Recent updates of iodinated contrast media hypersensitivity

Previously, immediate reactions to ionic high-osmolar iodinated contrast media (ICM) were regarded as nonimmunological. However, despite the use of lower-osmolar ICM, ICM hypersensitivity still occurs in some patients and recent studies suggest that there would be a true allergic response, especially in more severe form. Currently, it is important to identify the sensitized ICM and avoid the agent; however, the usefulness of skin tests and challenge tests has not yet been established, since there are few large-scale studies on them. Although, skin test-negative ICM can be safely used in clinical practice, conflicting results have been reported through various studies, depending on the challenge protocols used. Therefore, standard protocols need to provided. Even if a culprit agent is not proven by skin tests, its use should be avoided. Reuse of contrast media increases the risk of occurrence of hypersensitivity reactions. For patients with previous hypersensitivity reactions to contrast media, premedication can help prevent recurrence, but breakthrough in hypersensitivity is not fully achieved by premedication, especially when the previous reaction was a severe form such as anaphylaxis. Therefore, it is necessary to establish an optimal strategy to choose alternative ICM and premedication protocols to prevent recurrence of hypersensitivity reactions to nonionic contrast media.

Comparison of one-bag and multibag desensitization protocols for the prevention of rituximab hypersensitivity

Purpose@#Rituximab is prone to infusion-related reactions, which commonly requires desensitization to maintain its administration. Conventional desensitization protocols are using multistep infusion by diluting solutions. However, the process of diluting drugs and stepwise delivery needs additional time and effort. The objective of this study was to investigate the safety and efficacy of a nondiluting, one-bag protocol of rituximab desensitization. @*Methods@#A retrospective study was performed by reviewing the medical records of patients who underwent rituximab desensitization between 2009 and 2018. The completion rate, occurrence and severity of breakthrough reactions (BTR), and time required to complete the therapy were compared between one-bag protocol and multibag protocol. Results were analyzed by generalized estimation equation method, and odds ratios (ORs) of completion rate and BTR incidence were estimated. @*Results@#Total 190 cases of desensitization therapy were performed in 49 patients; the incidence of BTR was 16.84% and the overall completion rate was 96.32%. No significant difference in completion rate was found (OR, 3.58; 95% confidence interval [CI], 0.79– 16.38) and there was no significant difference in BTR incidence (OR, 0.81; 95% CI, 0.23–2.82) in one-bag protocol. BTR in the one-bag protocol tended to occur even through entire steps, whereas most of the BTR in the multibag protocol occurred at later steps of the process. The average time spent in the desensitization was 60 minutes shorter in the one-bag than the multibag protocol (258.15 minutes vs. 329.81 minutes, P< 0.001). @*Conclusion@#One-bag desensitization protocol showed no significant difference in safety and efficiency compared to the conventional multibag protocol, with shortening the time required for completion.

Association between Smartphone Usage and Mental Health in South Korean Adolescents: The 2017 Korea Youth Risk Behavior Web-Based Survey / 가정의학회지

Background@#Smartphone usage is indispensably beneficial to people’s everyday lives. However, excessive smartphone usage has been associated with physical and mental health problems. This study aimed to evaluate the association of smartphone usage with depressive symptoms, suicidal thoughts, and suicide attempts in Korean adolescents. @*Methods@#This cross-sectional study was conducted in 54,603 Korean adolescent participants (26,930 male and 27,673 female) in the Korea Youth Risk Behavior Survey in 2017 who reported their smartphone use. We performed multiple logistic regression analysis to evaluate the association of smartphone use with mental health after adjusting for relevant covariates. @*Results@#Among the participants, 25.6% of male students and 38.4% of female students reported using their smartphone for at least 30 hours per week. As time duration of smartphone usage increased, the risk of experiencing depressive symptoms, suicidal thoughts, and suicide attempt tended to increase, with odds ratios (95% confidence interval) of 1.18 (1.10–1.26), 1.18 (1.08–1.29), and 1.34 (1.11–1.60), respectively, for high smartphone usage compared with low smartphone usage. These associations remained significant with only slight change in odds ratios after consideration of problems that may be caused by smartphone usage, such as conflicts with family members or peers, or disturbance in school work. @*Conclusion@#Smartphone overuse was independently associated with an increased risk of mental health problems, which did not seem to be mediated by the problems caused by smartphone usage.

