Status of home blood pressure measurement in treated hypertensive patients. Results of a survey from two cities in Korea.

Knowledge of the status of real-world home blood pressure (BP) measurements is crucial for establishing policies promoting hypertension treatment through home BP monitoring. However, only a few studies have investigated the status of home BP measurements in real-world settings. This study investigated the practice of Korean patients in measuring BP at home. This study recruited participants aged ≥20 years who were taking antihypertensives and conducted a questionnaire-based survey on home BP measurements. Of 701 participants recruited between August 2018 and April 2020, 673 were included in the analysis. Of these, 359 (53.3%) possessed home BP measurement devices. The devices used by 184 (51.3%) participants were validated, 110 (30.6%) were nonvalidated, and 65 (18.1%) had an unknown validation status. Only 18 patients (5.0%) with home BP devices were aware of the validation tests for home BP measurement devices. Of the 673 participants, 278 (41.3%) measured BP at home (77.4% of the patients owned home BP measurement devices). Among them, at least 74 (26.6%) performed proper measurements (at least once a month, at least twice a day or twice at a time, after at least 1 minute of rest, with at least a 1-min interval between each measurement, and 30 min after drinking coffee, exercising, or smoking). In conclusion, our community-based survey in the nonpresentive Korean population revealed a low rate of home BP measurement, a high rate of using nonvalidated devices, and a high rate of inappropriate measurements, suggesting that more efforts toward patient education regarding home BP measurements are needed.

Unveiling the Therapeutic Potential and Healthcare Applications of Marine Therapy: A Systematic Review with Meta-Analysis and Meta-Regression.

This study was conducted to estimate the effectiveness of marine-derived resources for treating specific diseases, as well as identify the most effective methods for applying such resources in therapeutic applications. Bibliographic databases (PubMed, Embase, and Cochrane) were searched from their inception until May 2023 using Medical Subject Headings terms and text keywords related to seawater, mineral water, or ocean therapy. Fifteen eligible studies were included, involving 1325 participants aged 42.7-63.0 years. In the subgroup analysis based on treatment type, the mean difference was -1.581 (95% CI: -1.889, -1.274) for seawater with sun exposure and -1.210 (95% CI: -1.417, -1.002) for seawater with sun exposure, mud pack application, and sulfur pool therapy. The pooled standardized mean difference was calculated for different outcomes; the results were -1.110 (95% CI: -3.028, 0.806) for osteoarthritis severity, -0.795 (95% CI: -0.982, -0.607) for arthritis pain, -1.623 (95% CI: -2.036, -1.209) for fibromyalgia pain, and -1.498 (95% CI: -1.888, -1.108) for quality of life. Marine therapy is, therefore, promising for treating chronic skin issues, easing musculoskeletal discomfort, and enhancing the quality of life among patients with musculoskeletal pain.

Incidence and survival of gynecologic cancer including cervical, uterine, ovarian, vaginal, vulvar cancer and gestational trophoblastic neoplasia in Korea, 1999-2019: Korea Central Cancer Registry.

OBJECTIVE: To investigate the incidence, trends, and survival rates of all gynecologic cancers using the Korea Central Cancer Registry (KCCR) database from 1999-2019. METHODS: Gynecologic cancer data were obtained from the KCCR database between 1999 and 2019. Age-standardized incidence rates (ASRs), annual percentage changes, and average annual percentage changes (AAPCs) were calculated. The relative survival rate (RSR) was reported by age group, stage, and 6-year period (I: 1999-2005, II: 2006-2012, III: 2013- 2019). RESULTS: The gynecologic cancer ASRs were 26.2 and 24.9 per 100,000 individuals in 1999 and 2019, respectively. Trends of incidence in gynecologic cancer revealed a decrease in cervical cancer and gestational trophoblastic neoplasia (GTN) with AAPCs of -3.4 and -4.3, respectively. Conversely, the incidence of uterine, ovarian, and vulvar cancers increased with AAPCs of 4.7, 2.3, and 2.1, respectively. AAPC for vaginal cancer showed no change. The 5-year survival rate was highest for GTN (90.5%) and lowest for vaginal cancer (56.6%). An increase in age was correlated with poorer survival rates across all gynecologic cancers, excluding vaginal cancer. For all gynecologic cancer types, the prognosis deteriorates with advancing cancer stages. The RSR of uterine cancer improved consistently across all periods. The ovarian cancer RSR improved more in period III than in periods I or II. Additionally, the vulvar cancer RSR improved more in periods II and III than in period I. CONCLUSION: In Korea, the incidence of cervical cancer and GTN decreased, whereas the incidence of uterine, ovarian, and vulvar cancer increased from 1999 to 2019. The RSR for uterine, ovarian, and vulvar cancers showed consistent improvements over different periods. Effective screening programs and the adoption of advanced treatments may be necessary to further reduce the burden of gynecologic cancer.

