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Purpose: Pancreatic tumor treatment dose distribution variations associated with supine and prone patient positioning were evaluated., Methods: A total of 33 patients with pancreatic tumors who underwent CT in the supine and prone positions were analyzed retrospectively. Gross tumor volume (GTV), planning target volume (PTV), and organs at risk (OARs) (duodenum and stomach) were contoured. The prescribed dose of 55.2Gy (RBE) was planned from four beam angles (0°, 90°, 180°, and 270°). Patient collimator and compensating boli were designed for each field. Dose distributions were calculated for each field in the supine and prone positions. To improve dose distribution, patient positioning was selected from supine or prone for each beam field., Results: Compared with conventional beam angle and patient positioning, D2cc of 1st-2nd portion of duodenum (D1-D2), 3rd-4th portion of duodenum (D3-D4), and stomach could be reduced to a maximum of 6.4Gy (RBE), 3.5Gy (RBE), and 4.5Gy (RBE) by selection of patient positioning. V10 of D1-D2, D3-D4, and stomach could be reduced to a maximum of 7.2cc, 11.3cc, and 11.5cc, respectively. D95 of GTV and PTV were improved to a maximum of 6.9% and 3.7% of the prescribed dose, respectively., Conclusions: Optimization of patient positioning for each beam angle in treatment planning has the potential to reduce OARs dose maintaining tumor dose in pancreatic treatment., (Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Elucidation of the mechanism of adsorption of particles suspended in the gas-phase (aerosol) to the outer surfaces of leaves provides useful information for understanding the mechanisms of the effect of aerosol particles on the growth and physiological functions of trees. In the present study, we examined the localization of artificially deposited sub-micron-sized carbon-based particles on the surfaces of needles of Cryptomeria japonica, a typical Japanese coniferous tree species, by field-emission scanning electron microscopy. The clusters (aggregates) of carbon-based particles were deposited on the needle surface regions where epicuticular wax crystals were sparsely distributed. By contrast, no clusters of the particles were found on the needle surface regions with dense distribution of epicuticular wax crystals. Number of clusters of carbon-based particles per unit area showed statistically significant differences between regions with sparse epicuticular wax crystals and those with dense epicuticular wax crystals. These results suggest that epicuticular wax crystals affect distribution of carbon-based particles on needles. Therefore, densely distributed epicuticular wax crystals might prevent the deposition of sub-micron-sized carbon-based particles on the surfaces of needles of Cryptomeria japonica to retain the function of stomata.

Purpose: The clinical benefit of combination treatment with panitumumab and bevacizumab (PB) based on bevacizumab beyond progression (BBP) after the failure of second-line chemotherapy remains unclear. We assessed the tolerability and efficacy of PB as BBP in Japanese patients with metastatic colorectal cancer (mCRC)., Methods: This phase I study comprised two parts: (1) PB part to estimate the recommended PB dose, (2) CPB part to investigate the safety of PB with irinotecan (CPB). Three panitumumab doses (4, 5, and 6 mg/kg at Levels -1, 0 and 1, respectively) were set for the PB part, starting with Level 0. Bevacizumab was administered at a fixed dose of 5 mg/kg, regardless of panitumumab dose levels. All drugs were administered on day 1 and repeated every 2 weeks., Results: No dose-limiting toxicities were observed at Levels 0 (n = 3) and 1 (n = 3) for the PB part, determining the recommended dose as Level 1. During the whole treatment course at Level 1, grade 3 acneiform rash was observed in two patients with a partial response. For six patients (irinotecan biweekly, 150 mg/m(2) n = 3, 120 mg/m(2) n = 3) enrolled in the CPB part, grade 3 toxicities were leukopenia/neutropenia (n = 1), mucositis (n = 1), diarrhea (n = 1), rash acneiform (n = 1) and thromboembolic event (n = 1), and two of six patients achieved partial responses., Conclusion: Recommended doses for the PB regimen in mCRC were panitumumab 6 mg/kg and bevacizumab 5 mg/kg. PB and CPB showed manageable toxicities in KRAS wild-type patients previously managed with standard treatment, including bevacizumab.

Background and Purpose: Radiation-induced cancer is a serious late effect that may follow radiotherapy. A considerable uncertainty is associated with carcinogenesis from photon-based treatment, and even less established when including relative biological effectiveness (RBE) for particle therapy. The aim of this work was therefore to estimate and in particular explore relative risks (RR) of secondary cancer (SC) following particle therapy as applied in treatment of prostate cancer., Material and Methods: RRs of radiation-induced SC in the bladder and rectum were estimated using a bell-shaped dose-response model incorporating RBE and fractionation effects. The risks from volumetric modulated arc therapy (VMAT) were compared to intensity-modulated proton therapy (IMPT) and scanning carbon ions for ten patients., Results: The mean estimated RR (95% CI) of SC for VMAT/C-ion was 1.31 (0.65-2.18) for the bladder and 0.58 (0.41-0.80) for the rectum. Corresponding values for VMAT/IMPT were 1.72 (1.06-2.37) and 1.10 (0.78-1.43). The radio-sensitivity parameter α had the strongest influence on the results with decreasing RR for increasing values of α., Conclusion: Based on the wide spread in RR between patients and variations across the included parameter values, the risk profiles of the rectum and bladder were not dramatically different for the investigated radiotherapy techniques., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives/hypothesis: Transoral laser microsurgery (TLM) for hypopharyngeal cancer results in a lower incidence of complications than conventional open surgery. However, additional knowledge regarding the histoanatomical characteristics of the hypopharynx is necessary to prevent severe complications during TLM. The purpose of this study is to investigate the histoanatomical characteristics of the hypopharynx for TLM., Study Design: Histoanatomical study., Methods: Whole organ serial sections of three hypopharynges and larynges from autopsy cases were subjected to hematoxylin & eosin and Elastica van Gieson staining. Surgical histoanatomy of the hypopharynx was observed with each section, and the histoanatomical characteristics directly related to TLM performance were examined microscopically., Results: The histological structures of muscle layers showed obvious differences between each hypopharyngeal subsite. The posterolateral wall had two kinds of pharyngeal elevator muscles. These fasciae were connected to the perichondrium of the thyroid cartilage. The anterolateral wall between the superior horn and the lamina of the thyroid cartilage had no muscle layer. The superior laryngeal artery and the internal branch of the superior laryngeal nerve run into the larynx and hypopharynx at that site. The inner perichondrium of the thyroid cartilage was present beneath the mucosa. The dihedral angle of the anterior piriform fossa had a deep propria mucosa and paraglottic space. The postcricoid wall consisted of a multilayered structure, including cricoid cartilage covered with laryngeal muscles and mucosa., Conclusion: A precise understanding of the histoanatomical characteristics of the hypopharynx increases the success of TLM, decreases complication rates, and improves laryngeal preservation., Level of Evidence: N/A. Laryngoscope, 126:1783-1789, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Because of their rarity, there are no clear guidelines for the treatment of anal carcinomas; such tumors are normally subjected to the same modalities as recommended for rectal cancer. We report a patient with anal canal mucinous adenocarcinoma, with metastases in the pararectal and right inguinal lymph nodes, who was treated with abdominoperineal resection followed by mFOLFOX6 chemotherapy for 6 months (12 cycles). The patient has remained recurrence-free thus far, approximately 2 years since the surgery. As the optimal treatments for anal carcinomas have not been fully elucidated, we present this case to highlight a possible course of action for such patients that appears to be effective and promising.

