T helper 17 cells and related cytokines in systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor. Objective: To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients. Method: Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF-β genes were assessed by real-time PCR. Results: The percentage of Th17 cells (CD3+CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%) (p=0.003). The expression of TGF-β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment. Conclusion: This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity. © 2015, Shiraz University of Medical Sciences. All rights reserved

Atorvastatin treatment softens human red blood cells: An optical tweezers study

Optical tweezers are proven indispensable single-cell micro-manipulation and mechanical phenotyping tools. In this study, we have used optical tweezers for measuring the viscoelastic properties of human red blood cells (RBCs). Comparison of the viscoelastic features of the healthy fresh and atorvastatin treated cells revealed that the drug softens the cells. Using a simple modeling approach, we proposed a molecular model that explains the drug-induced softening of the RBC membrane. Our results suggest that direct interactions between the drug and cytoskeletal components underlie the drug-induced softening of the cells. © 2018 Optical Society of America

Impacto de la estabilidad en el rendimiento de los clubes de fútbol de la Copa del Golfo Pérsico

The objective of this study was to determine the impact of stability/instability on the performance of Persian Gulf Pro League football clubs. All the clubs that had participated in more than 3 seasons of the last 17 seasons (2001-2019) of the Persian Gulf Pro League were analyzed in this study (n=26). The performance of each team (improvement or worsening in ranking) and their stability were analyzed year after year in the period 2001-2019. The stability was divided in four components: CEO, head coach, players and club. The statistical analysis was performed with the software SPSS. Stability significantly (p<0.05) increased performance and instability significantly (p<0.05) decreased performance of the clubs in the four components studied: CEO, head coach, players and club. Therefore, it is expected that the results of this study encourage Iranian football clubs to increase their stability.El objetivo de este estudio fue determinar el impacto de la estabilidad/inestabilidad en el rendimiento de los clubes de fútbol de la Copa del Golfo Pérsico. Todos los clubes que habían participado en más de 3 temporadas de las últimas 17 temporadas (2001-2019) de la Copa del Golfo Pérsico fueron analizados en este estudio (n=26). El rendimiento de cada equipo (mejora o empeoramiento en el ranking) y su estabilidad se analizaron año tras año en el período 2001-2019. La estabilidad se dividió en cuatro componentes: director, entrenador, jugadores y club. El análisis estadístico se realizó con el software SPSS. La estabilidad aumentó significativamente (p<0.05) el rendimiento y la inestabilidad disminuyó significativamente (p<0.05) el rendimiento de los clubes en los cuatro componentes estudiados: director, entrenador, jugadores y club. Por lo tanto, se espera que los resultados de este estudio animen a los clubes de fútbol iraníes a aumentar su estabilidad

Atorvastatin treatment softens human red blood cells: An optical tweezers study

Optical tweezers are proven indispensable single-cell micro-manipulation and mechanical phenotyping tools. In this study, we have used optical tweezers for measuring the viscoelastic properties of human red blood cells (RBCs). Comparison of the viscoelastic features of the healthy fresh and atorvastatin treated cells revealed that the drug softens the cells. Using a simple modeling approach, we proposed a molecular model that explains the drug-induced softening of the RBC membrane. Our results suggest that direct interactions between the drug and cytoskeletal components underlie the drug-induced softening of the cells. © 2018 Optical Society of America

The Role of Calcineurin/NFAT in SFRP2 Induced Angiogenesis—A Rationale for Breast Cancer Treatment with the Calcineurin Inhibitor Tacrolimus

Tacrolimus (FK506) is an immunosuppressive drug that binds to the immunophilin FKBPB12. The FK506-FKBP12 complex associates with calcineurin and inhibits its phosphatase activity, resulting in inhibition of nuclear translocation of nuclear factor of activated T-cells (NFAT). There is increasing data supporting a critical role of NFAT in mediating angiogenic responses stimulated by both vascular endothelial growth factor (VEGF) and a novel angiogenesis factor, secreted frizzled-related protein 2 (SFRP2). Since both VEGF and SFRP2 are expressed in breast carcinomas, we hypothesized that tacrolimus would inhibit breast carcinoma growth. Using IHC (IHC) with antibodies to FKBP12 on breast carcinomas we found that FKBP12 localizes to breast tumor vasculature. Treatment of MMTV-neu transgenic mice with tacrolimus (3 mg/kg i.p. daily) (n = 19) resulted in a 73% reduction in the growth rate for tacrolimus treated mice compared to control (n = 15), p = 0.003; which was associated with an 82% reduction in tumor microvascular density (p<0.001) by IHC. Tacrolimus (1 µM) inhibited SFRP2 induced endothelial tube formation by 71% (p = 0.005) and inhibited VEGF induced endothelial tube formation by 67% (p = 0.004). To show that NFATc3 is required for SFRP2 stimulated angiogenesis, NFATc3 was silenced with shRNA in endothelial cells. Sham transfected cells responded to SFRP2 stimulation in a tube formation assay with an increase in the number of branch points (p<0.003), however, cells transfected with shRNA to NFATc3 showed no increase in tube formation in response to SFRP2. This demonstrates that NFATc3 is required for SFRP2 induced tube formation, and tacrolimus inhibits angiogenesis in vitro and breast carcinoma growth in vivo. This provides a rationale for examining the therapeutic potential of tacrolimus at inhibiting breast carcinoma growth in humans

