Influence of Antiplatelet Drugs in the Pathogenesis of Experimental Periodontitis and Periodontal Repair in Rats

Background: Platelets contain an array of biologic mediators that can modulate inflammation and repair processes including proinflammatory mediators and growth factors. Previous studies have shown that periodontitis and periodontal repair are associated with platelet activation. We hypothesized that drug-induced platelet inactivation may interfere in the processes of inflammation and repair in experimental periodontitis in rats by suppressing the release of biologic mediators from platelets to the site of injury. Methods: To measure the effects on periodontitis, ligatures were placed around first molars, and aspirin (Asp, 30 mg/kg) or clopidogrel (Clo, 75 mg/kg) was given intragastrically once daily for 15 days. Interleukin-6 (IL-6), tumor necrosis factor-a (TNF-alpha), and thromboxane A(2) levels were measured by enzyme-linked immunosorbent assay. To evaluate the effects of antiplatelet drugs on periodontal repair, ligatures were removed after 15 days of periodontitis induction, and Asp or Clo were administered beginning the following day for 15 days. Periodontal repair was assessed by microcomputed tomography. Results: On periodontitis phase, Asp and Clo significantly reduced levels of TNF-alpha and II-6 (P < 0.05), but only Asp decreased thromboxane A(2) (P < 0.05). Asp and Clo decreased inflammatory infiltration; however, this reduction was more pronounced with Clo treatment (P < 0.05). Histometric analysis showed that Asp and Clo impaired alveolar bone resorption. During the repair phase and after removal of the ligatures, microcomputed tomography analysis demonstrated that treatment with Asp and Clo did not impair alveolar bone repair. Conclusion: Systemic administration of Asp and Clo attenuates the inflammation associated with periodontitis without affecting the repair process when stimulus is removed. J Periodontol 2011;82:767-777.

Beef Carcass Contamination by Shiga Toxin-Producing Escherichia coli Strains in an Abattoir in Brazil: Characterization and Resistance to Antimicrobial Drugs

A survey was performed to estimate the frequency of Escherichia coli and Shiga toxin-producing E. coli (STEC) in carcasses obtained from an abattoir in Brazil between February 2006 and June 2007. A total of 216 beef carcasses were sampled at three stages of the slaughter process-preevisceration, postevisceration, and postprocessing-during the rain and dry seasons, respectively. Of the carcasses sampled, 58%, were preevisceration E. coli positive, 38% were postevisceration positive, and 32% postprocessing positive. At the postprocessing stage, the isolation of E. coli was twice as high in the rain season. E. coli was isolated from 85 carcasses of which only 3 (1.4%) were positive for stx-encoding genes. No E. coli O157 serogroup isolates were detected. No antimicrobial resistance was found in nine of the isolates (10% of the total). The most frequent resistances were seen against cephalothin (78%), streptomycin (38%), nalidixic acid (36%), and tetracycline (30%). Multidrug resistance (MDR) to three or more antimicrobial agents was determined in 28 (33%) E. coli isolates. The presence of STEC and MDR strains among the isolates in the beef carcasses emphasizes the importance of proper handling to prevent carcass contamination.

Structure-hepatic disposition relationships for cationic drugs in isolated perfused rat livers: Transmembrane exchange and cytoplasmic binding process

