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Selected AbstractsEffects of sub-antimicrobial dose doxycycline therapy on crevicular fluid MMP-8, and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitisJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2004Dong-Hoon Choi Objective:, To investigate whether sub-antimicrobial dose doxycycline (SDD) therapy for 120 d in chronic adult periodontitis patients had significant effects on gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) levels, and on gingival tissue MMP-9, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and interleukin-6 (IL-6) levels. Background:, Tetracycline can significantly inhibit MMP activity in GCF and in gingival tissue, even in much lower dosage then a traditional antimicrobial dosage used in conventional therapy. Sub-antimicrobial dose doxycycline (SDD) therapy has been shown to reduce periodontal disease activity to control MMP and pro-inflammatory cytokines. Methods:, A total of 32 patients with incipient to moderate (probing pocket depth ,,4,7 mm) chronic adult periodontitis were included in the study. Subjects were randomly assigned to two groups. After scaling and root planning (SRP), the SRP + SDD group received SDD, 20 mg bid, whereas the SRP + placebo group received placebo, 20 mg bid. In the follow-up, efficacy measures included the change in probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and gingival crevicular fluid MMP-8 levels, gingival tissue MMP-9, TIMP-1 and IL-6 levels from baseline to 120 d. Results:, After 120 d, PD and CAL improved significantly in the SRP + SDD group. Initial MMP-8 levels for the SRP + SDD group and the SRP + placebo group were 407.13 ± 114.45 ng/ml and 378.71 ± 189.39 ng/ml, respectively, with no statistical difference between the two groups. MMP-8 levels for the SRP + SDD group and the SRP + placebo group were: 235.35 ± 134.58 ng/ml and 364.04 ± 219.27 ng/ml at 30 d; 157.50 ± 95.95 ng/ml and 236.60 ± 186.16 ng/ml at 60 d; 102.70 ± 67.64 ng/ml and 208.56 ± 124.54 ng/ml at 90 d; and 63.77 ± 53.33 ng/ml and 229.13 ± 168.09 ng/ml at 120 d, respectively. The amount of decrease in MMP-8 levels for the SRP + SDD group was statistically significant compared to that for the SRP + placebo group, especially apparent at 120 d (p < 0.05). TIMP-1 levels in both groups increased from the baseline to 120 d with statistical significance (p -value < 0.05), but there was no significant difference between the two groups. Changes in MMP-9 and IL-6 levels were not statistically significant. Conclusion:, Adjunctive SDD therapy can improve the clinical parameters and this clinical improvement is reflected by controlled level of MMP-8 in chronic adult periodontitis after the therapy. [source] Oral mucosa alterations induced by cyclosporin in mice: morphological featuresJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2002A. T. Meller Background and objective:, The mechanisms involved in the pathogenesis of cyclosporin A-induced gingival hyperplasia are not well understood. The present work aimed at developing a mouse model with the characteristics of the human process, i.e. time of appearance, dose dependency and the capacity of developing in a variety of genetic backgrounds. This model would present the advantages of using a very well known animal species, small and easy to handle, with a number of experimental reagents (antibodies, etc.) already available against its products. Methods:, Three different strains of mice were used: CBA, F1(C57Bl × DBA), Balb/c. Groups of mice received different concentrations of cyclosporin A (CSA) (10 mg/kg, 25 mg/kg and 40 mg/kg body weight) intraperitoneally five times a week. Anatomical and histological alterations were recorded at various time intervals. Results:, All strains of mice presented gingival hyperplasia after 8 weeks of CSA treatment. A dose-dependency was observed with regard to the time of first appearance of alterations. Increased redness was seen in all animals at the sixth week, independent of the dosage used. Histologic examination exhibited increased vascularization, epithelial and connective tissue thickening, edema and a mononuclear infiltrate. Conclusions:, It was possible to develop CSA-induced gingival hyperplasia in mice with the characteristics described in humans and other species. The use of this animal model may help in the elucidation of the process involved in CSA-induced gingival overgrowth. [source] Therapeutic drug monitoring of tacrolimus in pediatric liver transplant patientsPEDIATRIC TRANSPLANTATION, Issue 2 2001Gordon D. MacFarlane Abstract: The