A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Laparoscopic sentinel node navigation surgery versus laparoscopic gastrectomy with lymph node dissection for early gastric cancer: short-term outcomes of a multicentre randomized controlled trial (SENORITA).

BACKGROUND: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection. METHODS: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study. RESULTS: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647). CONCLUSION: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio. RESULTADOS: Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.

Neurodevelopmental and neuropsychiatric disorders represent an interconnected molecular system.

Many putative genetic factors that confer risk to neurodevelopmental disorders such as autism spectrum disorders (ASDs) and X-linked intellectual disability (XLID), and to neuropsychiatric disorders including attention deficit hyperactivity disorder (ADHD) and schizophrenia (SZ) have been identified in individuals from diverse human populations. Although there is significant aetiological heterogeneity within and between these conditions, recent data show that genetic factors contribute to their comorbidity. Many studies have identified candidate gene associations for these mental health disorders, albeit this is often done in a piecemeal fashion with little regard to the inherent molecular complexity. Here, we sought to abstract relationships from our knowledge of systems level biology to help understand the unique and common genetic drivers of these conditions. We undertook a global and systematic approach to build and integrate available data in gene networks associated with ASDs, XLID, ADHD and SZ. Complex network concepts and computational methods were used to investigate whether candidate genes associated with these conditions were related through mechanisms of gene regulation, functional protein-protein interactions, transcription factor (TF) and microRNA (miRNA) binding sites. Although our analyses show that genetic variations associated with the four disorders can occur in the same molecular pathways and functional domains, including synaptic transmission, there are patterns of variation that define significant differences between disorders. Of particular interest is DNA variations located in intergenic regions that comprise regulatory sites for TFs or miRNA. Our approach provides a hypothetical framework, which will help discovery and analysis of candidate genes associated with neurodevelopmental and neuropsychiatric disorders.

Major early complications following open, laparoscopic and robotic gastrectomy.

BACKGROUND: Laparoscopic and robotic gastrectomy have been adopted rapidly despite lack of evidence concerning technical safety and controversy regarding additional benefits. This study aimed to compare clinically relevant complications after open, laparoscopic and robotic gastrectomy. METHODS: This was a retrospective analysis of prospectively collected data on surgical complications in patients undergoing gastrectomy with curative intent for histologically proven adenocarcinoma between 2005 and 2010 at the Department of Surgery, Yonsei University College of Medicine in Seoul, Korea. Complications were categorized into wound infection, bleeding, anastomotic leak, obstruction, fluid collection and other. RESULTS: In a total of 5839 patients (4542 open, 861 laparoscopic and 436 robotic gastrectomies), overall complication, reoperation and mortality rates were 10·5, 1·0 and 0·4 per cent respectively. There were no significant differences between the three groups. Ileus (P = 0·001) and intra-abdominal fluid collections (P = 0·013) were commoner after conventional open surgery. However, tumour stage was higher and more complex resections were performed in the open group. Anastomotic leak, the leading cause of death, occurred more often after a minimally invasive approach (P = 0·017). CONCLUSION: Laparoscopic and robotic gastrectomy had overall complication and mortality rates similar to those of open surgery, but anastomotic leaks were more common with the minimally invasive techniques.

Relevance of lymph node metastasis along the superior mesenteric vein in gastric cancer.

