Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis.

BACKGROUND: Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset. METHODS: Data from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that. RESULTS: A total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively). CONCLUSIONS: We identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis.

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: in vitro and in vivo analysis.

Cellular systems implanted into an injured nerve may produce growth factors or extracellular matrix molecules, modulate the inflammatory process and eventually improve nerve regeneration. In the present study, we evaluated the therapeutic value of human umbilical cord matrix MSCs (HMSCs) on rat sciatic nerve after axonotmesis injury associated to Vivosorb® membrane. During HMSCs expansion and differentiation in neuroglial-like cells, the culture medium was collected at 48, 72 and 96 h for nuclear magnetic resonance (NMR) analysis in order to evaluate the metabolic profile. To correlate the HMSCs ability to differentiate and survival capacity in the presence of the Vivosorb® membrane, the [Ca(2+)]i of undifferentiated HMSCs or neuroglial-differentiated HMSCs was determined by the epifluorescence technique using the Fura-2AM probe. The Vivosorb® membrane proved to be adequate and used as scaffold associated with undifferentiated HMSCs or neuroglial-differentiated HMSCs. In vivo testing was carried out in adult rats where a sciatic nerve axonotmesis injury was treated with undifferentiated HMSCs or neuroglial differentiated HMSCs with or without the Vivosorb® membrane. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index (SFI), extensor postural thrust (EPT), and withdrawal reflex latency (WRL). Stereological analysis was carried out on regenerated nerve fibers. In vitro investigation showed the formation of typical neuroglial cells after differentiation, which were positively stained for the typical specific neuroglial markers such as the GFAP, the GAP-43 and NeuN. NMR showed clear evidence that HMSCs expansion is glycolysis-dependent but their differentiation requires the switch of the metabolic profile to oxidative metabolism. In vivo studies showed enhanced recovery of motor and sensory function in animals treated with transplanted undifferentiated and differentiated HMSCs that was accompanied by an increase in myelin sheath. Taken together, HMSC from the umbilical cord Wharton jelly might be useful for improving the clinical outcome after peripheral nerve lesion.

Rifamycin SV administered by intra-articular infiltrations shows disease modifying activity in patients with pauci- or polyarticular juvenile rheumatoid arthritis.

The therapeutic activity of rifamycin SV administered by the intra-articular route was evaluated in 52 children with juvenile rheumatoid arthritis (oligopolyarthritis). Each active joint was injected once a week for 10 weeks; thereafter patients were followed for 3-48 months. The number of active joints and joints with limitation of motion, the erythrocyte sedimentation rate (ESR) and C-reactive protein improved significantly at the end of the treatment cycle, with progressive improvement during the subsequent period of observation. At 48-month of follow-up, 78% of joints did not present signs of inflammation; and 66% of joints showed no functional limitations. Joints without radiological lesions at baseline and large joints responded best to the rifamycin treatment. Persistent knee effusions were reabsorbed completely in most cases during the treatment and within the first 6 months of follow-up. Recurrences of synovitis were observed in 7% of joints. De novo radiological lesions in initially undamaged joints occurred during the second year of follow-up in only 10% of patients. At 24 months, 62% of patients with oligoarthritis and 24% with polyarthritis showed complete remission in all affected joints and recovered movement in all those joints which had shown limitations at baseline. There was also a normalization of inflammatory indexes (ESR, C-reactive protein) and regression of general features of disease. Further long term studies are now required to confirm these promising preliminary results.