Association between obsessive-compulsive disorder and the risk of schizophrenia using the Korean National Health Insurance Service-National Sample Cohort: a retrospective cohort study.

AIMS: Obsessive-compulsive disorder (OCD) and schizophrenia are often reported as co-morbid conditions. However, the evidence of an association between OCD and the risk of schizophrenia is limited. This study investigated the risk of schizophrenia in patients newly diagnosed with OCD using a nationally representative sample cohort in South Korea. METHODS: Data were obtained from the 2002-2013 Korean National Health Insurance Service-National Sample Cohort of the National Health Insurance Service. Using propensity score matching, 2509 patients with OCD and a control group of 7527 patients were included in the analysis. Chi-squared tests were used to investigate and compare the general characteristics of the study population. The risk of schizophrenia was analysed using the Cox proportional hazard model. RESULTS: The incidence rate was 45.79/10 000 person-year for patients with OCD and 4.19/10 000 person-year for patients without OCD. Patients with OCD had a higher risk of schizophrenia compared to the control group after adjusting for covariates (hazard ratio = 10.46, 95% confidence interval = 6.07-18.00). CONCLUSIONS: This study identified an association between the diagnosis of OCD and the risk of schizophrenia in a South Korean national representative cohort. Further research using a prospective design to clarify the causality of OCD in schizophrenia in a controlled environment should be conducted to validate these findings.

Combined effect of individual and neighborhood socioeconomic status on mortality in patients with newly diagnosed dyslipidemia: A nationwide Korean cohort study from 2002 to 2013.

BACKGROUND AND AIM: The study aims to determine whether dyslipidemia patients living in less affluent neighborhood are at a higher risk of mortality compared to those living in more affluent neighborhoods. METHODS AND RESULTS: A population-based cohort study was conducted using a stratified representative sampling from the National Health Insurance claim data from 2002 to 2013. The target subjects comprise patients newly diagnosed with dyslipidemia receiving medication. We performed a survival analysis using the Cox proportional hazard model. Of 11,946 patients with dyslipidemia, 1053 (8.8%) subjects died during the follow-up period. Of the dyslipidemia patients earning a middle-class income, the adjusted HR in less affluent neighborhoods was higher than that in the more affluent neighborhoods compared to the reference category of high individual SES in more affluent neighborhoods (less affluent; hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.35-1.99 vs. more affluent; HR = 1.48, 95% CI: 1.20-1.81, respectively). We obtained consistent results in patients with lower income, wherein the adjusted HR in less affluent neighborhoods was higher than that in more affluent neighborhoods (less affluent; HR = 1.52, 95% CI: 1.16-1.97 vs. more affluent; HR = 1.41, 95% CI: 1.04-1.92, respectively). CONCLUSION: Living in a less affluent neighborhood contributes to higher mortality among dyslipidemia patients. The individual- and neighborhood-level variables cumulatively affect individuals such that the most at-risk individuals include those having both individual- and neighborhood-level risk factors. These findings raise important clinical and public health concerns and indicate that neighborhood SES approaches should be essentially considered in health-care policies similar to individual SES.

Effects of in ovo injection with selenium on immune and antioxidant responses during experimental necrotic enteritis in broiler chickens.