BACKGROUND: The purpose of this study was to evaluate the prognostic value of lymph node metastasis along the superior mesenteric vein (station 14v) to determine the need for 14v dissection in gastric cancer surgery. METHODS: A total of 1104 patients with gastric cancer who underwent gastrectomy including 14v dissection were enrolled. Patients were categorized into two groups: those with and those without 14v lymph node involvement by metastasis. RESULTS: Of the total study population, 73 patients (6·6 per cent) had 14v-positive gastric cancer. These patients were more likely to have advanced tumour (T), node (N) and distant metastatic (M) status, and histologically undifferentiated gastric cancers. The 3- and 5-year survival rates of patients with 14v-positive disease were 24 and 9 per cent respectively. Survival in this group was similar to that of patients who had gastric cancer with distant metastasis (M1). Multivariable analysis demonstrated that 14v status was a significant prognostic factor for gastric cancer (hazard ratio 2·13; P < 0·001). After histologically complete (R0) resection, the overall survival of 14v-positive patients with any stage of cancer was significantly worse than that for 14v-negative patients with stage IV cancer (P = 0·006). CONCLUSION: 14v status is an independent prognostic factor for gastric cancer, with 14v-positive gastric cancer having a poor prognosis, similar to that of M1 disease. The exclusion of 14v in regional lymph node dissection should be considered.

Time-resolved measurements of PM2.5 carbonaceous aerosols at Gosan, Korea.

In order to better understand the characteristics of atmospheric carbonaceous aerosol at a background site in Northeast Asia, semicontinuous organic carbon (OC) and elemental carbon (EC), and time-resolved water-soluble organic carbon (WSOC) were measured by a Sunset OC/ EC and a PILS-TOC (particle-into-liquid sampler coupled with an online total organic carbon) analyzer, respectively, at the Gosan supersite on Jeju Island, Korea, in the summer (May 28-June 17) and fall (August 24-September 30) of 2009. Hourly average OC concentration varied in the range of approximately 0.87-28.38 microgC m-3, with a mean of 4.07+/- 2.60 microgC m-3, while the hourly average EC concentration ranged approximately from 0.04 to 8.19 .microgC m-3, with a mean of 1.35 +/- 0.71 microgC m-3, from May 28 to June 17, 2009. During the fall season, OC varied in the approximate range 0.9-9.6 microgC m-3, with a mean of 2.30 +/-0.80 microgC m-3, whereas EC ranged approximately from 0.01 to 5.40 microgC m-3, with a mean of 0.66 +/- 0.38 microgC m-3. Average contributions of EC to TC and WSOC to OC were 26.0% +/- 9.7% and 20.6% +/-7.4%, and 37.6% +/- 23.5% and 57.2% +/- 22.2% during summer and fall seasons, respectively. As expected, clear diurnal variation of WSOC/OC was found in summer, varying from 0.22 during the nighttime up to 0.72 during the daytime, mainly due to the photo-oxidation process. In order to investigate the effect of air mass pathway on the characteristics of carbonaceous aerosol, 5-day back-trajectory analysis was conducted using the HYSPLIT model. The air mass pathways were classified into four types: Continental (CC), Marine (M), East Sea (ES) and Korean Peninsula (KP). The highest OC/EC ratio of 3.63 was observed when air mass originated from the Continental area (CC). The lowest OC/EC ratio of 0.79 was measured when air mass originated from the Marine area (M). A high OC concentration was occasionally observed at Gosan due to local biomass burning activities. The contribution of secondary OC to total OC varied approximately between 8.4% and 32.2% and depended on air mass type.

Effect of myofiber characteristics and thickness of perimysium and endomysium on meat tenderness of chickens.

