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Biopharmaceuticals, including therapeutic genes and proteins, are characterized by highly-targeted, specific action and flexible pharmacological design and have a rapidly growing market share; however, because of high molecular weight and low stability, injection is the most common delivery route of biopharmaceuticals. Thus, pharmaceutical innovations are required to provide alternative delivery routes for biopharmaceuticals. Pulmonary drug delivery via inhalation is a promising approach, particularly for targeting local diseases of the lung, because it can exert therapeutic effects in small doses and can noninvasively and directly deliver drugs to airway surfaces. However, biopharmaceutical inhalers must ensure that the biopharmaceuticals maintain their integrity as they are subjected to several types of physicochemical stress, such as hydrolysis, ultrasound, and heating, at various stages during the process from manufacturing to administration. In this symposium, I present a novel dry powder inhaler (DPI) preparation method without heat-drying, with the goal of developing biopharmaceutical DPIs. Spray-freeze-drying is a nonthermal drying technique that produces a powder with porous shapes; this powder has suitable inhalation characteristics for DPI. A model drug, plasmid DNA (pDNA), was stably prepared as a DPI using the spray-freeze-drying process. Under dry conditions, the powders maintained high inhalation characteristics and maintained pDNA integrity for 12 months. The powder induced pDNA expression in mouse lungs that exceeded at higher levels than the solution did. This novel preparation method is suitable for DPI preparation for various drugs and may help expand the clinical application of DPIs.

Owing to their ability to induce excitation of specific molecular orbitals or initiate chemical reactions, photochemical reactions have the potential to be more effective at selectively activating target molecules than thermal reactions. The thermal reactions transfer thermal energy to activate molecules, which often leads to the activation of multiple molecular species, including undesired ones, resulting in non-selectivity. This nonselectivity may result in undesirable side reactions or decrease reaction efficiency. Additionally, photochemical reactions can induce selective activation by absorbing specific wavelengths of light. However, visible light-driven photocatalytic reactions typically require expensive transition metal catalysts or organic dyes, leaving plenty of room for improvement. To address the aforementioned issues, the photochemical properties of the main group elements, such as halogens, were optimized and methodologies for visible light-induced reactions were developed. Activation of molecular halogen, halogen-carbon bonds, and halogen bonding interactions were independently investigated and various methodologies were reported. These developed reactions are excellent methodologies that use inexpensive raw materials and are thus predicted to contribute significantly toward sustainability.

Barley tea (Mugicha), commonly consumed in Japan and other East Asian countries, is prepared by decocting roasted barley (Hordeum vulgare) seed with hot or cold water. Although barley tea is commonly consumed, studies on its health benefits are limited, especially regarding its bioactivity against thrombosis. During the evaluation of functional foods and drinks, barley tea extract was found to exhibit potential fibrinolysis-enhancing activity induced by urokinase. Therefore, the aim of this study was to explore the application of barley tea as a functional food and conduct a preliminary investigation to reveal the effects of barley tea on thrombosis. Hot water extract of roasted barley was treated with pancreatin and separated via various techniques using macroporous resin and silica gel and tangential flow filtration with an ultra-filtration membrane. The low-molecular-weight fraction of the roasted barley tea extract was found to possess activity. We further purified the extract and found that the activity of each fraction decreased. Thus, the different fractions of the roasted barley extract may not exhibit the activity individually, instead additive or synergistic effects of multiple components may occur. The results suggest the potential use of barley extract as a functional food to prevent thrombosis.

Controlled drug release in response to light irradiation is an important technique for focusing drug elution to specific sites and reducing the side effects of drugs in normal tissue. In one example, we used double-stranded DNA to modify gold nanorods. When the gold nanorods were heated by irradiation with near-infrared light, single-stranded DNA was released. Thus, we successfully prepared a controlled release system that responds to near-infrared irradiation by combining heat-labile linkers such as double-stranded DNA. However, the drug-loading capacity on the surface of the nanoparticles was limited. To improve the loading efficiency, we encapsulated gold nanorods in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, where PLGA acted as a drug payload. When the gold nanorod-containing PLGA nanoparticles were irradiated with a near-infrared laser, the PLGA nanoparticles were destroyed and significant drug release was observed. In another example, silver nanoplates were used as a near-infrared responsive photothermal nanodevice. Silver nanoparticles show antimicrobial activity that we expected could be controlled by light irradiation. First, we coated the silver nanoplates with gold atoms to mask the antimicrobial activity. When the gold-coated silver nanoplates were irradiated with a near-infrared pulsed laser, the shape of the silver nanoplates changed from plate-like to spherical, and silver ions were released. As a result, the antibacterial activity of the silver nanoplates was recovered. In this review, we outline examples of controlled release systems that respond to light irradiation. We believe that this review will contribute to improving the efficiency and safety of chemotherapy.

In Japan, the import quarantine procedure for dairy products was newly introduced in November 2017. The treatment such as 15 sec heating at 72℃ is required for virus inactivation when importing milk or dairy products from the area which is not free from foot and mouth disease. Moreover, the heating history of imported items is also inspected as import quality procedures. The IDF 63 method is known as one of the methods to confirm the heating history of milk by checking the alkaline phosphatase (ALP) activity. However, this procedure is complicated for daily quarantine inspection. Therefore, we attempted the ALP activity measurement based on the amount of fluorescent substance produced by the enzymatic reaction. Milk and dairy products derived from cow, sheep, and goat were tested after various heat treatment conditions. The ALP of heat-treated milk and dairy products derived from these species above were confirmed to be inactivated under substantially the same heat treatment for 15 sec at 72℃. The measurement method established in this study is simpler, faster, and requires smaller amount of sample compared to other methods. Additionally, the method was also applicable to confirm the heating history of various dairy products by making them into suspension.

