Cholinergic regulation of bone.

Bone remodeling is regulated by the two branches of the autonomic nervous system: the adrenergic and the cholinergic branches. Adrenergic activity favors bone loss, whereas cholinergic activity has been recently shown to favor bone mass accrual. In vitro studies have reported that cholinergic activity induces proliferation and differentiation of bone cells. In vivo studies have shown that the inhibition of cholinergic activity favors bone loss, whereas its stimulation favors bone mass accrual. Clinical studies have shown that bone density is associated with the function of many cholinergic-regulated tissues such as the hypothalamus, salivary glands, lacrimal glands and langerhans cells, suggesting a common mechanism of control. Altogether, these observations and linked findings are of great significance since they improve our understanding of bone physiology. These discoveries have been successfully used recently to investigate new promising therapies for bone diseases based on cholinergic stimulation. Here, we review the current understanding of the cholinergic activity and its association with bone health.

Acetylcholinesterase inhibitors and healing of hip fracture in Alzheimer's disease patients: a retrospective cohort study.

OBJECTIVES This study was designed to assess effects of cholinergic stimulation using acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate cholinergic receptors and are used to treat Alzheimer's disease (AD), on healing of hip fractures. METHODS A retrospective cohort study was performed using 46-female AD patients, aged above 75 years, who sustained hip fractures. Study analyses included the first 6-months after hip fracture fixation procedure. Presence of AChEIs was used as predictor variable. Other variables that could affect study outcomes: age, body mass index (BMI), mental state or type of hip fracture, were also included. Radiographic union at fracture site (Hammer index), bone quality (Singh index) and fracture healing complications were recorded as study outcomes. The collected data was analyzed by student's-t, Mann-Whitney-U and chi-square tests. RESULTS No significant differences in age, BMI, mental state or type of hip fracture were observed between AChEIs-users and nonusers. However, AChEIs-users had better radiographic union at the fracture site (relative risk (RR),2.7; 95%confidence interval (CI),0.9-7.8), better bone quality (RR,2.0; 95%CI,1.2-3.3) and fewer healing complications (RR,0.8; 95%CI,0.7-1.0) than nonusers. CONCLUSION In elderly female patients with AD, the use of AChEIs might be associated with an enhanced fracture healing and minimized complications.

Fracturas femorales periprotésicas de rodilla tratadas con clavo intramedular retrógrado y osteosíntesis con placa: comparación de resultados a medio-largo plazo

INTRODUCTION: The femoral periprosthetic fracture of the knee is one of the most feared complications because of its repercussions. Incidence are more and more likely due to the increase of total implanted arthroplasty of the knee, due to the increasing lifespan among the general population. The objective of this study is to analyze some of the perioperative aspects of the treatment of these fractures, comparing the use of osteosynthesis with plates and the retrograde nailing in those patients with femoral periprosthetic knee fractures with a stable implant. MATERIAL AND METODS: The study retrospectively examines 18 cases treated consecutively in our hospital (3 men and 15 women, average age of 72.7 years) between the years of 2000 and 2009. All fractures were located in the distal femur and on a stable implant. Eight were treated through retrograde nailing (Group I) and ten with plates (Group II). The cases are analyzed through the tests of the University of Mann-Withney and the exact Fischer test, with significant values of p≤0.05, the variables of median hospital stay, necessity of transfusion indicated with values of hemoglobin less than 8 mg/ml, preoperative radiological alignment and postoperative alignment of the total knee prosthesis (TKR), measured following the anatomical tibiofemoral axis, time of consolidation and incidence of localized complications in both groups. RESULTS: We did not find any statistically significant differences between the two groups in any of the variables analyzed. Localized complications are more frequent in Group I (62.5 percent of patients) than in Group II (10 percent of patients). The need for transfusion is greater in Group II (40 percent) than in Group I (12.5 percent). CONCLUSIONS: The type of implant used in treatment of femoral periprosthetic knee fracture does not significantly influence perioperative factors. The treatment for this type of fractures should be individually chosen in relation to the type of fracture, characteristics of the patient and stability and prosthesis model of the primary knee.

Ultrastructural and molecular analysis of Bowman's layer corneal dystrophies: an epithelial origin?

