Evaluation of Biological Equivalence for Generic Tulathromycin Injections in Cattle.

The recent expiration of patents for the antibiotic tulathromycin has led to a significant increase in the number of generic tulathromycin products (GTPs) available. This study aims to evaluate the bioequivalence of four GTPs, which experienced a rapid increase in market share. The bioequivalence was evaluated by performing pharmacokinetic assessments. The four selected GTPs (Tulaject, Tulagen, Toulashot, and T-raxxin) were compared with the reference product, Draxxin. A dose of 2.5 mg/kg.bw/day was administered via subcutaneous injection, and blood samples were collected 460 times from 20 Holstein cattle. Plasma concentrations of tulathromycin were measured over time using LC-MS/MS analysis. Bioequivalence was evaluated using a statistical program for pharmacokinetic parameters, including the area under the concentration time curve (AUC) and the maximum plasma concentration (Cmax). The bioequivalence was considered proven if the difference between the test and reference products was within 20% for both AUC and Cmax. The results showed that the confidence interval (CI, 90%) for both AUC and Cmax values was within the 80~120% range, demonstrating the bioequivalence of the four GTPs compared to Draxxin. This study provides evidence for the bioequivalence of the selected GTPs, contributing to their validation for use as effective antibiotics.

Post-vaccination Monitoring to Assess Foot-and-Mouth Disease Immunity at Population Level in Korea.

In South Korea, domestic cattle, pigs, and goats were subjected to mandatory foot-and-mouth disease (FMD) vaccination and year-round serosurveillance since 2011. In 2020, approximately USD 95 million was spent solely for FMD vaccine purchase for 59 million livestock, and 1.25 million samples were tested to estimate the population immunity and demonstrate the absence of virus circulation. As the FMD vaccination program was revised in 2018, the post-vaccination monitoring (PVM) was designed to evaluate the effectiveness of the vaccine program of three vaccines approved for routine use. To this end, monitoring post-vaccination immunity has been conducted by collecting 35,626 serum samples at 28 days post-vaccination following regular national vaccinations, which were carried out in April and in October in 2020. The design of the serological test for PVM was specially targeted at particular livestock groups, including dairy cattle, goats, and beef cattle aged 6-12 months, which were generally estimated to have a low expected seroprevalence. The risk factors had also been identified, considering the increased likelihood of infection in a particular location, herd size, and husbandry system applied in a targeted sample collection. Serum sample collection and SP-O and NSP antibody tests were performed by local veterinary laboratories using commercially available ELISAs. The current FMD vaccination program, which was performed twice a year following the regimen of primary vaccination and boost, resulted in over 80% population immunity. The seroprevalence monitored after the vaccination in fall was higher than the one studied in spring except in pigs. It was demonstrated that the seroprevalence of risk-based targeted samples ranged from 93.8 to 100% in cattle, 63.2 to 100% in pigs, and 20.0 to 100% in goats. Of note is the area near the North Korean borders which showed a relatively low seroprevalence among the targeted regions, and no NSP sero-positive reactor was detected in this region. When subpopulation immunity at the individual level was assessed, the seroprevalence in young cattle stock was slightly lower (95.8%) than that of adults (98.4%). In conclusion, the FMD vaccination campaign has been successfully implemented in Korea, and the PVM can be a supplementary program for massive routine surveillance in terms of providing timely information needed both to estimate population immunity and to properly target "risk-based surveillance."

Characterization of Transplasma Membrane Electron Transport Chain in Wild and Drug-Resistant Leishmania donovani Promastigote and Amastigote.

BACKGROUND: Leishmania donovani (L. donovani) is one of the parasites that cause leishmaniasis. The mechanisms by which L. donovani fights against adverse environment and becomes resistant to drugs are not well understood yet. OBJECTIVE: The present study was designed to evaluate the effects of different regulators on the modulation of Transplasma Membrane Electron Transport (transPMET) systems of susceptible and resistant L. donovani cells. MATERIALS AND METHODS: Effects of UV, different buffers, and electron transport inhibitors and stimulators on the reduction of α-lipoic acid (ALA), 1,2-naphthoquinone-4-sulphonic acid (NQSA) and ferricyanide were determined. RESULTS AND DISCUSSION: ALA reductions were inhibited in susceptible, sodium antimony gluconate (SAG)-resistant and paromomycin (PMM)-resistant AG83 amastigote cells, and stimulated in susceptible and SAG-resistant AG83 promastigote cells upon UV exposure. The results indicate that UV irradiation almost oppositely affect ALA reductions in amastigotes and promastigotes. ALA reductions were stimulated in sensitive and inhibited in resistant GE1 amastigotes upon UV exposure. Susceptible amastigotes and promastigotes inhibited, and resistant amastigotes and promastigotes stimulated NQSA reduction under UV irradiation. Thus, susceptible and drug-resistant amastigotes and promastigotes are different in the reduction of ALA. Susceptible and resistant AG83 amastigotes and promastigotes inhibited the ferricyanide reductions upon UV exposure, which indicates, there is no such difference in ferricyanide reductions among susceptible as well as resistant AG83 amastigotes and promastigotes. The reductions of extracellular electron excerptors in susceptible promastigotes requires the availability of Na+ and Cl- ions for maximal activity but susceptible amastigotes are mostly not dependent on the availability of Na+ and Cl- ions. Both in promastigotes and amastigotes, reductions of electron acceptors were strongly inhibited by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone. Furthermore, antimycin A, rotenone and capsaicin markedly inhibited the reductions of electron acceptors in promastigotes, but not in amastigotes. CONCLUSION: Results of this study suggest that the transPMET system is functionally different in wild and resistant strains of L. donovani.

Orexin-A modulates excitatory synaptic transmission and neuronal excitability in the spinal cord substantia gelatinosa.

Although intrathecal orexin-A has been known to be antinociceptive in various pain models, the role of orexin-A in antinociception is not well characterized. In the present study, we examined whether orexin-A modulates primary afferent fiber-mediated or spontaneous excitatory synaptic transmission using transverse spinal cord slices with attached dorsal root. Bath-application of orexin-A (100nM) reduced the amplitude of excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation of Aδ- or C-primary afferent fibers. The magnitude of reduction was much larger for EPSCs evoked by polysynaptic C-fibers than polysynaptic Aδ-fibers, whereas it was similar in EPSCs evoked by monosynaptic Aδ- or C-fibers. SB674042, an orexin-1 receptor antagonist, but not EMPA, an orexin-2 receptor antagonist, significantly inhibited the orexin-A-induced reduction in EPSC amplitude from mono- or polysynaptic Aδ-fibers, as well as from mono- or polysynaptic C-fibers. Furthermore, orexin-A significantly increased the frequency of spontaneous EPSCs but not the amplitude. This increase was almost completely blocked by both SB674042 and EMPA. On the other hand, orexin-A produced membrane oscillations and inward currents in the SG neurons that were partially or completely inhibited by SB674042 or EMPA, respectively. Thus, this study suggests that the spinal actions of orexin-A underlie orexin-A-induced antinociceptive effects via different subtypes of orexin receptors.