Anion-induced morphological regulation of cupric oxide nanostructures and their application as co-catalysts for solar water splitting.

Morphological control of nanomaterials is essential for their properties and potential applications, and many strategies have been developed. In this work, a new strategy for simultaneously preparing and modulating the morphological structure evolution of copper layered hydroxyl salts and oxides is introduced. By changing the nature of the anions in the electroplating solution, significant variations in the size and porosity of nanosheets are achieved. Porous CuO nanosheets with a higher surface area were obtained by the use of copper nitrate as a copper source, while CuO nanoflakes were produced from copper sulfate. Photoanodes combining these porous CuO nanomaterials and a typical light absorber (BiVO4) exhibited good morphology-dependent activities for photoelectrochemical water splitting. The composite electrode displays a negative shift of 180 mV for the onset potential and an approximately 2-fold enhancement in the photocurrent compared to the bare BiVO4. The charge recombination rate in the photoelectrode with the porous CuO nanosheets was significantly lower than the bare photoanode due to the favorable electron diffusion path and effective charge collection. This research offers an effective method for constructing a highly active photoelectrocatalytic system for overall water splitting.

Plasma Deposition and UV Light Induced Surface Grafting Polymerization of NIPAAm on Stainless Steel for Enhancing Corrosion Resistance and Its Drug Delivery Property.

When stainless steel is implanted in human bodies, the corrosion resistance and biocompatibility must be considered. In this study, first, a protective organic silicone film was coated on the surface of stainless steel by a plasma deposition technique with a precursor of hexamethyldisilazane (HMDSZ). Then, ultraviolet (UV) light-induced graft polymerization of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) in different molar ratios were applied onto the organic silicone film in order to immobilize thermos-/pH-sensitive composite hydrogels on the surface. The thermo-/pH-sensitive composite hydrogels were tested at pH values of 4, 7.4 and 10 of a phosphate buffer saline (PBS) solution at a fixed temperature of 37 °C to observe the swelling ratio and drug delivery properties of caffeine which served as a drug delivery substance. According to the results of Fourier Transformation Infrared (FTIR) spectra and a potential polarization dynamic test, the silicone thin film formed by plasma deposition not only improved the adhesion ability between the substrate and hydrogels but also exhibited a high corrosion resistance. Furthermore, the composite hydrogels have an excellent release ratio of up to 90% of the absorbed amount after 8h at a pH of 10. In addition, the results of potential polarization dynamic tests showed that the corrosion resistance of stainless steel could be improved by the HMDSZ plasma deposition.

The risk of cataract associated with repeated head and neck CT studies: a nationwide population-based study.

OBJECTIVE: Medical radiation-induced cataracts, especially those resulting from head and neck CT studies, are an issue of concern. The current study aimed to determine the risk of cataract associated with repeated radiation exposure from head and neck CT. MATERIALS AND METHODS: This study used information from a random sample of 2 million persons enrolled in the nationally representative Taiwan National Health Insurance Research Database. Exposed cases consisted of patients with head and neck tumor 10-50 years old who underwent at least one CT between 2000 and 2009. The nonexposed control group was composed of subjects who were never exposed to CT studies but who were matched by time of enrollment, age, sex, history of coronary artery disease, hypertension, and diabetes. RESULTS: There were 2776 patients in the exposed group and 27,761 matched subjects in the nonexposed group. The exposed group had higher overall incidence of cataracts (0.97% vs 0.72%; adjusted hazard ratio [HR], 1.76; 95% CI, 1.18-2.63). Further stratifying the number of CT studies in the exposed group into one or two, three or four, and five or more revealed that cataract incidence increased gradually with increasing frequency of CT studies (0.79%, 0.93%, and 1.45%, respectively) (p=0.001, adjusted for trend). Radiation exposure due to repeated head and neck CT studies was independently associated with an increased risk of developing cataracts when the cumulative CT exposure frequency involved more than four studies (adjusted HR, 2.12; 95% CI, 1.09-4.14). CONCLUSION: Repeated exposure to head and neck CT is significantly associated with increased risk of cataract.

Risk factors in patients with AFB smear-positive sputum who receive inappropriate antituberculous treatment.