clinical utility of tacrolimus monitoring in adults has been well documented. The present study compared tacrolimus monitoring in a pediatric population of 34 liver transplant patients in four US centers with an adult population of 111 patients in six US centers. Subjects (adult and pediatric) were evaluated, at defined intervals over 12 weeks post-transplantation (Tx), for tacrolimus trough concentrations and 12 additional laboratory chemistries. Pediatric patient and graft survival for the 12 weeks were 91% and 88%, respectively, as compared to 97% and 93%, respectively, for the adult population. The mean oral dosage of tacrolimus for pediatric patients was 0.13 ± 0.1 mg/kg/day at week 1, increased to 0.30 ± 0.3 mg/kg/day by week 3 and remained constant for the remainder of the study. These dosages were two- to three-fold higher than the dosage used in the adult population. In contrast, the mean whole-blood trough concentration, as determined by PRO-TracÔ II enzyme-linked immunosorbent assay (ELISA), decreased from 11.3 ± 5.1 ng/mL at week 1 to 6.3 ± 3.7 ng/mL by week 12 and was not significantly different from the trough concentration in adults. The incidence and distribution of the clinical end-points for the pediatric subjects (rejection, nephrotoxicity, death, re-Tx) were different from those observed in adults. The total percentage of pediatric subjects reaching any end-point was 74%, as compared to 54% in the adult population. These data indicate several differences between the adult and pediatric populations in their response to tacrolimus. [source] Systematic review on the safety of Harpagophytum preparations for osteoarthritic and Low back painPHYTOTHERAPY RESEARCH, Issue 2 2008J. Vlachojannis Abstract Harpagophytum products are a treatment option for osteoarthritic and low back pain. The aim of this study was to review the safety of treatment with Harpagophytum procumbens. The databases OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for studies with Harpagophytum procumbens. Twenty-eight clinical trials were identified of which 20 stated adverse events. In none of the double-blind studies was the incidence of adverse events during treatment with Harpagophytum procumbens higher than during placebo treatment. Minor adverse events occurred in around 3% of the patients, mainly gastrointestinal adverse events. A few reports of acute toxicity were found but there were no reports on chronic toxicity. Since the dosage used in most of the studies is at the lower limit and since long-term treatment with Harpagophytum products is advisable, more safety data are urgently needed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Efficacy of traditional and biologic agents in different clinical phenotypes of adult-onset Still's diseaseARTHRITIS & RHEUMATISM, Issue 8 2010Stefano Franchini Objective To evaluate the efficacy of antiinflammatory agents, steroids, immunosuppressants, and biologic agents in patients with adult-onset Still's disease (AOSD) who have either chronic articular disease or nonchronic disease. Methods Forty-five patients with AOSD were seen and followed up for at least 2 years at our institution, from 1991 to 2008. The majority of patients were treated with several therapeutic regimens; a total of 152 efficacy trials were administered. Data regarding the type of medication, the dosage used, and the outcome of these trials were collected and analyzed. Results Our data showed that the efficacy of monotherapy with a nonsteroidal antiinflammatory drug was very low (16%) and confirmed good efficacy of steroid therapy (63%), particularly in patients without chronic articular disease (78%). Patients whose disease did not respond to steroid therapy at the time of disease onset were at risk of the subsequent development of chronic arthritis. Disease-modifying antirheumatic drug (DMARD) monotherapy was successful in controlling steroid-resistant or steroid-dependent disease in 60% of patients. Methotrexate and cyclosporine showed the best response rates. The combination of high-dose steroids and cyclosporine was administered to successfully control some acute life-threatening complications. Only 6 patients had disease that was both steroid resistant and DMARD resistant. Treatment with biologic agents eventually led to satisfactory control of disease manifestations in 5 (83%) of these 6 patients. Conclusion Steroids were less effective in patients with chronic articular disease than in those with nonchronic disease. The administration of DMARDs early after disease onset could be beneficial in patients with steroid-resistant