Characteristics of the glycometabolic categories based on the oral glucose tolerance test results in Japanese adults without diabetes.

OBJECTIVE: We aimed to classify Japanese adults without diabetes into different categories based on the oral glucose tolerance test (OGTT) and characterize their insulin sensitivity and insulin secretion. PATIENTS AND METHODS: The OGTT was performed on 1,085 Japanese individuals without diabetes (aged 20-64 years); blood glucose and insulin levels were measured at 0, 30-, 60-, 90-, and 120-min. Fasting blood chemistry, hematology, and urine were analyzed. The participants were classified into four categories based on the following: (A) 30 min post-load plasma glucose levels < 157 mg/dL and/or (B) 120 min post-load plasma glucose levels < 126 mg/dL and Matsuda index > 4.97. Category 1 satisfied both conditions, category 2 satisfied condition A but not B, category 3 satisfied condition B but not A, and category 4 satisfied neither condition. RESULTS: Overall, 46%, 21%, 13%, and 20% of the participants were classified into categories 1, 2, 3, and 4, respectively. Compared with category 1, the characteristics of the other categories were: 2, low insulin sensitivity and high blood glucose levels during the later period; 3, low insulin secretion and a rapid increase in blood glucose levels; and 4, combined characteristics of categories 2 and 3. Most blood test values besides glucose metabolism in category 4 were also worse than those in category 1. Categories 1 and 2 had a high proportion of females, whereas categories 3 and 4 had a low proportion. CONCLUSIONS: Japanese adults without diabetes are classified into four categories with different insulin sensitivities and insulin secretion using OGTT results. Each category has different characteristics of age and sex distribution and clinical values besides glucose metabolism.

Randomized, double-blind, crossover, placebo-controlled clinical trial to evaluate the effects of chicken hot water extract on insulin secretion.

OBJECTIVE: Essence of chicken (EOC), a hot water extract of chicken, is widely consumed in Southeast Asia as a beverage. EOC has an inhibitory effect on the elevation of blood glucose levels and a secretagogue effect on insulin. However, the mechanism by which EOC promotes insulin secretion is unknown. We aimed to verify the postprandial hyperglycemic inhibitory effect and the insulin secretory effect of EOC in healthy adults under appropriate placebo settings. In addition, we aimed to understand the mechanism underlying the insulin secretory effect of EOC. PATIENTS AND METHODS: Thirty-four healthy Japanese adults were fed 68 mL of EOC or control food, followed by 200 g of cooked rice. Blood glucose and plasma insulin levels were measured at 30, 45, 60, 90, and 120 min after the participants ate cooked rice. The trial had a randomized, double-blind, crossover, placebo-controlled design. RESULTS: The ingestion of EOC induced an increase in the maximum blood concentration (Cmax) of insulin and shortened the time required to reach the maximum blood concentration following rice consumption. Ingestion of the test beverage resulted in a significantly higher insulinogenic index than that obtained after ingestion of the control beverage. No side effects were observed in this study. Mechanistic experiments revealed that EOC stimulated significant (p < 0.05) secretion of GLP-1 from NCI-H716 human intestinal L cells at 0.1, 1, and 10 mg/mL. CONCLUSIONS: Consuming EOC when eating rice supports pancreatic function. Daily consumption of EOC could elevate the early-phase insulin response; therefore, it could prevent diabetes in Asians with low insulin secretion.

Hop-derived prenylflavonoid isoxanthohumol suppresses insulin resistance by changing the intestinal microbiota and suppressing chronic inflammation in high fat diet-fed mice.