This work studied the structure-hepatic disposition relationships for cationic drugs of varying lipophilicity using a single-pass, in situ rat liver preparation. The lipophilicity among the cationic drugs studied in this work is in the following order: diltiazem. propranolol. labetalol. prazosin. antipyrine. atenolol. Parameters characterizing the hepatic distribution and elimination kinetics of the drugs were estimated using the multiple indicator dilution method. The kinetic model used to describe drug transport (the two-phase stochastic model) integrated cytoplasmic binding kinetics and belongs to the class of barrier-limited and space-distributed liver models. Hepatic extraction ratio (E) (0.30-0.92) increased with lipophilicity. The intracellular binding rate constant (k(on)) and the equilibrium amount ratios characterizing the slowly and rapidly equilibrating binding sites (K-S and K-R) increase with the lipophilicity of drug (k(on) : 0.05-0.35 s(-1); K-S : 0.61-16.67; K-R : 0.36-0.95), whereas the intracellular unbinding rate constant (k(off)) decreases with the lipophilicity of drug (0.081-0.021 s(-1)). The partition ratio of influx (k(in)) and efflux rate constant (k(out)), k(in)/k(out), increases with increasing pK(a) value of the drug [from 1.72 for antipyrine (pK(a) = 1.45) to 9.76 for propranolol (pK(a) = 9.45)], the differences in k(in/kout) for the different drugs mainly arising from ion trapping in the mitochondria and lysosomes. The value of intrinsic elimination clearance (CLint), permeation clearance (CLpT), and permeability-surface area product (PS) all increase with the lipophilicity of drug [CLint (ml . min(-1) . g(-1) of liver): 10.08-67.41; CLpT (ml . min(-1) . g(-1) of liver): 10.80-5.35; PS (ml . min(-1) . g(-1) of liver): 14.59-90.54]. It is concluded that cationic drug kinetics in the liver can be modeled using models that integrate the presence of cytoplasmic binding, a hepatocyte barrier, and a vascular transit density function.

Ring flexibility within tricyclic antidepressant drugs

The internal flexibility of the central seven-membered ring of a series of tricyclic antidepressant drugs (TCAs), imipramine {l}, amitriptyline {2}, doxepin {3}, and dothiepin {4}, has been investigated by H-1 and C-13 nuclear magnetic (NMR) techniques. Two dynamic processes were examined: ring inversion and bridge flexing. H-1 NMR lineshape analysis was used to obtain ring inversion barriers for 2-4. These studies yielded energy barriers of 14.3, 16.7, and 15.7 +/- 0.6 kcal/mol for the hydrochloride salts of doxepin, dothiepin, and amitriptyline, respectively. The barriers for the corresponding free bases were lower by 0.6 kcal/mol on average. (CT1)-C-13 relaxation measurements were used to determine the degree of bridge flexing associated with the central seven-membered ring for all four compounds. By fitting the T-1 data to a two-state jump model, lifetimes and amplitudes of rapid bridge flexing motions were determined. The results show that imipramine has the fastest rate of bridge flexing, followed by amitriptyline, doxepin, and dothiepin. The pharmacological profiles of the TCAs are complex and they interact with many receptor sites, resulting in numerous side effects and a general lack of understanding of their precise mode of action in different anxiety-related disorders. They all have similar three-dimensional structures, which makes it difficult to rationalize their differing relative potency in different assays/clinical settings. However, the clear finding here that there are significantly different degrees of internal mobility suggests that molecular dynamics should be an additional factor considered when trying to understand the mode of action of this clinically important family of molecules. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:713-721, 2001.

Effect of gender on ownership and income in veterinary practice

Objective To estimate the effect of gender on ownership and income in veterinary practice in Australia. Methods Questionnaire completed by private veterinary practitioners, and analysed using the SAS System for Windows 7.0. Results More than three-quarters (78%) of male but 36% of female private practitioners were partial or sole owners of practices. The median annual income for all male practitioners working more than 40 hours/week was $70K, but that for females was $43K. These disparities existed in both city and country practices, and in the case of income it increased with increasing time in the workforce. Male practice owners also reported higher incomes than female owners. Conclusions Female veterinary practitioners are less likely to own practices, and more likely to earn low incomes than males. These differentials do not appear to be due to location, hours worked or years since graduation or, in the case of income, to whether they are owners or employees. The evidence points to a lower interest by women than men in the business aspects of veterinary practice.

Veterinary employment patterns

Rolls and electronic records of The Veterinary Surgeons Board of Queensland between 1940 and 2000 were analysed to identify changes in the numbers and employment patterns of veterinarians. The number of veterinarians increased at a much more rapid rate than the population and on a state-wide level reached a plateau a decade ago at 340 per million. A plateau has not been reached in the capital city of Brisbane. The percentage of veterinarians employed with government funds has decreased, and the percentage of private practitioners increased to more than 80%. In 2000, single veterinarian practices represented 50% of all practices and 24% of practitioners. Women represented less than 10% of Queensland veterinarians until 1980, but 33% in 2000, and they are in higher concentration in Brisbane than elsewhere in the state.

