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Objective-To determine the circulating levels of nerve growth factor (NGF), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) in systemic sclerosis (SSc), and to correlate these levels with clinical and laboratory features. Methods-Forty four patients with SSc were evaluated for circulating NGF (immunoenzymatic assay), NPY and VIP (radioimmunoassay), anticentromere and antitopoisomerase I autoantibodies, lung disease (pulmonary function tests with carbon monoxide transfer factor (TLCO), ventilation scintiscan with 99m Tc DTPA radioaerosol, high resolution computed tomography (HRCT), pulmonary pressure (echo colour Doppler)), heart disease (standard and 24 ECG, echocardiography), cutaneous involvement (skin score), joint involvement (evidence of tender or swollen joints, or both), peripheral nervous system (PNS) involvement (electromyography), rheumatoid factor, angiotensin converting enzyme (fluorimetric method), von Willebrand factor (ELISA), and erythrocyte sedimentation rate (ESR) (Westergren). Results-Circulating NGF levels in SSc were significantly increased compared with controls (p<0.00001) and significantly higher in the diVuse than in the limited subset of patients (p<0.01). Patients with articular disease had significantly higher levels of NGF. A significant indirect correlation between NGF levels and TLCO was detected (p<0.01), but no correlation was found between NGF and HRCT, DTPA, skin score, PNS involvement and angiotensin converting enzyme and von Willebrand factor levels, antitopoisomerase or anticentromere antibodies, and ESR.

Substance P (SP) and somatostatin (SOM) have been identified in a distinct subpopulation of dorsal root sensory neurons and their peripheral endings.' Nerve fibers, stained for SP, have been observed in human joint synovia.' The role of peptidergic sensory neurons and of the "neurogenic inflammation" in rheumatoid arthritis (RA) and, particularly, in the involvement of SP in the articular destruction in experimental arthritis has been dem~nstrated.~" High levels of SP have been detected in synovial fluid (SF) of rheumatoid arthritis patients.6 We have assayed the SF levels of SP and SOM in patients affected with inflammatory joint diseases [RA and psoriatic arthritis (PA)] and degenerative joint disease [osteoarthritis (OA)]. PATIENTS AND METHODSThe SF samples were obtained by knee arthrocentesis from 18 patients with RA, 12 patients with OA, and 8 patients with PA. SF samples were collected in ice and were immediately frozen. SP and SOM immunoreactivities (SP-LI, SOM-LI) were assayed, in ethanol acid extracts, by radioimmunoassay (Amersham, United Kingdom; sensitivity of the assay was 1.1 fmol/tube for SP-LI and 0.8 fmol/tube for SOM-LI). Differences among groups were evaluated using Student's t test. Logarithmic regression analyses were used to compare the value of the erythrocyte sedimentation rate (ESR) and the SF neuropeptide levels. RESULTSThe SP-LI (pmol/mL) mean level was significantly higher in RA (P) (43.1 ? 9.8) than in OA (12.0 * 1.3) or PA (24.7 * 1.8). Likewise, SOM-LI was higher in RA (P) (22.8 +-1.4) than in OA (13.6 2 4.7) or PA (14.7 2 4.8). A significant correlation was found between the ESR and SP levels in RA SF (r = 0.447P). 435 ANNALS NEW YORK ACADEMY OF SCIENCES DISCUSSIONThe present data about higher SP levels in the SF of RA patients are in agreement with previous reports.' Various evidences indicate that SP is involved in the joint inflammatory process in rheumatic disease^.^" It may be hypothesized that the higher SP-LI levels detected in RA SF could be related with the intense inflammation of the knee joint of RA patients. We have demonstrated that intraarticular SOM induces a clinical improvement in RA patients.' The observation that SOM inhibits SP release from sensory nerves' might have some relationship with the high SOM-LI levels that we have detected in the SF of RA patients. Furthermore, the correlation between the high level of SP and the increase in ESR, a specific index of inflammation, further suggests that this peptide represents an important agent in the development of rheumatic disease.

Articular cartilage defects, an exceedingly common problem closely correlated with advancing age, is characterized by lack of spontaneous resolution because of the limited regenerative capacity of adult articular chondrocytes. Medical and surgical therapies yield unsatisfactory short-lasting results. Recently, cultured autologous chondrocytes have been proposed as a source to promote repair of deep cartilage defects. Despite encouraging preliminary results, this approach is not yet routinely applicable in clinical practice, but for young patients. One critical points is the isolation and ex vivo expansion of large enough number of differentiated articular chondrocytes. In general, human articular chondrocytes grown in monolayer cultures tend to undergo dedifferentiation. This reversible process produces morphological changes by which cells acquire fibroblast-like features, loosing typical functional characteristics, such as the ability to synthesize type II collagen. The aim of this study was to isolate human articular chondrocytes from elderly patients and to carefully characterize their morphological, proliferative, and differentiative features. Cells were morphologically analyzed by optic and transmission electron microscopy (TEM). Production of periodic acid-schiff (PAS)-positive cellular products and of type II collagen mRNA was monitored at different cellular passages. Typical chondrocytic characteristics were also studied in a suspension culture system with cells encapsulated in alginate-polylysine-alginate (APA) membranes. Results showed that human articular chondrocytes can be expanded in monolayers for several passages, and then microencapsulated, retaining their morphological and functional characteristics. The results obtained could contribute to optimize expansion and redifferentiation sequences for applying cartilage tissue engineering in the elderly patients.