Extracorporeal shockwaves as regenerative therapy in orthopedic traumatology: a narrative review from basic research to clinical practice.

Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.

IMMUNOMODULATORY EFFECTS OF VITAMIN D ON SKIN INFLAMMATION.

Vitamin D has a major role in calcium absorption and maintenance of healthy bones. Vitamin D is also involved in cancer, cardiovascular system, allergic diseases, immune regulation and immune disor¬ders. Irradiation of food as well as animals produces vitamin D and more than 90% of previtamin D3 synthesis in the skin occurs in the epidermis. Vitamin D receptor has been found in many cells including T and B lymphocytes, macrophages, mast cells, NK cells and Tregs, and it selectively binds with high affinity to its ligand. Vitamin D binds its receptor VDR, resulting in transcription of a number of genes playing a role in inhibition of MAPK. Its effect may be also mediated by the direct activation of PKC. Vitamin D has the ability to suppress inflammatory cytokines such as TNF, IL-1, IFN-gamma and IL-2; while it increases the generation of anti-inflammatory cytokines IL-4 and IL-10. In B cells, vitamin D3 have also been shown to suppress IgE antibody class switch partly through the inhibition of NF-kB. Here we discuss the relationship between vitamin D, immunity and skin disorders.

Role of TNF in mast cell neuroinflammation and pain.

Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor, are involved in the etiology of clinical neurological disorders. These cytokines activate nuclear factor-κB (NF-κB) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of microglia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs) which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-κB and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders.

Relationship between serotonin and mast cells: inhibitory effect of anti-serotonin.

Serotonin (5-HT) is an important neurotransmitter that acts in both central and peripheral nervous system, and has an impact on cell proliferation, migration and apoptosis. 5HT exerts its effects via several receptors. Treatment with anti-5-HT receptors diminish the severity of contact allergy in experimental animals, an effect mediated by mast cells; while an agonist reduces the stress level and relieves pruritus in patients with atopic dermatitis. Mast cells are important for both innate and adaptive immunity and they are activated by cross-linking of FceRI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Serotonin is present in murine mucosal mast cells and some authors reported that human mast cells may also contain serotonin, especially in subjects with mastocytosis. Here we report the interrelationship between mast cells, serotonin and its receptor inhibitor.

Interrelationship between IL-3 and mast cells.

It is well established that mast cells, which are found in the tissues in the proximity of small blood vessels and post-capillary venules, play a key role in the early phase of IgE-mediated allergic reactions. A greatly expanded understanding of the biology of IL-3 has emerged since the early 1980s. IL-3 is a specific factor that stimulates the growth of hematopoietic stem and progenitor cells of a variety of lineages and can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has been identified among the most important cytokines for regulation of mast cell growth and differentiation, migration and effector function activities of many hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates the formation of colonies for erythroid, megakaryocytic, granulocytic and monocytic lineages. It is predominantly produced by activated T cells, natural killer (NK) cells and mast cells and supports the growth-promoting effects of SCF on mast cell precursors. IL-3 causes severe hypersensivity reactions and plays a pivotal role in exacerbating the inflammatory response in vivo. Here we report the interrelationship between IL-3 and mast cells.

A study of postural changes after abdominal rectus plication abdominoplasty.

PURPOSE: Factors such as body masses and humour are known to influence human posture. Abdominoplasty, which causes a sudden change in body masses, significantly improves body image and self-esteem. The aim of this study was to assess postural changes after abdominoplasty by studding the position and orientation through space of the body and the centre of pressure. METHODS: Patients affected by excess abdominal skin and/or significant abdominal muscular anterior wall laxity due to undergo an abdominoplasty were enrolled. Posture was evaluated both before and for 1 year after surgery by quantifying the centres of mass, using the Fastrak™ system, and the centre of pressure, using stabilometry. The Wilcoxon signed-rank sum test was used to compare changes. RESULTS: Forty-six patients were enrolled. A retro-positioning of the pelvis with a compensatory advancement of the head and shoulders, confirmed by the baropodometric analysis, was evident in the early post-operative period. The biomechanical system subsequently stabilized, achieving a state of equilibrium 1 year after surgery. CONCLUSIONS: We believe that the change in posture following abdominoplasty is a consequence of both surgery (changes in body masses) and psychological factors that influence posture. Indeed, redundant abdominal skin and abdominal muscular anterior wall weakness are often associated with kyphosis since patients try to hide what they consider to be a source of embarrassment. The discovery of a new body image eliminates dissatisfaction, reduces anxiety and increases self-esteem, which provide psychological and physical benefits that improve the quality of life.