OBJECTIVE: To assess whether the hop-derived polyphenol isoxanthohumol suppresses insulin resistance by changing the intestinal microbiota. MATERIALS AND METHODS: Male C57BL/6J mice (7 weeks of age) were divided into five groups (n = 9-10): Normal Diet (ND), High Fat Diet (HFD), HFD + low dose isoxanthohumol (0.01%IX), HFD + medium dose isoxanthohumol (0.03% IX), and HFD + high dose isoxanthohumol (0.1% IX). Oral glucose tolerance tests (OGTTs) were performed at 4 and 8 weeks, and insulin tolerance tests (ITTs) were performed at 13 weeks. 16S rRNA gene sequencing analyses revealed the fecal microbiota profiles, and the relative abundance of Akkermansia muciniphila and Clostridium cluster XI was calculated by qRT-PCR. Plasma lipopolysaccharide (LPS) levels were measured by ELISA, and mRNA expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in epididymal adipose tissues were measured by qRT-PCR. RESULTS: Isoxanthohumol showed antibacterial activity towards several bacterial species and mitigated impaired glucose tolerance and insulin resistance induced by the HFD in a dose-dependent manner, as shown by OGTTs and ITTs. The concentration of phylum Verrucomicrobia bacteria dramatically increased in the 0.1% IX group, the relative abundance of A. muciniphila increased, and that of Clostridium cluster XI decreased. Moreover, the intake of isoxanthohumol decreased the levels of plasma LPS and mRNA expression of TNF-α and IL-1ß in epididymal adipose tissues. CONCLUSIONS: We found that isoxanthohumol can suppress HFD-induced insulin resistance by changing the intestinal microbiota and reducing the expression of inflammation factors.

The anti-inflammatory effect of 10-oxo-trans-11-octadecenoic acid (KetoC) on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide.

BACKGROUND: There is rapidly developing interest into the role of several anti-inflammatory agents to resolve inflammation in periodontal disease. A bioactive polyunsaturated fatty acid, 10-oxo-trans-11-octadecenoic acid (KetoC), is known to have various beneficial physiological effects; however, the effect of KetoC on inflammation remains unclear. Here, we investigated the effect of KetoC on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide, and explored the intracellular mechanism responsible for its anti-inflammatory effects. METHODS: RAW 264.7 cells were pre-treated with or without KetoC, and then stimulated with or without P. gingivalis lipopolysaccharide. Levels of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1ß were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Specific antagonists for G protein-coupled receptor (GPR)40 and GPR120 were used to clarify the receptor for KetoC. The intracellular mechanism was investigated using western blotting analysis to separate nuclear and cytosolic NF-κB p65 protein. RESULT: KetoC (5 µmol/L) was not toxic to RAW 264.7 cells, and significantly reduced the expression of TNFα and IL-6 mRNA and protein, and IL-1ß mRNA. No protein production of IL-1ß was observed. Additionally, when bound to GPR120, KetoC trended to downregulate nuclear NF-κB p65 protein levels. However, the antagonist for GPR40 failed to diminish the action of KetoC. CONCLUSION: KetoC suppressed the proinflammatory cytokines TNFα, IL-6 and IL-1ß via NF-κB p65, by binding to its receptor GPR120. KetoC is a promising candidate in future studies as a bioactive anti-inflammatory agent in treating periodontal disease.

Effects of rapid or slow body weight reduction on intramuscular protein degradation pathways during equivalent weight loss on rats.

The purpose of this study was to compare the effects of short-term fasting-induced rapid weight loss with those of slower but equivalent body weight loss induced by daily calorie restriction on muscle protein degradation pathways and muscle protein content. Male Fischer rats were subjected to either 30 % calorie restriction for 2 weeks to slowly decrease body weight (Slow) or 3-day fasting to rapidly decrease body weight by a comparable level of that of the Slow group (Rapid). The final body weights were about 15 % lower in both the Slow and Rapid groups than in the Con group (p<0.001). The total protein content and wet weight of fast-twitch plantaris muscle, but not slow-twitch soleus muscle, were significantly lower in the Rapid group compared with the control rats fed ad libitum. Substantial increases in the expression ratio of autophagosomal membrane proteins (LC3-II/-I ratio) and polyubiquitinated protein concentration, used as biomarkers of autophagy-lysosome and ubiquitin-proteasome activities, respectively, were observed in the plantaris muscle of the Rapid group. Moreover, the LC3-II/-I ratio and polyubiquitinated protein concentration were negatively correlated with the total protein content and wet weight of plantaris muscle. These results suggest that short-term fasting-induced rapid body weight loss activates autophagy-lysosome and ubiquitin-proteasome systems more strongly than calorie restriction-induced slower weight reduction, resulting in muscular atrophy in fast-twitch muscle.

