Experimental autoimmune encephalomyelitis can be prevented and cured by infection with Trypanosoma cruzi

Trypanosoma cruzi is an intracellular parasite that induces a strong Th1-type response and immunosuppression during the acute phase of infection. To study how the infection with T. cruzi would modulate the development of an autoimmune disease, we immunized C57BL/6 mice and IL-10 or iNOS knock-out mice of the same background with the encephalitogenic MOG 35-55 peptide and infected them with T. cruzi. Our results demonstrate that infection with T. cruzi completely prevents EAE development and furthermore induces complete and lasting remission in mice that were infected with this parasite after they had developed clinical EAE. Nitric oxide and IL-10 participate in triggering the mechanisms associated with EAE suppression by the infection. Decreased lymphoproliferation and increased frequencies of Annexin-positive cells and of T cells bearing CD95, CD95L or CTLA-4 were observed in the spleen from immunized/infected mice, as well as lower IL-2 and increased TGF-beta production in comparison with only immunized mice. Our results indicate that several effector and regulatory mechanisms of the immune response that arise during the acute phase of T. cruzi infection lastingly affect the expansion and/or effector functions of encephalitogenic cells, preventing the onset or inducing complete remission of EAE.     

Urinary arginine methylation index associated with ambulatory blood pressure abnormalities in children with chronic kidney disease

Arginine (ARG) metabolites are interrelated and are involved in chronic kidney disease (CKD) and cardiovascular disease. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) appears to correlate with cardiovascular outcomes. We investigated the relationship between ARG metabolites, and their combined ratios in urine, and the ABPM profiles of children and adolescents with CKD. This cross-sectional study included 45 children and adolescents (age, 5–18 years) with stage 1 to 4 CKD. Each child underwent office blood pressure (BP) measurements, 24-hour ABPM, and urinary ARG metabolite determinations. Seventy percent of children with CKD had abnormal 24-hour ABPM profiles, including nocturnal hypertension, increased BP load, and nondipping nocturnal BP. The urinary ARG-to-asymmetric dimethylarginine (ADMA) ratio was lower, and the ADMA-to-symmetric dimethylarginine (SDMA) ratio was higher in children with advanced CKD (stages 2–4) than those with stage 1 CKD. CKD patients with BP abnormalities also had reduced urinary ARG and dimethylamine (DMA) levels. The higher urinary (ADMA+SDMA)-to-ARG ratios were correlated to ABPM abnormalities, including increased systolic BP load and non-dipping nocturnal BP. ABPM abnormalities were significantly associated with a high urinary (ADMA+SDMA)-to-ARG ratio, suggesting the possible involvement of methylated ARG in the development of hypertension among children with CKD.     

Comparative Efficiency and Impact on the Activity of Blood Neutrophils Isolated by Percoll,Ficoll and Spontaneous Sedimentation Methods

Studies on the role of cells in physiological and pathological processes generally require isolation of some populations, such as neutrophils. In the literature, several methods used for isolating neutrophils are described; however, there is no consensus on the best technique to be used in cell functional studies. The present study compares the efficiency and impact on the chemotactic and phagocytic activity of neutrophils isolated from blood by three different methods: Percoll and Ficoll density centrifugation gradients and spontaneous sedimentation technique. The neutrophil chemotaxis, stimulated with lipopolysaccharide (LPS), autologous serum or homologous serum, was determined by using Boyden chambers. The phagocytic capacity was assessed by ingestion of zimosan particles, and digestion phase was analyzed by nitroblue tetrazolium test (NBT). The results obtained from neutrophil isolation by Percoll and Ficoll density gradients, as compared to spontaneous sedimentation technique, showed similar degrees of cell yields and higher purity; however, these methods affected neutrophil responsiveness, accompanied by elevated chemotaxis and reduced chemotactic capacity to respond to subsequent stimulation. Neutrophil isolation by spontaneous sedimentation, in contrast, did not affect cellular activity and resulted in cell preparation with high number of neutrophils. Although neutrophil phagocytosis results were similar between the different methods, digestion phase of phagocytosis was significantly enhanced after LPS-stimulation, only in the neutrophils isolated by spontaneous sedimentation technique. In conclusion, the present study shows that isolation of blood neutrophils by the spontaneous sedimentation technique is appropriate for the assessment of cellular activity, since it neither primes or activates the neutrophils nor does it affect their functional responsiveness.     

Improved Differentiation of Low-Grade and High-Grade Gliomas and Detection of Tumor Proliferation Using APT Contrast Fitted from Z-Spectrum

Purpose

The purpose of the study is to demonstrate the value of quantitative amide proton transfer (APT) imaging for differentiating glioma grades and detecting tumor proliferation.

