Doxycycline Group Research Articles

Short‐Term Effects of Photodynamic Therapy on Periodontal Status and Glycemic Control of Patients With Diabetes

Periodontitis is a major cause of tooth loss among adults. Several studies have shown a possible systemic impact of periodontal infection, including poor glycemic control in patients with diabetes. Recently, photodynamic therapy (PDT) was used to successfully treat periodontal infection. PDT provides a broad spectrum antimicrobial efficacy with no local or systemic side effects. The objective of this study was to examine the effect of the adjunctive use of PDT on periodontal status and glycemic control of patients with diabetes and periodontitis. Forty-five patients with type 2 diabetes and moderate to severe chronic periodontitis were selected and randomly assigned to one of the following three treatment modalities (15 subjects each): scaling and root planing (SRP) only, SRP plus systemic doxycycline, and SRP plus PDT. The plaque and bleeding scores, probing depth, clinical attachment level, and glycosylated hemoglobin (HbA1c) level were recorded at baseline and 3 months after periodontal treatment. Descriptive statistics, the paired t test, and analysis of variance (ANOVA) were used for data analysis. Statistically significant differences in the mean probing depth, clinical attachment level, plaque deposit, and bleeding on probing were found between baseline and 12 weeks post-treatment for all groups. No significant differences in periodontal parameters and glucose levels were detected among the three groups. Reduction in the mean HbA1c level after treatment was observed in all groups but was only significant for the SRP plus doxycycline group. The results of the present study indicate that PDT does not benefit conventional non-surgical periodontal therapy in patients with diabetes.

Macrofilaricidal Activity and Amelioration of Lymphatic Pathology in Bancroftian Filariasis after 3 Weeks of Doxycycline Followed by Single-Dose Diethylcarbamazine

In a placebo controlled trial, the effects of 21- and 10-day doxycycline treatments (200 mg/day) followed by single dose diethylcarbamazine (administered 4 months post treatment) on depletion of Wolbachia endobacteria from Wuchereria bancrofti, filaricidal activity, and amerlioration of scrotal lymph vessel dilation were studied in 57 men from Orissa, India. The 21-day doxycycline course reduced Wolbachia in W. bancrofti by 94% before diethylcarbamazine administration. After 12 months, all patients with this treatment were amicrofilaremic and different from the 10-day doxycycline (42.9%) and placebo (37.5%) groups, and significantly fewer were positive for scrotal worm nests (6.7%) compared with 10-day doxycycline (60%) and placebo (66.7%). Average scrotal lymph vessel diameters were reduced from 0.7 cm pre-treatment to 0.02 cm in patients after 21 days of treatment, while no significant changes were seen in the other groups. This latter feature confirms the beneficial effects of doxycycline on lymphatic dilation and thus adds to the existing evidence that doxycycline, in addition to being macrofilaricidal, may be used to prevent or reverse lymphatic pathology.

Doxycycline vs. levofloxacin in the treatment of community-acquired pneumonia

Community-acquired pneumonia (CAP) affects 5-10 million adults annually in the United States with approximately 1.1 million hospitalizations. Current guidelines recommend fluoroquinolones as monotherapy for treatment of CAP in general medical wards and doxycycline monotherapy for outpatient therapy only. Fluoroquinolones are expensive and development of bacterial resistance to them has become a concern. Therefore, we studied whether doxycycline is as efficacious as levofloxacin in treatment of CAP in general medical wards. In this prospective double-blinded trial, non-pregnant adults with clinical and radiological evidence of pneumonia requiring hospitalization were enrolled. Patients who were septic, hypoxic requiring intubations, nursing home residents, diagnosed with severe hepatic or renal dysfunction, recently hospitalized or immunocompromised were excluded from the study. Subjects were randomly assigned to either i.v. levofloxacin 500 mg daily or doxycycline 100 mg twice daily. After discharge, patients were followed for 2 months. There were 30 patients in the levofloxacin group and 35 patients in the doxycycline group. Groups were comparable in both clinical and laboratory profiles. Additionally, efficacy of treatment was not significantly different between the two groups (P = 0.844). Length of stay was 5.7 +/- 2.05 days in the levofloxacin group and 4.0 +/- 1.82 days in the doxycycline group (P < 0.0012). Failure rate was similar in both groups (P = 0.893). Total antibiotic cost was $122.07 +/- 15.84 for levofloxacin and $64.98 +/- 24.4 for doxycycline (P < 0.0001). Our study supports doxycycline as an effective and economical alternative therapy for levofloxacin in the empirical treatment of CAP in general medical wards.