Natural killer T cells mediate alveolar bone resorption and a systemic inflammatory response in response to oral infection of mice with Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: T and B cells are known to be involved in the disease process of periodontitis. However, the role of natural killer T cells in the pathogenesis of periodontitis has not been clarified. MATERIALS AND METHODS: To examine the role of these cells, C57BL/6J (wild-type), CD1d(-/-) and α-galactosylceramide (αGC)-stimulated wild-type mice were orally infected with Porphyromonas gingivalis strain W83. RESULTS: Apart from CD1d(-/-) mice, the level of alveolar bone resorption was elevated by the infection and was further accelerated in αGC-stimulated mice. The infection induced elevated levels of serum amyloid A and P. gingivalis-specific IgG in the sera, although the degree of elevation was much smaller in the CD1d(-/-) mice. Infection-induced RANKL elevation was only observed in αGC-stimulated mice. Although the cytokines produced by splenocytes were mainly T-helper 1 type in wild-type mice, those in αGC-stimulated mice were predominantly T-helper 2 type. In the liver, the infection demonstrated no effect on the gene expression for interferon-γ, interleukin-4 and RANKL except αGC-stimulated mice in which the infection upregulated the gene expressions. CONCLUSION: This study is the first to show that natural killer T cells upregulated systemic and local inflammatory responses induced by oral infection with P. gingivalis, thereby contributing to the progression of alveolar bone resorption.

Multicentred surgical site infection surveillance using partitioning analysis.

BACKGROUND: Surgical site infection (SSI) is an ongoing major public health problem throughout the world that increases healthcare costs. Utilizing a methodology that can help clinicians to continuously collect data about SSIs, analyse it and implement the feedback into routine hospital practice has been identified as a top national priority in Japan. AIM: To conduct an intervention study through 'operations research' using partitioning at multiple facilities, and to reduce the incidence and consequences of SSI. METHODS: The Setouchi SSI Surveillance Group, which consists of seven institutes, started SSI surveillance in 2006. Until May of 2008, there were four surveillance periods (A-D). In all, 3089 patients underwent gastrointestinal surgery and were followed up for 30 days after their operations. Twenty-six factors that have been reported to be related to SSI were evaluated for all patients. The top three factors from each surveillance period were determined and then actual practice improvements were planned for each subsequent period. FINDINGS: The total SSI occurrence was 6.9% for period A, 6.3% for period B, 6.4% for period C and 3.9% for period D. Comparing periods A and D, there was a statistical significance in the decrease of SSI occurrence (P = 0.012). CONCLUSION: Using the results and partitioning analysis of active SSI surveillance to contribute to action plans for improving clinical practice was effective in significantly reducing SSIs.

Determination of aflatoxins in food samples by automated on-line in-tube solid-phase microextraction coupled with liquid chromatography-mass spectrometry.

A simple and sensitive automated method for determination of aflatoxins (B1, B2, G1, and G2) in nuts, cereals, dried fruits, and spices was developed consisting of in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-mass spectrometry (LC-MS). Aflatoxins were separated within 8 min by high-performance liquid chromatography using a Zorbax Eclipse XDB-C8 column with methanol/acetonitrile (60/40, v/v): 5mM ammonium formate (45:55) as the mobile phase. Electrospray ionization conditions in the positive ion mode were optimized for MS detection of aflatoxins. The pseudo-molecular ions [M+H](+) were used to detect aflatoxins in selected ion monitoring (SIM) mode. The optimum in-tube SPME conditions were 25draw/eject cycles of 40 microL of sample using a Supel-Q PLOT capillary column as an extraction device. The extracted aflatoxins were readily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC-MS with SIM method, good linearity of the calibration curve (r>0.9994) was obtained in the concentration range of 0.05-2.0 ng/mL using aflatoxin M1 as an internal standard, and the detection limits (S/N=3) of aflatoxins were 2.1-2.8 pg/mL. The in-tube SPME method showed >23-fold higher sensitivity than the direct injection method (10 microL injection volume). The within-day and between-day precision (relative standard deviations) at the concentration of 1 ng/mL aflatoxin mixture were below 3.3% and 7.7% (n=5), respectively. This method was applied successfully to analysis of food samples without interference peaks. The recoveries of aflatoxins spiked into nuts and cereals were >80%, and the relative standard deviations were <11.2%. Aflatoxins were detected at <10 ng/g in several commercial food samples.

