Systemic Doxycycline Administration Research Articles

The Efficacy of Systemic Doxycycline Administration as an Inhibitor of Intimal Hyperplasia after Balloon Angioplasty Arterial Injury

Intimal hyperplasia (IH) is the most common indicator for secondary intervention in peripheral vascular disease. Matrix metalloproteinases (MMPs) play a role in IH development due to their degradation of the extracellular matrix. Doxycycline (Doxy), a member of the tetracycline family of antibiotics, is a potent MMP inhibitor. We have previously shown that Doxy inhibitsMMP activity and vascular smooth muscle cell migration invitro. We hypothesized that Doxy would decrease MMP activity invivo and inhibit the development of IH in a rodent model of vascular injury. Doxy (400mg/pellet) was delivered by a slow-release pellet implanted 3days prior to or at the time of balloon angioplasty (BA) of the common carotid artery in female rats. At 14days post-BA, intima-to-media (I:M) ratios were 0.77±0.21 and 1.04±0.32 in the Doxy treated groups, respectively, compared to 1.25±0.26 in the control group (P = not significant; n=3). Additionally, the tested dose of Doxy in either group had no inhibitory effect on membrane type 1-MMP or MMP-2 tissue levels, as measured by immunohistochemistry, or on systemic levels of MMP, as measured by total MMP serum levels using enzyme-linked immunosorbent assay. At 14days post-BA, VSMC proliferation in the injured artery was increased to Doxy treatment prior to and at the time of surgery (23.5±3.4 and 27.2±3.9%, respectively), compared to control (11.4±0.4%; n=3), as measured by proliferating cellular nuclear antigen immunostaining. In our invivo model of vascular injury, systemic Doxy administration prior to or at the time of vascular injury does not significantly hinder the progression of IH development. Additional doses and routes of administration could be examined in order to correlate therapeutic serum levels of Doxy with effective MMP inhibition in serum and arterial tissue. However, alternative drug delivery systems are needed in order to optimize therapeutic administration of targetedMMP inhibitors for the prevention of IH development.

Comparative evaluation of amoxicillin plus metronidazole and doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis

Aim and Objective: To evaluate the effects of a combination of amoxicillin plus metronidazole and doxycycline alone in the nonsurgical treatment of localized aggressive periodontitis (LAP) and compare their effects on clinical and microbiological parameters during 90 days followup in patients with LAP. Materials and Methods: A total of 20 patients with LAP were included in the study. Collection of subgingival plaque samples and recordings of clinical parameters, that is, plaque index (PI), gingival index (GI), probing pocket depth (PPD), and clinical attachment loss (CAL) was done at baseline. The subjects were randomly divided into two groups. Group I subjects were given a combination of amoxicillin plus metronidazole and Group II subjects were given doxycycline. Full-mouth scaling and root planing (SRP) was performed at day 10. Collection of subgingival plaque samples and recording of clinical parameters was repeated at days 10, 30, and 90. Results: There was a statistically highly significant difference ( P P P Conclusion: Systemic administration of doxycycline with full mouth SRP resulted in a better improvement of periodontal parameters and elimination/suppression of putative periodontal pathogens such as Aa, Pg, and Tf, than amoxicillin plus metronidazole in patients with LAP.

Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP-8 activity from 2 to 6 weeks post-injury, with peak increases in activity occurring at 4 weeks post-injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96 h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP-8 activity in situ. Our findings suggest that inhibition of MMP-8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon.

Efect of periodontal disease and non surgical periodontal treatment on C-reactive protein. Evaluation of type 1 diabetic patients

Objectives: The purpose of this study was to analyze how anti-infectious periodontal treatment affects C reactive protein (CRP) values in patients with type 1 diabetes, and correlate baseline CRP levels with periodontal disease severity. Study Design: A cohort of fifty three subjects with type 1 diabetes and moderate to severe periodontitis were recruited. Periodontal parameters were measured, and blood samples were obtained to evaluate high-sensitivity C-reactive protein (hs-CRP). Group 1 was treated with scaling, root planning, and systemic administration of doxycycline. Group 2 received only scaling and root planning. Results: Hs-CRP was reduced after periodontal treatment in group 1 (-0.22 mg/l) and 2 (-0.21 mg/l ) but this reduction was not statistically significant, even in the patients with the best response to periodontal treatment. However, significant correlation appeared between hs-CRP and mean probing pocket depth (PPD) (p=0, 01) and mean clinical attachment level (CAL) (p=0,03). Conclusions: Non-surgical periodontal treatment couldn’t reduce hs-CRP values, however, it was found an association between advanced periodontitis and elevated blood hs-CRP levels in patients with type 1 diabetes. It can be speculated that periodontal disease increases production of pro-inflammatory mediators in patients with type 1 diabetes, but other producing sources of these pro-inflammatory substances may exist. Key words:Periodontal disease, periodontitis, diabetes mellitus type 1, periodontal therapy, C reactive protein.

