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Objectives: To determine the frequency of intratumoural flow and peritumoural hepatofugal portal flow using colour Doppler sonography (CDS) on hepatic haemangiomas with arterioportal shunt (APS), and to investigate possible factors that may affect the capability of CDS to depict such findings., Methods: The study included 45 patients (35 men, 10 women; mean age, 56 years) with hepatic haemangiomas with APS on CT or MRI. Locating the tumour on greyscale sonography, the depth, size and echogenicity of the tumour were evaluated. CT or MR images were evaluated for fatty liver. CDS was performed to determine the presence of intratumoural flow and peritumoural hepatofugal portal flow. Differences in frequency of intratumoural flow and peritumoural hepatofugal portal flow according to the depth, size, echogenicity and fatty liver were evaluated by Student's t-test and Fisher's exact test., Results: On CDS, intratumoural flow and peritumoural hepatofugal portal flow were found in 66.7% and 60%, respectively. The tumour depth was the significant variable that affected the capability of CDS to depict such findings. The frequencies of intratumoural flow and peritumoural hepatofugal portal flow were as high as 88% and 80% for shallow (≤30 mm) lesions, and they were 40% and 35% for deep (>30 mm) lesions (p=0.0012; p=0.0051)., Conclusion: CDS can commonly depict intratumoural flow and peritumoural hepatofugal portal flow in patients with hepatic haemangiomas with APS. Therefore, CDS should be routinely performed when an incidental mass is encountered during the screening sonography, especially when the lesion is shallow.

Objective: The purpose of this study was (1) to evaluate the prevalence of the left and right central venous stenosis by measuring the narrowest area and (2) to assess the effects of the central venous stenosis on perivenous artifacts and reflux of contrast material, in CT of the neck., Materials and Methods: Images of a total of 443 CT of the neck with an injection of contrast material into the left (n = 249) or right (n = 194) arm were retrospectively reviewed. The maximum stenosis area in the central vein ipsilateral to the injection side was measured in each patient. We also graded the perivenous artifacts and reflux of contrast material with 4-point scale. These results were compared between patients with right arm injection and those with left arm injection., Results: The maximum stenosis area in the left arm was significantly smaller than that in the right arm. The stenosis was most frequently identified at the medial clavicular region. The mean scores of the perivenous artifacts and the reflux of contrast material were significantly higher in patients with left arm injection than in those with right arm injection. The perivenous artifacts and reflux of contrast material were more prominent in patients with central venous stenosis (maximum stenosis area <50mm(2)) than those without stenosis., Conclusions: The image degradation in CT of the neck, due to perivenous artifacts and venous reflux, can be reduced with the right arm injection of contrast material when compared with the left arm injection., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Cartilage oligomeric matrix protein (COMP) is a biomarker for joint destruction and its serum levels are used for assessing therapeutic efficacy. This study aims to compare changes in serum COMP levels in postmenopausal women with osteopenia/osteoporosis receiving estrogen and alendronate., Methods: A total of 62 postmenopausal women diagnosed with osteopenia or osteoporosis were treated with either estrogen (17β-estradiol 1 mg, n = 30) or bisphosphonate (alendronate 5 mg, n = 32) for 6 months. The controls were healthy postmenopausal women (n = 30). Serum COMP and osteocalcin levels were measured at baseline and after 6 months of treatment., Results: Estrogen decreased levels of COMP at 6 months compared to baseline levels (–8.35 ± 19.38%), whereas the bisphosphonate and control groups resulted in no significant changes (–5.50 ± 18.69 and –1.49 ± 25.34%, respectively). Concentrations of osteocalcin decreased significantly in both treatment groups (estrogen –25.60 ± 24.42% and alendronate –13.76 ± 23.89%, respectively). There was a significant positive correlation between changes after 6 months in COMP and osteocalcin (R = 0.48, p = 0.002)., Conclusions: Postmenopausal women treated with estrogen showed significantly decreased levels of COMP after 6 months. Estrogen might provide a further treatment modality in the prevention of joint destruction.

Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form "a carboxylate clamp" with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove but not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.

We report a case of an erroneously elevated bispectral index (BIS) during robot assisted thyroidectomy using an electromyographic endotracheal tube (EMG tube), which is safe and useful for laryngeal electromyographic monitoring. Ten minutes after start of the operation, a sudden increase of BIS value up to 98 was noticed. The BIS values were not decreased to < 65 with supplemental anesthetics. The anesthetic method was changed from total intravenous anesthesia to balanced anesthesia. The BIS sensor and monitor were changed and other models were used. These interventions did not alter BIS values. BIS levels remained between 60 and 70 throughout the main procedure and intermittently increased to the mid-90s without any trace of poor signal quality. At the end of the surgery, the BIS values returned to normal range. The patient did not complain of intraoperative recall. Knowledge of potential interference from the use of an EMG tube must be considered when interpreting BIS.

Cerebral infarctions are uncommon in neonates. However, they should be considered among causes of neonatal seizures. We describe seven neonates with cerebral infarctions. Clinical presentations, perinatal history, perinatal risk factors, cranial magnetic resonance imaging and electroencephalography findings, thrombophilic factors, and clinical outcomes were reviewed. Six patients manifested seizures, whereas one exhibited cyanosis. Six neonates manifested left middle cerebral artery infarctions, and one exhibited a borderzone infarction between the anterior cerebral and middle cerebral arteries. Electroencephalograms indicated epileptiform discharges on the left hemisphere in three neonates with left middle cerebral artery territory infarctions, and epileptiform discharges on both hemispheres in one patient. At most recent follow-up visit, five patients had achieved normal development, whereas one exhibited right hemiparesis and aphasia, and another manifested toe-in gait. These findings may help predict neurodevelopmental outcomes in neonates with cerebral infarctions., (Copyright © 2011. Published by Elsevier Inc.)

Background: If lung deflation increases the distance from the subclavian vein (SCV) to the pleura and the diameter of the vein, it might decrease the risk of pneumothorax and increase the success rate of subclavian venous cannulation. We evaluated the effect of lung deflation on the distance from the SCV to the pleura (SCV-pleura distance) and on the cross-sectional area (CSA) of the SCV in mechanically ventilated pediatric patients., Methods: Fifty patients (25 infants younger than 1 year and 25 children aged 1 to 8 years) were placed supine over a shoulder roll, and their lungs were ventilated with a tidal volume of 6 to 7 mL/kg. Lung deflation was achieved by opening the endotracheal tube to the atmosphere. The SCV-pleura distances and the SCV CSAs were measured using ultrasound at the end of inflation and 0, 30, 60, 90, and 120 seconds after lung deflation. A P value <0.05 was considered statistically significant. Increases of 5% in the distance and 25% in the CSA were defined as clinically relevant., Results: The available data from 43 patients, 22 infants and 21 children, were analyzed. No clinically relevant changes in the SCV-pleura distance or in the SCV CSA were induced by lung deflation. Neither the SCV-pleura distance nor the CSA showed any further increase with time., Conclusions: Lung deflation failed to increase the SCV-pleura distance and the CSA of the SCV. Its application is unlikely to be advantageous in avoiding pneumothorax or improving the success rate of subclavian venous cannulation.