This study was conducted to investigate the effects of in ovo injection of Se on modulating the immune system and antioxidant responses in broiler chickens with experimental necrotic enteritis. Broiler eggs were injected at 18 d of embryo age with either 100 µL of PBS alone or sodium selenite (Na2SeO3) in PBS, providing 0 (SS0), 10 (SS10), or 20 (SS20) µg of Se/egg. At 14 d posthatch, PBS-treated and uninfected chickens were kept as the control group, whereas the remaining chickens were orally infected with 1.0 × 10(4) sporulated oocysts of Eimeria maxima (SS0, SS10, SS20). At 18 d posthatch, E. maxima-infected chickens were orally infected with 1.0 × 10(9) cfu of Clostridium perfringens. Infected control SS0 group showed significantly decreased BW compared with the uninfected control. However, SS20 group showed significantly increased BW compared with the infected control SS0 group, whereas the BW were similar among uninfected control and infected SS10 and SS20 groups. The SS10 group showed significantly lower intestinal lesions compared with the SS0 group, and oocyst production was decreased in both SS10 and SS20 groups. Serum malondialdehyde level and catalase activity were also decreased in both SS10 and SS20 groups, whereas the superoxide dismutase level was significantly lower in the SS10 group compared with the SS0 group. The SS20 group showed significantly higher levels of transcripts for IL-1ß and IL-6 in intestine, and SS10 and SS20 groups had higher levels of transcripts for IL-8 and inducible nitric oxide synthase expression and decreased glutathione peroxidase 7 mRNA levels compared with the SS0 group. The SS10 and SS20 groups also showed increased serum antibody levels to C. perfringens α-toxin and NetB toxin compared with the SS0 group. These collective results suggest that the injection of Se into the amniotic cavity of developing eggs may be beneficial for enhancing immune and antioxidant responses in the hatched chickens exposed to the necrotic enteritis-causing pathogens.

In vitro effects of plant and mushroom extracts on immunological function of chicken lymphocytes and macrophages.

1. The present study was conducted to examine the effects of organic extracts from milk thistle (Silybum marianum), turmeric (Curcuma longa), reishi mushroom (Ganoderma lucidum), and shiitake mushroom (Lentinus edodes) on innate immunity and tumor cell viability. 2. Innate immunity was measured by lymphocyte proliferation and nitric oxide production by macrophages, and the inhibitory effect on tumor cell growth was assessed using a non-radioactive assay. For measuring the cytokine levels in the HD11 macrophages which were treated with extracts of turmeric or shiitake mushroom, the levels of mRNAs for interferon-alpha (IFN- alpha), interleukin-1beta (IL-1beta), IL-6, IL-12, IL-15, IL-18, and tumor necrosis factor superfamily 15 (TNFSF15) were quantified by real time RT-PCR. 3. In vitro culture of chicken spleen lymphocytes with extracts of milk thistle, turmeric, and shiitake and reishi mushrooms induced significantly higher cell proliferation compared with the untreated control cells. Stimulation of macrophages with extracts of milk thistle and shiitake and reishi mushrooms, but not turmeric, resulted in robust nitric oxide production to levels that were similar with those induced by recombinant chicken interferon-gamma. All extracts uniformly inhibited the growth of chicken tumor cells in vitro at the concentration of 6.3 through 100 microg/ml. Finally, the levels of mRNAs encoding IL-1beta, IL-6, IL-12, IL-18, and TNFSF15 were enhanced in macrophages that were treated with extracts of turmeric or shiitake mushroom compared with the untreated control. 4. These results document the immunologically-based enhancement of innate immunity in chickens by extracts of plants and mushrooms with known medicinal properties in vitro. In vivo studies are being planned to delineate the cellular and molecular mechanisms responsible for their mechanism of action.

Effects of direct-fed microbials on growth performance, gut morphometry, and immune characteristics in broiler chickens.

This study was conducted to compare growth performance, gut morphometry, and parameters of local and systemic immunity in broiler chickens fed for 22 consecutive days with a diet supplemented with Bacillus spp. as direct-fed microbials (DFM), a commercial product incorporating 3 DFM, or a nonsupplemented diet. Direct-fed microbials did not significantly modify BW gain and most failed to affect serum antibody levels in response to immunization with a recombinant Eimeria protein. However, altered intestinal morphometric measurements were readily apparent in DFM-fed chickens as revealed by increased villus height and crypt depth compared with non-DFM-fed controls. In addition, serum levels of alpha-1-acid glycoprotein as an inflammatory marker were reduced in DFM-fed birds, whereas splenic lymphocyte proliferation, intestine intraepithelial lymphocyte subpopulations, and cytokine mRNA levels in intraepithelial lymphocytes were increased, decreased, or unchanged compared with controls depending on the DFM used. These results provide a rational scientific basis for future studies to investigate DFM as immunomodulating agents to enhance host protective immunity against enteric pathogens in broiler chickens.