Anal canal adenocarcinoma is a relatively rare malignancy without established diagnostic and treatment criteria. Case reports of chemotherapy for anal canal adenocarcinoma with distant metastasis are limited, and there is no convincing evidence for treatment effectiveness. A 62-year-old man complained of difficulty in defecation, anal pain, and bleeding during bowel movement. He was diagnosed with moderately differentiated primary anal canal adenocarcinoma. A computed tomography scan revealed multiple metastases in the lung and liver. The patient was treated with abdominoperineal resection to control local tumor growth and then with chemotherapy consisting of mFOLFOX6 + bevacizumab. Because he had an activating KRAS mutation, anti-EGFR therapy was not considered. A reduction in the size of lung and liver metastases was observed after 4 courses of mFOLFOX6 + bevacizumab, and after 22 courses, maximum reduction in the metastatic lesions was achieved. The patient demonstrated tolerable levels of oxaliplatin-related peripheral neurotoxicity (grades 1-2) and was considered as having partial response to treatment. He is currently at the partial response state for 1 year. We plan to continue the treatment unless the patient develops progressive disease or intolerable adverse reactions. This case demonstrates that anal canal adenocarcinoma with distant metastases could be successfully treated with mFOLFOX6 + bevacizumab therapy according to the guidelines for rectal carcinoma. However, as anal canal carcinoma has multiple histological subtypes, it is important to establish subtype-specific treatment strategies.

The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of gastric pH on the oral absorption of poorly water-soluble drugs were consistent with observations in humans. In conclusion, the D/P system with the gastric phase may be a useful tool for better predicting the oral absorption of poorly water-soluble basic drugs. In addition, the effects of gastric pH on the oral absorption of poorly water-soluble drugs may be evaluated by the D/P system with and without the gastric phase., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells., Study Design: Animal experiment using eight beagles (including three controls)., Methods: A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed., Results: A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site., Conclusion: The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds.

Purpose: The aim of this study was to estimate normal tissue complication probability (NTCP) parameters for late rectal complications after carbon ion radiotherapy (C-ion RT) for prostate cancer., Methods and Materials: A total of 163 patients were used to derive NTCP parameters. These patients were treated with relative biological effectiveness (RBE)-weighted dose ranging from 57.6 Gy (RBE) up to 72 Gy (RBE) and included in dose escalation trials. The Lyman-Kutcher-Burman (LKB) model was used and the model parameters were fit to the relation between dose and complication observed after C-ion RT., Results: The resulting NTCP parameters were the volume effect parameter; n=0.035 (95% CI: 0.024-0.047), the steepness of the NTCP curve; m=0.10 (0.084-0.13), the tolerance dose associated with 50% probability of complication; TD50=63.6 Gy (RBE) (61.8-65.4 Gy (RBE)) for Grade⩾1, n=0.012 (0.0050-0.023), m=0.046 (0.033-0.062), TD50=69.1 Gy (RBE) (67.6-70.9 Gy (RBE)) for Grade⩾2., Conclusion: A new set of rectal NTCP parameters in C-ion RT was determined. The rather small n values suggest that the rectum was consistent with being strictly serial organ. The new derived parameter values facilitate estimation of rectal NTCP in C-ion RT., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: There is growing evidence that vocal fold stellate cells (VFSCs) in the human maculae flavae are tissue stem cells of the human vocal fold and that the maculae flavae are a stem cell niche. The origin of the cells in the human maculae flavae (CHMF) and the relationship with bone marrow-derived cells were investigated., Methods: Five human adult vocal fold mucosae were investigated. The CHMF were subcultured and morphological features were assessed. Immunoreactivity to antibodies directed to cytokeratin, desmin, GFAP, vimentin, CD34, CD45, and collagen type I was investigated., Results: Cultured CHMF formed a colony-forming unit, indicating they are mesenchymal stem cells or stromal stem cells in the bone marrow. The CHMF expressed hematopoietic markers (CD34, CD45) and collagen type I, which are the major makers for bone marrow-derived circulating fibrocytes. The cultured CHMF expressed epithelium-associated, muscle-associated, neural-associated, and mesenchymal cell-associated proteins, indicating the CHMF are undifferentiated and express proteins of all 3 germ layers., Conclusions: The CHMF are undifferentiated cells derived from the differentiation of bone marrow cells. The results of this study are consistent with the hypothesis that the VFSCs are tissue stem cells or progenitor cells of the human vocal fold mucosa., (© The Author(s) 2015.)

A case of silent perforated diverticulitis in the ascending colon combined with pylephlebitis, resulting in complete occlusion of the portal trunk, is presented. A 75-year-old man with no relevant medical history visited our hospital complaining of a fever, which had lasted for 2 weeks. Although his laboratory data were indicative of severe inflammation, an abdominal examination and a computed tomography (CT) scan did not produce any significant findings. On the 6th day after admission, an abdominal CT scan detected a thrombus extending from the superior mesenteric vein to the portal vein, but did not show any signs of infection. However, on the 40th day after admission, an abdominal CT scan detected an embolus in the portal vein completely occluding the main portal trunk, as well as marked edematous changes indicative of inflammation, and an abscess in the ascending colon. We performed laparotomy and iliocecal resection, during which a perforation of the ascending colon derived from diverticulitis was found. We report this rare case and a review of the literature.

