Background
Foot ulcers are a major complication of diabetes mellitus, often leading to amputation. Growth factors derived from blood platelets, endothelium, or macrophages could potentially be an ...important treatment for these wounds but they may also confer risks.
Objectives
To assess the benefits and harms of growth factors for foot ulcers in patients with type 1 or type 2 diabetes mellitus.
Search methods
In March 2015 we searched the Cochrane Wounds Group Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations, Ovid EMBASE and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting.
Selection criteria
Randomised clinical trials in any setting, recruiting people with type 1 or type 2 diabetes mellitus diagnosed with a foot ulcer. Trials were eligible for inclusion if they compared a growth factor plus standard care (e.g., antibiotic therapy, debridement, wound dressings) versus placebo or no growth factor plus standard care, or compared different growth factors against each other. We considered lower limb amputation (minimum of one toe), complete healing of the foot ulcer, and time to complete healing of the diabetic foot ulcer as the primary outcomes.
Data collection and analysis
Independently, we selected randomised clinical trials, assessed risk of bias, and extracted data in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I2 statistic. We subjected our analyses to both fixed‐effect and random‐effects model analyses.
Main results
We identified 28 randomised clinical trials involving 2365 participants. The cause of foot ulcer (neurologic, vascular, or combined) was poorly defined in all trials. The trials were conducted in ten countries. The trials assessed 11 growth factors in 30 comparisons: platelet‐derived wound healing formula, autologous growth factor, allogeneic platelet‐derived growth factor, transforming growth factor β2, arginine‐glycine‐aspartic acid peptide matrix, recombinant human platelet‐derived growth factor (becaplermin), recombinant human epidermal growth factor, recombinant human basic fibroblast growth factor, recombinant human vascular endothelial growth factor, recombinant human lactoferrin, and recombinant human acidic fibroblast growth factor. Topical intervention was the most frequent route of administration. All the trials were underpowered and had a high risk of bias. Pharmaceutical industry sponsored 50% of the trials.
Any growth factor compared with placebo or no growth factor increased the number of participants with complete wound healing (345/657 (52.51%) versus 167/482 (34.64%); RR 1.51, 95% CI 1.31 to 1.73; I2 = 51%, 12 trials; low quality evidence). The result is mainly based on platelet‐derived wound healing formula (36/56 (64.28%) versus 7/27 (25.92%); RR 2.45, 95% 1.27 to 4.74; I2 = 0%, two trials), and recombinant human platelet‐derived growth factor (becaplermin) (205/428 (47.89%) versus 109/335 (32.53%); RR 1.47, 95% CI 1.23 to 1.76, I2= 74%, five trials).
In terms of lower limb amputation (minimum of one toe), there was no clear evidence of a difference between any growth factor and placebo or no growth factor (19/150 (12.66%) versus 12/69 (17.39%); RR 0.74, 95% CI 0.39 to 1.39; I2 = 0%, two trials; very low quality evidence). One trial involving 55 participants showed no clear evidence of a difference between recombinant human vascular endothelial growth factor and placebo in terms of ulcer‐free days following treatment for diabetic foot ulcers (RR 0.64, 95% CI 0.14 to 2.94; P value 0.56, low quality of evidence)
Although 11 trials reported time to complete healing of the foot ulcers in people with diabetes , meta‐analysis was not possible for this outcome due to the unique comparisons within each trial, failure to report data, and high number of withdrawals. Data on quality of life were not reported. Growth factors showed an increasing risk of overall adverse event rate compared with compared with placebo or no growth factor (255/498 (51.20%) versus 169/332 (50.90%); RR 0.83; 95% CI 0.72 to 0.96; I2 = 48%; eight trials; low quality evidence). Overall, safety data were poorly reported and adverse events may have been underestimated.