A novel calpain inhibitor, ((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester, protects neuronal cells from cerebral ischemia-induced damage in mice.

Cerebral ischemia induces Ca(2+) influx into neuronal cells, and activates several proteases including calpains. Since calpains play important roles in neuronal cell death, calpain inhibitors may have potential as drugs for cerebral infarction. ((1S)-1((((1S)-1-Benzyl-3- cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945) is a novel calpain inhibitor that has good membrane permeability and water solubility. We evaluated the effect of SNJ-1945 on the focal brain ischemia induced by middle cerebral artery occlusion (MCAO) in mice. Brain damage was evaluated by assessing neurological deficits at 24 h or 72 h after MCAO and also by examining 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining of brain sections. When injected at 1 h after MCAO, SNJ-1945 at 30 and 100 mg/kg, i.p. decreased the infarction volume and improved the neurological deficits each assessed at 24 h. SNJ-1945 at 100 mg/kg, i.p. also showed neuroprotective effects at 72 h and reduced the number of TUNEL-positive cells at 24 h. SNJ-1945 was able to prevent neuronal cell death even when it was injected at up to 6 h, but not at 8 h, after MCAO. In addition, SNJ-1945 decreased cleaved alpha-spectrin at 6 h and 12 h, and active caspase-3 at 12 h and 24 h in ischemic brain hemisphere. These findings indicate that SNJ-1945 inhibits the activation of calpain, and offers neuroprotection against the effects of acute cerebral ischemia in mice even when given up to 6 h after MCAO. SNJ-1945 may therefore be a potential drug for stroke.

The Stenting to Internal Carotid Artery Stenosis (ICS) in Petrous Portion. The Evaluation of Plaque Figures in Magnetic Resonance Image.

SUMMARY: In the safety stenting, it is important to get to know the characteristics of a plaque. In petrous carotid artery stenosis, it is difficult to know the characteristics of the plaque.We paid our attention to the MPRAGE (Magnetization Prepared Rapid Acquisition with Gradient Echo) method on high resolving power MRI. By the MPRAGE method, low intensity was observed in these lesions of all cases. This result suggested that the plaque in petrous portion was a fibrous plaque. This method is useful to get to know the characteristics of a plaque in petrous portion before endovascular treatment.

A molecular biological study of anti-tumor mechanisms of an anti-cancer agent Oxaliplatin against established human gastric cancer cell lines.

We report that preoperative administration of Oxaliplatin, a new anti-cancer platinum agent, is an effective treatment for gastric cancer. The purpose of this in vitro study is to determine whether Oxaliplatin induces apoptosis in established human gastric cancer cell lines. Five established gastric cancer cell lines are used: MNK45, KATO-III, OKAJIMA, MNK28 and MNK74. Chemosensitivity to l-OHP is studied using a growth inhibition test. Induction of apoptosis in gastric cancer cells is analyzed by assessing DNA ladder formation, DNA fragmentation and actin cleavage. While all five gastric cancer cell lines are sensitive to Oxaliplatin, the poorly differentiated lines are the most sensitive. DNA ladder formation and/or DNA fragmentation are detected in all gastric cancer cell lines. However, actin cleavage is not detected in any of the cell lines. Oxaliplatin has an anti-cancer effect on human gastric cancer cell lines, particularly cell lines of poorly differentiated adenocarcinoma, indicating that Oxaliplatin would be an effective treatment for poorly differentiated gastric cancer. Oxaliplatin induces apoptosis in gastric cancer cell lines, but actin cleavage is not detected in cancer cells. This finding suggests that (1) the apoptotic caspase pathway leads mainly to DNA condensation and fragmentation, and (2) caspase-independent apoptotic pathways may be activated when gastric cancer cells are treated with Oxaliplatin.

Chronotherapy for cancer.