Role of mast cells in atherosclerosis: a classical inflammatory disease.

Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selection, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.

Impact of mast cells on the skin.

When through the skin a foreign antigen enters it provokes an immune response and inflammatory reaction. Mast cells are located around small vessels that are involved in vasaldilation. They mature under the influence of local tissue to various cytokines. Human skin mast cells play an essential role in diverse physiological and pathological processes and mediate immediate hypersensitive reaction and allergic diseases. Injection of anti-IgE in the skin or other agents that directly activate mast cells may cause the decrease in vascular tone, leakage of plasma and may lead to a fall in blood pressure with fatal anaphylactic shock. Skin mast cells are also implicated as effector cells in response to multiple parasites such as Leishmania which is primarily characterized by its tissue cutaneous tropism. Activated macrophages by IFNgamma, cytotoxic T cells, activated mast cells and several cytokines are involved in the elimination of the parasites and immunoprotection. IL-33 is one of the latest cytokines involved in IgE-induced anaphylaxis and in the pathogenesis of allergic skin disorders. IL-33 has been shown in epidermis of patients with psoriasis and its skin expression causes atopic dermatitis and it is crucial for the development of this disease. Here we review the impact of mast cells on the skin.

Vascular endothelial growth factor (VEGF), mast cells and inflammation.

Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis, therefore blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases. VEGF, expressed in response to soluble mediators such as cytokines and growth factors, is important in the physiological development of blood vessels as well as development of vessels in tumors. In cancer patients VEGF levels are increased, and the expression of VEGF is associated with poor prognosis in diseases. VEGF is a mediator of angiogenesis and inflammation which are closely integrated processes in a number of physiological and pathological conditions including obesity, psoriasis, autoimmune diseases and tumor. Mast cells can be activated by anti-IgE to release potent mediators of inflammation and can also respond to bacterial or viral antigens, cytokines, growth factors and hormones, leading to differential release of distinct mediators without degranulation. Substance P strongly induces VEGF in mast cells, and IL-33 contributes to the stimulation and release of VEGF in human mast cells in a dose-dependent manner and acts synergistically in combination with Substance P. Here we report a strong link between VEGF and mast cells and we depict their role in inflammation and immunity.

Luteolin inhibits mast cell-mediated allergic inflammation.

Mast cells are ubiquitous in the body and multifunctional immune cells; they are known to be primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens. Mature mast cells perform important beneficial roles in host defense, both in IgE-dependent immune responses to certain parasites and in natural immunity to bacterial infection. In IgE-associated biological responses, the crosslinking of FcεRI-bound IgE with multivalent antigens initiate the activation of mast cells by promoting aggregation of FceRI. This cross-linking receptor-bound IgE by multivalent Ag initiates a cascade of intracellular reactions leading to mediator release such as proinflammatory mediators, chemokines and cytokines. Luteolin belongs to a flavone group of compounds called flavonoids, it has anti-oxidant properties, inhibits some cancer cell proliferation and exerts a regulatory effect on mast cell-mediated inflammatory diseases and allergy. Here we report the impact of luteolin on mast cell activation.

Biomechanical modification and sense motor control of body posture after plastic surgery.

