Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Effects of methoctramine on bladder overactivity in a rat model

Objectives. To determine the functional effects of methoctramine as an M-2 muscarinic receptor antagonist on isolated detrusor strips in vitro and bladder overactivity in vivo in rats

Expression of CD44 and E-cadherin cell adhesion molecules in hypertrophied bladders during chronic partial urethral obstruction and after release of partial obstruction in rats

Objectives. To determine the functional changes in the bladder and the expression of adhesion molecules in bladder tissue during chronic partial urethral obstruction and after release of partial obstruction in rats

Fluid resuscitation in the treatment of uncontrolled hemorrhagic shock

Background: We evaluated the effect of continuous fluid resuscitation on the hemodynamic response and survival following massive splenic injury (MSI) in rats

Effect of melatonin on testicular damage in streptozotocin-induced diabetes rats

Background: It is well known that diabetes mellitus is associated with impairment of testicular function. In the present study, we aimed to demonstrate the effect of melatonin on testicular damage in male rats with streptozotocin (STZ)-induced diabetes. Methods: Male Wistar rats were divided into 4 groups: (1) control group, (2) melatonin-treated nondiabetic group, (3) diabetic group and (4) melatonin-treated diabetic group. Diabetes was induced by STZ injection. Melatonin was administered intraperitoneally at the dose of 10 mg/kg for 5 days. Testicular damage was examined by using hematoxylin and eosin staining and periodic acid-Schiff staining, and apoptosis was determined by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Potential disorders associated with seminiferous tubular sperm formation were evaluated using the Johnsen score. Results: Diabetic rats showed a reduction in seminiferous tubule diameter, increased thickening of the basement membrane in seminiferous tubules and degenerated germ cells. TUNEL-positive cells were significantly more numerous in diabetic rats than in control rats. Melatonin significantly attenuated the diabetes-induced morphological changes and germ cell apoptosis in the diabetic rat testis. The number of polymorphonuclear leukocytes was signifi cantly decreased in group 4 when compared to group 3. Conclusions: These results suggest that intraperitoneal administration of melatonin for 5 days is a potentially beneficial agent to reduce testicular damage in adult diabetic rats, probably by decreasing oxidative stress. Copyright (C) 2008 S. Karger AG, Basel

Esterified hyaluronic acid improves cartilage viability in experimental tracheal reconstruction with an auricular graft

PubMed: 21109076Objective The aim of this study was to determine the efficacy of esterified hyaluronic acid (HYAFF) on the vitality of auricular cartilage grafts used for tracheoplasty, with respect to macroscopic and microscopic parameters. Study Design Prospective, controlled. Setting Academic research laboratory. Subjects and Methods The study included 14 New Zealand rabbits acquired specifically for the study. The rabbits were divided into two groups: the control group, in which free cartilage grafts were not exposed to any materials or additional procedures (n = 7), and the hyaluronic acid (HA) treatment group, in which auricular grafts and anastomosis lines were covered with HYAFF (n = 7). Free auricular cartilage grafts used for the reconstruction of experimentally created tracheal defects were anastomosed extraluminally. All the rabbits were sacrificed two months post surgery. Samples were collected and examined histopathologically. The sections were stained with hematoxylin-eosin, Masson's trichrome, and inducible nitric oxide synthase (iNOS) and examined under a light microscope. Results Fibrosis and cartilage mass significantly differed between the control and HYAFF group (P < 0.05). Immunohistochemical examination showed that more chondrocytes stained with iNOS in the control group than in the HYAFF group, according to histologists' observations. Conclusion HYAFF catalyzed wound healing with less fibrous tissue formation, had chondroprotective and stimulatory effects on chondrocyte metabolism, and decreased nitric oxide production and apoptosis via improving the nourishment of free auricular cartilage grafts, subsequently preventing hypoxia and oxidative stress, particularly in the early postimplantation period. © 2010 American Academy of OtolaryngologyHead and Neck Surgery Foundation. All rights reserved

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats [Comparação dos efeitos de dexmedetomidina administrada em dois momentos diferentes para lesão de isquemia/reperfusão renal em ratos]

[No abstract available