Background:Mitochondrial Transcription Factor A (TFAM) is regarded as a histone-like protein of mitochondrial DNA (mtDNA), performing multiple functions for this genome. Aging affects mitochondria in a tissue-specific manner and only calorie restriction (CR) is able to delay or prevent the onset of several age-related changes also in mitochondria. Methods: Samples of the frontal cortex and soleus skeletal muscle from 6- and 26-month-old ad libitum-fed and 26-month-old calorie-restricted rats and of the livers from 18- and 28-month-old ad libitum-fed and 28-monthold calorie-restricted rats were used to detect TFAM amount, TFAM-binding to mtDNA and mtDNA content. Results:We found an age-related increase in TFAMamount in the frontal cortex, not affected by CR, versus an agerelated decrease in the soleus and liver, fully prevented by CR. The semi-quantitative analysis of in vivo binding of TFAM to specific mtDNA regions, by mtDNA immunoprecipitation assay and following PCR, showed a marked age-dependent decrease in TFAM-binding activity in the frontal cortex, partially prevented by CR. An agerelated increase in TFAM-binding to mtDNA, fully prevented by CR, was found in the soleus and liver. MtDNA content presented a common age-related decrease, completely prevented by CR in the soleus and liver, but not in the frontal cortex. Conclusions: The modulation of TFAM expression, TFAM-binding to mtDNA and mtDNA content with aging and CR showed a trend shared by the skeletal muscle and liver, but not by the frontal cortex counterpart. General significance: Aging and CR appear to induce similar mitochondrial molecular mechanisms in the skeletal muscle and liver, different from those elicited in the frontal cortex.

The behavior of the peroxisome proliferator-activated receptor-gamma coactivators PGC-1alpha/PGC-beta—dependent mitochondrial biogenesis signaling pathway, as well as the level of some antioxidant enzymes and proteins involved in mitochondrial dynamics in the liver of old rats before and after 2 months of acetyl-l-carnitine (ALCAR) supplementation, was tested. The results reveal that ALCAR treatment is able to reverse the ageassociated decline of PGC-1alpha, PGC-1beta, nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (ND1), and cytochrome c oxidase subunit IV (COX IV) protein levels, of mitochondrial DNA (mtDNA) content, and of citrate synthase activity. Moreover, it partially reverses the mitochondrial superoxide dismutase 2 (SOD2) decline and reduces the cellular content of oxidized peroxiredoxins. These data demonstrate that ALCAR treatment is able to promote in the old rat liver a new mitochondrial population that can contribute to the cellular oxidative stress reduction. Furthermore, a remarkable decline of Drp1 and of Mfn2 proteins is reported here for the first time, suggesting a reduced mitochondrial dynamics in aging liver with no effect of ALCAR treatment.

The age-related decay of mitochondrial function is a major contributor to the aging process. We tested the effects of 2-month-daily acetyl-L-carnitine (ALCAR) supplementation on mitochondrial biogenesis in the soleus muscle of aged rats. This muscle is heavily dependent on oxidative metabolism. Mitochondrial (mt) DNA content, citrate synthase activity, transcript levels of some nuclear-and mitochondrial-coded genes (cytochrome c oxidase subunit IV [COX-IV], 16S rRNA, COX-I) and of some factors involved in the mitochondrial biogenesis signaling pathway (peroxisome proliferator-activated receptor gamma [PPAR gamma] coactivator-1 alpha [PGC-1 alpha], mitochondrial transcription factor A mitochondrial [TFAM], mitochondrial transcription factor 2B [TFB2]), as well as the protein content of PGC-1 alpha were determined. The results suggest that the ALCAR treatment in old rats activates PGC-1 alpha-dependent mitochondrial biogenesis, thus partially reverting the age-related mitochondrial decay.

