Effect of Pioglitazone on Antioxidant Capacity and Oxidative Damage after Spinal Cord Injury in Rat

BACKGROUND AND OBJECTIVE: Reduction of the antioxidant capacity and oxidative damage has a crucial role in development of damage after spinal cord injury. Since pioglitazone (PPAR-gamma agonist) have a powerful antioxidant property, the present study aimed to evaluate the effect of pioglitazone on antioxidant capacity and oxidative damage in the injured areas of spinal cord in rat. METHODS: In the present experimental study eighteen male Wistar rats divided into three groups as follow (n=6); sham, control injured and pioglitazone-treated injured group. Spinal cord injury was performed according to the Ping-Weight Drop (contusion) model in rat. The animals received pioglitazone (3 mg/kg) intraperitoneally at times of 15 min after injury and then each 12 hours until a week. At the end, malondialdehyde level, activity of catalase and superoxide dismutase (SOD) enzymes and also histopathological alterations of spinal cord were assessed. FINDINGS: Induction of spinal cord injury in control injured animals significantly increased the malondialdehyde levels (56%) and decreased the activity of catalase (48%) and SOD (65%) enzymes compared to sham group (p=0.004, p=0.001 and P=0.008, respectively). Pioglitazone in treated injured group significantly decreased the malondialdehyde levels (38%) and increased the activity of catalase (34%) enzyme compared to control injured group (p=0.038 and p=0.014, respectively). Also, pioglitazone prevented the histopathological changes of injured areas in spinal cord. CONCLUSION: The findings of present study indicate that treatment with pioglitazone through potentiation of the antioxidant defense capacity of injured spinal cord decreases oxidative damage and also histopathological changes of spinal cord

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Role of image-guided fine-needle aspiration biopsy in the management of patients with splenic metastasis

BACKGROUND: Splenic metastases are very rare and are mostly diagnosed at the terminal phase of the disease or at the time of autopsy. The cytohistological diagnosis, when done, is made prevalently by splenectomy. Reports on splenic percutaneous biopsies in the diagnosis of splenic metastasis are fragmentary and very poor. The aims of this study are to analyse retrospectively the accuracy, safety and the clinical impact of ultrasound (US)-guided fine-needle aspiration biopsy (UG-FNAB) in patients with suspected splenic metastasis. METHODS: A retrospective analysis of 1800 percutaneous abdominal biopsies performed at our institute during the period from 1993 to 2003 was done and 160 patients that underwent splenic biopsy were found. Among these 160 patients, 12 cases with the final diagnosis of solitary splenic metastases were encountered and they form the basis of this report. The biopsies were performed under US guidance using a 22-gauge Chiba needle. All the patients underwent laboratory tests, CT examination of the abdomen and chest, US examination of abdomen and pelvis. RESULTS: There were 5 women and 7 men, median age 65 years (range 48–80). Eight patients had a known primary cancer at the time of the diagnosis of splenic metastasis: 3 had breast adenocarcinoma, 2 colon adenocarcinoma, 2 melanoma and 1 lung adenocarcinoma. Four patients were undiagnosed at the time of the appearance of splenic metastasis and subsequent investigations showed adenocarcinoma of the lung in 2 patients and colon adenocarcinoma in the remaining 2. There was a complete correspondence between the US and Computed Tomography (CT) in detecting focal lesions of the spleen. The splenic biopsies allowed a cytological diagnosis of splenic metastasis in all the 12 patients and changed clinical management in all cases. Reviewing the 160 patients that underwent UG-FNAB of the spleen we found no complications related to the biopsies. CONCLUSION: These results indicate that UG-FNAB is a successful technique for diagnosis of splenic metastasis allowing an adequate treatment of the affected patients

i Sexual function in breast cancer patients: a prospective study from Iran

Background: Sexual function in patients with breast cancer especially in younger patients is an important issue from clinical and psychosocial perspectives. This study aimed to assess sexual function among Iranian breast cancer patients. Methods: This was a prospective study of sexual function in breast cancer patients attending the Cancer Institute of Iran. Sexual function was assessed using the Female Sexual Function Index (FSFI) at two points in time: baseline (pre-treatment) and after completion of cancer treatment at follow-up visits (post-treatment). Pre- and posttreatment data were compared. In addition logistic regression analysis was performed to find out factors that contributing to post-treatment sexual dysfunction. Results: In all 277 breast cancer patients were approached. Of these, 231 patients (83%) were sexually active and data for 216 patients (93.5 % of sexually active patients) were available at pre-and post-treatment. Overall pre- and post-treatment sexual dysfunction was found to be 52 % and 84%, respectively indicating a significant deterioration in sexual function among breast cancer patients. The results obtained from multiple logistic regression analysis indicated that younger age [OR = 0.95, 95 % CI = 0.93-0.98; P = 0.04], receiving endocrine therapy [OR = 3.34, 95% CI = 1.37-7.91; P = 0.007] and poor sexual function at pre-treatment [OR = 12.3, 95 % CI = 3.93-39.0; P < 0.0001

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Energy Consumption, Carbon Emissions and Global Warming Potential of Wolfberry Production in Jingtai Oasis, Gansu Province, China

During the last decade, China's agro-food production has increased rapidly and been accompanied by the challenge of increasing greenhouse gas (GHG) emissions and other environmental pollutants from fertilizers, pesticides, and intensive energy use. Understanding the energy use and environmental impacts of crop production will help identify environmentally damaging hotspots of agro-production, allowing environmental impacts to be assessed and crop management strategies optimized. Conventional farming has been widely employed in wolfberry (Lycium barbarum) cultivation in China, which is an important cash tree crop not only for the rural economy but also from an ecological standpoint. Energy use and global warming potential (GWP) were investigated in a wolfberry production system in the Yellow River irrigated Jingtai region of Gansu. In total, 52 household farms were randomly selected to conduct the investigation using questionnaires. Total energy input and output were 321,800.73 and 166,888.80 MJ ha−1, respectively, in the production system. The highest share of energy inputs was found to be electricity consumption for lifting irrigation water, accounting for 68.52%, followed by chemical fertilizer application (11.37%). Energy use efficiency was 0.52 when considering both fruit and pruned wood. Nonrenewable energy use (88.52%) was far larger than the renewable energy input. The share of GWP of different inputs were 64.52% electricity, 27.72% nitrogen (N) fertilizer, 5.07% phosphate, 2.32% diesel, and 0.37% potassium, respectively. The highest share was related to electricity consumption for irrigation, followed by N fertilizer use. Total GWP in the wolfberry planting system was 26,018.64 kg CO2 eq ha−1 and the share of CO2, N2O, and CH4 were 99.47%, 0.48%, and negligible respectively with CO2 being dominant. Pathways for reducing energy use and GHG emission mitigation include: conversion to low carbon farming to establish a sustainable and cleaner production system with options of raising water use efficiency by adopting a seasonal gradient water pricing system and advanced irrigation techniques; reducing synthetic fertilizer use; and policy support: smallholder farmland transfer (concentration) for scale production, credit (small- and low-interest credit) and tax breaks

Genomic Restructuring in the Tasmanian Devil Facial Tumour: Chromosome Painting and Gene Mapping Provide Clues to Evolution of a Transmissible Tumour

Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860