Bacteria and nanosilver: the quest for optimal production.

Silver nanoparticles (AgNPs) have potential uses in many applications, but current chemical production methods are challenged by scalability, limited particle stability, and the use of hazardous chemicals. The biological processes present in bacteria to mitigate metallic contaminants in their environment present a potential solution to these challenges. Before commercial exploitation of this technology can be achieved, the quality of bacteriogenic AgNPs needs to be improved for certain applications. While the colloidal and morphological stabilities of biogenic AgNPs are widely regarded as superior to chemogenic particles, little control over the synthesis of particle morphologies has been achieved in biological systems. This article reviews a range of biosynthetic reaction conditions and how they affect AgNP formation in bacteria to understand which are most influential. While there remains uncertainty, some general trends are emerging: higher Ag+ concentrations result in higher AgNP production, up to a point at which the toxic effects begin to dominate; the optimal temperature appears to be heavily species-dependent and linked to the optimal growth temperature of the organism. However, hotter conditions generally favor higher production rates, while colder environments typically give greater shape diversity. Little attention has been paid to other potentially important growth conditions including halide concentrations, oxygen exposure, and irradiation with light. To fully exploit biosynthetic production routes as alternatives to chemical methods, hurdles remain with controlling particle morphologies and require further work to elucidate and harness them. By better understanding the factors influencing AgNP production, a foundation can be laid from which shape-controlled production can be achieved.

Vitamin D and spine surgery.

Vitamin D is crucial for musculoskeletal health, maintenance, and function. Vitamin D insufficiency is common among patients undergoing spine surgery and the ideal vitamin D level for spine surgery has yet to be investigated. There is a high prevalence of hypovitaminosis D in patients with musculoskeletal pain regardless of surgical intervention. With the frequency and costs of spine surgery increasing, it is imperative that efforts are continued to reduce the impact on patients and healthcare services. Studies into vitamin D and its associations with orthopaedic surgery have yielded alarming findings with regards to the prevalence of vitamin D deficiency. Importantly, altered vitamin D status also contributes to a wide range of disease conditions. Therefore, future investigations are still essential for better understanding the relationship between vitamin D and spine surgery outcomes. Whilst further research is required to fully elucidate the extent of the effects of hypovitaminosis D has on surgical outcomes, it is strongly advisable to reduce the impacts by appropriate vitamin D supplementation of deficient and at-risk patients.

Plasma and synovial fluid inflammatory cytokine profiles in primary knee osteoarthritis.

OBJECTIVE: The objective of this study is to compare inflammatory cytokine levels in primary knee osteoarthritis (OA) patients and healthy controls. METHODS: A total of 32 knee OA patients and 14 healthy controls were enrolled. A multiplex immunoassay was utilized for 10 cytokines in plasma and synovial fluid. RESULTS: Plasma IL-2, IL-4, and IL-6 concentrations were significantly greater in knee OA patients than controls. Moreover, both plasma IL-4 and IL-6 were positively correlated with the radiographic severity of knee OA. CONCLUSIONS: Plasma IL-4 and IL-6 may serve as biomarkers reflecting the severity of OA.

Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives.

Osteoarthritis is a debilitating and degenerative disease which affects millions of people worldwide. The causes and mechanisms of osteoarthritis remain to be fully understood. Vitamin D has been hypothesised to play essential roles in a number of diseases including osteoarthritis. Many cell types within osteoarthritic joints appear to experience negative effects often at increased sensitivity to vitamin D. These findings contrast clinical research which has identified vitamin D deficiency to have a worryingly high prevalence among osteoarthritis patients. Randomised-controlled trial is considered to be the most rigorous way of determining the effects of vitamin D supplementation on the development of osteoarthritis. Studies into the effects of low vitamin D levels on pain and joint function have to date yielded controversial results. Due to the apparent conflicting effects of vitamin D in knee osteoarthritis, further research is required to fully elucidate its role in the development and progression of the disease as well as assess the efficacy and safety of vitamin D supplementation as a therapeutic strategy.

Plasma and synovial fluid autotaxin correlate with severity in knee osteoarthritis.

