Amitriptyline and Acute Inflammation: A Study Using Intravital Microscopy and the Carrageenan-Induced Paw Edema Model

Background/Aims: Antidepressants are reported to exhibit antiinflammatory effects. However, mechanisms involved in this action have not been elucidated. Thus, the objectives of the present study were (a) to evaluate the effects of amitriptyline on the acute inflammatory process, and (b) to investigate the participation of alpha(1)-adrenergic receptors and glucocorticoids as possible mechanisms implicated in the amitriptyline action on inflammation. Methods and Results: Single and multiple doses of amitriptyline were administered to rats submitted to the carrageenan-induced paw edema model. The results showed a significant antiedematous reaction to amitriptyline, mainly when administered at each elimination half-life. The next step was to evaluate its effects on leukocyte behavior, using intravital microscopy. Amitriptyline produced a significant effect on leukocyte behavior. To investigate possible mechanisms involved, a glucocorticoid receptor antagonist (RU-486) and an alpha(1)-adrenergic receptor antagonist (prazosin) were used. RU-486 administration lacked the ability to decrease the amitriptyline antiinflammatory effects in the carrageenan-induced paw edema model. Prazosin pretreatment potentiated the amitriptyline antiinflammatory effect without presenting an effect per se. Conclusion:The present study shows the ability of amitriptyline to decrease edema and affect leukocyte behavior in an acute inflammatory process; and, for the first time to our knowledge, we suggest the involvement of alpha(1)-adrenoceptors in the antiinflammatory effects of amitriptyline. Copyright (C) 2010 S. Karger AG, Basel

Insulin Affects Tissue Organization and the Kinetics of Epithelial Cell Death in the Rat Ventral Prostate After Castration

Prostate growth and physiology are regulated by steroid hormones and modulated by multiple endocrine factors We investigated the action of insulin on the tissue organization and kinetics of epithelial cells in the rat ventral prostate (VP) in response to castration up to 120 hours after surgery by using an acute protocol of alloxan induced diabetes Diabetes caused a reduction in volume density (Vv(o)/) and volume of the epithelium The effects of castration on the epithelium were accelerated in the diabetic animals as determined by changes in V(o)/, and volume The smooth muscle cells became atrophic and apparently relaxed in response to castration in contrast to the spinous aspect observed in nondiabetic castrated rats Counting of apoptotic nuclei in the epithelium showed the classical apoptosis peak at 72 hours in nondiabetic rats and an advance of the apoptosis peak to 48 hours after castration in diabetic rats Insulin restored the time of the peak to 72 hours These results were confirmed after immunostaining for cleaved caspase 3 and suggest a survival and antiapoptotic effect on VP epithelial cells in both the presence and absence of androgen stimulation This idea is supported by the observation that insulin also reduced the overall rate of apoptosis at all experimental points analyzed before and after castration

Oviductal Fluid Proteins Associated with the Bovine Zona Pellucida and the Effect on In Vitro Sperm-Egg Binding, Fertilization and Embryo Development

Studies have demonstrated that oviductal fluid (ODF) proteins associate with eggs of numerous species including the bovine. In this study, the association of three ODF proteins, the bovine oestrus-associated protein, osteopontin (OPN), lipocalin-type prostaglandin D synthase (L-PGDS), with the bovine zona pellucida (ZP) was demonstrated by immunohistochemistry and western blot. The biological function of ODF derived egg-associated OPN and L-PGDS in sperm binding, fertilization and embryonic development was also explored. In vitro matured bovine oocytes were pre-incubated with ODF collected by cannula from cows in oestrus, or ODF with antibodies to OPN, L-PGDS and bovine serum albumin (BSA). Following incubation, oocytes were inseminated with 1 x 10(5) frozen-thawed spermatozoa, and they were evaluated for sperm binding, fertilization and embryonic development in vitro. Pre-treatment of ODF with antibodies to all of proteins reduced sperm binding to the ZP and fertilization in vitro. Cleavage rates were not significantly different among incubations, but rates of embryo development were significantly decreased. We conclude that antibodies to OPN, L-PGDS and BSA react with oocytes incubated with ODF and inhibit sperm binding, fertilization and embryonic development in vitro, suggesting a potential role of these proteins in these events.

Notes on market failure and the Paretian (Kaldor-Hicks) relevance and irrelevance of unfavourable externalities

The following are notes that have been distributed by me over the last few years to students in Environmental Economics at The University of Queensland. They give particular attention to whether externalities are Pareto or Kaldor-Hicks relevant from a policy point of view. Externalities are Kaldor-Hicks or Pareto irrelevant if no change is possible for which gainers could compensate losers. Both absolute and marginal externalities may be Kaldor-Hicks relevant. Infra-marginal negative externalities are often, but not always, Kaldor-Hicks irrelevant. There are at least two cases where such externalities can be relevant. First, the absolute impact of the negative externality may be so great that the source of the externality should be eliminated. Secondly, if the externality arises from production, its nature may depend on the type of production technique adopted. Although for the technique adopted, an infra-marginal negative externality occurs. That is Paretian irrelevant given that choice of this technique is the only available possibility, alternative techniques may actually be available in practice. Some of these may generate even smaller total external effects and be socially preferable. Both cases are outlined and illustrated in these notes. The analysis reveals the dangers of relying on marginalism for deciding on environmental policy. Total (external) effects are often of great social and economic importance and appropriate social choices cannot be made on the basis of marginalism alone.

Elastic modulus of posts and the risk of root fracture

The definition of an optimal elastic modulus for a post is controversial. This work hypothesized that the influence of the posts` elastic modulus on dentin stress concentration is dependent on the load direction. The objective was to evaluate, using finite element analysis, the maximum principal stress (sigma(max)) on the root, using posts with different elastic modulus submitted to different loading directions. Nine 3D models were built, representing the dentin root, gutta-percha, a conical post and the cortical bone. The softwares used were: MSC.PATRAN2005r2 (preprocessing) and MSC.Marc2005r2 (processing). Load of 100 N was applied, varying the directions (0 degrees, 45 degrees and 90 degrees) in relation to the post`s long axis. The magnitude and direction of the sigma(max) were recorded. At the 45 degrees and 90 degrees loading, the highest values of sigma(max) were recorded for the lowest modulus posts, on the cervical region, with a direction that suggests debonding of the post. For the 0 degrees loading, the highest values of sigma(max) were recorded for higher modulus posts, on the apical region, and the circumferential direction suggests vertical root fracture. The hypothesis was accepted: the effect of the elastic modulus on the magnitude and direction of the sigma(max) generated on the root was dependent on the loading direction.