Authors' conclusions
This Cochrane systematic review analysed a heterogeneous group of trials that assessed 11 different growth factors for diabetic foot ulcers. We found evidence suggesting that growth factors may increase the likelihood that people will have complete healing of foot ulcers in people with diabetes. However, this conclusion is based on randomised clinical trials with high risk of systematic errors (bias). Assessment of the quality of the available evidence (GRADE) showed that further trials investigating the effect of growth factors are needed before firm conclusions can be drawn. The safety profiles of the growth factors are unclear. Future trials should be conducted according to SPIRIT statement and reported according to the CONSORT statement by independent investigators and using the Foundation of Patient‐Centered Outcomes Research recommendations.
Wnt signalling is involved in numerous events in animal development, including the proliferation of stem cells and the specification of the neural crest. Wnt proteins are potentially important ...reagents in expanding specific cell types, but in contrast to other developmental signalling molecules such as hedgehog proteins and the bone morphogenetic proteins, Wnt proteins have never been isolated in an active form. Although Wnt proteins are secreted from cells, secretion is usually inefficient and previous attempts to characterize Wnt proteins have been hampered by their high degree of insolubility. Here we have isolated active Wnt molecules, including the product of the mouse Wnt3a gene. By mass spectrometry, we found the proteins to be palmitoylated on a conserved cysteine. Enzymatic removal of the palmitate or site-directed and natural mutations of the modified cysteine result in loss of activity, and indicate that the lipid is important for signalling. The purified Wnt3a protein induces self-renewal of haematopoietic stem cells, signifying its potential use in tissue engineering.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Antimicrobial growth promoters (AGPs) enhance animal health and improve agricultural productivity. • Mechanisms of AGP action are poorly understood; research has diverged into host- and ...bacteria-centric hypotheses. • Due to risks of antimicrobial resistance, AGPs are being phased out of livestock production. • Understanding the mechanisms of AGP action is critical in developing effective non-antibiotic alternatives.
We have characterized a cytokine produced by Th2 cells, designated as IL-25. Infusion of mice with IL-25 induced IL-4, IL-5, and IL-13 gene expression. The induction of these cytokines resulted in ...Th2-like responses marked by increased serum IgE, IgG
1, and IgA levels, blood eosinophilia, and pathological changes in the lungs and digestive tract that included eosinophilic infiltrates, increased mucus production, and epithelial cell hyperplasia/hypertrophy. In addition, our studies show that IL-25 induces Th2-type cytokine production by accessory cells that are MHC class II
high, CD11c
dull, and lineage
−. These results suggest that IL-25, derived from Th2 T cells, is capable of amplifying allergic type inflammatory responses by its actions on other cell types.
All plants synthesize a suite of several hundred terpenoid compounds with roles that include phytohormones, protein modification reagents, anti-oxidants, and more. Different plant lineages also ...synthesize hundreds of distinct terpenoids, with the total number of such specialized plant terpenoids estimated in the scores of thousands. Phylogenetically restricted terpenoids are implicated in defense or in the attraction of beneficial organisms. A popular hypothesis is that the ability of plants to synthesize new compounds arose incrementally by selection when, as a result of gradual changes in their biotic partners and enemies, the ‘old’ plant compounds were no longer effective, a process dubbed the ‘coevolutionary arms race’. Another hypothesis posits that often the sheer diversity of such compounds provides benefits that a single compound cannot. In this article, we review the unique features of the biosynthetic apparatus of terpenes in plants that facilitate the production of large numbers of distinct terpenoids in each species and how facile genetic and biochemical changes can lead to the further diversification of terpenoids. We then discuss evidence relating to the hypotheses that given ecological functions may be enhanced by the presence of mixtures of terpenes and that the acquisition of new functions by terpenoids may favor their retention once the original functions are lost.
Rings or arcs of fungus-regulated plant growth occur often on the floor of woodlands, in agricultural areas, and in grasslands worldwide. These rings are commonly called “fairy rings”. A plant-growth ...regulating compound was isolated from a fairy ring forming fungus, Lepista sordida , and its chemical structure was identified as imidazole-4-carboxamide (ICA) by spectroscopic analyses including single-crystal X-ray diffraction techniques. ICA inhibited the growth of turfgrass and rice seedling. On the other hand, in a greenhouse experiment, this compound increased rice grain yield by 26% compared with control.
