Diagnostic Value of Acute Phase Proteins in Periodontal, Psychosomatic and Cardiometabolic Diseases: Response to Treatment

Soory, Menaka; El-Shinnawi, Una

doi:10.5772/18048

Cited by 7 publications

(3 citation statements)

References 131 publications

(119 reference statements)

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“…Some of these actions could be applied to in vivo clinical presentations of metabolic syndrome and DM as comorbidities in periodontitis subjects; and responses to adjunctive treatment with doxycycline. In the context of inflammatory diseases mediated by cytokines and acute phase reactions [ 31 ], clinically successful periodontal therapy impacts on improved outcome for systemic comorbidities by reducing serum levels of cytokines and systemic inflammation. This has been demonstrated with regard to circulating levels of hs-CRP, fibrinogen, interleukins-4, 6, 8, 10 and TNF-α associated with metabolic control in Type 2 DM patients with periodontitis [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Response of Osteoblasts to Doxycycline in an Inflammatory Model Induced by C-reactive Protein and Interleukin-6

Tilakaratne¹,

Soory

2014

IDDT

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Objectives: Investigation of osteoblastic responses to oxidative stress, induced by C-reactive protein (CRP) and IL-6 and ameliorating effects of doxycycline (Dox); using assays for 5-alpha dihydrotestosterone (DHT) as an antioxidant marker of healing. IL-6 and CRP are risk markers of periodontitis and prevalent comorbidities in periodontitis subjects. Methods: Confluent monolayer cultures of osteoblasts were incubated with radiolabelled testosterone (14C-T) as substrate, in the presence or absence (Control) of pre-determined optimal concentrations of CRP, IL-6, Dox; alone and in combination (n=8) for 24h in MEM. The eluent was solvent-extracted for steroid metabolites. They were separated using TLC in a benzene/ acetone solvent system 4:1 v/v; and quantified using radioisotope scanning. The identity of formed metabolites was confirmed using the mobility of cold standards added to the samples and disclosed in iodine. Further confirmation of the authenticity of DHT was carried out by combined gas chromatrography-mass spectrometry, after derivatization to pentafluorobenzyloxime trimethyl silyl ether. Results: The yields of DHT from 14C-testosterone showed 2-fold and 1.8-fold- inhibition in response to IL-6 and CRP respectively and 28% stimulation in response to Dox, via the 5-alpha reductase pathway. The combination of IL-6 + CRP showed a 2-fold reduction in the yields of DHT, elevated to control values when combined with Dox (n=8; p<0.001). Yields of 4-androstenedione showed an inverse relationship to those of DHT, in response to the agents tested, in keeping with the 17-beta hydroxysteroid dehydrogenase pathway. Conclusions: Inhibition of DHT synthesis in osteoblasts by IL-6 and CRP was overcome by doxycycline. Oxidative actions of IL-6 and CRP; and antioxidant actions of Dox are reinforced by the metabolic yields of DHT in response to agents tested. Using a novel metabolically active model allows closer extrapolation to in vivo conditions; in the context of adjunctive therapeutic applications for periodontitis and prevalent comorbidities.

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Section: Discussionmentioning

confidence: 99%

Antioxidant Response of Osteoblasts to Doxycycline in an Inflammatory Model Induced by C-reactive Protein and Interleukin-6

Tilakaratne¹,

Soory

2014

IDDT

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“…Antioxidants as adjuncts to root surface debridement have been shown to improve treatment outcome in periodontitis patients 5 . In the context of periodontal disease and systemic comorbidities 6 7 , antioxidants could be beneficial in overcoming delayed wound healing induced by an imbalance in redox status. The stress-inducible protein heme oxygenase-1 expressed in human gingival fibroblasts exposed to nicotine was overcome by the addition of the glutathione precursor N-acetyl-L-cysteine 8 .…”

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confidence: 99%

Mechanisms for redox actions of nicotine and glutathione in cell culture, relevant to periodontitis

