Inactivation of foodborne pathogenic and spoilage micro-organisms using ultraviolet-A light in combination with ferulic acid.

The low energy of UV-A (315-400 nm) is insufficient for disinfection. To improve UV-A disinfection technology, we evaluated the effect of ferulic acid (FA) addition on disinfection by UV-A light-emitting diode (LED) (350-385 nm) against various food spoilers and pathogens (seven bacteria and four fungi species). Photoantimicrobial assays were performed at FA concentrations below the MIC. The MIC of the isomerized FA, consisting of 93% cis-form and 7% trans-form, was very similar to that of the commercially available FA (trans-form). Irradiation with UV-A (1·0 J cm-2 ) in the presence of 100 mg l-1 FA resulted in enhanced reducing of all of the tested bacterial strains. A combination of UV-A (10 J cm-2 ) and 1000 mg l-1 FA resulted in enhanced reducing of Saccharomyces cerevisiae and one of the tested filamentous fungi. These results demonstrated that the combination of a short-term application of UV-A and FA at a low concentration yielded synergistic enhancement of antimicrobial activity, especially against bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial contamination is one of the most serious problems for foods, fruit and sugar thick juices. UV light is suitable for the nonthermal decontamination of food products by inactivating the contaminating micro-organisms. However, UV-A exposure is insufficient for disinfection. This study demonstrates that the combination of UV-A LED light (350-385 nm), which is not hazardous to human eyes and skin, and ferulic acid (FA), a known phytochemical and food additive, provides synergistic antimicrobial activity against foodborne pathogenic and spoilage micro-organisms. Therefore, FA addition to UV-A light treatment may be useful for improvement of UV-A disinfection technology to prevent food deterioration.

A new control method depending on primary phase angle of transcutaneous energy transmission system for artificial heart.

A new control method for stabilizing output voltage of the transcutaneous energy transmission system for artificial heart is proposed. This method is primary side, is outside of the body, which is not depending on a signal transmission system from the implanted device. The impedance observed from primary side changes from inductive to capacitive and the output voltage decreases drastically when the output current is large and the coupling factor is higher than that of the optimal condition. In this case, the driving frequency should be changed to higher so that the phase angle of the primary impedance is zero degree. The preliminary examination showed that this control method can enhance the output voltage limit to twice and the feasibility of the primary side control.

Development of an implantable high-energy and compact battery system for artificial heart.

The purpose of this study was to demonstrate the feasibility of the use of an implantable, high-energy, and compact battery system for an undulation pump total artificial heart (UPTAH). The implantable battery system tested consists of six lithium-ion batteries in series, a charge unit, and a charge/discharge control unit. A lithium-ion battery is currently the best energy-storage device because it has more energy density, a better life cycle, and a smaller temperature rise than those of other secondary batteries. The performance of the implantable battery system was evaluated in an in vitro experiment using an electric load that simulated the UPTAH. Also, sufficiently reliable operation of a system for supplying energy to a UPTAH consisting of a transcutaneous energy transmission system (TETS) and an implantable battery system was confirmed in three experiments using goats. The results of the in vitro and in vivo experiments showed that the implantable battery system supplied sufficient current to the UPTAH for maintenance of physiological conditions in the goat with maximum rise in temperature to less than 43 degrees C.

Recent progress on the vibrating flow pump as a totally implantable ventricular assist device.

This study describes the present state of progress in the development of the vibrating flow pump (VFP) ventricular assist system. We have proceeded with development aiming at a totally implantable ventricular assist system with smaller size and lighter weight appropriate for Asians like the Japanese by increasing the drive frequency. An actuator is important for the development of the miniature sized and lightweight artificial heart. We applied a linear motor for the mechanical part at first. The step motor was applied after that. This form may be best if we want the lightweight small sized motor for an actuator. The cross slider form is applied at present. It succeeded in the miniaturization compared with the linear motor. In the VFP-type ventricular assist system, the blood contact parts are a central vibration tube with inflow and outflow chambers. We designed round diaphragms to prevent thrombus formation. In addition, we developed an energy transmission system for total implantation. The VFP creates a high frequency oscillated blood flow. It has a unique flow pattern. Brain blood flow increased although the total flow of the circulation did not change in the frequency of 25 to 30 Hz. The quantitative evaluation of the autonomic nerve function during the left heart assistance with an oscillated blood flow was carried out by spectral analysis. Some influences on an autonomic nerve were observed by the VFP left heart assistance. We will continue development research with the aim of clinical application.