In this study, we evaluated the efficiency of fly ash (FA) recycling technology, produced from a coal-fired power plant, with the capability to adsorb cesium ion[Cs(I)] and strontium ion [Sr(II)] from aqueous phase. Zeolite was produced from FA by hydrothermal treatment in an alkaline solution. Zeolite 12, 24, and 48 have a Garronite structure. Moreover, the specific surface area of Zeolite was greater than that of FA. Zeolite 12 demonstrated the adsorption capability of Cs(I) and Sr(II) from aqueous phase. Adsorption isotherms data fitted both the Langmuir equation (correlation coefficient: >0.895) and the Freundlich equation (correlation coefficient: >0.881). In addition, the kinetic data fitted the pseudo-second-order model when compared to the pseudo-first-order model. Cs(I) and Sr(II) were selectively adsorbed by Zeolite 12 in complex solution system. Our findings indicate that Zeolite can be produced from FA by hydrothermal treatment in an alkaline solution and shows the capability to adsorb Cs(I) and Sr(II) from aqueous phase. Therefore, Zeolite can be useful adsorbent for purification in water environments.

Epidemiological studies have shown that coffee consumption may be associated with a lower risk of developing several chronic disorders. To elucidate the molecular mechanism of the effects of coffee, we analyzed molecular response upon exposure to coffee extract using cellular and animal models of these diseases. As obesity is recognized as a major risk factor for these chronic diseases, we investigated the effect of coffee on adipogenesis using mouse preadipocyte 3T3-L1 cells. We found that coffee induced proteasomal degradation of IRS-1, leading to reduction of PPARγ expression, a master transcription factor for adipogenesis. Reduction in weight as well as in IRS-1 expression was detected in the fat tissues of the high fat-diet-fed mice when reared with 60% coffee for 7 weeks. As for Alzheimer's disease, we analyzed the effect of coffee on amyloid β (Aβ) production in human neuronal SH-SY5Y cells. We found a 20% reduction in Aβ production when treated with 2.5% coffee for 2 d. This reduction was due to proteasomal degradation of BACE1 (β-secretase), which was activated by protein kinase A. In addition, coffee ameliorates LPS-induced inflammatory responses in RAW264.7 macrophages by reducing NFκB activity and Nrf2 activation. Roasted coffee prevents selenite-induced cataractogenesis by ameliorating antioxidant loss. Pyrocatechol, a component of roasted coffee, also reduced Aβ production and exhibits anti-inflammatory effects by a similar mechanism as coffee. Our results suggest that roasting coffee beans to generate pyrocatechol is necessary for the preventive effects of coffee intake on the chronic diseases.

To determine the relationship between seasons and regions and aflatoxin M 1 (AFM 1 ) contamination of milk distributed in Fukuyama City, we conducted a survey once during the summer and once during the winter between June 2018 and January 2019. We compared the AFM 1 contamination levels in milk drinks available in Fukuyama City during the same period, to provide more about the factors causing AFM 1 contamination. All milk samples examined exhibited AFM 1 contamination levels below the standard AFM 1 contamination level (0.5 μg/kg). For the comparison based on seasons, one milk sample collected in the summer (0.07 μg/kg) exceeded the EU limit (heat-treated milk: 0.050 μg/kg). However, there was no significant difference in the AFM 1 contamination level (p>0.05). For the comparison based on regions, the AFM 1 contamination level in the milk sample from the Chugoku Region was significantly higher in the winter and significantly lower in the summer compared to those from other regions. AFM 1 contamination of milk did not have a direct relationship with seasons or regions, but was instead influenced by the type, amount, and management of feed supplied to dairy cattle. For the comparison between milk and milk drinks, the AFM 1 contamination levels in milk drinks were significantly lower (p<0.01). The highest AFM 1 concentration (0.08 μg/kg) was detected in one sample of milk drink sampled during the summer. The AFM 1 contamination of milk drinks is likely affected by the level of contamination in raw materials, the proportion of such raw materials in the drinks, and the process type. An increase in non-fat milk solids was assumed to be a factor that increases AFM 1 contamination.

DNA from hair that has undergone retort pouch sterilization shows considerably more fragmentation. Assessing the extent of DNA fragmentation using a PCR assay could therefore be applied to infer the sterilization history of a contaminated food sample. Such assessments could make it possible to determine whether a food sample had been contaminated by hair during the production process. To determine the extent of retort pouch sterilization, primers specific for the detection of human DNA were designed to give an amplification product of approx 500 bp. Hair was subjected to retort sterilization as a model of contamination, and PCR was performed using the extracted DNA as a template and the primer set for determining retort pouch sterilization. The results showed that no DNA amplification occurred in retort pouch samples, whereas amplification was observed in samples that were unheated, heated in hot water, or heated in a microwave oven. The present method was thus able to specifically detect thermal decomposition of DNA from hair that had undergone retort sterilization, and will be useful for determining whether hair discovered in a retort pouch was responsible for contamination.