Mutant Sodium Channel for Tumor Therapy

Viral vectors have been used to deliver a wide range of therapeutic genes to tumors. In this study, a novel tumor therapy was achieved by the delivery of a mammalian brain sodium channel, ASIC2a, carrying a mutation that renders it constitutively open. This channel was delivered to tumor cells using a herpes simplex virus-1/Epstein-Barr virus (HSV/EBV) hybrid amplicon vector in which gene expression was controlled by a tetracycline regulatory system (tet-on) with silencer elements. Upon infection and doxycycline induction of mutant channel expression in tumor cells, the open channel led to amiloride-sensitive sodium influx as assessed by patch clamp recording and sodium imaging in culture. Within hours, tumor cells swelled and died. In addition to cells expressing the mutant channel, adjacent, noninfected cells connected by gap junctions also died. Intratumoral injection of HSV/EBV amplicon vector encoding the mutant sodium channel and systemic administration of doxycycline led to regression of subcutaneous tumors in nude mice as assessed by in vivo bioluminescence imaging. The advantage of this direct mode of tumor therapy is that all types of tumor cells become susceptible and death is rapid with no time for the tumor cells to become resistant.

The effect of periodontal treatment on metabolic control of type 1 diabetes mellitus

The objective of this investigation was to study the effect of nonsurgical periodontal treatment, with or without systemic administration of doxycycline, on the metabolic control of patients with type 1 diabetes. Sixty type 1 diabetic subjects with moderate to severe periodontitis were recruited. Periodontal parameters were measured, and blood samples were obtained to evaluate glycosylated hemoglobin (HbA1c). Group 1 (30 patients) was treated with scaling, root planning, and chlorhexidine rinses for 3 months in conjunction with systemic administration of doxycycline (100 mg once a day for 15 days). Group 2 (30 patients) received the same periodontal treatment but without the use of doxycycline. The paired Student t-test was used to detect differences between glycosylated hemoglobin means before and 3 months after periodontal treatment in group 1 and group 2 separately. Changes in mean HbA1c after treatment were 0.07% in group 1 and -0.06% in group 2, which were not statistically significant after 3 months. Significant changes were not found even in patients with the best response to periodontal treatment. Periodontal treatment in type 1 diabetic patients after 3 months follow-up did not improve metabolic control of diabetes as measured by glycosylated hemoglobin.

Orthodontically induced root and alveolar bone resorption: inhibitory effect of systemic doxycycline administration in rats

The aim of the present study was to investigate the effect of systemic administration of low-dose doxycycline (DC) on orthodontic root resorption. The effect on alveolar bone, the cell population involved, and the amount of tooth movement were also evaluated.Fifty-six 40-50-day-old male Wistar rats were used. Six animals served as untreated controls. Six animals were only administered DC for 7 days, by means of a mini-osmotic pump implanted subcutaneously. In 44 animals the maxillary first molar was mesialized by a fixed orthodontic appliance exerting 50 g force upon insertion. In 28 of these animals DC was administered at the time of appliance insertion and throughout the experiment. The animals were sacrificed 7, 10 or 14 days after force application and block sections processed for analysis. An area including the mesial aspect of the distopalatal root and the adjacent inter-radicular alveolar bone was histomorphometrically evaluated. The root resorption area, absolute alveolar bone area, distance between first and second molars, number of odontoclasts, osteoclasts, mononuclear cells on the root, tartrate-resistant acid phosphatase (TRAP)-positive cells on the root, bone, and in the periodontal ligament (PDL) were compared between DC-treated and non-DC-treated animals. The results revealed a significant reduction in root resorption, the number of odontoclasts, osteoclasts, mononuclear cells on the root surface, and TRAP-positive cells on the root and bone for the DC-administered group. The absolute alveolar bone area was greater, whereas the distance between the first and second molars did not differ between groups. In conclusion, systemic administration of low-dose DC in rats may have an inhibitory effect on orthodontically induced resorptive activity.

Modulating the Effects of Diabetes on Osseointegration With Aminoguanidine and Doxycycline

The current knowledge of wound healing around implant surfaces is quite limited, particularly as it relates to the effects of systemic diseases such as diabetes. The purpose of our research is to histologically evaluate the effects of aminoguanidine and doxycycline in the modification of peri-implant wound healing around endosseous implants in diabetic rats. Thirty-two Sprague-Dawley rats were randomly assigned to four different treatment groups. One group served as the non-diabetic control, while diabetes was induced in other groups. Titanium plasma-sprayed (TPS) implants were placed in the femora of each animal 2 weeks following diabetic induction. One group of diabetic rats was given aminoguanidine via intraperitoneal injection, and another given doxycycline via oral gavage for 28 days beginning on the day of implantation. The third group of diabetic rats received no medication (controls). All animals were sacrificed following 28 days of healing. The results were measured by marrow bone-to implant contact (MBIC) between the groups. Values for MBIC were greater for the non-diabetic control group than the diabetic control group (P < 0.001). Aminoguanidine-treated diabetic animals had a significantly greater MBIC than the diabetic control group (P < 0.01). Diabetic animals receiving doxycycline did not differ significantly from the diabetic control group (P > 0.05). The results of this study using a rat model con- firm previous reports that diabetes inhibits osseointegration, as defined by MBIC. In addition, this study demonstrates that the detrimental effects of diabetes on osseointegration can be modified using aminoguanidine systemically. However, systemic administration of doxycycline only slightly enhances osseointegration.

