OBJECTIVETo explore the characteristic of the signal transduction in BEAS cells induced by the crocidolite fibers.

METHODSThe human respiratory airway epithelial cells BEAS-2B were cultured in vitro. The final 100 microg/ml crocidolite concentration and lOnM of epidermal growth factor were cocultured with BEAS-2B cells for 30 minutes and 120 minutes. Phosphorylated ERKl/2 and MEKl/2 were detected by Western Blotting using specific antibodies.

RESULTSA rapid phosphorylation expression of ERK1/2 (molecular weight at 44 kD and 42 kD, also called as p44 and p42) was observed by treatment of the BEAS-2B cells with 100 microg/ml crocidolite or 100 ng/ml EGF (the proven activator of the ERK signaling pathway) at 30 minutes. This phosphorylation could be still detected by incubation the cells at 2 hours. However no expression was changed for the total ERKl/2 expression at 30 minutes or 120 minutes. Treatment of BEAS cells with 100 microg/ml crocidolite fiber or 100 ng/ml EGF led to the rapid increased phosphorylation of MEK1/2 at 30 minutes; similarly, the overexpression of MEK1/2 could last 2 hours.

CONCLUSIONThe crocidolite induces the MAPK (ERK1/2 and MEK1/2) phosphorylation within a shorter time. It indicates that the MAPKs signals are involved in the process of crocidolite induced damage.

Asbestos, Crocidolite ; toxicity ; Bronchi ; cytology ; Cells, Cultured ; Epidermal Growth Factor ; pharmacology ; Epithelial Cells ; drug effects ; metabolism ; Humans ; MAP Kinase Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphorylation

Percutaneous endoscopic gastrostomy (PEG) is commonly performed for feeding difficulties, in patients suffering from complications of nasopharyngeal carcinoma and its treatment, namely radiotherapy and surgery. This case report describes the challenges in hemostasis and subsequent re-establishment of enteral access for feeding, in an elderly patient with a history of NPC, treated surgically, followed by radiotherapy, who presented with massive hematemesis following reinsertion of her PEG shortly after an accidental dislodgement. Her previous nasopharyngectomy, wide field radiation therapy, and radical neck dissection precluded nasogastric tube feeding, and the presence of a large hiatus hernia made reinsertion of a new PEG technically challenging. This case highlights the methods used to overcome the above challenges.
Aged ; Enteral Nutrition ; Esophageal Stenosis ; Gastrostomy ; Hematemesis ; Hemostasis ; Hernia, Hiatal ; Humans ; Intubation, Gastrointestinal ; Neck Dissection ; Radiotherapy ; Stomach Ulcer ; Ulcer

Purpose: The study aimed to investigate the utility of ultrasonographic (US) findings in predicting the subsequent radiographic parameters of developmental dysplasia of the hips. Methods: In this 12-year retrospective cohort study, all new-born infants with a positive clinical examination or risk factors were included. They were scheduled for hip ultrasonography in the first 3 months, and subsequent radiographs at 1 year of life. The US images were evaluated using the Graf classification, Harcke’s dynamic screening method, and Terjesen’s femoral head coverage method. The radiographic images were evaluated using the acetabular index and femoral head position. The overall US or radiographic findings were considered abnormal if they were classified as abnormal for any of their respective parameters. The overall US and radiographic parameters were correlated. Results: A total of 160 patients were included. The overall US and radiographic parameters showed no statistically significant difference (P=0.050). The sensitivity, specificity, and accuracy of the overall US parameters were 57.1%, 84.9%, and 81.3%, respectively. All three individual US parameters showed no statistically significant differences, with the overall radiographic findings and acetabular index (P>0.05). However, they showed a statistically significant difference, with the position of the femoral head (P<0.001), with the US parameters having an excellent negative predictive value of 100% for identifying an abnormal femoral head position. Conclusion The current study suggests that US findings evaluated in the first 3 months of life showed no statistically significant difference with radiographic findings evaluated at 1 year of life. The US parameters showed an excellent negative predictive value for abnormal femoral head position on radiographs.

To assess the effect of a NO-eluting stent on reducing neointimal thickening in a porcine coronary artery stent injury model, sodium nitroprusside (SNP), a NO donor, was incorporated into polyurethane (PU) polymer and coated onto metallic coil stents, and two types of stents with thin and thick barrier coatings were characterized. In vivo biological activity of the NO-eluting stents was assessed by measurement of coronary arterial cGMP levels in 32 pigs/64 arteries at days 1, 2, 7 and 14. Morphometric analyses were performed in 16 pigs to determine the effect of NO-eluting stents on neointimal hyperplasia 28 days following arterial injury. The SNP-coated stents released NO in a controlled manner for up to 4 weeks in the in vitro experiments and an increase in local tissue cGMP levels was demonstrated for up to 14 days. The neointimal area at 28 days was not diminished, however, by NO eluded from either stents of thin or thick barriers (control bare stent - 0.66 mm2, control PU stent - 0.68 mm2, SNP-PU thin coating stent - 0.78 mm2, SNP-PU thick coating stent - 0.85 mm2; all p=NS). In conclusion, the SNP-coated polymer stent exerted a local biological effect on the arterial wall, with sustained elevation of cGMP level. Although local delivery of NO from this device did not reduce neointimal hyperplasia in this porcine model, this polymer-coated stent might be a promising tool for administration of other agents that may modify the reparative tissue responses leading to restenosis.
Animal ; Coated Materials, Biocompatible ; Coronary Vessels/*injuries ; Nitric Oxide/*administration & dosage/pharmacology ; *Stents ; Swine ; Tunica Intima/*drug effects ; Wounds and Injuries/*pathology

