RESUMEN
Coccidiosis is a disease of economic importance in poultry causing morbidity and mortality. Reports show that Azadirachta indica and Khaya senegalensis have been used individually in the treatment of avian coccidiosis. We thus investigated the efficacy and safety of the combined aqueous extracts of these plants for the treatment of experimentally induced coccidiosis in broiler chickens using oocyst count, oxidative stress biomarkers, serum biochemistry, histology, and haematological parameters. The phytochemical screening revealed the presence of tannins, saponins, cardiac glycosides, and steroids in both extracts. In addition, alkaloids and flavonoids were present in Azadirachta indica. There was significant (p < 0.05) dose dependent decrease in oocyst count across the treatment groups with 400 mg/kg of the combined extract being the most efficacious dose. Immunomodulatory and erythropoietic activity was observed. There were decreased intestinal lesions and enhanced antioxidant activity across the treatment groups compared to the negative control. Administration of the combined extract did not cause damage to the liver as ALT, AST, and ALP levels were significantly reduced in the uninfected chickens treated with the extracts compared to control suggesting safety at the doses used. The combined aqueous extracts of K. senegalensis stem bark and Azadirachta indica leaves were ameliorative in chickens infected with coccidiosis.
RESUMEN
BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655, a 19-nucleotide, O-methyl stabilized, double-stranded small interfering ribonucleic acid targeting the RTP801 gene in patients with neovascular age-related macular degeneration (AMD). METHODS: Prospective, phase 1, clinical multicentre trial, enrolled 27 patients with neovascular AMD unresponsive to prior treatment and best corrected visual acuity (BCVA) ≤ 20/200 in the study eye in stratum 1: (dose-escalating, open-label: 50 to 3000 µg of PF-04523655) and 27 patients who had potential to benefit from therapy and BCVA of ≤ 20/100 and ≥ 20/800 in stratum 2 (parallel, masked study of 1000, 1500, 2250, and 3000 µg of PF-04523655). The primary outcome was safety and tolerability assessment as well as pharmacokinetic profiling following a single IVT injection of PF-04523655. RESULTS: Doses of PF-04523655 ≥ 400 µg were generally detectable in the plasma at 1, 4, and 24 h post-injection. And all doses were below the lowest level of quantification by day 14. A single IVT injection of 50 to 3000 µg of PF-045237655 was generally safe and well tolerated over 24 months. There were no dose-limiting toxicities. CONCLUSION: A single IVT injection of PF-0523655 ≤ 3000 µg seems safe and well tolerated in eyes with neovascular AMD.