The incidence, morbidity, and mortality of colorectal cancer are increasing, largely owing to an increasingly aging population. Additionally, along with the increasing age of cancer patients, the number of patients with various comorbidities such as membranous nephropathy is also rising, and problems associated with the administration of chemotherapy to elderly patients with these conditions are becoming more common. Herein, we describe a case involving an 80-year-old woman who presented with general malaise, edematous limbs, and pleural effusion. An abdominal CT revealed multiple, relatively large, metastatic lesions in a wide area of the liver and left pleural effusion, and she was accordingly diagnosed with membranous nephropathy secondary to ascending colon cancer and multiple liver metastases. Despite her advanced age and the presence of membranous nephropathy, her general condition was favorable and chemotherapy was hence administered. Taking the toxicity profiles and the patient's preference into consideration, S-1 and oxaliplatin (SOX) therapy was selected, which showed a good tolerability. An abdominal CT after 8 cycles of SOX therapy revealed a marked reduction in the metastatic lesions in the liver and a decrease in the left pleural effusion, and the levels of tumor markers also decreased (partial response). At the latest follow-up, after the completion of 16 cycles, the condition of the patient remained stable, without any apparent signs of progressive disease. Based on this case, we conclude that, even for elderly patients with systemic complications or comorbid diseases, standard treatments should be considered after their general conditions, and therapeutic regimens have been sufficiently examined.

Purpose: The purpose of this study was to obtain a set of correction factors of the radiophotoluminescent glass dosimeter (RGD) output for field size changes and wedge insertions., Methods: Several linear accelerators were used for irradiation of the RGDs. The field sizes were changed from 5 × 5 cm to 25 × 25 cm for 4, 6, 10, and 15 MV x-ray beams. The wedge angles were 15°, 30°, 45°, and 60°. In addition to physical wedge irradiation, nonphysical (dynamic/virtual) wedge irradiations were performed., Results: The obtained data were fitted with a single line for each energy, and correction factors were determined. Compared with ionization chamber outputs, the RGD outputs gradually increased with increasing field size, because of the higher RGD response to scattered low-energy photons. The output increase was about 1% per 10 cm increase in field size, with a slight difference dependent on the beam energy. For both physical and nonphysical wedged beam irradiation, there were no systematic trends in the RGD outputs, such as monotonic increase or decrease depending on the wedge angle change if the authors consider the uncertainty, which is approximately 0.6% for each set of measured points. Therefore, no correction factor was needed for all inserted wedges. Based on this work, postal dose audits using RGDs for the nonreference condition were initiated in 2010. The postal dose audit results between 2010 and 2012 were analyzed. The mean difference between the measured and stated doses was within 0.5% for all fields with field sizes between 5 × 5 cm and 25 × 25 cm and with wedge angles from 15° to 60°. The standard deviations (SDs) of the difference distribution were within the estimated uncertainty (1SD) except for the 25 × 25 cm field size data, which were not reliable because of poor statistics (n = 16)., Conclusions: A set of RGD output correction factors was determined for field size changes and wedge insertions. The results obtained from recent postal dose audits were analyzed, and the mean differences between the measured and stated doses were within 0.5% for every field size and wedge angle. The SDs of the distribution were within the estimated uncertainty, except for one condition that was not reliable because of poor statistics.

Purpose: Respiratory-gated irradiation is effective in reducing the margins of a target in the case of abdominal organs, such as the liver, that change their position as a result of respiratory motion. However, existing technologies are incapable of directly measuring organ motion in real-time during radiation beam delivery. Hence, the authors proposed a novel quantitative organ motion tracking method involving the use of diagnostic ultrasound images; it is noninvasive and does not entail radiation exposure. In the present study, the authors have prospectively evaluated this proposed method., Methods: The method involved real-time processing of clinical ultrasound imaging data rather than organ monitoring; it comprised a three-dimensional ultrasound device, a respiratory sensing system, and two PCs for data storage and analysis. The study was designed to evaluate the effectiveness of the proposed method by tracking the gallbladder in one subject and a liver vein in another subject. To track a moving target organ, the method involved the control of a region of interest (ROI) that delineated the target. A tracking algorithm was used to control the ROI, and a large number of feature points and an error correction algorithm were used to achieve long-term tracking of the target. Tracking accuracy was assessed in terms of how well the ROI matched the center of the target., Results: The effectiveness of using a large number of feature points and the error correction algorithm in the proposed method was verified by comparing it with two simple tracking methods. The ROI could capture the center of the target for about 5 min in a cross-sectional image with changing position. Indeed, using the proposed method, it was possible to accurately track a target with a center deviation of 1.54±0.9 mm. The computing time for one frame image using our proposed method was 8 ms. It is expected that it would be possible to track any soft-tissue organ or tumor with large deformations and changing cross-sectional position using this method., Conclusions: The proposed method achieved real-time processing and continuous tracking of the target organ for about 5 min. It is expected that our method will enable more accurate radiation treatment than is the case using indirect observational methods, such as the respiratory sensor method, because of direct visualization of the tumor. Results show that this tracking system facilitates safe treatment in clinical practice.

Background: Recent reports indicate that organic fertilisers have a suppressive effect on the pathogens of plants grown under hydroponic systems. Furthermore, microorganisms exhibiting antagonistic activity to diseases have been observed in organic hydroponic systems. This study evaluated the effect of corn steep liquor (CSL) on controlling lettuce root rot disease [Fusarium oxysporum f.sp. lactucae (FOL)] in a hydroponic system. The effect of CSL and Otsuka A (a chemical fertiliser) on the inhibition of FOL in terms of mycelial growth inhibition was tested in vivo., Results: Addition of CSL suppressed FOL infection rates. CSL inhibited FOL infection by 26.3-42.5% from 2 days after starting incubation. In comparison, Otsuka A inhibited FOL growth by 5.5-19.4%. In addition, four of 10 bacteria isolated from the nutrient media containing CSL exhibited inhibition zones preventing FOL mycelial growth., Conclusions: We found that CSL suppressed FOL in lettuce via its antifungal and biostimulatory effects. We suggest that activation of beneficial microorganisms present in CSL may be used to decrease lettuce root rot disease and contribute to lettuce root growth., (© 2014 Society of Chemical Industry.)