BACKGROUND: Acid-fast bacilli (AFB) smear-positive sputum is usually an initial clue in the diagnosis of pulmonary tuberculosis (TB); however, the test is not disease-specific. Nontuberculous mycobacterium-related colonization or lung disease often has AFB smear-positive sputum results, and physicians may prescribe unnecessary antituberculous drugs for these patients. The aim of this study was to analyze the clinical characteristics of patients with AFB smear-positive sputum who received unnecessary anti-TB treatment. METHODS AND PATIENTS: From January 2008 to July 2011, we retrospectively enrolled 97 patients with AFB smear-positive sputum who did not have pulmonary TB according to mycobacterial cultures and clinical judgment. We analyzed the clinical and radiographic features of the patients who received inappropriate and unnecessary anti-TB treatment. Preliminary analyses of chisquare and Fisher's exact tests were applied to determine factors unlikely to be associated with the independent variables. The relationship between independent covariates was then analyzed using multivariate logistic regression. RESULTS: Of the 97 enrolled patients, 25 (25.8%) were diagnosed with pulmonary TB and prescribed anti-TB drugs (mostly a combination of isoniazid, rifampicin, ethambutol, and pyrazinamide). The other 72 (74.2%) patients were not initially diagnosed with pulmonary TB and were classified as the control group. Compared to the control group, the patients who received inappropriate anti-TB treatment had more chronic cough as presentation symptom and heavy AFB Ziehl-Neelsen staining in sputum (>10/100 fields, grading 2+ to 4+). There were no significant differences in the radiographic analysis between the two groups. CONCLUSION: Among the patients with AFB smear-positive sputum that did not have pulmonary TB, chronic cough and heavy AFB staining (2+ to 4+) were risk factors for the inappropriate administration of unnecessary anti-TB treatment.

Bacterial pneumonia following acute ischemic stroke.

BACKGROUND: The most common serious complication following acute ischemic stroke is pneumonia, which may increase mortality and worsen clinical outcomes. The purpose of this study was to investigate the predictors of 30-day mortality in patients with pneumonia following acute ischemic stroke. METHODS: From June 2006 to May 2011, we retrospectively included 51 patients with pneumonia following acute ischemic stroke. We analyzed the clinical features, microbiologic data, and outcomes. Predictors of 30-day mortality were investigated by univariate and multivariate analysis. RESULTS: The acute ischemic strokes were caused by large-artery atherosclerosis in 37 (72.5%) of the 51 patients. We found that the most common pathogen responsible for poststroke pneumonia was Klebsiella pneumoniae, followed by Pseudomonas aeruginosa and Escherichia coli. Ultimately, 12 patients died of progressive sepsis due to pneumonia after the acute ischemic stroke. The 30-day mortality rate was 23.5%. In the univariate analysis, patients who died within 30 days had higher National Institutes of Health Stroke Scale scores, higher CURB-65 scores, elevated instability of hemodynamic status, and lower Glasgow Coma Scale (GCS) scores. In Cox regression analysis, a GCS score of <9 on the day of pneumonia onset was only significant indicator for 30-day mortality (hazard ratio, 6.72; 95% confidence interval, 2.12-21.30, p = 0.001). CONCLUSION: Pneumonia after acute ischemic stroke is a severe complication. Once stroke-related pneumonia develops, neurologic assessment, CURB-65 score, and shock can be used to predict the ultimate prognosis.

The value of positron emission tomography in early detection of lung cancer in high-risk population: a systematic review.

BACKGROUND: Early detection trials with chest radiography and sputum cytology were ineffective in decreasing lung cancer mortality. The advent of low-dose spiral chest computed tomography (LDCT) provided clinicians with a new tool that could be with early diagnosis; however, this also raised significant concerns regarding the systematic use of LDCT with its high false-positive rate for benign nodules. At this time, there is limited information about the true role of PET (positron emission tomography) for early detection of lung cancer. METHODS: We used systematic methods, including Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, to identify relevant studies, assess study eligibility, evaluate study methodological quality, and summarize findings regarding diagnostic accuracy and outcome. RESULTS: In total, only seven eligible studies were selected from 82 potentially relevant studies. The sensitivity of 18F-FDG-PET for the detection of T1 lung cancers ranged between 68% and 95%. The rate of detection tended to be lower for carcinoid tumors, adenocarcinoma and bronchoalveolar cell carcinomas. FDG-PET using SUV (standardized uptake value) level can predict the outcome of the screening detected lung cancer. A combination of FDG-PET and LDCT may improve screening for lung cancer in high-risk patients. CONCLUSIONS: PET or PET/CT may be used as a useful tool for early detection of lung cancer in high-risk population based on the existing information. However, there is still limited information with regards to evidence of survival benefits from PET screening in high-risk patients.