Cellular Functions of High-Temperature Requirement Factor A4 in Placenta.

The expression of High-temperature requirement factor A4 (HtrA4) mRNA is significantly lower in the chorionic villi of patients with recurrent pregnancy loss (RPL) than in the control group. We conducted an investigation into the cellular functions of HtrA4 using the CRISPR/Cas9 system and shRNA-HtrA4 to create knockout BeWo cells and HtrA4 knockdown JEG3 cells. Our results indicated that the knockout BeWo cells exhibited reduced capacity for invasion and fusion, but increased levels of proliferation and migration, with a significantly shortened cell cycle compared to wild-type cells. Wild-type BeWo cells highly expressed cell invasion- and fusion-related factors, while knockout BeWo cells highly expressed migration-, proliferation-, and cell cycle-related factors. The shRNA-HtrA4 JEG3 cells showed a decreased capacity for invasion, but an increased capacity for migration, accompanied by a decrease in the expression of cell invasion-related factors and an increase in migration-related factors. Moreover, our ELISA results revealed that the serum HtrA4 level was lower in patients with RPL than in the controls. These findings suggest that HtrA4 depletion may be associated with placental dysfunction.

Differential Expression of DUB Genes in Ovarian Cells Treated with Di-2-Ethylhexyl Phthalate.

Premature ovarian failure (POF) is defined as loss of ovarian function in women less than 40 years of age. The causes of POF are diverse and include environmental factors. Di-2-ethylhexyl phthalate (DEHP) is one factor that may cause POF. The ubiquitin-proteasome system maintains intracellular balance by promoting or inhibiting protein degradation. To investigate the differential expressions of deubiquitinating enzyme (DUB) genes in patients with POF, we developed two in vitro POF models by treating A2780 or OVCAR5 with DEHP. Using these models, a multiplex RT-PCR system for DUB genes was applied to identify biomarkers by comparing expression patterns and DUB mRNA levels; multiplex RT-PCR results were validated by qRT-PCR and Western blotting analyses. Observed differential expression levels of several DUB genes including USP12, COPS5, ATXN3L, USP49, and USP34 in A2780 and OVCAR5 cells at the mRNA and protein levels suggest that they should be investigated as potential biomarkers of POF.

Genetic variation in the Mcp-1 gene promoter associated with the risk of polycystic ovary syndrome.