Assessment of nerve involvement in the lumbar spine: agreement between magnetic resonance imaging, physical examination and pain drawing findings

<p>Abstract</p> <p>Background</p> <p>Detection of nerve involvement originating in the spine is a primary concern in the assessment of spine symptoms. Magnetic resonance imaging (MRI) has become the diagnostic method of choice for this detection. However, the agreement between MRI and other diagnostic methods for detecting nerve involvement has not been fully evaluated. The aim of this diagnostic study was to evaluate the agreement between nerve involvement visible in MRI and findings of nerve involvement detected in a structured physical examination and a simplified pain drawing.</p> <p>Methods</p> <p>Sixty-one consecutive patients referred for MRI of the lumbar spine were - without knowledge of MRI findings - assessed for nerve involvement with a simplified pain drawing and a structured physical examination. Agreement between findings was calculated as overall agreement, the p value for McNemar's exact test, specificity, sensitivity, and positive and negative predictive values.</p> <p>Results</p> <p>MRI-visible nerve involvement was significantly less common than, and showed weak agreement with, physical examination and pain drawing findings of nerve involvement in corresponding body segments. In spine segment L4-5, where most findings of nerve involvement were detected, the mean sensitivity of MRI-visible nerve involvement to a positive neurological test in the physical examination ranged from 16-37%. The mean specificity of MRI-visible nerve involvement in the same segment ranged from 61-77%. Positive and negative predictive values of MRI-visible nerve involvement in segment L4-5 ranged from 22-78% and 28-56% respectively.</p> <p>Conclusion</p> <p>In patients with long-standing nerve root symptoms referred for lumbar MRI, MRI-visible nerve involvement significantly underestimates the presence of nerve involvement detected by a physical examination and a pain drawing. A structured physical examination and a simplified pain drawing may reveal that many patients with "MRI-invisible" lumbar symptoms need treatment aimed at nerve involvement. Factors other than present MRI-visible nerve involvement may be responsible for findings of nerve involvement in the physical examination and the pain drawing.</p

Assessment of correlation between spinal canal shape and spinal cord injury in thoracolumbar spine fractures

Traumatic spinal cord injury is one of the important causes of disability. In some of vertebral fractures, spinal canal is deformed and compromised. The relationship between the shape of the cervical canal and spinal cord injury has been proved but such a correlation for thoracolumbar spine has not been documented yet. Thus, 100 consecutive patients with traumatic fracture of thoracolumbar spine [50 patients with compromised canal (cases) and 50 patients with intact canal] were evaluated in the light of spinal canal shape (Using CT scan), neurological defects (Using Frankle classification), mechanism of trauma and level of the spinal fracture. Of the 100 patients studied, 23 had spinal cord injury and most of injuries were at T12-L2. The most common mechanisms of trauma were road traffic accident and fall. The difference in age, sex and mechanism of trauma between the two groups was not statistically significant. No significant difference was found between canal intact group and canal compromised group in neurological deficit (P=0.09). In traumatic spinal cord injury, it seems that dynamic spinal canal encroachment is more important than static canal compromise. Keywords: Spinal cord injury, Thoracolumbar spine, Neurological defici

Evaluation of correlation between cases of depressed fracture and associated brain lesion

This cross-sectional study was performed on 382 patients with depressed skull fracture admitted to the neurosurgery ward of Kerman Bahonar Hospital between 1994 and 1999. 329 of the patients (86.1%) had open fractures, while the fracture was of closed type in 53 cases (13.9%). Of those with open fracture, 42% were associated with dura tearing, whereas the rate was 34% in closed fractures. The most common causes of depressed fracture were accidents with motor vehicles (59.4%). In most cases (77%) Glasgow Coma Scale (GCS) on admission was 13-15. There was no associated lesion in 247 patients (64.7%), but 135 (35.3%) had one or more lesions, with contusion (34%) and epidural hematoma (23.7%) as the most common ones. In cases when the fracture was caused by motor vehicle accidents, the occurence of clinical manifestations was more than that of the other causes. Of 15 patients who died (3.9%) 14 cases (93.3%) had associated lesions. Keywords: Depressed fracture, Brain lesion, Clinical sig

Effect of tool travel and rotation speeds on weld zone defects and joint strength of aluminium steel lap joints made by friction stir welding

In this study, Al-5083 and St-12 alloy sheets were friction stir lap welded at different travel (7-23 cm min(-1)) and rotation (750-1125 rev min(-1)) speeds of the welding tool. The welded joints were characterised by various methods including shear tensile and Vickers microhardness tests, optical and scanning electron microscopies and X-ray diffraction analysis. The results showed that the weld zone defects decreased, and the joint strength also improved significantly with the reducing tool travel speed from 23 to 7 cm min(-1). The travel speed of 11 cm min(-1) was an optimum speed within the travel speeds investigated in this work. Additionally, raising the tool rotation speed enhanced the joint strength slightly. The microhardness results confirmed the formation of intermetallic phase layer with the hardness of similar to 335 HV at the swirl layered structure