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Intracystic bleeding is a relatively rare complication of hepatic cysts, which is very difficult to diagnose by conventional sonography (US). Hence, a new US technique has been sought for this purpose. We present the case of a hepatic cyst with intracystic bleeding in which contrast-enhanced US showed microbubbles oozing from the cyst wall into the cystic cavity. Contrast-enhanced US is now an important diagnostic tool for diagnosing liver tumors, but contrast-enhanced US findings relating to intracystic bleeding have not been reported. Our observations suggest that this technique may be a useful new diagnostic tool for this purpose. [ABSTRACT FROM AUTHOR] more...

There is a marked paucity of reports on contrast-enhanced ultrasonography (US) for focal splenic disease in the literature, and there are no previously reported contrast-enhanced US findings for splenic granuloma. We report the case of a 77-year-old cirrhotic woman with isolated splenic granulomas. We detail the diagnostic difficulty encountered in this case and briefly review the literature. [ABSTRACT FROM AUTHOR] more...

We report the case of a 82-year-old man with primary carcinoid tumor of the liver. Abdominal ultrasonography (US) showed 2 well-demarcated, round tumors in the right lobe (4 x 4 cm and 1 x 1 cm). The lesions were both markedly echogenic with many small cystic areas. Contrast-enhanced US showed the whole tumor to be quickly and highly enhanced, suggesting the highly vascular nature of the lesion, and the findings corresponded well with hepatic angiographic results. The patient underwent a US-guided needle biopsy, which yielded histological results consistent with a carcinoid tumor. Considering his age, we selected radiofrequency ablation (RFA) for treatment. After treatment, contrast-enhanced US demonstrated complete disappearance of blood flow signals, indicating satisfactory treatment. Our case showed that US and contrast-enhanced US findings can lead to a high suspicion of carcinoid tumor. [ABSTRACT FROM AUTHOR] more...

Macaques are useful animal models for studying the pathogenesis of rheumatoid arthritis (RA) and the development of anti‐rheumatic drugs. The purpose of this study was to identify the major histocompatibility complex (MHC) polymorphisms associated with the pathology of collagen‐induced arthritis (CIA) and anti‐collagen IgG induction in a cynomolgus macaque model, as MHC polymorphisms affect the onset of CIA in other animal models. Nine female Filipino cynomolgus macaques were immunized with bovine type II collagen (b‐CII) to induce CIA, which was diagnosed clinically by scoring the symptoms of joint swelling over 9 weeks. MHC polymorphisms and anti‐b‐CII antibody titers were compared between symptomatic and asymptomatic macaques. Four of 9 (44%) macaques were defined as the CIA‐affected group. Anti‐b‐CII IgG in the affected group increased in titer approximately 3 weeks earlier compared with the asymptomatic group. The mean plasma IgG1 titer in the CIA‐affected group was significantly higher (p < 0.05) than that of the asymptomatic group. Furthermore, the cynomolgus macaque MHC (Mafa)‐DRB1*10:05 or Mafa‐DRB1*10:07 alleles, which contain the well‐documented RA‐susceptibility five amino acid sequence known as the shared epitope (SE) in positions 70 to 74, with valine at position 11 (Val11, V11) and phenylalanine at position 13 (Phe13, F13), were detected in the affected group. In contrast, no MHC polymorphisms specific to the asymptomatic group were identified. In conclusion, the presence of V11 and F13 along with SE in the MHC‐DRB1 alleles seems essential for the production of IgG1 and the rapid induction of severe CIA in female Filipino cynomolgus macaques. [ABSTRACT FROM AUTHOR] more...

Abstract: The one pot aqueous reaction of M(ClO4)2 (M=Cu2+ or Ni2+) with N-methylbis[2-(2-pyridylethyl)]amine (MeDEPA) and N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)ethylenediamine (bpmen) and 1,4,7,10-tetraazacyclododecane (cyclen) in presence of sodium dicyanamide (Nadca) yielded dicyanamido-bridged polynuclear complex {[Cu(MeDEPA)(μ-1,5-dca)]ClO4} n (1), and two dinuclear complexes [Cu2(bpmen)2(μ-1,5-dca)]2(ClO4)5dca (2) and [Ni(cyclen)(μ-1,5-dca)]2(ClO4)2 (3). These complexes were characterized by IR and UV–Vis spectroscopy. Room temperature single-crystal X-ray studies have confirmed that the Cu(II) centers in 1 and 2 adopt geometries that are more close to trigonal bipyramidal (TBP) in 1 and close to square pyramidal (SP) in 2, whereas in 3, the Ni(II) centers are located in octahedral environment with doubly bridged μ-1,5-dca bonding mode. The intermolecular M···M distances in these complexes are in the range of 7.3–8.6Å. Variable temperature magnetic susceptibility studies have confirmed that the dca-bridges mediate very weak antiferromagnetic interaction between the M(II) centers with J values of −0.35, −0.18 and −0.43cm−1 for 1, 2 and 3, respectively. The results are compared and discussed in the light of other related bridged μ-1,5-dca Cu(II) and Ni(II) complexes. [Copyright &y& Elsevier] more...