The safety management information related to heat generation in magnetic resonance imaging (MRI) examinations includes the specific absorption rate (SAR), the root mean square (RMS) of the MRI effective component of the B 1 field (B1+rms), and imaging time, which must be set appropriately before an MRI examination. However, unlike image attributes and data, these three parameters do not require any image storage; therefore, information collection and confirmation post-inspection are difficult. Therefore, in this study, we used Digital Imaging and Communications in Medicine of SAR and imaging time using the overlay function of the picture archiving and communication systems (PACS) to confirm the specific absorption rate B1+rms and imaging time post-inspection. The medicine identification tag information was displayed on the PACS viewer. For some imaging times, the console display during scanning and the PACS viewer display did not match. However, the SAR console display during scanning and the PACS viewer display matched well, thereby rendering it easier to manage safety in MRI examinations.

Polysaccharides (PS) are one form of biomass occurring in great abundance on earth and are promising organic material alternatives to petroleum-based ones. We have focused on PS produced by cyanobacteria. Aphanothece sacrum, which is a freshwater unicellular cyanobacterium, produces large amounts PS as a main component of the extracellular matrix. We successfully extracted the PS sacran from A. sacrum biomaterials and demonstrated that sacran contains carboxyls and sulfate groups. Furthermore, the constituent sugars of the sacran extracted were determined to be fucose, rhamnose, xylose, arabinose, mannose, glucose, galactose, glucuronic acid, galacturonic acid, and galactosamine. The sequence of sacran is still under investigation. In addition, we confirmed that the sacran was a supergiant with a high absolute molecular weight of 2.35×10 7 g/mol. Sacran shows a self-orienting behavior in dilute solution at a concentration range over 0.25 wt% to form a liquid crystalline structure. Using this property, it is possible to prepare a sacran cast film with an orientation structure, especially swelling in the thickness direction, to form anisotropic hydrogels. The anisotropy and degree of swelling of the hydrogels could be controlled by varying the heating temperature of the sacran cast file. Furthermore, sacran could be combined successfully with rayon as new fiber materials, and the sacran-rayon complex materials showed increased water absorption compared with the original rayon. This article introduces various applications of sacran in the industrial and medical fields.

Following the previous report, a rapid dialysis method was developed for the extraction and purification of four artificial sweeteners, namely, sodium saccharide (Sa), acesulfame potassium (AK), aspartame (APM), and dulcin (Du), which are present in various foods. The method was evaluated by the addition of 0.02 g/kg of these sweeteners to a cookie sample, in the same manner as in the previous report. Revisions from the previous method were: reduction of the total dialysis volume from 200 to 100 mL, change of tube length from 55 to 50 cm, change of dialysate from 0.01 mol/L hydrochloric aqueous solution containing 10% sodium chloride to 30% methanol solution, and change of dialysis conditions from ambient temperature with occasional shaking to 50℃ with shaking at 160 rpm. As a result of these revisions, the recovery reached 99.3-103.8% with one hour dialysis. The obtained recovery yields were comparable to the recovery yields in the previous method with four hour dialysis.

In magnetic resonance imaging (MRI), when radiofrequency (RF) is irradiated to a subject with metallic implant, it can generate heat by RF irradiation. Recently 3 T MRI scanner has spread widely and imaging for any regions of whole body has been conducted. However specific absorption rate (SAR) of 3 T MRI becomes approximately four times as much as the 1.5 T, which can significantly affect the heat generation of metallic implants. So, we evaluated RF heating of artificial hip joints in different shapes and materials in 1.5 T and 3 T MRI. Three types of artificial hip joints made of stainless alloy, titanium alloy and cobalt chrome alloy were embedded in the human body-equivalent phantom respectively and their temperature change were measured for twenty minutes by 1.5 T and 3 T MRI. The maximum temperature rise was observed at the bottom head in all of three types of artificial hip joints, the rise being 12°C for stainless alloy, 11.9°C for titanium alloy and 6.1°C for cobalt chrome alloy in 1.5 T. The temperature rise depended on SAR and the increase of SAR had a good linear relationship with the temperature rise. It was found from the result that the RF heating of metallic implants can take place in various kinds of material and the increase of SAR has a good linear relationship with the temperature rise. This experience shows that reduction of SAR can decrease temperature of metallic implants.

Objective: Approximately 19,000 people die in Japan each year from accidents that occur while bathing. Yamagata Prefectural Shounai public health center had educated residents about proper bathing practice. We evaluated residents' knowledge about safe bathing practices after an educational campaign in the area., Methods: We distributed a questionnaire to 3,078 people to gauge their awareness of bathing accidents in general and the effectiveness of a safety campaign from the public health center prevention. Participants included people who had attended a meeting, workshop, lecture, or event at the public health center., Results: A total of 2,697 people responded (87.6% response rate). A large majority (92%) knew about safe bathing practices in general. However, only 43% knew that bathing in hot water less than 41 degrees Celsius could help to reduce bathing accidents. Only 56% bathed in water below 41 degrees Celsius. Similarly, 81% knew about the preheating before bathing in dressing room and bathroom, but practiced only 50% of those. About recognition of the actual situation of the bathing accident and recognition of the prophylaxis, a student attending a lecture was higher than a lecture non-student attending a lecture more than 10%., Conclusion: Recognitions and practices of safe bathing practices had big difference, and development of an effective communication method will be important.