The objective of the present study was to evaluate the role of myofiber characteristics and the thickness of 2 major muscle membranes, perimysium and endomysium, in determining the breast meat tenderness of chickens. Birds from 2 breeds (White Leghorn and a line of broiler) were chosen. Chicks were sexed and wing-banded at hatch and were grown in separate cages in a single house. Sixty broilers and 60 White Leghorns were harvested at 6 wk of age, respectively, whereas another 60 White Leghorns were slaughtered at 18 wk of age. An equal number of males and females was maintained for each group. Body weight, breast muscle weight, pH, drip loss, cooking loss, Warner-Bratzler shear force value (SFV), total energy of shear force, fiber diameter, sarcomere length, myofiber density, and the thickness of endomysium and perimysium of the breast were determined for each bird. At 6 wk of age, histological examination indicated that the size of myofiber and thickness of endomysium and perimysium of broilers were larger than that those of White Leghorns (P < 0.01), whereas the SFV, drip loss, and cooking loss of broilers were smaller (P < 0.01). A comparison between the White Leghorns at 18 wk and the broilers at 6 wk, which were at similar BW but different ages, showed that the breast muscle weight of broilers was larger (P < 0.01) than that of White Leghorns. For breast muscle, the endomysium of broilers at 6 wk was thicker than that of White Leghorns at 18 wk (P < 0.01), whereas the perimysium was thinner (P < 0.01). The SFV, drip loss, and the cooking loss of broilers were smaller than those of White Leghorns at similar BW (P < 0.01). Meat tenderness was negatively correlated with myofiber density (-0.27) and the thickness of endomysium (-0.29) and positively correlated with the thickness of perimysium (0.20). It is suggested that muscle membrane should be considered in evaluating meat tenderness of the chicken.

MicroRNA-328 acts as an anti-oncogene by targeting ABCG2 in gastric carcinoma.

OBJECTIVE: To explore the regulatory mechanism of microRNA-328 expression level by targeting the protein ATP Binding Cassette Transporter G2 (ABCG2) in gastric cancer cells and seek for a biological marker of predicting gastric cancer. PATIENTS AND METHODS: SGC-7901 and MKN-28 human gastric cancer cell lines were cultured. Meanwhile, paired gastric cancer pathological tissues and the corresponding adjacent normal tissues were collected. Western blot analysis was used to validate the protein expression of ABCG2. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis was used to detect the mRNA expression level of miR-328 and ABCG2. Cell counting kit-8 (CCK-8) and colony formation assay were performed to validate the proliferous ability of human gastric cancer cells. The transwell invasion and migration were operated to determine the migratory and invasive capacity. Dual-Luciferase reporter assay, qRT-PCR and Western blot were used to prove the target of miR-328. RESULTS: Bioinformatics analysis made a prediction that ABCG2 was a direct functional target of miR-328. Position 619-625 of ABCG2 3'-UTR had a space structure that was complementary to miR-328 by bioinformatics analysis, and there was a significant reduction in the level of miR-328 in human gastric cancer cell lines and tissues. The expression of miR-328 down-regulated proliferation, invasion and migration of human gastric cancer cells in vitro, while silencing of miR-328 accelerated proliferation, invasion and migration of human gastric cancer cells in vitro. All results displayed ABCG2 was direct target protein of miR-328 owing the binding site and they presented a negative correlation. CONCLUSIONS: ABCG2 is the target protein of miR-328. It presents a negative correlation of the expression level between miR-328 and ABCG2. Down-regulation of miR-328 inhibits the proliferation, invasion and migration of gastric cancer cell lines. MiR-328 could predict generation and development of gastric cancer as a biomarker.

Indication for endoscopic mucosal resection in early signet ring cell gastric cancer.

BACKGROUND: The aim of this study was to compare the clinicopathological characteristics of an early signet ring cell carcinoma (SRC) with an early undifferentiated carcinoma (mucinous, poorly differentiated adenocarcinoma) and early differentiated carcinoma (well or moderately differentiated tubular adenocarcinoma, papillary adenocarcinoma) and find indications for endoscopic mucosal resection (EMR) in early SRC. METHODS: 1520 patients with early gastric cancer (EGC), who underwent a curative gastrectomy, were analyzed retrospectively. Among them, 388 patients with SRC were compared with 253 patients with undifferentiated carcinoma (UDC) and 879 with a differentiated carcinoma (DC). RESULTS: SRC was more common in young female patients than UDC. SRC had a tendency to be confined to the mucosa, with smaller size than UDC. The lymph node metastasis rate for SRC was lower than that for UDC, but similar to that of DC. Multivariate analysis revealed lymph node metastasis (LNM) to be associated with the depth of invasion, tumor size, histological type, and lymphatic involvement. SRC had no LNM in the case of a mucosal tumor, smaller than 2 cm, and in the absence of lymphatic involvement. The prognosis of SRC was more favorable than UDC. CONCLUSIONS: Early SRC has different characteristics from early UDC. In view of the lower rate of lymph node metastasis and better prognosis, we suggest that EMR can be performed on patients with early SRC limited to the mucosa, less than 2cm in size, and with no lymphatic involvement.

