From Basic Science to Clinical Applications
01 Jan 2009-
About: The article was published on 2009-01-01 and is currently open access. It has received 667 citations till now. The article focuses on the topics: Applied science.
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TL;DR: The currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect are reviewed.
1,109 citations
TL;DR: How the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function is highlighted.
Abstract: A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.
966 citations
Cites background from "From Basic Science to Clinical Appl..."
...The best-studied SCFA receptors are GPR43 and GPR41, later renamed free fatty acid receptor (FFAR2) and FFAR3, as well as GPR109a/HCAR2 (hydrocarboxylic acid receptor) andGPR164, which are expressed in a vast array of cells, from the gastrointestinal mucosa to the immune and nervous systems (82, 83)....
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TL;DR: This study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool from different donors with high reproducibility and its content characterization will allow us to understand and improve the clinical outcomes.
Abstract: Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 106 to 1.9 × 106 platelets/μl). Platelets were highly purified, because only <0.3% from the initial red blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF. Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool from different donors with high reproducibility. These findings support the use of PRP in therapies aiming for tissue regeneration, and its content characterization will allow us to understand and improve the clinical outcomes.
480 citations
Cites methods from "From Basic Science to Clinical Appl..."
...Consistent nomenclatures, standardized protocols to produce PRP as well as a full characterization of the final product are still missing and would highly improve the comparability of studies [40,41]....
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TL;DR: These findings indicate that treatment with PRP injections can reduce pain and improve knee function and quality of life with short-term efficacy, and further studies are needed to confirm these results and understand the mechanism of action.
Abstract: Purpose Platelet-rich plasma (PRP) therapy is a simple, low-cost and minimally invasive method that provides a natural concentrate of autologous blood growth factors (GFs) that can be used to enhance tissue regeneration. In a previous analysis of a 12-month follow-up study, promising results were obtained when treating patients affected by knee degeneration with PRP intra-articular injections. The main purpose of this study was to investigate the persistence of the beneficial effects observed. Methods Of the 91 patients evaluated in the previous 12-month follow-up study, 90 were available for the 2-year follow-up (24 patients presented a bilateral lesion, in a total of 114 knees treated). All of the patients presented a chronic knee degenerative condition and were treated with three intra-articular PRP injections. IKDC and EQ-VAS scores were used for clinical evaluation. Complications, adverse events and patient satisfaction were also recorded. Results All of the evaluated parameters worsened at the 24-month follow-up: these parameters were at significantly lower levels with respect to the 12-month evaluation (the IKDC objective evaluation fell from 67 to 59% of normal and nearly normal knees; the IKDC subjective score fell from 60 to 51), even if they remained higher than the basal level. Further analysis showed better results in younger patients (P = 0.0001) and lower degrees of cartilage degeneration (P \ 0.0005). The median duration of the clinical improvement was 9 months. Conclusions These findings indicate that treatment with PRP injections can reduce pain and improve knee function and quality of life with short-term efficacy. Further studies are needed to confirm these results and understand the mechanism of action, and to find other application modalities, with different platelet and GF concentrations and injection timing, which provide better and more durable results.
465 citations
Cites background from "From Basic Science to Clinical Appl..."
...Platelets contain storage pools of growth factors in their a-granules [9], including PDGF, TGF b, IGF-1, FGF and many others, as well as cytokines and chemokines [25]....
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...This therapy is widely experimented in different fields of medicine to test its potential to enhance tissue regeneration [9, 25]....
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TL;DR: It is supported that more than just platelets are playing a role in clinical responses to PRP, and the clinical use can theoretically be matched to the pathology being treated in an effort to improve clinical efficacy.
Abstract: Platelet concentrates such as platelet-rich plasma (PRP) have gained popularity in sports medicine and orthopaedics to promote accelerated physiologic healing and return to function. Each PRP product varies depending on patient factors and the system used to generate it. Blood from some patients may fail to make PRP, and most clinicians use PRP without performing cell counts on either the blood or the preparation to confirm that the solution is truly PRP. Components in this milieu have bioactive functions that affect musculoskeletal tissue regeneration and healing. Platelets are activated by collagen or other molecules and release growth factors from alpha granules. Additional substances are released from dense bodies and lysosomes. Soluble proteins also present in PRP function in hemostasis, whereas others serve as biomarkers of musculoskeletal injury. Electrolytes and soluble plasma hormones are required for cellular signaling and regulation. Leukocytes and erythrocytes are present in PRP and function in inflammation, immunity, and additional cellular signaling pathways. This article supports the emerging paradigm that more than just platelets are playing a role in clinical responses to PRP. Depending on the specific constituents of a PRP preparation, the clinical use can theoretically be matched to the pathology being treated in an effort to improve clinical efficacy.
461 citations
References
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TL;DR: Atherosclerosis is an inflammatory disease as discussed by the authors, and it is a major cause of death in the United States, Europe, and much of Asia, despite changes in lifestyle and use of new pharmacologic approaches to lower plasma cholesterol concentrations.
Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .
19,881 citations
Journal Article•
TL;DR: Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations, cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.
9,749 citations
TL;DR: The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.
Abstract: Background Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events. Methods We conducted a prospective, nested case–control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation. The markers included high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, and soluble intercellular adhesion molecule type 1 (slCAM-1). We also studied homocysteine and several lipid and lipoprotein measurements. Cardiovascular events were defined as death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronay-revascularization procedures. Results Of the 12 markers measured, hs-CRP was the strongest univariate predictor of the risk of cardiovascular events; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 (95 percent confidence interval, 2.2 to 8.9). Other markers significantly associated with the risk of cardiovascular events were serum amyloid A (relative risk for the highest as compared with the lowest quartile, 3.0), slCAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), low-density lipoprotein (LDL) cholesterol (2.4), apolipoprotein B-100 (3.4), high-density lipoprotein (HDL) cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone (P<0.001). The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter (3.4 mmol per liter), the target for primary prevention established by the National Cholesterol Education Program. In multivariate analyses, the only plasma markers that independently predicted risk were hs-CRP (relative risk for the highest as compared with the lowest quartile, 1.5; 95 percent confidence interval, 1.1 to 2.1) and the ratio of total cholesterol to HDL cholesterol (relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.9). Conclusions The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying women at risk for cardiovascular events.
5,895 citations
TL;DR: Dietary supplementation with n-3 PUFA led to a clinically important and statistically significant benefit and vitamin E had no benefit and its effects on fatal cardiovascular events require further exploration.
3,727 citations
TL;DR: Elevated levels of serum cholesterol are probably unique through the hepatic LDL receptor pathway, as evi-in being sufficient to drive the development of athero-denced by the fact that lack of functional LDL receptors sclerosis in humans and experimental animals, even in is responsible for the massive accumulation of LDL in the absence of other known risk factors.
2,995 citations