Gefitinib-related interstitial lung disease in Taiwanese patients with non-small-cell lung cancer.

BACKGROUND: Gefitinib (Iressa; AstreZeneca, Wilmington, DE) is effective in the treatment of NSCLC, especially in the Asian population. However, ILD is usually a serious pulmonary adverse effect and almost leads to cessation of gefitinib treatment. In this study, we investigated the incidence, clinical features, and prognosis of gefitinib-related ILD in Taiwanese patients with NSCLC. PATIENTS AND METHODS: This was a retrospective observational study conducted in 2 medical centers and a local teaching hospital. RESULTS: A total of 1080 patients with NSCLC, who received at least 1 dose (250 mg per day) of gefitinib treatment, were enrolled. Of these, 42 patients were diagnosed with ILD. Twenty-five of the 42 patients were diagnosed with gefitinib-related ILD (incidence, 2.3%). The main manifestations of ILD included dyspnea, cough, and hypoxemia. Six of the 25 patients (24%) with gefitinib-related ILD required invasive mechanical ventilation and all patients were treated with steroids. Twenty-two patients (88%) discontinued gefitinib treatment without further rechallenge. Ten (40%) patients died directly from ILD and in-hospital mortality was 52%. Eleven patients received subsequent cytotoxic chemotherapy with a mean of 33.5 days after ILD events. Kaplan-Meier analysis demonstrated that gefitinib nonresponder and gefitinib use rather than first-line treatment were associated with poor prognosis when ILD developed during gefitinib treatment. CONCLUSION: Taiwanese patients with NSCLC had a relatively high incidence of ILD during gefitinib treatment. Gefitinib-related ILD is usually life-threatening, especially in gefitinib nonresponders and gefitinib use rather than first-line treatment.

Association between uremic toxins and depression in patients with chronic kidney disease undergoing maintenance hemodialysis.

OBJECTIVE: Patients with chronic kidney disease (CKD) who are undergoing maintenance hemodialysis have a higher prevalence of depression than the general population. The underlying cause of this association is unknown, but may be related to accumulation of uremic toxins. Little is known about the association of accumulation of uremic toxins and depression in hemodialysis patients. METHOD: We conducted a cross-sectional study of 209 CKD patients from a single institution to evaluate the associations of a soluble small uremic toxin (urea), a soluble large uremic toxin (ß2 microglobulin) and two protein-bound uremic toxins [total p-cresol sulfate (PCS) and indoxyl sulfate (IS)] with the presence of depression. RESULTS: A total of 47 patients (22.4%) had depression. Depressive patients had lower body mass index, lower serum creatinine, lower serum albumin and lower total IS. Univariate and multivariate logistic regression analyses that adjusted for age, gender and other statistically significant variables indicated that depression was significantly and independently associated with lower serum albumin and lower total IS. The levels of urea, ß2 microglobulin and PCS were not significantly associated with depression. CONCLUSION: Our results indicate that depression in patients with CKD was significantly and independently associated with lower serum albumin and lower total IS. However, the pathological mechanisms underlying these associations are unknown.

Association between cold dialysis and cardiovascular survival in hemodialysis patients.

BACKGROUND: Higher cardiovascular mortality has been noted in patients with chronic kidney disease (CKD). CKD patients are also known to have impaired energy expenditure but the role of energy expenditure in cardiovascular disease is not yet known. Furthermore, the association between cold dialysis (CD) and clinical outcomes in hemodialysis patients is unclear. METHODS: This was a single-center retrospective cohort study consisting of two groups: a CD group with dialyzate temperature <35.5 °C and a standard dialysis (SD) group with dialyzate temperature between 35.5 and 37 °C. The end points of the study were overall mortality, cardiac mortality and non-cardiac mortality. The study analyzed the associations between dialyzate temperature and long-term survival in CD and SD groups. Propensity score analysis was used to control for intergroup baseline differences. RESULTS: Baseline characteristics of both groups were similar. Kaplan-Meier analysis showed that CD was significantly associated with a lower risk for overall mortality (P = 0.006) and cardiac mortality (P = 0.023) but not for non-cardiac mortality or infectious mortality. After multivariate Cox regression analysis, adjusting for propensity scores and other possible confounding factors, CD remained a significant beneficial factor for overall mortality (P = 0.030) and cardiac mortality (P = 0.034). CONCLUSION: Our studies show that CD is significantly and independently associated with a lower risk for overall mortality and cardiac mortality.