The purpose of this study was to analyze passive motion of the para- and retropharyngeal space (PRS) during swallowing using dynamic magnetic resonance imaging (MRI). We conducted a preliminary study involving 30 healthy volunteers who underwent dynamic MRI. Consecutive MRI axial images were obtained by examining the plane parallel to the hard palate at the level of the anterior inferior corner of C2. Anterior displacement of the posterior pharyngeal wall (PPW) was measured as a motion index of pharyngeal contraction. The displacement and internal angle of the bilateral external and internal carotid arteries (ECA and ICA) and the bilateral centroids of the PRS area, as well as the increase in PRS area, were calculated at rest and at maximum pharyngeal contraction. In most participants, the bilateral ECA, ICA, and centroids were anterointernally displaced by pharyngeal contraction. The normalized ECA displacement (r = 0.64, r (2) = 0.41), normalized ICA displacement (r = 0.60, r (2) = 0.37), and normalized centroid displacement (r = 0.43, r (2) = 0.19) were more than moderately positively correlated with the normalized PPW displacement. The normalized PRS area increase (r = 0.35, r (2) = 0.12) was weakly positively correlated with the normalized PPW displacement. These results revealed that PRS area increased as the ECA and ICA were drawn anterointernally via its passive motion by pharyngeal contraction.

Background: RAS-RAF-MEK-ERK and PI3K-AKT pathways form a significant cascade for potential molecular target therapy in advanced cancer. The clinical significance of mutations in these genes in advanced gastric cancer (AGC) is uncertain., Methods: We collected formalin-fixed, paraffin-embedded and fresh frozen tumor samples from AGC patients and analyzed the KRAS, NRAS, BRAF and PIK3CA mutations by direct-sequencing. We retrospectively investigated the clinicopathological features of these mutations in AGC patients, and selected patients with metastatic gastric cancer., Results: Among 167 AGC patients, mutations of KRAS codons 12/13 (N = 8/164, 4.9%), PIK3CA (N = 9/163, 5.5%), and NRAS codon 12/13(N = 3/159, 1.9%) were detected. Comparison of the clinicopathological features of the mutated KRAS, PIK3CA, NRAS genes with an all-wild type of these genes showed that the frequency of the intestinal type was significantly higher in patients whose tumor tissue contained KRAS mutations (P = 0.014). Among 125 patients with metastatic gastric cancer, patients with NRAS codon 12/13 mutations in their tumors had shorter overall survival compared with NRAS wild-type patients (MST: 14.7 vs 8.8 months, P = 0.011). By multivariate analyses, NRAS codon 12/13 mutation was an indicator for poor prognosis in patients with metastatic gastric cancer (adjusted HR 5.607, 95% CI: 1.637-19.203)., Conclusions: Our study indicated that mutations of KRAS, PIK3CA and NRAS were rare in AGC. NRAS mutations were likely to associate with poor prognosis in metastatic state of AGC patients, but further validation of other research is required.

Cricoid cartilage fractures usually occur concurrently with disorders of laryngeal function. In, particular, displaced cricoid lamina fractures can affect arytenoid movement. However, functional, recovery may require proper repositioning of the cricoid lamina, which is associated with a high rate of, complications. Here we present a case in which an isolated cricoid cartilage fracture with arytenoid, immobility due to displacement of the fracture in the cricoarytenoid joint space was successfully, treated. Our findings suggest that a combination of external approaches with temporary, cricothyrotomy and wide suturing of the entire cricoid framework has the potential to improve, arytenoid movement and prevent associated complications., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The aim of present study was to evaluate the qualities of chaste berry (fruit of Vitex agnus-castus L.) preparations using HPLC fingerprint analysis. Seven medicinal products 1 from Japan and 6 from Europe, and 17 health foods, 6 from Japan and 11 from the United States were analyzed. HPLC profile and 26 authentic peaks were compared medicinal products and health foods. Whereas medicinal products had similar HPLC profiles, health foods had various profiles and each peak was also greatly different. The measured amounts of two markers in 5 traditional medicinal products, agnuside and casticin specified in the European Pharmacopoeia (EP), the U.S. Pharmacopoeia (USP) or the WHO monographs of chaste berry, were much lower than those in 2 medicinal products defined as "well-established use" by the European Medicines Agency. The amounts of two markers for 17 health foods differed in a great deal from 14-5054% and 3-1272%, respectively. Furthermore the amount ratios of two markers, agnuside/casticin, in about half of the health foods were remarkably larger than the standard crude drug and the ratios were closer to one of the related Chinese herbs, Vitex negundo L. It is concluded that a combination of HPLC fingerprints and the amount ratios of the marker compounds of chaste berry preparations serves as a useful tool to evaluate the qualities of these preparations.

Insulin resistance associated with visceral fat obesity has been suggested to be the pathological basis of metabolic syndrome. Many studies have demonstrated increased oxidant stress in diabetic patients and animal models of diabetes mellitus. In this study, the effect of liver hydrolysate administration on the blood glucose was examined in SHR/NDmcr-cp (SHR-cp) rats that show spontaneously occurring metabolic syndrome-like abnormalities. The SHR-cp rats were fed diets containing 5% liver hydrolysate for 12 weeks, and the fasting blood glucose and HbA1c were determined every 3 weeks. After administration of the liver hydrolysate-containing feed for 12 weeks, an oral glucose tolerance test was conducted and the plasma angiotensin II (AngII) concentrations were determined. The liver hydrolysate administration had no effect on the blood insulin levels in the oral glucose tolerance test, but significantly inhibited the d-glucose-induced increases of the blood glucose levels. Furthermore, the liver hydrolysate had almost no effect on the fasting blood glucose level, but tended to inhibit the increase of HbA1c. The plasma AngII concentration after the 12-week administration of liver hydrolysate remained significantly lower than that in the control group. These results indicate that a component of liver hydrolysate inhibits d-glucose-induced increase of the blood glucose level, and may improve insulin resistance. The angiotensin converting enzyme (ACE)-inhibiting effect and antioxidant effect of liver hydrolysate may be involved in this effect.