Many studies have been recently reported that veterinary antibiotics released into the environment have a detrimental effect on humans such as the occurrence of antibiotic-resistant bacteria. However, only limited information is available regarding to the release of antibiotics in environmental compartments in Korea. Objectives of this study were to evaluate the concentrations of antibiotics in water, sediment, and soil adjacent to a composting facility in Korea and to determine the dilution effects of antibiotics when released into the environment. Seven antibiotics of chlortetracycline, oxytetracycline, tetracycline, sulfamethazine, sulfamethoxazole, sulfathiazole, and tylosin were evaluated by high-performance liquid chromatography-tandem mass spectrometry following pretreatment using solid-phase extraction to clean the samples. Results showed that the highest concentration of each antibiotic in both aqueous and solid samples was detected from a site adjacent to the composting facility. We also found that the studied water, sediment, and soil samples are contaminated by veterinary antibiotics throughout comparison with studies from other countries. However, relatively lower concentrations of each antibiotic were observed from the rice paddy soil located at the bottom of the water stream. Further research is necessary to continuously monitor the antibiotics release into ecosystems, thereby developing an environmental risk assessment.

Curcumin is a polyphenolic compound derived from the Indian spice turmeric. We used nanoparticle-encapsulated curcumin to treat medulloblastoma and glioblastoma cells. This formulation caused a dose-dependent decrease in growth of multiple brain tumor cell cultures, including the embryonal tumor derived lines DAOY and D283Med, and the glioblastoma neurosphere lines HSR-GBM1 and JHH-GBM14. The reductions in viable cell mass observed were associated with a combination of G(2)/M arrest and apoptotic induction. Curcumin also significantly decreased anchorage-independent clonogenic growth and reduced the CD133-positive stem-like population. Down-regulation of the insulin-like growth factor pathway in DAOY medulloblastoma cells was observed, providing one possible mechanism for the changes. Levels of STAT3 were also attenuated. Hedgehog signaling was blocked in DAOY cells but Notch signaling was not inhibited. Our data suggest that curcumin nanoparticles can inhibit malignant brain tumor growth through the modulation of cell proliferation, survival and stem cell phenotype.

Porcelain gallbladder is regarded as a risk factor of gallbladder cancer. A porcelain gallbladder with calcified regional lymph nodes was found using computed tomography (CT) and magnetic resonance imaging (MRI) in a 43-year-old man who presented with nausea, vomiting, and abdominal pain. His cholecystectomy specimen showed diffuse wall thickening and contained small gallstones. Histological examination revealed diffuse infiltrative adenocarcinoma with extensive intratumoral calcification (calcified carcinoma). The majority of the calcified material was located within or replaced the tumor glands, and was not found in the stroma. A lymph node was totally replaced with a calcified metastatic adenocarcinoma. To the best of our knowledge, only one case of calcified lymph node metastasis from a calcified carcinoma of the gallbladder has been previously reported in the literature. We herein add a case of calcified carcinoma of the gallbladder with calcified lymph node metastasis, presenting as a porcelain gallbladder on CT and MRI.

Pine wilt disease (PWD) is one of the most devastating forest diseases in Asia and Europe. The pine wood nematode, Bursaphelenchus xylophilus, has been identified as the pathogen underlying PWD, although the pathology is not completely understood. At present, diagnosis and confirmation of PWD are time consuming tasks that require nematode extraction and microscopic examination. To develop a more efficient detection method for B. xylophilus, we first generated monoclonal antibodies (MAbs) specific to B. xylophilus. Among 2304 hybridoma fusions screened, a hybridoma clone named 3-2A7-2H5 recognized a single protein from B. xylophilus specifically, but not those from other closely related nematodes. We finally selected the MAb clone 3-2A7-2H5-D9-F10 (D9-F10) for further studies. To identify the antigenic target of MAb-D9-F10, we analyzed proteins in spots, fractions, or bands isolated from SDS-PAGE, two-dimensional electrophoresis, anion exchange chromatography, and immunoprecipitation via nano liquid chromatography electrospray ionization quadrupole ion trap mass spectrometry (nano-LC-ESI-Q-IT-MS). Peptides of galactose-binding lectin-1 of B. xylophilus (Bx-LEC-1) were commonly detected in several proteomic analyses, demonstrating that this LEC-1 is the antigenic target of MAb-D9-F10. The localization of MAb-D9-F10 immunoreactivities at the area of the median bulb and esophageal glands suggested that the Bx-LEC-1 may be involved in food perception and digestion. The Bx-LEC-1 has two nonidentical galactose-binding lectin domains important for carbohydrate binding. The affinity of the Bx-LEC-1 to D-(+)-raffinose and N-acetyllactosamine were much higher than that to L-(+)-rhamnose. Based on this combination of evidences, MAb-D9-F10 is the first identified molecular biomarker specific to the Bx-LEC-1.

For tissue-engineering applications, a 3D porous chitosan scaffold was simply prepared from a mixture of acidic chitosan solution and sodium acetate particles as the porogen by a salt-leaching method. Differences in the porous structure in terms of pore morphology and interconnectivity between the salt-leached chitosan scaffold and phase-separated scaffold as the control were examined by using scanning electron microscopy, protein release and enzymatic degradation tests. A fibroblast (NIH-3T3) cell culture was performed for cell affinity evaluation. The chitosan scaffold prepared by salt-leaching showed good interconnectivity and improved mechanical properties. Furthermore, the chitosan scaffolds showed a high initial cell adhesion after 4 h cell culture and increased cell proliferation than the control. Thus, salt-leached chitosan scaffolds can be used for various tissue-engineering applications.

The levonorgestrel-releasing intrauterine system (LNG-IUS) is effective in the treatment of dysmenorrhea associated with adenomyosis. However, the mechanism of pain relief of LNG-IUS in patients with adenomyosis is unclear. We aimed to investigate the effects of LNG-IUS on the expression of nerve growth factor (NGF) and its receptors, NGFR p75 and TrkA in patients with adenomyosis. Endometrial and myometrial tissues were prepared from 17 LNG-IUS-treated patients and 15 hormonally untreated patients who had undergone hysterectomies for adenomyosis. Immunohistochemistry with antibodies against NGF, NGFR p75, and TrkA, was performed. The expression of NGF, NGFR p75, and TrkA in endometrium and myometrium of LNG-IUS-treated patients was significantly decreased compared to those of hormonally untreated patients. Our findings may indicate that the suppression of NGF and its receptors by LNG-IUS is another possible mechanism of relieving pain in patients with adenomyosis.

