Early goal-directed therapy is a term used to describe the guidance of intravenous fluid and vasopressor/inotropic therapy by using cardiac output or similar parameters in the immediate post-cardiopulmonary bypass in cardiac surgery patients. Early recognition and therapy during this period may result in better outcome. In keeping with this aim in the cardiac surgery patients, we conducted the present study. The study included 30 patients of both sexes, with EuroSCORE >or=3 undergoing coronary artery bypass surgery under cardiopulmonary bypass. The patients were randomly divided into two groups, namely, control and early goal-directed therapy (EGDT) groups. All the subjects received standardized care; arterial pressure was monitored through radial artery, central venous pressure through a triple lumen in the right internal jugular vein, electrocardiogram, oxygen saturation, temperature, urine output per hour and frequent arterial blood gas analysis. In addition, cardiac index monitoring using FloTrac and continuous central venous oxygen saturation using PreSep was used in patients in the EGTD group. Our aim was to maintain the cardiac index at 2.5-4.2 l/min/m2 , stroke volume index 30-65 ml/beat/m2 , systemic vascular resistance index 1500-2500 dynes/s/cm5/m2 , oxygen delivery index 450-600 ml/min/m2 , continuous central venous oximetry more than 70%, stroke volume variation less than 10%; in addition to the control group parameters such as central venous pressure 6-8 mmHg, mean arterial pressure 90-105 mmHg, normal arterial blood gas analysis values, pulse oximetry, hematocrit value above 30% and urine output more than 1 ml/kg/h. The aims were achieved by altering the administration of intravenous fluids and doses of inotropic or vasodilator agents. Three patients were excluded from the study and the data of 27 patients analyzed. The extra volume used (330+/-160 v/s 80+/-80 ml, P=0.043) number of adjustments of inotropic agents (3.4+/-1.5 v/s 0.4+/-0.7, P=0.026) in the EGDT group were significant. The average duration of ventilation (13.8+/-3.2 v/s 20.7+/-7.1 h), days of use of inotropic agents (1.6+/-0.9 v/s 3.8+/-1.6 d), ICU stay (2.6+/-0.9 v/s 4.9+/-1.8 d) and hospital stay (5.6+/-1.2 v/s 8.9+/-2.1 d) were less in the EGDT group, compared to those in the control group. This study is inconclusive with regard to the beneficial aspects of the early goal-directed therapy in cardiac surgery patients, although a few benefits were observed.

Tissue engineering with adult stem cells is a promising approach for the restoration of focal defects in articular cartilage. For this, progenitor cells would ideally be delivered to (and maintained within) the defect site via a biocompatible material and in combination with soluble factors to promote initial cell differentiation and subsequent tissue maturation in vivo. While growth factor delivery methods are continually being optimized, most offer only a short (days to weeks) delivery profile at high doses. To address this issue, we investigated mesenchymal stem cell (MSC) differentiation and maturation in photocrosslinkable hyaluronic acid (HA) hydrogels with transient exposure to the pro-chondrogenic molecule transforming growth factor-beta3 (TGF-β3), at varying doses (10, 50 and 100 ng/mL) and durations (3, 7, 21 and 63 days). Mechanical, biochemical, and histological outcomes were evaluated through 9 weeks of culture. Results showed that a brief exposure (7 days) to a very high level (100 ng/mL) of TGF-β 3 was sufficient to both induce and maintain cartilage formation in these 3D constructs. Indeed, this short delivery resulted in constructs with mechanical and biochemical properties that exceeded that of continuous exposure to a lower level (10 ng/mL) of TGF-β 3 over the entire 9-week time course. Of important note, the total TGF delivery in these two scenarios was roughly equivalent (200 vs. 180 ng), but the timing of delivery differed markedly. These data support the idea that acute exposure to a high dose of TGF will induce functional and long-term differentiation of stem cell populations, and furthers our efforts to improve cartilage repair in vivo.

IntroductionEpigallocatechin 3-gallate (EGCG), a polyphenol present in green tea, was shown to exert chondroprotective effects in vitro. In this study, we used a posttraumatic osteoarthritis (OA) mouse model to test whether EGCG could slow the progression of OA and relieve OA-associated pain.MethodsC57BL/6 mice were subjected to surgical destabilization of the medial meniscus (DMM) or sham surgery. EGCG (25 mg/kg) or vehicle control was administered daily for 4 or 8 weeks by intraperitoneal injection starting on the day of surgery. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical analysis to detect cleaved aggrecan and type II collagen and expression of proteolytic enzymes matrix metalloproteinase 13 (MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). Real-time PCR was performed to characterize the expression of genes critical for articular cartilage homeostasis. During the course of the experiments, tactile sensitivity testing (von Frey test) and open-field assays were used to evaluate pain behaviors associated with OA, and expression of pain expression markers and inflammatory cytokines in the dorsal root ganglion (DRG) was determined by real-time PCR.ResultsFour and eight weeks after DMM surgery, the cartilage in EGCG-treated mice exhibited less Safranin O loss and cartilage erosion, as well as lower OARSI scores compared to vehicle-treated controls, which was associated with reduced staining for aggrecan and type II collagen cleavage epitopes, and reduced staining for MMP-13 and ADAMTS5 in the articular cartilage. Articular cartilage in the EGCG-treated mice also exhibited reduced levels of Mmp1, Mmp3, Mmp8, Mmp13,Adamts5, interleukin 1 beta (Il1b) and tumor necrosis factor alpha (Tnfa) mRNA and elevated gene expression of the MMP regulator Cbp/p300 interacting transactivator 2 (Cited2). Compared to vehicle controls, mice treated with EGCG exhibited reduced OA-associated pain, as indicated by higher locomotor behavior (that is, distance traveled). Moreover, expression of the chemokine receptor Ccr2 and proinflammatory cytokines Il1b and Tnfa in the DRG were significantly reduced to levels similar to those of sham-operated animals.ConclusionsThis study provides the first evidence in an OA animal model that EGCG significantly slows OA disease progression and exerts a palliative effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0508-y) contains supplementary material, which is available to authorized users.

No abstract

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA, and no effective treatments which arrest or slow its progression. Current pharmacologic treatments such as analgesics may improve pain relief but do not alter OA disease progression. Prolonged consumption of these drugs can result in severe adverse effects. Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. Consequently, there is an urgent need for OA disease-modifying therapies which also improve symptoms and are safe for clinical use over long periods of time. Nutraceuticals—food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease—offer not only favorable safety profiles, but may exert disease- and symptom-modification effects in OA. Forty-seven percent of OA patients use alternative medications, including nutraceuticals. This review will overview the efficacy and mechanism of action of commonly used nutraceuticals, discuss recent experimental and clinical data on the effects of select nutraceuticals, such as phytoflavonoids, polyphenols, and bioflavonoids on OA, and highlight their known molecular actions and limitations of their current use. We will conclude with a proposed novel nutraceutical-based molecular targeting strategy for chondroprotection and OA treatment.