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The differences in rorqual feeding ecology have been linked to the presence of different morphological markers. The Antarctic minke whale (Balaenoptera bonaerensis Burmeister, 1867) and the common minke whale (Balaenoptera acutorostrata Lacepede, 1804) are closely related species, but their morphological differences have not been fully investigated. In this study, we compared 21 skull and 11 feeding apparatus (baleen and mouth-related parts) measurement points between these two species using hundreds of individuals covering a wide range of body lengths in both sexes. Their engulfment capacities were estimated using these measurements. Our results show that Antarctic minke whales have (i) proportionally larger skulls to the body length, (ii) more dorsoventrally and laterally curved rostra, (iii) proportionally larger feeding apparatuses to the condylobasal length, and (iv) significantly larger engulfment capacity than common minke whales. These differences could indicate that Antarctic minke whales have developed a feeding strategy suitable for feeding on krill, which forms large schools. In contrast, common minke whales have adapted to prey on small pelagic fishes that are agile and form small schools. Key words: Balaenoptera bonaerensis, Balaenoptera acutorostrata, Antarctic minke whale, common minke whale, skull morphology, feeding morphology, engulfment capacity. Les differences sur le plan de l'ecologie de l'alimentation chez les rorquals ont ete associees a la presence de differents marqueurs morphologiques. Bien que le rorqual antarctique (Balaenoptera bonaerensis Burmeister, 1867) et le petit rorqual (Balaenoptera acutorostrata Lacepede, 1804) soient des especes etroitement reliees, leurs differences morphologiques n'ont pas ete examinees de maniere exhaustive. Nous avons compare 21 et 11 mesures du crane et de l'appareil d'alimentation (fanons et parties buccales), respectivement, obtenues de centaines de specimens des deux especes couvrant une grande fourchette de longueurs du corps pour les deux sexes. La capacite d'engouffrement a ete estimee a la lumiere de ces mesures. Nos resultats montrent que les rorquals antarctiques ont (i) des cranes proportionnellement plus grands par rapport a la longueur du corps, (ii) des rostres a plus forte courbure dorsoventrale et laterale, (iii) des appareils d'alimentation proportionnellement plus grands par rapport a la longueur condylobasale et (iv) une capacite d'engouffrement significativement plus grande que les petits rorquals. Ces differences pourraient indiquer que les rorquals antarctiques ont developpe une strategie d'alimentation adaptee a la consommation de krill, qui forme de grands bancs, alors que les petits rorquals se sont adaptes a la consommation de petits poissons pelagiques agiles formant de petits bancs. [Traduit par la Redaction] Mots-cles : Balaenoptera bonaerensis, Balaenoptera acutorostrata, rorqual antarctique, petit rorqual, morphologie cranienne, morphologie de l'appareil alimentaire, capacite d'engouffrement., Introduction Feeding is one of the most fundamental aspects for any animal species, as it is directly tied to their survival. Each cetacean species has its own feeding ecology (i.e., [...]

The possibility of 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) for liver cancer was investigated using a chemically induced hepatocellular carcinoma (HCC) model. Endogenously synthesised protoporphyrin IX (PpIX) following the administration of ALA is an effective photosensitiser for PDT. We determined the fluorescence intensity of PpIX in HCC and nontumoral tissue in the liver. 5-Aminolaevulinic acid was intravenously injected to male Fisher rats with HCC at a dose of 500 mg x kg(-1), and the fluorescence intensity in each tissue sample excised from liver was measured with a spectrofluorometer at 1, 3 and 6 h after administration. Fluorescence intensity was at a peak of 3 h after administration in both HCC and nontumoral tissue. The accumulation of PpIX in HCC was higher than that in the nontumoral tissue at 1 h (P<0.001) and 3 h (P<0.05) after ALA administration. Based on these results, PDT was performed on HCC at 3 h after 500 mg x kg(-1) ALA administration before laser irradiation of 30 J per tumour. Antitumour effect was more evident in HCC than in the nontumoral tissue surrounding HCC. These findings suggest the possibility to detect HCC by fluorescence and to treat HCC by light. [ABSTRACT FROM AUTHOR]

Discusses the accumulation of butylin compounds and total tin in marine mammals. Distribution pattern in the body; Status of contamination; Age trends, sex difference and species-specific accumulation.

Magnetic resonance spectroscopy in situ was used to study changes in phosphorus 31 metabolism after photodynamic therapy (PDT) of transplanted HeLa cell tumours. Tumours were irradiated 2 h after administration of ATX-S10 (8-formyloximethylidene-7-hydroxy-3-ethenyl-2, 7, 12, 18, tetramethyl-porphyrin-13,17-bispropionil aspartate), a new photosensitizer and chlorin derivative. Nuclear magnetic resonance spectra were measured prior to illumination and 1, 3, 7, 14, 21 and 28 days after PDT on each mouse. A drastic decrease in adenosine triphosphate (ATP) and a concomitant increase in inorganic phosphate (Pi) were evident on the first day after PDT in all cases. The β-ATP/total phosphate (P) ratio was 0.64 ± 0.29% (average ± s.d.) in complete response, 0.67 ± 0.30% in recurrence and 2.45 ± 0.93% in partial response. Comparison of this ratio to the histological findings revealed that the β-ATP/total P ratio reflects the HeLa cell tumours which survived PDT. In other words, partial response on the one hand was distinguished from complete response and recurrence on the other with this ratio 1 day after PDT (P < 0.05). In addition, the ratio of phosphomonoester (PME) to Pi rose beyond 1.0 when macroscopic recurrence occurred, while it stayed under 1.0 in complete response. This finding suggests that the recurrence of HeLa cell tumours can be detected by the PME/Pi ratio. [ABSTRACT FROM AUTHOR]

