Glutamine has been used to treat canine patients with parvoviral enteritis. However, little is known about the effect of L-alanyl-L-glutamine (Ala-Gln) supplementation in dogs with parvoviral enteritis. The objective of this study was to determine whether Ala-Gln supplementation can improve dog survival and ameliorate clinical signs without adverse effects. We conducted a randomized, double-blind, placebo-controlled clinical trial involving 39 client-owned dogs. The dogs were randomly assigned to two groups and administered either an Ala-Gln solution (Dipeptiven, 0.4 g/kg, n = 20) or an equivalent volume of placebo (n = 19) orally twice daily. Of the 39 dogs, 17 were vaccinated (n = 9 in the Ala-Gln-treated group and n – 9 in the placebo group). All dogs received standard treatment while hospitalized. The dogs were monitored according to a clinical scoring system and evaluated diagnostically daily for 11 days. Survival rates in both groups were quantified using Kaplan‒Meier survival curves and statistically compared using the log-rank test. The total score for clinical signs did not differ between the groups, except on day 2. The survival rates differed significantly (p=0.038). Three Ala-Gln-treated dogs (15.0%) died during the study, whereas eight dogs in the placebo group died (42.1%). No adverse effects were found to be associated with Ala-Gln treatment. Oral administration of Ala-Gln improves survival in dogs with parvoviral enteritis without causing adverse effects.
Macrophages secrete various cytokines and inflammatory mediators, resulting in playing critical roles in inflammation and immunity. In this study, we investigated anti-inflammatory and immune enhancing properties of PB203, which is a water-soluble extract powder from the fruit of Actinidia polygama, in macrophages. A. polygama is a medicinal plant traditionally known to treat abdominal pain, stroke and rheumatoid arthritis. However, the molecular mechanism for the immune modulation of PB203 is still unclear. Therefore, we assessed the effects of PB203 on the lipopolysaccharide (LPS)-induced inflammation and immune activation, and elucidated its action mechanism in mouse macrophage, RAW264.7 cells. PB203 significantly suppressed not only the levels of nitric oxide (NO), prostaglandin E2, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), but also the mRNA expression of inducible NO synthase, cyclooxygenase-2, TNF-α and IL-1β in LPS-stimulated RAW264.7 cells. We also found that these anti-inflammatory activities of PB203 were mediated through the inhibition of toll-like receptor 4 and nuclear factor kappa B (NF-κB) induced by LPS. On the other hand, in normal macrophages, PB203 dose-dependently elevated the gene expression of immunomodulators including granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1 and TNF-α in a statistically significant manner. The expression of IL-10, IL-1β, IL-6, and interferon-γ were also remarkably upregulated by the treatment of 500 μg/mL PB203. In addition, PB203-mediated production of NO and TNF-α was attenuated by NF-κB inhibition in RAW264.7 cells. Interestingly, PB203 promoted the production of nuclear factor erythroid-2-related factor 2, resulting in the increased level of heme oxygenase-1, which is a representative antioxidant enzyme, in both LPS-stimulated and normal RAW264.7 cells. Taken all together, these results suggest that PB203 may have great potential as the candidate of anti-inflammatory agent for improving inflammatory diseases or immune enhancing agent for preventing infectious diseases. Keywords: Actinidia polygama extract (PB203); macrophages; immunomodulator; nuclear factor kappa B (NF-κB); heme oxygenase-1 (HO-1)
Toll-like receptor 4 (TLR4) is known to contribute to the modulation of insulin resistance and systemic inflammation seen in obesity and the metabolic syndrome. The present study was performed to investigate the fertility competence of TLR4 knock out male mice (TLR4 mice) on a high-fat diet (HFD), compared to a normal-chow diet (NCD). The controls included wildtype (WT) mice fed on a HFD or NCD. Six-week-old male mice were fed with either a NCD or HFD for 20 weeks. Body and organ weights, serum levels of glucose, triglycerides and hepatoxicity, sperm quality and spermatogenesis were observed after the sacrifice. Also, randomly selected male mice were mated with virgin female mice after feeding of 19 weeks. The weight of the body and organs increased in WT and TLR4 mice on a HFD compared to those of mice on a NCD. The weights of the reproductive organs did not vary among the treatment groups. The motility and concentration of the epididymal spermatozoa decreased in both WT and TLR4 mice fed a HFD. The pregnancy rate and litter size declined in the HFD-fed WT mice compared to the HFD-fed TLR4 mice. In conclusion, the HFD alters energy and steroid metabolism in mice, which may lead to male reproductive disorders. However, fertility competence was somewhat restored in HFD-fed TLR4 male mice, suggesting that the TLR4 is involved in testis dysfunction due to metabolic imbalance.
Patients experiencing out-of-hospital cardiac arrest (OOHCA) during the weekend are less likely to survive to hospital admission than those experiencing OOHCA on weekdays. We aimed to determine whether the survival rates of in-hospital cardiac arrest (IHCA) were lower on weekends than on weekdays. We comprehensively reviewed the records of patients who experienced IHCA at CBNUH between 2018 and 2020. A total of 861 IHCAs occurred during the study period; these data included recurrent IHCA cases, as some patients experienced more than one IHCA. Of these, 739 IHCA cases were included in the survival analysis, and the survival rate was 65.2%, which is higher than the rate reported in a previous study. There were no differences in the survival rate between weekdays and weekends. Additionally, the time of day at which IHCA occurred and pre-IHCA intubation status did not affect survival. Patients in wards were less likely to survive than those in intensive care units (60.0% vs. 66.0%). Although pre-IHCA intubation did not show any added value in preventing sudden cardiac arrests, meticulous patient care and monitoring in terms of intra- or extrapulmonary oxygen therapy is needed, as is the promotion of cardio-pulmonary-cerebral resuscitation (CPCR) equipment availability and quick rescuer responses for patients with IHCA. Our findings may be of value in improving CPCR guidelines and monitoring patients at risk of IHCA.
Babesiosis is a tick-borne disease caused by intraerythrocytic protozoa. Despite the increasing acknowledgement that babesiosis represents a threat to animal and human health, to date there have been few studies focusing on the disease in the Republic of Korea (ROK). In the present study, we report a Babesia capreoli infection in an Ixodes nipponensis tick obtained from a Korean water deer (Hydropotes inermis argyropus). The tick was identified with polymerase chain reaction analysis as I. nipponensis (Japanese hard tick). A phylogenetic analysis based on the 18S rRNA gene sequences revealed that the isolate found in I. nipponensis belonged to the B. capreoli lineage and was distinct from the Asian, European, and North American lineages of Babesia divergens. Although our isolate belonged to the B. capreoli lineage it did not form a cluster with others isolates in the same lineage; this may be due to differences in the tick species that transmit B. capreoli or in the host species. We were unable to identify the reservoir host for our case of B. capreoli transmission, though regional ticks may be the primary vector. This study confirms the presence of B. capreoli in the ROK, and its presence suggests that further study is warranted to determine its prevalence and pathogenicity in wild and domesticated animals.