Analysis of individual case safety reports of drug-induced anaphylaxis to the Korea Adverse Event Reporting System

PURPOSE: To identify causative agents of the drug-induced anaphylaxis (DIA) by using the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System (KIDS-KAERS) database (Ministry of Food and Drug Safety) in Korea and to check their labeling information regarding anaphylaxis.METHODS: Among Individual Case Safety Reports from January, 2008 to December 2017, cases of DIA were analyzed for demographics, causative agents and fatal cases resulting in death. The domestic drug labeling, Micromedex and U.S. Food and Drug Administration (FDA) drug package insert, were reviewed to check if the labeling information on suspected causative agents contains anaphylaxis.RESULTS: A total of 4,700 cases of DIA were analyzed. The mean age was 49.85±18.32 years, and 2,642 patients (56.2%) were females. Among 8,664 drugs reported as causative agents, antibiotics (27.4%) accounted for the largest portion. There were 18 fatal cases: antibiotics (7 cases), antineoplastic agents (4 cases) were the major causative drugs for the mortality cases. Of 513 drugs reported as suspected causative agents, 103 (20.1%) did not list anaphylaxis as an adverse effect on domestic drug labeling and 16 (3.1%) did not reflect anaphylaxis in any of 3 adverse drug information.CONCLUSION: Analysis of 10-year data showed that antibiotics were the main cause of DIA and the mortality rate was 0.7%. In 3.1% of suspected drugs, there was no description of anaphylaxis in any of the drug labeling.

New vaccines against influenza virus

Vaccination is one of the most effective and cost-benefit interventions that prevent the mortality and reduce morbidity from infectious pathogens. However, the licensed influenza vaccine induces strain-specific immunity and must be updated annually based on predicted strains that will circulate in the upcoming season. Influenza virus still causes significant health problems worldwide due to the low vaccine efficacy from unexpected outbreaks of next epidemic strains or the emergence of pandemic viruses. Current influenza vaccines are based on immunity to the hemagglutinin antigen that is highly variable among different influenza viruses circulating in humans and animals. Several scientific advances have been endeavored to develop universal vaccines that will induce broad protection. Universal vaccines have been focused on regions of viral proteins that are highly conserved across different virus subtypes. The strategies of universal vaccines include the matrix 2 protein, the hemagglutinin HA2 stalk domain, and T cell-based multivalent antigens. Supplemented and/or adjuvanted vaccination in combination with universal target antigenic vaccines would have much promise. This review summarizes encouraging scientific advances in the field with a focus on novel vaccine designs.

Environmental Factors Related to Enterobiasis in a Southeast Region of Korea

Pinworm infection can occur through contact with contaminated surfaces followed by ingestion or even through inhalation of infective eggs. We have limited information regarding environmental contamination by eggs of Enterobius vermicularis. In order to determine environmental risk factors associated with the rate of E. vermicularis infection, we investigated possible environmental risk factors using a questionnaire from 46 kindergartens in 3 different cities of the southeast area of Korea. In total, using the cellotape anal swab technique, 3,422 children were examined for E. vermicularis infection. We evaluated E. vermicularis egg of books, educational materials, toys, room door handles, dusts of window edges, desks, chairs, tables, and dusts of classrooms. The overall egg-positive rate for E. vermicularis was 6.0%, and the prevalence of enterobiasis in each kindergarten ranged between 0% and 16.9%. We found that 78.9% of egg positive kindergartens were managed by private foundations, which was significantly higher, compared with kindergartens managed by public foundations or the nation. Compared with public or national kindergartens, most private kindergartens were located in residential areas and the number of children in these areas was significantly higher. In conclusion, numbers of children in kindergartens was found to be an environmental risk factor associated with transmission of enterobiasis in Korea.

Alteration of Cytokine Production during Visceral Larva Migrans by Toxascaris leonina in Mice

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-alpha) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.