Objective: The purpose of this study was to determine the diagnostic accuracy of CT for detecting extrathyroidal invasion of thyroid cancer to adjacent structures., Materials and Methods: Eighty-four patients (19 men, 65 women; age range, 19-84 years; mean, 54.2 +/- 15.4 years) with 86 malignant tumors of the thyroid with extracapsular extension (37 T3, 49 T4) were retrospectively enrolled in this study. Two radiologists independently evaluated the CT findings of invasion of thyroid cancer into the trachea, esophagus, common carotid artery, internal jugular vein, and recurrent laryngeal nerve. These results were compared with the surgical and histopathologic findings., Results: The mean sensitivity, specificity, and accuracy of CT were as follows: 59.1%, 91.4%, and 83.2% for tracheal invasion; 28.6%, 96.2%, and 90.7% for esophageal invasion; 75.0%, 99.4%, and 98.8% for invasion of the common carotid artery; 33.3%, 98.8%, and 97.1% for invasion of the internal jugular vein; and 78.2%, 89.8%, and 85.5% for invasion to the recurrent laryngeal nerve. Interobserver agreement was moderate to good in the five categories of extrathyroidal invasion with a mean kappa value of 0.65 (range, 0.49-0.77)., Conclusion: Although the effectiveness is limited by low sensitivity, CT may be a valuable tool for evaluation of extrathyroidal invasion of thyroid cancer to adjacent structures.

Advancements in the field of proteomics have provided great opportunities for the development of diagnostic and therapeutic tools against human diseases. In this study, we analyzed haptoglobin and amyloid A protein levels of vivax malaria patients with combinations of depletion of the abundant plasma proteins, 2-dimensional gel electrophoresis (2-DE), image analysis, and mass spectrometry in the plasma between normal healthy donors and vivax malaria patients. The results showed that the expression level of haptoglobin had become significantly lower or undetectable in the plasma of vivax malaria patients due to proteolytic cleavage when compared to healthy donors on 2-DE gels. Meanwhile, serum amyloid A protein was significantly increased in vivax malaria patient's plasma with high statistical values. These 2 proteins are common acute phase reactants and further large scale evaluation with a larger number of patient's will be necessary to establish the possible clinical meaning of the existential changes of these proteins in vivax malaria patients. However, our proteomic analysis suggests the feasible values of some plasma proteins, such as haptoglobin and serum amyloid A, as associating factor candidates for vivax malaria.

Protease inhibitors have been usually isolated through a number of steps using various chromatographical methods, which are time consuming and tedious. In this report, an efficient and low-cost acrylamide affinity gel electrophoresis method for the detection and isolation of chymotrypsin inhibitor from a crude extract was studied. The affinity gel was obtained by immobilization of chymotrypsin on 5% (w/v) poly acrylamide-oleic acid gel, and the immobilized chymotrypsin showed high stability under varied concentrations of urea (0 to 8M), pH (4 to 10) and temperature (30 to 80 degrees C). The affinity gel made of immobilized chymotrypsin was applied to polyacrylamide affinity gel electrophoresis and reverse electrode electro-elution using a modified commercial electrophoresis kit. Polyacrylamide affinity gel electrophoresis method showed higher isolation efficiency for chymotrypsin inhibitor from Ganoderma lucidum crude extract than a chromatographical method. Specific activity and yield of chymotrypsin inhibitor increased around 2.3-folds and 1.4-folds, respectively, compared with a chromatographical method. Also, two isomers of the inhibitor could be isolated by this method. Therefore, this method can be applied for the detection and isolation of bio-active molecules as a fast and economical method., (Copyright 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Paraffin wax is usually used as an embedding medium for histological analysis of natural tissue. However, it is not easy to obtain enough numbers of satisfactory sectioned slices because of the difference in mechanical properties between the paraffin and embedded tissue. We describe a modified paraffin wax that can improve the histological analysis efficiency of natural tissue, composed of paraffin and ethylene vinyl acetate (EVA) resin (0, 3, 5, and 10 wt %). Softening temperature of the paraffin/EVA media was similar to that of paraffin (50-60 degrees C). The paraffin/EVA media dissolved completely in xylene after 30 min at 50 degrees C. Physical properties such as the amount of load under the same compressive displacement, elastic recovery, and crystal intensity increased with increased EVA content. EVA medium (5 wt %) was regarded as an optimal composition, based on the sectioning efficiency measured by the numbers of unimpaired sectioned slices, amount of load under the same compressive displacement, and elastic recovery test. Based on the staining test of sectioned slices embedded in a 5 wt % EVA medium by hematoxylin and eosin (H&E), Masson trichrome (MT), and other staining tests, it was concluded that the modified paraffin wax can improve the histological analysis efficiency with various natural tissues., ((c) 2010 Wiley-Liss, Inc.)

Purpose: Cosmetic injection of paraffin into cervicofacial tissues has been practiced in the past, especially in Asia, resulting in foreign body granuloma (paraffinoma). The purpose of this study was to describe the computed tomography (CT) findings of cervicofacial paraffinomas., Materials and Methods: CT images of 5 patients (4 women and 1 man; age range, 54-80 years; mean age, 67.6 years), who had received direct paraffin injections into cervicofacial tissues, were reviewed retrospectively., Results: The lesions were bilateral and located in the subcutaneous fat layer of the cheek (n = 5), buccal space (n = 2), periorbital area (n = 1), periauricular area (n = 1), neck (n = 1), and nose (n = 1). The predominant CT features were speckled mass formation (n = 3), fat-density nodule (n = 5), high-density nodule (n = 5), nodular calcification (n = 5), and rim calcification (n = 4)., Conclusion: Paraffinomas in the cervicofacial region have specific CT features that are distinct from other soft tissue masses.

Purpose: The aim of this study was to evaluate the long-term treatment outcome and major complication rates of abdominal sacrocolpopexy (ASC)., Materials and Methods: This retrospective study included 57 Korean women who underwent ASC with mesh for symptomatic uterine or vault prolapse and attended follow-up visits for at least 5 years. Forty-seven women with urodynamic stress incontinence concomitantly received a modified Burch colposuspension. The long-term anatomical and functional outcomes and complication rates were assessed., Results: The median follow-up was 66 months (range 60-108). Overall anatomical success rates (no recurrence of any prolapse >or= stage II according to the pelvic organ prolapse-quantification system) were 86.0%. Urinary urgency and voiding dysfunction were significantly improved after surgery, however, recurrent stress urinary incontinence developed in 44.7% (21/47) of cases and half of them developed within 1-3 months post-op. Bowel function (constipation and fecal incontinence) and sexual function (sexual activity and dyspareunia) did not significantly change after surgery. Major complication requiring reoperation or intensive care developed in 12 (21.0%) cases., Conclusions: ASC provides durable pelvic support, however, it may be ineffective for alleviating pelvic floor dysfunction except for urinary urgency and voiding dysfunction, and it contains major complication risk that cannot be overlooked.

Background: The reindeer lichen is the product of a mutualistic relationship between a fungus and an algae. Lichen demonstrate a remarkable capacity to tolerate dehydration. This tolerance is driven by a variety of biochemical processes and the accumulation of specific secondary metabolites that may be of relevance to the pharmaceutical, biotechnology and agriculture industries. These protective metabolites hinder in vitro enzymatic reactions required in cDNA synthesis. Along with the low concentrations of RNA present within lichen tissues, the process of creating a cDNA library is technically challenging., Findings: An evaluation of existing commercial and published protocols for RNA extraction from plant or fungal tissues has been performed and experimental conditions have been optimised to balance the need for the highest quality total ribonucleotides and the constraints of budget, time and human resources., Conclusion: We present a protocol that balances inexpensive RNA extraction methods with commercial RNA clean-up kits to yield sufficient RNA for cDNA library construction. Evaluation of the protocol and the construction of, and sampling from, a cDNA library is used to demonstrate the suitability of the RNA extraction method for expressed sequence tag production.

