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Biomedical subjects

M Matucci-Cerinic

Publications and source records attributed to M Matucci-Cerinic.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis.

OBJECTIVE: To describe cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) expression in muscle tissue in patients with idiopathic inflammatory myopathies (IIM) - dermatomyositis (DM) and polymyositis (PM) and to find out if any differences between affected and non-affected muscles detected by MRI exist. METHODS: Samples of muscle tissue from 7 patients with dermatomyositis (DM) and from 4 with polymyositis (PM) were obtained by needle biopsy from affected and non-affected sites distinguished by magnetic resonance imaging. In situ hybridization with antisense mRNA probes was employed to detect COX-1, COX-2 and 5-LOX mRNA. RESULTS: Expression of COX-1, COX-2, and 5-LOX mRNA was found in all samples - in the muscle cells, inflammatory cells and in vessels. COX-1 mRNA expression predominated in the inflammatory cells and vessels and was higher in affected than in non-affected sites detected by MRI (mean intensity 3.22+/-0.67 vs. 2.0+/-0.87; p = 0.0006). The expression of COX-2 mRNA was high mainly in inflammatory cells and/or vessels and was increased in MRI-detected affected tissues (3.5+/-0.88; 1.9+/-1.1; p = 0.003), as was the expression of COX-2 mRNA in muscle cells (2.1+/-1.0 vs. 1.3+/-1.0; p = 0.021). 5-LOX mRNA was largely expressed in muscle cells from MRI-detected affected sites and the signal intensity was higher in comparison with samples taken from non-affected tissues detected by MRI (3.22+/-0.7 vs. 1.67+/-0.7; p = 0.0007). CONCLUSION: Expression of COX-1, COX-2 and 5-LOX mRNA was observed for the first time in muscle tissues from IIM patients. This expression was increased in affected tissues detected by MRI, which may suggest a role of COX-1, COX-2, and 5-LOX in the pathogenesis of IIM.

Adult↗
PubMedDate not supplied

Regulation of substance P mRNA expression in human dermal microvascular endothelial cells.

Vascular endothelial cells have been identified as a source of substance P (SP) which may act in an autocrine/paracrine fashion to bring about nitric oxide (NO)-dependent vasodilatation and mitogen-induced cell division or immunologic and inflammatory responses. Whilst SP is localised in and released from endothelial cells, an endothelial mRNA expression of SP has not previously been shown. In the present study, mRNA expression of SP in human dermal microvascular endothelial cells is demonstrated using in situ hybridisation techniques with enhancement procedures. Incubation of microvascular endothelial cells with nerve growth factor (NGF) under conditions of increased shear stress increases the mRNA expression and release of SP Endothelin (ET) release is also enhanced. These changes are pertinent to circulatory, events that may occur in Raynaud's phenomenon in systemic sclerosis.

Cell Culture Techniques↗
PubMedDate not supplied

Gamma/delta T cells in placenta and skin: their different functions may support the paradigm of microchimerism in systemic sclerosis.

Increased amounts of foetal cells persisting after pregnancy could be involved in the pathogenesis of systemic sclerosis (SSc) and other autoimmune diseases. Evidence suggests a specific role for a subset of T lymphocytes showing the gamma/delta T cell receptor (TCR) at the foetal/maternal interface. gamma/delta T cells significantly increase in the early pregnancy decidua and recognize trophoblast antigens, probably a highly evolutionarily conserved molecule such as Hsp60 or Hsp60-derived peptides, and are likely to suppress the maternal anti-foetal immune response via TGFbeta production, thus contributing to pregnancy maintenance. The similarity between the presence of host gamma/delta T cells in pregnancy decidua and in SSc skin suggests that the functional activities of these cells can be differentially modulated by several mechanisms including the nature of the antigen and the involved organs. To support pregnancy, the decidual microenvironment might induce a Th2 activity of host Vdelta1 + T cells. On the contrary, either the presence of foetal cells in the skin of SSc patients or an as yet unidentified stimulus (i.e. infections), may trigger Vdelta1 + T cells toward the Th1 phenotype with the subsequent activation of cytotoxicity and modulation of the cytotoxic alpha/beta acquired T cell response. On these grounds, understanding the mechanisms which prevent the maternal immune system from rejecting a semiallogenic foetus could be helpful to understand the development of some autoimmune diseases, and potentially to develop new targeted therapeutic strategies.

Chimera↗
PubMedDate not supplied

The spectrum of dermatological symptoms of pachydermoperiostosis (primary hypertrophic osteoarthropathy): a genetic, cytogenetic and ultrastructural study.

