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Pastore S.,Dermatology Research Institute IDI IRCCS | Lulli D.,Dermatology Research Institute IDI IRCCS | Fidanza P.,Dermatology Research Institute IDI IRCCS | Potapovich A.I.,Dermatology Research Institute IDI IRCCS | And 6 more authors.
Antioxidants and Redox Signaling | Year: 2012

Aims: To evaluate mechanisms underlying modulation of inflammatory chemokines in primary human keratinocytes (normal human epidermal keratinocytes) and repair-related processes in wound models by plant polyphenols (PPs) with antioxidant and superoxide scavenging properties (verbascoside [Vb], resveratrol [Rv], polydatin [Pd], quercetin [Qr], and rutin). Results: Epidermal growth factor receptor (EGFR)-controlled chemokines CXCL8/interleukin 8 (IL-8), CCL2/monocyte chemotactic protein-1 (MCP-1), and CXCL10/interferon gamma-produced protein of 10 kDa (IP-10) were modulated by transforming growth factor alpha (TGF-α) and by the tumor necrosis factor alpha/interferon gamma combination (T/I). EGFR phosphorylation, nuclear translocation, and downstream cytoplasmic signaling pathways (extracellular regulation kinase [ERK]1/2, p38, STAT3, and PI-3K) were studied. All PPs did not affect TGF-α-induced STAT3 phosphorylation, whereas they suppressed T/I-activated NFkappaB and constitutive and T/I-induced but not TGF-α-induced ERK1/2 phosphorylation. Vb and Qr suppressed total EGFR phosphorylation, but they synergized with TGF-α to enhance nuclear accumulation of phosphorylated EGFR. Vb strongly inhibited TGF-α-induced p38 phosphorylation and T/I-induced NFkappaB and activator protein-1 (AP-1) binding to DNA. Vb was an effective inhibitor of T/I-stimulated chemokine synthesis, and it accelerated scratch wound healing in vitro. Anti-inflammatory and wound healing activities of Vb were confirmed in vivo in the full-thickness excision wound. Although Pd and Rv did not affect EGFR activation/translocation, they and Qr synergized with TGF-α and T/I in the induction of IL-8 transcription/synthesis while opposing enhanced MCP-1 and IP-10 transcription/synthesis connected with pharmacologically impaired EGFR functioning. Innovation: PPs perturb the EGFR system in human keratinocytes, and this effect may be implicated in the regulation of inflammatory and repair-related processes in the skin. Conclusion: Anti-inflammatory and wound healing effects of PPs depend on their interaction with EGFR-controlled cytoplasmic and nuclear pathways rather than on their direct redox properties. © 2012 Mary Ann Liebert, Inc. Source


Erlikh A.D.,Institute of Physical Chemical Medicine | Gratsiansky N.A.,Institute of Physical Chemical Medicine
Kardiologiya | Year: 2012