Plastic surgery offers a quite unique window on abrupt and permanent modifications of a human's body schema. Its impact is comparable to amputations or other severe injuries, with the evident advantage from the experimenter's (and patient's) point of view that it is planned, allowing longitudinal studies and quantification of the weight and distribution of modified bodily masses (e.g., weight of the prosthesis). One potential drawback is that modifications due to (aesthetic) plastic surgery are often too little to be revealed by motor control tasks, making it difficult to measure the time course of body schema readaptation. The aim of our study is measuring the capability of the body scheme to re-adapt to significant and abrupt changes, such as the distribution of mass centers, and in particular to assess what is the time course of such re-adaptation. For this reason, we have carried out a longitudinal study on postural modifications on a population of female patients (N = 30) who were subjected to additive or reductive plastic surgery. Posture and stabilometry evaluations were performed before surgery (T0), and after 1 months (T1), 4 months (T2), and 1 year (T3). Posture was reconstructed from spatial tracking system (FastrackTM Polhemus) recordings. Stabilometry analysis was performed by force platform (Globus Italia). The results document a modification in posture and a significant increase in the sway area after body mass alterations. Posture and stabilometry data return to equilibrium after 1 year. Our data suggest that posture control relies on, at least in part, feedforward than only on feedback strategies.

Flexible flatfoot treatment in children with mechanical sound vibration therapy.

UNLABELLED: The flat foot can be defined as a syndrome with multiple etiopathogenesis, characterized by an altered structure of the longitudinal arch of the plantar vault with its reduction in height. The plantar arch collapse can be counteracted by strengthening the muscles involved; for many years, specific physical exercises have been proposed with this purpose in physical and rehabilitation medicine. The aim of our work was to improve the plantar arch muscles' tone using high focal vibration therapy (300Hz) METHODS: 10 children with a 4th degree flat foot (age: 8,7±2,2; height: 132±15cm; weight: 35,2±12,3Kg) underwent 10 sessions, 2 days/wk, of 30 min of focused high vibratory therapy at a frequency of 300 Hz (Vissman, Italy). Before and after treatment stabilometry (StT), static and dynamic baropodometry tests were performed. RESULTS: Evaluation of StT showed an improvement of stability, a decrease of sway area and ellipse area. Baropodometry tests showed a decrease in foot surface. Also dynamic tests showed a decrease in both foot surfaces. DISCUSSION: The results lead us to consider this method as a method of first choice to a conservative approach in the rehabilitation of flat foot syndrome also for the 4th grade in children.

Treatment of lesions of the rotator cuff.

The impingement syndrome and tendinopathy of the rotator cuff are the most common causes (complaints) of pain and disability of the shoulder. The aim of this study is to evaluate the efficacy of a specific rehabilitative protocol, integrated with the administration of a nutritional supplement, in the conservative rehabilitative treatment, as well as in post-surgery, of patients with lesions of the rotator cuff. Two groups with syndrome of the rotator cuff were formed to follow different therapeutic courses, in relation to the choice of each subject to undergo the conservative treatment (Arm A) or the surgical one (Arm B). In Arm A the study included the association of therapy with ESWT (shock waves) with the proprioceptive Multi Joint System, for rehabilitating joint movement and muscle strength of the shoulder, and a specific nutritional supplement to reduce the pain and conserve the cartilage tissue. Between February 2009 and June 2009, we enrolled 30 subjects (randomized into three homogenous groups A1, A2, A3), average age 45±10 years, with rotator cuff syndrome with calcification of the shoulder, diagnosed through clinical examination and investigative instruments (X-ray, echography or NMR). In Arm B, from September 2009 to January 2010, we enrolled 50 patients (randomized into two groups, B1 and B2), 24 male (average age 58.4: min 28 and max 78) and 26 females (average age 59.5: min 30 and max 80), who had undergone rotator cuff operations and acromionplasty for non-massive lesions without important gleno-humeral instability, with either open or arthroscopic procedures. The analysis of the results of Arm A highlights that in terms of reducing pain the main benefits were found in Group A1 where the supplement was given. From the analysis of the data of Arm B, in both groups an improvement of the first 4 items evaluated was evident. In Group B1, 84 percent of the patients declared to be satisfied and improved and 16 percent were dissatisfied; in Group B2, where the nutritional supplement was given, 92 percent were satisfied and 8 percent were dissatisfied. In conclusion, we retain that in cases of rotator cuff syndrome, an integrated rehabilitative approach, whether conservative or post-surgical, directed at taking total control of the patient, must observe particular attention to the optimization of the articular tissular metabolic balance in order to favour better functional recovery.