Monocyte chemoattractant protein-1 (MCP-1) is a pivotal chemokine in the inflammatory response, which plays an important role in recruiting monocytes to sites of injury and infection. However, the exact mechanism of Mcp-1 associated with PCOS risk was unknown. In this study, we explored whether the Mcp-1 -2518G>A polymorphism increases the risk of PCOS. We performed a comparative study of -2518G>A polymorphism of the Mcp-1 gene with PCOS. In addition, luciferase reporter assay was performed to evaluate the Mcp-1 transcriptional activity. A strong association was observed between the -2518G>A polymorphism of Mcp-1 gene and PCOS (p-value = 0.016, odd ratio (OR) = 0.693). A p-value under 0.05 is considered statistically significant. The genotype and allelic frequencies were assumed to be in Hardy-Weinberg equilibrium (HWE). The luciferase assays in 2 cell lines showed that the Mcp-1 -2518G>A substitution can increase the expression of Mcp-1. MCP-1 levels in serum for PCOS group were significantly higher than those in serum for controls (p-value = 0.02). Furthermore, the patients carrying a genotype A/A had significantly increased levels of MCP-1 in serum compared with levels of the MCP-1 of the patients with genotypes G/G and G/A (p-value = 0.031). This is the first study on the genetic variation of the Mcp-1 gene and PCOS. This finding suggests that the Mcp-1 -2518G>A polymorphism is associated with PCOS risk by affecting transcriptional activity, leading to an increased expression level of Mcp-1.

54G/C polymorphism of SREBF-1 gene is associated with polycystic ovary syndrome.

OBJECTIVE: A sterol regulatory element-binding protein (SREBF-1) transcription factor is a major regulator of lipid metabolism, carbohydrate, and plays a key role in energy homeostasis. The 54(G/C) polymorphism of SREBF-1 gene was reported that it is related with metabolic diseases including obesity, type 2 diabetes, and dyslipidemia. Among these, polycystic ovary syndrome (PCOS) is known as a common metabolic-endocrine disorder of women in reproductive ages. STUDY DESIGN: Here, we performed a comparative study of 54(G/C) polymorphism of SREBF-1 gene with PCOS. The 54(G/C) polymorphism of SREBF-1 gene was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) of total 286 PCOS patients and 149 matched controls of healthy women. Statistical analysis was performed using HapAnalyzer. A p-value under 0.05 was considered statistically significant. RESULTS: There was a strong association between the 54(G/C) polymorphism of SREBF-1 gene and PCOS (OR: 0.65, 95% CI: 0.46-0.90, p: 0.0129). The genotype and allelic frequencies were in Hardy-Weinberg equilibrium (HWE). CONCLUSION: This is the first study on the genetic variation of SREBF-1 gene and PCOS. We concluded that 54(G/C) polymorphism of SREBF-1 gene is associated with PCOS. Therefore, our results suggest that SREBF-1 gene may play a role in genetic predisposition to PCOS, which is helpful in understanding the etiology of PCOS.

Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA).

PURPOSE: Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort. METHODS: The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia. RESULTS: The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004). CONCLUSION: The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.

Relationship between leptin receptor and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, which is involved in the multi-system disease, and its etiology is still not clearly understood. It is currently considered that not only the genetic factors but also the environment factors play a crucial role in the pathogenesis of PCOS. Obesity plays an important role through the insulin, leptin and endocannabinoid system in the pathological process of PCOS, leading to more severe clinical manifestations. The aim of our present study is to investigate whether there is association between single nucleotide polymorphisms (SNPs) of Gln223Arg and Pro1019Pro in the leptin receptor gene (LEPR) and PCOS in a Korean population. Interestingly, a significant association was found between the Pro1019Pro in LEPR gene and PCOS, and a highly significant association was found between the Gln223Arg in LEPR gene and PCOS (P=0.033, OR=1.523, 95% confidence interval and P<0.0001, OR=0.446, 95% confidence interval). Moreover, genotype combination and haplotype analyses indicate that Gln223Arg and Pro1019Pro polymorphisms of LEPR are significantly associated with the risk of PCOS.

What is the next step for gastric atypical epithelium on histological findings of endoscopic forceps biopsy?

