Paolo Borrione

Postnatal histogenesis in the peripheral nervous system.

The issue of postnatal neurogenesis has gained great importance over the last few years and the recent amazing scientific advancements, changing our viewpoint on the long‐lasting “no new neurons” dogma, have opened promising new perspectives on the treatment of the damaged nervous system. While most of the researchers have focused on the central nervous system, the peripheral nervous system has received little attention so far with respect to postnatal histogenesis. To attract scientific attention on this issue, the present article was written with the aim of reviewing the body of literature on postnatal histogenesis in the various districts of the peripheral nervous system, from the historical roots to the most recent reports.

Platelet-Rich Plasma in Muscle Healing

The muscle healing process is defined as a complex and dynamic process resulting in the restoration of anatomic continuity and function. This process is characterized by a cascade of events triggered by the tissue injury itself. It is widely accepted that growth factors play a central role in the healing processes by modulating the recruitment, duplication, activation, and differentiation of different cell types. This observation is the basis on which the use of platelet-rich plasma in several circumstances is founded; all of them requiring the activation or the modulation of the tissue repair process. There is an extensive documentation of in vitro and in vivo studies demonstrating the safety and efficacy of growth factors in the muscle healing process. Unfortunately, the precise biological efficacy and the lack of long-term side effects have not been clearly demonstrated. With regard to sports medicine, doping-related issues are still a matter of debate, especially regarding the treatment of muscle injuries. The purpose of this review is to examine the role of growth factors during muscle healing processes and to discuss the implications of platelet-rich plasma in its therapeutic applications. Sports medicine issues are also discussed particularly with regard to antidoping regulations.

Differential responses of serum and salivary interleukin-6 to acute strenuous exercise

Physical exercise is associated with elevation of serum levels of interleukin-6 (IL-6) because of its production in the muscles. The use of IL-6 measurements in saliva has been proposed in the field of immunopathology, mainly involving salivary gland disease. We evaluated the responses of serum and salivary IL-6 in two different groups of athletes submitted to different types of controlled strenuous exercise (spinning activity and maximal isokinetic test). Serum and salivary samples for IL-6 measurements, and serum samples for lactate and myoglobin determination before and after exercise, were obtained. Salivary IL-6 was measured by ELISA after dilution experiments and compared with results obtained by immunoradiometric assay. Spinning activity elicited significant increases in all the variables, and no correlation was found among the respective variations. A significant response to the isokinetic exercise was observed for serum IL-6, lactate and myoglobin only; no correlation was found between serum and salivary IL-6. Our study demonstrated that serum and salivary IL-6 responses to exercise are dissociated, possibly in relation to the lack of relationships between the systemic/muscular and the salivary routes of IL-6 production. Analytical issues that concern IL-6 measurement in saliva deserve attention, notably regarding the collection method used to absorb saliva. Concomitant monitoring of serum markers of inflammation, muscle metabolism and damage can provide information about muscle function properties and adaptations to physical effort in different types of athletes.

Adult stem cells and neurogenesis: Historical roots and state of the art

Over the last few years, an impressive number of papers have addressed the stem cell issue. However, as often occurs when a scientific subject undergoes a period of fast growth, some confusion is generated. To help reduce the existing uncertainty, this paper focuses on the concept of adult stem cells in relation to the classification of cell populations on the basis their proliferative behavior. Particular attention is dedicated to adult neural stem cells, an issue that has recently seen the most amazing advances. Finally, the concept of adult stem cells is differentiated from that of developmental stem cells in relation to the employment of stem cells for transplantation therapies. Anat Rec (New Anat) 265:132–141, 2001.

Platelet-rich plasma and skeletal muscle healing: a molecular analysis of the early phases of the regeneration process in an experimental animal model.