PURPOSE: Two mutations (R555Q and R124L) in the BIGH3 gene have been described in anterior or Bowman's layer dystrophies (CDB). The clinical, molecular, and ultrastructural findings of five families with CDB was reviewed to determine whether there is a consistent genotype:phenotype correlation. METHODS: Keratoplasty tissue from each patient was examined by light and electron microscopy (LM and EM). DNA was obtained, and exons 4 and 12 of BIGH3 were analyzed by polymerase chain reaction and single-stranded conformation polymorphism/heteroduplex analysis. Abnormally migrating products were analyzed by direct sequencing. RESULTS: In two families with type I CDB (CDBI), the R124L mutation was defined. There were light and ultrastructural features of superficial granular dystrophy and atypical banding of the "rod-shaped bodies" ultrastructurally. Patients from three families with "honeycomb" dystrophy were found to carry the R555Q mutation and had characteristic features of Bowman's dystrophy type II (CDBII). CONCLUSIONS: There is a strong genotype:phenotype correlation among CBDI (R124L) and CDBII (R555Q). LM and EM findings suggest that epithelial abnormalities may underlie the pathology of both conditions. The findings clarify the confusion over classification of the Bowman's layer dystrophies.

Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alveolar bone resorption by mitochondrial-related mechanisms.

BACKGROUND/OBJECTIVES Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats. METHODS/FINDINGS Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations. CONCLUSIONS The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.

Artrodesis de tobillo: resultados comparativos de diferentes técnicas

INTRODUCTION: Ankle arthrodesis in an intervention that may be performed using a variety of surgical approaches. The joint may be stabilized using diferent systems, with or without bone graft. MATERIAL AND METHODS: Retrospective study that collected the results of 40 patients who underwent ankle arthrodesis; the complications that arose were analyzed, results according to the AOFAS clinical rating system, global patient satisfaction and the relationship with the articular approach route, the !xation system or the usage of grafts.RESULTS: 55% of the patients presented one or more complication that motivated a total of 12 re-interventions in 10 patients (excludes removal of osteosynthesis material). The absence of consolidation, which required a new arthrodesis was more frequent in patients where osteosynthesis was not used (two out of three cases) than in those using screws (four out of 24 cases), while there was no register of this in 13 patients in which intramedullary pin. The use of the distal extreme of the fibula or the iliac crest as bone graft has failed to improve the consolidation. Arthroscopic approaches avoid the appearance of soft tissue complications, although the consolidation disorders were more frequent. The average score on the AOFAS clinical rating system was 56.4±21.2 and 55% of the patients were satisfied. CONCLUSIONS: Although the case histories fail to provide significant results, it is a demanding intervention, with an elevated complication rate. Intramedullary pins seem to favor improved consolidation.

¿Es posible tratar una fractura supraintercondilea de codo por artroscopia?

This paper presents a new approach to the treatment of acute fractures in the elbow area, with the support of arthroscopic equipment. There are only a few studies that describe the indications, techniques and results of the arthroscopy-assisted treatment of these pathologies. The authors believe that this tool can be useful for achieving a precise definition of the type of bone-ligament injuries in an elbow joint, thus optimizing treatment and supporting early functional recovery.

Localization of peroxisome proliferator-activated receptor alpha (PPARα) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus.

The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and palmithylethanolamide (PEA) are known to be endogenous ligands of PPARα receptors, and their presence requires the activation of a specific phospholipase D (NAPE-PLD) associated with intracellular Ca(2+) fluxes. Thus, the identification of a specific population of NAPE-PLD/PPARα-containing neurons that express selective Ca(2+)-binding proteins (CaBPs) may provide a neuroanatomical basis to better understand the PPARα system in the brain. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the co-existence of NAPE-PLD/PPARα and the CaBPs calbindin D28k, calretinin and parvalbumin in the rat hippocampus. PPARα expression was specifically localized in the cell nucleus and, occasionally, in the cytoplasm of the principal cells (dentate granular and CA pyramidal cells) and some non-principal cells of the hippocampus. PPARα was expressed in the calbindin-containing cells of the granular cell layer of the dentate gyrus (DG) and the SP of CA1. These principal PPARα(+)/calbindin(+) cells were closely surrounded by NAPE-PLD(+) fiber varicosities. No pyramidal PPARα(+)/calbindin(+) cells were detected in CA3. Most cells containing parvalbumin expressed both NAPE-PLD and PPARα in the principal layers of the DG and CA1/3. A small number of cells containing PPARα and calretinin was found along the hippocampus. Scattered NAPE-PLD(+)/calretinin(+) cells were specifically detected in CA3. NAPE-PLD(+) puncta surrounded the calretinin(+) cells localized in the principal cells of the DG and CA1. The identification of the hippocampal subpopulations of NAPE-PLD/PPARα-containing neurons that express selective CaBPs should be considered when analyzing the role of NAEs/PPARα-signaling system in the regulation of hippocampal functions.