Venous pain induced by oxaliplatin(L-OHP)is a clinical issue related to adherence to the Cape OX regimen. To prevent LOHP- induced venous pain, we provided nursing care to outpatients who were administered a preheated L -OHP diluted solution using a hot compress. We retrospectively evaluated the risk factors for colorectal cancer patients who had L -OHP induced phlebitis and venous pain. Furthermore, the preventive effect of nursing care was compared between inpatients and outpatients from January 2010 to March 2012. At the L-OHP administration site, any symptoms were defined as phlebitis, whereas pain was defined as venous pain. A total of 132 treatment courses among 31 patients were evaluated. Multivariate logistic regression analysis revealed that both phlebitis and venous pain were significantly more common in female patients (adjusted odds ratio, 2.357; 95%CI: 1.053-5.418; and adjusted odds ratio, 5.754; 95%CI: 2.119-18.567, respectively). The prevalence of phlebitis and venous pain did not differ between inpatients and outpatients (phlebitis, 61.3% vs 67.7%; venous pain, 29.0%vs 19.4%). These results suggest that administration of L-OHP via a central venous route should be considered in female patients.

Hypervalent organo-λ(3)-iodanes have attracted great interest in organic synthesis; however, the chemistry of hypervalent organo-λ(3)-bromanes remains largely unexplored, mainly because of synthetic difficulties. Iodobenzene is readily oxidized by common oxidants such as peracids under mild conditions, whereas bromobenzene is inert. Since the ionization potential of bromobenzene (8.98 eV) is higher than that of iodobenzene (8.69 eV), hypervalent-λ(3)-bromane would show much higher reactivity. We overcame this problem by using difluoro(aryl)-λ(3)-bromane (Frohn's reagent), which serves as a pivotal progenitor of various λ(3)-bromanes including imino-λ(3)-bromane, cyclopent-1-enyl-λ(3)-bromane, (E)-β-alkylvinyl-λ(3)-bromane, and diacetoxy-λ(3)-bromane. These reagents possess highly unusual reactivity based on the enormously enhanced nucleofugality of the aryl-λ(3)-bromanyl group.

Titanium (Ti) implants are increasingly being used for dental parts. There is no problem with the attraction of a static magnetic field for Ti in magnetic resonance imaging (MRI), since Ti is paramagnetic. However, there is a risk of radio frequency (RF) heat generation within Ti. 3.0 T-MRI scanners are becoming increasingly common. The specific absorption rate (SAR) of 3.0 T-MRI is quadruple that of SAR compared with 1.5 T-MRI due to its being proportional to the square of the strength of a static magnetic field. The effect of heat generation in 3.0 T-MRI can thus be greater than in 1.5 T-MRI. So, using 1.5 T and 3.0 T-MRI scanners, we measured the temperature of several Ti implants using the same scanning parameters during MRI scanning. Our measurements showed the rise in temperature of the Ti implants to be a maximum of 0.4 degrees C. In this study, however, Ti in a human mouth was not directly measured, so we need to attempt to perform MRI carefully on patients with Ti implants.

Venous pain induced by oxaliplatin (L-OHP) is a clinical problem in relation to adherence in the CapeOX regimen. We investigated the preventive effect of nursing care preheating administration of L-OHP a hot compress for colorectal cancer patients who received L-OHP via the peripheral venous route between January 2010 and January 2011. L-OHP was diluted in 500 mL of 5% glucose and administered by 2 hours. We evaluated a total of 64 courses among fifteen patients. The presence of any symptoms, any pain with or without touch, and some symptoms of numbness at the L-OHP-administered arm were defined as phlebitis, venous pain, and acute peripheral neuropathy, respectively. The prevalence of phlebitis, venous pain, and acute peripheral neuropathy in the nursing care group was 56.5%, 32.6%, and 25.8%, respectively, which was not significantly less in comparison with the control group (72.2%, 38.9%, and 54.5%, respectively). These results suggest that both types of nursing care, preheating administration and a hot compress, may be effective for the relief of acute peripheral neuropathy induced by L-OHP.

Objectives: In factories for glassware production, workers are exposed to intense visible light emitted from hot objects such as furnaces and molten glass. High exposure to short-wavelength visible light, called blue light, can cause photoretinopathy. The objective of this study was to quantify the blue-light hazards associated with glassware production., Methods: Spectral radiances of walls and heating elements inside furnaces were measured, as well as those of molten glass placed inside furnaces in a factory producing crystal glass crafts. The factory had two reheating furnaces, three melting furnaces, and a furnace for preheating blowpipes. The effective radiances of the inner furnace walls, the heating elements, and the molten glass were calculated from the measured spectral radiances and compared with the threshold limit value (TLV) in accordance with ACGIH guidelines. The temperature of each light source was determined by comparing the measured spectral radiance with that of a black body., Results: The measured effective radiances were in the range of 0.00498-0.708 mW/cm(2)sr and increased steeply with increasing light source temperatures in the range of 1,075-1,516 °C. The effective radiance of each light source was nearly equal to the effective radiance of the black body at the same temperature., Conclusions: The effective radiances of walls, heating elements, and molten glass inside the furnaces are lower than one tenth of the TLV for exposure durations longer than 10(4) s per day. Thus, it is not hazardous to view these light sources. However, the effective radiance at a higher light source temperature of approximately 1,800 °C will exceed the TLV. In this case, hot objects in a workplace for glassware production may present blue light hazards.