Hypertension and oxidant stress predispose to the onset and progression of arteriosclerotic diseases. In this study, the components of two kinds of porcine liver hydrolysates (LH-I and LH-II) were analyzed, and the antioxidant effects and angiotensin converting enzyme (ACE)-inhibiting effects of LH-I and LH-II were examined in vitro. Furthermore, the effects of LH-I and LH-II on the blood pressure were examined in spontaneously hypertensive rats (SHR). The results showed that peptides and amino acids accounted for 70% or more of the constituents of both LH-I and LH-II. The results of gel filtration HPLC showed that most of the nitrogen-containing components were peptides or amino acids with molecular weights of 6000 or less. The DPPH radical scavenging activities of LH-I and LH-II were 55.6 and 38.1 μM Trolox Equivalent/g, respectively. The IC(50) values for the ACE-inhibiting activity of LH-I and LH-II were 0.18 and 0.31 mg/mL, respectively. Oral administration of 1 g/rat of LH-I or LH-II to SHR resulted in significant lowering of the blood pressure. These findings indicate that both LH-I and LH-II have antioxidant activity and ACE-inhibiting activity. Moreover, both exerted a blood pressure-lowering effect in SHR. The antioxidant activity and ACE-inhibiting activity of LH-I and LH-II are presumed to be based on the actions of the component peptides.

It is reported that liver hydrolysate (LH) enhances liver function. However, the effects of LH on physical fatigue are unknown. The aim of this study was to investigate the effect of LH on alterations in locomotor activity and energy metabolism such as 5'-AMP-activated protein kinase (AMPK), glycogen content, and blood lactic acid, after forced walking. Adult male ddY mice were used. Locomotor activity, AMPK phosphorylation, and glycogen content in the liver and soleus muscle, as well as blood lactic acid were determined following LH treatment before and/or after forced walking. The locomotor activity significantly decreased after forced walking for 3 h. Two administrations of LH (30 or 100 mg/kg) significantly increased the locomotor activity, while a single administration either before or after forced walking did not show any specific effect. Administering LH twice activated AMPK in the liver and soleus muscle. Glycogen levels significantly decreased in both the liver and soleus muscle after forced walking, whereas the blood lactate level significantly increased. In contrast, administering LH twice increased muscle glycogen and decreased blood lactic acid. These findings indicate that LH produced an anti-fatigue effect and that this effect appears to involve the efficient glycogen utilization through activation of AMPK.

Background: Many studies on thyroid follicular tumors have reported the presence of somatic mutations to three forms of RAS: HRAS, KRAS, and NRAS. However, the frequency and clinical significance of these RAS mutations remain unclear, in large part due to the different methodologies being used for mutation analysis and the limited number of cases featured in studies. To clarify the significance of RAS mutations, we examined a large number of follicular adenomas and carcinomas obtained from a single institute using established methods for the analysis of RAS., Methods: Tumor samples from 40 follicular adenoma and 58 follicular carcinoma patients treated at the Kanagawa Cancer Center Hospital were analyzed. The three RAS mutations at codons 12 and 61 were assessed with a polymerase chain reaction-based loop-hybrid mobility shift assay followed by confirmation with direct sequencing. The relationships between mutation status and clinicopathological features at the time of the initial operation and the prognosis of the patients were also analyzed., Results: Twelve out of 40 (30%) adenomas harbored RAS mutations. In contrast, 33 out of 58 (57%) follicular carcinomas harbored RAS mutations, and the mutation was predominantly found in the NRAS codon 61 (22/33, 67%, p<0.01). The rate of gene mutations was significantly higher in the carcinomas than in the adenomas (p<0.01). The NRAS codon 61 mutation in follicular carcinomas was positively associated with distant metastases through the entire clinical course of the patients (p<0.05), and RAS mutations were associated with poor overall patient survival (p<0.05)., Conclusions: We investigated the frequency of RAS mutations in follicular thyroid tumors from a large number of cases obtained from a single institute. The predominance of NRAS codon 61 mutations as a feature of carcinomas indicates that the diagnosis of adenoma alongside the presence of this mutation should be made cautiously. Our study raises the possibility that follicular adenomas with the RAS mutations have an inherent malignant potential; however, the clinical significance of this finding should be further investigated in more patients and over a longer follow-up period.

A primary standard for the absorbed dose rate to water in a 60Co gamma-ray field was established at National Metrology Institute of Japan (NMIJ) in fiscal year 2011. Then, a 60Co gamma-ray standard field for therapy-level dosimeter calibration in terms of absorbed dose to water was developed at National Institute of Radiological Sciences (NIRS) as a secondary standard dosimetry laboratory (SSDL). The results of an IAEA/WHO TLD SSDL audit demonstrated that there was good agreement between NIRS stated absorbed dose to water and IAEA measurements. The IAEA guide based on the ISO standard was used to estimate the relative expanded uncertainty of the calibration factor for a therapy-level Farmer type ionization chamber in terms of absorbed dose to water (N(D,w)) with the new field. The uncertainty of N(D,w) was estimated to be 1.1% (k = 2), which corresponds to approximately one third of the value determined in the existing air kerma field. The dissemination of traceability of the calibration factor determined in the new field is expected to diminish the uncertainty of dose delivered to patients significantly.

The clinical efficacy and safety of CPT-11+CDDP therapy were studied retrospectively in 34 patients with advanced and recurrent gastric cancer. The overall response rate was 5. 9%; MST was 209 days. The adverse effects observed were grade 3 in 7 patients(20. 6%). CPT-11+CDDP therapy could be useful and safe as third-line chemotherapy.

We report three cases of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel (DOC). We administered S-1 orally at 80 mg/m² on days 1 to 7 and days 15 to 21, and DOC intravenously at 40 mg/m² on day 1 and 15, and evaluation was conducted every two courses. Case 1: A 73-year-old man with gastric cancer of cT4a, accompanied with bulky N2 lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by total gastrectomy, which revealed his histological grade to be 1b. Case 2: A 65-year-old man with gastric cancer of cT4a, accompanied with bulky lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by distal gastrectomy, which revealed his histological grade to be 1b. Case 3: A 76-year-old woman with gastric cancer of cT4b (panc), was treated with four courses of S-1 and DOC. After that, the main tumor was judged to be cT4a, followed by total gastrectomy, which revealed her histological grade to be 1b. Combined S-1 and DOC chemotherapy is an effective regimen for the treatment of unresectable gastric cancer.