BACKGROUND: Gastric atypical epithelium on endoscopic biopsy is borderline lesions between benign and malignant. Definitive management of this lesion remains debatable. AIMS: We aimed to analyze the final histological diagnosis for atypical epithelium on endoscopic biopsy and to examine the discrepancy rate between the final histological diagnosis and the initial endoscopic assessment. METHODS: This retrospective study finally enrolled 24 cases proven atypical epithelium on initial histology of an endoscopic biopsy. Of 24 cases, endoscopic submucosal dissection (n = 22), operation (n = 1) and follow-up biopsy without endoscopic submucosal dissection (n = 1) were performed. RESULTS: Of the 24 cases, early gastric cancer (n = 15, 62%) and adenoma (n = 7, 30%) lesions were finally diagnosed in 22 cases. Age, sex, endoscopic results and number of biopsy did not significantly influence the result of final outcome. Between the initial endoscopic assessment and the final histological diagnosis, 12 cases (50%) showed a concordant diagnosis, but eight (33%) and four cases (17%) showed upgraded and downgraded diagnoses, respectively. CONCLUSIONS: Of atypical epithelium cases, the rate of malignant and premalignant lesions was 92% and it was difficult to distinguish between malignant and benign lesions using the initial endoscopic findings. Therefore, endoscopic submucosal dissection can be considered in patients with atypical epithelium on endoscopic biopsy.

Clinically distinct characteristics in patients younger than 40 years old with non-cardiac chest pain.

BACKGROUND AND AIM: Little is known about non-cardiac chest pain (NCCP) in young patients. We aimed to examine the proportion of gastroesophageal reflux disease (GERD) in young patients with NCCP compared to the average-aged NCCP patients and to evaluate their symptomatic characteristics and the clinical efficacy of a 2-week proton pump inhibitor (PPI) trial. METHODS: Ninety-six patients with NCCP≥1/week were classified into the young-aged (≤ 40 years, n =38) and the average-aged groups (>40 years, n=58). Typical reflux symptoms were assessed. The patients were defined into a GERD group and non-GERD group according to reflux esophagitis on esophagogastroduodenoscopy and/or pathologic acid exposure on 24-h esophageal pH monitoring. Then the patients were treated with 30mg of lansoprazole bid for 14 days. RESULTS: Nine patients (23%) in the young-aged group and 22 patients (38%) in average-aged group were diagnosed with GERD-related NCCP (P=0.144). The proportion of typical reflux symptoms was higher in the GERD group compared with the non-GERD group in both age groups. A PPI test improved symptoms in the GERD group irrespective of age, but this improvement was not observed in non-GERD group. CONCLUSIONS: In young NCCP patients, the prevalence of GERD was relatively low compared to average-aged NCCP, but the difference was insignificant. The PPI test was very effective in diagnosing GERD in the NCCP patients in both age groups. Therefore, in young NCCP patients, if there is a negative response to a 2-week PPI trial, the possibility of extra-esophageal disease origin needs to be considered.

The promoter -1031(T/C) polymorphism in tumor necrosis factor-alpha associated with polycystic ovary syndrome.

BACKGROUND: A tumor necrosis factor-alpha is a multifunctional pro-inflammation cytokine, which has been considered as one of pathogenic factors for various diseases. The promoter -1031(T/C) polymorphism in the tumor necrosis factor-alpha gene was reported that it plays a part in reproduction-related diseases. Among these, polycystic ovary syndrome (PCOS) is known to be a common gynecological disease of women in reproductive age women. Here, we performed a comparative study of -1031(T/C) polymorphism of TNF-alpha gene with PCOS in a Korean population. METHODS: The -1031(T/C) polymorphism of TNF-alpha gene was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in a total of 217 PCOS patients and 144 matched female controls of healthy women. And statistical analysis was performed using HapAnalyzer. X2 test and logistic regression were utilized analyze the association between two groups. A p-value under 0.05 was considered statistically significant. RESULTS: The genotype and allelic frequencies were in Hardy-Weinberg equilibrium (HWE). There was strong association between the -1031(T/C) polymorphism in the promoter region of TNF-alpha gene and PCOS (p-value = 0.0003, odd ratio (OR) = 2.53). In addition, the frequency of C allele was significantly higher in PCOS patients compared with controls. Sequence analyses also showed the -1031(T/C) polymorphism of TNF-alpha gene. CONCLUSION: This is the first study on the -1031(T/C) polymorphism of TNF-alpha gene in PCOS. We concluded that the -1031(T/C) polymorphism of TNF-alpha gene is associated with PCOS in a Korean population. Therefore, it is possible that it may be considered as a clinical biomarker to diagnose for PCOS, and is helpful in understanding the etiology for the pathogenesis of PCOS.