disease who are at risk of the development of chronic articular disease. Biologic agents proved to be highly effective in both steroid-resistant and DMARD-resistant AOSD. [source] Studies of Photokilling of Bacteria Using Titanium Dioxide NanoparticlesARTIFICIAL ORGANS, Issue 2 2008Yang-Hwei Tsuang Abstract:, Metal pins used to apply skeletal traction or external fixation devices protruding through skin are susceptible to the increased incidence of pin site infection. In this work, we tried to establish the photokilling effects of titanium dioxide (TiO2) nanoparticles on an orthopedic implant with an in vitro study. In these photocatalytic experiments, aqueous TiO2 was added to the tested microorganism. The time effect of TiO2 photoactivation was evaluated, and the loss of viability of five different bacteria suspensions (Escherichia coli, Pseudomonas aeruginosa, Staphylococus aureus, Enterococcus hirae, and Bacteroides fragilis) was examined by the viable count procedure. The bactericidal effect of TiO2 nanoparticle-coated metal plates was also tested. The ultraviolet (UV) dosage used in this experiment did not affect the viability of bacteria, and all bacteria survived well in the absence of TiO2 nanoparticles. The survival curve of microorganisms in the presence of TiO2 nanoparticles showed that nearly complete killing was achieved after 50 min of UV illumination. The formation of bacterial colonies above the TiO2 nanoparticle-coated metal plates also decreased significantly. In this study, we clearly demonstrated the bactericidal effects of titanium dioxide nanoparticles. In the presence of UV light, the titanium dioxide nanoparticles can be applicable to medical facilities where the potential for infection should be controlled. [source] Comparison of Routes of Flumazenil Administration to Reverse Midazolam-induced Respiratory Depression in a Canine ModelACADEMIC EMERGENCY MEDICINE, Issue 5 2000Melanie S. Heniff MD ABSTRACT Objective: To determine whether flumazenil, a drug used to reverse benzodiazepine-induced respiratory depression and approved only for IV use, is effective by alternative routes. Methods: A randomized, controlled, nonblinded, crossover canine trial was performed to evaluate reversal of midazolam-induced respiratory depression by flumazenil when administered by alternative routes. Mongrel dogs were sedated with thiopental 19 mg/kg IV, then tracheally intubated. With the dogs spontaneously breathing, tidal volume, end-tidal CO2, and O2 saturation were observed until a stable baseline was achieved. Incremental doses of midazolam were administered until respiratory depression (30% decline in tidal volume, 10% decrease in O2 saturation, and 15% increase in end-tidal CO2) occurred. Flumazenil was administered by a randomly selected route [0.2 mg followed 1 minute later by 0.3 mg IV, sublingual (SL) or intramuscular (IM); or 1 mg followed 1 minute later by 1.5 mg per rectum (PR)]. Time to return to baseline respiratory functions was recorded ("time to reversal"). Each of 10 dogs was studied using all 4 routes of flumazenil administration with a washout period of at least 7 days. An additional dog served as a control (no flumazenil). Results: The control time to reversal was 1,620 seconds. The IV route was significantly faster (mean 120 ± 24.5 sec) than the other 3 routes (p < 0.005). The SL route was the second fastest (mean 262 ± 94.5 sec), the IM route was the third fastest (mean 310 ± 133.7 sec), and the PR route was the slowest (mean 342 ± 84.4 sec). The SL, IM, and PR routes did not differ significantly from one another. Conclusions: Flumazenil administered by all 4 routes reversed midazolam-induced respiratory depression in a dog model. For the selected dosages used, the IV route was significantly faster than all 3 other routes, and SL was the second fastest. [source] Evodia rutaecarpa protects against circulation failure and organ dysfunction in endotoxaemic rats through modulating nitric oxide releaseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2002Wen Fei Chiou Using a rat model of septic shock we studied the effects of Evodia rutaecarpa, a Chinese herbal medicine with antimicrobial and anti-inflammatory activity, on haemodynamic parameters, biochemical markers of organ function and nitric oxide (NO) production. Anaesthetized rats challenged with a high dosage of endotoxin (Escherichia coli lipopolysaccharide; LPS; 50 mg kg,1, i.v.) for 6 h showed a severe decrease in mean arterial pressure. This was accompanied by delayed bradycardia, vascular hyporeactivity to phenylephrine and increase in plasma levels of