Aging affects mitochondria in a tissue-specific manner and to date only calorie restriction (CR) is able to delay or prevent the onset of several age-related changes also in mitochondria. Mitochondrial Transcription Factor A (TFAM) is considered the histone-like protein of mitochondrial DNA (mtDNA), performing multiple functions for this genome including modulation of transcription, regulation of copy number and maintenance of mtDNA as well as constitution of mtDNA nucleoids. We used samples of frontal cortex and soleus skeletal muscle from 6- and 26-month-old ad libitum-fed and 26-month-old calorie-restricted rats and of livers from 18- and 28-month-old ad libitum-fed and 28-month-old calorie-restricted rats to determine TFAM amount, TFAM-binding to mtDNA and mtDNA content. We found an age-related increase in TFAM amount in frontal cortex, not affected by CR, versus an age-related decrease in soleus and liver, fully prevented by CR. The semi-quantitative analysis of in vivo binding of TFAM to specific mtDNA regions, by mtDNA immunoprecipitation assay, showed a marked age-dependent decrease in TFAM-binding activity in the frontal cortex, partially prevented by CR. Instead, an age-related increase in TFAM-binding to mtDNA, fully prevented by CR, was found in the soleus and liver. MtDNA content showed a common age-related decrease, completely prevented by CR in soleus and liver, but not in frontal cortex. We highlight for the first time a trend shared by skeletal muscle and liver, but not by the frontal cortex counterpart, in some relevant changes induced by aging and CR in mitochondria. Such trend involves the modulation of TFAM expression, TFAM-binding to mtDNA and mtDNA content and supports the existence of similar mitochondrial molecular mechanisms in skeletal muscle and liver but not in frontal cortex. Modulation of TFAM-binding to mtDNA, affecting mtDNA functions, appears to contribute to the tissue-specific alterations of mitochondrial biogenesis during aging as well as CR.

Aging markedly affects mitochondrial biogenesis and functions particularly in tissues highly dependent on the organelle’s bioenergetics capability such as the brain’s frontal cortex. Calorie restriction (CR) diet is, so far, the only intervention able to delay or prevent the onset of several age-related alterations in different organisms. We determined the contents of mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), and the 4.8-kb mtDNA deletion in the frontal cortex from young (6-monthold) and aged (26-month-old), ad libitum-fed (AL) and calorie-restricted (CR), rats. We found a 70 % increase in TFAM amount, a 25 % loss in mtDNA content, and a 35 % increase in the 4.8-kb deletion content in theaged AL animals with respect to the young rats. TFAM-specific binding to six mtDNA regions was analyzed by mtDNA immunoprecipitation and semiquantitative polymerase chain reaction (PCR), showing a marked age-related decrease. Quantitative realtime PCR at two subregions involved in mtDNA replication demonstrated, in aged AL rats, a remarkable decrease (60–70 %) of TFAM-bound mtDNA. The decreased TFAM binding is a novel finding that may explain the mtDNA loss in spite of the compensatory TFAM increased amount. In aged CR rats, TFAM amount increased and mtDNA content decreased with respect to young rats’ values, but the extent of the changes was smaller than in aged AL rats. Attenuation of the age-related effects due to the diet in the CR animals was further evidenced by the unchanged content of the 4.8-kb deletion with respect to that of young animals and by the partial prevention of the age-related decrease in TFAM binding to mtDNA.

Aging affects mitochondria in a tissue-specific manner. Calorie restriction (CR) is, so far, the only intervention able to delay or prevent the onset of several age-related changes also in mitochondria. Using livers from middle age (18- month-old), 28-month-old and 32-month-old ad libitum-fed and 28-month-old calorie-restricted rats we found an agerelated decrease in mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (TFAM) amount, fully prevented by CR. We revealed also an age-related decrease, completely prevented by CR, for the proteins PGC-1α NRF-1 and cytochrome c oxidase subunit IV, supporting the efficiency of CR to forestall the age-related decrease in mitochondrial biogenesis. Furthermore, CR counteracted the age-related increase in oxidative damage to proteins, represented by the increased amount of oxidized peroxiredoxins (PRX-SO3) in the ad libitum-fed animals. An unexpected age-related decrease in the mitochondrial proteins peroxiredoxin III (Prx III) and superoxide dismutase 2 (SOD2), usually induced by increased ROS and involved in mitochondrial biogenesis, suggested a prevailing relevance of the age-reduced mitochondrial biogenesis above the induction by ROS in the regulation of expression of these genes with aging. The partial prevention of the decrease in Prx III and SOD2 proteins by CR also supported the preservation of mitochondrial biogenesis in the anti-aging action of CR. To investigate further the ageand CR-related effects on mitochondrial biogenesis we analyzed the in vivo binding of TFAM to specific mtDNA regions and demonstrated a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR. A novel, positive correlation between the paired amounts of TFAM-bound mtDNA at these sub-regions was found in the joined middle age ad libitum-fed and 28-month-old calorie-restricted groups, but not in the 28-month-old ad libitum-fed counterpart suggesting a quite different modulation of TFAM binding at both origins of replication in aging and CR.

