Safety assessment of the commensal strain Bacteroides xylanisolvens DSM 23964

AbstractWe recently isolated and characterized the new strain Bacteroides xylanisolvens DSM 23964 and presented it as potential candidate for the first natural probiotic strain of the genus Bacteroides. In order to evaluate the safety of this strain for use in food, the following standard toxicity assays were conducted with this strain in both viable and pasteurized form: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration assay, and 90day subchronic repeated oral toxicity studies in mice. No mutagenic, clastogenic, or toxic effects were detected even at extremely high doses. In addition, no clinical, hematological, ophthalmological, or histopathological abnormality could be observed after necropsy at any of the doses tested. Hence, the NOAEL could be estimated to be greater than 2.3×1011 CFUs, and 2.3×1014 for pasteurized bacteria calculated as equivalent for an average 70kg human being. In addition, the absence of any in vivo pathogenic properties of viable B. xylanisolvens DSM 23964 cells was confirmed by means of an intraperitoneal abscess formation model in mice which also demonstrated that the bacteria are easily eradicated by the host’s immune system. The obtained results support the assumed safety of B. xylanisolvens DSM 23964 for use in food

Scientific Reports / Toxicological testing of allogeneic secretome derived from peripheral mononuclear cells (APOSEC): a novel cell-free therapeutic agent in skin disease

A cell-free approach using secretomes derived from stem cells or peripheral blood mononuclear cells is an active area of regenerative medicine that holds promise for therapies. Regulatory authorities classify these secretomes as biological medicinal products, and non- clinical safety assessment thus falls under the scope of ICH S6. A secretome of stressed peripheral blood mononuclear cells (APOSEC) was successfully tested in a toxicology program, supporting clinical use of the new drug candidate. Here, to allow for topical, dermal treatment of patients with diabetic foot ulcer, several non-clinical safety studies were performed. Acute toxicity (single dose) and neuropharmacological screening were tested intravenously in a rat model. Risk for skin sensitisation was tested in mice. A 4-week intravenous toxicity study in mice and a 4-week subcutaneous toxicity study in minipigs were conducted to cover the clinical setting and application in a rodent and a non-rodent model. Acute and repeated-dose toxicity studies show that APOSEC administered intravenously and subcutaneously does not involve major toxicities or signs of local intolerance at levels above the intended total human maximal dose of 3.3U/kg/treatment, 200U/wound/treatment, and 100U/cm/treatment. The non-clinical data support the safe topical use of APOSEC in skin diseases related to deficient wound healing.(VLID)493189

Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin - 1-year results of a randomized clinical trial - VIP report no. 1

Objective: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (m and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better. Intervention: Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water, n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000 mum larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present. Main Outcome Measures: The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis. Results: At baseline, move than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P 1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01), Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment. Conclusions: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients. Ophthalmology 2001; 108:841-852 (C) 2001 by the American Academy of Ophthalmology