Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model

Osteoporosis (OP) is one of the most prevalent bone diseases worldwide with bone fracture the major clinical consequence. The effect of OP on fracture repair is disputed and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer to this question still eludes us. The aim of this study was to clarify the effect of osteoporosis in a rodent fracture model. OP was induced in 3-month-old rats (n = 53) by ovariectomy (OVX) followed by an externally fixated, mid-diaphyseal femoral osteotomy at 6 months (OVX group). A further 40 animals underwent a fracture at 6 months (control group). Animals were sacrificed at 1, 2, 4, 6, and 8 weeks postfracture with outcome measures of histology, biomechanical strength testing, pQCT, relative BMD, and motion detection. OVX animals had significantly lower BMD, slower fracture repair (histologically), reduced stiffness in the fractured femora (8 weeks) and strength in the contralateral femora (6 and 8 weeks), increased body weight, and decreased motion. This study has demonstrated that OVX is associated with decrease in BMD (particularly in trabecular bone) and a reduction in the mechanical properties of intact bone and healing fractures. The histological, biomechanical, and radiological measures of union suggest that OVX delayed fracture healing. (C) 2007 Orthopaedic Research Society. Published by Wiley Periodicals.

Cytochrome P450 1B1 expression in rat esophageal tumorigenesis promoted by gastric and duodenal reflux.

Cytochrome P450 1B1 (CYP1B1) mRNA is constitutively expressed in most normal extra-hepatic tissues; however the protein is not detectable in these tissues but is expressed in a wide variety of tumors. CYP1B1 is responsible for the activation of a number of carcinogens present in tobacco smoke and food. A surgical model of rat esophageal tumorigenesis, promoted by gastric or duodenal reflux was used to determine CYP1B1 expression in premalignant esophageal tissue. Immunohistochemistry was performed using a modified amplified fluorescein tyramide protocol. CYP1B1 was not observed in normal esophageal mucosa, submucosa, or muscularis mucosa. Animals exposed to gastric reflux developed mild hyperplasia. Varying degrees of hyperplasia were observed in the duodenal reflux group. All regions of hyperplasia showed moderate or strong CYP1B1 immunoreactivity. Duodenal reflux induced a small number of premalignant changes: immunoreactivity was absent from the epithelium of squamous dysplasia (0/10), Barrett's esophagus (0/7), and majority of dysplastic Barrett's esophagus (1/4). Moderate or strong immunoreactivity was observed in the majority (7/8) of squamous cell carcinomas (SCCs) in situ. Immunoreactivity was also observed in the lamina propria and submucosa in association with inflammation, regardless of the severity of inflammation. The expression of CYP1B1 in hyperplasia, SCCs in situ, or in association with inflammation may increase the production of carcinogenic metabolites, which may promote esophageal tumorigenesis.

Sandstone response to salt weathering following simulated fire damage: a comparison of furnace heating and fire.

Fire has long been recognized as an agent of rock weathering. Our understanding of the impact of fire on stone comes either from early anecdotal evidence, or from more recent laboratory simulation studies, using furnaces to simulate the effects of fire. This paper suggests that knowledge derived from simulated heating experiments is based on the preconceptions of the experiment designer – when using a furnace to simulate fire, the operator decides on the maximum temperature and the duration of the experiment. These are key factors in determining the response of the stone to fire, and if these are removed from realworld observations then knowledge based on these simulations must be questioned. To explore the differences between heating sandstone in a furnace and a real fire, sample blocks of Peakmoor Sandstone were subjected to different stress histories in combination (lime rendering and removal, furnace heating or fire, frost and salt weathering). Block response to furnace heating and fire is discussed, with emphasis placed on the non-uniformity of the fire and of block response to fire in contrast to the uniform response to surface heating in a furnace. Subsequent response to salt weathering (by a 10% solution of sodium chloride and magnesium sulphate) was then monitored by weight loss. Blocks that had experienced fire showed a more unpredictable response to salt weathering than those that had undergone furnace heating – spalling of corners and rapid catastrophic weight loss were evidenced in blocks that had been subjected to fire, after periods of relative quiescence. An important physical side-effect of the fire was soot accumulation, which created a waxy, relatively impermeable layer on some blocks. This layer repelled water and hindered salt ingress, but eventually detached when salt, able to enter the substrate through more permeable areas, concentrated and crystallized behind it, resulting in rapid weight loss and accelerated decay. Copyright ©2007 John Wiley & Sons, Ltd.