Clinical significance of colonoscopic examination in patients with early stage of gastric neoplasm undergoing endoscopic submucosal dissection.

OBJECTIVE: We aimed to determine the frequency of colorectal neoplasm in patients with early gastric neoplasm who underwent endoscopic submucosal dissection (ESD) compared to healthy controls and to investigate their risk factors for colorectal neoplasm. METHODS: A total of 107 patients with gastric neoplasm including 54 gastric adenoma and 53 early gastric cancer (EGC) that underwent ESD and 107 sex/age-matched healthy controls were enrolled. All of the subjects underwent colonoscopy for routine check-up. High-risk colorectal neoplasm were defined as >1 cm, three or more polyps, adenoma with villous component, adenoma with high-grade dysplasia or adenocarcinoma. RESULTS: The frequency of overall colorectal neoplasm was 56.1% in the gastric neoplasm group and 34.6% in the control group (p < 0.005). High-risk colorectal neoplasm was found in 26.2% of patients with gastric neoplasm and 12.1% of controls (p < 0.01). In each gastric adenoma and EGC subgroups, the frequency of overall colorectal neoplasm was higher than each control subgroup. The frequency of high-risk colorectal neoplasm in EGC subgroup was significantly higher than that in the control subgroup, against not being in gastric adenoma subgroup. The risk factors for overall colorectal neoplasm were age and presence of gastric neoplasm, and that for high risk colorectal neoplasm was the only presence of gastric neoplasm. CONCLUSIONS: The frequency of overall and high-risk colorectal neoplasm in the gastric neoplasm group was higher than that in the control group. Therefore, a screening colonoscopy should be considered in patients with early gastric neoplasm undergoing ESD.

Attenuated expression and function of the RECK tumor suppressor under hypoxic conditions is mediated by the MAPK signaling pathways.

Downregulation of the tumor suppressor, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) has been reported under hypoxic conditions (Lee et al., 2010); however, the signaling pathways involved in this downregulation have not yet been identified. Hypoxia causes the silencing of RECK mRNA expression, but treatment with inhibitors of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated kinase (MAPK) (PD98059, SP600125, and SB203580 respectively) or their dominant negative mutants recovered RECK suppression induced by hypoxia as analyzed with semiquantitative RT-PCR analysis and a RECK promoter luciferase assay. Hypoxia increased phosphorylation of ERK1/2, JNK and p38 MAPKs. The activities of matrix metalloproteinase (MMP)-9 and MMP-2 were increased under hypoxic conditions but treatment with PD98059, SP600125 and SB203580 inhibited their activation in cancer cells, as seen by zymography. Moreover, treatment with the inhibitors blocked cancer cell migration induced by hypoxia in H-Ras transformed MCF10A mammary cells. RECK suppression under hypoxic conditions was inversely related to HIF-1α expression; however, treatment with PD98059, SP600125 and SB203580 did not influence binding of HIF-1α to the reverse hypoxia responsive element site of the RECK promoter in a DNA precipitation assay. These results suggest that the ERK, JNK and p38 MAPK signaling pathways are indirectly involved in RECK suppression but are not involved in the binding activity of HIF-1α to the reverse hypoxia responsive element site on the RECK promoter under hypoxic conditions.

Inhibitory effect of glyceollin isolated from soybean against melanogenesis in B16 melanoma cells.