Health effects of medical radiation on cardiologists who perform cardiac catheterization.

BACKGROUND: We investigated the health effects of low-dose radiation on cardiologists exposed to scattered radiation while performing cardiac catheterization (CC) in a hospital setting from 2003 to 2006. METHODS: We performed a 4-year retrospective study on 2, 292 medical doctors, using claims data from all contracted hospitals of the Bureau of National Health Insurance, Taiwan. We gathered statistical data regarding radiation-related diseases using the International Classification of Diseases, 9(th) Revision, Clinical Modification record numbers of each doctor. RESULTS: Of the 2,292 doctors evaluated, 1,721 were aged 35-50 years and the remaining 571 were aged 51-65 years. There were 892 cardiologists who performed CC (experimental group), and the majority of these (733/892, 82.17%) were aged 35-50 years. There were 1,400 medical doctors who performed no CC from 2003 to 2006 (control group). A total of 988 of these belonged to the 35-50 years age group and 412 to the 51-65 years group. In the 35-50 years group, the controls had significantly more medical visits for hematological and thyroid cancer (p <0.05), skin disease (p <0.001), and acute upper respiratory tract infection (p <0.001) compared with the experimental group. In contrast, cardiologists who performed catheterization had more cataracts compared with the control group, but this difference was not significant. CONCLUSION: Doctors who did not perform CC had more visits for radiation-related diseases than those who performed catheterization. In the experimental group, cardiologists aged 35-50 years who were exposed to radiation during CC had more visits for cataracts than the control group. We recommend that radiation protection concepts be emphasized to cardiologists, and that hospital managers be obligated to upgrade angiography equipment because the newer models have less scattered radiation.

Prevalence and risk factors of noise-induced hearing loss among liquefied petroleum gas (LPG) cylinder infusion workers in Taiwan.

We assessed the exposure levels of noise, estimated prevalence, and identify risk factors of noise-induced hearing loss (NIHL) among male workers with a cross-sectional study in a liquefied petroleum gas cylinder infusion factory in Taipei City. Male in-field workers exposed to noise and administrative controls were enrolled in 2006 and 2007. Face-to-face interviews were applied for demographics, employment history, and drinking/smoking habit. We then performed the measurements on noise levels in field and administration area, and hearing thresholds on study subjects with standard apparatus and protocols. Existence of hearing loss > 25 dBHL for the average of 500 Hz, 1 kHz, and 2 kHz was accordingly determined for NIHL. The effects from noise exposure, predisposing characteristics, employment-related factors, and personal habits to NIHL were estimated by univariate and multivariate logistic regressions. A total of 75 subjects were involved in research and 56.8% of in-field workers had NIHL. Between the in-field and administration groups, hearing thresholds on the worse ear showed significant differences at frequencies of 4 k, 6 k, and 8 kHz with aging considered. Adjusted odds ratio for field noise exposure (OR=99.57, 95% CI: 3.53, 2,808.74) and frequent tea or coffee consumption (OR=0.03, 95% CI: 0.01, 0.51) were found significant. Current study addressed NIHL in a specific industry in Taiwan. Further efforts in minimizing its impact are still in need.

Extracellular ATP activates the PLC/PKC/ERK signaling pathway through the P2Y2 purinergic receptor leading to the induction of early growth response 1 expression and the inhibition of viability in human endometrial stromal cells.

ATP is an extracellular signaling molecule that activates specific G protein-coupled P2Y receptors in most cell types to mediate diverse biological effects. ATP has been shown to activate the phospholipase C (PLC)/diacylglycerol/protein kinase C (PKC) pathway in various systems. However, little is known about the signaling events in human endometrial stromal cells (hESCs). The objective of this study was to examine the presence of the P2Y2 receptor and the effects of exogenous ATP on the intracellular mitogen-activated protein kinases (MAPKs) signaling pathway, immediate early genes expression, and cell viability in hESCs. Western blot analysis, gene array analysis, and MTT assay for cell viability were performed. The current study demonstrated the existence of the P2Y2 purinergic receptor in hESCs. UTP and ATP activated MAPK in a dose- and time-dependent manner. Suramin (a P2-purinoceptor antagonist), neomycin (a PLC inhibitor), staurosporin (a PKC inhibitor), and PD98059 (a MEK inhibitor) significantly attenuated the ATP-induced activation of MAPK. ATP activated ERK1/2 and induced translocation of activated ERK1/2 to the nucleus. The gene array for 23 genes associated with members of the mitogenic pathway cascade and immediate early genes revealed that the expression of early growth response 1 was increased. In addition, MTT assay revealed an inhibition effect of ATP on cell viability. ATP activated MAPKs through the P2Y2 purinoceptor/PLC/PKC/ERK signaling pathway and induced translocation of ERK1/2 into the nucleus. Further, ATP induced the expression of early growth response 1 and inhibited cell viability in hESCs.