Thiazolidinediones and type 2 diabetes: new drugs for an old disease

Thiazolidinediones are a new class of drugs for the treatment of type 2 diabetes, and act by improving insulin sensitivity in adipose tissue, liver and skeletal muscle. Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin. There is level II evidence that in patients with inadequate glycaemic control both drugs reduce the level of HbA(1c) and fasting plasma glucose (FPG) when used as monotherapy and in combination with sulfonylurea or metformin or insulin; and both drugs increase levels of HDL and LDL and lower free fatty acid levels, but only pioglitazone significantly lowers triglyceride levels. Both drugs lower fasting insulin and C-peptide levels. In monotherapy, they may be slightly less potent at reducing the level of HbA(1c) than sulfonylureas or metformin. The maximal effect of these agents may not be seen for 6-14 weeks after commencement. Both drugs are well tolerated but liver function must be checked at baseline every second month for the first year, and periodically thereafter. The drugs are currently contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation and in children. The main side effects include weight gain, oedema, and mild dilutional anaemia.

The role of handouts, note-taking and overhead transparencies in veterinary science lectures

Objective To study student and staff views of the role and use of handouts, note-taking and overhead transparencies in veterinary science lectures at the University of Queensland Methods The Nominal Group Technique was used to help develop a questionnaire, which was completed by 351 students (a response rate of 84%) and 35 staff (76%) from the 5 years of the veterinary course. The data were analysed using the SAS statistical computer package. Results Staff and students held different views as to the frequency with which handouts should be used, their educational value, and whether they should be complete or partial. Fewer students than staff agreed that handouts discourage further reading in a subject. Almost all staff and students saw the central functions of note-taking to be provision of notes for subsequent revision and encoding information given by the lecturer. More students than staff however, considered that note-taking in lectures interferes with understanding. Staff and students held similar views as to the uses of overheads in lectures. Interestingly however, more staff than students agreed that overheads often contain too much information. Conclusion Both students and staff saw the central role of note-taking as providing a set of good notes for revision. Generally students preferred that this information be provided in the form of partial or complete handouts, while staff preferred students to take notes and to read outside lectures. Surprisingly, more staff than students felt that overhead transparencies often contained too much information. Note-taking, handouts and overhead transparencies need to be linked in a coherent educational strategy to promote effective learning.

Longitudinal study of veterinarians from entry to the veterinary course to ten years after graduation: career paths

Objective To map out the career paths of veterinarians during their first 10 years after graduation, and to determine if this could have been predicted at entry to the veterinary course. Design Longitudinal study of students who started their course at The University of Queensland in 1985 and 1986, and who completed questionnaires in their first and fifth year as students, and in their second, sixth and eleventh year as veterinarians. Methods Data from 129 (96%) questionnaires completed during the eleventh year after graduation were coded numerically then analysed, together with data from previous questionnaires, with SAS System 7 for Windows 95. Results Ten years after they graduated, 80% were doing veterinary work, 60% were in private practice, 40% in small animal practice and 18% in mixed practice. The equivalent of 25% of the working time of all females was taken up by family duties. When part-time work was taken into account, veterinary work constituted the equivalent of 66% of the group working full-time. That 66% consisted of 52% on small animals, 7% on horses, 6% on cattle/sheep and 1% on pigs/poultry. Those who had grown up on farms with animals were twice as likely to be working with farm animals as were those from other backgrounds. Forecasts made on entry to the veterinary course were of no value in predicting who would remain in mixed practice. Conclusions Fewer than one-fifth of graduates were in mixed practice after 10 years, but the number was higher for those who grew up on farms with animals. Forecasts that may be made at interview before entry to the course were of little value in predicting the likelihood of remaining in mixed veterinary practice.