Upregulation of mGlu2 receptors via NF-kB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-kappa B p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-kappa B pathway, and in particular by p65 acetylation, and subsequent NF-kappa B-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressant

Effect of Betamethasone in combination with antibiotics on Gram positive and Gram negative bacteria

Betamethasone is an anti-inflammatory steroid drug used in case of anaphylactic and allergic reactions, of Alzheimer and Addison diseases and in soft tissue injuries. It modulates gene expression for anti-inflammatory activity suppressing the immune system response. This latter effect might decrease the effectiveness of immune system response against microbial infections. Corticosteroids, in fact, mask some symptoms of infection and during their use may occur superimposed infections. Thus the use of glucocorticoids in patients with sepsis remains extremely controversial. In this study we analyzed the in vitro effect of commercially formulation of betamethasone (Bentelan) on several Gram positive and Gram negative bacteria of clinical relevance. It is found to be an inhibitor of the growth of most of the strains examined. Also the effect of betamethasone in combination with some classes of antibiotics was evaluated. Antibiotic-steroid combination therapy is, in such cases, superior to antibiotic-alone treatment to impair bacterial growths. Such effect was essentially not observable at all on Staphylococcus aureus or Coagulase Negative Staphylococci (CoNS)

Rupture of the patellar tendon after platelet-rich plasma treatment. A case report

Introduction: Rupture of the patellar tendon is becoming more and more frequent, even in sports activities overloading the extensor mechanism of the knee. Platelet-rich plasma (PRP) treatment has been recently introduced in treatment for several knee- and sport-related injuries including muscle strain cartilage defect and tendinopathies. The aim of this case report is to present a case of rupture of the patellar tendon occurred after injections of PRP. CASE REPORT: A case of a 40-year-old male soccer player sustaining a patellar tendon rupture after a series of 4 PRP injections. At surgery, a complete rupture in the middle of the patellar tendon was found, with severe degenerative changes of the tendon tissue. This case questions the actual efficacy and safety of PRP in severe degenerative tendinopathies

L-carnitine and isovaleryl L-carnitine fumarate positively affect human osteoblast proliferantion and differentiation in vitro

Age-related bone loss is characterized by decreased osteoblast activity, possibly related to the reduction of energy production. Carnitine promotes energy availability and its concentration declines with age; Therefore, two Carnitine derivatives, L-carnitine fumarate (LC) and isovaleryl L-carnitine fumarate (Iso-V-LC), have been tested on several parameters of human osteoblasts in vitro. Both compounds significantly increased osteoblast activity, but the new compound Iso-V-LC was more efficient than LC at lower concentrations. They both significantly enhanced cell proliferation, [3H]-proline incorporation and the expression of collagen type I (COLLI), and the bone sialoproteins (BSPs) and osteopontin (OPN). The percentage of alkaline phosphatase (ALP)-positive cells and the secretion of osteocalcin were not modified by LC and Iso-V-LC. Both molecules increased the formation of mineralized nodules, but Iso-V-LC reached the maximum effect at a concentration 10-fold lower than that of LC. Furthermore, we showed that insulin-like growth factor (IGF)-I and IGF-II mRNA levels were not modified by the treatment. However, the two compounds induced an increase of insulin-like growth factor binding protein (IGFBP)-3 and a decrease of IGFBP-5 in both osteoblast lysates and the extracellular matrix (ECM). In conclusion these data suggest that carnitine and, in particular, its new derivative, Iso-V-LC supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss