Effects of sarpogrelate on blood viscosity.

The objective of the present study was to evaluate the effects and safety of sarpogrelate hydrochloride (sarpogrelate) in patients with elevated blood viscosity (BV), after 12 and 24 weeks of twice (BID) or thrice (TID) daily administrations of sarpogrelate (100 mg). The participants received oral sarpogrelate administration for 24 weeks and visited the hospital every 12 ± 2 week for blood viscosity measurements at shear rates of 5 and 300 s-1. The BV measured at shear rate of 5 s-1 in male patients decreased significantly from 18.91 cP at the baseline to 16.3 cP after 24 weeks of sarpogrelate administration (13.6 % drop, p < 0.001). The BV measured at 5 s-1 in female decreased more significantly from 17.5 cP at the baseline to 13.4 cP after 24 weeks of sarpogrelate administration (23.0 % drop, p < 0.001). In summary, sarpogrelate may be considered as a possible therapeutic option for improving BV in patients with elevated blood viscosity. In particular, the reduction of the low-shear BV with the help of a viscosity-reducing drug such as sarpogrelate may be considered as a potentially new pharmacological tool for microvascular disease.

Fat-to-muscle Ratio: A New Indicator for Coronary Artery Disease in Healthy Adults.

Background: Coronary artery disease (CAD) is an important issue in public health. Previous studies have shown that the ratio of fat to muscle mass is a significant predictor of metabolic disease, and it is known to be associated with atherosclerosis. In this study, we evaluated the association between the fat-to-muscle ratio (FMR) and CAD in healthy adults. Methods: A total of 617 participants without diabetes mellitus, hypertension, known CAD, or stroke who visited the Health Promotion Center from 2009 to 2018 were included in this study. Computed tomography imaging and bioelectrical impedance analysis were used to ascertain the coronary artery calcium (CAC) score, degree of CAD, and FMR. Results: Univariate logistic regression analysis showed that old age, male sex, smoking history, creatinine, aspartate aminotransferase, gamma-glutamyl transferase, uric acid, total cholesterol, and low-density lipoprotein cholesterol were significantly associated with CAC. After adjusting for potential confounding covariates, the presence of CAC was independently associated with FMR (OR, 1.014; 95% CI, 1.002-1.026; p = 0.019. The association was maintained even after adjusting for body mass index and waist circumference (odds ratio, 1.019; 95% confidence interval, 1.004 -1.034; P = 0.012). Conclusion: In this study, a high FMR was significantly associated with CAC. A large-scale prospective study on the association with FMR and cardiovascular diseases is necessary to confirm this relationship.

Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. METHODS: In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. RESULTS: Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. CONCLUSIONS: Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

The effect of balance taping for prevention of menstrual pain in female middle school students.

[Purpose] The age at menarche in Korean women has been declining sharply. However, for the students who are just beginning to menstruate, taking pain medication might become a long-term habit continuing until adulthood. Therefore, this study investigated whether balance taping would be more helpful than medication in relieving the pain. [Subjects and Methods] Subjects of this study included 125 female students. The participants were assigned to the balance taping group, the control group, and the medication group. The medication group was given 1 dose of Tylenol (acetaminophen 500 mg) and the balance-taping group had taping applied, and the changes in pain were measured before the taping, as well as1 hour, 4 hours, 8 hours, and 24 hours after. The measurement was done two times for the repeatability of the result. [Results] The balance-taping group showed a difference in pain from 1 hour after the taping compared with the control group, and the pain was significantly reduced until 24 hours after the taping. The balance taping group showed a statistically significant difference in pain compared with the medication group from 4 hours after the taping, and it lasted until 24 hours after the taping. The results were similar in the second measurement as well. [Conclusion] Balance taping was shown to be effective in relieving menstrual pain. Balance taping could be an effective alternative to medication in relieving menstrual pain and distress.

Relationship between metabolically healthy obesity and coronary artery calcification.