The Electricidal Effect Is Active in an Experimental Model of Staphylococcus epidermidis Chronic Foreign Body Osteomyelitis

Treatment with low-amperage (200 microA) electrical current was compared to intravenous doxycycline treatment or no treatment in a rabbit model of Staphylococcus epidermidis chronic foreign body osteomyelitis to determine if the electricidal effect is active in vivo. A stainless steel implant and 10(4) CFU of planktonic S. epidermidis were placed into the medullary cavity of the tibia. Four weeks later, rabbits were assigned to one of three groups with treatment administered for 21 days. The groups included those receiving no treatment (n = 10), intravenous doxycycline (n = 14; 8 mg/kg of body weight three times per day), and electrical current (n = 15; 200 microA continuous delivery). Following treatment, rabbits were sacrificed and the tibias quantitatively cultured. Bacterial load was significantly reduced in the doxycycline (median, 2.55 [range, 0.50 to 6.13] log10 CFU/g of bone) and electrical-current (median, 1.09 [range, 0.50 to 2.99] log10 CFU/g of bone) groups, compared to the level for the control group (median, 4.16 [range, 3.70 to 5.66] log10 CFU/g of bone) (P < 0.0001). Moreover, treatment with electrical current was statistically significantly more efficacious (P = 0.035) than doxycycline treatment. The electricidal effect (the bactericidal activity of low-amperage electrical current against bacterial biofilms) is active in vivo in the treatment of experimental S. epidermidis chronic foreign body osteomyelitis.

Stereological study of the effects of Doxycycline on hyperoxic lung injury In neonatal rats

Objective To explore the influence and potential protective effects of non-specific panMetrix Metalloproteinases(MMPs) inhibitor Doxycycline on hyperoxic lung injury and lung development in neonatal rats.Methods Neonatal SD rats were divided into 4 groups randomly within 12 hours after birth:air with normal saline(AN),air with doxycycline(AD),hyperoxia with normal saline(ON),and hyperoxia with doxycycline group(OD).Hyperoxia groups(ON and OD) were exposed to ≥90% O2.Doxycycline 20 mg/kg or equal volume of 0.9% saline(Doxycycline concentration 2 mg/ml) was administered by gastric gavage,twice daily from day 1 to experimental day,but it didn't exceed 14 days.Stereological study was carried out at day 1,3,7,14 and 21 after birth.Results Enlarged mean alveolar area was noted both in hyperoxia and Doxycycline groups.OD group had larger star volume than ON group on day 14.Except ON group,all other groups had increased alveolar septum and the condition was worsened by hyperoxia with Doxycycline.The percentage of collagen in lung parenchymal tissue in ON group increased persistently.This increasing trend was stopped in OD group on day 14,and collagen percentage had no significantly difference between OD and AN groups on day 14 and 21.Conclusion Both hyperoxia and Doxycycline influence neonatal lung development,percentage of coUgen in lung parenchymai can be reduced by Doxycycline in hyperoxic lung injury. Key words: Rats,neonatal; Lung injury; Stereology; Hyperoxia; Doxycycline