High-throughput gene expression analysis of intestinal intraepithelial lymphocytes after oral feeding of carvacrol, cinnamaldehyde, or Capsicum oleoresin.

Among dietary phytonutrients, carvacrol, cinnamaldehyde, and Capsicum oleoresin are well known for their antiinflammatory and antibiotic effects in human and veterinary medicine. To further define the molecular and genetic mechanisms responsible for these properties, broiler chickens were fed a standard diet supplemented with either of the 3 phytochemicals and intestinal intraepithelial lymphocytes were examined for changes in gene expression by microarray analysis. When compared with chickens fed a nonsupplemented standard diet, carvacrol-fed chickens showed altered expression of 74 genes (26 upregulated, 48 downregulated) and cinnamaldehyde led to changes in the levels of mRNAs corresponding to 62 genes (31 upregulated, 31 downregulated). Most changes in gene expression were seen in the Capsicum-fed broilers with 98 upregulated and 156 downregulated genes compared with untreated controls. Results from the microarray analysis were confirmed by quantitative real-time PCR with a subset of selected genes. Among the genes that showed >2.0-fold altered mRNA levels, most were associated with metabolic pathways. In particular, with the genes altered by Capsicum oleoresin, the highest scored molecular network included genes associated with lipid metabolism, small molecule biochemistry, and cancer. In conclusion, this study provides a foundation to further investigate specific chicken genes that are expressed in response to a diet containing carvacrol, cinnamaldehyde, or Capsicum oleoresin.

Protective effect of hyperimmune egg yolk IgY antibodies against Eimeria tenella and Eimeria maxima infections.

Avian coccidiosis is caused by several distinct species of Eimeria protozoa and is the major parasitic disease of poultry of economic importance. As an alternative strategy to control avian coccidiosis without using prophylactic medications, we have investigated the efficacy of inducing passive immunity against coccidiosis by orally feeding hyperimmune IgY antibodies. In this study, a commercially available egg yolk powder, Supracox (SC), a purified IgY fraction of egg yolk prepared from hens hyperimmunized with three major species of Eimeria oocysts, were continuously fed to young chicks from hatch. Upon orally infecting these broiler chicks with Eimeria tenella and Eimeria maxima oocysts at 1 week of age, they showed significantly higher body weight gains (P<0.05) compared to the untreated controls. Furthermore, SC-fed chicks showed significantly less intestinal lesions and reduced fecal oocyst output compared to the untreated controls following oral infections with E. tenella and E. maxima. These results provide clear evidence that passive immunization of chicks with hyperimmune egg yolk IgY antibodies provide significant protection against E. tenella or E. maxima infections.

Induction of passive immunity in broiler chickens against Eimeria acervulina by hyperimmune egg yolk immunoglobulin Y.

The protective effect of hyperimmune IgY fraction of egg yolk prepared from hens hyperimmunized with multiple species of Eimeria oocysts on experimental coccidiosis was evaluated in young broilers. Chickens were continuously fed from hatch with a standard diet containing hyperimmune IgY egg yolk powder or a nonsupplemented control diet and orally challenged at d 7 posthatch with 5.0 x 10(3) sporulated Eimeria acervulina oocysts. Body weight gain between d 0 and 10 and fecal oocyst shedding between d 5 and 10 postinfection were determined as parameters of protective immunity. Chickens given 10 or 20% hyperimmune IgY egg yolk powder showed significantly increased BW gain and reduced fecal oocyst shedding compared with control birds fed the nonsupplemented diet. In another trial, lower IgY concentrations (0.01, 0.02, and 0.05%) were used to treat birds with 1.0 x 10(4) oocysts of E. acervulina. Total oocyst shedding was significantly (P < 0.05) reduced in chickens fed the 0.02 and 0.05% hyperimmune IgY supplemented-diets compared with animals fed the nonsupplemented diet. Similarly, chickens fed 0.5% of hyperimmune IgY egg yolk powder diet and challenged with 1.0 x 10(4) oocysts exhibited reduced oocyst shedding compared with the control birds given 0.5% of IgY from nonimmunized hen eggs, although BW gain was not affected. We conclude that passive immunization of chickens with anti-coccidia IgY antibodies provide protective immunity against coccidiosis challenge infection.