[A case of nonresectable scirrhous type gastric cancer treated by hypertensive subselective chemotherapy with pharmacokinetic modulating chemotherapy].

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. A 62-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the upper gastric body. Histologic study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography revealed swollen paraaortic lymph nodes and peritonitis carcinomatosa. The patient was diagnosed as having a nonresectable scirrhous type gastric cancer with peritonitis carcinomatosa and paraaortic lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously implanted port system placed into the thoracic aorta. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as a pharmacokinetic modulating chemotherapy (PMC). After eight courses of treatment of PMC, paraaortic lymph node swelling and ascites decreased. This chemotherapy produced a partial response in the peritonitis carcinomatosa and paraaortic lymph nodes. This chemotherapy was repeated preoperatively. We reconsidered this case to show indications for operation. The patient died suddenly of acute heart failure before the operation. This therapy was considered an effective treatment for nonresectable gastric cancer.

Solubilization study of local anesthetics into sodium dodecyl sulfate micelle using anesthetic cation selective electrodes.

The free concentrations of local anesthetic cations in equilibrium with sodium dodecyl sulfate (SDS) micelle which solubilized the anesthetic were determined by using ion-selective electrodes sensitive to local anesthetics, procaine (PC), lidocaine (LC), and mepivacaine (MC). Solubilizate distribution between water and SDS micelle was analyzed by means of the stepwise mass-action model. Association constant, K(1), was found to depend upon the anesthetic concentration, which decreased exponentially as the concentration of free anesthetic increased. Therefore, K(1) should include the interaction function φ(A) as K(1)=K(int)exp{-φ(A)} where K(int) is an intrinsic association constant. φ(A) is an increasing function of the anesthetic concentration, which means that occupation of a solubilization site by a local anesthetic cation makes sequential solubilization more difficult. The binding affinity of an anesthetic with SDS micelle increased in the following order PC

Partitioning of uncharged local anesthetic benzocaine into model biomembranes.

The partitioning of uncharged local anesthetic benzocaine (BzC) into molecular aggregates formed by cationic surfactant decylammonium chloride (DeAC) and phospholipid dipalmitoylphosphatidylcholine (DPPC) was studied from the surface tension and light transmittance measurements. The quantities concerning the partitioning of BzC, the compositions of BzC in the surface-adsorbed film and micelle and three kinds of differential partition coefficients corresponding to phase transitions of the DPPC bilayer membrane were evaluated from thermodynamic analysis of the experimental data. The surface-adsorbed film and micelle were more abundant in BzC than the aqueous solution and significantly large differential partition coefficients for the DPPC membranes were observed. The results clearly showed that the BzC molecules greatly partitioned into hydrophobic environments produced by surfactant-monolayer and phospholipid-bilayer membranes. The partitioning behavior of BzC was also compared with that of charged local anesthetic procaine hydrochloride (PC.HCl). It was shown that the PC.HCl molecule did not or hardly partition into such hydrophobic environments. The contrasting results of the partitioning between BzC and PC.HCl are attributable to the drastic decrease of hydrophilicity of BzC due to the lacking of ionic polar head group in comparison with PC.HCl.

Partition coefficients of charged and uncharged local anesthetics into dipalmitoylphosphatidylcholine bilayer membrane: estimation from pH dependence on the depression of phase transition temperatures.

Effects of the local anesthetics, dibucaine, bupivacaine and lidocaine on the phase transition temperatures of dipalmitoylphosphatidylcholine (DPPC) bilayer membrane were studied by the optical method. We focus our attention on pH dependence of the depression of main transition and pretransition temperatures. The temperatures of both transitions of DPPC bilayer membrane were depressed by the addition of anesthetics; the higher the value of pH, the larger the depression of main transition temperature and/or pretransition temperature by anesthetics. By extending the colligative thermodynamic framework to the depression of main transition temperature by an anesthetic, we can estimate the differential partition coefficient, which is defined by the difference in partition coefficients of an anesthetic into the ripple gel and liquid crystal phases. The difference in partition coefficient between the lamellar and ripple gel phases can also be estimated from the depression of pretransition temperature. Since the differential partition coefficients include both contributions of the charged and uncharged anesthetics, we could estimate the partition coefficients of the charged and uncharged anesthetic into the membranes from the pH dependence of differential partition coefficients. The liquid crystalline membrane of DPPC bilayer was more receptive to the uncharged local anesthetics than the charged species. The partition coefficients of the charged and uncharged anesthetics into the liquid crystalline phase of DPPC bilayer membrane were 3540 and 249000 (for dibucaine), 1120 and 83900 (for bupivacaine), 256 and 11700 (for lidocaine), respectively. The transfer free energy of uncharged anesthetics from the aqueous phase to the liquid crystalline membrane was well correlated to the local anesthetic potency.