Persistent organochlorines such as polychlorinated biphenyls (PCBs),DDTs, chlordane compounds (CHLs), hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) were determined in the blubber of minke whaleand its diet collected from the Antarctic and the North Pacific Oceans. Residue levels of these compounds (except HCB) in minke whale from the Antarctic were apparently lower than those from the North Pacific. This is due to the lower levels of these pollutants in the southern hemisphere than in the northern hemisphere and the specific feeding habit of the minke whale from the Antarctic which feeds on lower trophic organisms, primarily euphausiids. The north-south difference for HCB residue levels was small, reflecting its dispersible nature through long-range atmospheric transport. Compositions of DDT and CHL compounds in minke whale from the Antarctic were similar to those from the North Pacific. However, the composition of HCH isomers was different between the Antarctic and the North Pacific as was observed in their diet, suggesting a larger or on-going usage of lindane in the southern hemisphere countries. In minke whale from the Antarctic, the elevated level of PCBs residues was noted during a period of 1984 to 1993, implying a continuous discharge of PCBs in the southern hemisphere. A similar discharge was also suggested in the North Pacific, whilea decreasing contamination by DDTs was apparent. [ABSTRACT FROM AUTHOR]

Rationale: Treatment strategies for rectal squamous cell carcinoma (rSCC) are yet to be established, given its rarity. Although squamous cell carcinoma has been reported to be highly sensitive to cetuximab and radiation, there is no report of combination therapy of cetuximab and radiation for rSCC. In this study, we firstly reported a case of rSCC in which a complete response was achieved with the original chemoradiotherapy comprising oxaliplatin, S-1, cetuximab, and simultaneous radiation., Patient Concerns: A 46-year-old women presented to our hospital with lower abdominal pain and fatigue., Diagnoses: Based on tumor marker analyses, histological examination of biopsy specimens, and comprehensive imaging, the patient was diagnosed with rSCC., Interventions: Neoadjuvant chemoradiotherapy (50.4 Gy) was administered in 28 fractions, along with concurrent chemotherapy comprising SOX (S-1: 80 mg/m2, days 1-5 and 8-12, oxaliplatin: 85 mg/m2, day 1) and cetuximab (400 mg/m2, day 1, 250 mg/m2, after day 8)., Outcomes: Five weeks after chemoradiation, the patient underwent laparoscopic partial intersphincteric resection, achieving a complete pathological response., Lessons: This case firstly highlights the usefulness of SOX plus cetuximab combined with radiation in the treatment of locally advanced rSCC. However, a large-scale study is required to establish safe and effective treatment regimens., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Baleen whales (Mysticeti) possess the necessary anatomical structures and genetic elements for olfaction. Nevertheless, the olfactory receptor gene ( OR ) repertoire has undergone substantial degeneration in the cetacean lineage following the divergence of the Artiodactyla and Cetacea. The functionality of highly degenerated mysticete OR s within their olfactory epithelium remains unknown. In this study, we extracted total RNA from the nasal mucosae of common minke whales ( Balaenoptera acutorostrata ) to investigate OR s' localized expression. All three sections of the mucosae examined in the nasal chamber displayed comparable histological structure. However, the posterior portion of the frontoturbinal region exhibited notably high OR expression. Neither the olfactory bulb nor the external skin exhibited the expression of these genes. Although this species possesses four intact non-class-2 OR s, all the OR s expressed in the nasal mucosae belong to class-2, implying the loss of aversion to specific odorants. These anatomical and genomic analyses suggest that OR s are still responsible for olfaction within the nasal region of baleen whales, enabling them to detect desirable scents such as prey and potential mating partners.

Effects of temperature on development of eggs, recently hatched larvae and L3 larvae of the marine parasitic nematodes Anisakis simplex sensu stricto (s.s.) and A. pegreffii were examined in vitro. The eggs of A. simplex s.s. hatched at 3-25 °C and those of A. pegreffii hatched at 3-27 °C. Days before hatching varied between 2 days at 25 °C and 35-36 days at 3 °C in A. simplex s.s. and between 2 and 3 days at 27 °C and 65 days at 3 °C in A. pegreffii. Hatching rates of A. simplex s.s. were maintained high at temperatures between 3 and 25 °C but decreased to 0% at 27 °C. In contrast, those of A. pegreffii were lowest particularly at 3 °C, but also at 27 °C. The mean 50% survivals of hatched larvae ranged from 5.3 days at 25 °C to 82.3 days at 9 °C in A. simplex s.s., while in A. pegreffii it ranged from 1.2 days at 27 °C to 77.2 days at 9 °C. L3 larvae of A. pegreffii exhibited higher survival rates and activity than those of A. simplex s.s., particularly at 20 and 25 °C. These results suggest that the early stages of A. simplex s.s. are more adapted to lower temperatures whereas those of A. pegreffii are more tolerant to warm environments, which may correspond to their distribution patterns in Japan and Europe., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: A colo-duodenal fistula is a very rare complication of colon cancer that presents with not only severe clinical symptoms, but a poor prognosis due to locally advanced cancer. A novel immune checkpoint inhibitor for colon cancer patients provides a high objective response rate. Recently, radiation therapy combined with immune checkpoint inhibitor therapy has been reported to have a synergistic antitumor effect. A case of complete closure of a colo-duodenal fistula in a patient with locally advanced colon cancer after combined pembrolizumab and radiation therapy is reported., Case Presentation: A 66-year-old man presented with abdominal distention. Abdominal contrast-enhanced computed tomography (CT) showed a 80-mm bulky mass in the right upper quadrant. The tumor created a fistula to the second portion of the duodenum. Upper gastrointestinal endoscopy showed a colo-duodenal fistula. Gastro-jejunal bypass and ileostomy were performed to prevent bowel obstruction, followed by systemic chemotherapy. MSI-high was diagnosed on examination of the biopsy specimen. Treatment was then changed to immunotherapy using pembrolizumab; after six courses, the tumor markers were decreased to within normal ranges, but the main tumor increased. Radiation therapy was then given for local control of the main tumor, after which CT showed that all of the tumor, including the main tumor, lymph node metastases, and the colo-duodenal fistula, had gradually shrunk. Follow-up upper gastrointestinal endoscopy showed that the colo-duodenal fistula had closed completely. PET-CT showed no abnormal uptake in all tumors, and clinical complete response was diagnosed. Now, 21 months after diagnosis, the tumor is well controlled without evidence of regrowth., Conclusions: Pembrolizumab combined with radiation therapy has a potentially dramatic therapeutic effect for advanced colon cancer., (© 2021. The Author(s).)