BACKGROUND: This study aimed to investigate the relationships between plasma and synovial autotaxin and the severity in knee osteoarthritis (OA) patients. METHODS: A total of 90 participants (70 knee OA patients and 20 controls) were recruited. Autotaxin and high-sensitivity C-reactive protein (hs-CRP) levels were determined. The symptomatic and radiographic severity of OA was assessed using the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores and the Kellgren-Lawrence grades. RESULTS: OA patients had significantly higher circulating autotaxin and hs-CRP than controls. Plasma autotaxin was directly correlated with synovial fluid autotaxin (r=0.639, P<0.001). Additionally, plasma and synovial fluid autotaxin were associated with radiographic severity (P<0.001). Furthermore, plasma and synovial fluid autotaxin levels were positively correlated with WOMAC scores (r=0.558, P<0.001 and r=0.371, P=0.002, respectively). CONCLUSION: Plasma and synovial fluid autotaxin levels were positively correlated with the severity of OA. Thus, autotaxin has potential as a biomarker reflecting the severity of knee OA.

Cytokines as biochemical markers for knee osteoarthritis.

Osteoarthritis (OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly being considered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and anti-inflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin (IL)-6 and the relationship to disease burden of IL-1ß, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.

Angiogenic cytokine expression profiles in plasma and synovial fluid of primary knee osteoarthritis.

PURPOSE: The aim of this study was to compare angiogenic cytokine levels in knee osteoarthritis (OA) patients and healthy controls and to investigate the relationships between angiogenic cytokines and the OA severity. METHODS: Thirty-one knee OA patients and 15 healthy controls were recruited. Nine angiogenic cytokines (angiopoietin-2, follistatin, granulocyte-colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interleukin (IL)-8, leptin, platelet-derived growth factor-BB (PDGF-BB), platelet endothelial cell adhesion molecule (PECAM)-1, and vascular endothelial growth factor (VEGF)) in plasma and synovial fluid were measured using a multiplex immunoassay. RESULTS: PECAM-1, HGF, VEGF, angiopoietin-2, follistatin, G-CSF, and IL-8 concentrations in plasma were significantly higher in OA patients than those in controls. Plasma angiopoietin-2 was significantly greater in advanced OA than in early OA. Synovial fluid VEGF was positively correlated with the severity (r = 0.367, P = 0.04). Plasma follistatin was significantly lower in advanced knee OA than in early OA and was negatively correlated with the severity (r = -0.374, P < 0.05). CONCLUSIONS: Angiogenic cytokine concentrations in plasma can distinguish between controls and OA patients. Local and circulating levels of angiogenic cytokines could give an insight into the pathophysiology of OA. Follistatin, angiopoietin-2, and VEGF may have potential as biochemical markers for the assessment of OA severity.

Plasma and synovial fluid sclerostin are inversely associated with radiographic severity of knee osteoarthritis.

OBJECTIVE: The purpose of this study was to analyze sclerostin in plasma and synovial fluid of knee osteoarthritis (OA) patients and to investigate the association between sclerostin levels and radiographic severity. DESIGN AND METHODS: A total of 190 subjects (95 knee OA patients and 95 healthy controls) were recruited in the present study. Sclerostin levels in plasma and synovial fluid were assessed using an enzyme-linked immunosorbent assay. OA grading was performed using the Kellgren-Lawrence classification. RESULTS: Plasma sclerostin levels were significantly lower in OA patients than in healthy controls (P=0.004). Additionally, sclerostin levels in plasma were significantly higher with respect to paired synovial fluid (P<0.001). Moreover, sclerostin levels in plasma and synovial fluid demonstrated a significant inverse correlation with the radiographic severity of knee OA (r=-0.464, P<0.001 and r=-0.592, P<0.001, respectively). Subsequent analysis revealed that there was a positive correlation between plasma and synovial sclerostin levels (r=0.657, P<0.001). CONCLUSIONS: Sclerostin was significantly lower in OA plasma samples when compared with healthy controls. Plasma and synovial fluid sclerostin levels were inversely associated with the radiographic severity of knee OA. Therefore, sclerostin may be utilized as a biochemical marker for reflecting disease severity in primary knee OA.