Simultaneous determination of four aconitine analogues (ACs) (AC; aconitine, HA; hypaconitine, JA; jesaconitine, MA; mesaconitine) in leaves and roots of wild Aconitum plants (Aconitum japonicum THUNBERG, Aconitum okuyamae Nakai) was carried out to elucidate the relation between toxicity to mice and ACs content determind by liquid chromatography tandem mass spectrometry. The total amounts of ACs in leaves, roots, petals and nectaries of Aconitum japonicum collected at Sagae-shi Tashiro were 5.9 μg/g, 928.1 μg/g, 46.1 μg/g, and 69.8 μg/g, respectively. Despite the high contents in nectary, commercial honey contained no ACs. Extract of wild Aconitum japonicum roots which contained ACs (2.69 mg/g) was administered to 5 mice orally at 1.0 g/kg (fresh root equivalent), and 2 mice died. On the other hand, 3 of 5 mice died after being given the standard AC (3.0 mg/kg, p.o.). These findings confirmed good coincidence between toxicity and quantitative values. Mice given extract of Aconitum okuyamae root (100 g/kg, p.o.) without ACs showed no toxic symptoms. Residual ACs in Aconitum leaves were examined after boiling. The remaining percentage of ACs in leaves after 0.5 minutes boiling was 31.6%, and the amount in the boiling water was 54.5%. MA is converted into benzoylmesaconine by hydrolysis (by boiling). Therefore food poisoning caused by Aconitum plants is explained by detection of benzoylmesaconine formed during food preparation.

Purpose: The aim of this study is to investigate the possibility of reducting vascular pain with peripheral vein administration of oxaliplatin (L-OHP)by heating infusion routes during XELOX therapy., Methods: (1) EXPERIMENT: The temperature of the 5%glucose injection solution was measured at the leading edge of the infusion route when it was heated to 36°Cor 40°C. (2) CASES: Among five patients receving XELOX therapy for colorectal cancer, we examined the occurrence of vascular pain by heating the L-OHP solution to 40°C., Results: (1) EXPERIMENT: The injection temperatures were reduced to 25°C and 31°C while passing through the infusion route when L-OHP solution was heated to 36°C and 40°C, respectively. (2) CASE: vascular pain did not occur in all five patients treated with XELOX therapy completely by heating the L-OHP solution at 40°C, including two patients who could not continue treatment caused by vascular pain without the heating method., Conclusion: The method using the heat infusion route of L-OHP at 40°C is useful for reducing vascular pain from L-OHP administered intravenously.

Changes in egg protein contents by cooking were measured with an ELISA kit using Tris-HCl buffer in model foods including cake, meatballs, pasta and pudding made with whole egg, egg-white and egg-yolk. The egg protein contents were lowest in the deep-fried model foods of cakes and meatballs. Ovalbumin (OVA) was undetectable (<1 µg/g) and ovomucoid (OVM) was lowest in pouched meatballs, suggesting that processing temperature and uniform heat-treatment affect the detection of egg protein. Furthermore, egg protein contents were below 6 µg/g in the pouched meatballs and pasta made with egg-yolk, and OVA and OVM were not detected by Western blotting analysis with human IgE from patients' serum. On the other hand, processed egg proteins were detected with an ELISA kit using a surfactant and reductant in the extract buffer.

In Aichi Cancer Center Hospital, we investigated the incidence of injection-site reactions associated with the administration of Oxaliplatin into a peripheral vein. We evaluated the frequency and severity of symptoms, and studied ways to manage its adverse reactions from September 2009 through March 2010. Oxaliplatin was injected into a peripheral vein in more than 90% of patients, suggesting that there would be a high risk of injection-site reactions. About 60% of patients had a numeric rating score of 5 or higher in this study, and more than 60% of injection-site reactions were improved by warming the injection site. Our results suggest that warming the injection site is one effective way to manage local adverse reactions when Oxaliplatin is administered into a peripheral vein.

Human norovirus is the most important foodborne virus in Japan. According to the statistics of food poisoning by the Ministry of Health, Labour, and Welfare (MHLW), the number of patients infected with norovirus has accounted for half of all the patients with food poisoning in recent years. One of the most important measures for the control of infectious diseases is establishing of techniques for inactivating pathogens. For the prevention of food poisoning caused by norovirus, MHLW recommends that foods be subjected to heat treatment at 85 degrees C for 1 min or more; moreover, it recommends the use of sodium hypochlorite to inactivate (disinfect) this virus. However, application of these treatments is not always feasible because heat results in denaturation and sodium hypochlorite can be toxic to the human body and can cause discoloration. Therefore, it is necessary to develop and improve the efficacy of disinfectants and physiochemical treatments against the virus. Human norovirus cannot be propagated in cell culture or in a small animal. This matter is the greatest hindrance for testing the stability of this virus in environments or for evaluating the efficacy of disinfectants, heat treatment, pH treatment, ultraviolet or gamma irradiation, high hydrostatic pressure treatment, and other methods for the inactivation of the virus. Hence, some viruses such as human enterovirus, feline calicivirus, or mouse norovirus have been used as surrogates of human norovirus. The data on inactivation and stability of surrogate viruses are exclusively used as the data of human noroviruses. In recent years, some attempts to distinguish between infectious and noninfectious virus particles by genetic methods such as polymerase chain reaction have been made. These methods include pretreatments by RNase for digesting viral RNAs from non-intact or destroyed virus particles, or addition of a reagent such as ethidium monoazide for inhibiting PCR amplification of viral RNAs from them, before RNA extraction. Non-intact virus particles, which may represent virus particles with some damage (s) in the structural protein(s), are not necessarily synonymous with non-infectious virus particles. However, the results of methods using these treatments, compared to the results of traditional methods without these treatments, seem to be more correlated to the amount of the infectious virus particles. Although many disinfectants or physiochemical treatments have been reported, traditional techniques such as removal of virus particles by washing in running water, heat treatment, or disinfection by sodium hypochlorite are still important control measures. Establishment of control measures for human norovirus and successful propagation of the virus in cell culture are strongly desired.

