Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite-induced asthma mouse model.

House dust mites (HDMs) are a common source of allergens that trigger both allergen-specific and innate immune responses in humans. Here, we examined the effect of allergen concentration and the involvement of Toll-like receptor 4 (TLR4) in the process of sensitization to house dust mite allergens in an HDM extract-induced asthma mouse model.　Intranasal administration of HDM extract induced an immunoglobulin E response and eosinophilic inflammation in a dose-dependent manner from 2.5 to 30 µg/dose. In TLR4-knockout mice, the infiltration of eosinophils and neutrophils into the lung was decreased compared with that in wild-type mice in the early phase of inflammation (total of three doses). However, in the late phase of inflammation (total of seven doses), eosinophil infiltration was significantly greater in TLR4-knockout mice than in wild-type mice. This suggests that the roles of TLR4 signaling are different between the early phase and the later phase of HDM allergen-induced inflammation. Thus, innate immune response through TLR4 regulated the response to HDM allergens, and the regulation was altered during the phase of inflammation.

Comparison of ultrasonographic joint and tendon findings in hands between early, treatment-naïve patients with systemic lupus erythematosus and rheumatoid arthritis.

Although both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) may lead to joint deformity, SLE arthritis is typically non-erosive and often accompanied by Jaccoud's deformity. Therefore, we examined characteristics of joint and tendon lesions in patients with SLE and RA by ultrasonography. Fifteen treatment-naïve SLE patients and 40 treatment-naïve RA patients with joint symptoms were included in this study. The hand joints and related tendons were ultrasonographically examined using grey-scale (GS) and power Doppler (PD). Joint involvement was comparably observed in patients with SLE and RA (80% versus 95%, p = 0.119). However, tendon involvement was more frequent in SLE than in RA (93% versus 65%, p = 0.045), especially in the wrist joints (73% versus 40%, p = 0.037). When we investigated the intensity of US findings, the joint synovitis score (GS + PD) per affected joint was lower in SLE than RA (2.0 versus 2.6, p = 0.019), while tendon inflammation score was not significantly different (2.1 versus 2.2, p = 0.738). Finally, the examination of concordance between joint and tendon involvement in the same finger revealed that joint lesion appeared in only 49% of fingers having tendon involvement in the SLE group, which was significantly less than 74% in the RA group ( p = 0.010). Thus, as compared with RA, SLE arthropathy is characterized by the predominance of tenosynovitis/periextensor tendon inflammation, which is likely to develop independently from joint synovitis.

Decreased immunoglobulin G levels after living-donor liver transplantation is a risk factor for bacterial infection and sepsis.

BACKGROUND: Several studies have suggested an association between post-transplant immunoglobulin (Ig) levels and the development of infection in solid organ transplantation. We therefore conducted exploratory analyses of potential factors associated with bacterial infection/sepsis after living-donor liver transplantation (LDLT). METHODS: Blood samples from 177 recipients who received primary LDLT between September 1999 and November 2011 were available for study. Hypogammaglobulinemia was defined as having at least 1 IgG level <650 mg/dL within 7 days after LDLT. Risk factors for developing post-transplant bacterial infection and sepsis within 3 months after LDLT were analyzed. RESULTS: Fifty (28.2%) recipients experienced bacterial infection within 3 months of LDLT. Eighty-four (47.5%) recipients had hypogammaglobulinemia, although no recipients had hypogammaglobulinemia before LDLT. Hypogammaglobulinemia, undergoing hepaticojejunostomy, and portal pressure at closure >15 mmHg were independent risk factors for developing bacterial infection within 3 months of LDLT (P < 0.0001 P = 0.0008, and P = 0.011, respectively). The odds ratio (OR) and confidence interval (CI) for hypogammaglobulinemia were 4.79 and 2.27-10.7, respectively. Twenty-four (13.6%) recipients developed bacterial sepsis within 3 months. Hypogammaglobulinemia, operative time >14 h, model for end-stage liver disease score >15, and no mycophenolate mofetil use were independent risk factors for developing bacterial sepsis (P = 0.009, P = 0.001, P = 0.003, and P = 0.005, respectively). The OR and CI for hypogammaglobulinemia were 3.83 and 1.38-12.0, respectively. CONCLUSIONS: Hypogammaglobulinemia within 7 days of LDLT was a significant risk factor for post-transplant bacterial infection and sepsis.