Thiouracil (TU), synthesized for its thyroid-regulating capacities and alternatively misused in livestock for its weight-gaining effects, is acknowledged to have an endogenous origin. Discrimination ...between low-level abuse and endogenous occurrence is challenging and unexplored in an experimental setting. Therefore, cows (n = 16) and calves (n = 18) were subjected to a rapeseed-supplemented diet or treated with synthetic TU. Significant higher urinary TU levels were recorded after TU administration (<CCα, 15 642 μg L–1) compared to rapeseed supplementation (<CCα, 65.8 μg L–1), however, with overlapping values. TU was not detected in the edible meat; however, concentrations between the CCα and 10 μg kg–1 were noted in thyroid tissue of calves and cows following rapeseed supplementation. The latter concentrations were significantly higher in thyroid tissue of calves (22.9–41.8 μg kg–1) and cows (16.9–36.7 μg kg–1) after synthetic TU administration. These results strongly point toward thyroid analysis as a discriminatory tool.
Chronic lung infections with opportunistic bacterial and fungal pathogens are a major cause of morbidity and mortality especially in patients with cystic fibrosis. Pseudomonas aeruginosa is the most ...frequently colonizing bacterium in these patients, and it is often found in association with the filamentous fungus Aspergillus fumigatus. P. aeruginosa is known to inhibit the growth of A. fumigatus in situations of direct contact, suggesting the existence of interspecies communication that may influence disease outcome. Our study shows that the lung pathogens P. aeruginosa and A. fumigatus can interact at a distance via volatile-mediated communication and expands our understanding of interspecific signaling in microbial communities.
Microbiota studies have shown that pathogens cannot be studied individually anymore and that the establishment and progression of a specific disease are due not to a single microbial species but are the result of the activity of many species living together. To date, the interaction between members of the human microbiota has been analyzed in situations of direct contact or liquid-mediated contact between organisms. This study showed unexpectedly that human opportunistic pathogens can interact at a distance after sensing volatiles emitted by another microbial species. This finding will open a new research avenue for the understanding of microbial communities.
We have biologically characterized two new members of the IL-17 cytokine family: IL-17F and IL-25. In contrast to conventional in vitro screening approaches, we have characterized the activity of ...these new molecules by direct in vivo analysis and have compared their function to that of other IL-17 family members. Intranasal administration of adenovirus expressing IL-17, IL-17C, or IL-17F resulted in bronchoalveolar lavage neutrophilia and inflammatory gene expression in the lung. In contrast, intranasal administration of IL-25-expressing adenovirus or IL-25 protein resulted in the production of IL-4, IL-5, IL-13, and eotaxin mRNA in the lung and marked eosinophilia in the bronchoalveolar lavage and lung tissue. Mice given intranasal IL-25 also developed epithelial cell hyperplasia, increased mucus secretion, and airway hyperreactivity. IL-25 gene expression was detected following Aspergillus and Nippostrongylus infection in the lung and gut, respectively. IL-25-induced eosinophilia required IL-5 and IL-13, but not IL-4 or T cells. Following IL-25 administration, the IL-5(+) staining cells were CD45R/B220(+), Thy-1(+/-), but were NK1.1-, Ly-6G(GR-1)-, CD4-, CD3-, and c-kit-negative. gamma-common knockout mice did not develop eosinophilia in response to IL-25, nor were IL-5(+) cells detected. These findings suggest the existence of a previously unrecognized cell population that may initiate Th2-like responses by responding to IL-25 in vivo. Further, these data demonstrate the heterogeneity of function within the IL-17 cytokine family and suggest that IL-25 may be an important mediator of allergic disease via production of IL-4, IL-5, IL-13, and eotaxin.
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