Purpose: To investigate the influence of warming the periocular region for 10 minutes after visual display terminal (VDT) work on the near reflex, and the differences in influence between lid closure, dry and wet warming, and the amounts of water vapor., Subjects and Methods: Subjects in the first trial were 10 healthy volunteers (10 eyes). Following VDT, subjects wore either a warming eye steamer (water vapor: 200 mg/10 min) or an eye mask with their eyelids closed for 10 minutes. Subjects in the second trial were 5 healthy volunteers (5 eyes). Following VDT, subjects applied either a dry-warming sheet (water vapor: 0 mg/10 min) or a wet-warming sheet (water vapor: 20, 35, 160 and 200 mg/10 min) to there eyelids and the periocular region for 10 minutes. In both experiments, subjective amplitude of accommodation, pupillary reaction, convergence reaction, near vision, and breakup time were measured before and immediately after VDT work and after 2 experimental settings., Results: The warming eye steamer significantly improved amplitude of accommodation (p<0.05), and near vision (p<0.05). Warming the periocular region with water vapor improved subjective amplitude of accommodation, and near vision, the effect of which depended on the amount of water vapor (p<0.05)., Conclusions: Warming the periocular region with water vapor improved subjective amplitude of accommodation, near vision and the effect depended on the amount of water vapor.

The white of an egg, rendered opaque by boiling, can be converted into a thin, transparent and rigid material like glass by evaporating the moisture. This phenomenon is known as the vitrification of heat-denatured proteins. We applied vitrification technology to a collagen gel and converted it into a rigid glass-like material. We attempted to rehydrate the glass-like material and succeeded in preparing a novel stable state of collagen gel that was a thin and transparent membrane with excellent gel strength and protein permeability. We called it "collagen vitrigel" because it was produced from the vitrification process of a traditional hydrogel. Further, a framework-embedded collagen vitrigel membrane that can be easily turned inside out with tweezers was prepared by inserting a nylon membrane ring in the collagen sol prior to the gelation, thereby allowing the membrane to function as a removable cell culture substratum. Different types of anchorage-dependent cells could be cultured on both surfaces of the substratum by the manipulation of two-dimensional cultures, and consequently a three-dimensional crosstalk model with paracrine effects from each cell type was reconstructed. Also, the collagen vitrigel membrane containing a bioactive molecule provided a drug delivery system (DDS) with sustainable release. In this review, we summarize the recent progress of applied studies using the collagen vitrigel membrane as follows: a corneal model for eye irritant and permeability tests, a skin model for sensitization test, a renal glomerular model for evaluating blood filtration, an endometrial model for developing a new treatment and a DDS of hepatocyte growth factor for improving liver disorder.

In the inspection of genetically modified rice, rice taxon-specific DNA could not be detected in processed rice food (bifun: rice vermicelli). The effects of using PCR the ratio of rice powder content and temperature of processing on the detection of taxon-specific DNA were examined by means of processing model experiments using cornstarch with 0, 2, 5, 10% rice powder by weight. Cornstarch and rice powder were blended with water and subjected to heating, steam-treatment, and autoclaving. The rice taxon-specific DNA was detectable in 2% rice powder following heat and steam treatments. After autoclaving, rice taxon-specific DNA was detected only in the 10% rice powder product. In the processing model experiment using rice powder, it was found that autoclaving caused severe DNA degradation.

When unheated whole samples of crustaceans (shrimp, prawn and crab) were analyzed with our ELISA kit (FA test EIA-Crustacean 'Nissui') using anti-tropomyosin antibodies, a remarkable reduction in reactivity was recognized. This reduction in activity was found to be due to the digestion of tropomyosin during the extraction process by proteases contained in cephalothorax. To avoid the digestion of tropomyosin by proteases, we developed an extraction method (heating method) suitable for the detection of tropomyosin in unheated crustaceans including cephalothorax. Experiments with unheated whole samples of various species of crustaceans confirmed that the heating method greatly improved the low reactivity in the standard method; the heating method gave extraction efficiencies of as high as 93-107%. Various processed crustaceans with cephalothorax, such as dry products (unheated or weakly heated products) and pickles in soy sauce (unheated products), that showed low reactivity with the standard method were confirmed to give superior results with the heating method. These results indicated that the developed heating method is suitable for detecting unheated crustaceans with cephalothorax by means of the ELISA kit.

