Emergence of new types of Theileria orientalis in Australian cattle and possible cause of theileriosis outbreaks

Theileria parasites cause a benign infection of cattle in parts of Australia where they are endemic, but have, in recent years, been suspected of being responsible for a number of outbreaks of disease in cattle near the coast of New South Wales. The objective of this study was to identify and characterize the species of Theileria in cattle on six farms in New South Wales where disease outbreaks have occurred, and compare with Theileria from three disease-free farms in Queensland that is endemic for Theileria. Special reference was made to sub-typing of T. orientalis by type-specific PCR and sequencing of the small subunit (SSU) rRNA gene, and sequence analysis of the gene encoding a polymorphic merozoite/piroplasm surface protein (MPSP) that may be under immune selection. Nucleotide sequencing of SSU rRNA and MPSP genes revealed the presence of four Theileria genotypes: T. orientalis (buffeli), T. orientalis (ikeda), T. orientalis (chitose) and T. orientalis type 4 (MPSP) or type C (SSU rRNA). The majority of animals showed mixed infections while a few showed single infection. When MPSP nucleotide sequences were translated into amino acids, base transition did not change amino acid composition of the protein product, suggesting possible silent polymorphism. The occurrence of ikeda and type 4 (type C) previously not reported to occur and silent mutation is thought to have enhanced parasite evasion of the host immune response causing the outbreak

Development of Indinavir Submicron Lipid Emulsions Loaded with Lipoamino Acids—In Vivo Pharmacokinetics and Brain-Specific Delivery

The aim of our present work was to develop indinavir O/W submicron lipid emulsions (SLEs) loaded with lipoamino acids for specific delivery to brain. Tetradecyl aspartic acid (A) and decyl glutamic acid (G) loaded stable SLEs of indinavir having a mean size range of 210–220 nm and average zeta potential of −23.54 ± 1.2 mV were developed using homogenization and ultrasonication. The cumulative % drug release from different SLEs varied in between 26% and 85%. The formulations, SLE, SLE-A3, and SLE-G3 were stable to the centrifugal stress, dilution stress, and storage at RT. The total drug content and entrapment efficiency were determined by HPLC method. During pharmacokinetic studies in male Wistar rats there was no significant difference in the serum levels of indinavir for SLE, SLE-A3 and SLE-G3 formulations at all time points. In tissue distribution studies, the therapeutic availability (TA) of indinavir in brain and kidneys for SLE-A3 were 4.27- and 2.66-fold whereas for SLE-G3 were 2.94 and 2.12 times, respectively, higher than that of indinavir solution. But when compared with that of SLE, in brain tissue the levels of indinavir from SLE-G3 and SLE-A3 varied in between 2.5- and 3.38-fold. While in case of the kidney, it was between 1.23- and 1.54-fold only. However, the TA is not significantly different in tissues like the heart, liver, and spleen. Thus, brain-specific delivery of indinavir was improved by including tetradecyl aspartic acid and decyl glutamic acid in submicron lipid emulsions