Pachydermoperiostosis (PDP) is characterized by finger clubbing, periostosis and peculiar skin involvement (pachydermia, seborrhea and folliculitis). The aim of our work was to determine the occurrence of dermatological symptoms in patients with PDP and their relatives, and to study ultrastructural skin changes in the complete and incomplete forms of the disease. A genetic and cytogenetic study was performed in order to identify the mechanism of transmission, to discover possible links to other genetic and non-genetic diseases and to determine the chromosomal complement and eventual chromosomal anomalies. Pachydermia was the most frequent skin alteration together with seborrhea; folliculitis was present in five patients. In the relatives mild pachydermia was detected in 2 out of 26, while seborrhea was present in 6 subjects. Light microscopic observation showed acanthotic epidermis and endothelial hyperplasia in the dermis with partial occlusion of the lumen, lymphohistiocytic infiltrate, and thickening and packing of collagen fibers. Electron microscopy showed fibroblast activation with increased fibrillogenic activity as shown by hypertrophic Golgi complexes and rough endoplasmatic reticulum with cisternae filled with microfibrils. Endothelial cells partially or completely occluded the capillary lumen and presented an increased amount of Weibel Palade bodies. These data show that skin involvement in PDP is a prominent feature, that sometimes these symptoms may also be present in their relatives, and that endothelial and fibroblast activation is present in the skin. Unfortunately the cytogenetic study did not provide any information about possible karyotype abnormalities.

Adult↗
PubMedDate not supplied

Pachydermoperiostosis (primary hypertrophic osteoarthropathy): in vitro evidence for abnormal fibroblast proliferation.

Pachydermoperiostosis (PDP) is a disease characterized by the presence of pachydermia, periostosis and finger clubbing. Evidence that the skin and soft tissues are involved in the disease prompted the in vitro investigation of the behaviour of fibroblasts obtained from cutaneous biopsies of involved and apparently uninvolved PDP skin. PDP fibroblasts from affected skin demonstrated an abnormal proliferation, very rapid and tumultuous when compared to the growth of fibroblasts derived from apparently uninvolved skin and fibroblasts from the skin of healthy subjects. This characteristic was confirmed by the rate of thymidine incorporation, which was increased in PDP-affected fibroblasts (1152 dpm) compared to apparently non-PDP involved fibroblasts (273 dpm) and controls (262 dpm). Ultracentrifuged and non-centrifuged conditioned medium (CM) of fibroblasts affected or apparently not affected with PDP were used to evaluate the effect on the proliferation of healthy skin fibroblasts, compared to the effect of CM derived from healthy fibroblasts and from healthy fibroblasts incubated with 10% and 1% foetal calf serum. The CM of non-centrifuged PDP fibroblasts resulted in a statistically significant stimulation of fibroblast growth when compared to that expressed by ultracentrifuged PDP CM, healthy fibroblast CM and 10% stimulated CM. These data show that PDP fibroblasts maintain in vitro the capacity to proliferate at a higher rate than healthy fibroblasts and that in the CM residual cells and/or their debris may be present, inducing the abnormal growth of healthy fibroblasts. This evidence suggests that fibroblasts in PDP may play a role in the development of the disease.

Cell Division↗
PubMedDate not supplied

The medical and surgical treatment of finger clubbing and hypertrophic osteoarthropathy. A blind study with colchicine and a surgical approach to finger clubbing reduction.

In fourteen patients affected with pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy, the efficacy of colchicine (0.5 mg day for one month) versus placebo on the main clinical features of the disease (finger clubbing, arthritis and pachydermia) was evaluated. In addition, in one patient the usefulness of surgical reduction of clubbed fingertips was investigated. Colchicine did not demonstrate any appreciable effect on finger clubbing (expressed in degrees) or pachydermia, while an effect on arthralgia (as evaluated by the Ritchie Index and Pain Scale) was observed. The surgical treatment of clubbed fingertips failed to show a satisfactory and stable reduction of the fingertips; two months after surgery the nail matrix apparently produced new tissue, once again enlarging and deforming the finger. These results suggest that low dose colchicine cannot be considered the drug of first choice for the treatment of PDP, while higher dosages, although effective, are not tolerated because of the severe side effects. An effective medical and surgical treatment for PDP will be found only when the pathogenetic mechanisms of the disease are clarified.

Adult↗
PubMedDate not supplied

Recommendations of the Italian Society for Rheumatology for the use of biologic (TNF-alpha blocking) agents in the treatment of psoriatic arthritis.