A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells.

The rat small eye strain (rSey) lacks eyes and nose in the homozygote, and is similar to the mouse Sey strain with mutations in the Pax-6 gene. We isolated Pax-6 cDNA clones from an rSey homozygote library, and found an internal deletion of about 600 basepairs in the serine/threonine-rich domain. At the genomic level, a single base (G) insertion in an exon generates an abnormal 5' donor splice site, thereby producing the truncated mRNA. Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain.

Impact of human T cell leukemia virus type 1 in living donor liver transplantation.

Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development.

Olive oil polyphenol oleuropein inhibits smooth muscle cell proliferation.

OBJECTIVES: The Mediterranean diet, with a high content of olive oil, is associated with a reduced risk of coronary artery disease. The aim of this study was to determine the effect of oleuropein, one of the polyphenols in olive oil, on vascular smooth muscle cell (SMC) proliferation in vitro. DESIGN: This was an experimental study. MATERIALS AND METHODS: Bovine vascular SMCs were cultured in the presence of 100 µM of oleuropein. On days 1, 3 and 5, cell number was counted. Cell cycle analysis was performed by flow cytometry. Cell cycle regulators were assessed by immunoblotting. RESULTS: Cell proliferation in the presence of oleuropein was significantly inhibited by 92%. Cell cycle analysis revealed that oleuropein treatment blocked cells in the G1-S phase compared with the non-treated group. Among G1 phase regulators, retinoblastoma protein, cyclinD, p21 and p27 were not affected by oleuropein, but extracellular signal-regulated kinase 1/2 (ERK1/2) activation was inhibited. Growth of SMC treated with 100 µM of the mitogen-activated protein (MAP) kinase/ERK kinase 1 (MEK1) inhibitor PD98059 was also significantly inhibited by 70%. CONCLUSIONS: Oleuropein inhibited SMC proliferation through a cell cycle block between the G1 and the S phases, which may be regulated by ERK1/2. These results suggest a mechanism by which olive oil consumption may have beneficial effects on cardiovascular mortality by inhibiting SMC proliferation.

Investigation of the thermal tolerance of silicon-based lateral spin valves.

Improvement in the thermal tolerance of Si-based spin devices is realized by employing thermally stable nonmagnetic (NM) electrodes. For Au/Ta/Al electrodes, intermixing between Al atoms and Au atoms occurs at approximately 300 °C, resulting in the formation of a Au/Si interface. The Au-Si liquid phase is formed and diffuses mainly along an in-plane direction between the Si and AlN capping layers, eventually breaking the MgO layer of the ferromagnetic (FM) metal/MgO electrodes, which is located 7 µm away from the NM electrodes. By changing the layer structure of the NM electrode from Au/Ta/Al to Au/Ta, the thermal tolerance is clearly enhanced. Clear spin transport signals are obtained even after annealing at 400 °C. To investigate the effects of Mg insertion in FM electrodes on thermal tolerance, we also compare the thermal tolerance among Fe/Co/MgO, Fe/Co/Mg/MgO and Fe/Co/MgO/Mg contacts. Although a highly efficient spin injection has been reported by insertion of a thin Mg layer below or above the MgO layer, these thermal tolerances decrease obviously.

Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation.

Epidemiologic investigations have shown that exercise reduces morbidity and mortality from coronary artery disease. In this study, using a rat model, we attempted to determine whether exercise can reduce ischemic injury to the heart and elucidate a mechanism for the cardioprotective effect of exercise. Results showed that exercise significantly reduced the magnitude of a myocardial infarction in biphasic manner. The time course for cardioprotection resembled that of the change in manganese superoxide dismutase (Mn-SOD) activity. The administration of the antisense oligodeoxyribonucleotide to Mn-SOD abolished the expected decrease in infarct size. We showed that the level of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) increased after exercise. The simultaneous administration of the neutralizing antibodies to the cytokines abolished the exercise-induced cardioprotection and the activation of Mn-SOD. Furthermore, TNF-alpha can mimic the biphasic pattern of cardioprotection and activation of Mn-SOD. An antioxidant completely abolished cardioprotection and the activation of Mn-SOD by exercise or the injection of TNF-alpha as well as exercise-induced increase in TNF-alpha and IL-1beta. The production of reactive oxygen species and endogenous TNF-alpha and IL-1beta induced by exercise leads to the activation of Mn-SOD, which plays major roles in the acquisition of biphasic cardioprotection against ischemia/reperfusion injury in rats.