In this study, Anisakis nematodes isolated from toothed and baleen whales from localities around Japan were molecularly (PCR-RFLP) identified. In Wakayama, common bottlenose dolphins (Tursiops truncatus) were infected with A. simplex sensu stricto (s.s.), A. typica and A. pegreffii, while A. typica was the only species found in pantropical spotted dolphin (Stenella attenuata) and striped dolphin (S. coeruleoalba). Offshore common minke whales (Balaenoptera acutorostrata) and sei whales (B. borealis) were almost exclusively infected with A. simplex s.s.. However, in common minke whales from two Hokkaido localities, mature worms mostly consisted of A. simplex s.s. in some individuals and of A. pegreffii in others, but immature worms were mainly A. simplex s.s.. Gross and histopathological examination on gastric mucosa attached by anisakids resulted in mild and superficial reactions by the two baleen whale species in contrast to severe inflammatory reaction associated with ulcer formations by common bottlenose dolphin. Host specificity and adaptability of Anisakis spp. in these baleen and toothed whales were discussed from the points of view of adult worm size, worm population and pathological reactions by hosts. Interestingly, most of the common minke whales predominantly harboring mature A. pegreffii adults belonged to the Yellow Sea - East China Sea stock (J stock), which migrates through the Sea of Japan, whereas most of those mainly parasitized by mature A. simplex s.s. adults were from the Okhotsk Sea - West Pacific stock (O stock), mostly inhabiting the Pacific side, suggesting that these sibling species may have utility as biological tags to differentiate whale stocks. These results represent the first definitive host records for A. pegreffi in the Northwestern Pacific Ocean., (Copyright © 2020. Published by Elsevier B.V.)

On the basis of the evidence that the basolateral amygdala (BLA) modulates hippocampal memory processes via synaptic plasticity, here we report that adrenergic β receptor activation in the BLA rescues amyloid β 1-42 (Aβ 1-42 )-induced attenuation of long-term potentiation (LTP) at perforant pathway-dentate granule cell (DGC) synapses. When 500 μM isoproterenol (2 μl), an adrenergic β receptor agonist, was injected into the BLA 20 min before LTP induction, LTP was enhanced. Isoproterenol-mediated enhancement of LTP was blocked by co-injection with 100 μM ZnAF-2DA, an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ is required for the intracellular signaling cascade after adrenergic β receptor activation in the BLA. Aβ 1-42 -induced attenuation of LTP, which was induced by Aβ 1-42 injection into the dentate gyrus 60 min before LTP induction, was rescued by isoproterenol injection into the BLA 20 min before LTP induction, but not by 500 μM phenylephrine (2 μl), an adrenergic α 1 receptor agonist, injection into the BLA, which did not enhance LTP unlike the case of isoproterenol injection. Interestingly, Aβ 1-42 -induced attenuation of LTP was also rescued by 100 μM isoproterenol injection into the BLA 20 min before LTP induction, which did not enhance LTP. The present study demonstrates that adrenergic β receptor activation in the BLA, which is linked with intracellular Zn 2+ signaling, rescues Aβ 1-42 -induced attenuation of dentate gyrus LTP. It is likely that adrenergic β receptor activation in the BLA is a strategy for rescuing Aβ 1-42 -induced cognitive decline that is associated with hippocampal synaptic plasticity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hippocampus-dependent memory is modulated by the amygdala. However, it is unknown whether intracellular Zn 2+ signaling in the amygdala is involved in hippocampus-dependent memory. On the basis of the evidence that intracellular Zn 2+ signaling in dentate granule cells (DGC) is necessary for object recognition memory via LTP at medial perforant pathway (PP)-DGC synapses, the present study examined whether intracellular Zn 2+ signaling in the amygdala influences object recognition memory via modulation of LTP at medial PP-DGC synapses. When ZnAF-2DA (100 μM, 2 μl) was injected into the basolateral amygdala (BLA), intracellular ZnAF-2 locally chelated intracellular Zn 2+ in the amygdala. Recognition memory was affected when training of object recognition test was performed 20 min after ZnAF-2DA injection into the BLA. Twenty minutes after injection of ZnAF-2DA into the BLA, LTP induction at medial PP-DGC synapses was attenuated, while LTP induction at PP-BLA synapses was potentiated and LTP induction at BLA-DGC synapses was attenuated. These results suggest that intracellular Zn 2+ signaling in the BLA is involved in BLA-associated LTP and modulates LTP at medial PP-DGC synapses, followed by modulation of object recognition memory., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study aimed to compare the tissue stiffness of pancreatic ductal adenocarcinoma (PDAC) with that of pancreatic parenchyma using virtual touch quantification (VTQ). SWV was measured in 34 PDAC lesions and in pancreatic parenchyma of both controls and patients. SWVs in PDAC lesions were significantly higher than in pancreatic parenchyma in both healthy controls and in patients with PDAC. The area under the ROC for diagnosis of PDAC was 0.94 for pancreatic parenchyma in healthy controls, and 0.85 for pancreatic parenchyma in patients with PDAC. VTQ can provide a useful and additional information for diagnosis of PDAC., (Copyright © 2016. Published by Elsevier Inc.)