Aims: The aim of this study was to clarify the histopathological features of fundic gland polyps (FGPs) in patients treated with proton pump inhibitors (PPIs) and to investigate the mechanism of enlargement of FGPs after PPI treatment. Methods and results: A total of 196 biopsy specimens of FGPs, which consisted of 87 FGPs in patients treated with PPIs (PPI group) and 109 FGPs in patients treated without PPIs (non‐PPI group) were compared histologically using haematoxylin and eosin staining, Ki67 immunohistochemistry and multiplex immunohistochemical stain with Ki67, MUC5AC and MUC6. The significant histological features of FGPs in the PPI group were: larger size of dilated fundic gland cysts, larger number of foveolar and mixture type fundic gland cysts, foveolar cell hyperplasia, parietal cell protrusion, mononuclear cell infiltration and a higher percentage of Ki67‐positive cells in the deeper layers of the glands. Multiplex immunohistochemical stain showed that Ki67‐positive cells were also positive for MUC5AC, and the Ki67‐positive rate was significantly higher in MUC5AC‐positive cells of the PPI group than of the non‐PPI group. Gene mutations of β‐catenin were found in only 9.7% of FGPs in the PPI group. Conclusions: Enlargement of fundic gland cysts due to foveolar cell proliferation and parietal cell protrusion might promote the enlargement of FGPs in patients treated with PPIs. β‐catenin gene mutations might not be associated with these histological changes of FGPs after PPI treatment. [ABSTRACT FROM AUTHOR] more...

Abstract: Pathogenicity of influenza B virus was examined in cynomolgus macaques to establish a macaque model suitable for vaccine and antiviral drug development. We prepared influenza B viruses for inoculation with minimal passages after isolation from patients. Macaques inoculated with influenza B virus showed higher body temperature than that before infection for 6 to 12days. Virus was detected in nasal, tracheal, and bronchial samples until 6days after inoculation followed by an increase in neutralizing antibody. High levels of IL-6 and TNF-α in nasal swabs from the infected macaques were correlated with fever. Symptoms and duration of the viral replication would be sufficient to evaluate efficacy of vaccines and antiviral agents. In addition, measurement of immune responses including antibody and cytokine production would provide an immunological rationale in efficacy of vaccines and antiviral agents. The results suggest that cynomolgus macaques are appropriate model animals for research of influenza B virus. [ABSTRACT FROM AUTHOR] more...

Background Highly pathogenic avian influenza virus (HPAIV) infection has a high mortality rate in humans. Secondary bacterial pneumonia with HPAIV infection has not been reported in human patients, whereas seasonal influenza viruses sometimes enhance bacterial pneumonia, resulting in substantial morbidity and mortality. Therefore, if HPAIV infection were accompanied by bacterial infection, an increase in mortality would be expected. We examined whether a vaccine against HPAIV prevents severe morbidity caused by mixed infection with HPAIV and bacteria. Methods H7N7 subtype of HPAIV and Streptococcus pneumoniae were inoculated into cynomolgus macaques with or without vaccination of inactivated whole virus particles . Results Vaccination against H7N7 HPAIV decreased morbidity caused by HPAIV and pneumonia caused by S. pneumoniae. Bacterial replication in lungs was decreased by vaccination against HPAIV, although the reduction in bacterial colonies was not significant. Conclusions Vaccination against HPAIV reduces pneumonia caused by bacterial superinfection and may improve prognosis of HPAIV-infected patients. [ABSTRACT FROM AUTHOR] more...

