Utilisation of locally delivered doxycycline in non‐surgical treatment of chronic periodontitis

Wennström, Jan L.; Newman, H. N.; MacNeill, Simon R.; Killoy, William J.; Griffiths, Gareth; Gillam, DG; Krok, Lena; Needleman, Ian; Weiss, Gina; Garrett, Steven

doi:10.1034/j.1600-051x.2001.280806.x

Cited by 98 publications

(103 citation statements)

References 16 publications

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“…Doxycycline, given in a subantimicrobal dose, is also the only MMP inhibitor approved by the U.S. Food and Drug Administration. It is currently used for the treatment of periodontal disease (Wennström et al, 2001) and rosacea (Del Rosso et al, 2007). We hypothesized that MMP inhibition in the mouse experimental model of vEDS would shift the balance between collagen degradation and synthesis in the vascular wall and protect against vascular damage.…”

Section: Introductionmentioning

confidence: 99%

Doxycycline Ameliorates the Susceptibility to Aortic Lesions in a Mouse Model for the Vascular Type of Ehlers-Danlos Syndrome

Briest¹,

Cooper²,

Tae³

et al. 2011

J Pharmacol Exp Ther

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The vascular form of Ehlers-Danlos syndrome (vEDS), a rare disease with grave complications resulting from rupture of major arteries, is caused by mutations of collagen type III [␣1 chain of collagen type III (COL3A1)]. The only, recently proven, preventive strategy consists of the reduction of arterial wall stress by ␤-adrenergic blockers. The heterozygous (HT) Col3a1 knockout mouse has reduced expression of collagen III and recapitulates features of a mild presentation of the disease. The objective of this study was to determine whether changing the balance between synthesis and degradation of collagen by chronic treatment with doxycycline, a nonspecific matrix metalloproteinase (MMP) inhibitor, could prevent the development of vascular pathology in HT mice. After 3 months of treatment with doxycycline or placebo, 9-month-old HT or wild-type (WT) mice were subjected to surgical stressing of the aorta. A 3-fold increase in stress-induced aortic lesions found in untreated HT mice 1 week after intervention (cumulative score 4.5 Ϯ 0.87 versus 1.3 Ϯ 0.34 in WT, p Ͻ 0.001) was fully prevented in the doxycycline-treated group (1.1 Ϯ 0.56, p Ͻ 0.001). Untreated HT mice showed increased MMP-9 activity in the carotid artery and decreased collagen content in the aorta; however, in doxycycline-treated animals there was normalization to the levels observed in WT mice. Doxycycline treatment inhibits the activity of tissue MMP and attenuates the decrease in the collagen content in aortas of mice haploinsufficient for collagen III, as well as prevents the development of stress-induced vessel pathology. The results suggest that doxycycline merits clinical testing as a treatment for vEDS.

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Section: Introductionmentioning

confidence: 99%

Doxycycline Ameliorates the Susceptibility to Aortic Lesions in a Mouse Model for the Vascular Type of Ehlers-Danlos Syndrome

Briest¹,

Cooper²,

Tae³

et al. 2011

J Pharmacol Exp Ther

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“…Gingival crevicular fluid (GCF) concentrations to peak with a concentration of 1473-1986 mg/ml at 2 hours and gradually decreased to 309 mg/ml at the end of 7 days which was above the minimum inhibiting concentration for doxycycline [17]. Several studies comparing SRP with doxycycline local gels have revealed similar results, which indicates either SRP or doxycycline gel alone may be favorable [18]. However, as this material i.e.…”

Section: In-vitro Release Studies Of Doxmentioning

confidence: 56%

Doxycycline Poly E-Caprolactone Nanofibers in Patients with Chronic Periodontitis – A Clinical Evaluation

Chaturvedi¹

2013

JCDR

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“…Doxy in a sub- antimicrobal dose is also the only MMP inhibitor approved by the Food and Drug Administration. It is currently used for the treatment of periodontal disease (Wennström et al, 2001) and rosacea (Del Rosso et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Chronic Treatment with a Broad-Spectrum Metalloproteinase Inhibitor, Doxycycline, Prevents the Development of Spontaneous Aortic Lesions in a Mouse Model of Vascular Ehlers-Danlos Syndrome

Tae

Marshall²,

Zhang³

et al. 2012

J Pharmacol Exp Ther

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There is no proven therapy or prevention for vascular EhlersDanlos syndrome (vEDS), a genetic disorder associated with the mutation of procollagen type III and characterized by increased fragility of vascular and hollow organ walls. Heterozygous COL3A1-deficient (HT) mice recapitulate a mild presentation of one of the variants of vEDS: haploinsufficiency for collagen III. Adult HT mice are characterized by increased metalloproteinase (MMP) activity, reduced collagen content in the arterial walls, and spontaneous development of various severity lesions in aorta. We hypothesized that chronic treatment with a MMP inhibitor would increase collagen content and prevent the development of spontaneous aortic lesions. HT mice were treated since weaning with the broad-spectrum MMP inhibitor doxycycline added to food. At the age of 9 months MMP-9 expression was twice as high in the tunica media of aorta in untreated HT mice, whereas total collagen content was 30% lower (p Ͻ 0.01) and the cumulative score of aortic lesions was eight times higher than in wild-type (WT) mice (p Ͻ 0.01). After 9 months of doxycycline treatment, MMP-9 activity, collagen content, and lesions in the aortas of HT mice were at the level of those of WT mice (p Ͼ 0.05). In the mouse model of collagen III haploinsufficiency treatment with broad-spectrum MMP inhibitor that was started early in life normalized increased MMP activity, reduced aortic collagen content in adults, and prevented the development of spontaneous aortic lesions. Our findings provide experimental justification for the clinical evaluation of the benefit of doxycycline at least in the haploinsufficient variety of vEDS.

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Utilisation of locally delivered doxycycline in non‐surgical treatment of chronic periodontitis

Abstract: The results indicate that simplified subgingival instrumentation combined with local application of doxycycline in deep periodontal sites can be considered as a justified approach for non-surgical treatment of chronic periodontitis.

Cited by 98 publications

References 16 publications

Doxycycline Ameliorates the Susceptibility to Aortic Lesions in a Mouse Model for the Vascular Type of Ehlers-Danlos Syndrome

Doxycycline Ameliorates the Susceptibility to Aortic Lesions in a Mouse Model for the Vascular Type of Ehlers-Danlos Syndrome

Doxycycline Poly E-Caprolactone Nanofibers in Patients with Chronic Periodontitis – A Clinical Evaluation

Chronic Treatment with a Broad-Spectrum Metalloproteinase Inhibitor, Doxycycline, Prevents the Development of Spontaneous Aortic Lesions in a Mouse Model of Vascular Ehlers-Danlos Syndrome

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