Protective effects of doxycycline in ischemia/reperfusion injury on kidney

Renal ischemia and reperfusion injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. The aim of this study was to evaluate whether doxycycline, a member of the tetracycline family of antibiotics, protects kidney tissue or not. 36 Sprague-Dawley rats (200-250 g) were used. The animals were divided into three groups: control, ischemia/reperfusion and ischemia/reperfusion+doxycycline group. Rats were subjected to renal ischemia by clamping the left pedicle for 1 h, and then reperfused for 1 h. The ischemia/reperfusion+doxycycline group were pretreated intraperitoneally with doxycycline suspension (10 mg/kg) 2 h before the induction of ischemia. Our results indicate that malondialdehyde, matrix-metalloproteinase-2, interleukin-2, interleukin-6, interleukin-10, interleukin 1-beta and tumor necrosis factor-alpha levels were significantly higher in the ischemia/reperfusion group than those in the control group. Doxycycline administration significantly decreased these parameters. Tissue inhibitor of metalloproteinases-1 levels also increased after ischemia/reperfusion and decreased with doxycycline pretreatment, but these changes were not significantly different. Glutathione levels significantly decreased after ischemia/reperfusion injury when compared with the control group and doxycycline pretreatment significantly increased glutathione levels when compared with the ischemia/reperfusion group. Apoptotic cells and p53 positive cells were significantly decreased in doxycycline treated group. These results suggest that doxycycline reduces renal oxidative injury and facilitates repair. Doxycycline may play a role in a renoprotective therapeutic regimen.

Levonorgestrel effects on serum androgens, sex hormone–binding globulin levels, hair shaft diameter, and sexual function

To determine the effects of levonorgestrel (LNG) on serum androgens, sex hormone-binding globulin (SHBG), hair shaft diameter, and sexual function in women. Substudy of a prospective randomized double-blind study in women using an LNG SC implant (LNG-SI), who were treated with doxycycline or placebo. Medical school department of obstetrics and gynecology. Forty women were enrolled; 36 completed the study. Participants were randomized to doxycycline 20 mg or an identical placebo orally twice a day after LNG-SI insertion. Serum levels of total T (TT), free T (FT), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), androstanediol glucuronide (AG), SHBG, and LNG; hair shaft diameter; and sexual function using the Brief Index of Sexual Function for Women and the Arizona Sexual Experiences Scale were assessed. Serum TT, A, DHT, DHEAS, and SHBG declined after LNG-SI insertion. No changes were found in FT, AG, hair shaft diameter, or sexual function. Serum LNG correlated with SHBG levels. There were no differences between the placebo and doxycycline groups. LNG reduced serum TT, A, DHT, DHEAS, and SHBG but had no effect on sexual function or markers of androgen bioactivity.

Inhibitory effect of doxycycline on vasculogenic mimicry in retinoblustoma cell line in vitro

Objective To investigate the effect of doxycycline on the proliferation and vasculogenic mimicry in retinoblastoma (RB) cell line in vitro. Methods RB cell line were tested for their ability to form perfusable tubular networks in 3-D culture with doxycycline in the concentrations ranging from 5 to 20 mg/L, and CoCl2 was used as chemical hypoxia-inducing reagent to mimic tumor hypoxic microenvironment. The effect of doxycycline on proliferation were detected by MTT assay in vitro, and the effect on tube formation of RB cells were detected by tube-like structure formation assay and PAS staining. The mRNA levels of MMP-2 and MMP-9 at different hypoxic culture and different doxyeycline concentrations were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results The micrograph showed that RB cells linked each other to form cavity and network tructure in 3-D culture, the number of tubules in doxycycline group were significantly lower than which in the control group in the concentrations ranging from 5 to 20 mg/L (P<0.001). OD of doxycycline group was significantly lower than which in the control group (t=15.320,P<0.01), The proliferation of RB cells had a negative correlation with the concentration of doxycycline (r=-0.924, P<0.01). The levels of MMP-2 and MMP-9 mRNA of RB cells under hypoxia were significantly higher than which in the control group (t= 16. 469,P<0.01). As the concentration of doxycycline increased, the expression of MMP-2 and MMP-9 decreased. The result of double staining also showed that VM, formed by CD34-negative and PAS-positive tumor cells, existed in 12 simples of retinoblastoma. Conclusion RB cells have the capacity of self-metamorphosing and vasculorizing in 3-D culture. Doxyeycline can inhibit their proliferation and vasculogenic mimicry formation in vitro by down-regulating the expression of MMP-2 and MMP-9. Key words: Retinoblastoma/drug therapy; Doxycycline/administration & dosage; Matrix tnetalloproteinase 9; Matrix metalloproteinase 2; Vasculogenic mimicry

Evaluation of a magnetic resonance biomarker of osteoarthritis disease progression: doxycycline slows tibial cartilage loss in the Dunkin Hartley guinea pig.