There is a lack of consensus regarding universally accepted criteria for metabolic health (MH). A simple definition of MH was systematically derived in a recent prospective cohort study. The present cross-sectional study aimed to explore the applicability of these criteria in Korean population, using coronary calcification as an indicator of cardiovascular risk. In total, 1049 healthy participants, who underwent coronary artery calcification testing at university hospital health promotion centers between January and December 2022, were included. Applying the main components of the newly derived definition, MH was defined as follows: (1) systolic blood pressure < 130 mmHg and no use of blood pressure-lowering medication; (2) waist circumference < 90 cm for males and < 85 cm for females; and (3) absence of diabetes. Multivariate logistic regression was conducted to examine the odds ratio (OR) and 95 % confidence interval (CI) for coronary artery calcium score across different phenotypes. The prevalence of coronary artery calcification in this study was 41.1 %. Compared with metabolically healthy, normal weight subjects, those with the metabolically healthy obesity phenotype did not exhibit increased odds for coronary atherosclerosis. (OR 0.93 [95 % CI 0.48-1.79]) Conversely, metabolically unhealthy subjects had increased risk, regardless of their body mass index category (OR 3.10 [95 % CI 1.84-5.24] in metabolically unhealthy normal weight; OR 3.21 [95 % CI 1.92-5.37] in metabolically unhealthy overweight; OR 2.73 [95 % CI 1.72-4.33] in metabolically unhealthy obese phenotype). These findings suggest that the new definition for MH has the potential to effectively distinguish individuals at risk for cardiovascular disease from those who are not.

Association between Homocysteine and Vitamin D Levels in Asymptomatic Korean Adults.

An increased homocysteine level is a risk factor for cardiovascular disease, venous thromboembolism, cerebrovascular disease, and chronic kidney disease. In addition, vitamin D deficiency is associated with coronary artery disease and metabolic disorders. The present study included data from 1375 adults (895 men and 480 women) with a mean age of 52.62 ± 9.94 years who visited the Health Promotion Center of the University Hospital in Gyeonggi-do, Republic of Korea from January 2018 to December 2022 for routine checkups that included assessments of their homocysteine and vitamin D levels. Homocysteine levels were positively associated with age, a history of hypertension, a history of diabetes, current smoking habits, and levels of low-density lipoprotein cholesterol, creatinine, uric acid, and high-sensitivity C-reactive protein. By contrast, vitamin D levels were negatively associated with serum levels of homocysteine after adjusting for covariates (ß = -0.033, p < 0.001). Additional long-term prospective studies are needed to elucidate the presence of a causal relationship between vitamin D status and serum levels of homocysteine in asymptomatic Korean adults. An intervention trial is warranted to determine whether the administration of vitamin D is helpful for the primary prevention of cardiovascular disease by lowering the homocysteine level in this population.

Assessment of Fatigue and Associated Factors in Patients with Inflammatory Bowel Disease: A Questionnaire-Based Study.

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue.

Relationship between irritable bowel syndrome, worry and stress in adolescent girls.

The aim of this study is to investigate prevalence of irritable bowel syndrome (IBS) among adolescents and difference in worry and stress between normal and IBS groups. Questionnaire survey was conducted at a girl's middle and high school. Students from seventh to eleventh grade participated in the examination on Rome II criteria, lifestyle and dietary habits. Worry and stress were measured with the Korean version Penn State Worry Questionnaire-Children and the Korean version Brief Encounter Psychosocial Instrument. Worry score was significantly higher in the IBS group (22.07 ± 9.38, P < 0.001) than in the normal group (18.65 ± 8.99) and was higher in high school students than in middle school students (P = 0.02). Stress score also was higher in the IBS group than in the normal group (P < 0.001) and was higher in the high school girls than in the middle school ones (P = 0.04). Of all the lifestyle factors influencing IBS preference for fatty foods, preference for salty foods, drinking alcohol and sleeping for less than six hours a day were found to be significant. Worry and stress seem to be associated with IBS symptoms. The findings of this study draw a clue that less worry and stress will help decrease IBS symptoms.

Changes in Vitamin D Status in Korean Adults during the COVID-19 Pandemic.

The aim of this study was to investigate changes in 25(OH)D (25-hydroxyvitamin D) levels and in the vitamin D status of Korean adults before and during the coronavirus disease (COVID-19) pandemic. This study compared serum 25(OH)D levels before and after the pandemic in 1483 adults aged 19 years and older who were screened at a university hospital. Subjects were selected only from participants tested in the same season before and after the pandemic. The pre-COVID-19 testing period was from 1 March 2018 to 31 November 2019; the testing period in the COVID-19 era was from 1 June 2020 to 31 November 2021. The mean 25(OH)D level for all participants was 21.4 ± 10.2 ng/mL prior to the outbreak of COVID-19, which increased to 23.6 ± 11.8 ng/mL during the COVID-19 lockdown period (p < 0.001). The increase was particularly dramatic in elderly females (28.8 ± 12.3 ng/mL to 37.7 ± 18.6 ng/mL, p = 0.008). The prevalence of vitamin D deficiency decreased in both males (48.4% to 44.5%, p = 0.005) and females (57.0% to 46.0%, p < 0.001). In conclusion, 25(OH)D levels in Korean adults increased during the COVID-19 era, and the prevalence of vitamin D deficiency decreased accordingly.