Natural products with non-toxic and environmentally friendly properties are good resources for skin-whitening cosmetic agents when compared to artificial synthetic chemicals. Here, we investigated the effect of glyceollin produced to induce disease resistance responses of soybean to specific races of an incompatible pathogen, phytophthora sojae, on melanogenesis and discussed their mechanisms in melanin biosynthesis. We found that glyceollin inhibits melanin synthesis and tyrosinase activity in B16 melanoma cells without cytotoxicity. To elucidate the mechanism of the effect of glyceollin on melanogenesis, we conducted western blot analysis for melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2. Glyceollin inhibited tyrosinase and TRP-1 protein expression. Additionally, glyceollin effectively inhibited intracellular cAMP levels in B16 melanoma cells stimulated by alpha-melanocyte stimulating hormone (alpha-MSH). These results suggest that the whitening activity of glyceollin may be due to the inhibition of cAMP involved in the signal pathway of alpha-MSH in B16 melanoma cells.

Downregulation of a tumor suppressor RECK by hypoxia through recruitment of HDAC1 and HIF-1alpha to reverse HRE site in the promoter.

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a tumor suppressor and the suppression of RECK is induced by Ras or Her-2/neu oncogenes. However, regulation of RECK under hypoxic microenvironment is largely unknown. Here, we identified that hypoxia significantly downregulates RECK mRNA and protein expression using semiquantitative RT-PCR, real-time RT-PCR and western blot analysis. This repression was reversed by the HDAC inhibitor, trichostatin A (TSA) and HIF-1 inhibitor, YC-1. Hypoxia-induced downregulation of RECK was abolished by knockdown of HDAC1 and HIF-1alpha with respective small interfering RNAs (siRNAs), whereas overexpression of HDAC1 and HIF-1alpha suppressed RECK expression similar to the level under hypoxic conditions. Transfection of a deletion mutant of the second reverse HRE (rHRE2, -2345 to -2333) site of RECK promoter completely removed RECK suppression under hypoxia, indicating that the rHRE2 site is responsible for the inhibition of RECK. Chromatin immunoprecipitation and DNA affinity precipitation assays demonstrated that HDAC1 and HIF-1alpha were recruited to the rHRE2 region of RECK promoter under hypoxic conditions, but the treatment of TSA or YC-1 inhibited their binding to the rHRE2 site. Moreover, TSA and YC-1 inhibited hypoxia-induced cancer cell migration, invasion and MMPs secretion. Taken together, we can conclude that hypoxia induces RECK downregulation through the recruitment of HDAC1 and HIF-1alpha to the rHRE2 site in the promoter and the inhibition of hypoxic RECK silencing would be a therapeutic and preventive target for early tumorigenesis.

Acute dermatomyositis associated with generalized subcutaneous edema.

Generalized subcutaneous edema is an uncommon manifestation of inflammatory myopathy. We report a 48-year-old female patient who presented with severe generalized edema, an erythematous skin rash, dysphagia and proximal muscle weakness. She was diagnosed with dermatomyositis from the clinical signs, increased muscle enzymes, electromyographic findings and a muscle biopsy. Magnetic resonance imaging revealed increased signal intensity in the muscular and subcutaneous layers. The conditions causing generalized edema were excluded. It was concluded that the generalized edema was secondary to dermatomyositis. Aggressive treatments with high-dose glucocorticoids and immunosuppressive agents were used to control the severe subcutaneous edema.

Vascular endothelial growth factor induces endothelin-1 production via matrix metalloproteinase-2 rather than endothelin-converting enzyme-1.

OBJECTIVE: To investigate the mechanism of vascular endothelial growth factor (VEGF)-induced endothelin-1 production in human umbilical vein endothelial cells (HUVECs). METHODS: Endothelin-1 levels were measured in conditioned medium of women with preeclampsia HUVECs were treated with different concentrations of VEGF(165) and at various time intervals. Next, we measured endothelin-1 levels after HUVECs were also incubated with VEGF and endothelin-converting enzyme-1 (ECE-1) inhibitor or tissue inhibitors of matrix metalloproteinase-2 (TIMP-2). Additionally, the circulating levels of total and free VEGF, matrix metalloproteinase-2 (MMP-2), and endothelin-1 were measured in 20 preeclamptic patients and 20 healthy pregnant controls. RESULTS: HUVECs treated with VEGF increased their endothelin-1 production in a concentration and time-dependent manner. The production of endothelin-1 was inhibited by TIMP-2, but not by the ECE-1 inhibitor. Total VEGF, MMP-2, and endothelin-1 concentrations were higher in preeclampsia and showed significant positive correlations between them. CONCLUSION: These findings suggest that VEGF-induced endothelin-1 production might be mediated by MMP-2 rather than by ECE-1 upregulation.