The objective was to assess the effect of doxycycline treatment on a magnetic resonance imaging (MRI) biomarker of cartilage volume loss, and on matrix metalloproteinase (MMP) activity in a guinea pig osteoarthritis model. Guinea pigs (9 months old) were dosed with vehicle or doxycycline, 0.6, 3.0 mg/kg/day for 66 days. Fat-suppressed 3D gradient-echo MRI of the left knee was acquired pre- and post dosing. Change in medial tibial plateau (MTP) cartilage volume (MT.VC) was determined using image analysis. At termination, MTP cartilage was removed from knees and proteolytic MMP activity determined using a fluorescent peptide substrate assay. Vehicle-treated animals lost 20.5% (95% CI mean 25.6-15.1) MT.VC. The doxycycline (0.6 mg/kg/day) group lost 8.6% (P < 0.05, 95% CI 20.6 to -5.3) whilst the 3.0 mg/kg/day group lost 10.0% (P < 0.05, 95% CI 13.9-6.0%). Endogenous levels of active MMPs were below limits of detection in all samples. However, doxycycline treatment ablated amino phenyl mercuric acid activated MMP-13 and MMP-8 levels, reduced MMP-9 levels by 65% and MMP-1 levels by 24%. Doxycycline treatment resulted in partial protection from MT.VC loss and was associated with complete reduction in MMP-13 and MMP-8, and partial reduction in MMP-9 activity. These data imply a role of MMPs in cartilage degeneration but incomplete protection suggests that additional doxycycline insensitive mechanisms are important in this model. The protective effect of doxycycline correlates with the clinical finding of lessened joint space narrowing, strengthens the utility of this animal model in identifying disease-modifying osteoarthritic drugs and supports the use of MRI biomarkers of cartilage loss.

Use of pradofloxacin to treat experimentally induced Mycoplasma hemofelis infection in cats

To evaluate the efficacy of the fluoroquinolone pradofloxacin in the treatment of cats experimentally infected with Mycoplasma hemofelis. 23 young adult specific-pathogen-free cats. Cats were inoculated with M hemofelis from a chronically infected donor and assigned to 1 of 4 treatment groups: a doxycycline group, a low-dose-pradofloxacin group, a high-dose-pradofloxacin group, and an untreated control group. Treatment was initiated for 14 days when M hemofelis infection was detected via PCR assay and clinical signs of hemoplasmosis were present. Cats that had negative PCR assay results after treatment were administered a glucocorticoid and monitored via PCR assay for an additional 4 weeks. All cats yielded positive results for M hemofelis via conventional PCR and quantitative PCR assays and developed anemia. The low-dose-pradofloxacin group had significantly lower M hemofelis copy numbers than the doxycycline group. Six cats treated with pradofloxacin yielded negative results during treatment. Of those cats, 4 yielded negative conventional PCR assay results and all yielded negative quantitative PCR assay results for M hemofelis 1 month after administration of high-dose glucocorticoids. Pradofloxacin had anti-M hemofelis effects similar to those of doxycycline. In addition, pradofloxacin may be more effective at long-term M hemofelis organism clearance than doxycycline.