Disturbances in social interaction occur along with pathophysiological deficits following sub-chronic phencyclidine administration in the rat.

A sub-chronic administration of phencyclidine to the rat brings about enduring pathophysiological and cognitive changes that resemble some features of schizophrenia. The present study aimed to determine whether the behavioural consequence of this phencyclidine regime extends to a long-term disruption of social interaction that might provide a parallel with some negative symptoms of the disease. Rats were treated with phencyclidine (2mg/kg bi-daily for 1 week) or vehicle followed by a drug-free period. Social interaction was assessed 24h, 1 week, 3 weeks and 6 weeks post-treatment. A long-lasting disturbance of social behaviour was observed in the phencyclidine group, namely more contact and non-contact interaction with an unfamiliar target rat at all time points. Six weeks post-phencyclidine, analysis of brains showed a reduction in expression of parvalbumin immunoreactive neurons in the hippocampus with significant reductions localised to the CA1 and dentate gyrus regions. These results show that sub-chronic phencyclidine produces long-lasting disruptions in social interaction that, however, do not model the social withdrawal seen in patients with schizophrenia. These disturbances of social behaviour may be associated with concurrent pathophysiological brain changes.

Liver fluke (Fasciola hepatica)-derived peptides activate rat peritoneal mast cells

Short peptides with sequences derived from those found in the tegumental antigen of Fasciola hepatica have been synthesised. Incubation of some of these peptides with rat peritoneal mast cells resulted in the degranulation of the cells as measured by a histamine release assay. This activity was shown to be associated with the proline-lysine-proline motif, which is responsible for the induction of mast cell degranulation by the mammalian bioactive peptide substance P. Studies on the mode of action of the fluke-derived peptide indicated that it was operating through the same biochemical pathways as substance P. The implications of these findings for the development of immune responses during parasite infections are discussed. (C) 2003 Elsevier Science B.V. All rights reserved.

Cell-specific processing of chromogranin A in endocrine cells of the rat stomach

The rat stomach is rich in endocrine cells. The acid-producing (oxyntic) mucosa contains ECL cells, A-like cells, and somatostatin (D) cells, and the antrum harbours gastrin (G) cells, enterochromaffin (EC) cells and D cells. Although chromogranin A (CgA) occurs in all these cells, its processing appears to differ from one cell type to another. Eleven antisera generated to different regions of rat CgA, two antisera generated to a human (h) CgA sequences, and one to a bovine Ib) CgA sequence, respectively, were employed together with antisera directed towards cell-specific markers such as gastrin (G cells), serotonin (EC cells), histidine decarboxylsae (ECL cells) and somatostatin (D cells) to characterize the expression of CgA and CgA-derived peptides in the various endocrine cell populations of the rat stomach. In the oxyntic mucosa, antisera raised against CgA(291-319) and CGA(316-321) immunostained D cells exclusively, whereas antisera raised against bCgA(82-91) and CgA(121-128) immunostained A-like cells and D cells. Antisera raised against CgA(318-349) and CgA(437-448) immunostained ECL cells and A-like cells, but not D cells. In the antrum, antisera against CgA(291-319) immunostained D cells, and antisera against CgA(351-356) immunostained G cells. Our observations suggest that each individual endocrine cell type in the rat stomach generates a unique mixture of CgA-derived peptides, probably reflecting cell-specific differences in the post-translational processing of CgA and its peptide products. A panel of antisera that recognize specific domains of CgA may help to identify individual endocrine cell populations.