The levels of circulating vascular endothelial growth factor and soluble Flt-1 in pregnancies complicated by preeclampsia.

To evaluate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of preeclampsia, we measured total VEGF, free VEGF and soluble Flt-1 (sFlt-1) concentrations and determined their relationships. Maternal serum samples were collected from 20 patients with preeclampsia and 20 normotensive women with uncomplicated pregnancies matched with the patients with preeclampsia for gestational age and parity. The serum concentrations of total VEGF (2.39+/-0.75 vs. 0.28+/-0.14) and sFlt-1 (934.5+/-235.5 vs. 298.0+/-161.2) were significantly increased in the patients with preeclampsia compared to the women with uncomplicated pregnancies. However the serum concentration of free VEGF (21.5+/-6.3 vs. 134.0+/-16.3) was lower in patients with preeclampsia. There was a positive correlation between the serum concentrations of total VEGF and sFlt-1 with systolic and diastolic blood pressure, respectively. There was a negative correlation between the serum concentration of free VEGF and systolic and diastolic blood pressure. There was a strong negative correlation between free VEGF and sFlt-1 concentrations. In conclusion, we found VEGF and sFlt-1 were related to the pathogenesis of preeclampsia. Although reduced concentrations of free VEGF might interfere with endothelial cell function and survival, further studies are required to clarify its specific role in the pathogenesis of preeclampsia.

Can human papillomavirus DNA testing substitute for cytology in the detection of high-grade cervical lesions?

CONTEXT: High-risk human papillomaviruses (HPVs) are causal factors of cervical carcinomas. OBJECTIVE: To evaluate the sensitivity and efficiency of HPV DNA testing in comparison with conventional cytology for detection of cervical intraepithelial neoplasia (CIN) and cancer. DESIGN: Both testing procedures were administered to 593 women, aged 14 to 88 years (average, 41.7 years), who were referred for abnormal cytology from January 2000 through December 2001 at Korea University Guro Hospital (Seoul, Korea). After histologic confirmation by either colposcopically directed biopsy or endocervical curettage, the efficiency of the detection methods for high-grade cervical lesion was evaluated for the following 3 data sets: HPV DNA testing, conventional cytology, and the 2 tests combined. RESULTS: The sensitivity, specificity, and positive predictive, and negative predictive values for the detection of CIN 2 or higher were 92.4%, 52.4%, 49.3%, and 93.2% for HPV DNA testing; 76.3%, 65.8%, 52.8%, and 84.7% for cytology; and 97.8%, 36.7%, 49.2%, and 97.3% for the combined tests. Among the 151 patients diagnosed with CIN 2 or CIN 3, 137 patients (90.7%) were HPV positive, 116 patients (76.8%) were proven to have abnormal cytology, and 147 patients (97.6%) were positive for either HPV DNA testing or cytology. The sensitivity values for HPV DNA testing and cytology were 97.9% (46/47) and 74.5% (35/47), respectively, for invasive cervical cancer detection, and the combined tests showed 100% (47/47) sensitivity. Depending on the patient's age and the grade of the cervical lesion, HPV DNA testing proved to be significantly more sensitive than cytology for the primary detection of cervical abnormalities (P <.001). CONCLUSION: Human papillomavirus DNA testing for the detection of high-grade cervical lesions was more sensitive than cytology alone. In addition, the screening sensitivity can be further improved by combining cytology with HPV DNA testing. This approach is especially beneficial in detecting cancer precursors in women older than 60 years.