Decrease in particle‐induced osteolysis in ovariectomized mice

Postmenopausal osteoporosis is a common disorder that results from increased osteoclastic activity caused by estrogen deficiency. Whether postmenopausal bone remodeling can alter the response to particulate debris is unknown. The purpose of this study was to evaluate the bone response to polyethylene particles in an ovariectomized murine model. Polyethylene particles were implanted onto the calvaria of seven control mice and seven ovariectomized (OVX) mice, as compared with calvaria from sham‐operated and OVX mice. Calvaria were harvested after 14 days. Skulls were analyzed with a high‐resolution micro‐CT and by histomorphometry after staining with Stevenel blue and picrofuschine, and for tartrate‐specific alkaline phosphatase. As assessed by micro‐CT, particle implantation induced a significant decrease in bone thickness in control mice, while bone thickness remained stable in OVX mice. In particle‐implanted animals, the osteoclast number was 2.84 ± 0.3 in control mice and 1.74 ± 0.22 in OVX mice. Mean bone loss was ?12% ± 1.9% in control mice and ?4.7% ± 1.7% in OVX animals. The reduction of osteolytic response suggests that ovariectomy may have a protective role against particle‐induced bone resorption. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:178–183, 2010     

Antioxidant impregnated ultra‐high molecular weight polyethylene wear debris particles display increased bone remodeling and a superior osteogenic:osteolytic profile vs. conventional UHMWPE particles in a murine calvaria model

Periprosthetic osteolysis remains a major limitation of long‐term successful total hip replacements with ultra‐high molecular weight polyethylene (UHMWPE) bearings. As intra and extracellular reactive oxygen species are know to contribute to wear debris‐induced osteoclastic bone resorption and decreased osteoblastic bone formation, antioxidant doped UHMWPE has emerged as an approach to reduce the osteolytic potential of wear debris and maintain coupled bone remodeling. To test this hypothesis in vivo, we evaluated the effects of crosslinked UHMWPE wear debris particles (AltrX^?), versus similar wear particles made from COVERNOX^? containing UHMWPE (AOX^?), in an established murine calvaria model. Eight‐week‐old female C57B/6 mice (n = 10/Group) received a pre‐op micro‐CT scan prior to surgical implantation of the UHMWPE particles (2mg), or surgery without particles (sham). Dynamic labeling was performed by intraperitoneal injection of calcein on day 7 and alizarin on day 9, and the calvaria were harvested for micro‐CT and histology on day 10. Surprisingly, we found that AOX particles induced significantly more bone resorption (1.72‐fold) and osteoclast numbers (1.99‐fold) vs. AltrX (p < 0.001). However, AOX also significantly induced 1.64‐fold more new bone formation vs. AltrX (p < 0.01). Moreover, while the osteolytic:osteogenic ratio of both particles was very close to 1.0, which is indicative of coupled remodeling, AOX was more osteogenic (Slope = 1.13 ± 0.10 vs. 0.97 ± 0.10). Histomorphometry of the metabolically labeled undecalcified calvaria revealed a consistent trend of greater MAR in AOX vs. AltrX. Collectively, these results demonstrate that anti‐oxidant impregnated UHMWPE particles have decreased osteolytic potential due to their increased osteogenic properties that support coupled bone remodeling. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:845–851, 2016.

     

The effect of E. Coli and E. Coli endotoxin on peristalsis in the canine ureter

Summary The association of ureteric dilatation and urinary infection has been attributed to a direct toxic effect of E. Coli endotoxin on ureteric muscle. A specific causal relationship could not be established in this study in dogs.     

The relationship between calcium accumulation in osteoclast mitochondrial granules and bone resorption

In the process of bone resorption, calcium is considered to be transported within vesicles in osteoclasts and eventually released. We studied the ultramicromorphology of calcium (Ca) transport in osteoclasts by preparing samples of osteoclasts collected from rat femurs in which calcium was maximally preserved and subjected them to high-pressure quick-freezing and freeze-substitution. We then examined the localization of calcium by Electron Energy Loss Spectroscopy (EELS). The structures of cell membranes were preserved, suggesting the suitability of this high-pressure quick-freezing and freeze-substitution technique.Osteoclast mitochondria adjacent to the ruffled border were rich in mitochondrial granules and contained a large amount of Ca. In contrast, mitochondria in the basolateral region contained few granules. Moreover, by an osteoclast-culturing experiment, differences in the morphology of mitochondrial granules were noted between culturing on a dentin slice and that on a gold plate, i.e., few mitochondrial granules were noted in osteoclasts cultured on a non-dentin plate.These findings suggest an association between the morphology of mitochondrial granules in osteoclasts and bone resorption as well as a new transport route for Ca resorbed by osteoclasts. We propose that Ca accumulates in mitochondria granules to prevent increased Ca concentration in cytoplasm of osteoclasts during bone resorption.     