A 73-year-old man with gastric cancer of Borrmann type 3 accompanied with N3 was treated by combination therapy of S-1 and docetaxel (DOC). He received DOC intravenously at 45 mg/m/2 on day 1 and 15, and S-1 orally at 120 mg/body on day 1 to 7 and day 15 to 21. This treatment was repeated every 28 days as one course. After 4 courses of treatment, a CT scan revealed partial response of the lymph node metastases, and imaging modalities showed complete response of the primary lesion. The serum CEA value normalized after 4 courses of treatment. Toxicities included leukocytopenia (grade 3-4) and neutropenia (grade 3-4). Chemotherapy in the outpatient setting was possible by reduction of dose (DOC 45-->40-->35 mg/m2). Total gastrectomy was performed after 4 courses of treatment. The histological effect of primary lesion was judged to be Grade 2.

Background: We retrospectively evaluated the efficacy of weekly paclitaxel therapy as second-line treatment for patients with advanced gastric cancer that was refractory to S-1., Patients and Methods: In total, 33 patients received intravenous paclitaxel (80 mg m(-2)) on days 1, 8 and 15 as part of a 4-week cycle., Results: Eight patients showed a partial response, 11 showed stable disease and 14 showed disease progression. In total, 171 courses (mean=5.2; range=3-16) were administered. Thirteen cases subsequently underwent third-line treatment. The median survival time and time to progression from the time of second-line treatment was 8.0 months and 4.2 months, respectively. The most common haematological toxicities were leukopenia and neutropenia. Non-haematological toxicities were generally mild to moderate and controllable., Conclusion: This study showed favourable therapeutic outcomes for advanced gastric cancer patients. However, it will be necessary to confirm the advantages of paclitaxel treatment for S-1-refractory advanced gastric cancer in a larger population.

A 31-year-old woman with cancer of the right breast underwent surgery in 1996. Histological examination demonstrated a solid tubular carcinoma that was positive lymph node metastasis and hormonal receptor, but negative for HER2 expression. The patient underwent adjuvant therapy with CAF and tamoxifen. At the age of 40 years old, Multiple liver metastasis appeared to the patient. We treated her with paclitaxel. But multiple liver metastasis became progressive disease. Next we treated with capecitabine and vinorelbine. The liver metastasis reduced, and, in the eighth month, the liver metastasis disappeared after 9 cycles. We changed treatment to goserelin, and anastrozole. The period of complete response was 1 year 3 months.

We report a 45-year-old woman with arrhythmogenic right ventricular dysplasia (ARVD). Because of congestive heart failure and atrial fibrillation, she underwent tricuspid valvular replacement and warfarin was prescribed. She suddenly had dysarthria, left hemiparesis and left hemispatial neglect. After brain CT examination, and cerebral angiography, she was diagnosed as cardiogenic brain embolism and infusion of low molecular heparin was started. On day 25, she suddenly had ventricular tachycardia and died in spite of treatment for arrhythmia. This is the first report of the case of cardiogenic brain embolism following ARVD. In this type of case, we must take care of arrhythmia besides the management of atrial fibrillation and brain infarction.

Objective: In this study, clinical findings were evaluated in 16 patients with reversible left ventricular dysfunction (RLVD) who showed a clinical picture similar to that of acute myocardial infarction, in addition to akinesis or dyskinesis of the left ventricular apex without showing any abnormalities in the coronary artery., Results: The frequency of RLVD was markedly higher in women than in men in these 16 patients (men:women = 1:7). In addition, these patients showed ECG changes similar to those observed in ischemic heart diseases, such as ST elevation or depression, negative T waves and QT prolongation. However, the serum cardiac markers were only slightly increased, and no specific changes were detected by histological examinations of the heart muscle., Conclusion: These patients also showed a clinical picture similar to the stunned myocardium caused by myocardial ischemia. However, the frequency of RLVD was higher in women than in men compared to the frequency of other coronary artery diseases, and there was no severe stenosis in the coronary artery. Moreover, most of these patients showed negative results for the coronary spasm provocation test. Therefore, RLVD may be an atypical ischemic heart disease if it is caused by coronary arteriosclerosis. Since RLVD developed during the course of other diseases or under severe mental stress, autonomic nerves may be involved in the etiology of RLVD. Furthermore, 2 patients who received the coronary spasm provocation test during the acute phase showed positive results. Therefore, other factors that transiently increase the sensitivity of the coronary artery may also be involved in the etiology of RLVD.

The enhancing effects of maltitol (alpha-D-glucopyranosyl-1,4-sorbitol) on absorption of calcium by the rat intestine have been studied by use of [45Ca]CaCl2 in-vivo. After intragastric administration of [45Ca]CaCl2 solution with maltitol, plasma 45Ca concentration remained at the maximum level for more than 80 min, whereas for animals given [45Ca]CaCl2 solution without maltitol, plasma 45Ca concentration declined sharply after the peak. Determination of 45Ca radioactivity remaining in the various segments of the gastrointestinal tract revealed that administration of maltitol elicited slower gastric emptying and slower intestinal transit, resulting in extensive 45Ca distribution along the small intestine throughout the experimental period. The luminal contents of the small intestine were significantly higher in rats given maltitol than in the control group. These results suggest that the enhancing action of maltitol on intestinal calcium absorption could be attributed to reduced gastrointestinal calcium transit and increased luminal fluid content, presumably because of the osmotic activity of maltitol; this would not only accelerate the dissolution of calcium into the increased luminal contents, but also enable a larger area of the small intestine to absorb calcium for a longer period of time.