Platelet-rich plasma (PRP) has received increasing interest in applied medicine, being widely used in clinical practice with the aim of stimulating tissue healing. Despite the reported clinical success, there is still a lack of knowledge when considering the biological mechanisms at the base of the activity of PRP during the process of muscle healing. The aim of the present study was to verify whether the local delivery of PRP modulates specific molecular events involved in the early stages of the muscle regeneration process. The right flexor sublimis muscle of anesthetized Wistar rats was mechanically injured and either treated with PRP or received no treatment. At day 2 and 5 after surgery, the animals were sacrificed and the muscle samples evaluated at molecular levels. PRP treatment increased significantly the mRNA level of the pro-inflammatory cytokines IL-1β, and TGF-β1. This phenomenon induced an increased expression at mRNA and/or protein levels of several myogenic regulatory factors such as MyoD1, Myf5 and Pax7, as well as the muscular isoform of insulin-like growth factor1 (IGF-1Eb). No effect was detected with respect to VEGF-A expression. In addition, PRP application modulated the expression of miR-133a together with its known target serum response factor (SRF); increased the phosphorylation of αB-cristallin, with a significant improvement in several apoptotic parameters (NF-κB-p65 and caspase 3), indexes of augmented cell survival. The results of the present study indicates that the effect of PRP in skeletal muscle injury repair is due both to the modulation of the molecular mediators of the inflammatory and myogenic pathways, and to the control of secondary pathways such as those regulated by myomiRNAs and heat shock proteins, which contribute to proper and effective tissue regeneration.

Structural cardiac disease diagnosed by echocardiography in asymptomatic young male soccer players: implications for pre-participation screening

Purpose To evaluate the prevalence of structural cardiac lesions using echocardiography in apparently healthy boys referred for pre-participation screening (PPS). Subjects and methods 3100 male soccer players were evaluated by echocardiography in addition to the standard PPS. Results In 56 subjects (1.8%), a structural cardiac lesion with potential future complication was detected. Specifically, hypertrophic cardiomyopathy (HCM) was found in two boys; bicuspid aortic valve (BAV) in 24; mitral valve prolapse in 10 and atrial septal defects (ASDs) in 20. Resting physical examination (PE) failed to identify any abnormalities in the majority of the subjects. All the boys presented an uncomplicated echocardiography, except two boys with HCM, one with BAV associated with aortic dilatation and one with a large ASD. Conclusion Asymptomatic young athletes may have a structural cardiac alteration with the potential of present or future haemodynamic and arrhythmic consequences. A majority of mild cardiac lesions are difficult to diagnose or suspect by the current screening based on medical history, PE and ECG. Transthoracic echocardiography significantly improves the diagnostic power of screening in the detection of both mild and serious cardiac conditions in the athletic population.

Sport-related hyperhomocysteinaemia: a putative marker of muscular demand to be noted for cardiovascular risk

Objective: Regular physical activity is associated with a reduction of cardiovascular morbidity and mortality; however, evidence of unfortunate cardiovascular events accompanying elite sport involvement continues to accumulate. To date, no information is available on possible peculiarities of the cardiovascular risk profile in athletes. Design: The aim of this study was to evaluate plasma homocysteine levels in a group of athletes and to search for relationship with vitamin status and other metabolic variables in order to confirm the existence of a “sport-related hyperhomocysteinaemia” and to explain its clinical significance. The study population was composed of 82 athletes (59 male and 23 female) practising different sports and 70 healthy age-matched subjects (40 male and 30 female) as a control group. Besides the general clinical and analytical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and high-density lipoprotein (HDL) cholesterol, lactate dehydrogenase (LDH), creatine kinase (CPK) and interleukin-6 (IL-6). Results: The prevalence of hyperhomocysteinaemia (>15 μmol/l) in athletes and controls was 47% and 15%, respectively. No correlation was found between homocysteine and any of the other investigated variables, in particular plasma folate, blood pressure, LDH, CPK, total and HDL cholesterol and IL-6. Conclusion: The results of this study confirm the existence of a sport-related hyperhomocysteinaemia which appears linked neither to the same variables found in the general population, nor to specific training-related variables. We suggest that it would represent an adaptation to training but the possibility of a secondary vascular damage cannot be excluded.