Comparison of Functional Gene Annotation of Toxascaris leonina and Toxocara canis using CLC Genomics Workbench

The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common gastrointestinal helminths encountered in dogs. In order to understand biological differences of 2 ascarids, we analyzed gene expression profiles of female adults of T. canis and T. leonina using CLC Genomics Workbench, and the results were compared with those of free-living nematode Caenorhabditis elegans. A total of 2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively. The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820 bp. Overall, our results showed that most functional gene annotations of 2 ascarids were quite similar to each other in 3 major categories, i.e., cellular component, biological process, and molecular function. Although some different transcript expression categories were found, the distance was short and it was not enough to explain their different lifestyles. However, we found distinguished transcript differences between ascarid parasites and free-living nematodes. Understanding evolutionary genetic changes might be helpful for studies of the lifestyle and evolution of parasites.

Trichinella spiralis Infection Suppressed Gut Inflammation with CD4+CD25+Foxp3+ T Cell Recruitment

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of CD4+CD25+Foxp3+ T (regulatory T; Treg) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-gamma, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-beta, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of Treg cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and Treg cells recruitment.

Compliance with the Protocol Considered Emetogenic Potential for Prophylaxis of Chemotherapy Induced Nausea and Vomiting / 종양간호학회지

PURPOSE: The purpose of this study was to identify the compliance with the protocol, which was developed considering the emetogenic potential for prophylaxis of chemotherapy. METHODS: Data was collected from 144 patients who received chemotherapy from June 15 to August 31, 2010 in C University Hospital in Jeollanamdo, Korea. The level of chemotherapy-induced nausea and vomiting (CINV) and the compliance with the protocol for prophylaxis of CINV were measured. RESULTS: There was statistically significant difference of CINV in morning sickness and anticipatory nausea of general and clinical characteristics. Also, the compliance with the protocol developed according to emetogenic potential of chemotherapy was statistically significant. There was no difference in CINV in regard to the compliance with the protocol. CONCLUSION: There was a good compliance with the protocol for prophylaxis according to emetogenic potential. But it should be recommended to use antiemetics for prophylaxis aggressively to relieve CINV for the patients who already experienced morning sickness and anticipatory nausea. In addition, the oncology nurses should respond sensitively to the complaints of nausea and vomiting no matter what the emetogenic potentials of chemotherapy regimen are.

Seroprevalence of Antibodies against Anisakis simplex Larvae among Health-Examined Residents in Three Hospitals of Southern Parts of Korea

The present study was performed to estimate the seroprevalence of larval Anisakis simplex infection among the residents health-examined in 3 hospitals in southern parts of Korea. A total of 498 serum samples (1 serum per person) were collected in 3 hospitals in Busan Metropolitan city, Masan city, and Geoje city in Gyeongsangnam-do (Province) and were examined by IgE-ELISA and IgE-western blotting with larval A. simplex crude extract and excretory-secretory products (ESP). The prevalence of antibody positivity was 5.0% and 6.6% with ELISA against crude extracts and ESP, respectively. It was also revealed that infection occurred throughout all age groups and higher in females than in males. A specific protein band of 130 kDa was detected from 10 patients with western blot analysis against crude extract and ESP among those who showed positive results by ELISA. Our study showed for the first time the seroprevalence of anisakiasis in Korea. The allergen of 130 kDa can be a candidate for serologic diagnosis of anisakiasis.

A 24 kDa Excretory-Secretory Protein of Anisakis simplex Larvae Could Elicit Allergic Airway Inflammation in Mice

We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific IgE and IgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-alpha (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.

Protease-Activated Receptor 2 Is Involved in Th2 Responses against Trichinella spiralis Infection

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

Parasitic Helminth Cystatin Inhibits DSS-Induced Intestinal Inflammation Via IL-10+F4/80+ Macrophage Recruitment

Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-alpha in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10+F4/80+ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.

Parents' Knowledge about Enterobiasis Might Be One of the Most Important Risk Factors for Enterobiasis in Children

To know the prevalence of Enterobius vermicularis infection and what are the most important risk factors, we evaluated the incidence and risk factors of enterobiasis among children attended in kindergartens in Busan metropolitan city, Republic of Korea. A total of 1,674 children from 21 kindergartens in 11 of 16 autonomous districts of Busan were evaluated for E. vermicularis infection by the cellotape anal swab technique. The overall egg-positive rate for E. vermicularis was 10.7% (179/1,674), and the prevalence of enterobiasis in each kindergarten ranged between 0% and 32.4%. There was an increasing tendency of the egg positive rate according to the population density; the higher the population density communities had, the higher egg-positive rate for E. vermicularis was detected (P = 0.001). Among personal hygiene factors involving children, thumb-sucking (P = 0.036) and fingernail-trimming (P = 0.024) were highly associated with enterobiasis. In addition, taking anthelmintic medications against E. vermicularis infection was strongly associated with enterobiasis (P = 0.014). Moreover, parents' knowledge of enterobiasis was correlated significantly with the incidence of enterobiasis of their children (P = 0.006). In conclusion, we need to consider not only personal hygiene but also parents' knowledge about enterobiasis as a factor in order to develop new strategies for elimination or to complete reduction of enterobiasis in Korea.

