Giuliano Giorgio Cerulli

Prevention of anterior cruciate ligament injuries in soccer. A prospective controlled study of proprioceptive training.

Proprioceptive training has been shown to reduce the incidence of ankle sprains in different sports. It can also improve rehabilitation after anterior cruciate ligament (ACL) injuries whether treated operatively or nonoperatively. Since ACL injuries lead to long absence from sports and are one of the main causes of permanent sports disability, it is essential to try to prevent them. In a prospective controlled study of 600 soccer players in 40 semiprofessional or amateur teams, we studied the possible preventive effect of a gradually increasing proprioceptive training on four different types of wobble-boards during three soccer seasons. Three hundred players were instructed to train 20 min per day with 5 different phases of increasing difficulty. The first phase consisted of balance training without any balance board; phase 2 of training on a rectangular balance board; phase 3 of training on a round board; phase 4 of training on a combined round and rectangular board; phase 5 of training on a so-called BABS board. A control group of 300 players from other, comparable teams trained “normally” and received no special balance training. Both groups were observed for three whole soccer seasons, and possible ACL lesions were diagnosed by clinical examination, KT-1000 measurements, magnetic resonance imaging or computed tomography, and arthroscopy. We found an incidence of 1.15 ACL injuries per team per year in the control group and 0.15 injuries per team per year in the proprioceptively trained group (P<0.001). Proprioceptive training can thus significantly reduce the incidence of ACL injuries in soccer players.Proprioceptive training has been shown to reduce the incidence of ankle sprains in different sports. It can also improve rehabilitation after anterior cruciate ligament (ACL) injuries whether treated operatively or nonoperatively. Since ACL injuries lead to long absence from sports and are one of the main causes of permanent sports disability, it is essential to try to prevent them. In a prospective controlled study of 600 soccer players in 40 semiprofessional or amateur teams, we studied the possible preventive effect of a gradually increasing proprioceptive training on four different types of wobble-boards during three soccer seasons. Three hundred players were instructed to train 20 min per day with 5 different phases of increasing difficulty. The first phase consisted of balance training without any balance board; phase 2 of training on a rectangular balance board; phase 3 of training on a round board; phase 4 of training on a combined round and rectangular board; phase 5 of training on a so-called BABS board. A control group of 300 players from other, comparable teams trained “normally” and received no special balance training. Both groups were observed for three whole soccer seasons, and possible ACL lesions were diagnosed by clinical examination, KT-1000 measurements, magnetic resonance imaging or computed tomography, and arthroscopy. We found an incidence of 1.15 ACL injuries per team per year in the control group and 0.15 injuries per team per year in the proprioceptively trained group (P<0.001). Proprioceptive training can thus significantly reduce the incidence of ACL injuries in soccer players.

Clinical classification of patellofemoral pain syndrome: guidelines for non-operative treatment

The patellofemoral pain syndrome (PFPS) remains a challenging musculoskeletal entity encountered by clinicians. Reviewing the literature, conflicting data seem to exist regarding the effect of non-operative treatment in PFPS patients. A possible explanation may be lack of a clear classification system of patients with PFPS. It is our opinion that the term PFPS still is a ‘wastebasket’, which probably comprises several different entities. Therefore, it seems important to subdivide this broad group of patients into different categories with a specific rehabilitation approach. In this study, we introduce a classification system, which reflects a consensus reached by the European Rehabilitation Panel. This classification system should help the clinicians to identify the cause(s) of patellofemoral pain, and consequently help to select the most appropriate non-operative treatment. The authors are aware that no rehabilitation protocol will work for all PFPS patients, since the underlying mosaic of pathophysiology and tissue-healing responses are unique. Therefore, the aim of this study with a classification system was to guide the clinician through clinical examination in order to develop a non-operative treatment protocol, specific for each individual with PFPS.

Anti-chemokine therapy for inflammatory diseases.

Chemokines are inflammatory proteins acting via G-protein coupled chemokine receptors that trigger different signaling pathways. Monocyte chemoattractant protein-1 (CCL2/MCP-1) and regulated on activation, normal T expressed and secreted (CCL5/RANTES) are the two major members of the CC chemokine beta subfamily. The roles of RANTES and MCP-1 are emerging in regulating the recruitment of inflammatory cells into tissue during inflammation. The inhibition of MCP-1 and RANTES with corresponding antibodies or other inhibitors may provide benefits in different clinical scenarios including cancer, inflammation, CNS disorders, parasitic disease, autoimmune and heart diseases. RANTES and MCP-1 may represent targets for diagnostic procedures and therapeutic intervention, and may be useful as a prognostic factor in the above diseases.

The clinical significance of electromyography normalisation techniques in subjects with anterior cruciate ligament injury during treadmill walking

This study investigated the clinical interpretation of three electromyographic (EMG) normalisation techniques to detect neuromuscular alterations in patients diagnosed with anterior cruciate ligament knee injury during treadmill walking. The EMG signal was normalised using the mean value during the gait cycles (MEA), the maximum value during the gait cycles (MAX), and a maximum voluntary isometric contraction (MVC) test in 16 male and female subjects. The MAX method detected an increase in total muscle activity in the injured limb rectus femoris (11.6%; P=0.02) while the MVC method detected decreased injured limb gastrocnemius medialis (GM) overall muscle activity (34.4%; P=0.02). The MAX method identified decreased GM activity in three portions of the gait cycle. This study indicates the importance of choosing the appropriate normalisation technique since its choice will change outcome measures and subsequent clinical interpretation.