Cancer chronotherapy is attracting attention as a novel and logical therapy in which anti-cancer drugs are administered with optimal timing according to circadian rhythms of anti-cancer action and those of adverse effects on normal cells. Advances in chronobiology have identified the suprachiasmatic nucleus (SCN) as the center of biological rhythms and the area in which clock genes such as PER1, PER2, PER3, CLOCK, BMAL1, TIM, CRY1, CRY2, tau act to generate and coordinate biological rhythms. These findings have led to the development of chronotherapy. Clinically, patients with advanced gastrointestinal cancer have been treated by chronomodulated chemotherapy with good response. For colorectal cancer patients with unresectable liver metastases, chronotherapy with l-OHP + 5-FU + FA (folinic acid) has been reported to allow complete surgical resection of liver metastases, resulting in 39-50% 5-year survival. Many believe that chronotherapy will become accepted as a refined and advantageous therapeutic option for not only cancer but also for other diseases, due to its universally applicable principles.

Dural arteriovenous fistula of the transverse sinus with concomitant ipsilateral meningioma.

A 69-year-old female complained of headache and tinnitus. Computed tomography, magnetic resonance imaging, and angiography showed a tumour in the right transverse sinus extending to the transverse-sigmoid sinus junction, a dural arteriovenous fistula (AVF), and right transverse-sigmoid sinus thrombosis with the downstream from the right sigmoid sinus involved by the tumour. Right external carotid angiography showed the tumour to be supplied by many branches of the right occipital artery, the posterior branches of the middle meningeal artery, and the posterior auricular artery, and the dural AVF fed by the occipital artery and the meningeal branches of the right vertebral artery. She underwent surgery via a combined right supra- and infratentorial approach. The tumour had invaded and blocked the right transverse sinus, which was resected. After surgery the patient was free of headache and tinnitus was diminished. Histological examination found that the tumour was a fibrous meningioma and that the orifice of the vein at the transverse sinus was blocked by the tumour. Serial follow-up cerebral angiography 2 months after surgery showed no change in the AVF, but 9 months after surgery confirmed disappearance of the AVF. This AVF was caused by occlusion of the right transverse sinus by the meningioma and was an acquired lesion.

Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients with brain tumors.

Although specific immunotherapy is one candidate treatment of brain tumor, the molecular basis of T-cell-mediated recognition of brain tumors has not yet been elucidated. In this study, we tried to identify brain tumor antigens using HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs). As an HLA-A2-restricted OK-CTL line contained CTLs capable of responding to HLA-A2+ malignant glioma cells, this cell line was used for identification of brain tumor antigens. After screening a cDNA library from brain tumor cells, this CTL line was found to produce interferon (IFN)-gamma when cultured with COS-7 cells, which were cotransfected with both a cDNA clone (clone 1) and HLA-A0207 cDNA. Data base searches indicated that the clone 1 was 98% identical to that of the human ADP-ribosylation factor 4-like (ARF4L). Two peptides, ARF4L 15-24 and ARF4L 69-77, possessed the ability to induce HLA-A2-restricted and tumor-reactive CTLs from peripheral blood mononuclear cells of patients with brain tumors. Although ARF4L seemed to be ubiquitously expressed at the mRNA level, ARF4L-reactive CTLs failed to exhibit cytotoxicity against normal lymphoid blasts. These results indicate that these two ARF4L peptides could be targets for immunotherapy of HLA-A2+ patients with brain tumors.

UDP-Gal: betaGlcNAc beta1, 3-galactosyltransferase, polypeptide 3 (GALT3) is a tumour antigen recognised by HLA-A2-restricted cytotoxic T lymphocytes from patients with brain tumour.

Patient prognosis in the case of malignant brain tumours is generally poor, despite significant improvements in the early detection of the tumours, and thus the development of new treatment modalities is needed. One of the most prominent modalities is specific immunotherapy, for which the elucidation of antigenic molecules of malignant brain tumours recognized by T cells is essential. We report here a gene, UDP-Gal: betaGlcNAc beta1, 3-galactosyltransferase, polypeptide 3, encoding three epitope peptides recognised by tumor-reactive cytotoxic T lymphocytes in an HLA-A2-restricted manner. Two of the three peptides possessed an ability to induce HLA-A2-restricted and tumour-reactive cytotoxic T lymphocytes from peripheral blood mononuclear cells of patients with brain tumours. These peptides may be useful in the peptide-based specific immunotherapy for patients with malignant brain tumours.

Low-dosage intravenous immunoglobulin in the management of a patient with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance.