To establish expressed sequence tag databases of the two life stages (the dispersal and propagative stages) of pinewood nematode Bursaphelenchus xylophilus, subtractive EST libraries that were specific to the dispersal 4th larval stage (D4S) and the pine-grown propagative mixed (PGPS) stage were constructed by suppressed subtractive hybridization, and annotated by BLASTx and Gene Ontology (GO). A total of 1112 (57.7%) contigs from the D4S-cDNA library and 1215 (46.7%) contigs from the PGPS-specific cDNA libraries had matched BLASTx hits (E

High-mobility group box 1 protein (HMGB1) has been studied as a key mediator of inflammatory diseases, including sepsis. Regulating secretion is important in the control of HMGB1-mediated inflammation. Previously, it was shown that HMGB1 needs to be phosphorylated for secretion. In this study, we show that HMGB1 is phosphorylated by the classical protein kinase C (cPKC) and is secreted by a calcium-dependent mechanism. For this study, RAW264.7 cells and human peripheral blood monocytes were treated with PI3K inhibitors wortmannin, LY294002, and ZSTK474, resulting in inhibition of LPS-stimulated HMGB1 secretion, whereas inhibitors of NF-kappaB and MAPKs p38 and ERK showed no inhibition. Akt inhibitor IV and mammalian target of rapamycin inhibitor rapamycin did not inhibit HMGB1 secretion. However, the PKC inhibitors Gö6983 (broad-spectrum PKC), Gö6976 (cPKC), and Ro-31-7549 (cPKC) and phosphoinositide-dependent kinase 1 inhibitor, which results in protein kinase C (PKC) inhibition, inhibited LPS-stimulated HMGB1 secretion. PKC activators, PMA and bryostatin-1, enhanced HMGB1 secretion. In an in vitro kinase assay, HMGB1 was phosphorylated by recombinant cPKC and by purified nuclear cPKC from LPS-stimulated RAW264.7 cells, but not by casein kinase II or cdc2. HMGB1 secretion was also induced by the calcium ionophore A23187 and inhibited by the Ca(2+) chelators BAPTA-AM and EGTA. These findings support a role for Ca(2+)-dependent PKC in HMGB1 secretion. Thus, we propose that cPKC is an effector kinase of HMGB1 phosphorylation in LPS-stimulated monocytes and PI3K-phosphoinositide-dependent kinase 1 may act in concert to control HMGB1 secretion independent of the NF-kappaB, p38, and ERK pathways.

Background: This study used static posturography to investigate the neurotoxic effects on workers exposed to mixed organic solvents at low concentrations under the levels of the threshold limit values (TLV)., Methods: Forty-one workers from four plants exposed to mixed solvents and 90 non-exposed referents were examined. The lifetime cumulative biological exposure (CE) was estimated according to subject's occupational history and biological monitoring results. Static posturography and questionnaire were the basis of data collection., Results: The mean exposure index of mixed organic solvents of four plants was 0.47 (SD: 0.33, range: 0.08-1.39). The exposed group showed a larger sway area and length under the eye open condition than did the non-exposed group. In a multiple linear regression, a significant positive association was demonstrated between postural sway area and CE., Conclusions: This study results suggest that the exposure to organic solvents under TLV levels may cause disturbance in postural stability., (Copyright 2009 Wiley-Liss, Inc.)

Background: This study is aimed to investigate the effect of tramadol on the bispectral index (BIS) during anesthesia with desflurane., Methods: One hundred fifty adults, ASA class 1 and 2 patients, scheduled for general anesthesia for elective surgical procedures were included in this study. None of the patients were premedicated and anesthesia was induced with propofol 2 mg/kg and maintained with air-oxygen (FiO2 0.5) and desflurane, adjusted to keep the BIS between from 50 and 60. Forty minutes before completing surgery, the subjects were randomly allocated into 3 groups to receive saline (control group), tramadol 1.5 mg/kg (T1 group) or 3.0 mg/kg (T2 group) intravenously. Hemodynamics and BIS values were then recorded every 5 minutes until completion of the operation, during which time the concentrations of desflurane were not modified., Results: The mean BIS values after tramadol administration weren't significantly different from the control group throughout the period of observation. No significant changes in the hemodynamics were noted, except systolic and diastolic arterial blood pressure in the T1 and T2 groups significantly increased in the first 5 minutes after the tramadol injection., Conclusions: The results indicate that the administration of tramadol while maintaining anesthesia with desflurane, adjusted to keep the BIS between 50 and 60, does not modified BIS values. So, we propose that tramadol can be safely administered as an immediate postoperative analgesia without concern about intra-operative awareness.

Background: The ant species Pachycondyla chinensis, which has spread from Far Eastern Asia to New Zealand and North America, induces anaphylactic reactions in human with its sting. However, the major allergens of P. chinensis have not yet been characterized., Methods: We selected seven patients with histories of anaphylaxis induced by P. chinensis. Two-dimensional electrophoresis (2-DE) was used to identify the major allergens. We subsequently performed Western blots for P. chinensis-specific IgEs, N-terminal amino acid sequencing, ESI-MS/MS, and RT-PCR using primers based on the N-terminal sequence., Results: Six of the anaphylactic subjects had an IgE specific to a 23 kDa allergen of P. chinensis. Two candidates for major allergens, 23 kDa (pI 8.7) and 25 kDa (pI 6.2), were revealed by 2-DE using P. chinensis-specific IgE immunoblotting. In N-terminal sequencing and ESI-MS/MS analysis, 23 kDa (pI 8.7) and 25 kDa (pI 6.2) allergens, belonging to the protein families of antigen 5, were identified and share marked amino acid sequence similarity. The 23 kDa allergen is 206 amino acids in length and homology searches showed 54.0% and 50.0% homology with Sol i 3 and Ves v 5, respectively., Conclusion: The major allergens of P. chinensis are 23 kDa (pI 8.7) and 25 kDa (pI 6.2) proteins that belong to the antigen 5 family of proteins.

Background: Intrathecal opioids in combination with bupivacaine has been shown to provide adequate sensory blockade and early recovery from spinal anesthesia. This study was investigated the added effects of intrathecal fentanyl 10 microgram to bupivacaine for spinal anesthesia., Methods: Sixty patients undergoing lower extremity surgery were into three groups. Group I received bupivacaine 10 mg (0.5%), gruop II received bupivacaine 5 mg with normal saline 1 ml, and group III received bupivacaine 5 mg with fentanyl 10 microg and normal saline 0.8 ml., Results: There was no significant difference between group I and group III in the peak level and duration of sensory block. But the intensity of motor blockade was decreased in group III compared with group I and side effects of spinal anesthesia with local anesthetics was decreased in group III compared with group I. In Group II, 7 patients were complained the pain during surgery., Conclusions: Intrathecal fentanyl 10 microgram with bupivacaine 5 mg on spinal blockade provide reliable anesthesia for lower extremity surgery.