Effects of chronic expression of the HIV-induced protein, transactivator of transcription, on circadian activity rhythms in mice, with or without morphine

Patients with human immunodeficiency virus (HIV) infection exhibit changes in sleep patterns, motor disorders, and cognitive dysfunction; these symptoms may be secondary to circadian rhythm abnormalities. Studies in mice have shown that intracerebral injection of an HIV protein, transactivator of transcription (Tat), alters the timing of circadian rhythms in a manner similar to light. Therefore, we tested the hypothesis that chronic Tat expression alters circadian rhythms, especially their entrainment to a light-dark (LD) cycle, by using transgenic mice in which Tat expression in the brain was induced via a doxycycline (DOX)-sensitive, glial fibrillary-associated, protein-restricted promoter. Because opiate substance abuse, which shares comorbidity with HIV infection, also disrupts sleep, a final experiment assessed the effects of morphine exposure on circadian rhythms in wild-type and Tat transgenic mice. Mice housed in cages equipped with running wheels were fed chow with or without DOX. Experiment 1 revealed a small but significant (P < 0.05) difference between groups in the phase angle of entrainment and a 15% decrease in the wheel running in the DOX group (P < 0.005). During exposure to constant darkness, DOX did not alter the endogenous period length of the circadian rhythm. Experiment 2 investigated the effect of DOX on circadian rhythms in wild-type and Tat(+) mice during exposure to a normal or phase-shifted LD cycle, or morphine treatment without any change in the LD cycle. Tat induction significantly decreased wheel running but did not affect entrainment to the normal or shifted LD cycle. Morphine decreased wheel running without altering the phase angle of entrainment, and the drug's effects were independent of Tat induction. In conclusion, these findings suggest that chronic brain expression of Tat decreases locomotor activity and the amplitude of circadian rhythms, but does not affect photic entrainment or reentrainment of the murine circadian pacemaker.

Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial

Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis. From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00138801. Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8.5 [SD 4.1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4.5 (95% CI 3.6 to 5.5) points and that in the ceftriaxone group (n=48) was 4.4 (3.4 to 5.4) points (95% CI for difference between groups -0.9 to 1.1; p=0.84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups -4% to 34%; p=0.13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (-28% to 9%; p=0.30). Three patients discontinued ceftriaxone treatment owing to adverse events. Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis.

Inhibition of Experimental Angiogenesis of Cornea by Various Doses of Doxycycline and Combination of Triamcinolone Acetonide With Low-molecular-weight Heparin and Doxycycline

To evaluate the effect of topically administered doxycycline in various doses; the combination of triamcinolone acetonide and low-molecular-weight heparin (LMWH); and the combination of triamcinolone acetonide and doxycycline on experimental corneal neovascularization in rats. This project is the combination of 2 separate studies. First, the chemical cauterization of corneas in 36 eyes of 36 Long Evans male rats was performed by using silver nitrate/potassium nitrate sticks. Topical instillation of doxycycline at 0.05% (pH = 3.3), 0.1% (pH = 3.1), 1% (pH = 2.3), 2% (pH = 2.1), 2% (pH neutralized to 7.4), and normal saline continued for 7 days. Second, the chemical cauterization of the corneas in 24 eyes of 24 rats was achieved by application of silver nitrate/potassium nitrate sticks. Topical instillation of triamcinolone acetonide (10 microg/mL) and either LMWH (10 mg/mL) or doxycycline (10 mg/mL) was compared with normal saline treatment of 7 days. For both studies, the percent area of the cornea covered by neovascularization and scar in each group was calculated separately by using computer software on digital photographs. All corneas were evaluated histopathologically in study and control groups. The mean percent area of corneal neovascularization determined in the eyes given doxycycline 0.05%, 0.1%, 1%, 2%, and 2% (pH neutralized) study groups and control groups was 69.8% +/- 18.0%, 64.5% +/- 14.0%, 56.4% +/- 20.8%, 54.8% +/- 6.0%, 36.2% +/- 4.3%, and 69.4% +/- 5.7%, respectively. The mean of percent area of neovascularization in the 2% doxycycline (pH neutralized) doxycycline group was significantly less than that of the control group and the <1% doxycycline concentrations (P < 0.05). The percent corneal neovascularization in the 2% (pH neutralized) doxycycline group was not significantly different from that of the 1% and 2% doxycycline groups (P < 0.05). There was no significant difference in percent area of corneal scar between control and study groups (P > 0.05). The mean percent area of corneal neovascularization in triamcinolone acetonide and LMWH, triamcinolone acetonide and doxycycline, and control groups was 2.35% +/- 4.42%, 9.42% +/- 6.8%, and 64.7% +/- 10.0%, respectively. The mean percent area of neovascularization in the triamcinolone acetonide plus LMWH or triamcinolone acetonide plus doxycycline groups was significantly different from that of the control group (P = 0.001 for both). There was no significant difference between study groups with regard to percent area of neovascularization or percent area of corneal scar between the control and study groups. Topically administered combinations of triamcinolone acetonide plus LMWH or triamcinolone acetonide plus doxycycline had effects that contributed to efficient suppression of corneal neovascularization; these drugs were ineffective at similar concentrations used alone. Topically administered 2% (pH neutralized) doxycycline has antiangiogenic effects, which contributed to significant suppression on corneal neovascularization. This drug may be therapeutically beneficial in treatment of corneal neovascularization in clinical trials.