In a long-term, large-scale serologic study in the western North Pacific Ocean, anti-Brucella antibodies were detected in common minke whales (Balaenoptera acutorostrata) in the 1994-2010 offshore surveys (21%, 285/1353) and in the 2006-2010 Japanese coastal surveys (20%, 86/436), in Bryde's whales (B. edeni brydei) in the 2000-2010 offshore surveys (9%, 49/542), in sei whales (B. borealis) in the 2002-2010 offshore surveys (5%, 40/788) and in sperm whales (Physeter macrocephalus) in the 2000-2010 offshore surveys (8%, 4/50). Anti-Brucella antibodies were not detected in 739 Antarctic minke whales (B. bonaerensis) in the 2000-2010 Antarctic surveys. This suggests that Brucella was present in the four large whale populations inhabiting the western North Pacific, but not in the Antarctic minke whale population. By PCR targeting for genes of outer membrane protein 2, the Brucella infection was confirmed in tissue DNA samples from Bryde's whales (14%, 2/14), sei whales (11%, 1/9) and sperm whales (50%, 2/4). A placental tissue and an apparently healthy fetus from a sperm whale were found to be PCR-positive, indicating that placental transmission might have occurred and the newborn could act as a bacterial reservoir. Marked granulomatous testes were observed only in mature animals of the three species of baleen whales in the western North Pacific offshore surveys, especially in common minke whales, and 29% (307/1064) of total mature males had abnormal testes. This study provides an insight into the status of marine Brucella infection at a global level.

Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Figs. 3 and 4; essentially, there was the direct duplication of a panel between Fig. 3B, upper left‑hand panel (the G1-10W data) and Fig. 4B, also the upper left-hand panel (the G1-14W data). In the upper-left panels of Fig. 3B and 4B, we wanted to demon-strate microscopic features of the control liver at 10 weeks and 14 weeks, respectively. After having re-examined our original data, we note that we inadvertently duplicated the picture of the control liver at 14 weeks in the upper‑left panel of Fig. 3B. A corrected version of Fig. 3 is presented below, in which the G1-10W data in Fig. 3B are now correctly shown. Since G1-10W and G1-14W are control images of the liver, exhibiting a normal appearance, this error did not affect the findings in the study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. [the original article was published in the International Journal of Oncology 40: 1779-1788, 2012; DOI: 10.3892/ijo.2012.1343].

Aims: The kidney becomes atrophic in advanced chronic kidney disease, and renal size and parenchymal volume correlate with renal function. However, alterations in renal parenchymal volume have not been adequately studied in terms of the renal cortex and medulla. We investigated the relationship between the changes in the renal cortex and medulla and renal function., Methods: Renal ultrasound (US) parameters including renal length, parenchymal thickness, cortical thickness and medullary thickness were assessed in 176 subjects, who were categorized into 4 groups based on the estimated glomerular filtration rate (ml/min/1.73 m2): group 1, ≥ 90; group 2, ≥ 60 but < 90; group 3, ≥ 30 but < 60; and group 4, < 30. Renal US parameters in both kidneys were compared among the 4 groups., Results: We found stepwise associations in renal length, cortical thickness and parenchymal thickness with decreased renal function. Medullary thickness showed no changes among groups 1-3. Multiple linear regression analysis including sex, age and renal US parameters showed that only renal length was an independent predictor of renal function. When analyzed in groups 1-3, cortical thickness was the strongest associated parameter. Lower cortical left/right ratio (left cortical thickness/right cortical thickness) showed a stepwise association with a decrease in renal function., Conclusion: Renal length and cortical thickness measured by US were correlated with renal function. In particular, left cortical thickness could help to detect early changes in renal function., (© 2015 S. Karger AG, Basel.)