The use of mechanical acoustic vibrations to improve abdominal contour.

Adaptive effects caused by mechanical acoustic vibrations on the neuromuscular system are widely described. These vibrations applied to the muscle belly cause the "vibration tonic reflex" characterized by an improvement in power contraction of the stimulated muscle. Mechanical acoustic vibrations of moderate strength placed on limited body areas produce a positive muscle activity without damage. A prospective study from January to September 2006 investigated 60 sedentary patients presenting with muscular hypotrophy associated or not associated with lipodystrophy of the abdominal region who desired a substantial contour improvement of such area without invasive procedures. Of these patients, 40 were subjected to a treatment protocol with mechanical acoustic vibrations applied to the abdomen, associated or not associated with physical aerobic exercise of moderate intensity. The remaining 20 patients engaged only in the physical training. The study aimed to evaluate whether the application of mechanical acoustic vibrations could improve body contour.

Submaximal aerobic exercise with mechanical vibrations improves the functional status of patients with chronic fatigue syndrome.

AIM: Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of uncertain aetiology and other nonspecific symptoms. Typically CFS patients complain of a severe fatigue made worse by exercise, with a consistent reduction of working activity. A physical deconditioning could explain CFS features as well as a neuromuscular dysfunction, of central or peripheric origin. METHODS: Ten CFS patients were enrolled in a protocol of a rehabilitative treatment over a six-month period: they underwent a submaximal and predominantly aerobic exercise with a reduced O2 consumption using a Galileo 2000 system that provides mechanical vibrations characterised by sinusoid vertical sollecitations. Before and after such treatment, all patients underwent a pressure pain thresholds profile, an evaluation of physical and psychosocial parameters using the visual analogue scale (VAS) of Scott-Huskisson, and a muscle performance analysis by the CIBEX 6000 dynamometer. RESULTS: After the six-month period of study there was an overall improvement of the above described parameters as compared to the basal determinations. CONCLUSION: We conclude that the rehabilitative exertion provides an useful treatment for CFS patients particularly to realize an effective training of the explosive strength.

Alteration of spatial-temporal parameters of gait in Chronic Fatigue Syndrome patients.

Chronic Fatigue Syndrome (CFS) has been widely studied and a lot of information is available in the literature regarding the immunological, virological, neuroendocrinal and psychiatric aspects of the disease, but its aetiology is still poorly understood. Great attention has also been paid to the alteration of the muscular function caused by CFS. The aim of the present work was to study CFS patients' gait in order to find out objective measures which can better characterize the pathology. Spatial and temporal parameters of gait were collected from a group of 12 CFS informed volunteers by using the typical instrumentation of movement analysis, and raw data were statistically elaborated. Comparisons with reference data from a population of healthy subjects revealed significant abnormalities in the symmetry indices of the bilateral parameters and in the linear relationships among parameters, and between these parameters and the physical characteristics of the patients. Interestingly, the abnormalities were present as from the beginning of the gait, which indicates that they are unlikely to be caused by the rapid increasing fatigue. This strengthens the hypothesis of a direct involvement of the central nervous system (CNS) in the onset of the disease.

Lumbosacral hyperlordosis due to fibrosis of the paravertebral muscles. Case report.

The authors present a case of lumbosacral hyperlordosis due to primary fibrosis of the paravertebral muscles. This very rare lesion in described and the surgical treatment used in this case is illustrated. The clinical and cosmetic results were both excellent.