The efficacy of preoperative endoscopic retrograde cholangiopancreatography in the detection and clearance of choledocholithiasis.

BACKGROUND AND OBJECTIVES: Endoscopic retrograde cholangiopancreaticography has been reported to have a high success rate in the detection and treatment of choledocholithiasis. Although there is growing enthusiasm for laparoscopic common bile duct clearance, many patients who present with gallbladder disease and suspected choledocholithiasis have endoscopic retrograde cholangiopancreatography performed with choledocholithiasis cleared if detected. These patients are then referred for laparoscopic cholecystectomy. The purpose of this study is to determine the efficacy of preoperative endoscopic retrograde cholangiopancreatography in the diagnosis and clearance of bile duct stones at our institution. METHODS: A retrospective review was performed of all patients at this institution who underwent preoperative endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis followed by laparoscopic cholecystectomy from January 1997 through July 1998. RESULTS: Common bile duct stones were detected endoscopically in 12 of 17 (71%) patients. We found serum bilirubin level to be the best predictor of choledocholithiasis. In 12 of 12 procedures, the endoscopist performed an endoscopic sphincterotomy with stone extraction and reported a fully cleared common bile duct. Intraoperative cholangiogram performed during subsequent cholecystectomy revealed choledocholithiasis in 4 of these 12 patients. Laparoscopic techniques successfully cleared the choledocholithiasis in 3 of these patients with open techniques necessary in the fourth. CONCLUSIONS: Our data suggests that even after presumed successful endoscopic clearance of the bile duct stones, many patients (33% in our series) still have choledocholithiasis present at the time of cholecystectomy. We recommend intraoperative cholangiography at the time of cholecystectomy even after presumed successful endoscopic retrograde cholangiopancreatography with further intervention, preferably laparoscopic, to clear the choledocholithiasis as deemed necessary.     

铁蓄积对2型糖尿病患者骨密度影响的相关性研究

目的 通过分析2型糖尿病（T2DM）患者体内铁储量与骨密度的相关性,探讨铁蓄积对T2DM患者骨质疏松症患病风险的独立影响。方法 回顾性分析2018年12月1日至2020年12月31日在江苏大学附属昆山医院内分泌科住院治疗的T2DM 患者,收集患者的基本资料包括年龄、体质指数、腰椎和股骨颈骨密度、血清铁蛋白以及血脂等生化指标。首先对T2DM患者骨密度的潜在影响因素进行单因素分析,然后通过分层分析和曲线拟合探究不同性别T2DM患者中血清铁蛋白与骨密度的变化关系。最后通过多元回归模型调整混杂因素,分析血清铁蛋白对T2DM患者骨质疏松症患病风险的影响。结果 本研究共纳入411名T2DM患者（188名女性,223名男性）。T2DM女性和男性患者体内血清铁蛋白的中位浓度分别为139.65 μg/Ｌ和243.10 μg/Ｌ,两者骨质疏松患病率分别为38.83 %和25.56 %。单因素分析显示T2DM患者血清铁蛋白浓度与骨密度成负相关;曲线拟合显示,T2DM患者的骨密度随着血清铁蛋白浓度的升高而降低。多元回归分析显示,在调整混杂因素后,T2DM女性和男性患者中血清铁蛋白高浓度组患骨质疏松症的风险分别是低浓度组的17.163和3.732倍（P＜0.05）。结论 T2DM患者中铁储量与不同部位骨密度之间存在负性关系。血清铁蛋白浓度上升是T2DM患者骨密度下降的独立危险因素,铁蓄积可能会增加T2DM患者骨质疏松患病率的风险。     

Effects of propranolol pretreatment on cerebral blood flow, oxygen uptake and catecholamines during metabolic acidosis following E. coli endotoxin in dogs