Psychiatric disorders in cancer patients: descriptive analysis of 1721 psychiatric referrals at two Japanese cancer center hospitals.

BACKGROUND: Although a diagnosis of cancer today may no longer be considered to be the equivalent of a death sentence, many previous studies in Western countries have revealed that such a diagnosis places many kinds of emotional burden on a patient. However, few studies have focused on the nature of psychiatric disorders in Japanese cancer patients. METHODS: We investigated the characteristics, reason for psychiatric consultation and psychiatric diagnosis of cancer patients by analyzing the database of patients referred to the Psychiatry Divisions at the National Cancer Center Hospital and the National Cancer Center Hospital East, Japan. RESULTS: Among a total of 1721 referrals, most of the cancer patients (78%) were inpatients. Patients with lung cancer (19%) were the most common, followed by patients with breast cancer (13%) and with head and neck cancer (10%). More than half of the patients had recurrent and/or metastatic cancer and 60% of the patients had pain. The most common reason for the consultation was psychiatric evaluation (35%), followed by sleep disorders (19%), anxiety or fear (18%) and depression (18%). Regarding the psychiatric diagnosis, adjustment disorders were the most common (34%), followed by delirium (17%) and major depression (14%). The diagnosis of cancer had been disclosed to more than 99% of the patients. CONCLUSION: The common psychiatric disorders observed in Japanese cancer patients were similar to those in the Western countries provided the cancer diagnosis is disclosed.

Effects of age and gender on the expression of brain-derived neurotrophic factor mRNA in rat retrosplenial cortex following administration of dizocilpine.

Using in situ hybridization, we studied the effects of age and gender on the expression of brain-derived neurotrophic factor (BDNF) mRNA and heat shock protein hsp-70 mRNA in the rat retrosplenial cortex following administration of the noncompetitive NMDA receptor antagonist (+)-MK-801 (dizocilpine). Male and female Sprague-Dawley rats (5 weeks, 12 weeks, or 10 months old) were given a single intraperitoneal injection of saline (1 ml/kg) or dizocilpine (0.3, 1.0, or 3.0 mg/kg). No expression of BDNF mRNA and hsp-70 mRNA was detected in the rat retrosplenial cortex after administration of saline (1 ml/kg, IP). Administration of dizocilpine (0.3, 1.0, or 3.0 mg/kg, IP) caused a marked induction of BDNF mRNA and hsp-70 mRNA in the retrosplenial cortex of male and female rats, in a dose-dependent manner. Female rats were more sensitive to the induction of BDNF mRNA and hsp-70 mRNA in the retrosplenial cortex by dizocilpine as compared to male rats. It was also found that adult (12 weeks old) and aged (10 months old) rats were more sensitive to the induction of hsp-70 mRNA and BDNF mRNA in the retrosplenial cortex by dizocilpine as compared to young (5 weeks old) rats. These results suggest that the age and gender differences observed in the expression of BDNF mRNA and hsp-70 mRNA in the retrosplenial cortex by dizocilpine may be associated with the differences in dizocilpine-induced neurotoxicity observed with gender and age within the same region.

[A case of successful management of nonresectable pancreas cancer with liver metastasis by intra-arterial infusion chemotherapy with angiotensin-II and administration of tegafur/uracil].

Nontypical chemotherapy regimens exist for advanced pancreatic cancer. We herein report a 62-year-old man whose nonresectable pancreatic cancer was treated effectively with a new method of intra-arterial regional chemotherapy with angiotensin-II (AT-II). The patient was admitted to our hospital with obstructive jaundice and anorexia. He was diagnosed as having inoperable advanced pancreatic cancer with liver metastasis. Enteric-coated tegafur/uracil (400 mg) was administered for 3 weeks. Simultaneously, intraarterial infusion with 5-fluorouracil (500 mg) and infusion of methotrexate (100 mg) with 50 micrograms of AT-II was given every week. A catheter connected to a subcutaneously implanted port system was placed into the common hepatic artery. As a result of this treatment, the maximum diameter of the pancreatic tumor decreased from 3 cm to 2 cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 24,000 U/ml to 186 U/ml. Moreover, the performance status of patient also improved, and he was discharged from our hospital despite his terminal cancer. This regimen could well be effective in cases of advanced pancreatic cancer.