Background & Aims: The aim of this study was to investigate the feasibility of ablative margin (AM) grading by magnetic resonance imaging (MRI) with Gd-EOB-DTPA administered prior to radiofrequency ablation (RFA), and to identify factors for achieving a sufficient AM and predictors for local tumor progression., Methods: A total of 124 hepatocellular carcinomas (HCCs) were treated by RFA after Gd-EOB-DTPA administration. MRI and enhanced CT were performed within seven hours and one month after RFA. The AM assessment was categorized using three grades: AM (+), low-intensity area with continuous high-intensity rim; AM zero, low-intensity area with discontinuous high-intensity rim; and AM (-), low-intensity area extends beyond the high-intensity rim. Patients were followed and local tumor progression was observed., Results: AM (+), AM zero, AM (-), and indeterminate were found in 34, 33, 26, and 31 nodules, respectively. The overall agreement rate between MRI and enhanced CT for the diagnosis of AM was 56.8%. The κ coefficient was 0.326 (p<0.001), indicating moderate agreement. Multivariate logistic regression analysis showed that a significant factor for the achievement of AM (+) on MRI was no contiguous vessels. The cumulative local tumor progression rates (0% at 1, 2, and 3 years) in 33 AM (+) nodules were significantly lower than those (3.6%, 11.5%, and 18.3% at 1, 2, and 3 years respectively) in 32 AM zero nodules. A multivariate Cox proportional hazards model identified tumor size as an independent predictor for local tumor progression., Conclusion: Gd-EOB-DTPA-MRI enabled an early assessment of RFA effectiveness in the majority ofHCC nodules. Local tumor progression was not detected in AM (+) nodules during the follow-up., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Mercury accumulates at high levels in marine mammal tissues. However, its speciation is poorly understood. The main goal of this investigation was to establish the relationships among mercury species and selenium (Se) concentrations in toothed-whale muscles at different mercury levels. The concentrations of total mercury (T-Hg), methylmercury (MeHg), inorganic mercury (I-Hg) and Se were determined in the muscles of four toothed-whale species: bottlenose dolphins (n=31), Risso's dolphins (n=30), striped dolphins (n=29), and short-finned pilot whales (n=30). In each species, the MeHg concentration increased with increasing T-Hg concentration, tending to reach a plateau. In contrast, the proportion of MeHg in T-Hg decreased from 90-100% to 20-40%. The levels of T-Hg and Se showed strong positive correlations. Se/I-Hg molar ratios rapidly decreased with the increase of I-Hg and reached almost 1 in all species. These results suggested that the demethylated MeHg immediately formed Se/I-Hg equimolar complex of mercury selenide (HgSe) in their muscles. In addition, an X-ray absorption fine structure analysis (XAFS) of a bottlenose dolphin muscle confirmed that the dominant chemical form of the Se/I-Hg equimolar complex was HgSe. HgSe was mainly localized in cells near the endomysium using electron probe microanalysis (EPMA). These results suggested that the demethylated MeHg finally deposits within muscle cells of bottlenose dolphin as an inert HgSe., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The influx of extracellular Zn(2+) into dentate granule cells is nonessential for dentate gyrus long-term potentiation (LTP) and the physiological significance of extracellular Zn(2+) dynamics is unknown in the dentate gyrus. Excess increase in extracellular Zn(2+) in the hippocampal CA1, which is induced with excitation of zincergic neurons, induces memory deficit via excess influx of Zn(2+) into CA1 pyramidal cells. In the present study, it was examined whether extracellular Zn(2+) induces object recognition memory deficit via excess influx of Zn(2+) into dentate granule cells. KCl (100 mM, 2 µl) was locally injected into the dentate gyrus. The increase in intracellular Zn(2+) in dentate granule cells induced with high K(+) was blocked by co-injection of CaEDTA and CNQX, an extracellular Zn(2+) chelator and an AMPA receptor antagonist, respectively, suggesting that high K(+) increases the influx of Zn(2+) into dentate granule cells via AMPA receptor activation. Dentate gyrus LTP induction was attenuated 1 h after KCl injection into the dentate gyrus and also attenuated when KCl was injected 5 min after the induction. Memory deficit was induced when training of object recognition test was performed 1 h after KCl injection into the dentate gyrus and also induced when KCl was injected 5 min after the training. High K(+)-induced impairments of LTP and memory were rescued by co-injection of CaEDTA. These results indicate that excess influx of Zn(2+) into dentate granule cells via AMPA receptor activation affects object recognition memory via attenuated LTP induction. Even in the dentate gyrus where is scarcely innervated by zincergic neurons, it is likely that extracellular Zn(2+) homeostasis is strictly regulated for cognition., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects.

Concentrations of polychlorinated biphenyls (PCBs), dichlorodiphenyl trichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and chlordane compounds (CHLs) were determined in the blubber of males (20-25 years old) of Antarctic minke whales, Balaenoptera bonaerensis, from the International Whaling Commission (IWC) management Areas IV (70°-130°E) and V (130°E-170°W), south 60°S. The ranges of concentrations (ng g(-1) lipid wt.) for each compound were, PCBs: 7.7-89; DDTs: 29-340; HCHs: 0.20-4.3; HCB: 75-430; CHLs: 10-120, which were much lower than those in common minke whales, Balaenoptera acutorostrata, from the northern hemisphere. The levels of PCBs, HCHs, HCB and CHLs in Area IV were significantly higher than those in Area V, while the levels of DDTs in both areas were similar. For comparing the fate among four pesticides in the Antarctic Ocean avoiding the effect of variance due to food intake, the ratios of the pesticides to PCBs, which has an extremely high chemical stability and environmental persistence, were examined. The HCHs/PCBs ratio decreased by a factor of about 20 in a span of 16 years in both Areas IV and V, while temporal trends of DDTs/PCBs, HCB/PCBs and CHLs/PCBs ratios were not observed. These results indicate that PCBs, DDTs, HCB and CHLs levels did not vary or slightly decreased in Areas IV and V during the study period. However HCHs levels clearly decreased. Spatial differences seems to be related to differences in food intake among whales, and temporal differences seems to be related to the length stay of OCs in the Antarctic Ocean., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: The purpose of this study was to evaluate the usefulness of contrast-enhanced ultrasound (CEUS) with Sonazoid (perfluorobutane) in patients with liver abscess. Sonazoid is a contrast agent with a low mechanical index and is phagocytosed by Kupffer cells., Methods: Twenty-two patients with liver abscess were evaluated with conventional US, real-time CEUS with Sonazoid, and enhanced computed tomography (CT). After 0.5 mL of Sonazoid was administrated i.v., CEUS images in the vascular and post-vascular phases were observed., Results: Conventional US showed hypoechoic lesions in 13 (59.1%), isoechoic in four (18.2%), hyperechoic in two (9.1%), mixed echoic in two (9.1%) and undetected in one (4.8%) patient. CEUS showed perilesional enhancement in 19 (86.4%) lesions in the vascular phase and well-defined unenhanced areas in 22 (100%) lesions in the post-vascular phase. CEUS revealed that 18 abscesses were cystic type and three were honeycomb type. Twenty-one abscesses (95.5%) had clearer appearances on CEUS than on conventional US in regard to the extent of necrotic or liquefied lesions seen. We could confirm reduction of the lesions after therapy in 13 (92.9%) of 14 patients followed up by CEUS., Conclusion: Most of the liver abscesses showed perilesional enhancement in the vascular phase and unenhanced areas in the post-vascular phase. The appearance of liver abscesses was clearer on CEUS than on conventional US. CEUS with Sonazoid can be a more effective diagnostic and therapeutic tool for liver abscess., (© 2014 The Japan Society of Hepatology.)