After an intravenous injection of E. coli endotoxin in dogs a decrease in cerebral blood flow (CBF) and an increase in cerebral metabolic rate of oxygen (CMRo₂) have been shown to occur. In metabolic acidosis following endotoxin CMRo₂ increased with decreasing pH. A possible explanation for the increased CMRo₂ after endotoxin and metabolic acidosis seems to be a damage of the blood-brain barrier (BBB) by endotoxin. This gives possibilities for a leakage of hydrogen ions and circulating monoamines from the blood to the brain, thus affecting the cerebral blood flow and metabolism.
The effects of an E. coli endotoxin injection on CBF and CMRo₂ during metabolic acidosis and P-adrenoceptor blockade were studied in eight anaesthetized dogs. All the dogs were pretreated with propranolol (PPL), per os 12.5 mg . kg^-1 twice a day for one week. Metabolic acidosis (pH 7.01–7.30) was achieved by an intravenous infusion of hydrochloric acid. Endotoxin E. coli lipopolysaccharide O 111:B 4 was given as an intravenous injection of 1 mg . kg^-1 bodyweight over a 5 min period. Another five animals, published earlier, with the same experimental protocol but without PPL, constituted a control group.
After endotoxin no increase in CMRo₂ or CBF was observed with increasing acidosis in the PPL-group. In the control group, after endotoxin, both CBF and CMR02 increased with decreasing pH. This resulted in a significant difference in both CBF and CMRo₂ between the groups in the pH range 7.01—7.15.
The present results indicate that the increase in CMRo₂ and CBF with metabolic acidodis in endotoxinaemia is mediated via P-adrenoceptors.     

Reciprocity of exposure time and irradiance on energy density during photoradiation on wound healing in a murine pressure ulcer model

BACKGROUND: Energy density and exposure time reciprocity is assumed and routinely used in low-level light therapy (LLLT) regimens. This study examined dose reciprocity effects on wound healing. METHODS: Pressure ulcers were created on seven groups of C57/BL mice (n = 18). Photoradiation was administered (18 days; 5 J/cm(2)/day @ 670 nm) using a custom LED apparatus and treatment matrix varying both intensity and exposure. Control animals were treated similarly, without photoradiation. Ulcer staging was performed using a standardized scale. Changes in stage, wound area and wound closure rates were measured. Histology was performed. RESULTS: Photostimulatory effects at day 7 occurred with parameters of 125 seconds @ 40 mW x 1/day; 625 seconds @ 8 mWx1/day; 62.5 seconds @ 40 mWx2/day; and 312.5 seconds @ 8 mWx2/day; and at day 18 using 625 seconds @ 8 mW and 312.5 seconds @ 8 mWx2/day. Statistically significant increases in wound closure rates occurred using 625 seconds @ 8 mW; 62.5 seconds @ 40 mWx2/day; and 312.5 seconds @ 8 mWx2/day treatments. Mean ulcer grade scores were similar to controls. CONCLUSIONS: Varying irradiance and exposure time to achieve a specified energy density affects phototherapy outcomes in this model. Variation of exposure time and irradiance may account for conflicting results in the literature. Further studies of these effects are warranted.     

The role of the liver in the changes of acid-base balance and plasma lipids during surface-induced deep hypothermia

The role of the liver in the changes of acid-base balance and plasma lipids in surface-induced deep hypothermia for open-heart surgery was investigated clinically and experimentally. The metabolic acidosis generally observed in open-heart surgery under surface-induced deep hypothermia is derived from lactacidemia. Although the accelerated anaerobic glycolysis is partly responsible, the depressed acidic metabolite-disposing ability of the liver also plays an important role. The evidence which is presented to show the decrease of plasma lipids other than NEFA under hypothermia is probably due to the hepatic accumulation of lipids and the decreased lipids release from the liver.     

Crosstalk between substance P and calcitonin gene‐related peptide during heterotopic ossification in murine Achilles tendon

Heterotopic ossification (HO) is abnormal bone formation within soft tissue, usually predisposed by neurogenic or musculoskeletal trauma. Inflammation resulting from trauma is considered to be the main trigger for HO by eliciting changes within the injury site, including elevation of bone morphogenetic proteins (BMPs). Recent research, however, has also associated changes in sensory neuropeptide expression with HO. Substance P (SP) and calcitonin gene‐related peptide (CGRP) are two of those neuropeptides that have been implicated with various aspects of HO, including regulation of inflammation and BMP signaling. Despite discoveries associating SP and CGRP with soft tissue HO, it remains unclear whether SP and CGRP have a direct role in the induction of HO. Here, we investigated the effect of SP and CGRP in vivo with the aid of inkjet‐based biopatterning technology to controllably deliver these neuropeptides onto a murine Achilles tendon. While we did not observe any significant effect with CGRP, SP alone promoted HO in vivo with increased expression of BMP2. Remarkably, when SP and CGRP were delivered together, CGRP counteracted the effect of SP and essentially blocked SP‐induced HO. This report contributes to the understanding of the complex problem of HO pathophysiology and warrants more study to better elucidate the interplay between SP and CGRP in the induction of HO. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1444–1455, 2018.