Psychological Effects and Medication Adherence among Korean Patients with Inflammatory Bowel Disease during the Coronavirus Disease 2019 Pandemic: A Single-Center Survey.

BACKGROUND AND AIM: This study evaluated the impact of coronavirus disease 2019 (COVID-19) on the mental health of inflammatory bowel disease (IBD) patients. We quantified anxiety, depression, and medication adherence among IBD patients through a single-center survey in South Korea during the COVID-19 pandemic. METHODS: An electronic survey was made available to patients at the IBD clinic in Daejeon St. Mary's hospital from July 2021 to September 2021. The validated Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety. The Korean version of the Medication Adherence Rating Scale (KMARS) questionnaire was used to assess medication adherence. RESULTS: In total, 407 patients (56.5%; ulcerative colitis, 43.5%; Crohn's disease) participated in the survey. Among the respondents, 14.5% showed significant anxiety and 26.3% showed significant depression. Female sex, presence of mental disease, unvaccinated status, and the presence of Crohn's disease were associated with greater risks of anxiety and depression. Among medications, immunomodulators were associated with a greater risk of anxiety. In terms of KMARS, patients reported favorable medication adherence despite the psychological burden of the pandemic. The KMARS score was 7.3 ± 1.5 (mean ± SD) of 10.0 points. High anxiety and depression were associated with a slight decrease in medication adherence. CONCLUSIONS: COVID-19 has increased anxiety and depression among IBD patients, whose medication adherence has nevertheless remained good. Furthermore, anxiety and depression were found to have a negative correlation with adherence. Our results provide insights concerning psychological response and medication adherence among IBD patients in South Korea during the COVID-19 pandemic.

Reliability and Validity of Korean Version of Crohn's and Ulcerative Colitis Questionnaire-8.

Background: Patients with inflammatory bowel disease (IBD) have a decreased quality of life (QoL), the improvement of which is a treatment goal. The CUCQ-8 is a verified simple and effective QoL measurement tool. We validated the Korean version of CUCQ-8 with the approval of its developer. Methods: We investigated the correlation between the Korean version of CUCQ-8 and the IBDQ-32 in patients with IBD. Results: In all, 147 subjects (male, 97 (66.0%); female, 50 (34.0%); mean age 36.2 ± 13.5 years) were analyzed. Cronbach's alpha coefficient of the CUCQ-8 was 0.833, indicating very high internal consistency. The Korean version of the CUCQ-8 showed a significant correlation with the IBDQ-32 and its subscales (correlation coefficient, >0.75). Conclusions: The Korean version of the CUCQ-8 has high reliability and construct validity and can be used to evaluate the QoL of patients with IBD.

Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death.

NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays showed that E2 and its receptors (ERalpha and ERbeta) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5 cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK.

Effect of dance exercise on cognitive function in elderly patients with metabolic syndrome: a pilot study.

Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K). Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048), word list delayed recall (p = 0.038), word list recognition (p = 0.007), and total CERAD-K score (p = 0.037). However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome. Key pointsMetabolic syndrome (MS) is associated with an increased risk of cognitive impairment.Aerobic exercise improves cognitive function in elderly people and contributes to the prevention of degenerative neurological disease and brain damage. Dance sport is a form of aerobic exercise that has the additional benefits of stimulating the emotions, promoting social interaction, and exposing subjects to acoustic stimulation and music.In the present study, dance exercise for a 6-month period improved cognitive function in older adults with MS. In particular, positive effects were observed in verbal fluency, word list delayed recall, word list recognition, and the total CERAD-K score.Our data suggest that the implementation of dance exercise programs may be an effective means of prevention and treatment of cognitive disorders.

Reflux Esophagitis and Fatigue: Are They Related?