Effects of zonisamide on isolated head tremor.

BACKGROUND AND PURPOSE: The medical treatment available for patients with essential tremor (ET) is often inadequate. Furthermore, the efficacy of the medical treatments currently available for patients with ET of cranial nerve areas is less satisfactory than that of the medical treatments available for patients with ET involving the upper extremities. This pilot study was performed to evaluate whether zonisamide (ZNS) is effective in the treatment of patients with isolated head tremor. METHODS: All subjects with isolated head tremor were randomly treated with either ZNS or propranolol. After a washout period, the subjects were switched to the alternative drug. RESULTS: ZNS was found to be more effective in the treatment of patients with isolated head tremor than propranolol. No severe adverse effects were reported with either ZNS or propranolol. CONCLUSION: ZNS may be more useful than propranolol for the treatment of ET patients with head tremor.

Primary malignant retroperitoneal tumors: analysis of a single institutional experience.

AIMS: In order to achieve complete resection in the surgical management of retroperitoneal tumors, it is crucial to know the tumor's anatomical location relative to neighboring organs. METHODS: Forty-nine patients with primary malignant retroperitoneal tumors were divided by tumor location into two groups [upper abdomen (group 1) or lower abdomen (group 2)], and clinicopathological features, tumor recurrence, and patient survival were assessed. RESULTS: No significant differences in preoperative clinical characteristics existed between two groups, and liposarcoma was the most frequently observed tumor type. The difference in the rates of complete resection between the two groups was not statistically significant (75.9% for group 1 and 85% for group 2). En-bloc combined resection was performed in 52% and 30% of patients in groups 1 and 2, respectively. The local recurrence rate in group 2 (31.3%) was higher than that in group 1 (9.5%), despite the fact that the differences in rates of complete resection and distant recurrence rates (14.3% in group 1 and 12.5% in group 2) between the two groups were not statistically significant. The overall 5-year survival rates were 67.9% for group 1 and 43.2% for group 2 (p=0.038). The 5-year survival rate of patients with tumors smaller than 10 cm was 78.4%, while that of patients with tumors larger than 10 cm was 38.1% (p=0.017). The 5-year survival rate after complete excision was 61%, whereas that after incomplete resection or biopsy only was 40.0% (p<0.0001). CONCLUSIONS: An upper abdominal tumor location is a positive prognostic factor even if small tumor size (<10 cm) and complete resection of the tumor are still more important factors to improve outcome in patients with malignant primary retroperitoneal tumors. Because complete resection was shown to be the most important prognostic factor, an aggressive and careful surgical approach is recommended for the treatment of such tumors.

Gastric GIST: a single institutional retrospective experience with surgical treatment for primary disease.