The antibody levels against the C-terminal region of the merozoite surface protein 1 of Plasmodium vivax (PvMSP1c) were measured in 276 patients with P. vivax malaria (patient group), 320 malaria-naïve healthy individuals (control group 1), and 70 malaria-naïve individuals with various disorders (control group 2) using the immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) and the direct sandwich ELISA. To evaluate the antibody response during relapse, 5 relapsed patients were tested using the IgM capture ELISA. The IgM antibodies were negative in 99.7% of control group 1 and in 100% of control group 2; they were positive in 90.6% of the patient group. The total antibody levels were positive in 88.4% of the patient group with the direct sandwich ELISA. The sera from the second malaria episode, i.e., relapsed patients, were 100% positive on the IgM capture ELISA. The results of this study suggest that the IgM capture ELISA may be a useful diagnostic method for P. vivax malaria for both primary infection and relapse.

Although diagnosis of Plasmodium vivax malaria has been difficult when it is present at a low parasite density, it was recently revealed that an antibody assay was a good method of screening for malaria in blood banks. However, the use of this method for the diagnosis of malaria is limited due to the persistence of specific immunoglobulin (Ig) G. Therefore, we evaluated specific IgM antibody responses against the C-terminal region of the merozoite surface protein 1 of P. vivax (PvMSP1c) in sera obtained from patients with vivax malaria using various assays. The IgM capture enzyme-linked immunosorbent assay showed good sensitivity (97.7%; 308/315) and specificity (99.1%, 446/450). In addition, the results of this assay were not related to parasite density, and a high reactivity was observed when there was a low level of parasitemia. Furthermore, we found that patients with cases of malaria that had relapsed still had the IgM titers against PvMSP1c. Therefore, the use of IgM ELISA for the detection of specific IgM that was not involved in memorial immune activity could be an alternative tool for the diagnosis of malaria and blood screening, even in areas in which malaria is endemic.

Objective: To determine the publication rate of abstracts presented by Korean investigators at national and international radiological meetings, and to identify predictive factors of publication., Materials and Methods: Abstracts presented at the annual meetings of the Korean Radiological Society (KRS), and abstracts presented by Korean investigators at the annual meetings of the Radiological Society of North America (RSNA) and European Congress of Radiology (ECR) from 2001 to 2002 were searched for subsequent publication, using PubMed and the Korean Medical Database. The following variables were evaluated. 1) The overall publication rate; 2) the publication rates according to the radiological subspecialty, presentation type (oral or poster), sample size (< or = 20, 21-50, or > 50), study design (prospective or retrospective), statistical analysis (present or absent), and study outcome (positive or negative); 3) the time to publication; 4) the journal where the study was published; 5) consistency between the abstract and the final publication., Results: Of 1,097 abstracts, 301 (27.4%) were subsequently published, at an average of 15.8 +/- 13.8 months after presentation in 48 journals. The publication rates for studies presented at the RSNA (35.4%) and ECR (50.5%) conferences were significantly higher than that for the KRS conference (23.6%, p < 0.05). Vascular/interventional radiology studies had the highest publication rate (33.1%), whereas musculoskeletal radiology studies had the lowest publication rate (17.1%). Other factors associated with subsequent publication were prospective design, use of statistical testing, and a positive study outcome., Conclusion: The publication rate is significantly lower for the KRS (23.6%) meeting abstracts as compared to those of the RSNA (35.4%) and ECR (50.5%). Prospective design, use of statistical testing, and positive study outcome have a statistically significant effect on the publication rate.

Angiomyofibroblastoma is a rare benign soft tissue neoplasm that predominantly occurs in the genital region of middle-aged women. We present a case of an angiomyofibroblastoma that involved the posterior perivesical space in a 48-year-old woman. We have documented the magnetic resonance imaging features of this case.

Rationale and Objectives: We sought to evaluate the diagnostic performance of an artificial neural network (ANN) and binary logistic regression (BLR) in differentiating malignant from benign thyroid nodules on ultrasonography., Materials and Methods: Two experienced radiologists, who were unaware of the histopathological diagnosis, analyzed ultrasonographic (US) features of 109 pathologically proven thyroid lesions (49 malignant and 60 benign) in 96 patients. Each radiologist was asked to evaluate US findings and categorize nodules into one of the two groups (malignant vs. benign) in each case. The following 8 US parameters were assessed for each nodule: size, shape, margin, echogenicity, cystic change, microcalcification, macrocalcification, and halo sign. Statistically significant US findings were obtained with backward stepwise logistic regression and were used for training and testing of the ANN and the BLR. The performance of the ANN and BLR was compared to that of the radiologists using receiver-operating characteristic (ROC) analysis., Results: Statistically significant US findings were size, margin, echogenicity, cystic change, and macrocalcification of the nodules. The area under the ROC curve (Az) values of ANN and BLR were 0.9492 +/- 0.0195 and 0.9046 +/- 0.0289, respectively. The Az value was 0.8300 +/- 0.0359 for reader 1 and 0.7600 +/- 0.0409 for reader 2. The Az values for ANN and BLR were significantly higher than those for both radiologists (all p < .05)., Conclusion: The performance of the ANN and the BLR was better than that of the radiologists in the distinction of benign and malignant thyroid nodules.

The taxonomic criterion of Antithamnion sparsum was reappraised in comparison with A. densum and A. defectum based on crossing experiments, morphological observation, chromosome study and Random Amplified Polymorphic DNA (RAPD) analysis. These species had a very similar morphology but were sexually isolated. The chromosome number was n = ca. 24 for A. densum, n = ca. 21 for A. defectum, and n = ca. 44 for A. sparsum. All isolates of A. sparsum and A. densum showed polysiphonia-type life history Asexual reproduction was induced by favorable environmental conditions. In A. sparsum, 1-2% of male plants developed mitotic tetrasporangia together with spermatangia. In A. densum, 5-10% of tetraspores developed into asexual tetrasporophytes. Phylogenetic relationships between these species were examined using RAPD analysis, and A. glanduliferum was used as an outgroup. A total of 167 polymorphic RAPD markers amplified from 15 different primers were analyzed. Results suggested that these species were closely related, with A. defectum placed in the middle of A. sparsum and A. densum. Chromosome study and RAPD analysis implied that A. sparsum first separated from A. defectum through polyploidization and later A. densum evolved. These species may present another example of the narrow species concept in the genus Antithamnion.

The association between fetal sex and outcome of pregnancy and labor has been well documented in western populations. However, no studies in Malaysia or other developing countries have examined the effect of fetal sex on such outcomes.The main objective of this study was to determine the influence of fetal sex on the outcome of labor at term in a cohort of Malaysian nulliparae.A retrospective observational study was designed using data from 4644 Malaysian nulliparae who gave birth consecutively to singleton male babies at Hospital Sultanah Aminah, Johor Bahru, after normal full-term pregnancies.The results of this study indicate that mothers giving birth to male infants have a greater risk of requiring cesarean delivery because male babies are heavier and have statistically significantly greater head circumference (P < .001). These findings concur with those obtained in western populations and suggest that the differences in outcome observed are biological, not dictated by race, ethnicity, or environmental conditions. Such information could help in the antenatal assessment of Malaysian patients and stimulate more comprehensive studies of the mechanisms involved in this sex-based difference in outcomes. Reasons for such differences are proposed.

Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Glucocorticoids, on the other hand, exert immunosuppressive and anti-inflammatory actions. We have previously reported that interleukin (IL)-1beta induces HBD-2 mRNA expression through the activation of nuclear factor-kappaB (NF-kappaB) transcriptional factor, as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase/AKT in A549 cells. In this study, we further investigated whether dexamethasone (Dex) controls IL-1beta-induced HBD-2 mRNA expression in A549 cells and the molecular mechanism associated with it. Dex suppressed IL-1beta-induced HBD-2 mRNA expression, which is mediated by a glucocorticoid receptor, at the transcriptional level. Interestingly, Dex attenuated IL-1beta-mediated activation of p38 MAPK and JNK, but not of AKT. Dex increased the expression of MAPK phosphatase (MKP)-1, which dephosphorylated p38 MAPK, but not JNK, by IL-1beta. However, although Dex did not inhibit the nuclear translocation of p65 NF-kappaB in response to IL-1beta, it profoundly inhibited NF-kappaB promoter- and HBD-2 promoter-driven luciferase activities. These results suggest that Dex acts to inhibit IL-1beta-induced HBD-2 mRNA expression through blockage of the nuclear transcriptional activation of p65 NF-kappaB as well as through inactivation of p38 MAPK and JNK. Specifically, Dex-induced MKP-1 expression is responsible for the inactivation of p38 MAPK, but not JNK, in response to IL-1beta in A549 cells.

Objective: The aim of this prospective study was to investigate the effect of different volumes of contrast material on vascular enhancement in 16-channel multi-detector row computed tomographic angiography of the brain., Methods: A total of 194 patients were divided into 3 groups who received different volumes of contrast material: 100 (n = 62), 80 (n = 72), and 60 mL (n = 60). The attenuation values were measured on transverse images at 12 different intracranial vessels (right and left internal carotid arteries, A2s, M2s, and P2s, basilar artery, vein of Galen, superior sagittal sinus, and dominant sigmoid sinus). The image quality parameters (intra-arterial contrast, arterial delineation, venous contamination, and confidence in diagnosis) were graded by 2 observers in consensus using a 5-point scale., Results: The attenuation values at the left A2 segment, superior sagittal sinus, and sigmoid sinus were significantly lower in the 60-mL group than those in other groups, whereas no significant differences were found between the 3 groups for the remaining intracranial vessels. For qualitative evaluation, arterial delineation was rated higher in the 100- and 80-mL groups, whereas less venous contamination was found in the 60-mL group. There was no significant difference in overall image quality (the sum of the scores for 4 image quality parameters) between the 3 groups., Conclusions: A contrast material volume of 60 mL (18 g iodine) provides excellent image quality of cerebral multi-detector row computed tomographic angiography comparable to those achievable with 100 and 80 mL.

Hypoxia is a state of deficiency of available oxygen in the blood and tissues, and it occurs during several pathophysiological processes, including tumorigenesis. Under hypoxia, hypoxia-inducible factor-1 (HIF-1) plays an essential role in cellular oxygen homeostasis. In the present article protein kinase C-delta (PKC-delta) is activated by hypoxia, increases the protein stability and transcriptional activity of HIF-1alpha in human cervical adenocarcinoma cells. Moreover, the knockdown of PKC-delta inhibited vascular endothelial growth factor expression and angiogenic activity under hypoxia. These effects were completely reversed by PKC-delta overexpression following the knockdown of PKC-delta. Collectively, these findings demonstrate the role of PKC-delta as a new regulator of hypoxia-induced angiogenesis.

The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity. We have previously demonstrated that IL-1beta induced HBD-2 mRNA expression in A549 cells through activation of nuclear factor-kappaB (NF-kappaB) transcriptional factor as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase (PI3K). In this study, we investigated effects of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells. Triptolide inhibited IL-1beta-induced HBD-2 mRNA expression in a dose-dependent manner. Addition of triptolide did not suppress activation of p38 MAPK, JNK, or PI3K in response to IL-1beta. Triptolide inhibited IL-1beta-induced MAPK phosphatase-1 expression at the transcriptional level and resulted in sustained phosphorylation of JNK or p38 MAPK, explaining the little effect of triptolide on IL-1beta-induced phosphorylation of these kinases. Although triptolide partially suppressed IL-1beta-mediated degradation of IkappaB-alpha and nuclear translocation of p65 NF-kappaB, triptolide potently inhibited NF-kappaB promoter-driven luciferase activity in A549 cells. These results collectively suggest that the inhibitory effect of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells seems to be at least in part mediated through nuclear inhibition of NF-kappaB transcriptional activity, but not inhibition of p38 MAPK, JNK, or PI3K. This inhibition may explain the ability of triptolide to diminish innate immune response.

Although percutaneous vertebroplasty is a simple and generally safe method for the management of vertebral compression fractures, cement leakage outside the vertebral body is a potential source of serious complications. We report a patient who presented with dyspnea and edema five years after percutaneous vertebroplasty and underwent open-heart surgery. This case demonstrates an intraatrial thrombus and pulmonary thromboembolism caused by venous leakage of polymethylmethacrylate as a late complication of the procedure.

Variable lymphocyte receptors (VLRs) are recently discovered leucine-rich repeat (LRR) family proteins that mediate adaptive immune responses in jawless fish. Phylogenetically it is the oldest adaptive immune receptor and the first one with a non-immunoglobulin fold. We present the crystal structures of one VLR-A and two VLR-B clones from the inshore hagfish. The hagfish VLRs have the characteristic horseshoe-shaped structure of LRR family proteins. The backbone structures of their LRR modules are highly homologous, and the sequence variation is concentrated on the concave surface of the protein. The conservation of key residues suggests that our structures are likely to represent the LRR structures of the entire repertoire of jawless fish VLRs. The analysis of sequence variability, prediction of protein interaction surfaces, amino acid composition analysis, and structural comparison with other LRR proteins suggest that the hypervariable concave surface is the most probable antigen binding site of the VLR.

Background and Purpose: The aim of our study was to compare multidetector row CT angiography (MDCTA) with digital subtraction angiography (DSA) in the detection and characterization of intracranial aneurysms., Materials and Methods: In our blinded prospective study, 85 patients with suspected intracranial aneurysm (47 women, 38 men; age range, 19-83 years) underwent both 16-channel MDCTA and DSA. The MDCT angiograms were interpreted for the presence, location, size, ratio of the neck to the dome (N/D ratio), and lobularity of the aneurysms and relationship of the aneurysm with the adjacent arterial branches, by using volume-rendering techniques. MDCTA and DSA images (reference standard) were interpreted by 2 independent readers, and the results were compared., Results: A total of 93 aneurysms were detected at DSA in 71 patients, whereas no aneurysms were detected in 14 patients. Compared with DSA, the overall sensitivity, specificity, and accuracy of MDCTA on a per-aneurysm basis were 92.5%, 93.3%, and 92.6%, respectively, for both independent readers. For aneurysms of <3 mm, however, MDCTA had a sensitivity of 74.1% for reader 1 and 77.8% for reader 2. There was excellent agreement between readers in the detection of aneurysms (kappa = 0.822). In addition, MDCTA was also accurate in determining N/D ratio of aneurysms, aneurysm lobularity, and adjacent arterial branches., Conclusion: MDCTA is accurate in the detection and characterization of intracranial aneurysms and can be used as a reliable alternative imaging technique to DSA in selected cases.

