The pathogenesis of systemic sclerosis (SSc) is characterized by activation of the immune system, impaired angiogenesis, and activated dermal fibroblasts. The effects of the immunosuppressive agent bucillamine (SA 96) on fibroblasts and angiogenic factors have not been examined. SA 96, and particularly its metabolite SA 981, increased the levels of vascular endothelial growth factor (VEGF) mRNA and protein dose-dependently in dermal fibroblasts from patients with SSc and healthy control subjects without influencing cell viability. SSc fibroblast cultures showed consistently a higher inducibility of VEGF than cultures from healthy control subjects. Preincubation with the SP-1 inhibitor mithramycin as well as blockade of nuclear factor (NF)-B signaling with pyrrolidine dithiocarbamate treatment and IB transfection reduced significantly the transcription of VEGF, indicating that both transcription factors contribute to the activation of VEGF by SA 981. Specific binding of NF-B protein to its binding site after treatment with SA 981 was confirmed by electrophoretic mobility shift assay. In contrast, SA 981 did not influence the stability of VEGF mRNA as analyzed with actinomycin D assays. The study provides evidence for a role of NF-B in the transcriptional regulation of the VEGF gene. SA 96 might have positive aspects on the impaired angiogenesis in patients with SSc.

Resting energy expenditure (REE) was investigated in 8 children with propionic and methylmalonic acidaemias because a lowered REE has been reported in the literature. We observed a marginally elevated REE and think that adequate caloric intake and the use of a synthetic amino acid mixture are responsible for this.

Two hundred and forty newly weaned pigs (PIC, Hendersonville, TN) were used to determine if supplementing additional arginine (Arg) either in the water or in the feed, and the combinations thereof, improved intestinal integrity and growth performance in nursery pigs. Each of the 80 pens contained 3 pigs (21 ± 2 days of age) which were randomly allotted to treatments in 4 x 3 factorial arrangement consisting of four water treatments (0, 4, 8, and 12% Arg stock delivered through a 1:128 medication delivery system) in combination with 3 dietary Arg treatments (1.35, 1.55 and 1.75% standardized ileal digestible Arg; SID). Pigs and feeders were weighed at the d0, d6 (water and diet change), d20 (diet change), and d41 for the calculation of average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Eighty pigs, 1 pig/pen, were euthanized at d6 for ileum evaluation of villus height and crypt depth. The remaining pigs were taken off the Arg-water treatment and fed phase-2 diets formulated to contain 1.35, 1.55, and 1.75% SID Arg. All pigs received a common diet from d 20 to d41. Data were analyzed by pen as repeated measures (SAS 9.4). No interaction between water- and dietary- Arg were detected on nursery pig growth performance. There was a significant quadratic effect of SID Arg in the feed on pig final body weight (BW), ADG, ADFI, and G:F (P ≤ 0.037), where feeding 1.55% dietary Arg tended to improve growth performance compared to the 1.35% level for the 41 days of the trial (P ≤ 0.088). The use of the stock 8% Arg in the water resulted in a reduction in crypt depth (0: 132.5, 4: 140.7, 8: 117.3, 12: 132.0; P ≤ 0.01) and an improvement in intestinal permeability. The 4% oral Arg significantly reduced villous height:crypt depth ratio (0: 2.50, 4: 2.09, 8: 2.56, 12: 2.43; P ≤ 0.02). In conclusion, the feeding of 1.55% Arg resulted in an improvement in nursery pig ADG, ADFI, G:F, and final BW but did not alter intestinal villi morphology; however, the use of Arg in the water resulted in an improvement in intestinal villi, but no phenotypical change in piglet growth in the nursery.

controls) of IL-2 positive cells; 6 patients and 1 control of IL-4 positive cells and 7 patients and 0 control of IFN-g positive cells. Six patients presented increased percentages of both IL-2 and IL-4 and IFN-g (i.e. they had both Th1 and Th2 activation), 4 of IL-2 positive cells and 1 IFN-g only (isolated Th1 activation).After PMA stimulation 6 patients presented increased percentages of IFN-g positive cells; 1 of IL-4 and 0 patient of IL-2 positive cells. Conclusion Our study demonstrates that Th1 activation occurs in peripheral blood of SSc patients. The role, if any, of such activation must be investigated.

The objective of this experiment was to evaluate the impact of lowering floor space allowance in finishing hogs from 65 to 120 kg when fed high versus low energy diets on growth performance. Eighty-eight mixed-sex pens with 24 ± 1 pigs per pen were randomly assigned by weight in a complete block design to one of eight treatments in a 2 x 4 factorial arrangement with two energy levels: low (LE, 3267 ± 15 kcal/kg) vs. high (HE, 3389 ±15 kcal/kg) accomplished through fat inclusion; and four floor space allowances: 0.6, 0.63, 0.65, 0.67 m 2 per pig. Assigned floor space was accomplished by moveable gates in the rear of the pen which were adjusted at each pig removal until the marketing phase. Pen weight was measured at days 0, 29, and 48, with feed disappearance measured at day 29 and 48 to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (GF). Data were analyzed by pen (SAS 9.4, Cary, NC), as repeated measures, with the fixed effects of floor space allowance, dietary energy level, and the interaction between floor space allowance and energy level. For the overall experiment, decreased floor space had no effect (P>0.1) on ADG, ADFI, or GF. Energy had a significant effect (P<0.01) on ADFI (3.17 vs 3.12 kg for LE and HE, respectively) and GF (0.35 and 0.36 for LE and HE, respectively), and tended to impact (P= 0.08) ADG (1.12 vs 1.13 kg, for LE and HE, respectively). In conclusion, reducing space allowance from 0.67 m 2 down to 0.6 m 2 did not affect the growth performance of pigs from 65 to 120 kg. Pigs fed LE consumed more than the HE diets but had generally similar growth and no difference in BW.