Extracellular ATP activates nuclear translocation of ERK1/2 leading to the induction of matrix metalloproteinases expression in human endometrial stromal cells.

ATP has been shown to activate the mitogen-activated protein kinase (MAPK) signaling pathway in various systems. However, little is known about the signaling events and the effects in human endometrial stromal cells (hESCs). The present study examined the effect of ATP on activating MAPKs and its subsequent events in hESCs. This study demonstrated the expression of the P(2U)/P2Y(2) receptor in hESCs by reverse transcription-PCR (RT-PCR). A PCR product with a sequence identical to the reported 599 bp P(2U)/P2Y(2) receptor cDNA was obtained. Western blot analysis, using a monoclonal antibody against the phosphorylated forms of ERK1/2, demonstrated that ATP activated MAPK in a dose- and time-dependent manner. Confocal microscopy showed an evident nuclear translocation of phosphorylated ERKs after 10 microM ATP treatment, but this effect was blocked by PD98059. To study the gene(s) induced by exogenous ATP, mRNA was extracted from hESCs in the presence or absence of 10 microM ATP. The gene array for 96 genes associated with members of human matrix metalloproteinases (MMPs) and adhesion molecules revealed that the expression of MMP-2, -3, -10, and -24 genes was increased and the effect was attenuated by PD98059. Furthermore the effects of ATP on the expression of MMP genes were confirmed by semiquantitative RT-PCR. To our knowledge, this is the first demonstration of the ATP-induced nuclear translocation of phospho-ERK1/2 that mediates MMPs gene expression in human endometrial cells. These results support the notion that the ERK1/2 signaling pathway is involved in mediating ATP actions in the human reproductive system.

Risk for hypertension in workers exposed to carbon disulfide in the viscose rayon industry.

BACKGROUND: Chronic exposure to carbon disulfide (CS(2)) has been associated with hypertension, elevated cholesterol, arteriosclerosis, ischemic heart disease and related mortality, adverse nervous and reproductive health effects, and hearing impairment. This study assessed the hypertension risk for male rayon workers exposed to CS(2). METHODS: A total of 251 rayon workers and 226 administrative clerks at two plants in Taiwan received health examination and interviews, and were compared for hypertension risk. On-site CS(2) levels were measured. RESULTS: The hypertension was more prevalent in the exposure group (43.4%) than in controls (7.1%) with greater impact on systolic blood pressure than diastolic. Multivariate logistic regression analysis showed a significant dose-response relationship between hypertensive risk and cumulative exposure index (CEI) with an odds ratio of 15.1 for workers exposed to 343-468 year-ppm of CS(2). The overall risk was elevated to 7.6 times higher for rayon workers. The risk increased significantly after more than 10 years of employment. CONCLUSIONS: This study suggests that it takes a long exposure period to develop hypertension for rayon workers with CS(2) exposure.

Hearing loss in workers exposed to toluene and noise.

In this study we investigated the risk of hearing loss among workers exposed to both toluene and noise. We recruited 58 workers at an adhesive materials manufacturing plant who were exposured to both toluene and noise [78.6-87.1 A-weighted decibels; dB(A)], 58 workers exposed to noise only [83.5-90.1 dB(A)], and 58 administrative clerks [67.9-72.6 dB(A)] at the same company. We interviewed participants to obtain sociodemographic and employment information and performed physical examinations, including pure-tone audiometry tests between 0.5 and 6 kHz. A contracted laboratory certified by the Council of Labor in Taiwan conducted on-site toluene and noise exposure measurements. The prevalence of hearing loss of >or=25 dB in the toluene plus noise group (86.2%) was much greater than that in the noise-only group (44.8%) and the administrative clerks (5.0%) (p<0.001). The prevalence rates were 67.2, 32.8, and 8.3% (p<0.001), respectively, when 0.5 kHz was excluded from the estimation. Multivariate logistic regression analysis showed that the toluene plus noise group had an estimated risk for hearing loss>or=25 dB, 10.9 times higher than that of the noise-only group. The risk ratio dropped to 5.8 when 0.5 kHz was excluded from the risk estimation. Hearing impairment was greater for the pure-tone frequency of 1 kHz than for that of 2 kHz. However, the mean hearing threshold was the poorest for 6 kHz, and the least effect was observed for 2 kHz. Our results suggest that toluene exacerbates hearing loss in a noisy environment, with the main impact on the lower frequencies.