Hepatic concentrations of persistent organochlorines (OCs) were determined in the common minke whale (Balaenoptera acutorostrata) from the North Pacific. To investigate the effects of OCs on the transcriptome in the minke whale, the present study constructed a hepatic oligo array of this species where 985 unique oligonucleotides were spotted and further analyzed the relationship between the OC levels and gene expression profiles of liver tissues. The stepwise multiple linear regression analysis identified 32 genes that correlated with hepatic OC levels. The mRNA expression levels of seven cytochrome P450 (CYP) genes, CYP1A1, 1A2, 2C78, 2E1, 3A72, 4A35, and 4V6 showed no clear correlations with the concentration of each OC, suggesting that the accumulated OCs in the liver did not reach levels that could alter CYP expression. Among the genes screened by the custom oligo array analysis, hepatic mRNA expression levels of 16 genes were further measured using quantitative real-time reverse transcription polymerase chain reaction. The mRNA levels of vitamin D-binding protein (DBP) were negatively correlated with non-ortho coplanar polychlorinated biphenyl (PCB) levels. Androgen receptor-associated coregulator 70 (ARA70) expression levels showed a significant positive correlation with concentrations of non-ortho coplanar PCB169. These correlations suggest that coplanar PCB-reduced DBP expression could suppress vitamin D receptor-mediated signaling cascades in peripheral tissues. Alternatively, the suppression of vitamin D receptor signaling cascade could be enhanced through competition with the androgen receptor signaling pathway for ARA70. In addition, a negative correlation between kynureninase and PCB169 levels was also observed, which suggest an enhanced accumulation of an endogenous aryl hydrocarbon receptor agonist, kynurenine in the minke whale population. Further studies are necessary to translate the changes in the transcriptome to toxicological outcomes including the disruption of the nervous and immune systems., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We experienced a case of acute congestive heart failure in a 73-year-old man who had been followed up due to mild-to-moderate aortic stenosis and moderate-to-severe aortic regurgitation. A huge aortic valve aneurysm was found to extend from his right coronary cusp to a left ventricular outflow tract, resulting in moderate subaortic obstruction and severe aortic regurgitation. Surgical repair was performed and a perforated aneurysm of right aortic cusp was identified. Histological examinations suggested that healed infective endocarditis was responsible for the formation of an aneurysm in the aortic valve. < Learning objective: Aortic valve aneurysm is an uncommon complication of infective endocarditis. The infective process of a cardiac valve is thought to augment valvular tissue injury, resulting in aneurysmal formation and perforation of the valvular aneurysm. We report an uncommon case of aortic valve aneurysm that was histologically suggested to be caused by subclinical infective endocarditis. The subaortic obstruction and aortic regurgitation were successfully treated using a surgical procedure.>.

The aim of this study was to investigate the anticarcinogenic effects of silymarin in diethylnitrosamine (DEN)-induced hepatocarcinogenic rat models. Severe and mild models of hepatocellular carcinoma (HCC) were generated by the intraperitoneal administration of 40 mg/kg DEN once a week for 18 weeks and 100 mg/kg DEN every 2 weeks for 6 weeks in male Wistar rats, respectively. In the severe and mild models of HCC, the rats were treated with 0.1 and 0.5% silymarin for 18 weeks and with 0.1% silymarin for 5 weeks, respectively. Serum transaminase levels were not significantly decreased by the silymarin treatment in either model. Macroscopic and microscopic features indicated that the silymarin-containing formulations did not significantly inhibit the hepatic tumor formation induced by DEN. Furthermore, immunohistochemical and western blot analyses demonstrated that the expression levels of proliferating cell nuclear antigen and glutathione S -transferase P, which are hepatocarcinogenic markers, were not significantly modified by the silymarin treatment. These results indicate that silymarin may not be considered as a candidate agent against hepatocarcinogenesis.