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.

BACKGROUND: Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients. METHODS: All consecutive patients with cirrhosis who underwent splenectomy in Kyushu University Hospital between 1998 and 2004 were included in this retrospective study. They were divided into two groups based on the presence or absence of postoperative PVT. Preoperative and operative factors were compared, and the relationships between formation of PVT and its independent variables were analysed. In some cases, portal venous flow was measured before and after splenectomy using duplex Doppler ultrasonography. RESULTS: PVT developed after surgery in 17 (24 per cent) of 70 patients studied. Multivariable analysis showed that increased splenic vein diameter and low white cell count were significant independent risk factors for PVT. Portal venous flow after splenectomy was greatly reduced in the PVT group, but not in patients without PVT. CONCLUSION: Large splenic vein diameter and low white cell count are independent risk factors for PVT after splenectomy in patients with cirrhosis and portal hypertension.

An innovative technique for endoscopic submucosal dissection of early gastric cancer using a new spring device.

BACKGROUND AND STUDY AIMS: In recent years, endoscopic submucosal dissection (ESD) has been applied for the treatment of gastric tumors, and the en-bloc resection rate of early gastric cancer has greatly improved. Herein, we introduce spring-assisted ESD, for quicker submucosal dissection. PATIENTS AND METHODS: ESD was carried out in 32 patients (20 men, 12 women; mean age 72.6 years, range 53 - 88 years) for early gastric cancer, with tumors over 10 mm in diameter. The patients were divided retrospectively into two groups (spring-assisted ESD, n = 20; conventional ESD, n = 12). To comparatively evaluate the performance speed of ESD, the circumferential length and the area of the resected specimen were calculated by the approximation formula for ellipse. Then, the circumferential cutting speed, the submucosal dissection speed, and the total ESD speed were calculated as index scores. The scores for spring-assisted ESD and conventional ESD were compared. RESULTS: The mean (+/-SD) circumferential cutting speeds in spring-assisted ESD and conventional ESD were 0.53 +/- 0.27 and 0.60 +/- 0.30 cm/minute, respectively ( P = 0.51). The mean submucosal dissection speeds in spring-assisted ESD and conventional ESD were 0.67 +/- 0.41 and 0.32 +/- 0.24 cm (2)/minute, respectively ( P = 0.005). The mean total ESD speeds in spring-assisted ESD and conventional ESD were 0.25 +/- 0.10 and 0.17 +/- 0.07 cm (2)/minute, respectively ( P = 0.015). The mean total ESD times were 57 and 75 minutes in the spring and conventional group, respectively ( P = 0.30). CONCLUSION: Using the aforementioned indices, we evaluated the performance speed of ESD. Spring-assisted ESD may allow faster submucosal dissection.

A pilot study to assess the efficacy of photodynamic therapy for Japanese patients with actinic keratosis in relation to lesion size and histological severity.

BACKGROUND/PURPOSE: Topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) is effective for actinic keratosis (AK); few studies have examined Oriental patients. The aim of this study is to assess the efficacy of PDT for the treatment of Japanese AK patients classified by lesion size and histological severity. METHODS: Thirty patients with solitary AK lesions were divided into two groups according to diameter: a small lesion group (SL), diameter < or =10 mm and a larger lesion group (LL), diameter >10 mm, and histological severity: Group I (mild and moderate) and Group II (severe). After application of 20% ALA for 4 h, exposure to an excimer-dye laser at 630 nm was performed at a dose of 50 J/cm(2) three times at an interval of 7 days. Therapeutic effects were assessed and followed for 12 months. RESULTS: In all 10 SL patients, atypical cells disappeared after PDT and did not recur for 12 months. However, for the 20 LL patients, recurrence was seen in 2 of the 14 Group I patients, while 4 of 6 Group II patients showed residual tumor cells after the first PDT session. CONCLUSION: The present study demonstrated that ALA-PDT might be useful for treatment of Japanese AK. The therapeutic outcome might depend on the lesion size and the histopathological severity.