Mitochondrial biogenesis is among the organelle’s features affected by aging in tissue-specific ways. The only intervention, so far, able to delay or prevent the onset of several age-related changes, also in mitochondria, is calorie restriction (CR). Aging and CR both influence in a relevant manner mitochondrial structure and function in rat liver. Using livers from 18-month-old, 28-month-old, 32-month-old ad libitum-fed and 28-month-old calorie-restricted rats we found an age-related decrease in mitochondrial DNA (mtDNA) content and Mitochondrial Transcription Factor A (TFAM) amount, fully prevented by CR. Also the proteins PGC-1 and NRF-1 as well as the nuclear-encoded cytochrome c oxidase subunit IV revealed an age-related decrease, confirming the reduction in mitochondrial biogenesis with aging, that was completely prevented by CR. The already described age-related increased oxidative stress was verified and also prevented by CR. We reported with aging a decrease in peroxiredoxin III (Prx III) and in mitochondrial superoxide dismutase 2 (SOD2) proteins, usually sensitive to an increased ROS presence and also involved in mitochondrial biogenesis, which suggested a prevailing relevance of the age-reduced mitochondrial biogenesis above the induction by ROS in the regulation of expression with aging. Furthermore, the full prevention of the decrease in Prx III and SOD2 by CR suggested that, in rat liver, the preservation of the mitochondrial biogenesis might be more relevant than the reduction of the oxidative stress in the anti-aging action of CR. We then analyzed the in vivo TFAM binding to specific mtDNA regions finding a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR. Joining the data from the 18-month-old ad libitum-fed and the 28-month-old calorie-restricted samples we could find a novel, positive correlation between the coupled amounts of TFAM-bound mtDNA at the origins of replication, not present in the 28-month-old ad libitum-fed animals, thus suggesting a quite different modulation of TFAM binding at these sub-regions in aging and in CR, likely involved in the respective alterations of mitochondrial biogenesis.

In recent years, the application of fibrin sealant has been shown to be efficacious in the management of intraoperative and postoperative hemostasis. We designed a prospective randomized controlled clinical trial to assess the efficacy of two different dosages of fibrin sealant (5 and 10 ml) in patients undergoing total knee arthroplasty, as compared with the untreated control group. A total of 90 patients entered the study, randomly assigned to one of the three groups: treatment with 5 ml fibrin sealant (30 patients), with 10 ml fibrin sealant (30 patients) or no treatment (30 patients). A statistically significant difference in the mean reduction of hemoglobin concentrations was found on the first postoperative day in the treated groups as compared with the controls: 5 ml fibrin sealant (2.6 mg/dl) and 10 ml fibrin sealant (2.5 mg/dl) vs. controls (3.7 mg/dl) (P = 0.024). The mean number of blood transfusions was significantly lower in the treated groups: 5 ml (0.5) and 10 ml (0.3) of fibrin sealant vs. controls (1) (P = 0.0019). Functional recovery was also better in the treated groups: on the seventh day, the joint ROM (range of motion) was statistically superior in the 5 ml group (96.5°) and 10 ml group (98.8°) as compared with the controls (75.5°) (P < 0.0001). This study supports the efficacy of administering fibrin sealant in the perioperative management of bleeding after total knee arthroplasty and shows that a 5 ml dosage yields a comparable outcome to the 10 ml dosage previously reported in the literature.