Procedures

This study included 32 subjects with 16 low-grade gliomas (LGG) and 16 high-grade gliomas (HGG) confirmed by histopathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging with APT weighting was performed on a 3 T scanner. After B₀ correction, Z-spectra were fitted with Lorentzian functions corresponding to the upfield semi-solid magnetization transfer and nuclear overhauser enhancement (MT&NOE) effect, the direct saturation (DS) effect, and the downfield APT effect centered at around ??1.5, 0, and +?3.5 ppm, respectively. To compute the Z-spectral fitted APT (fitted_APT) in solid tumor tissue, double-peak histogram fitting of pixel MT&NOE effect from the whole tumor was used to remove necrosis regions. The fitted APT was then compared with the conventional APT based on magnetization transfer ratio asymmetry. Receiver operating characteristic (ROC) analysis was used to compare the performance between Z-spectral fitted contrasts and the con_APT for LGG versus HGG differentiation. Additionally, the correlations between the imaging contrasts (fitted_APT, con_APT, and fitted_MT&NOE) and Ki-67 labeling index for tumor proliferation were also evaluated.

Results

Z-spectral fitted_APT shows improved statistical power for differentiating HGG and LGG (7.58?±?0.99 vs. 6.79?±?1.05 %, p?<?0.05) than con_APT (4.34?±?0.95 vs. 4.05?±?2.02 %, p?>?0.05) in solid tumor tissues. Analyses of whole tumor, on the other hand, have less differentiating power for both fitted_APT (p from 0.032 to 0.08) and con_APT (p from 0.696 to 0.809). Similarly, based on ROC analyses, fitted_APT shows larger area under the curve (AUC?=?0.723) than con_APT (AUC?=?0.543). The combination of fitted APT, DS, and MT&NOE further improved the specificity (75 %), diagnostic accuracy (78.2 %), and area under the curve (0.758) in differentiating LGG and HGG. Consistently, fitted_APT (r?=?0.451, p?=?0.018) is better correlated with Ki-67 than con_APT (r?=?0.331, p?=?0.092).

Conclusions

Fitted APT from Z-spectrum improves differentiation of low- and high-grade gliomas and better correlated with tumor proliferation than conventional APT.

     

The Natural Progression of Parkinson's Disease in a Small Cohort with 15 Drug-na?ve Patients

Background:

The studies of the natural progression of Parkinson''s disease (PD) in Chinese populations have been lacking. To address this issue and obtain a preliminary data, we conducted a PD progression assessment in 15 adults with de novo PD from a nutritional intervention trial (NIT) cohort in Lin County China.

Methods:

Using the Copiah County screening questionnaire and United Kingdom Parkinson''s Disease Society Brain Bank diagnostic criteria, we surveyed the available NIT cohort members in 2000 and diagnosed 86 patients as PD. In 2010, we resurveyed all PD patients and confirmed definite PD diagnosis in 15 cases with the rest of them being dead (54); having probable (10) PD or vascular Parkinsonism (3); refusing to participate (2); or being away (2). In both surveys, we used Hoehn and Yahr (HY) scale and assessed the disease progression. Unified Parkinson''s Disease Rating Scale (UPDRS) was added to the second survey.

Results:

In 2010, the average disease duration for 15 definite PD patients was 13.6 ± 7.3 years. Over a 10-year time span, 9 out of 15 patients remained at the same HY stage while the remaining 6 progressed. Rigidity (47% vs. 100%; P = 0.002) and postural instability (7% vs. 47%; P = 0.005) worsened significantly. The mean UPDRS motor scores in 2010 were 39.4 ± 23.7.

Conclusions:

Overall worsening of motor function in PD seems to be the rule in this untreated cohort, and their rate of progression seemed to be slower than those reported in the western populations.     

Multi‐lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells ‐ pathological implication

Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper‐vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS‐SCs), and by comparing to the MSCs from normal synovium (Syn‐SCs) of the same individual, we investigated whether PVNS‐SCs differed in the capacity for multi‐differentiation and inducing angiogenesis. We first demonstrated that PVNS‐SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS‐SCs had better osteogenic differentiation potential than Syn‐SCs, whereas Syn‐SCs had better capacity for adipogenic and chondrogenic differentiation. By genome–wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn‐SCs, we identified in PVNS‐SCs a distinct gene expression profile characterized by up‐regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS‐SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS‐SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:395–403, 2016.