Study Objective: To observe (1) whether the reperfusion is one of the causes underlying the development of diffuse alveolar injury following pulmonary embolism, and (2) whether polymorphonuclear leukocyte (PMN) accumulation occurs in the reperfused lobe, and (3) whether the production of superoxide is increased from cells obtained by BAL., Design: The condition of pulmonary embolism was simulated by occluding the pulmonary artery branch using a balloon catheter in anesthetized closed-chest dogs. The occlusion was maintained for 24 h in the occlusion group, and a 2-h period of occlusion was followed by reperfusion in the reperfusion group. Histologic examination was performed at 24 h after occlusion in both groups (n = 8). Using a different group of dogs (n = 12), local cellular changes in the occluded and reperfused lobes were evaluated through BAL performed at 1, 2, and 3 h after reperfusion in the reperfusion group and at 3 h after occlusion in the occlusion group. Superoxide generation from BAL cells was measured by the chemiluminescence method., Results: There was no histologic evidence of alveolar injury in the occluded lobe, but there were numerous leukocytes and erythrocytes along with exudate and damaged alveoli in the reperfused lobe. In the BAL study, the total cell counts recovered by BAL remained unchanged in all groups. However, the number of PMNs increased significantly in the late stages of reperfusion. Enhanced superoxide generation was observed in BAL cells obtained from reperfused lobe., Conclusion: Reperfusion is one of the causes underlying the development of alveolar injury in pulmonary embolism by triggering immigration of PMNs to alveoli, which results in the increased superoxide generation in BAL cells.

The effects of the structures of non-ionic surfactants on the uptake of butyl p-hydroxybenzoate (BP) into Escherichia coli cells and its antibacterial activity were systematically studied using polyoxyethylene alkyl ethers (PAEs) possessing various oxyethylene and hydrocarbon chain lengths. The uptake of BP into bacterial cells in an aqueous PAE solution was proportional to free BP in an aqueous phase, depending on the structures of PAEs. The antibacterial activity of BP decreased in the presence of PAEs, whereas it was greater than that anticipated from free BP. However, only PAE with 12 carbons in the hydrophobic group caused unusual increases in the uptake and antibacterial activity of BP, and the surfactant was more extensively incorporated into bacterial cells, differing from other PAEs, which were much less incorporated. The PAEs were thus concluded to increase the susceptibility of bacteria against BP due to direct interactions with the cells. Particularly, the PAE with 12 carbons in the hydrophobic group, which penetrated abundantly into the cells, might result in an increase in the fluidity of the cellular lipid matrix and a decrease in the resistance of drug permeation.

The relationship between the uptake and antimicrobial activity of p-hydroxybenzoic acid esters (parabens) was studied using Escherichia coli. The uptake into bacterial cells and the antibacterial activity of parabens were logarithmically proportional to the carbon number of the alkyl group from methyl to butyl paraben. The free energy change for the transfer of the methylene group of parabens from the aqueous to the cell phase was less than that obtained from the n-hexane and n-octanol-water partition systems. This demonstrates that the hydrophilicity of the cells is larger than n-hexane and n-octanol. The uptake of hydrophobic ethyl benzoate was less than that of the more hydrophilic butyl paraben possessing a phenolic hydroxyl group. Parabens may thus be incorporated into cells by both hydrophobic and hydrophilic interactions. The apparent concentration of parabens in the bacterial cells required to produce the same antibacterial activity decreased logarithmically with an increasing carbon number of the alkyl group. The dependence of the antibacterial activity of parabens on the alkyl chain length may thus be concluded to be due to the alkyl group, not only for uptake into bacterial cells but also for accumulation or concentration on biological receptors after incorporation into the cells.

A decreased concentration of dehydroepiandrosterone sulfate (DHEA-S) in patients with Alzheimer's disease (AD) has been reported but is still controversial. In the present study, serum concentrations of DHEA and DHEA-S were determined in 19 patients with AD, 21 patients with cerebrovascular dementia (CVD) and 45 age- and gender matched elderly control individuals from the Japanese community at large. Serum concentration of DHEA among controls, patients with AD and patients with CVD did not significantly differ from one another. However, patients with AD and patients with CVD were found to have lower concentration of serum DHEA-S and a lower DHEA-S/DHEA ration compared to normal control individuals. No significant difference was observed in the concentration of serum DHEA-S or the DHEA-S/DHEA ratio between patients with AD and those with CVD. These results suggest that reduced concentrations of serum DHEA-S may not be unique to AD, but instead reflect a common phenomenon in dementing diseases. However, since serum concentration of DHEA in these patients remained unchanged, the significance of DHEA in dementia remains unclear.

Possible risk factors associated with mortality were studied in a community using data derived from annual mass health examinations for the aged mandated by law. A total of 1,804 adults (685 men and 1,119 women) aged 40 or older in A-town, located on Tsushima Island, Nagasaki Prefecture, Japan who had participated in annual health examinations at least once between 1984 and 1990, were followed for a mean period of 4.9 years. After adjustment for age using Cox proportional hazards models, in men liver dysfunction (aspartate aminotransferase > 40 U/l or alanine aminotransferase > 35 U/l), fasting blood glucose > or = 110 mg/dl and glucosuria, and in women serum creatinine > or = 1.2 mg/dl, fasting blood glucose > or = 110 mg/dl and proteinuria were found to be associated with a significantly increased risk of total mortality. In multivariate analysis using all independent variables that were significantly associated with mortality in age-adjusted bivariate analysis, in men liver dysfunction and hyperglycemia, and in women hypercreatininemia and hyperglycemia, were significant predictors of mortality. These independent variables remained significant or marginally significant predictors of total mortality even after excluding the effects of 3 pancreatic cancer cases with liver dysfunction or hyperglycemia or 12 deaths within the first year of follow-up, being associated with at least two-fold increased hazard rate ratios. From these results, it is recommended that persons with these risk factors be followed intensively and counseled by public health personnel to modify risk factors.

The effects of nitric oxide (NO) on xanthine oxidase (XOD) activity and the site(s) of the redox center(s) affected were investigated. XOD activity was determined by superoxide (O2-) generation and uric acid formation. NO reversibly and dose-dependently suppressed XOD activity in both determination methods. The suppression interval also disclosed a dose-dependent prolongation. The suppression occurred irrespective of the presence or absence of xanthine; indicating that the reaction product of NO and O2-, peroxynitrite, is not responsible for the suppression. Application of synthesized peroxynitrite did not affect XOD activity up to 2 microM. Methylene blue, which is an electron acceptor from Fe/S center, prevented the NO-induced inactivation. The results indicate that NO suppresses XOD activity through reversible alteration of the flavin prosthetic site.