Purpose: The purpose of this study was to evaluate the injury and recovery of the inferior alveolar nerve in orthognathic patients at 1 and 4 weeks after surgery using electronic thermography., Materials and Methods: Twenty subjects with Class III dentofacial deformity were studied. All patients underwent bilateral sagittal split ramus osteotomy. To image the temperature of the face, 1 anteroposterior view and 1 lateral view were taken from both the right and left sides. Similar images were taken at 1 and 4 weeks after surgery. The control was the presurgical temperature of the 20 patients who showed unilateral or bilateral nerve damage after surgery., Results: In the patients with unilateral nerve damage (n = 14), on the anteroposterior views, the temperatures of the mentum on the 2 sides differed by 0.64 degrees C at 1 week after surgery, and the difference decreased to 0.23 degrees C at 4 weeks after surgery. On the lateral images, the differences in temperature between the mentum areas were 0.10 degrees C at 1 week and 0.27 degrees C at 4 weeks after surgery. In the patients with bilateral nerve injury (n = 6), on the anteroposterior views, the temperatures of the mentum on the 2 sides differed by 0.20 degrees C at 1 week after surgery and 0.13 degrees C after 4 weeks. On the lateral views, the differences were 0.18 degrees C at 1 week and 0.34 degrees C at 4 weeks after surgery. Using the repeated measurement analysis method, the anteroposterior view showed statistically significant results in the patients with unilateral nerve damage., Conclusion: The infrared body temperature method is an objective method that can be applied as a supplemental diagnostic method for inferior alveolar nerve injury.

To elucidate the oncogenic H-Ras network, we have established various stable and inducible oncogenic H-Ras-expressing NIH/3T3 mouse embryonic fibroblast cell clones, which express G12V H-Ras and G12R H-Ras proteins under the influence of a strong cytomegalovirus promoter and under the tight control of expression by an antibiotic, doxycycline, respectively. Here we provide a catalogue of proteome profiles in total cell lysates derived from oncogenic H-Ras-expressing NIH/3T3 cells. In this biological context, we compared total proteome changes by the combined methods of 2-DE, quantitative image analysis and MALDI-TOF MS analysis using both a stable expression system as well as an inducible expression system. There were a large number of common targets for oncogenic H-Ras, which were identified in both cell lines and consisted of 64 proteins (36 up-regulated and 28 down-regulated). Differentially regulated expression was further confirmed for some subsets of candidates by Western blot analysis using specific antibodies. Taken together, the results presented here show that comparative analysis of the proteome from the oncogenic H-Ras-expressing cells yielded interpretable data to elucidate protein networks directly and/or indirectly.

Urbanization can result in alteration of a watershed's hydrologic response and water quality. To simulate hydrologic and water quality impacts of land use changes, the Long-Term Hydrologic Impact Assessment (L-THIA) system has been used. The L-THIA system estimates pollutant loading based on direct runoff quantity and land use based pollutant coefficients. The accurate estimation of direct runoff is important in assessing water quality impacts of land use changes. An automated program was developed to calibrate the L-THIA model using the millions of curve number (CN) combinations associated with land uses and hydrologic soil groups. L-THIA calibration for the Little Eagle Creek (LEC) watershed near Indianapolis, Indiana was performed using land use data for 1991 and daily rainfall data for six months of 1991 (January 1-June 30) to minimize errors associated with use of different temporal land use data and rainfall data. For the calibration period, the Nash-Sutcliffe coefficient was 0.60 for estimated and observed direct runoff. The calibrated CN values were used for validation of the model for the same year (July 1-December 31), and the Nash-Sutcliffe coefficient was 0.60 for estimated and observed direct runoff. The Nash-Sutcliffe coefficient was 0.52 for January 1, 1991 to December 31, 1991 using uncalibrated CN values. As shown in this study, the use of better input parameters for the L-THIA model can improve accuracy. The effects on direct runoff and pollutant estimation of the calibrated CN values in the L-THIA model were investigated for the LEC. Following calibration, the estimated average annual direct runoff for the LEC watershed increased by 34%, total nitrogen by 24%, total phosphorus by 22%, and total lead by 43%. This study demonstrates that the L-THIA model should be calibrated and validated prior to application in a particular watershed to more accurately assess the effects of land use changes on hydrology and water quality.

Tetramethrin, a synthetic pyrethroid insecticide, is used globally for agriculture, and thus potential environmental exposure to tetramethrin is a concern. Environmental chemicals that are hormonally active (particularly estrogen or androgen) may adversely affect the reproductive and endocrine systems. However, little is known about the estrogenic and androgenic activities of tetramethrin. In this study, uterine CaBP-9k gene expression assay and a uterotrophic assay were conducted for estrogenic activity assessment of tetramethrin, and a Hershberger assay was conducted for androgenic activity. Estrogen receptor (ERalpha and ERbeta) protein levels were also measured in tetramethrin-treated rat uteri. Northern blot analysis showed reduction in uterine CaBP-9k mRNA levels in response to tetramethrin, as well as when rats were given both tetramethrin and 17beta-estradiol (E2). In the uterotrophic assay using 18-d-old female Sprague-Dawley rats, subcutaneous treatment with tetramethrin (5 to 800 mg/kg/day) for 3 d led to a statistically significant decrease in absolute and relative uterine wet weights at all doses tested. Moreover, tetramethrin blocked the effect of E2 on uterine weights. In addition, tetramethrin reduced absolute and relative vaginal wet weights, and also inhibited the increases of vaginal weights produced by E2. Tetramethrin showed no androgenic on antiandrogenic activities in the Hershberger assay. These results suggest that tetramethrin might exert endocrine-disrupting effects on female rats through antiestrogenic action.

Urban expansion is a major driving force altering local and regional hydrology and increasing non-point source (NPS) pollution. To explore these environmental consequences of urbanization, land use change was forecast, and long-term runoff and NPS pollution were assessed in the Muskegon River watershed, located on the eastern coast of Lake Michigan. A land use change model, LTM, and a web-based environmental impact model, L-THIA, were used in this study. The outcomes indicated the watershed would likely be subjected to impacts from urbanization on runoff and some types of NPS pollution. Urbanization will slightly or considerably increase runoff volume, depending on the development rate, slightly increase nutrient losses in runoff, but significantly increase losses of oil and grease and certain heavy metals in runoff. The spatial variation of urbanization and its impact were also evaluated at the subwatershed scale and showed subwatersheds along the coast of the lake and close to cities would have runoff and nitrogen impact. The results of this study have significant implications for urban planning and decision making in an effort to protect and remediate water and habitat quality of Muskegon Lake, which is one of Lake Michigan's Areas of Concern (AOC), and the techniques described here can be used in other areas.