AIMS: Because gastric GISTs show variable clinical behavior, we reviewed our experience with primary gastric GISTs after surgical treatment and imatinib mesylate treatment for advanced disease. METHODS: Between December 1995 and December 2005, 111 patients who underwent surgical treatment for primary gastric GISTs were enrolled in this study. Patients were grouped according to the risk assessment classification, and clinicopathological features, tumor recurrence and patient survival were assessed. RESULTS: One patient was included in the very low risk group, 35 in the low risk group, 31 in the intermediate risk group and 44 in the high-risk group. All patients with very low, low and intermediate risk GISTs and 70% of patients with high risk GISTs underwent R0 resection. While there was no recurrence or metastasis in patients with very low, low and intermediate risk GISTs, 23% of those with high risk GISTs showed a distant metastasis at diagnosis and 35% of these patients had a recurrence after R0 resection. The overall 5-year survival rate of the high risk patients was 77.1%. Nineteen patients received imatinib mesylate therapy due to an incomplete resection or recurrence; 7 with no measurable lesion at the CT scan by a local tumor control showed no tumor progression after imatinib mesylate therapy, however, 12 patients with measurable lesions showed variable clinical courses after treatment. The overall 5-year survival rate of 19 patients with imatinib mesylate treatment was 80.0%. CONCLUSIONS: The clinical outcome of the very low, low and intermediate risk gastric GISTs was excellent, while high risk gastric GISTs had a high rate of recurrence and therefore a less favorable outcome. A complete resection is the most important treatment for cure; however imatinib mesylate treatment may improve the clinical outcome of the patients with metastatic or recurrent gastric GISTs.

Who may benefit from robotic gastrectomy?: A subgroup analysis of multicenter prospective comparative study data on robotic versus laparoscopic gastrectomy.

AIMS: Robotic gastrectomy for gastric cancer has been proven to be a feasible and safe minimally invasive procedure. However, our previous multicenter prospective study indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. This study aimed to identify which subgroups of patients would benefit from robotic gastrectomy rather than from conventional laparoscopic gastrectomy. METHODS: A prospective multicenter comparative study comparing laparoscopic and robotic gastrectomy was previously conducted. We divided the patients into subgroups according to obesity, type of gastrectomy performed, and extent of lymph node dissection. Surgical outcomes were compared between the robotic and laparoscopic groups in each subgroup. RESULTS: A total of 434 patients were enrolled into the robotic (n = 223) and laparoscopic (n = 211) surgery groups. According to obesity and gastrectomy type, there was no difference in the estimated blood loss (EBL), number of retrieved lymph nodes, complication rate, open conversion rate, and the length of hospital stay between the robotic and laparoscopic groups. According to the extent of lymph node dissection, the robotic group showed a significantly lower EBL than did the laparoscopic group after D2 dissection (P = 0.021), while there was no difference in EBL in patients that did not undergo D2 dissection (P = 0.365). CONCLUSION: Patients with gastric cancer undergoing D2 lymph node dissection can benefit from less blood loss when a robotic surgery system is used.

Glycoconjugated hypocrellin: synthesis of [(beta-D-glucosyl)ethylthiyl]hypocrellins and photosensitized generation of singlet oxygen.

In order to improve the water solubility and specific affinity for malignant tumors of hypocrellin, glycoconjugated hypocrellins have been synthesized using an improved Königs-Knörr reaction from mercaptoethanol substituted hypocrellin B and 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide precursors. Deprotection of glucose moieties allows the production of derivatives which had improved solubility in neutral aqueous solution and covered a range of amphiphilic character. The structures of these new protected and unprotected compounds were characterized by UV-Vis, IR, 1H-NMR and MS data. The present strategy should prove applicable to the synthesis of other glycoconjugated perylenequinone compounds. In addition, the quantum yield of singlet oxygen generation photosensitized by these glycoconjugated hypocrellins has been determined.

Biological nutrient removal in simple dual sludge system with an UMBR (upflow multi-layer bioreactor) and aerobic biofilm reactor.