Tinti

Soory

2012

Sci Rep

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The oxidative effect of nicotine was investigated using androgen biomarkers of redox status and wound healing in fibroblasts; using the antioxidant glutathione for confirmation of responses. Cultures of human gingival (HGF) and periosteal fibroblasts (HPF) were incubated with substrates 14C-testosterone/14C-4-androstenedione in the presence or absence of serial concentrations of nicotine (N100-500), glutathione (G1–5) and their combinations, in medium. At 24 h the medium was solvent extracted for metabolites, separated by TLC and quantified using radioisotope scanning. Nicotine caused significant inhibition in yields of the physiologically active metabolite 5α-dihydrotestosterone (DHT) in HGF and HPF, overcome to varying degrees by the anti-oxidant glutathione (n = 6; p<0.01, one way ANOVA); this is suggestive of moderation of an oxidative mechanism induced by nicotine. Down-regulation of 5α-reductase activity by nicotine resulting in reduced yields of DHT was overcome by glutathione. Overcoming oxidative stress in a redox environment is applicable to treatment outcome.

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“…The prevalence of cardiovascular disease (CVD) seems to be highest in those individuals in whom periodontitis coexists with elevated CRP levels; there is a stronger link between fatal myocardial events and raised CRP in periodontal patients [11]. CRP may be considered to be an important comediator of lipid metabolism in a milieu of inflammation.…”

Section: Introductionmentioning

confidence: 99%

Osteoblastic Responses to LPS, Glucose-oxidised LDL and Minocycline: Therapeutic Targets for Periodontal and Cardiometabolic Diseases

Tilakaratne

Soory²

2012

EMI

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Objectives: To study redox responses of cultured osteoblasts, mediated by bacterial lipopolysaccharide (LPS), glucose (G), glucose-oxidised low density lipoprotein (GLDL) and minocycline (M) using radiolabelled steroid markers of redox status and wound healing. The clinical relevance of this concept in periodontitis patients with cardiometabolic risk markers is addressed. Methods: A well differentiated osteoblastic cell-line was cultured in Eagle's MEM in confluent monolayer, in 24 well multiwell plates. Radiolabelled testosterone was used as the steroid substrate. Experiments were set up with controls in the absence of agents, optimal concentrations (previously determined) of G, GLDL, LPS, M, GLDL+LPS and the latter combined with M (n = 8). At the end of a 24h incubation period, the reaction was terminated and the medium analysed for yields of the steroid metabolite 5 -dihydrotestosterone (DHT), the redox marker relevant to wound healing, the weaker androgen 4-androstenedione (4-A) and the diols. Analysis entailed thin layer chromatography and radioisotope scanning. Results: The yields of DHT showed 1.4-fold and 2.3-fold decreases in response to GLDL and LPS respectively and a 1.3-fold reduction in response to the combination, when compared with controls in the absence of agents. Minocycline stimulated the yield of DHT by 1.4-fold, and when combined with GLDL+LPS, the decreased yield was overcome and raised to 2-fold above the combination in response to the addition of minocycline (n = 8; p < 0.001), when compared with controls. The trends in the yields of 4-A and diols were inversely related to each other with increases and decreases over controls respectively, in keeping with enzymic pathways. Conclusions: Decreased yields of the oxidative stress marker DHT in response to LPS, G and GLDL were overcome in the presence of minocycline, which demonstrates its potential role as an adjunctive therapeutic agent in an environment of oxidative stress. These applications could be extrapolated to periodontal disease and co-existing cardiometabolic risk markers, in the context of its antiinflammatory and antioxidant actions relevant to healing. In this paper, recent patents relevant to adjunctive therapeutic management of periodontal disease co-existing with cardiometabolic risk markers are addressed. There have been significant advances in therapeutic interventions for overcoming oxidative stress-inducing mechanisms that are common to these disease entities.

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Diagnostic Value of Acute Phase Proteins in Periodontal, Psychosomatic and Cardiometabolic Diseases: Response to Treatment

Cited by 7 publications

References 131 publications

Antioxidant Response of Osteoblasts to Doxycycline in an Inflammatory Model Induced by C-reactive Protein and Interleukin-6

Antioxidant Response of Osteoblasts to Doxycycline in an Inflammatory Model Induced by C-reactive Protein and Interleukin-6

Mechanisms for redox actions of nicotine and glutathione in cell culture, relevant to periodontitis

Osteoblastic Responses to LPS, Glucose-oxidised LDL and Minocycline: Therapeutic Targets for Periodontal and Cardiometabolic Diseases

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