Etretinate enhances the susceptibility of human skin squamous cell carcinoma cells to 5-aminolaevulic acid-based photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (5-ALA) is a noninvasive and effective treatment for superficial skin cancers. Etretinate, a derivate of vitamin A, with the chemical formula ethyl(2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nona-tetraenoate, has been reported to have antitumour effects and to regulate the proliferation and differentiation of skin cancers. OBJECTIVE: In order to develop more efficient PDT, we investigated whether etretinate enhanced the cytotoxic action of ALA-based PDT against human squamous cell carcinoma cell line, HSC-5. METHOD: The in vitro cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic cells were detected by double-staining with fluorescent annexin V and propidium iodide. Intracellular protoporphyrin IX (PpIX) converted from exogenous ALA was measured by a fluorescence meter. RESULTS: HSC-5 cells pretreated with a nontoxic concentration of etretinate became more susceptible to the cytotoxic action of ALA-based PDT. Etretinate-pretreated cells underwent apoptosis in response to ALA-based PDT. Etretinate pretreatment resulted in enhanced accumulation of ALA-dependent intracellular PpIX. CONCLUSIONS: The results suggest that etretinate enhances the susceptibility of HSC-5 cells to ALA-based PDT via the intracellular increase of ALA-dependent PpIX. Etretinate might be useful for improvement of ALA-based PDT.

Discussion on the application of UV/H(2)O(2), O(3) and O(3)/UV processes as technologies for sewage reuse considering the removal of pharmaceuticals and personal care products.

The applicability of O(3), UV/H(2)O(2) and O(3)/UV treatment processes as technologies for water reuse considering pharmaceuticals and personal care products (PPCPs) removal was investigated. Electrical energies required for the effective removal of various PPCPs in secondary effluent were 0.09 kWh/m(3), 0.54 kWh/m(3) and 1.09 kWh/m(3) for O(3), UV/H(2)O(2) and O(3)/UV treatments, respectively, showing that O(3) treatment is the most cost-effective treatment option for the PPCPs removal. O(3) treatment showed the effective PPCPs removal at O(3) dose of 6 mg/L; however, the formation of bromate is expected for O(3) treatment using O(3) dose of more than 4 mg/L. In particular, bromate formation will be a critical issue when the reclaimed water is used for direct/indirect potable reuses. Therefore, in order to suppress the bromate formation as well as achieve the effective PPCPs removal, O(3)/UV treatment will be recommended. UV/H(2)O(2) treatment will be also a profitable treatment method because no bromate will be formed during the process. The evaluation for ecological risk of PPCPs by the applied processes showed that all the processes could decrease the ecological risk caused by parent PPCPs considerably. This means that the investigated treatment processes can play an important role in reducing unpredictable side effects caused by PPCPs in the aquatic environment.

Survey of perfluorinated compounds (PFCs) in surface waters of Poland.

Perfluorochemicals (PFCs) are wide-spread contaminants on a global scale. There is an increasingly growing number of data on environmental occurrence, sources and risk of PFCs to humans and aquatic biota in highly industrialised countries but inadequate information exists for less industrialised regions. In the present study, concentrations and profiles of PFCs were examined in surface waters (rivers, lakes, streams, coastal region of the Baltic Sea) of Poland. PFOS was the dominant compound found in water at most of the sites surveyed and its concentration varied between < 0.5 and 150 ng/L and next was PFHxS with < 0.25 to 110 ng/L, while at much smaller concentration of < 0.5 to 18 ng/L occurred PFOA. The long-chain carboxylates (C11-C16) could be found only in water of a drainage ditch near to the Sarzyna site, i.e., PFUnDA occurred at 0.17 ng/L, PFTeDA of 0.06 ng/L, PFDoDA at 0.1 ng/L and PFHxDA at 0.12 ng/L. PFDA was found at several locations in the Gulf of Gdansk and its concentration varied between < 0.01 and 0.07 ng/L. The profile of PFCs in surface water at several sites of Poland with PFOS as a major compound, followed by PFOA is similar to that reported for other countries in Europe as well as for India, while this is different from that of Korea, Japan and the USA, where PFOA was the predominant contaminant.

Estimating transboundary transported anthropogenic sulfate deposition in Japan using the sulfur isotopic ratio.