Aim: To compare data on pre- and inhospital treatment of non ST-elevation (NSTE) acute coronary syndromes (ACS) in Russian ACS registers RECORD (recruitment from 11.2007 to 02.2008) and RECORD-2 (from 04/2009 to 04.2011). Material. Four of 7 hospitals participating In RECORD-2 were invasive (57.1 % vs. 55.6% in RECORD). In RECORD-2 10-30 consecutive patients with NSTEACS were included monthly in each center; recruitment in RECORD was described elsewhere. Results. Mean age of patients was similar in two registries. Portion of women was significantly higher in RECORD-2 (42.9% vs. 26.0% in RECORD; p<0.0001). Although markers of necrosis were measured in higher proportion of patients in RECORD-2, frequency of troponin determination was not significantly different (47.0 vs. 43.5% in RECORD; p=0.64). Patients in RECORD-2 more frequently received prehospital aspirin (51.6 vs 33.5%; p<0.0001), aspirin in recommended initial dose 160- 325 mg (64.3 vs. 47.1%; p=0.03), and clopidogrel during hospitalization (47.0 vs. 27.6%; p<0.0001). Rates of inhospital use of parenteral anticoagulants in both registries were similar, but among anticoagulants in RECORD 2 proportion of fondaparinucs became noticeable (9.5%) and that of low molecular weight heparin (LMWH) became significantly higher (21.2 vs. 11.6% in RECORD). Almost one third of patients in RECORD-2 who were treated with unfractionated heparin (UFH) received it subcutaneously. About half of patients treated with intravenous infusion of UFH received it for less than 48 hours. Although higher proportion of patients hospitalized in invasive hospitals were subjected to diagnostic coronary angiography in RECORD-2 (80.8 vs. 54.3% in RECORD; p<0.0001) differences between registries in rates of percutaneous coronary interventions (PCI) (all - 37.3 vs. 29.9%; p=0.051; first 72 hours - 22.7 vs. 24.8%; p=0.55), and coronary artery bypass graftings (5.6 vs. 5.8%; p=0.12) were not significant. There were no significant differences in rates of any inhospital unfavorable events. Analysis of treatment and outcomes in groups of high risk patients (GRACE score >140) gave results close to those in all patients except mortality which was statistically similar but numerically higher in RECORD-2 (9.3 vs. 7.9% in RECORD; p=0.68). Conclusion. Comparison of data of 2 limited NSTEACS registers conducted with interval of about 2 years showed only modest shift towards fulfillment of contemporary recommendations which was not associated with increase in rates of PCI and improvement of outcomes especially in high risk patients. Source


Kostryukova E.S.,Moscow Institute of Physics and Technology | Karpova I.Y.,Kazan Federal University | Larin A.K.,Kazan Federal University | Popenko A.C.,Institute of Physical Chemical Medicine | And 2 more authors.
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry | Year: 2015

The comparative study of seven different methods for extraction of total DNA from human feces has been carried out. All these methods are recommended in protocols for metagenomic analysis of human gut microbiota. The relative abundance of human DNA in such samples registered by shotgun sequencing on a SOLiD 4 genetic analyzer has been investigated. It was shown that either initial amount of feces or a method applied for total DNA extraction insignificantly influenced the final relative human DNA proportion, which did not exceed 1% in healthy people. Invariance of this parameter allows to consider the increased proportion of human DNA in metagenomic samples as a potential marker of inflammatory bowel diseases. © 2015, Pleiades Publishing, Ltd. Source


Erlikh A.D.,Institute of Physical Chemical Medicine | Gratsianskii N.A.,Institute of Physical Chemical Medicine
Diabetes Mellitus | Year: 2012

Aims. To analyze basic clinical characteristics, inhospital therapeutic approaches and outcomes in patients with acute coronary syndrome (ACS) and diabetes mellitus (DM). Materials and methods. Patients were included in this study according to the protocol, established for Russian ACS Registry (RECORD), based on data from 18 hospitals operating in 13 Russian cities. Results. 796 patients took part in the current study. 15.6% reported diagnosis of DM at admission. We observed positive correlation between initial glycemic levels and presence of DM (r=0.43; p<0,001). Patients with DM were elder and more often had other cardiovascular risk factors, signs of chronic heart failure and increased GRACE score at admission. However, therapeutic approach did not significantly differ between patients with and without DM, while hospital mortality rate was substantially higher in diabetic patients as compared to non-diabetic (16.9% and 5.2%, respectively; p<0,0001). We determined a certain dependence of outcomes on the aggressiveness of treatment. In particular, we show that percutaneous coronary intervention and clopidogrel were more effective in patients with DM, who suffered from ST-elevation ACS (STEACS). Conclusion. Patients with ACS and DM comorbidity tend to have worse prognosis, and diagnosis of DM is an independent predictor of lethal inhospital outcomes. Nevertheless, treatment tactics remains similar between patients with DM and without it. Source

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