Hepatoprotective effect of baicalin, a major flavone from Scutellaria radix, on acetaminophen-induced liver injury in mice.

The protective effects of baicalin (BA), a major flavone from Scutellaria radix, on acetaminophen (AP)-induced hepatotoxicity and the possible mechanism(s) of its protective action were investigated in mice. Treatment with BA (300 mg/kg, p.o.) 0.5 h after AP administration significantly prevented an increase in plasma alanine aminotransferase and aspartate aminotransferase activities and AP-induced hepatic necrosis, and also reduced AP-induced mortality from 43% to 0%. In addition, oral treatment with BA significantly prevented AP-induced depletion of glutathione (GSH) contents. However, BA treatment, by itself, did not affect hepatic GSH contents. The effect of BA on the cytochrome P450 2E1 (CYP2E1), the major isozyme involved in AP bioactivation, was investigated. Oral treatment of mice with BA resulted in a significant decrease in AP-induced CYP2E1 activity together with its inhibition of AP-induced CYP2EI expression. These results show that the hepatoprotective effects of BA against AP overdose may be due to its ability to block the bioactivation of AP by inhibiting CYP2E1 expression.

Inhibitory effects of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) on the productions of tumor necrosis factor-alpha and nitric oxide by the lipopolisaccharide-stimulated RAW 264.7 macrophages.

In order to validate the use of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) as an anti-inflammatory drug in the traditional Korean medicine, we have investigated the effects of the methanol extract of this folk medicine on the productions of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) on RAW 264.7 macrophages activated with the endotoxin lipopolysaccharide. The extract inhibited the productions of TNF-alpha and NO with significant decreases in mRNA levels of TNF-alpha and inducible NO synthase, suggesting that the stem bark of Catalpa ovata may have therapeutic potential in the control of inflammatory disorders.

Inhibition of TNF-alpha, IL-1beta, and IL-6 productions and NF-kappa B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide, an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae).

Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniaceae), was found to inhibit the productions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and the activation of nuclear factor kappaB (NF-kappaB) in RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Catalposide also inhibited the expressions of TNF-alpha, IL-1beta, and IL-6 genes and the nuclear translocation of p65 subunit of NF-kappaB in LPS-activated RAW 264.7 cells. Flow cytometric analysis revealed that catalposide suppressed the binding of FITC-conjugated LPS to CD14 on the surface of cells, probably resulting in the inhibitory effects on TNF-alpha, IL-1beta, and IL-6 productions and NF-kappaB activation. These findings suggest that catalposide could be an attractive candidate for adjunctive therapy in gram-negative bacterial infections.

The genes encoding geranylgeranyl transferase alpha-subunit and transglutaminase 1 are very closely linked but not functionally related in terminally differentiating keratinocytes.

We report here the entire exon/intron structure of the gene encoding the alpha-subunit of human Rab geranylgeranyl transferase (RABGGTA) gene, which is positioned in a tandem head-to-tail arrangement with the transglutaminase 1 (TGM1) gene, and its polyadenylation signal sequence is located just 2.3 kbp upstream of the capsite of TGM1. Even though TGM1 and RABGGTA have different functions, their close localization raised the question as to whether they are functionally related in the epidermis. To address this question, we have studied the expression of the two genes by RT-PCR in normal human epidermal keratinocytes cultured under various differentiation conditions. While the expression of the TGM1 gene is markedly affected by the calcium concentration of the medium, all trans retinoic acid, vitamin D3, and TPA treatment, the expression of the RABGGTA gene was unaffected by these reagents. Taken together, even though these two genes are unusually closely linked, they are not functionally related in the terminal differentiation program of epidermal keratinocytes.