Contrary to the commonly held misconception, bone is a relatively dynamic organ that undergoes significant turnover as compared to other organs in the body. This review details how complex intercellular signalling, between the osteoprogenitor cells and mature osteoblasts, osteocytes and osteoclasts, regulates and balances activities of bone cells during remodelling and growth. Both systemic, as well as local autocrine and paracrine factors are discussed. A number of recent important advances in cell biology of bone have led to a new paradigm in understanding of the subject. In this regard, the interaction between the immune system and bone cells is of particular interest, leading to the emergence of a new discipline termed osteoimmunology. The role of lymphocytes and a number of key cytokines in the regulation of osteoclastogenesis and osteoblast function is critically examined. The intracellular signalling regulating key cellular pathways involved in cell differentiation and activity are outlined. The emerging evidence of osteocytes as mechanosensors as well as regulators of mineralisation is discussed.

Background:Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2′-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer.Methods:Patients progressing 6–12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) on day 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma.Results:After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated with the combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin and carboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatin hypersensitivity (47% vs 21%).Conclusions:With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partially platinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents should be considered in future combination studies.

Seven Holstein steers (234 +/- 6.4 kg) surgically fitted with pancreatic cannulas, ruminal and abomasal infusion cannulas, and hepatic-portal vein catheters were used in a 4 x 7 incomplete Latin square design experiment to examine the influence of ruminal and abomasal carbohydrate infusion on enzyme secretion and composition of pancreatic juice. Four treatments were arranged in a 2 x 2 factorial: 1) ruminal starch hydrolysate (SH; 34.2 g/[h.site]) or abomasal water and 2) abomasal SH or ruminal water. Starch hydrolysate is raw cornstarch that has been partially digested by a heat-stable alpha-amylase. Experimental periods were 14 d with 9 to 10 d of adaptation, 4 d of pancreatic collection, and blood collection on d 14. Abomasal SH infusion tended (P < .10) to increase pancreatic fluid secretion. The pH of pancreatic juice was higher (P < .01) for ruminal SH infusion, and abomasal SH infusion tended (P < .10) to result in lower pH of pancreatic juice. alpha-Amylase concentrations (units/milliliter and units/milligram of protein) and secretion (units/hour) were less (P < .002) for abomasal SH infusion. Chymotrypsin concentration (units/liter; P < .01) and secretion (units/hour; P < .10) were less for abomasal SH infusion; however, a rumen x abomasal interaction was found (P < .05). Chloride concentration (milligrams/deciliter) and secretion (milligrams/hour) were increased (P < .01) for abomasal SH infusion. Abomasal SH infusion resulted in increased (P < .01) portal blood glucose concentrations; however, portal plasma insulin concentration was not affected (P > .10). Abomasal SH infusion altered alpha-amylase secretion in steers, but ruminal SH infusion had minimal effect on alpha-amylase secretion. These changes suggest abosamal infusion of SH may negatively impact secretion of pancreatic alpha-amylase.

No abstract

Nine mature mongrel dogs were used to evaluate a surgical technique for the cannulation of the terminal ileum and used in two experiments to determine the effect of carbohydrate source on starch and dry matter digestion. Dogs (16.2 +/- 2.0 kg body weight; means +/- SD) were fitted with an ileal T-cannula constructed of polyvinyl chloride pipe. The cannula was inserted into the terminal ileum approximately 10 cm proximal to the ileocecal junction and the cannula was exteriorized through a small incision on the right flank. Dogs recovered quickly from surgery (5d). A preliminary study using Cr:EDTA in the food indicated that sampling for 12 h postprandially allowed near complete representation of digesta flow for a meal; peak flow occurred 4-to 8-h postfeeding. Two experiments were performed evaluating the effect of carbohydrate source on ileal starch and dry matter digestibility. Dogs were fed two meals daily with Cr2O3 used as a digesta marker. Diets contained 67% extruded grain (corn, rice, oats or barley) and 33% canned meat supplement on a dry matter basis. Starch digestion was complete (> 98%) within the small intestine and was unaffected by carbohydrate source. In experiment 1, prececal and total tract dry matter digestibilities were higher for rice than corn, and in experiment 2, barley was higher than oats. The ileal T-cannula allows for measurement of small intestinal nutrient disappearance without the confounding effects of colonic microflora. This method may be useful when applied to the study of other nutrients in dogs.