996 resultados para 37.014
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Introduction: As a result of chronic inflammation during periodontal disease the junctional epithelium becomes micro-ulcerated. The inflammatory process is mediated by both bacterial and host cell products. Host defence peptides such as defensins, secretory leucocyte protease inhibitor (SLPI) and the sole human cathelicidin, LL-37, are secreted by both periodontal cells and neutrophils into gingival crevicular fluid (GCF). They have the ability to modulate the immune response in periodontitis and are thought to have a potential role in periodontal wound healing. Objectives: The aims of this study were to determine the role of LL-37 in the production of Interleukin (IL)-8, IL-6, hepatocyte growth factor (HGF) and basic-fibroblast growth factor (bFGF) by gingival fibroblasts. The role of LL-37 in modulating total matrix metalloproteinase (MMP) activity and expression of tissue inhibitors of metalloproteinase (TIMP)-1 and -2 by gingival fibroblasts was also investigated. Methods: Primary gingival fibroblasts were co-cultured with concentrations of LL-37 (1, 5 and 10µg/ml) for 24 hours and their supernatants tested for levels of IL-8 and IL-6, HGF, bFGF, TIMP-1 and TIMP-2 by ELISA. Rates of MMP turnover in the supernatants were tested by fluorogenic assay using fluorescence resonance energy transfer (FRET) peptide substrates. Cytotoxicity was measured by MTT assay. Statistical significance was measured using the independent t-test and p<0.05 was considered significant. Results: LL-37 significantly upregulated levels of IL-8, IL-6, HGF, bFGF and TIMP-1 (p<0.05) in a dose-dependent fashion. LL-37 significantly decreased the total MMP activity (p<0.05). None of the LL-37 concentrations tested were cytotoxic to gingival fibroblasts. Conclusion: These results indicate that LL-37 is involved in periodontal wound healing. LL-37 increased levels of proinflammatory cytokines and increased levels of growth factors involved in re-epithelialisation. LL-37 has the ability to regulate remodelling of the periodontium by controlling MMP overactivity both directly and by stimulating production of inhibitors by gingival fibroblasts.
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Host defence peptides, including the cathelicidin LL-37, play an important role in mucosal immunity, functioning as both antimicrobial agents and modulators of the inflammatory response. In the current climate of antibiotic resistance, the idea of using naturally occurring antimicrobial peptides, or their synthetic mimetics, to combat oral infection is particularly appealing. Objectives: The aim of this study was to investigate the effects of parent LL-37, and two peptide mimetics (KR-12 and KE-18), on cytokine expression and response to bacterial challenge by gingival fibroblasts. Methods: KR-12 and KE-18 are peptide mimetics of the biologically active, mid-region sequence of LL-37. The effects of commercially available LL-37, KR-12 and KE-18 on gingival fibroblast response to E coli and P gingivalis LPS challenge, analysed by IL-6 and IL-8 expression, were determined in cell culture by ELISA. The direct effects of each peptide on IL-6, IL-8, CXCL-1 and HGF expression were also determined by ELISA. The MTT assay was used to evaluate peptide effects on fibroblast viability. Results: LL-37 and KE-18, but not KR-12, inhibited LPS induction of inflammatory cytokine expression and directly stimulated CXCL-1 production by fibroblasts. All 3 peptides stimulated production of IL-8 and HGF. Neither LL-37 nor KE-12 affected cell viability, while KE-18, at higher concentrations, induced cell death. Conclusions: Shorter, peptide mimetics of LL-37, in particular KE-18, retain the immunomodulatory effects of the parent molecule and possess excellent potential as therapeutic agents in the treatment of oral infections including periodontal disease.
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Background: Candida albicans is a commensal organism and a constituent of the normal oral flora. Cell concentrations of 1x102 cells/ml and below are indicative of commensal colonisation in the oral cavity, above this level C. albicans can become an opportunistic pathogen; it is the most prevalent human fungal pathogen and a causal agent of the oral infection, candidiasis. The capacity of C. albicans to cause infection arises from its ability to exist in a biofilm ecosystem. Mature C. albicans biofilms display a high level of resistance to antifungals and the need for other therapeutic options has become paramount. Objectives: The objectives of the current study were to determine the antifungal activity of LL-37 (a member of the human cathelicidin family) and two truncated peptide mimetics against C. albicans in both planktonic and biofilm form. Methods: Radial diffusion assays were used to obtain the minimum inhibitory concentration (MIC) of LL-37 and the truncated mimetics KE-18 and KR-12 against planktonic C. albicans. A 96 well microtitre plate assay was employed to study the effects of the peptides on early candida biofilm formation (up to 24 hours) compared with the antifungal drug fluconazole. Biofilm quantification was achieved using the crystal violet assay. Results: MIC values obtained: LL-37 >250µg/ml; KE-18 51µg/ml; and KR-12 11µg/ml. LL-37 significantly reduced the quantity of biofilm formed by C.albicans at both the 4 h and 24 h timepoints (p <0.0001). KE-18 showed significant biofilm reduction over 4 h and 24 h (p=0.0002, p=0.013 respectively), KR-12 showed significant reduction at the 24 h time point only (p=0.0256). Conclusions: Results suggest that LL-37 has the ability to disrupt early biofilm formation of C. albicans with its potency of action similar with that of fluconazole.