Gastroesophageal reflux disease (GERD) is a chronic, recurrent disease. Reflux esophagitis can interfere with sleep via acid reflux, which can cause daytime sleepiness or fatigue. However, little is known about the association between reflux esophagitis and fatigue. OBJECTIVES: We evaluated the association between fatigue and reflux esophagitis in subjects seen at health check-ups. METHODS: Consecutive patients who were scheduled for screening endoscopies were enrolled prospectively at the Comprehensive Medical Examination Center of St. Vincent Hospital and Eunpyeong St. Mary's Hospital, Korea. Three validated questionnaires were used to assess fatigue, daytime hypersomnolence, anxiety, and depression: the Multidimensional Fatigue Inventory-Korean version (MFI-K), Epworth Sleepiness Scale (ESS), and Hospital Anxiety and Depression Scale (HADS). RESULTS: We investigated 497 consecutive eligible subjects. The reflux esophagitis and symptomatic GERD groups comprised 103 (20.7%) and 92 (18.5%) subjects, respectively. The MFI-K total, ESS, HADS-anxiety, and HADS-depression scores did not differ between the esophagitis and non-esophagitis groups (50.0 ± 11.5 vs. 49.7 ± 10.9, p = 0.661; 6.2 ± 2.8 vs. 6.1 ± 3.1, p = 0.987; 5.8 ± 3.1 vs. 5.2 ± 3.2, p = 0.060; 6.2 ± 3.6 vs. 6.0 ± 3.3, p = 0.561). However, the MFI-K total, ESS, HADS-anxiety, and HADS-depression scores were higher in the symptomatic group than in the non-symptomatic group (54.7 ± 12.7 vs. 48.6 ± 10.3, p < 0.001; 7.1 ± 3.5 vs. 5.9 ± 2.9, p = 0.002; 6.4 ± 3.3 vs. 5.1 ± 3.1, p < 0.001; 7.5 ± 4.0 vs. 5.7 ± 3.1, p < 0.001). Multiple regression analysis showed that the MFI-K total was correlated with GERD symptoms (p = 0.021), women (p = 0.001), anxiety (p < 0.001), and depression (p < 0.001). CONCLUSION: There was no statistically significant association in which reflux esophagitis could cause daytime sleepiness, fatigue, anxiety, or depression. However, fatigue was associated with GERD symptoms, women, anxiety, and depression. Further studies should clarify the association between fatigue and reflux esophagitis.

Insulin-secreting cells from human eyelid-derived stem cells alleviate type I diabetes in immunocompetent mice.

Various attempts have been made to develop stem cell-based therapy to alleviate type I diabetes using animal models. However, it has been a question whether human insulin produced from explanted cells is solely responsible for the normoglycemia of diabetic animals. In this study, we isolated neural crest-like stem cells from the human eyelid fat and examined their therapeutic potentials for diabetes. The human eyelid adipose-derived stem cells (HEACs) displayed characteristics of neural crest cells. Using a two-step culture condition combined with nicotinamide, activin, and/or GLP-1, we differentiated HEACs into insulin-secreting cells and examined in vivo effects of differentiated cells by transplantation experiments. Following differentiation in vitro, HEACs released insulin and c-peptide in a glucose-dependent manner. Upon their transplantation under kidney capsules of streptozotocin-treated immunocompetent mice, we observed normalization of hyperglycemia in 10 of 20 recipient mice until sacrifice after 2 months. Only the human, but not the mouse, insulin and c-peptide were detected in the blood of recipient mice. Removal of the kidneys transplanted with HEACs resulted in a sharp increase of blood glucose level. Removed kidney tissues showed distinct expression of various human genes including insulin, and colocalization of the human insulin and the human nuclear protein in many cells. However, they showed diminished or null expression of some immune-related genes. In conclusion, human insulin alone produced from eyelid-derived stem cells following differentiation into insulin-secreting cells and transplantation could normalize type I diabetes in mice.

Reliability and validity of the Korean version of the Penn State Worry Questionnaire in primary school children.

Worry is a generalized psychological phenomenon seen among most people. When worry is excessive and nearly uncontrollable, people usually suffer psychological pain. The Penn State Worry Questionnaire for Children (PSWQ-C) was developed to measure worry objectively. It comprises 14 items for measuring excessive, generalized, and uncontrollable worry in children. This study, conducted with a large group of elementary children (3rd through 6th graders, ages 8-12 yr; N=973), investigated the reliability and validity of the Korean version of the Penn State Worry Questionnaire for Children (PSWQ-CK). The PSWQ-CK showed high reliability by test-retest and also excellent internal consistency results. To examine the validity of the PSWQ-CK, we calculated its correlation with the Revised Children's Manifest Anxiety Scale (RCMAS). The PSWQ-CK had a higher correlation with the worry/oversensitivity factor than with other subscales of the RCMAS, and it showed no correlation with the lie factor. When 3 reversed PSWQ-CK items were eliminated, the instrument showed higher internal consistency. However, this did not improve its correlation with other anxiety-measuring tools. In conclusion, the PSWQ-CK's reliability and validity were satisfactory, and it is a useful tool for objectively measuring the worry of Korean children of this age group.

Fatigue and Mental Status of Caregivers of Severely Chronically Ill Patients.