High emissions of air pollutants from Northeast Asia are strongly influenced by air quality as well as by ecosystems. This study investigated the spatiotemporal variations in the sulfur isotopic ratio (δ34S) in atmospheric deposition at eleven monitoring stations in Japan from 2011 to 2016 and estimated the amount of transboundary transported anthropogenic sulfate (TRB) deposition using mass balance calculations. The δ34S of sulfate in precipitation ranged from -0.42 to +22.7‰. Sea salt (SS), TRB, and domestic anthropogenic sources (DOM) were the dominant sources of sulfate deposition in Japan. TRB sulfate deposition was largest on the Sea of Japan side, with an annual average value of 1.5 ±â€¯0.3-6.9 ±â€¯0.5 mg m-2 d-1 (36-44%), followed by Mt. Happo (4.5 ±â€¯0.1 mg m-2 d-1; 88%), the Pacific Ocean side (1.5 ±â€¯0.8, 4.3 ±â€¯0.9 mg m-2 d-1; 24-50%), and the remote islands in the North Pacific Ocean (1.1 ±â€¯0.2, 2.0 ±â€¯0.8 mg m-2 d-1; 19-32%). TRB sulfate deposition on the Sea of Japan side was 2-12 times higher in winter and 1-2 times higher in summer than that of DOM. In contrast, TRB sulfate deposition on the Pacific Ocean side was 1.5-3 times higher in summer than in winter due to high precipitation levels. In Tokyo, the annual contribution from DOM sulfate deposition is approximately three times higher than that from TRB. Annual TRB sulfate deposition is lowest at Ogasawara at 1.1 ±â€¯0.2 mg m-2 d-1, and the annual oceanic DMS contribution to sulfate deposition is high, accounting for 1.3 mg m-2 d-1 (20 ±â€¯6%). The contribution of Asian dust was estimated to be 1-5.2 mg m-2 d-1(3-6%), which occurred in a single Asian dust event on the Sea of Japan side.

Removal of antibiotics from wastewater by sewage treatment facilities in Hong Kong and Shenzhen, China.

Concentrations of nine antibiotics [erythromycin-H(2)O (ERY-H(2)O); trimethoprim (TMP); tetracycline (TET); norfloxacin (NOR); penicillin G (PEN G); penicillin V (PEN V); cefalexin (CLX); cefotaxim (CTX); and cefazolin (CFZ)] were measured in influent and effluent samples from four sewage treatment plants (STPs) in Hong Kong as well as in influent samples from one STP in Shenzhen. Levels of PEN V and CFZ were below method detection limits in all of the samples analyzed. CLX concentrations were the highest in most of the Hong Kong samples, ranging from 670 to 2900 ng/L and 240 to 1800 ng/L in influent and effluent samples, respectively, but CLX was not detected in the samples from Shenzhen. Comparatively lower concentrations were observed for ERY-H(2)O (470-810 ng/L) and TET (96-1300 ng/L) in the influent samples from all STPs in Hong Kong. CTX was found to be the dominant antibiotic in the Shenzhen STP influents with a mean concentration of 1100 ng/L, but occurred at lower concentrations in Hong Kong sewage. These results likely reflect regional variations in the prescription and use patterns of antibiotics between Hong Kong and Shenzhen. Antibiotic removal efficiencies depended on their chemical properties and the wastewater treatment processes used. In general, relatively higher removal efficiencies were observed for NOR (5-78%) and TET (7-73%), which are readily adsorbed to particulate matter, while lower removal efficiencies were observed for ERY-H(2)O (9-19%), which is relatively persistent in the environment. Antibiotics were removed more efficiently at Hong Kong STPs employing secondary treatment processes compared with those using primary treatment only. Concentrations of NOR measured in effluents from STPs in Hong Kong were lower than the predicted no-effect concentration of 8000 ng/L determined in a previous study. Therefore, concentrations of antibiotics measured in this preliminary study would be unlikely to cause adverse effects on microorganisms used in wastewater treatment processes at the sampled STPs.

Historical trends of organic pollutants in sediment cores from Hong Kong.