We previously reported the ability of dietary supplementation with acetyl-L-carnitine (ALCAR) to prevent agerelated decreases of mitochondrial biogenesis in skeletal muscle and liver of old rats. Here, we investigate the effects of ALCAR supplementation in cerebral hemispheres and cerebellum of old rats by analyzing several parameters linked to mitochondrial biogenesis, mitochondrial dynamics and antioxidant defenses. We measured the level of the coactivators PGC-1α and PGC-1β and of the factors regulating mitochondrial biogenesis, finding an age-related decrease of PGC-1β, whereas PGC-1α level was unvaried. Twenty eight-month old rats supplemented with ALCAR for one and two months showed increased levels of both factors. Accordingly, the expression of the two transcription factors NRF-1 and TFAM followed the same trend of PGC-1β. The level of mtDNA, ND1 and the activity of citrate synthase, were decreased with aging and increased following ALCAR treatment. Furthermore, ALCAR counteracted the age-related increase of deleted mtDNA. We also analyzed the content of proteins involved in mitochondrial dynamics (Drp1, Fis1, OPA1 and MNF2) and found an age-dependent increase of MFN2 and of the long form of OPA1. ALCAR treatment restored the content of the two proteins to the level of the young rats. No changes with aging and ALCAR were observed for Drp1 and Fis1. ALCAR reduced total cellular levels of oxidized PRXs and counteracted the age-related decrease of PRX3 and SOD2. Overall, our findings indicate a systemic positive effect of ALCAR dietary treatment and a tissue specific regulation of mitochondrial homeostasis in brain of old rats. Moreover, it appears that ALCAR acts as a nutrient since in most cases its effects were almost completely abolished one month after treatment suspension. Dietary supplementation of old rats with this compound seems a valuable approach to prevent age-related mitochondrial dysfunction and might ultimately represent a strategy to delay age-associated negative consequences in mitochondrial homeostasis.

BACKGROUND: In literature there is a general consensus that the use of the mirror improves proprioception. During rehabilitation the mirror is an important instrument to improve stability. In some sports, such as dancing, mirrors are widely used during training. The purpose of this study is to evaluate the effectiveness of the use of a mirror on balance in young dancers. Sixty-four young dancers (ranging from 9-10 years) were included in this study. Thirty-two attending lessons with a mirror (mirror- group) were compared to 32 young dancers that attended the same lessons without a mirror (non-mirror group). Balance was evaluated by BESS (Balance Error Scoring System), which consists of three stances (double limb, single limb, and tandem) on two surfaces (firm and foam). The errors were assessed at each stance and summed to create the two subtotal scores (firm and foam surface) and the final total score (BESS). The BESS was performed at recruitment (T0) and after 6 months of dance lessons (T1). RESULTS: The repeated measures ANOVA analysis showed that for the BESS total score there is a difference due to the time (F = 3.86; p < 0.05). No other differences due to the group or to the time of measurement were found (p > 0.05). The analysis of the multiple regression model showed the influence of the values at T0 for every BESS items and the dominance of limb for stability on an unstable surface standing on one or two legs. CONCLUSIONS: These preliminary results suggest that the use of a mirror in a ballet classroom does not improve balance acquisition of the dancer. On the other hand, improvement found after 6 months confirms that at the age of the dancers studied motor skills and balance can easily be trained and improved.

Tenosynovial chondromatosis is an uncommon type of chondro-dysplasia of synovial and connective tissue. We report a case of a patient with a primary right wrist extra-articular chondromatosis extending to the flexor and the extensor compartments.

The development of metallosis as a complication following rupture of a hip replacement is known to occur as a result of contact with metal components of the prosthesis (1).In such cases, high cobalt (Co), chromium (Cr) and molybdenum (Mo) levels in the blood have been reported by several Authors (2).Recently, it has been stressed that the clinical investigation should focus on general reactions to high circulating metal levels, such as toxicity for the central nervous system (CNS) and the immune system (3).Despite the increasing interest of literature in ceramic-on-ceramic hip arthroplasty (4),little is known about these complications, and in particular of metallosis. To our knowledge this is the first description of a condition of extensive metallosis and radiographic signs presenting as a result of wear of a ceramic-on-ceramic prosthesis

Painful hip prosthesis is the most feared immediate and remote complication of a primary implant and usually represents the failure of one or more therapeutic moments. In cases of aseptic implant failure, the causes invoked may be represented by an incorrect indication, the quality of materials, local and general condition of the patient and especially from a bad joint biomechanics. In cases of septic loosening, however, the cause of failure to be found in the location of pathogens within the implant. In planning a revision is necessary to respect many important steps. They are represented by the exact identification of the causes of failure, the correct preoperative planning, by respecting the skin incisions, the proper choice of the prosthesis, planning the surgical technique, and finally by an appropriate rehabilitation program. In the evaluation of hip failure the first diagnostic step is to recognize exactly those aseptic and septic forms anyway to exclude the diagnosis of infection.