[Prostatic cancer developing after transurethral resection of the prostate for benign prostatic hyperplasia].

From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.

Effect of local anesthetics on the bilayer membrane of dipalmitoylphosphatidylcholine: interdigitation of lipid bilayer and vesicle-micelle transition.

The phase transitions of dipalmitoylphosphatidylcholine (DPPC) bilayer membrane were observed by means of differential scanning calorimetry (DSC) as a function of the concentration of local anesthetics, dibucaine (DC x HCl), tetracaine (TC x HCl), lidocaine (LC x HCl) and procaine hydrochlorides (PC x HCl). LC x HCl and PC x HCl depressed monotonously the temperatures of the main- and pre-transition of DPPC bilayer membrane. The enthalpy changes of both transitions decreased slightly with an increase in anesthetic concentration up to 160 mmol kg(-1). In contrast, the addition of TC x HCl or DC x HCl, having the ability to form a micelle by itself, induced the complex phase behavior of DPPC bilayer membrane including the vesicle-to-micelle transition. The depression of both temperatures of the main- and pre-transition, which is accompanied with a decrease in enthalpy, was observed by the addition of TC x HCl up to 21 mmol kg(-1) or DC x HCl up to 11 mmol kg(-1). The pretransition disappeared when these concentrations of anesthetic were added, and the interdigitated gel phase appeared above these concentrations. The appearance of the interdigitated gel phase, instead of the ripple gel phase, brings about the stabilization of the gel phase by 1.8-2.4 kcal mol(-1). In the concentration range of 70-120 mmol kg(-1) TC x HCl (or 40-60 mmol kg(-1) DC x HCl), the enthalpy of the main transition exhibited a drastic decrease, resulting in the virtual disappearance of the main transition. This process includes the decrease in vesicle size with increasing anesthetic concentration, resulting in the mixed micelle of DPPC and anesthetics. Therefore, in this range of anesthetic concentration, the DPPC vesicle solubilized an anesthetic which coexists with the DPPC-anesthetic mixed micelle. Above the concentration of 120 mmol kg(-1) TC x HCl (or 60 mmol kg(-1) DC x HCl), there exists the DPPC-anesthetic mixed micelle. Two types of new transitions concerned with the mixed micelle of DPPC and micelle-forming anesthetics were observed by DSC.

Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites.

Brevican is a member of the lectican family of chondroitin sulfate proteoglycans that is predominantly expressed in the central nervous system. The susceptibility of brevican to digestion by matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9, -10, and -13 and membrane type 1 and 3 MMPs) and aggrecanase-1 (ADAMTS4) was examined. MMP-1, -2, -3, -7, -8, -10, and -13 degraded brevican into a few fragments with similar molecular masses, whereas the degradation products of aggrecanase-1 had apparently different sizes. NH(2)-terminal sequence analyses of the digestion fragments revealed that cleavages of the brevican core protein by these metalloproteinases occurred commonly within the central non-homologous domain. MMP-1, -2, -3, -7, -8, -10, and -13 preferentially attacked the Ala(360)-Phe(361) bond, whereas aggrecanase-1 cleaved the Glu(395)-Ser(396) bond, which are similar to the cleavage sites observed with cartilage proteoglycan (aggrecan) for the MMPs and aggrecanase-1, respectively. These data demonstrate that MMP-1, -2, -3, -7, -8, -10, and -13 and aggrecanase-1 digest brevican in a similar pattern to aggrecan and suggest that they may be responsible for the physiological turnover and pathological degradation of brevican.

[Centennial for the Meyer-Overton rule: anesthetics and receptors].

As a backlash to the dominance of lipid theories of anesthesia for almost a century, protein theories are prevalent at present. Lipid theories assume nonspecific interaction with membranes. Protein theories assume specific interaction with specific receptors in specific proteins. The Meyer-Overton rule does not specify the anesthetic action site to lipid membranes. The correlation between the olive oil solubility to the anesthetic potency means that the action sites have similar physical properties to olive oil. It does not discriminate between lipids and proteins. Olive oil is homogeneous (isotropic) liquid whereas membranes and proteins are structured (anisotropic). The physical properties of proteins and membranes are not uniform throughout the structure. The rule shows that the anesthetics bind multiple areas in nonspecific proteins and membranes. The diversity of anesthetic structures is difficult to reconcile with the idea that there is a specific receptor on specific proteins.