Background and Aims: Fatigue is an unpleasant experience accompanied by functional deterioration involving both mental and physical factors. Caregivers of patients with severe illnesses who require long-term treatment often experience marked physical and mental fatigue. This study investigated the factors affecting fatigue among caregivers of patients with severe chronic diseases. Methods: The study enrolled 100 caregivers of patients providing home care nursing at a university hospital in Gyeonggi-do of Korea, including 47 caregivers caring for cancer patients and 53 caregivers caring for chronic disease patients (e.g., dementia, amyotrophic lateral sclerosis, and Parkinson's disease). The degree of fatigue was measured using the Korean version of the multidimensional fatigue inventory (MFI-K). Caregiver depression and anxiety were examined using the Hospital Anxiety and Depression Scale. Results: The average MFI-K score of all caregivers was 60.43 ± 13.77 and did not differ significantly between those caring for cancer patients and those caring for patients with severe chronic diseases (62.15 ± 13.27 vs. 58.49 ± 14.20, respectively, p=0.186). The longer the disease duration, the greater the general and physical fatigue of the caregiver (r = 0.284, p=0.004). However, caregiver mental fatigue did not differ according to disease duration (r = 0.169, p=0.094). The main factors affecting caregiver general and physical fatigue were caregiver anxiety and depression and patient's disease duration. Conclusions: The caregivers of patients with cancer or chronic severe illnesses experience high levels of fatigue: the longer the disease duration, the greater the degrees of depression, anxiety, and physical fatigue experienced by the caregivers. Such caregivers need strategies to manage their fatigue and depression.

Expression and role of TTF-1 in the rat suprachiasmatic nucleus.

We have previously reported that TTF-1, a homeodomain-containing transcription factor, regulates circadian rhythm of pituitary adenylate cyclase-activating polypeptide gene expression in the rat hypothalamus. In this study we found that TTF-1 mRNA was specifically expressed in the rat suprachiasmatic nucleus (SCN) and colocalized with Period 2 (Per2), a circadian feedback loop controller. Interaction between TTF-1 and Per1 and Per2 was demonstrated by immunoprecipitation and immunoblot assays. Moreover, TTF-1 and Per proteins additively stimulated a transcriptional activity of angiotensinogen (AoGen) gene. TTF-1 also activated in vitro rhythm of AoGen transcription determined by secretary alkaline phosphatase (SEAP) reporter system in the NIH3T3 cells. These results suggest that TTF-1 plays a role in the circadian rhythm regulation of the AoGen gene expression via interacting with Per proteins in the rat SCN.

Effects of cadmium on the expression of placental lactogens and Pit-1 genes in the rat placental trophoblast cells.

Cadmium is an endocrine disrupter (ED) with detrimental effects on mammalian reproduction. The placenta is a primary target for cadmium toxicity during pregnancy. Very little of this metal crosses the placenta to the fetus, and consequently it accumulates in high concentrations in the placenta. Cadmium affects on steroid synthesis and has estrogen- and androgen-like activities. In this study, we investigated the toxic effects of cadmium on placental trophoblast cells as well as the mRNA levels of placental lactogens (PLs), which are under the control of estrogen and play a pivotal role during pregnancy. Pregnant F344 Fisher rats were injected subcutaneously with 0, 0.2, and 2.0mg/kg BW/day of cadmium (CdCl(2)) dissolved in saline from days 11 to 19 of pregnancy and were sacrificed on day 20. The mRNA levels of the PL-Iv and -II genes and Pit-1alpha and beta isotype genes, the trans-acting factor of PLs, were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction, respectively. The frequency of the placental trophoblast cells was observed histochemically. Developmental data and apoptotic chromosomal DNA fragmentation of placental cells were also observed. The mRNA levels of PL-Iv and -II were reduced in a dose-dependent manner by cadmium. The mRNA levels of the Pit-1alpha and beta isotype genes were also reduced by cadmium. In the uterus-conjugated region of the placental junctional zone, the frequency rates of trophoblast cells were lower in the cadmium-treated groups than in the control group. High-dose cadmium exposure (2.0mg) induced not only the reduction of trophoblast cell frequency but also apoptotic chromosomal DNA fragmentation in the junctional zone of the placenta. Developmental metrics such as placental and fetal weights and a number of live fetuses, decreased, while a numbers of resorptions, dead fetuses, and post-implantation losses increased significantly (p<0.05) in the cadmium-treated groups compared to the control. These data suggested that cadmium inhibits the expression of PL genes and reduces the number of trophoblast cells in the rat placenta via an estrogen-like activity, leading to significant toxic effects on placental growth and physiological function in rats.