Fracture nonunion is a dreadful entity and can account for a high percentage of both surgeon and patient’ s stress and frustration. Fracture nonunion is often anticipated after a severe traumatic injury, such as an open fracture with segmental bone loss, but it may also make an unanticipated appearance after treatment of a low-energy fracture that seemed destined to heal. The most basic requirements for fracture healing include both biological and mechanical factors. Biological factors are distinguished as local and systemic and are physiological and pathological condition of bone and of the whole subject. Mechanicalfactors able to determine nonunion are essentially distinguished in quality of reduction, quality and quantity of fixation, devices positioning. The introduction of new surgical devices is the evidence of the understanding of biomechanical issues of bone. Those precious innovative instruments must be known by the surgeon in a theoretical mode; only respecting the biomechanical rules of bone healing and applying those to his surgical practice he could finally benefit of them and avoid the causes connected to nonunion events.

Total knee arthroplasty (TKA) is often associated with a severe local inflammatory reaction which, unless controlled, leads to persistent pain up to one year after surgery. Standard and accelerated rehabilitation protocols are currently being implemented after TKA, but no consensus exists regarding the long-term effects. Biophysical stimulation with pulsed electromagnetic fields (PEMFs) has been demonstrated to exert an anti-inflammatory effect, to promote early functional recovery and to maintain a positive long-term effect in patients undergoing joint arthroscopy. The aim of this study was to evaluate whether PEMFs can be used to limit the pain and enhance patient recovery after TKA.

Klippel-Trenaunay syndrome (KTS) is characterized by a cutaneous vascular nevus of the involved extremity, as well as bone and soft tissue hypertrophy of the extremity and venous malformations. We present the case of a 52-year-old man with a femoral fracture and a history of haemangiomas, limb bone hypertrophy and varicosity. The patient was Wnally diagnosed with KTS and treated in mini-invasive surgery by endomedullary fracture nailing in general anaesthesia. Clinical management was particularly demanding, not only because of the need to monitor the risk of haemorrhage and thrombosis but also because of the onset of a rare picture of neuropathic pain with hyperalgesia and allodynia, never previously reported in patients aVected by KTS, that required the administration of major opioid drugs. According to our knowledge, this is the second case of KTS managed for femoral fracture. Unlike the previous report in literature, in this case a severe disabling neuropathic pain complicated the clinical management.

BACKGROUND: An increase in mitochondrial DNA (mtDNA) content and mitochondrial biogenesis associated with the activation of PGC-1alpha signalling pathway was previously reported in type I endometrial cancer. The aim of this study has been to evaluate if mtDNA content and the citrate synthase (CS) activity, an enzyme marker of mitochondrial mass, increase in progression from control endometrium to hyperplasia to type I endometrial carcinoma. RESULTS: Given that no statistically significant change in mtDNA content and CS activity in endometrium taken from different phases of the menstrual cycle or in menopause was found, these samples were used as control. Our research shows, for the first time, that mtDNA content and citrate synthase activity increase in hyperplastic endometrium compared to control tissues, even if their levels remain lower compared to cancer tissue. In particular, mtDNA content increases seem to precede increases in CS activity. No statistically significant change in mtDNA content and in CS activity was found in relation to different histopathological conditions such as grade, myometrial invasion and stage. CONCLUSION: MtDNA content and citrate synthase activity increases in pre-malignant lesions could be a potential molecular marker for progression from hyperplasia to carcinoma.

Type I endometrial cancer (EC) is the most common form of EC, displaying less aggressive behavior than type II. The development of type I endometrial cancer is considered a multistep process, with slow progression from normal endometrium to hyperplasia, the premalignant form, and endometrial cancer as a result of an unopposed estrogenic stimulation. The role of mitochondria in type I EC tumor progression and prognosis is currently emerging. This review aims to explore mitochondrial alterations in this cancer and in endometrial hyperplasia focusing on mitochondrial DNA mutations, respiratory complex I deficiency, and the activation of mitochondrial quality control systems. A deeper understanding of altered mitochondrial pathways in type I EC could provide novel opportunities to discover new diagnostic and prognostic markers as well as potential therapeutic targets.