Endosymbionts of Acanthamoeba Isolated from Domestic Tap Water in Korea

In a previous study, we reported our discovery of Acanthamoeba contamination in domestic tap water; in that study, we determined that some Acanthamoeba strains harbor endosymbiotic bacteria, via our molecular characterization by mitochondrial DNA restriction fragment length polymorphism (Mt DNA RFLP). Five (29.4%) among 17 Acanthamoeba isolates contained endosymbionts in their cytoplasm, as demonstrated via orcein staining. In order to estimate their pathogenicity, we conducted a genetic characterization of the endosymbionts in Acanthamoeba isolated from domestic tap water via 16S rDNA sequencing. The endosymbionts of Acanthamoeba sp. KA/WP3 and KA/WP4 evidenced the highest level of similarity, at 97% of the recently published 16S rDNA sequence of the bacterium, Candidatus Amoebophilus asiaticus. The endosymbionts of Acanthamoeba sp. KA/WP8 and KA/WP12 shared a 97% sequence similarity with each other, and were also highly similar to Candidatus Odyssella thessalonicensis, a member of the alpha-proteobacteria. The endosymbiont of Acanthamoeba sp. KA/WP9 exhibits a high degree of similarity (85-95%) with genus Methylophilus, which is not yet known to harbor any endosymbionts. This is the first report, to the best of our knowledge, to show that Methylophilus spp. can live in the cytoplasm of Acanthamoeba.

Expressed Sequence Tags of Trichinella spiralis Muscle Stage Larvae

In order to obtain greater insight into the relevant genomic expression patterns of Trichinella spiralis, 992 expressed sequence tags (ESTs) were collected from a cDNA library of T. spiralis muscle stage larvae and assembled into 60 clusters and 385 singletons. Of them, 445 (44.7%) ESTs were annotated to their homologous genes, and small fractions were matched to known genes of nematodes. The annotated ESTs were classified into 25 eukaryotic orthologous groups (KOG). Cytochrome C oxidase (34 clones) was found to be most frequent species.

Effects of Indomethacin on Ischemia-induced Brain Injury / 대한해부학회지

Cerebral ischemia can have severe results and disrupt quality of life. Current medicine is not effective at overcoming these problems. To find out more effective therapies, it is necessary to understand the microenvironment of cerebral injury after the ischemia. In the present study, to investigate the effects of inflammatory reaction, indomethacin, an anti-inflammatory drug, was used in a photothrombotic focal infarction rat model. It was revealed that cerebral ischemia increased neurogenesis in the subventricular (SVZ) and subgranular zones (SGZ), and in the penumbral region. Indomethacin treatment reduced the cerebral ischemia-induced neurogenesis by 86.2%, 53.8%, and 52.8% respectively. Cerebral ischemia increased gliosis and angiogenesis in the penumbral region and indomethacin reduced gliosis and angiogenesis by 48.2% and 58.1%, respectively. These results suggest that indomethacin treatment after the cerebral ischemia can reduce neurogenesis, angiogenesis, and gliosis in the penumbral region.

Effects of retinoic acid on ischemic brain injury-induced eurogenesis

Neurogenesis can be induced by pathological conditions such as cerebral ischemia. However the molecular mechanisms or modulating reagents of the reactive neurogenesis after the cerebral ischemia are poorly characterized. Retinoic acid (RA) has been shown to increase neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain neuroblasts. Here, we examined whether RA can modulate the reactive neurogenesis after the cerebral ischemia. In contrast to our expectation, RA treatment decreased the reactive neurogenesis in subventricular zone (SVZ), subgranular zone (SGZ) and penumbral region. Furthermore, RA treatment also decreased the angiogenesis and gliosis in penumbral region.