Immune Modulatory Activities of Arginyl-Fructose (AF) and AF-Enriched Natural Products in In-Vitro and In-Vivo Animal Models.

The immune system plays an important role in maintaining body homeostasis. Recent studies on the immune-enhancing effects of ginseng saponins have revealed more diverse mechanisms of action. Maillard reaction that occurs during the manufacturing processes of red ginseng produces a large amount of Amadori rearrangement compounds (ARCs), such as arginyl-fructose (AF). The antioxidant and anti-hyperglycemic effects of AF have been reported. However, the possible immune enhancing effects of non-saponin ginseng compounds, such as AF, have not been investigated. In this study the effects of AF and AF-enriched natural product (Ginofos, GF) on proliferation of normal mouse splenocytes were evaluated in vitro and male BALB/c mice models. The proliferation of splenocytes treated with mitogens (concanavalin A, lipopolysaccharide) were further increased by addition of AF (p < 0.01) or GF (p < 0.01), in a dose dependent manner. After the 10 days of oral administration of compounds, changes in weights of spleen and thymus, serum immunoglobulin, and expression of cytokines were measured as biomarkers of immune-enhancing potential in male BALB/c mice model. The AF or GF treated groups had higher weights of the thymus (0.94 ± 0.25 and 0.86 ± 0.18, p < 0.05, respectively) than that of cyclophosphamide treated group (0.59 ± 0.18). This result indicates that AF or AF-enriched extract (GF) increased humoral immunity against CY-induced immunosuppression. In addition, immunoglobulin contents and expression of cytokines including IgM (p < 0.01), IgG (p < 0.05), IL-2 (p < 0.01), IL-4 (p < 0.01), IL-6 (p < 0.01), and IFN-γ (p < 0.05) were also significantly increased by supplementation of AF or GF. These results indicate that AF has immune enhancing effects by activation of adaptive immunity via increase of expression of immunoglobulins and cytokines such as IgM, IgG, IL-2, IL-4, IL-6 and thereby proliferating the weight of thymus. Our findings provide a pharmacological rationale for AF-enriched natural products such as ginseng and red ginseng that can possibly have immune-enhancement potential and should be further evaluated.

Optimal sessions of hyperbaric oxygen therapy in patients with carbon monoxide poisoning: A prospective observational study.

INTRODUCTION: Hyperbaric oxygen (HBO) therapy may be a useful treatment to prevent the development of delayed neuropsychiatric sequelae (DNS) in patients with acute carbon monoxide (CO) poisoning. However, there is no clear consensus regarding the optimal number of HBO therapy sessions in patients with CO poisoning. Here, we compared the development of DNS after 3 and > 3 sessions of HBO therapy in patients with acute CO poisoning. METHODS: This prospective observational study recruited 299 patients with CO poisoning. Demographic and clinical information were obtained, including comorbidities, vital signs, and symptoms. Patients were divided into two groups according to whether they received 3 or > 3 sessions of HBO therapy (3 HBO vs. >3 HBO). A propensity score-matching process was used to balance potential prognostic factors in both groups. RESULTS: Of the 299 patients with acute CO poisoning enrolled in this study, 183 (59.0%) were included in the analysis. Patients were excluded for the following reasons: age < 18 years, not underwent HBO therapy, discharged against medical advice, and loss to follow-up. The overall rate of DNS development was 17.5%. The >3 HBO group had a higher incidence of DNS development compared to the 3 HBO group (36.3% vs. 16.3%; p = 0.09). Propensity score-matching analysis revealed similar incidences of DNS (31.3% vs. 28.1%, respectively; p > 0.99). CONCLUSIONS: There is a critical need to determine the optimal number of HBO therapy sessions for patients with acute CO poisoning. This study showed no difference in DNS development after 3 and > 3 sessions of HBO therapy.

Effect of ethanol in carbon monoxide poisoning and delayed neurologic sequelae: A prospective observational study.

OBJECTIVES: Carbon monoxide (CO) is one of the most common poisoning substances, which causes mortality and morbidity worldwide. Delayed neurologic sequelae (DNS) have been reported to occur from several days to months after exposure to CO. Thus, there is a need for prevention, recognition, and treatment of DNS. Patients with CO poisoning as a component of intentional suicide often also consume ethanol, but there is debate regarding its role in DNS. We explored whether ethanol has a neuroprotective effect in CO poisoning. METHODS: This prospective observational study included patients who visited the emergency department from August 2016 to August 2019 due to CO poisoning. After treatment of acute CO poisoning, patients were interviewed by telephone to ascertain whether DNS had occurred within 2 weeks, 1 month, and 3 months from the time of CO exposure. RESULTS: During the study period, 171 patients were enrolled. 28 patients (16.37%) developed DNS. The initial Glasgow Coma Scale (GCS) scores were 15 (10.5-15) for the non-DNS group and 10 (7-15) for the DNS group (p = 0.002). The ethanol levels were 11.01 ± 17.58 mg/dL and 1.49 ± 2.63 mg/dL for each group (p < 0.001). In multivariate logistic regression analysis, the GCS score had an odds ratio of 0.770 (p < 0.001) and the ethanol level had 0.882 (p < 0.030) for onset of DNS. CONCLUSIONS: Higher ethanol level and higher initial GCS score were associated with lower incidence of DNS. Ethanol could have a neuroprotective effect on the occurrence of DNS in CO poisoning patients.

Hyperbaric Oxygen Therapy Did Not Prevent Delayed Neuropsychiatric Sequelae in a Prospective Observational Study With Propensity Score Matching in 224 Patients With Acute Carbon Monoxide Toxicity.

BACKGROUND: It is important to prevent the development of delayed neuropsychiatric sequelae (DNS) in acute carbon monoxide (CO) intoxication, but no effective treatment has been clearly identified. Hyperbaric oxygen (HBO) therapy is one of the treatment options in acute CO poisoning; however, whether it can prevent the development of DNS is controversial. OBJECTIVES: The purpose of this study is to compare the effectiveness of normobaric oxygen (NBO) and HBO in preventing DNS. METHODS: This prospective observational study was conducted on all patients with CO poisoning admitted to the emergency department of a tertiary hospital from 2016 to 2019. We followed-up patients to determine whether symptoms of DNS occurred at ≤6 months. We matched the propensity score to an equivalent distribution of potential covariates. RESULTS: A total of 224 patients with CO poisoning were enrolled in this study. NBO was used for 26 patients and HBO for 198 patients. DNS occurred in 40 patients. There were significant differences between the NBO and HBO groups in terms of carboxyhemoglobin, loss of consciousness, dizziness, chest pain, hospitalization, and length of hospital stay. The incidence of DNS was 19.2% in the HBO group, which was higher than the 7.7% observed in the NBO group, but the difference was not significant (p = 0.18). After propensity score matching, the incidence of DNS did not differ between the NBO and HBO groups (8.3% vs. 10.4%, p > 0.99). CONCLUSION: There was no difference in the incidence of DNS between groups receiving HBO and NBO in acute CO intoxication.

A study on evaluator factors affecting physician-patient interaction scores in clinical performance examinations: a single medical school experience.

BACKGRUOUND: This study is an analysis of evaluator factors affecting physician-patient interaction (PPI) scores in clinical performance examination (CPX). The purpose of this study was to investigate possible ways to increase the reliability of the CPX evaluation. METHODS: The six-item Yeungnam University Scale (YUS), four-item analytic global rating scale (AGRS), and one-item holistic rating scale (HRS) were used to evaluate student performance in PPI. A total of 72 fourth-year students from Yeungnam University College of Medicine in Korea participated in the evaluation with 32 faculty and 16 standardized patient (SP) raters. The study then examined the differences in scores between types of scale, raters (SP vs. faculty), faculty specialty, evaluation experience, and level of fatigue as time passes. RESULTS: There were significant differences between faculty and SP scores in all three scales and a significant correlation among raters' scores. Scores given by raters on items related to their specialty were lower than those given by raters on items out of their specialty. On the YUS and AGRS, there were significant differences based on the faculty's evaluation experience; scores by raters who had three to ten previous evaluation experiences were lower than others' scores. There were also significant differences among SP raters on all scales. The correlation between the YUS and AGRS/HRS declined significantly according to the length of evaluation time. CONCLUSION: In CPX, PPI score reliability was found to be significantly affected by the evaluator factors as well as the type of scale.

Adverse effects of BDE-47 on in vivo developmental parameters, thyroid hormones, and expression of hypothalamus-pituitary-thyroid (HPT) axis genes in larvae of the self-fertilizing fish Kryptolebias marmoratus.