Long-Term Doxycycline Is More Effective Than Atenolol to Prevent Thoracic Aortic Aneurysm in Marfan Syndrome Through the Inhibition of Matrix Metalloproteinase-2 and -9

Beta-blockers, eg, atenolol, are the cornerstone therapy for thoracic aortic aneurysm (TAA) in patients with Marfan syndrome; however, continued aortic dilatation has been reported. We have demonstrated that matrix metalloproteinase (MMP)-2 and -9 were upregulated during progression of TAA in Marfan syndrome, accompanied with degenerated elastic fibers and vasomotor dysfunction. We hypothesized that doxycycline, a nonspecific inhibitor of MMPs, would ameliorate TAA by attenuating elastic fiber degeneration and improving vasomotor function. A well-characterized mouse model of Marfan syndrome (Fbn1(C1039G/+)) was used. Mice were untreated (n=40), given doxycycline (0.24 g/L, n=30), or given atenolol (0.5 g/L, n=30) in drinking water at 6 weeks of age. The Fbn1(+/+) mice served as control (n=40). At 3, 6, and 9 months, aortic segments from the ascending, arch, and descending portions were used to obtain the "average" value of the whole thoracic aorta. TAA was prevented in the doxycycline group, whereas mild aneurysm was evident in the atenolol group. Doxycycline improved elastic fiber integrity, normalized aortic stiffness, and prevented vessel weakening. The impairment of vasocontraction and endothelium-dependent relaxation in the untreated and atenolol groups were improved by doxycycline. The upregulation of transforming growth factor-beta in the Marfan aorta was suppressed by doxycycline. Doxycycline augmented expression ratios of tissue inhibitors of MMP to MMPs. Intraperitoneally injected neutralizing antibodies against MMP-2 and -9 yielded similar effects to doxycycline. We concluded that long-term treatment with doxycycline, through the inhibition of MMP-2 and -9, is more effective than atenolol in preventing TAA in Marfan syndrome by preserving elastic fiber integrity, normalizing vasomotor function, and reducing transforming growth factor-beta activation.

Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole

Melioidosis, a potentially fatal disease of humans and animals, is caused by the gram-negative bacterium, Burkholderia pseudomallei. There is no approved vaccine or effective prophylaxis. Given its potential as a bioterrorism agent and a cause of serious laboratory-acquired infection, we studied the efficacy of pre- and post-exposure oral antibiotic prophylaxis in BALB/c mice infected with aerosolized B. pseudomallei through the inhalational route. Amoxicillin/clavulanic acid, doxycycline or co-trimoxazole was administered 48 h before infection as pre-exposure prophylaxis, orally, twice daily and continued up to 10 days post-challenge. In the post-exposure prophylaxis regimen, the oral antibiotics were administered twice daily, at 0, 10, 24 and 48 h and continued for 10 days. Survival of all animals was observed until 21 days. All infected control animals developed infection between 24 and 48 h, and died within 5 days. Animals receiving amoxicillin/clavulanic acid as pre-exposure prophylaxis succumbed to the disease at day 7, whereas those in the co-trimoxazole and doxycycline groups had survival rate of 100% and 80%, respectively, at day 21. As post-exposure prophylaxis, all antibiotics were not effective when treatment was initiated 48 h post-challenge. However, animals receiving co-trimoxazole had a 100% survival rate when the antibiotic was started 0, 10 and 24 h post-infection, and amoxicillin/clavulanic acid was the least effective. Co-trimoxazole appears to be an effective oral antibiotic both as pre- and post-exposure prophylaxis to B. pseudomallei. Data derived from this study have important implications on the management of laboratory accidents or following an intentional release of B. pseudomallei, a potential bioterrorism agent.