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Background: LL-37, composed of 37 amino acid residues, is an innate host defence peptide of the cathelicidin family. It is expressed by neutrophils, monocytes and epithelial cells and exhibits both anti-bacterial and immunomodulatory properties. LL-37 is however prone to proteolytic degradation by proteinases, thus potentially limiting its inherent host defence properties in the inflammatory milieu. Objectives: The present study was designed to determine whether LL-37 was degraded by components of gingival crevicular fluid (GCF) from healthy subjects or those with periodontitis. In addition, we aimed to deduce whether degradation of the peptide was accelerated in GCF samples which were determined to be positive for the periodontopathic bacterium Porphyromonas gingivalis. Methods: GCF and bacterial plaque samples, pre- and post non-surgical periodontal treatment, were collected from 4 individual sites in patients presenting with advanced periodontitis. In healthy subjects, GCF samples only were collected. Plaque samples were analysed by QPCR for the presence or absence of P. gingivalis. Pooled GCF samples from healthy sites; periodontitis sites which were P. gingivalis negative (Pg-); or periodontitis sites which were P. gingivalis positive (Pg+), were incubated with synthetic LL-37 for 0 – 180 min. The degradation products were then analysed by matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS). Results: LL-37 was not degraded when incubated with GCF from healthy subjects. In contrast, LL-37 was degraded after 30 min when incubated with Pg- GCF. However degradation of LL-37 was apparent after only 2 min incubation with Pg+ GCF and the parent molecule was almost completely degraded after 30 min. Conclusions: The rapid degradation of LL-37, particularly in Pg+ sites, highlights the limited role which this host defence peptide may play in the presence of biologically active proteinases. It also underscores a potent virulence mechanism of P. gingivalis used to circumvent innate host responses.
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BACKGROUND: The experienced smoker maintains adequate nicotine levels by 'puff-by-puff self-control' which also avoids symptomatic nauseating effects of nicotine overdose. It is postulated that there is a varying 'dynamic threshold for nausea' into which motion sickness susceptibility provides an objective toxin-free probe. Hypotheses were that: (i) nicotine promotes motion sickness whereas deprivation protects; and (ii) pleasurable effects of nicotine protect against motion sickness whereas adverse effects of withdrawal have the opposite effect. METHODS: Twenty-six healthy habitual cigarette smokers (mean±SD) 15.3±7.6cigs/day, were exposed to a provocative cross-coupled (coriolis) motion on a turntable, with sequences of 8 head movements every 30s. This continued to the point of moderate nausea. Subjects were tested after either ad-lib normal smoking (SMOKE) or after overnight deprivation (DEPRIV), according to a repeated measures design counter-balanced for order with 1-week interval between tests. RESULTS: Deprivation from recent smoking was confirmed by objective measures: exhaled carbon monoxide CO was lower (P<0.001) for DEPRIV (8.5±5.6ppm) versus SMOKE (16.0±6.3ppm); resting heart rate was lower (P<0.001) for DEPRIV (67.9±8.4bpm) versus SMOKE (74.3±9.5bpm). Mean±SD sequences of head movements tolerated to achieve moderate nausea were more (P=0.014) for DEPRIV (21.3±9.9) versus SMOKE (18.3±8.5). DISCUSSION: Tolerance to motion sickness was aided by short-term smoking deprivation, supporting Hypothesis (i) but not Hypothesis (ii). The effect was was approximately equivalent to half of the effect of an anti-motion sickness drug. Temporary nicotine withdrawal peri-operatively may explain why smokers have reduced risk for postoperative nausea and vomiting (PONV).