Aneurysm Growth, Elastinolysis, and Attempted Doxycycline Inhibition of Elastase-induced Aneurysms in Rabbits

To establish the relationship between elastin degradation and aneurysm growth in New Zealand white rabbit model aneurysms, and to explore the potential for pharmacologic inhibition of elastinolysis and aneurysm growth with use of the matrix metalloproteinase (MMP) inhibitor doxycycline. Elastase-induced, saccular aneurysms created in the right common carotid artery in 30 animals randomly divided into controls (n = 16) and doxycycline treated (n = 14) were studied. Aneurysm growth was determined by angiography and aneurysm specimens were collected at 7 and 14 days for histologic and immunohistochemical analysis. Aneurysms were characterized by marked elastin degradation and thickening of the arterial wall media in the absence of inflammatory cell markers. There was no evidence for expression of MMPs in the aneurysm wall at any time point. Aneurysm formation and growth were not prevented by the systemic administration of doxycycline. Mean aneurysm width increased from 3.1 +/- 0.7 mm at 3 days to 3.7 +/- 0.8 mm at 7 days and 4.2 +/- 0.8 mm at 14 days (P =.012 and P =.017, respectively). There was no statistically significant difference in aneurysm size and elastin content at any time point between doxycycline treated and control animals. Elastase-induced rabbit aneurysm formation is accompanied by total elastin destruction that was not inhibited by the administration of doxycycline. Aneurysms in this model may be caused by the initial infusion of elastase, rather than by ongoing degradation from endogenous proteases released by inflammatory cells.

Histomorphometric evaluation of the effect of doxycycline on the healing of bone defects in experimental diabetes mellitus: A pilot study

Purpose: Bone healing is impaired in diabetes mellitus, particularly due to increased collagen breakdown. Recently, tetracyclines have been used to treat experimental bone defects because they have anticollagenolytic properties, and positive effects on the healing process have been obtained. The objective of this study was to develop a computer-assisted histomorphometric technique to quantitatively determine the amount of regenerating bone within experimental bone defects in a diabetic rodent model. Materials and Methods: This study examined the effects of systemic doxycycline administration on the healing of tibial bone defects in healthy albino rats and in experimentally induced diabetic rats. Twenty-four female albino rats were assigned to 4 groups: diabetic, diabetic plus doxycycline, control, or control plus doxycycline. The standardized bone defects were histomorphometrically examined 10 and 30 days postoperatively. Histomorphometric analysis of the amount of new bone formation was performed using the Zeiss Vision image analysis program KS 400 (Kontron Elektron GmbH, Eching, Germany). Results: At 10 days of healing, the diabetic groups exhibited inferior healing compared with the control groups in terms of the amount of new bone formation within the defects. However, the effect of doxycycline administration to the diabetic and control groups was not statistically different. At 30 days of healing, there were no statistically significant differences between the amount of newly formed bone in any of the groups. Conclusions: This study found that doxycycline administration did not significantly alter the amount of new bone formation during the healing of bone defects in control and diabetic rats. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:898-904, 2002

Doxycycline prevents root resorption and alveolar bone loss in rats after periodontal surgery

The effect of systemic doxycycline administration on frequency of root resorption cavities and extent of bone loss following periodontal surgery was studied in albino rats. Thirty Wistar rats with healthy gingiva were divided into four groups. Six untreated animals (Group 1) served as controls. Gingivectomy (Group 2, six rats), mucoperiosteal flap operation (Group 3, eight rats), and mucoperiosteal flap operation with doxycycline added to the drinking water (Group 4, 10 rats) were performed on the palatal aspect of maxillary left molars. After a healing period of 3 wk, the rats were killed by an overdose of sodium pentothal, and specimens of first molars were prepared for light microscopy. Root resorption was absent in normal and gingivectomized animals (Groups 1 and 2). Resorption cavities occurred in all flap-operated animals (Group 3) and in one of 10 doxycycline-treated animals (Group 4). The distance from cementoenamel junction to alveolar bone crest remained unchanged in gingivectomized (Group 2) and doxycycline-treated animals (Group 4), as compared with control specimens. In flap-operated animals (Group 3), the crestal bone level was located more apically than in doxycycline-treated rats (Group 4). This study has shown that root resorption and bone loss were associated with flap operations involving exposure of periodontal ligament and bone. Systemic doxycycline prevented both root resorption and bone loss.