[A case of metastatic extradural seminoma suspected intradural invasion by the measurements of HCG beta concentration in CSF].

A 34-year-old man underwent left orchidectomy for his left testicular seminoma. One month later, he developed paraplegia, hypesthesia under Th10 level and vesicorectal disturbance. He was diagnosed as having compressive myelopathy secondary to metastatic neoplasm at thoracic vertebra 10 and its extradural space which were revealed on magnetic resonance imaging. After administration of combination chemotherapy with cisplatin, etoposide and bleomycin, the extradural lesions diminished and the neurological symptoms gradually improved. In this case, intradural invasion of tumor cells was suspected because the level of human chorionic gonadotrophin beta subunit (HCG beta) concentration in cerebrospinal fluid (CSF) was higher than that in plasma, while radiographic scanning demonstrated regional tumor located at extradural space of Th10 level. It is important to evaluate the spread of tumor cells for the choice of therapy and the monitoring of HCG beta (plasma:CSF ratio) was considered to be one of the useful methods to detect the presence of central nerve system metastases from HCG-producing tumor.

Artificial SMA valve for treatment of urinary incontinence: upgrading of valve and introduction of transcutaneous transformer.

This paper is concerned with the development of an artificial urethral valve driven by shape memory alloy actuators, which is attached onto the urethra of a urinary incontinence sufferer for treating the involuntary micturition. Three types of compact cylindrical valves are assembled and their opening and closing functions are examined experimentally. The updated valve is heated and opened by using the transcutaneous energy transformer consisting of a pair of flexible spiral-formed copper wire coils. The experiment using the canine urinary canal verifies that the total system of the valve and the transformer works well as an artificial sphictor muscle and controls the urinary flow through the canal appropriately.

Increased expression of zif268 mRNA in rat retrosplenial cortex following administration of phencyclidine.

Phencyclidine (PCP) has been shown to cause neurotoxicity in rat retrosplenial cortex following a single administration, although the precise mechanism underlying PCP-induced neurotoxicity is unclear. Using in situ hybridization and immunohistochemistry, we studied the effects of PCP on expression of immediate early gene zif268 mRNA and zif268 protein in the rat brain. High constitutive levels of zif268 mRNA and zif268 immunoreactivity were observed in the brain of control rats. Administration of PCP (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of zif268 mRNA in the rat retrosplenial cortex, in a dose-dependent manner. However, the basal levels of zif268 mRNA in the other regions of cerebral cortex were decreased by administration of PCP. Emulsion-autoradiographical study suggested that marked expression of zif268 mRNA was observed in the layers III and IV of retrosplenial cortex where the neurotoxicity of PCP was detected. Furthermore, zif268 immunoreactivity in the layer IV of retrosplenial cortex was not changed by administration of PCP (25 mg/kg, i.p., 5 h), but that in the other layers of retrosplenial cortex was reduced by PCP. These results suggest that immediate early gene zif268 may, in part, play a role in the neurotoxicity of NMDA receptor antagonists such as PCP.

Non-Hodgkin lymphoma and coexisting primary cancers: a retrospective clinical analysis of 10 patients.

The simultaneous occurrence of non-Hodgkin lymphoma (NHL) and primary cancers is rare, and the treatment strategy for both malignancies is unclear. The authors analyzed the clinical records of 10 patients with NHL and coexisting primary cancers. All patients initially had symptoms of NHL, and all carcinomas were found at the initial workup of NHL by chance. The most common primary sites of coexisting cancers were the stomach (six patients) and the colon (two). Histologically, the majority of NHLs were intermediate grade, and all lesions were B-cell type. All primary cancers were adenocarcinoma. Initially, NHL was treated with radiotherapy or chemotherapy. Six primary cancers were resected surgically or endoscopically after the remission of NHL. The remaining four patients received no treatment for primary cancers because of advanced stages or early relapse of NHL. Three patients died of NHL, one died of cancer, and six were still alive, five without evidence of disease and one with disease. The authors conclude that early detection of a coexisting cancer and appropriate treatment after the remission of NHL may increase the possibility of a cure.