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Type 2 diabetes is a multifactorial metabolic disease characterized by defects in β-cells function, insulin sensitivity, glucose effectiveness and endogenous glucose production (1). It is widely accepted that insulin and exercise are potent stimuli for glucose transport (2). Acute exercise is known to promote glucose uptake in skeletal muscle via an intact contraction stimulated mechanism (3), while post-exercise improvements in glucose control are due to insulin-dependant mechanisms (2). Hypoxia is also known to promote glucose uptake in skeletal muscle using the contraction stimulated pathway. This has been shown to occur in vitro via an increase in β-cell function, however data in vivo is lacking. The aim of this study was to examine the effects of acute hypoxia with and without exercise on insulin sensitivity (SI2*), glucose effectiveness (SG2*) and β-cell function in individuals with type 2 diabetes. Following an overnight fast, six type 2 diabetics, afer giving informed written consent, completed 60 min of the following: 1) normoxic rest (Nor Rest); 2) hypoxic rest [Hy Rest; O2 = 14.6 (0.4)%]; 3) normoxic exercise (Nor Ex); 4) hypoxic exercise [Hy Ex; O2 = 14.6 (0.4)%]. Exercise trails were set at 90% of lactate threshold. Each condition was followed by a labelled intravenous glucose tolerance test (IVGTT) to provide estimations of SI2*, SG2* and β-cell function. Values are presented as means (SEM). Two-compartmental minimal model analysis showed SI2* to be higher following Hy Rest when comparisons were made with Nor Rest (P = 0.047). SI2* was also higher following Hy Ex [4.37 (0.48) x10-4 . min-1 (μU/ml)] compared to Nor Ex [3.24 (0.51) x10-4 . min-1 (μU/ml)] (P = 0.048). Acute insulin response to glucose (AIRg) was reduced following Hy Rest vs. Nor Rest (P = 0.014 - Table 1). This study demonstrated that 1) hypoxia has the ability to increase glucose disposal; 2) hypoxic-induced improvements in glucose tolerance in the 4 hr following exposure can be attributed to improvements in peripheral SI2*; 3) resting hypoxic exposure improves β-cell function and 4) exercise and hypoxia have an additive effect on SG2* in type 2 diabetics. These findings suggest a possible use for hypoxia both with and without exercise in the clinical treatment of type 2 diabetes.
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Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP
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This paper analyzes several natural and man-made complex phenomena in the perspective of dynamical systems. Such phenomena are often characterized by the absence of a characteristic length-scale, long range correlations and persistent memory, which are features also associated to fractional order systems. For each system, the output, interpreted as a manifestation of the system dynamics, is analyzed by means of the Fourier transform. The amplitude spectrum is approximated by a power law function and the parameters are interpreted as an underlying signature of the system dynamics. The complex systems under analysis are then compared in a global perspective in order to unveil and visualize hidden relationships among them.
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BACKGROUND: The aim of the current study was to assess whether widely used nutritional parameters are correlated with the nutritional risk score (NRS-2002) to identify postoperative morbidity and to evaluate the role of nutritionists in nutritional assessment. METHODS: A randomized trial on preoperative nutritional interventions (NCT00512213) provided the study cohort of 152 patients at nutritional risk (NRS-2002 ≥3) with a comprehensive phenotyping including diverse nutritional parameters (n=17), elaborated by nutritional specialists, and potential demographic and surgical (n=5) confounders. Risk factors for overall, severe (Dindo-Clavien 3-5) and infectious complications were identified by univariate analysis; parameters with P<0.20 were then entered in a multiple logistic regression model. RESULTS: Final analysis included 140 patients with complete datasets. Of these, 61 patients (43.6%) were overweight, and 72 patients (51.4%) experienced at least one complication of any degree of severity. Univariate analysis identified a correlation between few (≤3) active co-morbidities (OR=4.94; 95% CI: 1.47-16.56, p=0.01) and overall complications. Patients screened as being malnourished by nutritional specialists presented less overall complications compared to the not malnourished (OR=0.47; 95% CI: 0.22-0.97, p=0.043). Severe postoperative complications occurred more often in patients with low lean body mass (OR=1.06; 95% CI: 1-1.12, p=0.028). Few (≤3) active co-morbidities (OR=8.8; 95% CI: 1.12-68.99, p=0.008) were related with postoperative infections. Patients screened as being malnourished by nutritional specialists presented less infectious complications (OR=0.28; 95% CI: 0.1-0.78), p=0.014) as compared to the not malnourished. Multivariate analysis identified few co-morbidities (OR=6.33; 95% CI: 1.75-22.84, p=0.005), low weight loss (OR=1.08; 95% CI: 1.02-1.14, p=0.006) and low hemoglobin concentration (OR=2.84; 95% CI: 1.22-6.59, p=0.021) as independent risk factors for overall postoperative complications. Compliance with nutritional supplements (OR=0.37; 95% CI: 0.14-0.97, p=0.041) and supplementation of malnourished patients as assessed by nutritional specialists (OR=0.24; 95% CI: 0.08-0.69, p=0.009) were independently associated with decreased infectious complications. CONCLUSIONS: Nutritional support based upon NRS-2002 screening might result in overnutrition, with potentially deleterious clinical consequences. We emphasize the importance of detailed assessment of the nutritional status by a dedicated specialist before deciding on early nutritional intervention for patients with an initial NRS-2002 score of ≥3.