AIM: To propose recommendations for the use of biologic (TNF-alpha blocking) agents in the treatment of psoriatic arthritis (PsA). METHODS: We developed these recommendations by reviewing the evidence published in medical journals and in abstracts of the American College of Rheumatology (ACR) and of the European League against Rheumatism. A draft of the recommendations was circulated to a group of Italian Rheumatologists with a special interest in PsA and in therapy with biologic agents, and their suggestions were incorporated in the final version. RESULTS: A consensus was achieved regarding the initiation and the monitoring of anti-TNF-alpha agents in PsA. More specifically, we propose that anti-TNF-alphaagents be considered in active PsA resistant to non-steroidal anti-inflammatory drugs, to at least two local steroid injections and at least 2 conventional disease-modifying anti-rheumatic agents (in cases of oligo/monoarthritis and/or enthesitis), and to at least two conventional disease-modifying anti-rheumatic agents (in patients with peripheral joints synovitis). Disease activity monitoring should be based on a variety of outcome measures including the ACR response criteria modified for use in PsA, the Bath ankylosing spondylitis disease activity index (BASDAI), and the Maastricht ankylosing spondylitis enthesis score (MASES). A favorable Expert opinion, based on evaluation of clinical symptoms and signs, of laboratory investigations (particularly acute phase reactants), and of imaging studies (whenever appropriate) should also be obtained. CONCLUSION: These recommendations may be used for guidance in deciding which patients with PsA should receive biologic therapy. Regular updates of these recommendations will be implemented on the basis of the results of new clinical studies and of data from post-marketing surveillance.

Antibodies, Monoclonal↗
PubMedDate not supplied

Local venomotor response to intravenous infusion of substance P and glyceryl trinitrate in systemic sclerosis.

Endothelial injury has been shown in ultrastructural studies in systemic sclerosis (SSc). In the present study, we tested the functional response of the endothelium in the early phase of the disease and at a more advanced stage. Substance P (SP) (25 and 50 ng) and glyceryl trinitrate (GT) (100 and 200 ng) were infused intravenously in 6 control subjects and in 6 female patients affected with early systemic sclerosis (SSc) to verify whether or not a lack of endothelial function could be detected. Venous compliance was assessed with a linear variable differential technique. Endothelial injury was evaluated by the von Willebrand Factor Antigen (vWF:Ag) plasma level and platelet aggregation by the platelet aggregate ratio (PAR). Endothelial-mediated response to SP was deficient in SSc patients in comparison with controls, whereas endothelium independent vasodilation was detected after the infusion of GT both in patients and controls. All vWF:Ag levels were in the normal range while in vivo platelet aggregation was increased as demonstrated by the PAR levels in the SSc subjects. The experiment was repeated in the same patients when the clinical status worsened and the levels of vWF:Ag were noted to rise: the endothelium dependent vasodilatory response to SP was still deficient as before and a decrease in vasodilatory response to GT was noted. vWF:Ag levels were significantly increased and the PAR still demonstrated an increased platelet aggregation. These data clearly indicate that an early functional deficit of the endothelial function is present before the onset of extensive visceral and skin involvement. The mechanism that provokes the impairment of the endothelial function need further investigation.

Female↗
PubMedDate not supplied

[Patterns of ventricular late potentials in systemic sclerosis: a noninvasive method in the study of cardiac involvement].

The aim of our study was to ascertain the prevalence of ventricular late potentials (VLP) in systemic sclerosis (SSc) and their correlation with the immunologic patterns and cutaneous and pulmonary involvement of the disease. Ventricular late potentials, which are low-amplitude high-frequency signals present in the terminal portion of the QRS complex, express the delayed and fragmented depolarization of ventricular myocardial fibers. Observed in myocardial interstitial fibrosis, they are characteristic of the myocardial alterations occurring in SSc. Twenty-six patients with SSc (1 man, 25 women) with a confirmed lack of cardiac involvement (negative history and normal clinical, electrocardiographic, and echocardiographic findings) underwent signal averaged high resolution electrocardiography. Pulmonary involvement was evaluated by pulmonary function tests and high resolution computed tomography. The degree of cutaneous involvement was assessed by skin score. In the patients with SSc, VLP presence with time-domain analysis was 30.8% when a 25-250 Hz pass-band filter was used and 26.9% when a 40-250 Hz pass-band filter was used whereas with frequency domain analysis it was 23.1%. Ventricular late potentials were confirmed in 7.7% of the control subjects, no matter what filter or technique was used. No significant correlations among VLP, pulmonary involvement, skin score and specific antibody patterns were found. Although this technique requires further consolidation, it seems to have the potential for use as an early index of myocardial fibrosis.

Adult↗
PubMedDate not supplied

Iliopsoas bursitis in rheumatoid arthritis.

A 58-year-old woman with rheumatoid arthritis (RA) presented with persistent hip pain and an inguinal mass. Considerable liquid had collected inside the iliopsoas bursa, apparently not in communication with the hip joint, as shown by ultrasonography and computed tomography (CT). After one month of systemic steroidal therapy (25 mg/day prednisone), the palpable inguinal mass and pain had disappeared. Iliopsoas bursitis should be suspected in RA patients with a long history of disease presenting with an inguinal mass, persistent groin pain or unilateral leg swelling. The lack of communication between the hip joint cavity and bursa may be considered as a favourable prognostic index. Steroid treatment should be always attempted in order to avoid surgery.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Effect of melatonin on normal and sclerodermic skin fibroblast proliferation.