Medical school is intrinsically stressful, and high levels of stress have untoward effects. Although surveys have revealed some sources of stress among medical students, little is known about the qualitative aspects of these stressors and their associated coping behaviours, particularly among medical students in Singapore. Our exploratory pilot study found that relationship issues and examinations were the major sources of stress for medical students. The respondents described multiple context-sensitive coping styles, as well as reported 'avoidance' or 'wishful thinking' coping strategies as ineffective. Their stress-and-coping process suggests the influence of Asian culture and medical school culture. Our findings thus indicate the need for further research, potentially using new methodologies such as the critical incident analysis technique, and thoughtful consideration of culture when implementing programmes in Singapore medical schools to improve the students' stress-and-coping responses.
Adaptation, Psychological ; Adult ; Asian Continental Ancestry Group ; Cultural Characteristics ; Female ; Humans ; Male ; Pilot Projects ; Schools, Medical ; Singapore ; Social Support ; Stress, Psychological ; psychology ; Students, Medical ; Surveys and Questionnaires ; Young Adult

Clinical Trials as Topic ; Humans ; Information Dissemination ; ethics ; methods ; International Cooperation

Methods: Patients who had T4N0M0 Pancoast tumors invading the spine and underwent a single-stage posterior approach were retrospectively recruited. The following data were obtained and examined: demographics, tumor histology, preoperative and postoperative therapy, complications, spinal reconstruction technique, tumor resection extent, survival time, and disease recurrence. Results: Eighteen patients were included. The mean population age was 61±17 years, and the most common pathological type was adenocarcinoma (61.1%). Complete resection (R0) was obtained in 15 patients (83.3%), positive surgical margins (R1) were found in three patients (16.7%), and the 90-day mortality rate was 0%. Postoperative major complications were detected in 12 patients (66.7%), who required reoperation. The mean survival time was 67±24 months, but the median survival time was not reached. Among the patients, 10 (55.6%) are still alive at the end of the study. The 2- and 5-year actual survival rates were 59% (95% confidence interval [CI], 35.7%–82.3%) and 52.5% (95% CI, 28.4%–76.6%), respectively. Conclusions En bloc resection and spinal stabilization through a single-stage posterior approach might be effective for T4 Pancoast tumors invading the spine.

Traumatic brain injury (TBI) causes disability and death, accelerating the progression towards Alzheimer’s disease and Parkinson’s disease (PD). TBI causes serious motor and cognitive impairments, as seen in PD that arise during the period of the initial insult. However, this has been understudied relative to TBI induced neuroinflammation, motor and cognitive decline that progress towards PD. Neuronal ubiquitin-C-terminal hydrolase- L1 (UCHL1) is a thiol protease that breaks down ubiquitinated proteins and its level represents the severity of TBI. Previously, we demonstrated the molecular action of glia maturation factor (GMF); a proinflammatory protein in mediating neuroinflammation and neuronal loss. Here, we show that the weight drop method induced TBI neuropathology using behavioral tests, western blotting, and immunofluorescence techniques on sections from wild type (WT) and GMF-deficient (GMF-KO) mice. Results reveal a significant improvement in substantia nigral tyrosine hydroxylase and dopamine transporter expression with motor behavioral performance in GMF-KO mice following TBI. In addition, a significant reduction in neuroinflammation was manifested, as shown by activation of nuclear factor-kB, reduced levels of inducible nitric oxide synthase, and cyclooxygenase- 2 expressions. Likewise, neurotrophins including brain-derived neurotrophic factor and glial-derived neurotrophic factor were significantly improved in GMF-KO mice than WT 72 h post-TBI. Consistently, we found that TBI enhances GFAP and UCHL-1 expression and reduces the number of dopaminergic TH-positive neurons in WT compared to GMF-KO mice 72 h post-TBI. Interestingly, we observed a reduction of THpositive tanycytes in the median eminence of WT than GMF-KO mice. Overall, we found that absence of GMF significantly reversed these neuropathological events and improved behavioral outcome. This study provides evidence that PD-associated pathology progression can be initiated upon induction of TBI.

OBJECTIVETo observe the effect of combining red yeast rice and Lactobacillus casei (L. casei) in lowering cholesterol in patients with primary hyperlipidemia, the later has also been shown to remove cholesterol in in vitro studies.

METHODSA double-blind clinical trial was conducted to evaluate the cholesterol-lowering effect of the combination of red yeast rice and L. casei. Sixty patients with primary hyperlipidemia were recruited and randomized equally to either the treatment group (red yeast rice + L. casei) or the control group (red yeast rice + placebo). One red yeast rice capsule and two L. casei capsules were taken twice a day. The treatment lasted for 8 weeks, with an extended follow-up period of 4 weeks. The primary endpoint was a difference of serum low-density lipoprotein cholesterol (LDL-C) level at week 8.

RESULTSAt week 8, the LDL-C serum level in both groups was lower than that at baseline, with a decrease of 33.85±26.66 mg/dL in the treatment group and 38.11±30.90 mg/dL in the control group; however, there was no statistical difference between the two groups (P>0.05). The total cholesterol was also lower than the baseline in both groups, yet without a statistical difference between the two groups. The only statistically signifificant difference between the two groups was the average diastolic pressure at week 12, which dropped by 2.67 mm Hg in the treatment group and increased by 4.43 mm Hg in the placebo group (P<0.05). The antihypertensive activity may be associated with L. casei. Red yeast rice can signifificantly reduce LDL-C, total cholesterol and triglyceride.

CONCLUSIONThe combination of red yeast rice and L. casei did not have an additional effect on lipid profifiles.