Andrea Speziali

Material and structural tensile properties of the human medial patello-femoral ligament

The medial patellofemoral ligament (MPFL) is considered the most important passive patellar stabilizer and acts 50-60% of the force of the medial soft-tissue which restrains the lateralization of the patella between 0° and 30°. In this work, 24 human knees have been tested to evaluate the material properties of MPFL and to determine the structural behavior of femur-MPFL-Patella complex (FMPC). Particular attention was given to maintain the anatomical orientation between the patella and MPFL and to the evaluation of the elongation during the mechanical tests. The ultimate stress of the isolated ligament was 16±11MPa, the ultimate strain was 24.3±6.8%, the Young׳s Modulus was 116±95MPa and the strain energy density was 2.97±1.69MPa. The ultimate load of the whole structure, FMPC, was 145±68N, the ultimate elongation was 9.5±2.9mm, the linear stiffness was 42.5±10.2N/mm and the absorbed energy was 818.8±440.7Nmm. The evaluation of material and structural properties of MPFL is fundamental to understand its contribution as stabilizer and for the selection of repair and reconstruction methods.

ASTHMA AND MAST CELL BIOLOGY

Asthma is a chronic inflammatory disease of the lung and its pathophysiology is initiated by mast cell activation in response to the antigen binding to IgE receptor as well as by TH2 cell activation. Mast cells are well established effector cells in asthma where they exacerbate the inflammatory response, playing a key role in early phase, degranulating and increasing histamine. Human mast cells possess high affinity IgE receptors and are ubiquitous but predominantly localized in mucosal and connective tissue and are distributed along blood vessels. There are two types of mast cells: connective tissue mast cells (TC) and mucosal mast cells (T mast cells). TC mast cells contain more heparin, whereas T mast cells contain more chondroitin sulfate. In asthma, mast cell activation can trigger degranulation, releasing secretory granule complex and preformed mediators, such as histamine and proteases, along with the synthesis of leukotrines and prostaglandins, and induction of cytokines and chemokines. Leukotrine inhibitors and omalizumab, which inhibits IgE, both relieve the asthma exacerbation when administered to humans and permit to reduce the use of other drugs. The release of cytokines by mast cells, such as TNF-alpha, IL-1, IL-6 and IL-33, participate in the pathogenesis of asthma. Stress worsens asthma, and this effect is also mediated by mast cell activation through the release of cytokines. Administration of IL-33 in experimental animals provokes pathological effects in the mucosal tissues and augments antibody IgE and IgA in blood vessels. Here, we report the impact of mast cell biology in asthma pathogenesis.

IgE generation and mast cell activation

IgE is an important marker for allergy and plays a central role in the induction of allergic diseases through its binding of the high affinity receptor on mast cells. Mast cells can influence B cell survival, proliferation and differentiation into CD138+cells. Among TH2 cytokines, interleukin (IL)-4 and IL-13 are responsible for class-switching in B cells which resolves in production of allergen-specific IgE antibodies that bind to specific receptor on mast cells. IgE synthesis by B cells is regulated by CD40 ligand, IL-4 and interferon-gamma, therefore inhibition of B cell antigen-specific IgE may prevent the cleavage of CD23 from B cells, having a therapeutic impact which also includes the removal of circulating free IgE, omalizumab, corticosteroids, mast cell stabilizers, leukotriene receptor antagonist, and others. B cell differentiation into IgE-producing cells requires two signals provided by TH2 cells and IL-4, however IL-4, IL-1 and IL-10 as well as several hormones are critical for the development of TH2 cells, while cytokines, such as interferon (IFN)-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)-beta play a negative role. However, the exact mechanism of this process has not yet been defined.

Quasi-linear viscoelastic properties of the human medial patello-femoral ligament

The evaluation of viscoelastic properties of human medial patello-femoral ligament is fundamental to understand its physiological function and contribution as stabilizer for the selection of the methods of repair and reconstruction and for the development of scaffolds with adequate mechanical properties. In this work, 12 human specimens were tested to evaluate the time- and history-dependent non linear viscoelastic properties of human medial patello-femoral ligament using the quasi-linear viscoelastic (QLV) theory formulated by Fung et al. (1972) and modified by Abramowitch and Woo (2004). The five constant of the QLV theory, used to describe the instantaneous elastic response and the reduced relaxation function on stress relaxation experiments, were successfully evaluated. It was found that the constant A was 1.21±0.96MPa and the dimensionless constant B was 26.03±4.16. The magnitude of viscous response, the constant C, was 0.11±0.02 and the initial and late relaxation time constants τ1 and τ2 were 6.32±1.76s and 903.47±504.73s respectively. The total stress relaxation was 32.7±4.7%. To validate our results, the obtained constants were used to evaluate peak stresses from a cyclic stress relaxation test on three different specimens. The theoretically predicted values fit the experimental ones demonstrating that the QLV theory could be used to evaluate the viscoelastic properties of the human medial patello-femoral ligament.

Obesity, Inflammation and Neurological Alterations

Inflammation, neurodegeneration, imbalance of neurotransmitter systems, oxidative stress and depression are all risk factors for obesity. There is evidence regarding the cross-talk between adipose tissue and the immune system and obese patients may show an alteration of immune functions with major depression, including immune suppression with reduced T-cell and macrophage activity. Obesity is mediated by inflammatory cells such as lymphocytes, macrophages and mast cells which release pro-inflammatory cytokines and chemokines. Obesity-induced leukocyte infiltrations in adipose tissue cause cytokine/chemokine release and inflammation. Here, we report the relationship between obesity, neurological alterations and inflammation.

Postpartum Sacral Stress Fracture: An Atypical Case Report

Sacral stress fractures are common in elderly people. However, sacral stress fracture should be always screened in the differential diagnoses of low back pain during the postpartum period. We present a case of sacral fracture in a thirty-six-year-old woman with low back pain and severe right buttock pain two days after cesarean section delivery of a 3.9 Kg baby. The diagnosis was confirmed by MRI and CT scan, while X-ray was unable to detect the fracture. Contribution of mechanical factors during the cesarean section is not a reasonable cause of sacral fracture. Pregnancy and lactation could be risk factors for sacral stress fracture even in atraumatic delivery such as cesarean section. Our patient had no risk factors for osteoporosis except for pregnancy and lactation. Transient or focal osteoporosis is challenging to assess and it cannot be ruled out even if serum test and mineral density are within the normal range.