In this study, a simple dual sludge process was developed for small sewage treatment. It is a hybrid system that consists of upflow multi-layer bioreactor (UMBR) as anaerobic and anoxic reactor with suspended growth microorganisms and post aerobic biofilm reactor with inclined plates. UMBR is a multifunction reactor that acts as primary sedimentation tank, anaerobic reactor, anoxic reactor, and thickener. The sludge blanket in the UMBR is maintained at a constant level by automatic control so that clear water (30 mg-SS/L) can flow into the post aerobic biofilm reactor. It leads to improving performance of the biofilm reactor due to preventing of excess microbial attachment on the media surface and no requirment for a large clarifier caused by low solid loading. The HRT in the UMBR and the aerobic biofilm reactor were about 5.8 h and 6.4 h, respectively. The temperature in the reactor during this study varied from 12.5 degrees C to 28.3 degrees C. The results obtained from this study show that effluent concentrations of TCOD, TBOD, SS, TN, and TP were 29.7 mg/L, 6.0 mg/L, 10.3 mg/L, 12.0 mg/L, and 1.8 mg/L, which corresponded to a removal efficiency of 92.7%, 96.4%, 96.4%, 74.9%, and 76.5%, respectively. The sludge biomass index (SBI) of the excess sludge in the UMBR was about 0.55, which means that the sludge in the UMBR was sufficiently stabilized and may not require further treatment prior to disposal.

The intracellular pathway of the acetylcholine-induced contraction in cat detrusor muscle cells.

1. The present study was aimed to investigate intracellular pathways involved in acetylcholine (ACh)-induced contraction in cat detrusor muscle cells 2. Contraction was expressed as per cent shortening of length of individually isolated smooth muscle cells obtained by enzymatic digestion. Dispersed intact and permeabilized cells were prepared for the treatment of drugs and antibody to enzymes, respectively. Using Western blot, we confirmed the presence of related proteins. 3. The maximal contraction to ACh was generated at 10(-11) M. This response was preferentially antagonized by M3 muscarinic receptor antagonist rho-fluoro-hexahydrosiladifenidol (rhoF-HSD) but not by the M1 antagonist pirenzepine and the M2 muscarinic receptor antagonist methoctramine. We identified G-proteins (Gq/11), (Gs), (G0), (Gi1), (Gi2) and (Gi3) in the bladder detrusor muscle. ACh-induced contraction was selectively inhibited by (Gq/11) antibody but not to other G subunit. 4. The phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitor neomycin reduced ACh-induced contraction. However, the inhibitors of the phospholipase D, the phospholipase A2 and protein kinase C did not attenuate the ACh-induced contraction. ACh-induced contraction was inhibited by antibody to PLC-beta1 but not PLC-beta3 and PLC-gamma. Thapsigargin or strontium, which depletes or blocks intracellular calcium release, inhibited ACh-induced contraction. Inositol 1,4,5-triphosphate IP3 receptor inhibitor heparin reduced ACh-induced contraction. 5. These results suggest that in cat detrusor muscle contraction induced by ACh is mediated via M3 muscarinic receptor-dependent activation of Gq/11 and PLC-beta1 and IP3-dependent Ca(2+) release.

Biological desulfurization in an optical-fiber photobioreactor using an automatic sunlight collection system.

Biological desulfurization using C. thiosulfatophilum has many more advantages over conventional physico-chemical methods due to low operational cost and no production of secondary pollutants. However, it requires effective and economical supply of light energy, which is a key factor in determining the success of commercialization. In this study, optical-fiber photobioreactor with internal illumination system was applied to increase the light availability. Furthermore, sunlight was used as the main light energy in the daytime and metal-halide lamp was applied as an additional light energy at night. Most UV light was eliminated by the chromatic aberration of the aspherical lenses in the solar light collector and 60% of infrared light intensity was eliminated. Physical scratching optical fibers enhanced the light availability about five times as much as that with unscratched ones in the previous study, but it resulted in the adsorption problem of elementary sulfur particles deteriorating light diffusivity considerably in a long operation. In order to solve this problem, scratched optical fibers were inserted into pyrex-glass tubes, which made light diffusivity nearly the same as that without glass tubes. Removal rate per unit cell concentration, using sunlight in the daytime and a metal-halide lamp at night, was 0.41 <0.73 micromol H(2)S min(-1)/(mg protein l(-1)) using a 400 W metal-halide lamp day and night, since the automatic sunlight collection system can transmit the light intensity as only 10% of that with a metal-halide lamp.