Intracortical connectivity of layer VI pyramidal neurons in the somatosensory cortex of normal and barrelless mice.

In mice, barrels in layer IV of the somatosensory cortex correspond to the columnar representations of whisker follicles. In barrelless (BRL) mice, barrels are absent, but functionally, a columnar organization persists. Previously we characterized the aberrant geometry of thalamic projection of BRL mice using axonal reconstructions of individual neurons. Here we proceeded with the analysis of the intracortical projections from layer VI pyramidal neurons, to assess their contribution to the columnar organization. From series of tangential sections we reconstructed the axon collaterals of individual layer VI pyramidal neurons in the C2 barrel column that were labelled with biocytin [controls from normal (NOR) strain, 19 cells; BRL strain, nine cells]. Using six morphological parameters in a cluster analysis, we showed that layer VI neurons in NOR mice are distributed into four clusters distinguished by the radial and tangential extent of their intracortical projections. These clusters correlated with the cortical or subcortical projection of the main axon. In BRL mice, neurons were distributed within the same four clusters, but their projections to the granular and supragranular layers were significantly smaller and their tangential projection was less columnar than in NOR mice. However, in both strains the intracortical projections had a preference for the appropriate barrel column (C2), indicating that layer VI pyramidal cells could participate in the functional columnar organization of the barrel cortex. Correlative light and electron microscopy analyses provided morphometric data on the intracortical synaptic boutons and synapses of layer VI pyramidal neurons and revealed that projections to layer IV preferentially target excitatory dendritic spines and shafts.

Fractura bilateral de calcáneo en edad pediátrica. A propósito de un caso

OBJECTIVE: Propose and debate the treatment management for unusual traumatic pathology, both due to the age of the patient and the bilateral location. CLINICAL CASE: Bilateral calcaneal fracture in a ten year old male, after falling three meters to land on his heels. Examination revealed pain and swelling at that level, with no distal neurovascular alterations. After the clinical study, x-rays were taken, as well as a CAT scan which revealed a complex fracture of both calcanei. After 72 hours and verifying that the soft tissue was in optimal condition, the left calcaneus was immobilized with a closed cast while the right was trans!xed with a Steinmann pin following the Essex-Lopresti technique, achieved under scope to attain an acceptable reduction of the fracture and the congruency of all a"ected joints.

Luxación cerrada de astrágalo: a propósito de un caso

Total and closed dislocation of the talus is a extremely rare injury characterized by a full disruption of the ankle, subtalar and talonavicular joints and it requires an emergency treatment consisting in early reduction of the dislocation. A young male patient a ected of a closed full dislocation of the talus after a tra c accident is presented. e bibliography of the condition is reviewed.

Thorax, pelvis and hip pattern in the frontal plane during walking in unilateral transtibial amputees: biomechanical analysis.

BACKGROUND Lower limb amputees exhibit postural control deficits during standing which can affect their walking ability. OBJECTIVES The primary purpose of the present study was to analyze the thorax, pelvis, and hip kinematics and the hip internal moment in the frontal plane during gait in subjects with Unilateral Transtibial Amputation (UTA). METHOD The participants included 25 people with UTA and 25 non-amputees as control subjects. Gait analysis was performed using the Vicon(r) Motion System. We analyzed the motion of the thorax, pelvis, and hip (kinematics) as well as the hip internal moment in the frontal plane. RESULTS The second peak of the hip abductor moment was significantly lower on the prosthetic side than on the sound side (p=.01) and the control side (right: p=.01; left: p=.01). During middle stance, the opposite side of the pelvis was higher on the prosthetic side compared to the control side (right: p=.01: left: p=.01). CONCLUSIONS The joint internal moment at the hip in the frontal plane was lower on the prosthetic side than on the sound side or the control side. Thorax and pelvis kinematics were altered during the stance phase on the prosthetic side, presumably because there are mechanisms which affect postural control during walking.

Osteoarticular Expression of Musashi-1 in an Experimental Model of Arthritis.