Aim: We analyzed data obtained from cow's milk challenge with single-blind manner in our department., Subjects and Methods: We have performed 83 cow's milk challenges in the hospital from 1995 to 2005, and patient profiles and results of the challenges were analyzed., Results: Positive rate of cow's milk challenges were 44.6% (37/83), and evoked symptoms by cow's milk challenges were most frequently seen in skin, followed by respiratory tract, and gastrointestinal system. Cases of anaphylaxis were seen in 8.1%. Seventy six percentages of symptoms started within one hour after the challenge, and 56.8% among positive cases were medicated. Adrenaline was injected in 9 cases out of 37 positive challenge cases. And all anaphylaxis patients recovered. We performed 19 open challenges with heated-cow's milk among 37 positive cases, and only one negative case existed. When we compared profiles of negative cow's milk challenges and positive ones, significant higher rate on positive skin prick tests (SPT) against cow's milk and complication of bronchial asthma were recognized in positive group. Sensitivity of SPT was 97.3% and specificity was 17.4%. Sensitivity of IgE CAP-RAST was 100% and specificity was 15.2%., Conclusions: Single-blinded challenge tests were safe. And they were useful in judgment of the acquisition of oral tolerance in cow's milk allergy. It was only one case that effect of the heating un-matched in food provocation test results. Although we experienced fairly high prevalence of respiratory symptoms during cow's milk challenge tests, appropriate medication especially adrenaline introduction made our test safe enough.

The amount of industrial wastes with asbestos such as dismantled construction materials has increased. We have reviewed the effect of asbestos-containing products subjected to harmless treatment on the lungs. Usually, the harmless treatment of asbestos is confirmed by the disappearance of fibrous materials and crystal structures by electron microscopy and X-ray diffraction. However, it is very important to perform animal studies and in vitro studies in order to examine the effect of the treated asbestos-containing products on the lungs. From previous treatments of asbestos using acids or high temperature, almost treated materials tended to show decreased toxicity in vitro and in vivo studies. There are some reports of the adverse effects of the treatment. If new harmless treatments of asbestos are developed, it is necessary to perform animal studies and in vitro studies of asbestos-containing products using new harmless treatments.

Asthma, chronic obstructive pulmonary disease, and diffuse panbronchiolitis are syndromes associated with chronic airway inflammation. In the conventional definition of inflammation, local pyrexia at the site of inflammation should be observed. However, there are very few reports that have evaluated the "heat" in inflammatory respiratory diseases. We considered that the evaluation of allergic airway inflammation such as asthma might be possible by measuring the exhaled air temperature, and devised an original device that stabilizes the flow rate, which is a very important factor for the direct measurement of heat. Moreover, an expiratory heat flux meter, which can detect a change in air temperature more precisely and immediately, was also incorporated into our original device. As a result, we succeeded in the measurement and evaluation of the heat flux and air temperature in healthy subjects and asthmatic patients, and, further, the air temperature was straightforwardly evaluated by a portable spirometer including a temperature sensor. These findings suggest that the heat flux and temperature of exhaled air can be used to objectively monitor airway inflammation noninvasively, and assist in the diagnosis/monitoring of inflammatory respiratory diseases, including asthma.

Purpose: Several reports have suggested that unusual thermal injuries in magnetic resonance (MR) imaging have occurred due to a closed conducting loop formed accidentally in a part of the patient's body. In this study, we investigated the relationship between the increases in temperature and several parameter settings for MR imaging by use of a human body-equivalent phantom., Method and Materials: A standard clinical 1.5T MR system (SIGNA HORIZON; GE) and a pelvic phased-array coil were used. The human body-equivalent phantom (agar, 0.9% saline, antiseptic) simulated a part of the pelvis and both femurs in a patient. A closed conducting loop could be reproduced when two ends of femurs contacted each other at a point, so that we could measure the temperature changes without and with a closed conducting loop. The temperature of the phantom was measured at the contact point of a closed conducting loop and the center of phantom by use of an optical fiber thermometer which was immune to the influences of radiofrequency (RF) and magnetic and electronic fields. We tested two imaging sequences of spin echo (SE) and fast spin echo (FSE) with 60 minutes of scanning time. In addition to the standard imaging sequences we measured temperature changes without the RF irradiation or gradient magnetic fields. The average temperature changes were recorded from five measurements which were repeated at intervals of more than one day., Results: When the closed conducting loop was reproduced, the temperatures at the contact point significantly increased (p<0.001) compared with the temperatures at the center of phantom. The temperature changes at 60 minutes of scanning time were 7.0 and 8.1 degrees C by use of the SE and FSE, respectively. There were no significant temperature changes when the imaging was performed without the RF irradiation., Conclusion: Our result obtained by use of a human body-equivalent phantom demonstrated that local heating, which can lead to thermal injuries accidentally, could occur when a closed conducting loop was formed in part of the patient body. CLINICAL RELEVANCE/APPLICATION: Radiologists should be more careful about local heating which can occur in patients during clinical MR imaging by a closed conducting loop.

The purpose of this study was to examine changes in the control of sweating by heat acclimation by using frequency of sweat expulsion (Fsw), an index of central sudomotor activity. Eight healthy young volunteers underwent a six-day heat acclimation program [a total of 80-min exercise at 50% peak rate of oxygen consumption in the heat (36 degrees C)]. In the days before and after the heat acclimation program, we examined the local sweating rate (SR) at the chest and forearm, Fsw and esophageal temperature (Tes) during whole body heating using a water-perfused suit. Heat acclimation decreased (P < 0.01) the Tes thresholds for initiation of chest and forearm sweating. Heat acclimation did not change the slopes of the SR at either site or Fsw versus Tes during heating, but shifted the slopes to a lower Tes. Heat acclimation did not change the slopes of the SR at either site versus Fsw, and the SR values at a given Fsw were similar between before and after heat acclimation. These findings suggest that short-term heat acclimation modulates central sudomotor mechanisms, decreasing the temperature threshold for sweating. We did not find a significant change in the peripheral mechanism for sweating by the heat acclimation program.

