Lyophilized B. subtilis ZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study in Wistar Rats.

A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strain B. subtilis ZB183. Lyophilized spores at doses of 109, 1010, and 1011 CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days. B. subtilis ZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 1010 and 1011 CFU/kg/day doses without an increase in total protein in males or females and was considered a nonadverse effect. The "No Observed Adverse Effect Level (NOAEL)" is defined at the highest dose of 1011 CFU/kg body weight/day for lyophilized B. subtilis ZB183 Spores under the test conditions employed.

Toxicity and toxicokinetic study of RPh201 in Sprague-Dawley rats.

Mastic gum is used for health products and in the food industry, and is being tested for several clinical indications. Nevertheless, information on its safety is scarce. Our aim was to test the local and systemic toxicity of RPh201, a botanical extract of gum mastic, and to assess the toxicokinetic profile of the mastic gum constituents masticadienonic acid (MDA) and isomasticadienonic acid (IMDA). 340 Sprague-Dawley rats were administered twice weekly subcutaneously with placebo or different doses of RPh201 for 6 months with an interim group at 3 months and a 4-week recovery group. No systemic toxicity was observed with RPh201. Local injection site reactions were observed in all animals, with comparable severity and frequency in the placebo and high dose groups. However, given the relative increase in tissue reaction in the high dose group, these changes were attributed to RPh201 administration. Nevertheless, considering the minor local irritation effects and clear trend for reversibility, the effects were not judged to be adverse. The toxicokinetic study revealed that the MDA and IMDA exposure increased with dose and the increase was supra-proportional on all days. This study supports a "no observed adverse effect level" (NOAEL) of 300 mg/kg body weight in Sprague-Dawley rats.

Twice-weekly palliative radiotherapy for locally very advanced head and neck cancers.

PURPOSE: The purpose of the following study is to evaluate the efficacy of a twice-weekly hypofractionated palliative radiotherapy schedule in locally very advanced head and neck cancers. MATERIALS AND METHODS: Patients with locally very advanced, head and neck cancers were prospectively evaluated after twice-weekly palliative radiotherapy regimen of 32 Gy in 8 fractions. Median age was 55.5 years and the predominant primary site was oral cavity (46%). Majority (70.6%) had Stage IV B disease. Disease related distressing symptoms such as pain, bleeding, skin fungation, respiratory symptoms due to tumor burden, were prospectively assessed before the start of treatment, at conclusion and at 6-12 weeks of completion of treatment. RESULTS: A total of 126 patients were enrolled in the study. Ninety three (73.8%) patients who completed the planned treatment of 32 Gy in 8 fractions were included in the symptom analysis. Overall response rates were 42% at primary disease and 55% at nodal disease. At conclusion of radiotherapy 76.3% of the patients reported improvement in pain scores (P = 0.001) and 42.8% patients reported improvement in anxiety and depression levels (P = 0.001). At first follow-up after 6-12 weeks significant improvement in pain scores (P = 0.001) and anxiety/depression levels (P = 0.001) persisted. The median survival of the patients was 5.5 months. Acute grade III mucositis was seen in one patient (1.2%) while none had grade III skin reactions. CONCLUSION: The proposed radiotherapy regimen is effective for sustained symptom palliation with low acute toxicity in locally very advanced head and neck cancers. It delivers a moderately high dose while being logistically simpler for the patient.

Evaluation, grafting success and field establishment of cashew rootstock as influenced by VAM fungi.

Seven isolates of vesicular arbuscular mycorrhizal (VAM) fungi were isolated from cashew rhizosphere soil of different cashew growing regions of South India. These seven isolates along with two more VAM fungi namely Acaulospora laevis and Glomus mosseae, which were found to be better symbionts for cashew during our earlier study were used to study their effectiveness on the growth and nutrition of cashew rootstock Ullal-1. Four promising VAM fungi were selected based on this study. Rootstocks inoculated with these four fungi were evaluated for their vigour through grafting success, using Ullal-3 cashew variety as scion. Grafting success was more in rootstocks inoculated with A. laevis and one of local isolates Glomus etunicatum. Grafts with rootstock treated with G. etunicatum and A. laevis survived and performed better when planted in the field compared to the uninoculated and other VAM fungal treatments.