Background: Our aim was to determine how well ablative margin (AM) grading assessed by magnetic resonance imaging (MRI) with ferucarbotran administered prior to radiofrequency ablation (RFA) predicts local tumor progression in comparison with enhanced computed tomography (CT)., Methods: 101 hepatocellular carcinomas were treated by RFA after ferucarbotran administration. We performed T2*-weighted MRI after 1 week and enhanced CT after 1 month. The assessment was categorized in three grades: AM(+): high-intensity area with continuous low-intensity rim; AM zero: high-intensity area with discontinuous low-intensity rim; and AM(-): high-intensity area extending beyond the low-intensity rim., Results: AM(+), AM zero, AM(-) and indeterminable were found in 47, 36, 8 and 10 nodules, respectively. The overall agreement rate between MRI and enhanced CT for the diagnosis of AM was 71.3%. The κ coefficient was 0.523 (p < 0.001), indicating moderate agreement. Multivariate logistic regression showed that a significant factor for the achievement of AM(+) on MRI was only segment location (odds ratio 5.9, non-segment 4 + 8 vs. segment 4 + 8). The cumulative local tumor progression rates (4.4, 7.6, and 7.6% in 1, 2, and 3 years) in 47 AM(+) nodules were significantly lower than those (13.9, 33.4, and 41.8% in 1, 2, and 3 years) in 36 AM zero nodules. A multivariate Cox proportional hazards model identified contiguous vessels (odds ratio 12.0) and AM(+) on MRI (odds ratio 0.19) as independent factors for local tumor progression., Conclusion: AM assessment by MRI using ferucarbotran can predict local tumor progression after RFA and enable early and less invasive diagnosis.

Morbillivirus infection is a severe threat to marine mammals. Mass die-offs caused by this infection have repeatedly occurred in bottlenose dolphins (Turiops truncatus) and striped dolphins (Stenella coeruleoalba), both of which belong to the family Delphinidae, but not in other cetaceans. However, it is unknown whether sensitivity to the virus varies among cetacean species. The signaling lymphocyte activation molecule (SLAM) is a receptor on host cells that allows morbillivirus invasion and propagation. Its immunoguloblin variable domain-like (V) region provides an interface for the virus hemagglutinin (H) protein. In this study, variations in the amino acid residues of the V region of 26 cetacean species, covering almost all cetacean genera, were examined. Three-dimensional (3D) models of them were generated in a homology model using the crystal structure of the marmoset SLAM and measles virus H protein complex as a template. The 3D models showed 32 amino acid residues on the interface that possibly bind the morbillivirus. Among the cetacean species studied, variations were found at six of the residues. Bottlenose and striped dolphins have substitutions at five positions (E68G, I74V, R90H, V126I, and Q130H) compared with those of baleen whales. Three residues (at positions 68, 90 and 130) were found to alternate electric charges, possibly causing changes in affinity for the virus. This study shows a new approach based on receptor structure for assessing potential vulnerability to viral infection. This method may be useful for assessing the risk of morbillivirus infection in wildlife., (© 2013 The Societies and Wiley Publishing Asia Pty Ltd.)

Objective: It is important to detect post-liver biopsy hemorrhage early and confirm hemostasis in the clinical setting. Contrast-enhanced ultrasound (CEUS) is a sensitive and highly specific tool for detecting active bleeding. The aim of this study was to investigate the rate of detection of track microbubble flow signals on CEUS with perflubutane following liver biopsy and to assess the disappearance of these signals., Methods: Microbubble flow signals along the needle track on CEUS were examined in 100 patients who underwent percutaneous US-guided liver biopsies. The microbubble flow signals were examined repeatedly until their disappearance. The patients were followed up with clinical and laboratory data to detect clinically significant hemorrhaging., Results: Microbubble flow signals on CEUS following percutaneous liver biopsy were seen in 33% of the patients. There were no significant differences in the platelet count, prothrombin time or length of the biopsy specimen between the patients with and those without microbubble flow signals on CEUS. The microbubble flow signals disappeared over time in all patients. There were no cases of clinically significant hemorrhaging in the present study., Conclusion: Track microbubble flow signals on CEUS are frequently observed after biopsies. The disappearance of a microbubble flow signal is a useful index for confirming hemostasis of postbiopsy hemorrhaging.