A Randomized Double Blind Controlled Trial to Compare Metronidazole with Doxycycline for the Treatment of Oral Lichen Planus

The aim of this study was to compare the efficacy of metronidazole with doxycycline in treatment of oral lichen planus. A double blind clinical trial was performed on twenty patients with asymptomatic oral lichen planus, confirmed by biopsy. After initial examination, patients were randomly assigned to receive 250 mg metronidazole or 100 mg doxycycline twice daily for 4 weeks. Target lesions were assessed at weeks 0, 2, 4 by grid measurement. Complete blood examination and liver function tests were done at fourth week. At the end of the trial, in the doxycycline group one (10%) patient showed partial remission and nine (90%) patients showed no response. In the metronidazole group one (10%) patient showed partial remission and one (10%) patient showed completed remission. Eight (80%) patients were unresponsive to metronidazole. No side-effects were reported from the subjects and there were no significant changes in complete blood examination and liver function test after four weeks of treatment in either group. Results of present study suggest that these drugs are not much effective in treatment of oral lichen planus and statistically significant difference was not seen between the two groups in respect to response to therapy at the end of treatment period (p>0.05, p = 0.503).

Inhibitory Effect of Oral Doxycycline on Neovascularization in a Rat Corneal Alkali Burn Model of Angiogenesis

Purpose: To examine the efficacy of oral doxycycline treatment (as compared to oral and topical dexamethasone) for inhibiting corneal neovascularization (CNV). Methods: Following corneal alkali burn, rats were treated daily with oral doxycycline, oral dexamethasone, or topical dexamethasone for 14 days. Control rats were injured but were not treated. At days 3, 7, and 14 post injury, length and area of CNV were evaluated, as well as corneal epithelial healing and ulceration. Tissues were obtained from a subset of rats from each group for histopathological analysis. Results: At days 7 and 14 post-injury, CNV length in the doxycycline group was significantly less than in the untreated control (p < 0.008). The area of CNV was significantly smaller in doxycycline as compared to control rats on days 3, 7, and 14 post-injury. Inhibition of CNV (indicated by area and length) was significantly greater in both dexamethasone groups compared to the doxycycline group (p < 0.008 for all comparisons). However, epithelial healing was significantly more rapid in the doxycycline group compared to both dexamethasone groups (p < 0.008). Epithelial ulceration was apparent in both oral and topically treated dexamethasone rats, but not in doxycycline-treated rats. Conclusions: Oral doxycycline inhibits CNV without the harmful side effects associated with dexamethasone use. Further investigation is warranted to assess the mechanisms through which doxycycline acts to cause CNV inhibition, and the applicability of doxycycline use for treating CNV in the clinical setting.

In Vivo Evidence for the Role of CD44s in Promoting Breast Cancer Metastasis to the Liver