Electrocardiographic abnormality for workers exposed to carbon disulfide at a viscose rayon plant.

OBJECTIVE: This study investigated electrocardiography (ECG) manifestations for male workers with carbon disulfide exposure at rayon manufacturing plants. METHODS: A total of 251 men in the exposure group and 226 administrative clerks in the reference group received physical examinations and completed questionnaires. RESULTS: The prevalence of ECG abnormalities was much higher in the carbon disulfide exposure group (25.9%, n = 65) than in the reference group (2.7%, n = 6), with an odds ratio (OR) of 12.8 (95% confidence interval [CI] = 5.4-30.2). The foremen were at the highest risk of abnormal ECG (OR = 20.6, 95% CI = 6.5-65.2), followed by filament-spinning workers (OR = 14.2, 95% CI = 5.7-35.3), viscose-manufacturing workers (OR = 11.3, 95% CI = 4.3-30.1), and carbon disulfide-manufacturing workers (OR = 8.1, 95% CI = 2.7-25.6). The multivariate logistic regression analysis based on cumulative exposure index also showed a dose-response relationship with the exposure, and the risk of ECG abnormality could be initiated at the exposure history of 31 to 57 year-ppm with an OR of 7.2 (95% CI = 1.5-36.7). CONCLUSIONS: In general, the ECG abnormalities observed in workers at the permissible exposure level of carbon disulfide implicate the importance of environmental control of the chemical and of workers' education in exposure prevention at work.

Adenosine triphosphate induces activation of caspase-3 in apoptosis of human granulosa-luteal cells.

Adenosine triphosphate (ATP) has been shown to induce programmed cell death in various systems. However, little is known about the effect of ATP on human granulosa-luteal cells (hGLCs). The present study was designed to examine the effect of ATP on the activation of the caspase signaling pathway and its role in inducing programmed cell death. Human GLCs were collected from patients undergoing in vitro fertilization programs, and then were cultured in FBS-supplemented DMEM for 3 days prior to our studies. To examine the dose-response relationship, hGLCs were treated with increasing concentrations of ATP (10 microM, 100 microM, 1 mM or 10 mM) for 24 hours. For time-course experiments, hGLCs were treated with 10 mM ATP for 6, 12, or 24 hours. Western blot analysis was performed using antibodies against the pro- and active forms of caspase-3, -9, or PARP. To quantify the induction of apoptosis, DNA fragmentation was measured using the cell death detection enzyme-linked immunosorbent assay. To examine the effect of human chorionic gonadotropin (hCG) in protecting cells from apoptosis, hGLCs were treated with 10 IU hCG in the presence of 10 mM ATP for 12 hours. It was demonstrated that ATP was capable of inducing DNA fragmentation in a dose- and time-dependent manner. Furthermore, Western blot analysis, which detected the pro- and active forms of caspase-3, or PARP, demonstrated that ATP activated the caspase-signaling pathway, leading to the proteolytic conversion of pro-caspase-3 to active caspase-3, and the subsequent cleavage of the caspase substrate PARP. Based on our observation, caspase-9 was not triggered by ATP. Interestingly, hCG attenuated the effect of ATP in activating the caspase signaling pathway. To our knowledge, this is the first demonstration of the ATP-induced activation of the caspase signaling pathway in the human ovary. These results support the notion that the caspase-signaling pathway is involved in mediating ATP actions in the human ovary.

Adenosine 5'-triphosphate activates nuclear translocation of mitogen-activated protein kinases leading to the induction of early growth response 1 and raf expression in human granulosa-luteal cells.