lactate dehydrogenase, aspartate aminotransferase, bilirubin and creatinine, as well as NOx (NO,2 plus NO,3). Pretreatment with ethanol extract of E. rutaecarpa (25,50 and 100 mg kg,1, i.v.), 1 h before LPS, dose-dependently prevented the circulation failure, vascular hyporeactivity to phenylephrine, prevented liver dysfunction and reduced the NOx over-production in plasma in endotoxaemic rats. A selective inducible NO-synthase (iNOS) inhibitor, aminoguanidine (15 mg kg,1, i.v.), also effectively ameliorated the above pathophysiological phenomenon associated with endotoxaemia so that the normal condition was approached. Endotoxaemia for 6 h resulted in a significant increase in iNOS activity in the liver homogenate, which was attenuated significantly by E. rutaecarpa pretreatment. In summary, E. rutaecarpa, at the dosages used, exerted these beneficial effects probably through inhibition of iNOS activity and subsequent modulation of the release of NO. These significant results may offer E. rutaecarpa as a candidate for the treatment of this model of endotoxaemia. [source] Combination Therapy with Digoxin and Diltiazem Controls Ventricular Rate in Chronic Atrial Fibrillation in Dogs Better than Digoxin or Diltiazem Monotherapy: A Randomized Crossover Study in 18 DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009A.R.M. Gelzer Background: Atrial fibrillation (AF) with excessively high ventricular rates (VR) occurs in dogs with advanced heart disease. Rate control improves clinical signs in these patients. Optimal drug therapy and target VR remain poorly defined. Hypothesis: Digoxin-diltiazem combination therapy reduces VR more than either drug alone in dogs with high VR AF. Animals: Eighteen client-owned dogs (>15 kg) with advanced heart disease, AF, and average VR on 24-hour Holter > 140 beats per minute (bpm). Methods: After baseline Holter recording, dogs were randomized to digoxin or diltiazem monotherapy, or combination therapy. Repeat Holter evaluation was obtained after 2 weeks; dogs were then crossed over to the other arm (monotherapy or combination therapy) for 2 weeks and a third Holter was acquired. Twenty-four hour average VR, absolute and relative VR changes from baseline, and percent time spent within prespecified VR ranges (>140, 100,140, and <100 bpm) were compared. Correlations between serum drug concentrations and VR were examined. Results: Digoxin (median, 164 bpm) and diltiazem (median, 158 bpm) decreased VR from baseline (median, 194 bpm) less than the digoxin-diltiazem combination (median, 126 bpm) (P < .008 for each comparison). With digoxin-diltiazem, VR remained <140 bpm for 85% of the recording period, but remained >140 bpm for 88% of the recording period with either monotherapy. Serum drug concentrations did not correlate with VR. Conclusions and Clinical Importance: At the dosages used in this study, digoxin-diltiazem combination therapy provided a greater rate control than either drug alone in dogs with AF. [source] Antiepileptic drugs in Australia: 2002,2007,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2010Samantha A Hollingworth BSc (Hons) Abstract Purpose With the marketing of a number of new antiepileptic drugs (AEDs) in recent years it seemed possible that the pattern of Australian prescribing for patients with epilepsy may have been changing. We examined the trends in the prescribing of subsidised AEDs in the Australian population from 2002 to 2007. Methods We analysed the Medicare Australia and Drug Utilisation Sub-Committee databases for script data for AEDs from 2002 to 2007 in 5-year age groups by gender and by class of prescriber. Scripts were converted to defined daily doses (DDDs)/1000/day using Australian Bureau of Statistics population data. Results Overall AED use (mainly valproate, lamotrigine and levetiracetam) increased progressively in 2002,2007 from 9.33 to 10.12 DDD/1000 population/day. Sodium valproate was the most widely used agent followed by carbamazepine then phenytoin. Amount of AED used increased in those aged in their 20s and 30s to plateau between 40 and 90 years. Use peaked in those aged 80,84 years and was slightly higher in males than females. Conclusions The rate of increase in the prescribing of AEDs remained steady between 2002 and 2007. The gender differences in prescribing reflect the higher prevalence of epilepsy in men and higher individual dosages used when many AEDs are prescribed on a body weight basis. The high use of some of these drugs in elderly people (,80 years) warrants further exploration. There is growing use of lamotrigine and gabapentin for indications apart from epilepsy,most likely neuropathic pain and mood disorders. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effects of different dosages of astaxanthin on giant freshwater prawn Macrobrachium rosenbergii (De Man) challenged with Lactococcus garvieaeAQUACULTURE RESEARCH, Issue 1 2009Isagani P Angeles Jr Abstract The effects of astaxanthin (AX) injected at 0.67 and 1.34 nmol g,1 BW,1 on the survival, antioxidant capacity, total haemocyte count (THC) and hepatopancreas astaxanthin content of giant freshwater prawn, Macrobrachium rosenbergii, challenged with Lactococcus garvieae were evaluated. AX-injected M. rosenbergii at 1.34 nmol g,1 BW,1 had significantly (P,0.05) higher survival rates. However, AX showed no significant effects on the capacity of certain antioxidant indicators (superoxide dismutase, glutathione peroxidase and glutathione reductase). This implies that L. garvieae infection suppressed the activity of the haemolymph antioxidant system of infected M. rosenbergii. This result suggests that the two different dosages used in this study could not exert significant effects on the tested antioxidant capacity of L. garvieae -infected M. rosenbergii. On the other hand, AX-injected M. rosenbergii at either dose showed a significant increase in the THC and hepatopancreas AX content when compared with the challenged control group. Overall, the results of this study indicate that the injected AX led to an improvement in M. rosenbergii's resistance against L. garvieae infection. [source] A Comparison of Salicylic Acid Levels in Normal Subjects after Rectal versus Oral DosingACADEMIC EMERGENCY MEDICINE, Issue 2 2009Roger Maalouf MD Abstract Objectives:, The common practice is to use 162 mg of aspirin orally in the emergency department (ED) for patients presenting with myocardial infarction. If the patient cannot take aspirin orally in the authors' facility, then 600 mg of aspirin is given rectally. However, no strong evidence exists as to whether the oral and rectal doses provide equivalent risk protection. The authors hypothesized that the salicylic acid levels for orally and rectally administered aspirin will not be similar, because of the different dosages used and the different routes of administration. Methods:, The study sample consisted of healthy, nonpregnant, adult volunteers without active illness, who did not take any medication regularly. Each subject served as his or her own control to account for any confounding factors. The study was conducted on 2 days, separated by a 1-week washout period. On the first day, 162 mg of oral aspirin was chewed and swallowed. Salicylic acid levels were obtained at baseline (i.e., before taking the aspirin) and then 30, 60, and 90 minutes after dosing. The 600-mg aspirin suppository was self-administered 1 week later with a sample for laboratory measures again drawn at baseline and then 30, 60, and 90 minutes after dosing. Results:, Twenty-four subjects completed the study. The rectal suppository provided significantly more salicylic acid into the blood than the oral tablets over 90 minutes (p < 0.001). No statistical difference was noted between oral and rectal administration from baseline to 30 minutes (p > 0.05). However, mean salicylic acid levels from the rectal suppository were statistically higher than from the oral tablets from 30 to 60 minutes (p < 0.001) and from 60 to 90 minutes (p = 0.002). More than 60% of the subjects had an increasing salicylic acid level response over time to the rectal suppository. The salicylic acid level response to the oral administration was more evenly divided between those subjects whose salicylic acid levels peaked quickly and then fell or held steady (33%), those whose salicylic acid levels increased over time (29%), and those whose salicylic acid levels were measureable only after 60 minutes (25%). Although not statistically significant, these differences in group distributions for the type of salicylic acid level response between oral and rectal doses suggested the possibility of a rectal advantage. Conclusions:, Whether the higher salicylic acid levels and faster absorption of the rectal aspirin translate into better clinical outcomes is unknown and cannot be concluded from our study. Previous evidence, however, has shown that 162 mg of aspirin chewed and swallowed provided lower mortality in patients presenting with myocardial infarction. Our results suggested the rectal administration of a 600-mg suppository provides sufficient levels of salicylic acid within 90 minutes to meet or exceed that of oral aspirin. [source] | ||||||||||