Recent studies have indicated the occurrence of a wide range of trace organic contaminants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in the Hong Kong environment. These contaminants are potentially harmful to ecological systems, particularly in coastal areas. In this study, two sediment cores (4m) were collected from southern waters of Hong Kong in 2004 to study the historical trends, distribution patterns, and potential sources of trace organic contaminants. DDTs (p,p'-DDT, o,p'-DDT, p,p'-DDD, o,p'-DDD and p,p'-DDE), hexachlorohexanes (HCHs) (alpha and gamma), hexachlorobenzene (HCB), and PCBs were detected in the samples, whereas other target compounds were all below detection limits. Many OCPs have not been produced or used for many years due to toxicological or environmental concerns and PCB use is prohibited in Hong Kong. However, some compounds were still detectable in recent years, and were found to be widely distributed in the environment, likely because of pollutant inputs from the highly industrialized Pearl River Delta region. These results provide important information on current and historical contamination in Hong Kong, and help to reconstruct the pollution history of these trace organic pollutants in Hong Kong coastal waters.

The first introduction of reclaimed wastewater to dry-farming field in Okinawa Island, Japan.

Reclaimed wastewater (RWW) will be introduced to the first large-scale irrigation project for dry-farming on Okinawa Island, Japan. The wastewater reclamation for agricultural use sounds attractive to the water resource management. Since there are no specific standards for the RWW irrigation, the monitoring and other demonstrative experiments have been conducted using the experimental reclamation facility, which is based on the criteria "Title22". The experiments showed that the existing system is sufficient to meet the above criteria of pathogens, protozoa and viruses, and the concentrations of hazardous chemicals are lower than the environmental standards in Japan. In addition, several laboratory soil column experiments were conducted to address the environmental issues. An increase of denitrification due to the continuous irrigation was observed. Salt and nitrate accumulation in the surface soil was observed as well. We can conclude that the RWW of the above facility assures the safety for human health, and further research based on environmental issues is needed in addition to an integrated risk assessment and communication.

Removal efficiency of 66 pharmaceuticals during wastewater treatment process in Japan.

Both biological treatment processes including conventional activated sludge (CAS) and biological nutrient removal (BNR) processes, and physico-chemical treatment processes including ozonation process and Title 22 process consisting of coagulation, sedimentation and filtration followed by UV or chlorination disinfection after the above biological processes, were compared from the viewpoint of removal efficiency. 66 pharmaceuticals including antibiotics, analgesics, psychoneurotic agents were measured with SPE-LC/MS/MS. 26 compounds out of 66 were detected in the influent ranging ng/L to microg/L order. Particularly, disopyramide, sulpiride, and dipyridamole that have been rarely detected before in the WWTP, occurred at concentration levels of more than 100 ng/L. The total concentration of the individual pharmaceuticals in the influent was efficiently removed by 80% during the biological treatment. But removal efficiencies of carbamazepine and crotamiton were less than 30%. The total concentration of the individual pharmaceuticals in the effluent from CAS process was 1.5 times higher than that from BNR process. Further, the total concentration of the individual pharmaceuticals in the discharge from WWTPs applying ozonation following activated sludge process was reduced to less than 20%. Physico-chemical treatment train called Title 22 treatment after CAS could not efficiently remove the pharmaceuticals. However, ozonation process followed by biological activated carbon process could efficiently reduce all the residual pharmaceuticals below their quantification limits.

Angiotensin II and vasopressin stimulate calcium-activated chloride conductance in rat mesangial cells.

In an attempt to clarify the mechanisms by which angiotensin II (AII) and arginine vasopressin (AVP) regulate mesangial cell function, we examined the membrane potential change of mesangial cells and found that cells contracted and membrane potential depolarized in response to AII and AVP. The depolarization was associated with decreased input resistance. Ca ionophore A23187 caused similar mesangial cell contraction and depolarization. The reversal potential (Vr) of the depolarization response to AII and AVP was -29 +/- 3 and -25 +/- 7 mV (mean +/- SD), respectively. Not only the Vr of the AII-induced depolarization but also Vr of the Ca ionophore-induced response was dependent upon the extracellular Cl- concentration. Further, AII and AVP caused cell contraction and membrane depolarization in Ca++-free medium containing 0.5 mM EGTA. These data suggest the presence of Ca++ -activated Cl- channels in the mesangial cells and that AII and AVP increase Cl- permeability via an elevation of [Ca++]i released from the intracellular organellae.