Background. Collagen-induced arthritis (CIA), a murine experimental disease model induced by immunization with type II collagen (CII), is used to evaluate novel therapeutic strategies for rheumatoid arthritis. Adult stem cell marker Musashi-1 (Msi1) plays an important role in regulating the maintenance and differentiation of stem/precursor cells. The objectives of this investigation were to perform a morphological study of the experimental CIA model, evaluate the effect of TNFα-blocker (etanercept) treatment, and determine the immunohistochemical expression of Msi1 protein. Methods. CIA was induced in 50 male DBA1/J mice for analyses of tissue and serum cytokine; clinical and morphological lesions in limbs; and immunohistochemical expression of Msi1. Results. Clinically, TNFα-blocker treatment attenuated CIA on day 32 after immunization (P < 0.001). Msi1 protein expression was significantly higher in joints damaged by CIA than in those with no lesions (P < 0.0001) and was related to the severity of the lesions (Spearman's rho = 0.775, P = 0.0001). Conclusions. Treatment with etanercept attenuates osteoarticular lesions in the murine CIA model. Osteoarticular expression of Msi1 protein is increased in joints with CIA-induced lesion and absent in nonlesioned joints, suggesting that this protein is expressed when the lesion is produced in order to favor tissue repair.

Localization of the cannabinoid CB1 receptor and the 2-AG synthesizing (DAGLα) and degrading (MAGL, FAAH) enzymes in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus.

The retrograde suppression of the synaptic transmission by the endocannabinoid sn-2-arachidonoylglycerol (2-AG) is mediated by the cannabinoid CB1 receptors and requires the elevation of intracellular Ca(2+) and the activation of specific 2-AG synthesizing (i.e., DAGLα) enzymes. However, the anatomical organization of the neuronal substrates that express 2-AG/CB1 signaling system-related molecules associated with selective Ca(2+)-binding proteins (CaBPs) is still unknown. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the expression of the 2-AG/CB1 signaling system (CB1 receptor, DAGLα, MAGL, and FAAH) and the CaBPs calbindin D28k, calretinin, and parvalbumin in the rat hippocampus. CB1, DAGLα, and MAGL labeling was mainly localized in fibers and neuropil, which were differentially organized depending on the hippocampal CaBPs-expressing cells. CB(+) 1 fiber terminals localized in all hippocampal principal cell layers were tightly attached to calbindin(+) cells (granular and pyramidal neurons), and calretinin(+) and parvalbumin(+) interneurons. DAGLα neuropil labeling was selectively found surrounding calbindin(+) principal cells in the dentate gyrus and CA1, and in the calretinin(+) and parvalbumin(+) interneurons in the pyramidal cell layers of the CA1/3 fields. MAGL(+) terminals were only observed around CA1 calbindin(+) pyramidal cells, CA1/3 calretinin(+) interneurons and CA3 parvalbumin(+) interneurons localized in the pyramidal cell layers. Interestingly, calbindin(+) pyramidal cells expressed FAAH specifically in the CA1 field. The identification of anatomically related-neuronal substrates that expressed 2-AG/CB1 signaling system and selective CaBPs should be considered when analyzing the cannabinoid signaling associated with hippocampal functions.

Valoración del perfil lipídico y de la densidad mineral ósea en pacientes trasplantados renales

INTRODUCTION: Alterations in lipid metabolism and bone mineral metabolism disturbances are common disorders among renal transplant patients, contributing to the apparition of oxidative metabolic and cardiovascular diseases that threaten the integrity of the graft. AIMS: Describe and observe the evolution of alterations in bone mineral density (BMD) and lipid abnormalities in a population of kidney transplant patients. MATERIAL AND METHOD: The samples consisted of 119 kidney transplant patients of both sexes, measurements were performed pretransplant and posttransplant for five years of biochemical parameters, anthropometric measurements and measurement of bone mineral density at the lumbar spine, femur and radioulnar. RESULTS: During the five years after transplantation a significant increase in biochemical parameters, BMI, dyslipidemia, diabetes and hypertension occurs. At six months there is a high percentage of patients with pathologic BMD increase by 4.1% per year of transplantation. CONCLUSIONS: After kidney transplantation, a large increase of hyperlipidemia associated with a characteristic pattern of altered lipid with elevated total cholesterol, low density lipoprotein, high density lipoprotein, and the resulting increase in triglycerides, occurs despite statin therapy, leading to an increase in risk factors for diabetes, hypertension, diseases and cardiovascualres further loss of bone mass which carries a high risk of serious fractures occurs, threatening kidney graft and quality of life of patients.