Soluble Protein Hydrolysate Ameliorates Gastrointestinal Inflammation and Injury in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice.

Inflammatory bowel diseases (IBD) are chronic, recurring gastrointestinal diseases that severely impair health and quality of life. Although therapeutic options have significantly expanded in recent years, there is no effective therapy for a complete and permanent cure for IBD. Well tolerated dietary interventions to improve gastrointestinal health in IBD would be a welcome advance especially with anticipated favorable tolerability and affordability. Soluble protein hydrolysate (SPH) is produced by the enzymatic hydrolysis of commercial food industry salmon offcuts (consisting of the head, backbone and skin) and contains a multitude of bioactive peptides including those with anti-oxidant properties. This study aimed to investigate whether SPH ameliorates gastrointestinal injury in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Mice were randomly assigned to four groups: Control (no colitis), Colitis, Colitis/CP (with control peptide treatment), and Colitis/SPH (with SPH treatment). Colitis was induced by cutaneous sensitization with 1% TNBS on day -8 followed by 2.5% TNBS enema challenge on day 0. Control peptides and SPH were provided to the mice in the Colitis/CP or Colitis/SPH group respectively by drinking water at the final concentration of 2% w/v daily from day -10 to day 4. Then, the colon was harvested on day 4 and examined macro- and microscopically. Relevant measures included disease activity index (DAI), colon histology injury, immune cells infiltration, pro- and anti-inflammatory cytokines and anti-oxidative gene expression. It was found that SPH treatment decreased the DAI score and colon tissue injury when compared to the colitis-only and CP groups. The protective mechanisms of SPH were associated with reduced infiltration of CD4+ T, CD8+ T and B220+ B lymphocytes but not macrophages, downregulated pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6), and upregulated anti-inflammatory cytokines (transforming growth factor-ß1 and interleukin-10) in the colon tissue. Moreover, the upregulation of anti-oxidative genes, including ferritin heavy chain 1, heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, and superoxide dismutase 1, in the colons of colitis/SPH group was observed compared with the control peptide treatment group. In conclusion, the protective mechanism of SPH is associated with anti-inflammatory and anti-oxidative effects as demonstrated herein in an established mice model of colitis. Clinical studies with SPH as a potential functional food for the prevention or as an adjuvant therapy in IBD may add an effective and targeted diet-based approach to IBD management in the future.

A new mouse model for temporal- and tissue-specific control of extracellular superoxide dismutase.

The extracellular isoform of superoxide dismutase (EC-SOD, Sod3) plays a protective role against various diseases and injuries mediated by oxidative stress. To investigate the pathophysiological roles of EC-SOD, we generated tetracycline-inducible Sod3 transgenic mice and directed the tissue-specific expression of transgenes by crossing Sod3 transgenic mice with tissue-specific transactivator transgenics. Double transgenic mice with liver-specific expression of Sod3 showed increased EC-SOD levels predominantly in the plasma as the circulating form, whereas double transgenic mice with neuronal-specific expression expressed higher levels of EC-SOD in hippocampus and cortex with intact EC-SOD as the dominant form. EC-SOD protein levels also correlated well with increased SOD activities in double transgenic mice. In addition to enabling tissue-specific expression, the transgene expression can be quickly turned on and off by doxycycline supplementation in the mouse chow. This mouse model, thus, provides the flexibility for on-off control of transgene expression in multiple target tissues.

Subthreshold transpupillary thermotherapy in Chinese patients with myopic choroidal neovascularization: one- and two-year follow up.

BACKGROUND: To perform a safety and efficacy study of subthreshold transpupillary thermotherapy (TTT) in Chinese patients with choroidal neovascularization (CNV) secondary to pathologic myopia. METHODS: In a prospective study, patients with subfoveal or juxtafoveal CNV secondary to high myopia underwent subthreholdTTT with fixed treatment and follow-up protocols. From October 2002 to July 2005, 12 and 24 months of follow up were completed for 21 eyes and 13 eyes respectively. RESULTS: The mean best-corrected visual acuities (BCVA) were maintained at the baseline level at 1 and 2 years. Seventy-two per cent of eyes and 63% of eyes had stable or improved BCVA at 12 and 24 months.Thirty-four per cent and 39% of eyes had a moderate gain in vision (improved by three or more lines) at 12 and 24 months respectively.The average number of subthreshold TTT treatments was 1.7. The major complication of subthresholdTTT included laserrelated low-grade retinal pigment epithelium atrophy in two eyes of young patients with clear lenses. The final VA was significantly associated with pretreated VA (r = 0.614, P = 0.003).The final VA improvement was significantly associated with pretreatment VA in negative correlation (r=-0.731, P = 0.0002, Person correlation test). CONCLUSIONS: Subthreshold TTT in Chinese patients with pathologic myopia and subfoveal or juxtafoveal CNV generally maintained vision at 1- and 2-year follow up. Using decreased power of subthreshold TTT, especially in the younger patients with a clear lens, is suggested.

Transpupillary thermotherapy in chinese patients with choroidal neovascularization secondary to age-related macular degeneration: emphasis on the influence of power setting.

PURPOSE: To perform a safety and efficacy study of transpupillary thermotherapy (TTT) in Chinese patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). METHODS: In a prospective study, patients with subfoveal or juxtafoveal CNV secondary to ARMD underwent TTT with fixed treatment and follow-up protocols. From August 2002 to December 2004, 26 patients (27 eyes) completed > or =6 months of follow-up and were included in this report. RESULTS: Fourteen eyes (52%) had improved or stable visual acuity (loss of <3 lines) and 13 eyes (48%) had vision loss of > or =3 lines. The serial mean visual acuity initially decreased during follow-up, then stabilized by 6 months. In the subgroup of occult or minimally classic CNV (20 eyes), 13 eyes (65%) had improved or stable vision. The major complication of TTT included laser-related retinal pigment epithelium (RPE) atrophy in 10 eyes (37%). Six eyes had mild RPE atrophy, 4 eyes had severe RPE-choroid atrophy (macular burn). Analysis of possible risk factors for macular burn showed that 3 eyes had to have the power amplified due to nuclear sclerosis, and 1 pseudophakic eye had regular power. CONCLUSIONS: TTT in Chinese ARMD patients with occult or minimally classic CNV, according to our protocol, prevented severe vision loss in the majority of patients, but power amplification due to medium lens opacity induced RPE atrophy or burn in some patients.