2,2',4,4'-tetrabromodiphenylether (BDE-47) is known to have the potential to disrupt the thyroid endocrine system in fishes due to its structural similarity to the thyroid hormones triiodothyronine (T3) and thyroxine (T4). However, the effects of BDE-47 on thyroid function in fishes remain unclear. In this study, abnormal development (e.g. deformity, hemorrhaging) and an imbalance in thyroid hormone (TH) homeostasis was shown in the early developmental stages of the mangrove killifish Kryptolebias marmoratus in response to BDE-47 exposure. To examine the thyroid endocrinal effect of BDE-47 exposure in mangrove killifish K. marmoratus larvae, transcript levels of genes involved in TH homeostasis and hypothalamus-pituitary-thyroid (HPT) axis-related genes were measured. The expression of thyroid hormone metabolism-related genes (e.g. deiodinases, UGT1ab) and HPT axis-related genes was up-regulated and there were significant changes in TH levels (P < 0.05) in response to BDE-47 exposure. This study provides insights into the regulation of TH homeostasis at the transcriptional level and provides a better understanding on the potential impacts of BDE-47 on the thyroid endocrine system of fishes.

Cross-reactivities of mammalian MAPKs antibodies in rotifer and copepod: Application in mechanistic studies in aquatic ecotoxicology.

The mitogen-activated protein kinases (MAPKs) family is known to mediate various biological processes in response to diverse environmental pollutants. Although MAPKs are well characterized and studied in vertebrates, in invertebrates the cross-reactivities of MAPKs antibodies were not clearly known in response to environmental pollutants due to limited information of antibody epitopes with material resources for invertebrates. In this paper, we performed phylogenetic analysis of MAPKs genes in the marine rotifer Brachionus koreanus and the copepods Paracyclopina nana and Tigriopus japonicus. Also in rotifer and copepods, several studies of Western blot of MAPK signaling pathways were shown in response to environmental pollutants, including multi-walled carbon nanotubes (MWCNTs), water-accommodated fractions (WAFs) of crude oil, and microplastics. This paper will provide a better understanding of the underlying mechanistic scenario in terms of cross-reactivities of mammalian antibodies in rotifer and copepod.

Antimicrobial Characterization of Inula britannica against Helicobacter pylori on Gastric Condition.

The antimicrobial effects of methanol and ethanol extracts of Inula britannica against several Helicobacter pylori strains (26695, J99, and SS1) were evaluated in vitro, to determine their applicability as functional foods. In the paper disc diffusion method, the antimicrobial effects of the I. britannica extracts against the H. pylori strains were apparent. Viable cell counting also showed that the extracts at 100 µg/ml concentration dramatically decreased the viability of the H. pylori strains. In particular, the methanol and ethanol extracts at a concentration of 100 µg/ml reduced the H. pylori SS1 cell number to 2.46 log CFU/ml and 1.08 log CFU/ml, respectively. In the presence of 100 µg/ml extracts, the urease production of H. pylori SS1 was decreased to more than 30%, whereas that of H. pylori J99 and H. pylori 26695 was decreased to about 20%, relative to the controls. The extracts inhibited the attachment of the H. pylori strains to human gastric AGS cells as well as caused the detachment of already attached H. pylori cells. In addition, the H. pylori morphology was changed to a coccoidal shape in the presence of the extracts. In conclusion, the I. britannica extracts were effective against H. pylori strains in vitro, irrespective of genotype status, and could therefore be used as novel functional foods.

A fatal case of severe hemolytic disease of newborn associated with anti-Jk(b).

The Kidd blood group is clinically significant since the Jk antibodies can cause acute and delayed transfusion reactions as well as hemolytic disease of newborn (HDN). In general, HDN due to anti-Jk(b) incompatibility is rare and it usually displays mild clinical symptoms with a favorable prognosis. Yet, we apparently experienced the second case of HDN due to anti-Jk(b) with severe clinical symptoms and a fatal outcome. A female patient having the AB, Rh(D)-positive blood type was admitted for jaundice on the fourth day after birth. At the time of admission, the patient was lethargic and exhibited high pitched crying. The laboratory data indicated a hemoglobin value of 11.4 mg/dL, a reticulocyte count of 14.9% and a total bilirubin of 46.1 mg/dL, a direct bilirubin of 1.1 mg/dL and a strong positive result (+++) on the direct Coomb's test. As a result of the identification of irregular antibody from the maternal serum, anti-Jk(b) was detected, which was also found in the eluate made from infant's blood. Despite the aggressive treatment with exchange transfusion and intensive phototherapy, the patient died of intractable seizure and acute renal failure on the fourth day of admission. Therefore, pediatricians should be aware of the clinical courses of hemolytic jaundice due to anti-Jk(b), and they should be ready to treat this disease with active therapeutic interventions.