Conectar
by Chien-Hsien Kitty Yang, Xiu Ting Yiew, Robert G. Hahn, William Muir, Carolyn Kerr, Shane Bateman
This prospective experimental study evaluated the disposition of a crystalloid and a colloid solution in 10 healthy cats under general anesthesia. Each cat was randomly assigned to receive either 20 mL/kg of a balanced isotonic crystalloid solution (PLA) or 5 mL/kg of 6% tetrastarch 130/0.4 solution (T-HES), administered over 15 minutes, in a 2-period, 2-treatment crossover design. Blood samples were collected, and urine output was measured during a 3-hour experimental period. Plasma dilution was calculated using serial hemoglobin concentrations and red blood cell count. Volume kinetics (distribution and elimination) of each fluid were determined using non-linear mixed effects pharmacokinetic modeling software. Data from a previous study with a similar methodology in healthy conscious cats were included in the population kinetic analysis, revealing anesthesia as a significant covariate for k21 (peripheral-to-central intercompartmental rate constant) for PLA and k10 (dilution-dependent first-order elimination rate constant) for T-HES. Cumulative urine output under general anesthesia was approximately 3.5 times lower for PLA and 2.5 times lower for T-HES compared to conscious cats. Overall, our data suggest that the elimination of PLA and T-HES is markedly reduced, and a bolus of PLA produces a short period of plasma expansion with the potential to cause significant peripheral fluid accumulation in cats during general anesthesia.
by Vivian Y. Tat, Aleksandra K. Drelich, Pinghan Huang, Kamil Khanipov, Jason C. Hsu, Steven G. Widen, Chien-Te Kent Tseng, George Golovko
Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after β-CoVs or mock infection of Calu-3/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (BST2), Z-DNA Binding Protein 1 (ZBP1), C-X-C Motif Chemokine Ligand 11 (CXCL11), and Interferon Induced Transmembrane Protein 1 (IFITM1), were identified as potential drug targets against β-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses.
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