Purpose: The aim of this study was to evaluate the feasibility of magnetic resonance imaging (MRI) without a contrast agent to visualize the ablative margin after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), compared with enhanced CT., Methods: Twenty-five HCCs in 19 patients were treated by RFA. T1-weighted MRI was performed before and after RFA, and the signal intensities of the tumors and surrounding liver tissues were measured. Treatment efficacy was assessed based on three grades: margin (+), a continuous high-intensity rim around the index tumor; margin zero, a partially discontinuous high-intensity rim; margin (-), the tumor extends beyond the high-intensity rim., Results: Twelve (86%) of fourteen low-intensity tumors on the pre-MRI were visualized as low-intensity tumors on post-MRI, and the ablative margins were visualized as high-intensity rims. Two (67%) of three high-intensity tumors on pre-MRI were visualized as higher-intensity tumors in the high-intensity ablative margin. Because the signal intensities of tumors and surrounding tissues in 14 tumors that were low- or high-intensity tumors on pre-MRI increased to the same extent, the tumors and ablative margin could be distinguished on post images. In 6 (75%) of the 8 iso-intensity tumors on pre-MRI, the ablative margin and tumor could also not be discriminated on post-MRI. The overall agreement between MRI and CT for the ablative margin was good (κ coefficient=0.716, p=0.00002)., Conclusion: In 82% of low- or high-intensity tumors on pre-MRI, post-MRI without a contrast agent enabled visualization of the ablative margin as a high-intensity rim, and it was possible to evaluate the ablative margin earlier and easier than with enhanced CT., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: Our aim was to investigate whether magnetic resonance imaging (MRI) with ferucarbotran administered prior to radiofrequency ablation could accurately assess ablative margin when compared with enhanced computed tomography (CT) with iodized oil marking., Materials and Methods: We enrolled 27 patients with 32 hepatocellular carcinomas in which iodized oil deposits were visible throughout the nodule after transcatheter arterial chemoembolization. For these nodules, radiofrequency ablation was performed after ferucarbotran administration. We then performed T2-weighted MRI after 1 week and enhanced CT after 1 month. T2-weighted MRI demonstrated the ablative margin as a low-intensity rim. We classified the margin into three grades; margin (+): high-intensity area with a continuous low-intensity rim; margin zero: high-intensity area with a discontinuous low-intensity rim; and margin (-): high-intensity area extending beyond the low-intensity rim., Results: In 28 (86%) of 32 nodules, there was agreement between MRI and CT. The overall agreement between for the two modalities in the assessment of ablative margin was good (κ=0.759, 95% confidence interval: 0.480-1.000, p<0.001). In four nodules, ablative margins on MRI were underestimated by one grade compared with CT., Conclusion: MRI using ferucarbotran is less invasive and allows earlier assessment than CT. The MRI technique performed similarly to enhanced CT with iodized oil marking in evaluating the ablative margin after radiofrequency ablation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Chemopreventive effects of caffeine and curcumin were evaluated in the diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model. Animals injected with DEN for 10 weeks (G2-10w) and 14 weeks (G2-14w) were hepato-carcinogenic rats. Animals injected with DEN and treated with curcumin and caffeine for 10 weeks (G3-10w, G4-10w) and 14 weeks (G3-14w, G4-14w) were compared with those in G2. Macroscopic and microscopic features suggested that treatment with caffeine, but not curcumin, for 10 and 14 weeks was effective in inhibiting DEN-induced hepatocarcinogenesis. Immunohistochemical and western blot analysis with proliferating cell nuclear antigen and glutathione S-transferase-P antibodies also showed that expression levels of these hepato-carcinogenic markers were more efficiently reduced by treatment with caffeine than curcumin. Our data demonstrate that caffeine could be a more potent compound than curcumin for prevention of hepatocarcinogenesis in DEN-induced rats.

In the present study, we examined the sequential changes of diethylnitrosamine (DEN)-induced hepatocarcinogenesis in Wistar rats. After 14 weeks of DEN treatment, hyperplastic nodules developed as a consequence of the appearance of renewed hepatocytes, degenerated hepatocytes, oval cells and fibrotic changes. Total bilirubin and alanine aminotransferase levels were significantly higher in the DEN group compared to the control group throughout the experimental period. Our data may prove beneficial to future analyses of chemopreventive compounds during various stages of hepatocarcinogenesis in rats.

Since the majority of hepatocellular carcinoma (HCC) arises from a background of chronic liver diseases caused by infection with hepatitis C virus (HCV) and hepatitis B virus (HBV), chemoprevention targeting patients at high risk of HCC is feasible. In this review article, we summarize current knowledge of chemoprevention against HCC mostly using phytochemicals which have less toxicity than pharmaceutical agents. We describe in vivo and in vitro evidence and proposed mechanisms of beneficial effects of several compounds on the liver, including acyclic retinoid (ACR), angiotensin-converting enzyme inhibitors (ACEIs), caffeine, capsaicin, cepharanthine (CEP), cinnamaldehyde, curcumin, diallyl sulfide (DAS), eicosapentaenoic acid (EPA), epigallocatechin-3-gallate (EGCG), genistein, lycopene, resveratrol, silymarin, sulforaphane (SFN), and xanthohumol (XN). Because antihepatocarcinogenic effects by these compounds are mostly based on experimental studies, clinical evidence is urgently necessary.

Objective: Health-care associated pneumonia (HCAP) is a new category of pneumonia. We investigated differences of epidemiology, pathogens, and outcomes between HCAP patients in large hospitals and those in small hospitals., Methods: This was a retrospective observational study of patients hospitalized with HCAP from December 2009 to March 2010. HCAP was defined according to ATS/IDSA criteria. A large hospital was defined as ≥ 200 beds and a small hospital was <200 beds., Results: Of 117 patients, 61 patients were admitted to large hospitals and 56 patients were admitted to small hospitals. There was a significant difference of HCAP diagnostic criteria between the two groups. The A-DROP severity class was worse in the large hospital group than the small hospital group (P<0.05). Respiratory failure and disturbance of consciousness were more frequent in the large hospital group (P<0.05). The mortality rate was 8.2% in the large hospital group versus 1.8% in the small hospital group. Patients in the very severe A-DROP class had a high mortality rate of 33% in both groups., Conclusion: Patients with severe HCAP were more likely to be admitted to large hospitals. Patients in the very severe A-DROP class should receive intensive antibiotic therapy, but not all patients need broad-spectrum therapy.

Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 (MD-2) are essential for recognizing the lipopolysaccharides (LPS) of Gram-negative bacteria. We determined the sequences of cDNAs encoding TLR4 and MD-2 from cetaceans and generated three-dimensional (3D) models for a better understanding of their modes of interaction and LPS recognition. The 3D reconstructions showed that cetacean TLR4 and MD-2 formed a horseshoe-like structure comprised of parallel β-strands and a β-cup structure consisting of two anti-parallel β-sheets, respectively. The (TLR4-MD-2)(2) duplex-heterodimer was shown to form a symmetrical structure. Comparison with the interfaces of the complexes in other mammals revealed that cetacean TLR4s have some amino acid residue substitutions involved in duplex-heterodimer formation and in species variation for LPS recognition. These substitutions in the changed amino acid residues may alter the interaction among TLR4, MD-2, and LPS and modify the TLR4/MD-2 immunological responses., (Copyright © 2010 Elsevier Ltd. All rights reserved.)