The ratio adipsin/MCP-1 is strongly associated with structural changes and CRP/MCP-1 with symptoms in obese knee osteoarthritis subjects: data from the Osteoarthritis Initiative.

OBJECTIVE: There is a need to identify reliable biomarkers that can predict knee osteoarthritis (OA) progression. We investigated a panel of adipokines and some related inflammatory factors alone and their ratios for their associative value at assessing cartilage volume loss over time and symptoms in obese [High body mass index (BMI)] and non-obese (Low BMI) OA subjects. DESIGN: Human OA serum was from the Osteoarthritis Initiative Progression subcohort. Baseline levels of adiponectin (high and low molecular weight forms), adipsin, chemerin, leptin, visfatin, C-reactive protein (CRP), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were evaluated with specific assays. Cartilage volume was assessed at baseline and 48 months by quantitative magnetic resonance imaging (MRI), and symptoms using baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Data were analysed by linear regression with confounding factors at baseline, followed by multiple comparison adjustment. RESULTS: The levels of the nine biomarkers and their ratios (36) were studied. Among High BMI subjects, only the ratio adipsin/MCP-1 was associated with cartilage volume loss over time in the lateral compartment [ß, -2.95; 95% confidence interval (CI), -4.42, -1.49; P = 0.010], whereas MCP-1 was associated with WOMAC pain (-1.74; -2.75, -0.73; P = 0.030) and the ratio CRP/MCP-1 with WOMAC pain (0.76; 0.37, 1.14; P = 0.023), function (2.43; 1.20, 3.67; P = 0.020) and total (3.29; 1.58, 5.00; P = 0.027). No associations were found for biomarkers or ratios in Low BMI OA. CONCLUSION: In this study, the ratio adipsin/MCP-1 was found to be associated with the knee structural changes and that of CRP/MCP-1 with symptoms in obese OA subjects. Our data further underline the relevance of ratios as biomarkers to a stronger association to OA progression and symptoms.

Combined transanal total mesorectal excision (taTME) with laparoscopic instruments and abdominal robotic surgery in rectal cancer.

Laparoscopic surgery for rectal cancer can be technically challenging. We describe a hybrid technique combining abdominal robotic dissection and transanal total mesorectal excision. This procedure was performed in a 50-year-old man with rectal adenocarcinoma at 5 cm from the dentate lane. Preoperative staging was T2N0M0. Surgery went well without complications, and estimated blood loss was less than 50 mL. Robotic surgical time was 90 min, and total operative time was 160 min. The patient was discharged on postoperative day 3. Pathology analysis revealed an intact mesorectum (TME grade 3) and a T2N0 tumor with negative margins. Hybrid surgery with pelvic robotic dissection and transanal total mesorectal excision was feasible, quick and safe in this patient and may be a method that can be developed further.

Cleavage of intracellular hepatitis C RNA in the virus core protein coding region by deoxyribozymes.

Hepatitis C virus (HCV) infection represents an important global health problem. Current antiviral therapeutics for HCV have proven inadequate in stemming the disease process. A novel therapeutic strategy involves the use of deoxyribozymes, also known as DNA enzymes or DNAzymes. These catalytic DNA molecules, designed to target and cleave specific RNA sequences, have shown promise in in vitro experimental models for various diseases and may serve as an alternative or adjunct to current HCV drug therapy. We designed and tested several deoxyribozymes that can bind and cleave highly conserved RNA sequences encoding the HCV core protein in in vitro systems. One of these deoxyribozymes reduced the level of our HCV RNA target by 32% and 48% after 24 h of cell exposure when tested in human hepatoma and epithelial cell lines, respectively. As this deoxyribozyme showed significant cleavage activity against HCV core protein target RNA in human cells, it may have potential as a therapeutic candidate for clinical trial in HCV infected patients.

Serum and plasma for total and free anticonvulsant drug analyses: effects on EMIT assays and ultrafiltration devices.

The suitability of serum and plasma anticoagulated with heparin, EDTA, citrate, or oxalate was assessed for analysis of free and total phenytoin, carbamazepine, and valproic acid. The free fraction was isolated by ultrafiltration through FreeLevel devices (Syva, Palo Alto, CA). Serum, heparin, and EDTA plasma were satisfactory for both free and total phenytoin and carbamazepine. EDTA could not be used for EMIT (Syva) analysis of valproate. Citrate and, to a lesser degree, oxalate cause a significant negative interference in the concentration of these three drugs as measured both by EMIT and gas-liquid chromatography.

The effect of aspirin on the hypotonic shock response.

The effect of aspirin on the hypotonic shock response was studied at 2, 6, 24, and 48 hours after ingestion of 1.6 g of acetylsalicylic acid. There was a marked acceleration of the recovery phase of the response at two hours. This steadily decreased and by 48 hours had returned to near normal values. In most cases there was also a change in the initial phase of the shock response. We have interpreted these results to indicate a change in membrane permeability (first phase effect) as well as an activation of the energy-dependent recovery (second phase). The latter process possibly is the result of an increase in the levels of available ATP. As previously reported, the response to aggregating agents was impaired in the presence of ASA. Normal and aspirinated platelets were mixed in an attempt to overcome the ASA effect. Using two hour postingestion samples we noted considerable impairment of both the hypotonic shock response and aggregation even in the presence of very high concentrations of normal platelets.

Affinity purification and some molecular properties of human liver alkaline phosphatase.

Alkaline phosphatase from human liver was purified to homogeneity. The purification procedure included solubilization with butanol, fractionation with acetone, and chromatography on concanavalin A-Sepharose, DEAE-cellulose, Sephadex G-200 and DEAE-Sephadex. Purity was established by standard and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The isoelectric point of the protein was determined to be 4.0. Sephadex-gel filtration gave a mol.wt. of 146000, although a higher value was obtained in the presence of 100mM-NaC1. The subunit mol.wt. 76700, was determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Neuraminidase treatment resulted in two enzyme-activity bands on isoelectric-focused gels with isoelectric points of 6.6 and 6.8. The desialylated enzyme gave only one protein band on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis with a subunit molecular weight indistinguishable from that of the non-neuraminidase-treated protein. The desialylated enzyme was more readily denatured by sodium dodecyl sulphate in the presence of mercaptoethanol than was the native enzyme.