Effects of Intermittent Femoral Nerve Injections of Bupivacaine, Levobupivacaine, and Ropivacaine on Mitochondrial Energy Metabolism and Intracellular Calcium Homeostasis in Rat Psoas Muscle

Background: Long-acting local anesthetics cause muscle damage. Moreover, long-acting local anesthetics act as uncoupler of oxidative phosphorylation in isolated mitochondria and enhance sarcoplasmic reticulum Ca2+ release. The aim of the study was to evaluate effects of perineural injections of local anesthetics on mitochondrial energetic metabolism and intracellular calcium homeostasis in vivo.

Methods: Femoral nerve block catheters were inserted in adult male Wistar rats. Rats were randomized and received seven injections (1 ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h intervals. Rats were killed 8 h after the last injection. Psoas muscle was quickly dissected from next to the femoral nerve. Local anesthetic concentrations in muscle were determined. Oxidative capacity was measured in saponin-skinned fibers. Oxygen consumption rates were measured, and mitochondrial adenosine triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial respiratory chain complexes were evaluated. Local calcium release events (calcium sparks) were analyzed as well as sarcoplasmic reticulum calcium content in saponin-skinned fibers.

Results: Eight hours after the last injection, psoas muscle concentration of local anesthetics was less than 0.3 [mu]g/g tissue. Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were significantly decreased in the muscle of rats treated with local anesthetics. A global decrease (around 50%) in all of the enzyme activities of the respiratory chain was observed. Levobupivacaine increased the amplitude and frequency of the calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.     

Genetic evidence points to an osteocalcin‐independent influence of osteoblasts on energy metabolism

The skeleton has been shown recently to regulate glucose metabolism through an osteoblast‐specific hormone, osteocalcin, which favors β‐cell proliferation, insulin secretion, insulin sensitivity, and energy expenditure. An implication of this finding is that a decrease in osteoblast numbers would compromise glucose metabolism in an osteocalcin‐dependent manner. To test this hypothesis, osteoblasts were inducibly ablated by cross‐breeding transgenic mice expressing a tamoxifen‐regulated Cre under the control of the osteocalcin promoter with mice in which an inactive form of the diphtheria toxin A chain was introduced into a ubiquitously expressed locus. Ablation of osteoblasts in adult mice profoundly affected glucose metabolism. In a manner similar to what is seen in the case of osteocalcin deficiency, a partial ablation of this cell population resulted in hypoinsulinemia, hyperglycemia, glucose intolerance, and decreased insulin sensitivity. However, and unlike what is seen in osteocalcin‐deficient mice, osteoblast ablation also decreased gonadal fat and increased energy expenditure and the expression of resistin, an adipokine proposed to mediate insulin resistance. While administration of osteocalcin reversed (fully) the glucose intolerance and reinstated normal blood glucose and insulin levels, it only partially restored insulin sensitivity and did not affect the improved gonadal fat weight and energy expenditure in osteoblast‐depleted mice. These observations not only strengthen the notion that osteoblasts are necessary for glucose homeostasis and energy expenditure but also suggest that in addition to osteocalcin, other osteoblast‐derived hormones may contribute to the emerging function of the skeleton as a regulator of energy metabolism. © 2011 American Society for Bone and Mineral Research     

Natural history of adolescent-onset cystinosis

Cystinosis is a rare autosomal recessive disease caused by mutations of the CTNS gene in which cystine accumulates throughout the body as a result of a defective efflux of cystine from lysosomes. Three phenotypic forms have been described according to the age of onset and the severity of the clinical symptoms: infantile, intermediate, and ocular non-nephropathic cystinosis. Here we report the natural history of cystinosis in a 55-year-old man with intermediate nephropathic cystinosis diagnosed at 9 years of age. Although tubulopathy was unnoticed in the early years, he required transplantation at age 16. Sequencing analysis of all the CTNS exons revealed that the proband is homozygous for a 21-bp in-frame deletion in exon 5 (c. 198_218del21), resulting in an in-frame deletion of 7 amino acids from the N-terminal domain of the cystinosin protein. Our patient has had relatively mild extra-renal disease despite lack of early cysteamine therapy. He has been able to attend university and pursue a professional career into the 6th decade.     

The Influence of Non-union of the Ulnar Styloid on Pain, Wrist Function and Instability after Distal Radius Fracture

The influence of non-union on the outcome of distal radius fractures is debated. We tested the null hypothesis that there is no difference in pain, wrist function, or instability between patients with union or non-union of an ulnar styloid base fracture after operative treatment of a fracture of the distal radius. Eighteen adults with an ulnar styloid base non-union were compared to 16 patients with union of an ulnar styloid base fracture with a mean post-operative follow-up of 30 months. None of the patients had distal radioulnar joint instability, there were no significant differences in pain, complications, or function, and patients with nonunion had significantly greater grip strength. Ulnar styloid nonunion is not associated with pain, instability, or diminished function after fracture of the distal radius.     

Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering

Fetal bone cells were shown to have an interesting potential for therapeutic use in bone tissue engineering due to their rapid growth rate and their ability to differentiate into mature osteoblasts in vitro. We describe hereafter their capability to promote bone repair in vivo when combined with porous scaffolds based on poly(l-lactic acid) (PLA) obtained by supercritical gas foaming and reinforced with 5 wt.% beta-tricalcium phosphate (TCP). Bone regeneration was assessed by radiography and histology after implantation of PLA/TCP scaffolds alone, seeded with primary fetal bone cells, or coated with demineralized bone matrix. Craniotomy critical size defects and drill defects in the femoral condyle in rats were employed. In the cranial defects, polymer degradation and cortical bone regeneration were studied up to 12 months postoperatively. Complete bone ingrowth was observed after implantation of PLA/TCP constructs seeded with human fetal bone cells. Further tests were conducted in the trabecular neighborhood of femoral condyles, where scaffolds seeded with fetal bone cells also promoted bone repair. We present here a promising approach for bone tissue engineering using human primary fetal bone cells in combination with porous PLA/TCP structures. Fetal bone cells could be selected regarding osteogenic and immune-related properties, along with their rapid growth, ease of cell banking and associated safety.     

Cross-sectional study of pain and disability at knee replacement surgery for osteoarthritis in 299 patients

ObjectiveTo evaluate pain and disability at the time of knee replacement surgery for osteoarthritis.MethodsIn this multicenter cross-sectional study, 299 patients at 12 orthopedic surgery centers in Lyon, France were evaluated on the day before knee replacement surgery. Pain severity was assessed on a visual analog scale (VAS) and function using the Lequesne index and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC).ResultsThere were 207 women and 92 men with a mean age of 73 years. Mean (±SD) VAS pain score upon walking was 55.8 ± 24 mm. Compared to patients with very severe disability (Lequesne index > 12), those with mild-to-severe disability (Lequesne index ≤ 12) were more likely to be older than 70 years (odds ratio [OR], 2.85; 95% confidence interval [95%CI], 1.25–5) and male (OR, 2.5; 95%CI, 1.3–5); they were less likely to have a body mass index > 27 kg/m² (OR, 2.2; 95%CI, 1.3–3.3) and to engage in sporting activities (OR, 3.3; 95%CI, 1.4–10).ConclusionPatients about to undergo knee replacement surgery had high levels of pain and disability, with little variation across centers. Nevertheless, the severity of pain and disability may depend in part on age, gender, body mass index, and sporting activities, which probably influence the decision to perform knee replacement surgery.     

Tattooing Breast Cancers Treated with Neoadjuvant Chemotherapy

Background In breast carcinomas treated with neoadjuvant chemotherapy, intraoperative identification of residual tumors may be difficult. A well-tolerated, low-diffusion charcoal suspension has been designed to tattoo breast tumors. In this study, we investigated whether this tattooing technique is efficient for localizing the tumor after treatment with chemotherapy. Methods In a series of 109 patients with large breast tumors, a 4% or 10% charcoal suspension was injected at the time of the initial biopsy before preoperative chemotherapy. Results Tolerance was good. After three or four cycles of chemotherapy, 91 patients underwent conservative treatment, and the surgical specimen was examined intraoperatively. The charcoal was detected in 94% of the cases. The charcoal was seen in the nodule or at the periphery in the surgical specimen without any acute inflammatory reaction or diffusion. Conclusions On the basis of these results, this micronized charcoal suspension at a defined granulometry and a concentration of 10% seems to be ideal for tattooing breast carcinomas over a period of 3 months in patients in whom neoadjuvant chemotherapy is planned.     

Hepatic vein obstruction in idiopathic hypereosinophilic syndrome

We report an association between idiopathic hypereosinophilic syndrome and obstruction of the hepatic veins (Budd-Chiari syndrome). Budd-Chiari syndrome was assessed by liver biopsy and hepatic phlebography and documented by computed tomography. Postmortem examination revealed fibrous occlusion of the hepatic venous tree, as well as fibrosis of the endocardium and of myocardial and pulmonary vessels. To our knowledge, the association between idiopathic hypereosinophilic syndrome and Budd-Chiari syndrome has never previously been reported. Since it has been suggested that hypereosinophilia might cause endothelium damage, a link between these two entities is postulated.     

Combining Cadherin Expression with Molecular Markers Discriminates Invasiveness in Growth Hormone and Prolactin Pituitary Adenomas

Although growth hormone (GH)‐ and prolactin (PRL)‐secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell‐type specific. Somatotrophs and lactotrophs express mainly E‐cadherin and cadherin 18, whereas N‐cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E‐cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E‐cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, β‐catenin and p120 catenin. Strikingly, de novo expression of N‐cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.