The hyaluronan receptor CD44 plays an important role in facilitating invasion and metastasis of a variety of tumors, including breast carcinomas. CD44 functions as a bioactive signaling transmitter. Although a number of studies have implicated CD44 in breast tumor invasion, the evidence is still circumstantial. We have developed a tetracycline-regulated CD44s (standard form) system in the weakly metastatic breast cancer cell MCF7, which exhibits low endogenous expression of CD44 and generated a new cell line, MCF7F-B5. Induction of CD44s alone affected the growth characteristics of MCF7F-B5 cells by increasing their abilities to proliferate, migrate, and invade in vitro. In addition, we have identified and validated cortactin as a novel transcriptional target of hyaluronan/CD44s signaling in underpinning breast tumor invasion. To test these observations in vivo, we developed a doxycycline (DOX)-regulated CD44s breast cancer xenograft model. Induction of CD44s did not affect the growth rate or local invasion of the primary tumor. However, although no mice from the +DOX group developed metastasis, 8 of 11 mice from the -DOX group developed secondary tumors to the liver only. Interestingly, metastatic breast tumors expressed high levels of CD44. This study provides in vivo evidence for the role of the standard form of CD44 in promoting breast tumor invasion and metastasis to the liver.

Abstract 1166: In-vivo Serial Assessment of Aortic Aneurysm Formation in a Hyperlipidimic Mouse Model

Introduction Abdominal aortic aneurysms (AAA) can be consistently produced in hyperlipidimic mice by continuous infusion of Angiotensin-II (Ang-II). MRI allows for AAA visualization in-vivo with sufficient spatial resolution to assess changes in aneurysm size and morphology. Bright-blood contrast allows for detection of medial breaks, an index of AAA severity, and USPIO contrast agent uptake allows for detection of macrophage activity in AAA. For this study we used MRI to characterize AAA development in a murine model and examined the effect of the broad-based MMP inhibitor, doxycycline, on AAA progression over a 4 week period. Methods Osmotic pumps were implanted subcutaneously in ApoE−/− mice for infusion of Ang-II (1000 ng/kg/min) over 4 weeks. Animals were given 30 mg/kg/day doxycycline or vehicle (n=15 per group) via drinking water. Weekly scans were performed using a 9.4T MRI scanner. In addition, uptake of USPIO (Combidex, 1000 μmol/kg) in AAA was measured. Results MRI revealed two distinct features of AAA development: remodeling of the adventitia which compresses the aortic lumen (Fig 1B ) and a break in the medial wall characterized by bright-blood signal within the AAA (Fig 1C ). Higher incidence of AAA formation in the vehicle vs. doxycycline group was detected along with a significantly larger (P&lt;.01) AAA area. For mice given USPIO, MRI revealed signal loss in the periphery and shoulder region of the AAA which corresponded to macrophage rich regions as determined by IHC. Conclusion These results demonstrate MRI’s potential for non-invasively and temporally assessing AAA development and pharmacological intervention in this pre-clinical cardiovascular disease model.

Evaluation of Azithromycin in Treatment of Acne Vulgaris Compared to

Introduction: Acne vulgaris is the most common dermatological disorder in adolescence. Treatment is essential to prevent physical and psychological scarring. Although many treatments for acne are available, effective management has become increasingly challenging with the emergence of antibiotic-resistant strains of Propnionibacterium acnes. Aim: The aim of this study is to evaluate the efficacy of oral azithromycin in acne by comparing its effect with the most common therapy used for acne; doxycycline. Method: An opened label randomized comparative study was carried out in 40 patients of mild, moderate and Sever acne vulgaris divided into two groups, group (A) 20 patients received azithromycin capsules in a specified and scheduled dose regimen and group (B) 20 patients administered doxycycline tablets as a usual regimen of therapy. Results: The results obtained from oral azithromycin therapy when compared with oral doxycycline showed that there was statistically no difference between the two drugs in response at end of 22 weeks. The overall efficacy measured in terms of reduction of the severity of condition was up to 83% with azithromycin compared to 50% with doxycycline. In assessment of adverse effects and dropped-out rates the higher dropped- out rate was found in doxycycline group. Also the patients’ opinion as an outcome measure confirmed that most of patients felt much better with azithromycin. Conclusion: The conclusion from the present study is that oral azithromycin provides additionally effective and safe treatment option to the patients, and benefits may be further extended to those patients not responding to currently recommended antibiotic therapy. Sudan Joural of Medical Studies Vol. 2 (1) 2007: pp. 29-31