Many environmental chemicals including pesticides have been reported to possess hormonal activities, and thus are classified as endocrine disruptors. Permethrin, a synthetic pyrethroid insecticide, is used worldwide, which provides potential environmental exposure. However, relatively few studies have reported on hormonal activities, particularly estrogenic and androgenic activities of permethrin, and the results of these studies are in some respects contradictory. Therefore, this study investigated the potential estrogenic and androgenic activities of permethrin in vitro and in vivo. We conducted an uterine Calbindin-D9k (CaBP-9k) gene expression assay and an uterotrophic assay for estrogenic activity, and a Hershberger assay for androgenic activity. The CaBP-9k gene, one of the intracellular calcium binding proteins, is estrogen-responsive in the uterus. The rat uterotrophic and Hershberger assays are generally used as in vivo short-term screening assays for detecting the estrogenic and androgenic activities of chemicals, although these assays are still being validated by the Organization for Economic Cooperation and Development (OECD). Northern blot analysis showed the induction of uterine CaBP-9k mRNA level in response to permethrin as well as co-administration of permethrin with E2. In the uterotrophic assay using 18-day-old female rats, subcutaneous treatments with permethrin (10 to 800 mg/kg) for three days increased relative uterine wet weights, and E2-induced uterine weights. These effects were statistically significant at 800 and 200 mg/kg, respectively. Moreover, permethrin-induced uterine weights were inhibited by the co-administration of ICI 182,780, an antiestrogen. In the Hershberger assay, the administration of permethrin orally to testosterone propionate-treated castrated male rats led to statistically significant reductions in androgen-dependent sex accessory tissue (ventral prostate, seminal vesicles, levator ani and bulbocavernosus muscles, Cowper's gland and glans penis) weights at all doses tested (10, 50 and 100 mg/kg). These results suggest that permethrin might have estrogen-like effects on female rats, but antiandrogen-like effects on males.

3-Monochloro-1,2-propanediol (3-MCPD) is a food contaminant that is often found in foods containing acid-hydrolyzed (AH) protein, like seasonings and savory food products. The purpose of the present study was to investigate the effects of 3-MCPD on male fertility, sperm, and hormonal levels and its antifertility mechanism. In vivo male fertility testing was performed to observe the adverse effects of 3-MCPD on the functioning of the male reproductive system and pregnancy outcome. 3-MCPD (0.01-5 mg/kg) was administered daily by gavage to Sprague-Dawley (SD) male rats for 4 wk. At the end of the pretreatment period, male rats were mated overnight with untreated females. Males successfully inducing pregnancy were sacrificed to assess sperm parameters, reproductive organ histopathology, and spermatogenesis. The resulting pregnant females were sacrificed on 20 of gestation to evaluate pregnancy outcome. The paternal administration of 3-MCPD (5 mg/kg) was found to result in adverse effects on male fertility and pregnancy outcome without inducing remarkable histopathological changes in testes and epididymides. Additionally, 3-MCPD (5 mg/kg) significantly reduced sperm motility, copulation, fertility indices, and the number of live fetuses showed steep dose-response curves. 3-MCPD did not affect spermatogenesis or induce hormonal changes in the blood and testes of male rats. An in vitro hormone assay using primary isolated Leydig cells showed no significant changes in related hormone levels after 3-MCPD treatment. To evaluate the effects of 3-MCPD on apoptotic induction and H+-ATPase levels in the testis and epididymis, 10 or 100 mg/kg of 3-MCPD was administered by gavage to male rats and testes and epididymides were examined at 3, 6, 12, and 24 h later. Apoptosis was not detected in the testes of animals treated with 100 mg/kg 3-MCPD. However, the level of H+-ATPase in the cauda epididymis was reduced by 3-MCPD treatment. These results indicate that 3-MCPD induced a spermatotoxic effect, which was mediated by reduced H+-ATPase expression in the cauda epididymis, and suggest that an altered pH level in the cauda epididymis might lead to a disruption of sperm maturation and the acquisition of motility.

Induction of human beta-defensin 2 (HBD-2) by interleukin-1beta (IL-1beta) in epithelial cells has been reported. However, the mechanism by which IL-1beta up-regulates HBD-2 remains poorly understood. In this study, we investigated the effect of IL-1beta on induction of HBD-2 in A549 cells. IL-1beta markedly increased HBD-2 mRNA expression in concentration- and time-dependent manners. HBD-2 mRNA expression in response to IL-1beta was attenuated by pretreatment of GF109203X, Go6976, and staurosporine [inhibitors of protein kinase C (PKC)], SB203580 [an inhibitor of p38 mitogen-activated protein kinase (MAPK)], SP600125 [an inhibitor of c-Jun N-terminal kinase (JNK)], and LY294002 [an inhibitor of phosphatidylinositol-3-kinase (PI3K)], but not PD98059 [an inhibitor of extracellular signal-regulated kinase (ERK)], suggesting involvement of PKC, p38 MAPK, JNK, and PI3K in this response. Interestingly, IL-1beta induced nuclear factor-kappaB (NF-kappaB) activation in A549 cells, which was shown by increased nuclear translocation of p65 NF-kappaB and degradation of IkappaB-alpha. Importantly, IL-1beta-induced HBD-2 mRNA expression was inhibited by blockage of NF-kappaB activation using NF-kappaB inhibitors, including pyrrolidine dithiocarbamate and MG132. Specifically, IL-1beta-induced nuclear translocation of NF-kappaB was in part attenuated by LY294002, but not by GF109203X, SB203580, and SP600125, suggesting PI3K-dependent nuclear translocation of NF-kappaB in response to IL-1beta. Together, these results suggest that IL-1beta induces HBD-2 mRNA expression in A549 cells, and the induction seems to be at least in part mediated through activation of NF-kappaB transcription factor as well as activation of signaling proteins of PKC, p38 MAPK, JNK, and PI3K, but not ERK.

Tetrandrine, which is isolated from Chinese herb Stephania tetrandrae, possesses anti-inflammatory, immunosuppressive, and cytoprotective properties. Though it was previously shown that tetrandrine causes a G1 blockade and apoptosis in various cell types, however, the mechanism by which tetrandrine initiates apoptosis remains poorly understood. In present study, we investigated the mechanisms of apoptosis induced by tetrandrine in U937 leukemia cells. Tetrandrine inhibited U937 cell growth by inducing apoptosis. After treatment of U937 cells with tetrandrine (10microM) for 24h, alteration of cell morphology, chromatin fragmentation, cytochrome c release, and caspase activation were observed. Tetrandrine also induced early oxidative stress, which resulted in activation of JNK, but not ERK and p38 MAPK. A broad-spectrum caspase inhibitor and antioxidants significantly blocked tetrandrine-induced caspase-3 activation. However, inhibition of the JNK activity with SP600125 did not block tetrandrine-induced apoptosis. Tetrandrine-induced apoptosis of U937 cells also required activity of PKC-delta, because pretreatment with a specific PKC-delta inhibitor greatly blocked tetrandrine-induced caspase-3 activation. In addition, the apoptotic response to tetrandrine was significantly attenuated in dominant-negative PKC-delta transfected MCF-7 cells, suggesting that PKC-delta plays an important role in tetrandrine-induced apoptosis and can induce caspase activation. These results suggest that tetrandrine induces oxidative stress, JNK activation, and caspase activation. However, JNK activation by ROS is not involved in the tetrandrine-induced apoptosis. In addition, tetrandrine induces caspase-dependent generation of a catalytically active fragment of PKC-delta, and this fragment also appears to play a role in the activation of caspases.