OBJECTIVE: We studied the effect of melatonin (MLT) (N-acetyl 5-methoxytryptamine) on the growth rate of normal skin fibroblasts and of fibroblasts from involved and apparently uninvolved skin of patients affected by systemic sclerosis (SSc). METHODS: The growth rate was evaluated on the basis of growth curves and a 3H-thymidine incorporation assay. RESULTS: Our results demonstrate that a dose of 200 micrograms/ml of MLT inhibits (> 80%) both control and SSc fibroblasts. Inhibition was dose-dependent and was greater than 70% for MLT concentrations of 100 micrograms/ml, 200 micrograms/ml and 400 micrograms/ml. 3H-thymidine incorporation was correlated with the effect on the growth curves (81% at 200 micrograms/ml of MLT). In contrast, at a low dosage of 6 micrograms/ml, MLT exerted a stimulatory effect on cell proliferation in all the cell lines analyzed. Cell viability was not affected by MLT at any of the concentrations tested. A recovery study indicated that replacement of MLT-containing medium with MLT-free medium resulted in a re-establishment of cell growth. CONCLUSIONS: These results suggest that MLT, at higher dosages, is a potent inhibitor of the proliferation of fibroblasts derived from the skin of healthy and SSc patients.

Cell Count↗
PubMedDate not supplied

Raynaud's phenomenon and systemic sclerosis.

In systemic sclerosis, the exaggerated generalized vasospastic tendency is clinically represented by Raynaud's phenomenon as shown by an early digital arterial closure after cold stimulation, and by an inadequate vasodilatory response to heat. The phenomenon is not restricted to the extremities, and can also occur in internal organs. Repeated attacks of Raynaud's phenomenon may contribute to vascular disease in systemic sclerosis by a mechanism of reperfusion injury of the endothelium, and may contribute to tissue fibrosis. Although the aetiology and pathogenesis of Raynaud's phenomenon remain unknown, recent advances in the understanding of mechanisms of vascular tone control provide us with an opportunity to reconsider the pathogenetic process of Raynaud's phenomenon. It is now clear that neuropeptides, the vascular endothelium, and platelets are the three major contributors to the control of vascular tone. Our hypothesis suggests the presence of a sensory nervous system failure, leading to an unopposed endothelial and platelet control of vascular tone. Endothelial injury and platelet activation in systemic sclerosis lead to a shift in vascular function to a pro-vasospastic function not balanced by a vasodilatory sensory input; thus, enhanced vasospasm is generated. The investigation of the role of local vascular mediators in vasospasm may lead to a better understanding of vascular tone control and of Raynaud's phenomenon pathophysiology in systemic sclerosis.

Humans↗
PubMedDate not supplied

Peripheral nervous system involvement in systemic sclerosis: the median nerve as target structure.

OBJECTIVES: To investigate the frequency and the main electrophysiological characteristics of the canalicolar passage nerve involvement in patients with systemic sclerosis (SSc). METHODS: Thirty-two SSc patients were enrolled in the study, classified according to the type (diffuse or limited) and the duration (> / < 5 years) of the disease. Sensory-motor nerve conduction studies (NCS) of the upper and lower limbs, in particular at the critical canalicolar points, were conducted by recording the Compound Muscular Action Potential (CMAP) and the Sensory Action Potential (sNAP). The following parameters were evaluated: Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity; distal and proximal latency of the CMAP and the onset and peak latency of the sNAP; peak-peak amplitude and negative-peak area of the CMAP and sNAP; and the Terminal Latency Index (TLI) (Terminal Distance/MCNV x Distal latency). RESULTS: Four (12.5%) patients had a distal neuropathy of the upper limbs (one with monolateral and two with bilateral involvement of the median nerve and one bilateral involvement of the ulnar nerve). Fourteen (43.7%) patients showed a decrement of the median nerve TLI and seven (21.8%) of either the median or the ulnar nerve (Table I). Motor and sensitive conduction velocity and latency studies did not show a statistical difference between SSc patients and controls. The amplitude and area of the CMAP (distal and proximal), sNAP and of the median nerve TLI were significantly decreased in patients with respect to controls. CONCLUSION: Distal mononeuropathy of the median nerve was the most frequent result in our patients. The involvement of the peripheral nervous system seems to be strictly topographical, following the modifications of the tissues and vascular tone (Raynaud's phenomenon) at the upper acral level. The neurophysiological alterations detected in our study at the wrist level may not be linked merely to a compressive event but also to microvascular involvement. Nerve involvement closely connected with the pathogenesis and distribution of SSc should be considered when peripheral nervous system involvement is the initial symptom of the disease.

Adult↗