With an increasing number of studies describing the negative correlation of coffee consumption and the risk for type 2 diabetes mellitus, we were compelled to elucidate the nutrients which bring pharmacological effects on risk reduction for diabetes. In this review, the author's interest is focused on chlorogenic and caffeic acids derived from lightly roasted coffee beans, as well as nicotinic acid, volatile Maillard reaction products (vMRPs), and another structurally unknown compound contained in heavily roasted beans. Caffeine is a common compound in both lightly and heavily roasted beans and its anti-inflammatory effects on degenerative diseases such as diabetes mellitus has been reevaluated recently. The prophylactic effects of coffee on diabetes involve pleiotropy of plural components in accordance to the degree of the roasting. A new concept of nutritional blended coffee may be important to optimize the prophylactic effects of coffee on lowering the risk factors of diabetes and delaying the progress of diabetes complications as well.

Purpose: The purpose of this study was to investigate the coefficients of thermal expansion and shrinkage of an all-ceramic system (cercon) smart ceramics, DeguDent) utilizing tetragonal stabilized zirconia., Methods: The coefficients of thermal expansion and shrinkage of the core material and the layering porcelains (dentin and enamel) used in this study were measured according to the ISO 9693 standard. Five specimens for the core material and ten specimens for each layering porcelain were tested. The core specimens were milled, sintered, ground and polished. Five of the specimens for each layering porcelain were fired two times, and the remaining five specimens were fired four times. The fired layering porcelain specimens were ground and polished. The coefficients of thermal expansion and shrinkage were evaluated using a push-rod dilatometer at a heating rate of 5 degrees C /min over temperature ranges of 25-700 degrees C for the core, and 25-550 degrees C for the layering porcelain. For each specimen, the coefficients of thermal expansion was determined to be between 25 and 500 degrees C from the plotted curve of expansion versus temperature., Results: For the core material, the coefficients of thermal expansion and shrinkage showed almost the same value (10.8 x 10(-6)/ degrees C). For the layering porcelains, the coefficients of thermal expansion and shrinkage ranged from 9.3-11.1 x 10(-6)/ degrees C. The difference of the coefficients of thermal expansion and shrinkage between the core materials and the layering porcelains was -0.3-1.5 x 10(-6)/ degrees C. The specimens fired two times and the specimens fired four times exhibited almost the same value for each layering porcelain., Conclusion: The core material and layering porcelains have a suitable relationship.

Ocular circulation is regulated to maintain the homeostasis of retinal function in response to physiological stimulus. It is important to understand the mechanism of the regulation of ocular circulation under physiological conditions because the impairment of ocular circulation should cause severe retinal disorders. We previously investigated the physiological mechanism of ocular circulation in response to hypoxia, hypercapnia, and acute increased systemic blood pressure. In addition, it was reported that transpupillary thermotherapy might change ocular blood flow in patients with age-related macular degeneration. However, it still remains unclear whether the increased ocular tissue temperature may be associated with alteration of the ocular blood flow. Therefore, we examined the effect of ocular warming on retinal blood flow (RBF) and subfoveal choroidal blood flow (CBF) in humans. Ocular warming was induced in 10 healthy volunteers using an ocular warming lamp for 10 minutes. The RBF in the retinal artery and vein and the CBF in the foveal region were examined with a retinal laser Doppler velocimetry system and a laser Doppler flowmeter, respectively. Ocular warming increased RBF in the retinal artery and vein but decreased CBF in the foveal region. The CBF in the foveal region may contribute to maintaining a constant retinal temperature in response to ocular warming.

The producibility of thermostable direct hemolysin (TDH) is the most important pathogenic factor in Vibrio parahaemolyticus. TDH (+) V. parahaemolyticus is usually isolated from patients having V. parahaemolyticus food-borne disease. TDH (+) V. parahaemolyticus is, however, very difficult to isolate from food and environmental samples. In the 5 years from 2000 to 2004 in Tokyo, V. parahaemolyticus was isolated from food samples related to 67 of 227 V parahaemolyticus food-borne outbreaks. In these outbreaks, TDH (+) strains were also tried to isolate using PCR as the screening methods. TDH (+) V. parahaemolyticus strains were able to isolate from enrichment broth in which toxR and tdh genes become positive in PCR. TDH (+) strains of the same serotype with patients were able to be isolated from 23 food samples related to 11 outbreaks (16.4%); 3 outbreaks in 2000, 2 in 2001, 2 in 2002, 1 in 2003, and 3 in 2004. The serotypes of V. parahaemolyticus isolated from food were O3 : K6 (10 samples), O3 : K5 (6 samples), O1 : K25 (4 samples), O3 : K29 (2 samples), O4 : K 8 (1 sample), and O4 : K11 (1 sample). The isolation rate of the TDH (+) strain from enrichment broth differed with samples. In several samples TDH (+) strains were isolated easily only by examining 3 colonies, hence no TDH (+) strains were isolated in spite of the examination of 250 colonies. No correlation was seen between the number of V. parahaemolyticus and the isolation rate of TDH (+) strains in food samples. Screening using PCR is very effective method for isolating TDH (+) V. parahaemolyticus from food samples.