Hip and neck femur fracture surgery was associated with high post-operative mortality and poor functional results. The decision-making process with regards to the elderly with hip or neck femur fractures was of great importance, requiring consideration of ethical, medico legal and economic factors in addition to the purely medical ones. An important component in the decision-making process was the precise knowledge of the expected mortality. We considered here several articles from 1 January 2002 to 31 August 2010 that identified the possible scoring system to predict mortality in the elderly undergoing hip or neck femur fracture surgery. We found seven studies which included a total of 12,177 patients that were assigned to hip/neck femur fracture surgery. Each study identified the possible scoring system to predict mortality in the elderly undergoing hip/neck femur fracture surgery. By reviewing the literature available, it was shown that there were more multidimensional prognostic indexes in the elderly after hospitalization than multidimensional prognostic indexes with hip or neck femur fracture which could be used as a simple point scoring system at the bedside to predict mortality in the elderly undergoing hip or neck femur fracture surgery. Although, all the prognostic indexes searched worked well for a general population, but they were of limited validity in the specific, relatively homogeneous population of hip/neck femur fracture patients.

The effect of acetyl-L-carnitine (ALCAR) supplementation to 3-month-old rats in normal-loading and unloading conditions has been here investigated by a combined morphological, biochemical and transcriptional approach to test whether ALCAR might cause a remodeling of the metabolic/ contractile phenotype of soleus muscle. Morphological assessment demonstrated an increase of type I oxidative fiber content and cross-sectional area in ALCAR-treated animals both in normal-loading and in unloading conditions. ALCAR prevented loss of mitochondrial mass in unloaded animals whereas no ALCAR-dependent increase of mitochondrial mass occurred in normal-loaded muscle. Validated microarray analysis delineated an ALCAR-induced maintenance of a slow-oxidative expression program only in unloaded soleus muscle. Indeed, the muscle adjustment of the expression profile of factors underlying mitochondrial oxidative metabolism, protein turnover, fiber type differentiation and an adaptation of voltage-gated ion channel expression was distinguishable with respect to the loading status. This selectivity may suggest a key role of muscle loading status in the manifestation of ALCAR effects. The results extend to a broader level of biological informations the previous notion on ALCAR positive effect in rat soleus muscle during unloading and point to a role of ALCAR for the maintenance of its slow-oxidative fiber character.

Patellar tendon rerupture is a relatively uncommon condition that severely compromises the function of the extensor mechanism of the knee. Few cases described in the literature does not show a unique mode of treatment for this type of lesion. We report the case of a young athlete with traumatic patellar tendon rerupture. The first rupture was treated with the use of Statak anchors. Following a second rerupture incident as a result of a sporting accodent, the tendon was reconstructed with the use of an autologous graft tendon of semitendinosus and biological augmentation with gracilis tendon. For both tendons the distal insertion part was preserved to facilitate the healing process. The treatment was completed with the application of a neutralization cerclage wire and with local injection of plateket reach plasma (PRP). At 12 months follow up, a full recovery of the structure and function of the extensor mechanism was observed and the patient was able to resume normal sports competitive activity

Background and aims: Cachexia and muscle atrophy are common derivations of cancer and chemotherapy treatments (cisplatin). Growth Hormone Secretagogues (GHSs) are synthetic peptidic and nonpeptidic molecules, able to stimulate Growth Hormone secretion and to target a specific receptor in skeletal muscle counteracting cachexia. We report the effects of GHSs on skeletal muscle mitochondrial biogenesis and dynamics in a rat model of cisplatin induced cachexia. Methods: Cachexia was induced in adult rats by intraperitoneal injection of cisplatin (1 mg/kg) once daily for 3 days. The treatment with GHSs was hexarelin, 160 μg/Kg and JMV2894, 320 μg/Kg, ip, and b.i.d, for 5 days. Results: We measured in rat tibialis anterior of cisplatin treated group, a decrease of the level of mtDNA, PGC-1α and TFAM (proteins involved in mitochondrial biogenesis), PRX3 and SOD2 (antioxidant mitochondrial enzymes) and an increase of the oxidized total cellular PRXs which suggest an increase of ROS damages. GHSs treatment increased mtDNA, PGC-1α and TFAM, PRX3 and SOD2 level while reduced the oxidized total cellular PRXs. The MFN2 and Drp1 proteins level increased with cisplatin administration, whereas it decreased after GHSs treatment. These results demonstrated that cisplatin treatment depresses several parameters linked to mitochondrial biogenesis and integrity and that the GHSs administration prevents these alterations. It is involved in the disease the activation of proteolysis due to AKT and FoxO3a dephosphorylation, whereas PGC-1α is able to inhibit the transcriptional activity of FoxO3a, suppressing atrogenes expression and protein degradation. In particular, GHSs stimulated the phosphorylation of AKT and FoxO3a, thus inducing a recovery of skeletal muscle mass. In addition, the here reported increase of PGC-1α prevents the activation of atrogenes by blocking the FoxO3a function. Conclusions: These data indicate that treatment with GHSs exert a muscle protective effect in cisplatin-induced model of cachexia and may be a therapeutic promising tool for supportive care in cachexia.