We report herein the case of a 69-year-old Japanese man with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance who developed IgG1-kappa antibodies against von Willebrand factor (VWF). The patient was urged to undergo tooth extractions because of alveolar pyorrhea, and a low-dosage intravenous immunoglobulin (IV-Ig) therapy (0.3 g of IgG/kg/day for 3 days) was chosen for him. On the 4th day after the infusion, VWF antigen and VWF ristocetin cofactor increased to 40 and 78% of the control, respectively, and dental extractions were performed successfully. On the 7th day, these values reached a maximum, i.e. 95 and 160% of the control, respectively. Then, they quickly decreased to 35 and 75% on the 10th day, and 6 months later, they became 16 and <3% of the control, respectively. Upon analysis of plasma VWF multimers (VWFMs) in this patient, those with large to medium molecular masses more selectively disappeared before the IV-Ig infusion than did those with small molecular masses. On the 4th day, the pattern of VWFMs was completely normalized and appeared to persist until the 10th day. Six months later, a small amount of large to medium-sized VWFMs was still present, but at 7-8 months, the pattern of VWFMs became almost the same as that before infusion. Throughout the patient's clinical course, the activity of plasma VWF-cleaving protease, which specifically cleaves the Tyr842-Met843 bond of the subunit and reduces its multimeric sizes, was quite normal (95-119%). These results provided consistent evidence that the selective absence of VWFMs with large to medium molecular masses in this patient is caused by the heightened clearance of a complex of IgG inhibitor and VWFMs from the circulation, presumably through IgG binding to the Fc receptor of macrophages. Furthermore, these results also indicated that a low-dosage IV-Ig therapy is effective enough for hemostatic management for programmed surgery.

Bcl-2, Bcl-xL and c-FLIP(L) potentially regulate the susceptibility of human peripheral blood monocyte-derived dendritic cells to cell death at different developmental stages.

We examined the susceptibility of human monocyte-derived dendritic cells (DCs) to spontaneous and CD95-mediated cell death at different developmental stages. Time course experiments revealed that the susceptibility of mature dendritic cells (mDCs) to spontaneous cell death was significantly lower than that of immature dendritic cells (iDCs) in a long-term culture under cytokine-free conditions, and the treatment with GM-CSF rescued these cells from spontaneous cell death at the late culture period. iDCs and mDCs expressed similar levels of CD95 whereas both cell types were relatively resistant to CD95-mediated cell death. Antigen (Ag)-specific and nonspecific cognate interaction with T cells failed to cause cell death of iDCs and mDCs. iDCs constitutively expressed transcripts and intracellular products of Bcl-2 and Bcl-xL, but not cellular FLICE-inhibitory protein(long (c-FLIP(L)), while the increased expressions of Bcl-2, Bcl-xL and c-FLIP(L) were observed in mDCs. These results suggest that the selective expressions of Bcl-2, Bcl-xL and c-FLIP(L) may be involved in the difference in the susceptibility to cell death between iDCs and mDCs.

Inhibition of growth of human breast cancer cells in culture by neutron capture using liposomes containing 10B.

Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4 microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation.

Simultaneous removal of nitrogen and phosphorus with A2/O process using immobilized media.

It is necessary to introduce nitrogen and phosphorus removal processes in the existing wastewater treatment plants of Fukuoka City to improve the water quality of Hakata Bay. An A2/O (anaerobic-anoxic-oxic) process using immobilized media is proposed here, as a high-end technology to meet stricter discharge standards when faced with treatment space limitations. In order to investigate the applicability of the process, a pilot-scale study using municipal wastewater was conducted. Fluidized immobilization media were added to the aerobic reactor to maintain a high concentration of nitrifying bacteria and nitrification rate. Relationships between nutrient removal performance and varied operating conditions were examined. The results of the pilot plant test indicated that the process performs well for removal of nitrogen and phosphorus. Under the condition of HRT = 8 hr, it was possible to obtain an effluent water quality as follows: T-N<8.0 mg/L; T-P<1.0 mg/L. It was observed that reaction time needed for a complete nitrification was shortened by the addition of immobilized media to the aerobic reactor, and longer reaction time would be needed for a completed phosphorus uptake process other than complete nitrification in an aerobic tank. Therefore, the phosphorus uptake rate, as well as nitrification process, should be considered as one of the important factors affecting the design parameters of an aerobic reactor.