With the stimulation of many types of cell surface receptors, MAPKs are activated. We have previously demonstrated an effect of extracellular ATP on ERKs and gonadotropin- induced progesterone secretion, implicating the significance of ATP in the regulation of ovarian function. However, little is known about the specific role of ATP in the subsequent MAPK-induced signaling cascade in human granulosa-luteal cells (hGLCs). The present study was designed to examine the effect of ATP on the activation of the MAPK signaling pathway, including nuclear translocation and the expression of the immediate early genes in hGLCs. Western blot analysis, using a monoclonal antibody, which detected the total and phosphorylated forms of ERK1 and ERK2 (p42(mapk) and p44 (mapk), respectively), demonstrated that exogenous ATP evoked ERKs in a dose- and time-dependent manner. In contrast, p38 and JNK were not significantly activated after ATP treatment. To examine the translocation of activated ERKs, fluorescein isothiocyanate-conjugated secondary antibody was used to detect the distribution of total and phosphorylated ERKs. Immunofluorescent staining revealed that phosphorylated ERKs were translocated from cytoplasm into nucleus subsequent to 10 microm ATP treatment. To study the gene(s) induced by exogenous ATP, mRNA was extracted from hGLCs in the presence or absence of 10 microm ATP. Gene array for 23 genes associated with members of the mitogenic pathway cascade and immediate early genes revealed that the expression of early growth response 1 and c-raf-1 was increased. To our knowledge, this is the first demonstration of the ATP-induced nuclear translocation of MAPKs in the human ovary. These results suggest that the MAPK signaling pathway plays a role in mediating ATP actions in the human ovary.

The effect of personal factors on the relationship between carbon disulfide exposure and urinary 2-thiothiazolidine-4-carboxylic acid levels in rayon manufacturing workers.

BACKGROUND: Few studies have been conducted to explore how personal factors-personal hygiene, personal protective equipment, and skin exposure affect the exposure-dose relationship in workers exposed to carbon disulfide (CS(2)). METHODS: Personal environmental monitoring of airborne CS(2) and 2-thiothiazolidine-4-carboxylic acid (TTCA) levels in post-shift urine were determined for sixty-five rayon workers. The personal factors affecting the CS(2)-TTCA relationship were measured by questionnaire and dermatological diagnosis. RESULTS: In simple linear regression analyses, we found shower right after work, respirator, gloves, apron, and skin disease were significantly associated with U-TTCA levels among all personal factors. Skin disease was, however, the only personal factor that remained significant throughout multivariate linear regression analyses. CONCLUSIONS: In this study, the personal factor like host's skin disease was found to possibly affect the relations of U-TTCA to the occupational exposure to CS(2). The skin exposure to CS(2) for those who have skin problems on the sites possibly or potentially exposed to CS(2) in the occupational environment such as in the rayon manufacturing process is noteworthy. Workers with susceptible skins should either be assigned to work in areas without contacting hazardous materials directly or required to wear appropriately protective clothing.

Decreased expression of mitochondrial genes in human unfertilized oocytes and arrested embryos.

OBJECTIVE: To evaluate the relationship between mitochondrial gene expression of oocytes/embryos and their fertilizability in unfertilized oocytes, arrested embryos, and tripronucleate zygotes, because both nuclear and cytoplasmic factors contribute to oocyte activation, fertilization, and subsequent development. DESIGN: Prospective laboratory research. SETTING: In vitro fertilization (IVF) laboratory in a university hospital. PATIENT(S): Seventy-five unfertilized oocytes, 45 arrested embryos, and 24 tripronucleate (3PN) embryos from 45 female patients undergoing IVF. INTERVENTION(S): Analysis of mitochondrial gene expression by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE(S): Comparison of the expression levels of mitochondrial genes including ND2, CO I, CO II, ATPase 6, CO III, ND3, ND6, and Cyt b in three groups. RESULT(S): Significantly decreased transcription levels were expressed in unfertilized oocytes and arrested embryos. The average expression levels of the eight determined genes compared with the control (GAPDH) was 4.4 +/- 0.7, 6.4 +/- 1.1, and 13.2 +/- 1.1 in unfertilized oocytes, arrested embryos, and 3PN embryos, respectively. Significantly decreased expressions of the ATPase 6, CO III, and ND3 genes were detected from samples with 4977-bp common deletion in the mitochondrial DNA (mtDNA) compared with the non-deletion group. CONCLUSION(S): The present study is the first report to present globally decreased mitochondrial gene expression levels in human compromised oocytes and embryos. These data support the notion that the down-regulation of mitochondrial RNA by defective oxidative phosphorylation genes possibly affects oocyte quality including fertilization and further embryo development.