Tuning multi/pluri-potent stem cell fate by electrospun poly(L-lactic acid)-calcium-deficient hydroxyapatite nanocomposite mats

In this study, we investigated whether multipotent (human-bone-marrow-derived mesenchymal stem cells [hBM-MSCs]) and pluripotent stem cells (murine-induced pluripotent stem cells [iPSCs] and murine embryonic stem cells [ESCs]) respond to nanocomposite fibrous mats of poly(L-lactic acid) (PLLA) loaded with 1 or 8 wt % of calcium-deficient nanohydroxyapatite (d-HAp). Remarkably, the dispersion of different amounts of d-HAp to PLLA produced a set of materials (PLLA/d-HAp) with similar architectures and tunable mechanical properties. After 3 weeks of culture in the absence of soluble osteogenic factors, we observed the expression of osteogenic markers, including the deposition of bone matrix proteins, in multi/pluripotent cells only grown on PLLA/d-HAp nanocomposites, whereas the osteogenic differentiation was absent on stem-cell-neat PLLA cultures. Interestingly, this phenomenon was confined only in hBM-MSCs, murine iPSCs, and ESCs grown on direct contact with the PLLA/d-HAp mats. Altogether, these results indicate that the osteogenic differentiation effect of these electrospun PLLA/d-HAp nanocomposites was independent of the stem cell type and highlight the direct interaction of stem cell-polymeric nanocomposite and the mechanical properties acquired by the PLLA/d-HAp nanocomposites as key steps for the differentiation process.

Environmental and occupational stress and autoimmunity

The immune system and the neuroendocrine system machinery modulate each other, including life events-induced stresses and interpersonal conflicts, promoting the synthesis of proinflammatory cytokines, overproduction of which influence behaviour. In addition, the balance of systemic and local pro-inflammatory cytokines to systemic and local anti-inflammatory cytokines, is impaired to such an extent that, in genetically-predisposed individuals, this aberrancy may lead to autoimmune diseases. Occupational stress likely influences their onset. For example, subclinical autoimmune hypothyroidism has been identified in numerous shift-workers of an Italian hospital. Such a threat impacts the policy of health surveillance of the workers and requires dedication of further studies to the relationship between occupational stress and autoimmunity.

Can a post-operative brace in slight hyperextension prevent extension deficit after anterior cruciate ligament reconstruction?

It has been our observation that post-operative anterior cruciate ligament (ACL) braces together with the post-operative bandages do not always allow the knee to reach full extension. In ten uninjured knees with known hyperextension, the knees were bandaged in the same way as after an ACL-reconstruction. The knees were then studied radiologically in a Hypex brace set at 0°, −5° and −10° of knee extension. Not a single knee was found to be straight in the brace set at 0°. At −5° most of the knees were straight or in slight hyperextension. It took −10° to get all knees straight or in hyperextension. In a prospective randomised study 44 patients who underwent an arthroscopic ACL-reconstruction with a bone patellar tendon bone graft were randomised to use either a brace set at −5° or a straight brace (0°) for at least the first three postoperative weeks. Before and three months after surgery range of motion was determined, using a goniometer with long arms, and sagittal knee laxity was measured with a KT-2000 arthrometer at manual max. Pre- and post-operative pain was evaluated with the Visual Analogue Scale (VAS). The same examiner (blindfolded to what type of brace was used) performed all the measurements. At three months, two of the 22 patients with the brace set at −5° and twelve of the 22 patients with the straight brace had a loss of full extension of 2° or more (p<0.001). No significant differences were found between the groups in terms of knee flexion, sagittal knee laxity or post-operative pain. Although extension deficit after ACL-reconstruction can be prevented also in other ways, a Hypex brace set at −5° seems to be an easy way of ensuring full knee extension.

Autism and immunity: revisited study.

Autism spectrum disorder is of interest neurochemically because it represents a relatively homogeneous disorder with regard to disease development, abnormal cognitive development and intellectual development disturbance. A consistent finding in autistic children is a high number of mast cells and a high level of serotonin which is also found at elevated concentrations in the urine of autistic patients. In addition, a dysfunction of clinical conditions, such as gastrointestinal and immunological symptoms, is frequently noted in autistic children, however, IgE does not appear to be prevalent in these children but probably an increase of cytokines/chemokines produced by mast cells at an early age may play an important role. Therefore an immune hypothesis, involving also autoimmunity, is one possible pathogenetic mechanism in autism. In conclusion, mast cell activation could contribute to immune and neuroinflammatory abnormalities that are evident in patients with autism spectrum disorders.

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 IFNγ, 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.

Biology of neurotensin: revisited study.

The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary neurotransmitter or neuromodulator of classical neurotransmitters. Morphological and functional in vitro and in vivo studies have demonstrated the existence of close interactions between NT and dopamine both in limbic and in striatal brain regions. Additionally, biochemical and neurochemical evidence indicates that in these brain regions NT also plays a crucial role in the regulation of the aminoacidergic signalling. Immune cells, such as lymphocytes, macrophages and mast cells are reported to be activated by neuropeptides, such as neurotensin; this activation leads to cytokine and immunoglobulin production. In addition, neurotensin increases calcium level and the production of nitric oxide, therefore neurotensin is deeply involved in immunity and inflammation but its real function still remains to be elucidated.