Synthesis, characterization and photodynamic activity of amino-substituted hypocrellin derivatives.

Three new hypocrellin derivatives, amino- or amino acid-substituted on the side ring of hypocrellin B (HB), were synthesized by the reactions of HB with 3-methoxypropylamine, 6-aminohexanoic acid and gamma-amino-n-butyric acid, respectively. The structures of these compounds were characterized with proton nuclear magnetic resonance spectra, infrared spectra and mass spectra. The UV-visible absorption spectra, singlet oxygen-generating quantum yield and amphiphilicities of hypocrellin derivatives were measured and compared with HB, the parent compound. These derivatives showed strong absorption in the domain of the phototherapeutic window (600-900 nm) and improved amphiphilicity. HB and the derivatives were preliminarily tested for their photodynamic effects on human oral cavity epithelial carcinoma KB cell line in vitro. Two amino acid-substituted hypocrellins showed phototoxicity to the KB cell line. At an inhibitory dosage of 50% killing only 0.51 mumol L-1 compound 3 (or 0.88 mumol L-1 compound 2) and 0.5 J cm-2 irradiation were required. The hypocrellins exhibited some dark toxicity to the KB cell line. HB and amino acid-substituted hypocrellins showed lower dark toxicity to the KB cell line than amino-substituted hypocrellins in the assessment of cell survival.

Hypocrellin-A sensitized photooxidation of bilirubin.

Hypocrellin A (HA) extracted from Hypocrellia bambusae (b.et Br.) sace, a derivative of 3,10-dihydroxy-4,9-perylenequinone, is a highly effective photosensitizer. Kinetic studies of the HA-sensitized photooxidation of bilirubin IX alpha (BR) in different solvents in the presence of various active oxygen quenchers indicate that in aprotic solvents the photooxidation goes via a Type II (1O2) mechanism, whereas in alkaline protic solvents Type I (electron transfer from an excited state of HA to the ground state of oxygen or the BR substrate). Type II and probably free radical reactions may occur simultaneously.

Pharmacokinetics, tissue distribution and photodynamic therapy efficacy of liposomal-delivered hypocrellin A, a potential photosensitizer for tumor therapy.

Hypocrellin A, from Hypocrella bambusae, is a novel photosensitizer of high singlet oxygen quantum yield for photodynamic therapy (PDT). Tissue distributions were studied in tumor-bearing mice as a function of time following administration. The tumor model was S-180 sarcoma transplanted into one hind leg of male Kunming mice; hypocrellin A (HA) was delivered to the mice by intravenous injection of 5 mg/kg of body weight as a suspension either as a unilamellar liposome or in dimethyl sulfoxide (DMSO)-solubilized saline. The HA was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin. Quantitation was performed by a high-performance liquid chromatographic technique with detection that utilizes the native fluorescence of HA. Independent of the delivery system, the dye was retained in tumors at higher concentrations than in normal tissues, except for kidney, liver, lung and spleen. The dye retention in tumors was high and was vehicle dependent. For the liposomal system, the maximal accumulation in tumor and maximal ratios of dye in tumor versus peritumoral muscle and skin occurred 12 h postinjection; for the DMSO saline system, the maximal ratio occurred earlier, 6 h postadministration. Liposomal delivery improved the selective accumulation of the dye in tumor with higher maximal levels in tumor and higher ratios of tumor-to-muscle and tumor-to-skin. Levels of dye were very low or not detectable in the brain. The PDT efficacy of HA in the liposome and DMSO saline systems was determined by evaluating the tumor volume regression percent. The PDT efficacy of HA in liposomes was highest when light treatment was performed at 12 h postinjection, consistent with the highest retention of HA in tumors. Similarly, the maximal PDT efficacy in DMSO saline was attained at 6 h postinjection, the highest HA retention point in tumor. Moreover, the peak PDT efficacy of HA in liposomes was much higher than that of HA in DMSO saline and even hematoporphyrin monomethylether.