Recently, 5,5-dibromo-4-nitrosobenzenesulfonate (DBNBS) has been applied to detect biological free radicals. However, DBNBS has various non-specific reactions which lead to preplexing results. Thus, we investigated some basic reactions of DBNBS in combination of other nitroso spin traps to assign DBNBS spin adducts derived from human platelets which presumably related to the endothelium-derived relaxing factor (EDRF). The collagen activated platelets yielded four spin adducts (ST, LT, SS, and LS) in the presence of DBNBS (40 mM). The broad triplet due to ST was also observed by bubbling NO gas into a DBNBS solution. To identify ST, nitrosobenzene (NB) in dry dioxane was mixed with NO-saturated dioxane. The NB-NO spin adduct was observed but decomposed into diphenyl aminoxyl by the addition of H2O indicating that the primary adduct formed by the reaction of NO and DBNBS is unstable and turns into a dimerization product. Although ST could be eliminated by the inhibitor of EDRF, ST was shown to be produced by non-specific reactions. Another triplet was assigned to an S-centered radical because thiyl radicals which were generated from either the decomposition of S-nitrosothiol, or glutathione oxidation exhibited almost identical triplet signals. The other two sextets were assigned to C-centered radical adducts. Thus, DBNBS detected NQ-related, S-centered, and two C-centered radicals derived from human platelets. Special cautions are necessary for the identification of DBNBS spin adducts in a biological system to exclude artifactual radicals.

Endogenous substances which inhibited the binding of [3H]flunitrazepam ([3H]FNZ) to bovine synaptosomal membranes have been purified from the hot acetic acid extracts of the bovine brain. Three peaks of inhibitory activity were obtained by Sephadex G-10 gel chromatography. Two of the peaks (Peak 2, and Peak 3) which had lower molecular weights than that of peak 1 were identified as inosine and hypoxanthine by TLC methods. Another peak (Peak 1) was further purified to homogeneity using both cation and anion ion-exchange chromatography and the following two-step reversed-phase HPLC. The purified substance inhibited the [3H]FNZ binding dose-dependently and competitively but did not have an effect on the binding of the peripheral-type BZ ligand [3H]Ro 5-4864. It was also shown that the substance was heat-stable and resistant to proteolytic degradation (trypsin, alpha-chymotrypsin, pronase). However, a significant loss of inhibitory activity to [3H]FNZ binding was observed after acid hydrolysis. Molecular weight estimates based on gel filtration methods were less than 500 dalton, and the maximal ultraviolet absorption peak was at 314 nm. These results suggest that this substance is a new endogenous ligand for the central BZ receptor and may play an important role in regulating the GABAergic tone in the central nervous system.

The El mouse is an animal model with genetically determined epilepsy. To elucidate the mechanism of convulsive seizures in El mice, the effects of L-glutamate and glycine on the binding of (+)[3H]MK-801 were studied in well-washed membranes from forebrains of ddY, BALB/c and El (stimulated and non-stimulated) mice. There were no significant differences in affinity (Kd) or density (Bmax) among the 4 groups of mice under basal conditions. Incubation in the presence of L-glutamate and/or glycine led to an increase in apparent density, but not in affinity. No significant change was observed in either Kd, Bmax, or the percentage increase in (+)[3H]MK-801 binding amount the 4 groups in the presence of L-glutamate and/or glycine. These results suggest that the seizure susceptibility of El mice cannot be explained by changes in affinity or density of the NMDA receptor/channel complex.

The effects of dietary zinc status on the development of convulsive seizures, and zinc concentrations in discrete hippocampal areas and other parts of the limbic system were studied in the El mouse model receiving zinc-adequate, zinc-deficient or zinc-loaded diets. Seizure susceptibility of the El mouse was increased by zinc deficiency, and decreased by zinc loading, while an adequate diet had no effect. Zinc loading was accompanied by a marked increase in hippocampal zinc content in the El mouse. Conversely, hippocampal zinc content declined in the El mouse fed a zinc-deficient diet. These results suggest that zinc may have a preventive effect on the development of seizures in the El mouse, and hippocampal zinc may play an important role in the pathophysiology of convulsive seizures of epilepsy.

In the present study, zinc content was determined in discrete hippocampal and amygdaloid areas of 3 strains of mice (El, ddY and CBA) using an atomic absorption spectrophotometer. Zinc content was significantly lower in the dentate area of El strain compared to ddY and CBA strains. The El mouse is considered an animal model for epilepsy and the seizures in this mouse appear to originate in the hippocampus. The results suggest the possible involvement of hippocampal zinc in the pathophysiology of convulsive seizures in the epileptic mouse.

To evaluate the effect of calcium disodium ethylenediamine tetraacetate (CaEDTA) on concentrations of lead and zinc in plasma, erythrocytes, whole blood, and urine, we administered CaEDTA by intravenous infusion for 1 hr to seven lead workers with blood lead concentrations of 46-67 micrograms/100 g (mean 54 micrograms/100 g). The plasma lead concentration (PPb) and the mobilization yield of lead in urine by CaEDTA were highest during the period between 1 and 2 hr after the infusion was started. In contrast, the lead concentration in erythrocytes (EPb) and in whole blood (BPb) remained unchanged during the 24 hr following infusion. Plasma zinc concentration (PZn) also fell rapidly following CaEDTA infusion; the decline was followed by a gradual rise in the zinc concentration in erythrocytes (EZn) without alteration in the zinc in whole blood. The mobilization yield of zinc in urine by CaEDTA (MZn) reached its highest level within 1 hr after the start of the infusion. Delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes gradually increased for 5 hr following CaEDTA infusion. These observations suggest that (1) PPb concentration is a more sensitive indicator of the body burden of chelatable lead than is either BPb or EPb; (2) MZn is mobilized mostly from plasma during the first several hours following the start of CaEDTA infusion, and the fall in PZn concentration following infusion is compensated first by a rise in EZn concentration and then by an immediate redistribution of zinc in other organs to the blood; and (3) Pb-inhibited ALAD activity is reactivated by the increased EZn during and shortly after CaEDTA infusion.