Distribution of T-cell signalling molecules in human myeloma

It is controversial whether altered levels of TCR/CD3‐associated signalling molecules play a role in the T‐cell dysfunction of cancer patients. In multiple myeloma (MM), peripheral blood T (PBT) lymphocytes are functionally impaired by prolonged exposure to tumour cells, and so we investigated the organization of the TCR/CD3‐associated signal transduction machinery. The aim of this study was two‐fold: first, to investigate the levels of CD3ζ, p56lck, p59fyn, ZAP‐70, protein kinase C‐α (PKC‐α) and phospholipase C‐γ (PLC‐γ) in MM PBT cells; second, to determine whether levels of expression were correlated with clinical or prognostic factors. Forty‐four MM patients were studied and 25 age‐matched normal donors served as controls. On average, PKC‐α was the only significantly decreased (P<0.001) signalling molecule, whereas levels of CD3ζ, p56lck, p59fyn, PLC‐γ and ZAP‐70 were not statistically different. However, there was wide variation between individual patients, and levels for each single protein also varied. A 75% or greater decrease in protein expression was observed, ranging from 8% (p59fyn) to 68% (PCK‐α) of MM patients. When patients were grouped according to the cut‐off values of prognostic factors such as the serum levels of C reactive protein (CRP), β2‐microglobulin (β2M), neopterin (NPT) and the labelling index (LI%) of bone marrow (BM) plasma cells, the only difference observed was the lower PKC‐α expression in patients with high serum NPT values. None of the T‐cell signalling molecule levels was affected by the duration of tumour exposure, calculated on the number of years and/or months that had elapsed since diagnosis, or by disease status. In conclusion, there was a significant decrease of PCK‐α in MM T cells; however, neither this decrease nor the heterogenous levels of the other T‐cell signalling molecules were clearly correlated with prognosis, duration of tumour exposure, and disease status.

Effects of physical activity in Parkinson's disease: A new tool for rehabilitation

Parkinsons disease (PD) is a common neurodegenerative disease characterized by bradykinesia, tremor, rigidity, and postural instability. Motor disorders are composite and combined, adversely affecting the patients health. Tremor and rigidity are correlated with worsening manual dexterity as well as postural changes such as akinesia and camptocormia. Moreover, gait alteration as well as postural instability, with consequent impairment in balance, increase the risk of falls. It is well known that these symptoms respond poorly to pharmacologic therapy in PD patients. Physical therapy is the most effective non-pharmacological aid to PD patients. Available data in the literature indicate that any rehabilitation protocol has to focus on: cognitive movement strategies, cueing strategies, and improved physical capacity and balance. Different training programs for PD patients have been designed and evaluated but only specific training strategies, tailored and individualized for each patient, may produce improvements in gait speed and stride length, decrease motor and balance symptoms and improve quality of life. Furthermore, aerobic training may improve muscle trophism, strength and mobility. It seems reasonable to state that tailored physical activity is a valid tool to be included in the therapeutic program of PD patients, considering that this approach may ameliorate the symptoms as well as the overall physical incapacity, reduce the risk of falls and injuries, and ultimately improve quality of life.

Participation in a 9-month selected physical exercise programme enhances psychological well-being in a prison population.

BACKGROUND There is general population evidence that physical exercise is effective in reducing the risk of depression and has positive effects on mood. Some prisons encourage exercise, but there is no evidence specific to this group on its benefits or the relative merits of different programmes. AIMS To test the effect of physical exercise on the psychological well-being of prisoners and to determine which mental disorders are most affected by physical activity. METHODS Sixty-four participants were randomly assigned across three groups: cardiovascular plus resistance training (CRT), high-intensity strength training (HIST) and no exercise. Before and after the 9-month experimental period, all participants completed the Symptom Checklist-90-Revised. RESULTS Each form of exercise significantly reduced depression scale scores compared with those in the control group, in which average depression scale scores actually increased. The CRT group also showed a significant decrease in GSI scores on the Symptom Checklist-90 and on its interpersonal sensitivity scale, whereas the HIST group also significantly improved on the anxiety, phobic anxiety and hostility scale scores. CONCLUSIONS Our evidence, taken together with general population studies, supports introduction of supervised, moderately intense exercise for at least 1 h per week for men in prison. They form a high risk group for mental disorders, and such exercise reduces depression and anxiety. Minimal special equipment is needed for CRT. Further research should replicate the study in a larger, multi-centre trial, and examine impact on shorter-term and longer-term prisoners, female prisoners and effects on recidivism.