Oxidative stress has a central role in aging and in several age-linked diseases such as neurodegenerative diseases, diabetes and cancer. Mitochondria, as the main cellular source and target of reactive oxygen species (ROS) in aging, are recognized as very important players in the above reported diseases. Impaired mitochondrial oxidative phosphorylation has been reported in several aging tissues. Defective mitochondria are not only responsible of bioenergetically less efficient cells but also increase ROS production further contributing to tissues oxidative stress. Acetyl-L-carnitine (ALCAR) is a biomolecule able to limit age-linked mitochondrial decay in brain, liver, heart and skeletal muscles by increasing mitochondrial efficiency. Here the global changes induced by aging and by ALCAR supplementation to old rat on the mitochondrial proteome of rat liver has been analyzed by means of the two-dimensional polyacrylamide gel electrophoresis. Mass spectrometry has been used to identify the differentially expressed proteins. A significant age-related change occurred in 31 proteins involved in several metabolisms. ALCAR supplementation altered the levels of 26 proteins. In particular, ALCAR reversed the age-related alterations of 10 mitochondrial proteins relative to mitochondrial cristae morphology, to the oxidative phosphorylation and antioxidant systems, to urea cycle, to purine biosynthesis.

Introduction Extracorporeal shockwave therapy (ESWT) produces good results in the treatment of insertional Achilles tendinopathy. The efficacy of combined administration of dietary supplements with ESWT has not yet been studied. Methods In this prospective, randomized clinical trial, Shock Waves therapy and Arginine for Achilles Tendinopathy (SWAAT), subjects affected by insertional Achilles tendinopathy were enrolled. Between January and October 2011, all participants underwent three sessions of ESWT. In addition, the patients in the experimental group received a daily dietary supplement containing arginine, Vinitrox (Bio Serae Laboratories SAS, Bram, France), collagen, methyl-sulfonyl-methane, vitamin C, and bromelain, while the control group patients received placebo. Results There was no statistically significant difference in the visual analog scale (VAS) score between the two groups at 2 months (3.9 vs. 5.1; P = 0.07), whereas at 6 months the value was significantly lower in the experimental group (2.0 vs. 2.9; P = 0.04). The difference in the Ankle-Hindfoot Scale score at 2 and 6 months of follow-up (FU) was significantly in favor of the experimental group (2 months: 85.4 vs. 72.1; P = 0.0035; 6 months: 92.4 vs. 76.5; P = 0.0002). The Roles and Maudsley score also showed a statistically significant difference between the two groups in favor of the experimental arm as regards patient satisfaction (at 2 months: 1.7 vs. 2.8; P &lt; 0.0001; at 6 months: 1.5 vs. 2.3; P &lt; 0.001). There was a statistically significant reduction in tissue oximetry values compared to baseline in both treatment groups at 2 and 6 months of FU. Comparing the groups, only at the last FU, at 6 months, was a significantly lower oximetry value observed in the experimental group versus controls (60.2 vs. 66.0; P = 0.007). Conclusion On the basis of the results obtained in this study, the authors conclude that in the treatment of insertional Achilles tendinopathy, ESWT induces a hemodynamic re-equilibrium with an in tendon trophism. The addition of specific dietary supplements could improve the therapeutic response

Due to a growing numbers of lateral fragility fractures of the femur and their high social costs the need to work out an effective strategy in order to find a better solution for these patients is warranted. From January 2010 to July 2011, we carried out a prospective randomized clinical study comparing the results of patients with femoral lateral fractures treated by nail and cephalic hydroxyapatite coated screws (study group including 27 patients) compared to the patients with the same fractures treated with nail and head standard screws (control group including 27 patients). We defined the two parts of the femoral neck as ROI 1 (under the head screw) and ROI 2 (above the femoral screw) on the AP view. The bone density of the two areas was calculated using DEXA at T0 (1st day post-surgery), at T1 (40th day post-surgery), at T2 (3 months later), at T3 (1 year later). The clinical-radiography evaluations were based on the Harris Hip Score (HHS), ADL test and x-ray views of the hip. As far as the bone mineral density average of ROI 1 and ROI 2 is concerned, we found a significant statistical increase at T1 and T3 in the study group, while it was not significant in the control group. We could account for this data through the higher mechanical stability of hydroxyapatite coated screws than standard screws. In fact, this material was responsible for improved implant osteointegration. Thanks to a 1 year follow-up we were able to demonstrate the implant utility associated with augmentation and the importance of densitometry exams such as easily repeatable and low cost diagnostics to prevent the onset of complications linked to screw loosening

The biomechanical understanding of increasing anterior column load with progressing kyphosis leading to subsequent vertebral compression fracture (VCF) established the basic rationale for kyphoplasty. The lumbar spine can support an effort of 500 kg in the axis of the vertebral body, and a bending moment of 20 Nm in flexion. Consequently, if this effort is forward deviated of only 10 cm, the acceptable effort will be reduced to 20 kg so it is important to restore the vertebral anterior wall after a VCF: the authors describe the biomechanical modifications in the spine after kyphoplasty

Tumoral calcinosis is a rare condition described in literature as a deposition of calcium salts in soft tissues. We here report a rare case of Tumoral calcinosis in the index finger of a hand in a 22-year-old woman. Because of the absence of any trauma, normal serum phosphate and calcium levels and no symptoms but a cosmetic defect, our case is classified as a primary tumoral calcinosis. As well as described in literature, also in this case the surgical excision was the mainstay treatment for this benign pathology. For the particular area involved we performed a radical excision followed by an interesting reverse homodigital artery flap from the ulnar side of the index.

Background: In the general population visual-spatial ability is better in males, due to the influence of biological and socio-cultural factors. We know that sport activity improves motor skills. The aim of this work is to determine if these gender differences exist in young athletes. The orientation test described by Terzi and standardized by Cesaroni, used to measure spatial ability, was carried out on 60 volleyball or 60 tennis athletes as well as on 60 non-sporting subjects. Results: The data analysis revealed a worse performance for non-athletes in comparison with athletes in both components of test (p < 0.0001; p = 0.04), with no differences between the volleyball and tennis groups. As far as gender comparison is concerned, as expected in the non- sport group the males presented better values (p < 0.001; p = 0.006). However in both sports groups there weren’t any gender differences in either part of the test (p = 0.18; p = 0.056). Conclusions: These results confirm that during athletic preparation in volleyball and tennis the specific training is able to develop spatial ability. Besides, boys and girls have similar performance demands and training experience. It appears that this specific training could be responsible for modifying gender differences in performance of spatial ability during adolescence

Vitamin D is the main hormone regulating calcium phosphate homeostasis and mineral bone metabolism. Vitamin D deficiency is indeed extremely frequent in musculoskeletal diseases. Recent studies have shown that the treatment of osteoporosis needs to have an optimal vitamin D and calcium supplementation for its efficacy. Actually no agreement exists on the estabilished dose of vitamin D to administer in deficency states. We conducted a prospective study to develop a practical cholecalciferol loading dose regimen that would enable rapid correction of vitamin D deficiency. Sixty post-menopausal age woman were enrolled secondary to a fragility fracture (hip, vertebral, wrist) and screened for 25-hydroxyvitamin D (25(OH)D), calcium, and PTH at baseline (T0), after one month (T1), two months (T2), three months (T3) and six months (T4). Secondary to initial blood values of vitamin D patients were divided into 2 groups; the first group (group A, n=30) included patients with 25(OH)D values between 10-30 ng/ml and the second group (group B, n=30) with values under 10 ng/ml. Each group was then divided in 3 subgroups secondary to the randomized administered dose of 25(OH)D. By this, patients can alternatively receive 25000 UI two times monthly, 100000 UI monthly, 10000 UI (25 drops) weekly. The highest values of mean increase of 25(OH)D were observed in patients treated with 100000 UI. Patients treated with 10000 UI weekly did never achieve the target value. Additionally, as vitamin levels increased, pain intensity decreased. Vitamin D supplementation of 100000 UI monthly seems to be adequate to ensure that serum 25(OH)D values reach the threshold level; by this, it will confer the expected effects without risks of toxicity.