Abstract: Development of H7N7 highly pathogenic avian influenza virus (HPAIV) vaccines is an urgent issue since human cases of infection with this subtype virus have been reported and most humans have no immunity against H7N7 viruses. We made an H7N7 vaccine combining components from an influenza virus library of non-pathogenic type A influenza viruses. Antibody and T cell recall responses specific against the vaccine strain were elicited by subcutaneous inoculation with the whole virus particle vaccine with or without alum as an adjuvant in cynomolgus macaques. No significant difference was observed in magnitude of antibody responses between vaccination with alum and vaccination without alum, though vaccination with alum induced longer recall responses of CD8+ T cells than did vaccination without alum. After challenge with a subtype of H7N7 HPAIV, the virus was detected in nasal swabs of unvaccinated macaques for 8 days but only for 1 day in the animals vaccinated either with or without alum, although the macaques vaccinated with alum showed elevated body temperature more briefly after infection. These findings demonstrated that this H7N7 HPAIV strain is pathogenic to macaques and that the vaccine conferred protective immunity to macaques against H7N7 HPAIV infection. [Copyright &y& Elsevier] more...

Abstract: Outbreaks of highly pathogenic avian influenza viruses (HPAIVs) would cause disasters worldwide. Various strategies against HPAIVs are required to control damage. It is thought that the use of non-pathogenic avian influenza viruses as live vaccines will be effective in an emergency, even though there might be some adverse effects, because small amounts of live vaccines will confer immunity to protect against HPAIV infection. Therefore, live vaccines have the advantage of being able to be distributed worldwide soon after an outbreak. In the present study, we found that intranasal administration of a live H5N1 subtype non-pathogenic virus induced antibody and cytotoxic T lymphocyte responses and protected mice against H5N1 HPAIV infection. In addition, it was found that a small amount (100PFU) of the live vaccine was as effective as 100μg (approximately 1010–11 PFU of virus particles) of the inactivated whole particle vaccine in mice. Consequently, the use of live virus vaccines might be one strategy for preventing pandemics of HPAIVs in an emergency. [Copyright &y& Elsevier] more...

Contrast-enhanced sonography (CEUS) is a very important diagnostic imaging tool in clinical settings. However, it is associated with possible artifacts, such as B-mode US-related artifacts. Sufficient knowledge of US physics and these artifacts is indispensable to avoid the misinterpretation of CEUS images. This review aims to explain the basic physics of CEUS and the associated artifacts and to provide some examples to avoid them. This review includes problems related to the frame rate, scanning modes, and various artifacts encountered in daily CEUS examinations. Artifacts in CEUS can be divided into two groups: (1) B-mode US-related artifacts, which form the background of the CEUS image, and (2) artifacts that are specifically related to the CEUS method. The former includes refraction, reflection, reverberation (multiple reflections), attenuation, mirror image, and range-ambiguity artifacts. In the former case, the knowledge of B-mode US is sufficient to read the displayed artifactual image. Thus, in this group, the most useful artifact avoidance strategy is to use the reference B-mode image, which allows for a simultaneous comparison between the CEUS and B-mode images. In the latter case, CEUS-specific artifacts include microbubble destruction artifacts, prolonged heterogeneous accumulation artifacts, and CEUS-related posterior echo enhancement; these require an understanding of the mechanism of their appearance in CEUS images for correct image interpretation. Thus, in this group, the most useful artifact avoidance strategy is to confirm the phenomenon's instability by changing the examination conditions, including the frequency, depth, and other parameters. more...

Chronic inflammation and insulin resistance lead to metabolic syndrome and there is an urgent need to establish effective treatments and prevention methods. Our previous study reported that obese model Zucker (fa/fa) rats fed with ozonated olive oil alleviated fatty liver and liver damage by suppressing inflammatory factors. However, differences among animal species related to the safety and efficacy of ozonated olive oil administration remain unclear. Therefore, this study investigated the effects of oral intake of ozonated olive oil on lipid metabolism in normal mice and mice in the obesity model. C57BL/6J and db/db mice were fed the following AIN-76 diets for four weeks: the mice were either fed a 0.5% olive oil diet (Control diet) or 0.5% ozonated olive oil diet (Oz-Olive diet) in addition to 6.5% corn oil. The results indicated that four weeks of Oz-Olive intake did not adversely affect growth parameters, hepatic lipids or serum parameters in normal C57BL/6J mice. Subsequent treatment of db/db mice with Oz-Olive for four weeks reduced the levels of hepatic triglycerides, serum alkaline phosphatase, and serum insulin. These effects of Oz-Olive administration might be due to suppression of fatty acid synthesis activity and expression of lipogenic genes, as well as suppression of inflammatory gene expression. In conclusion, this study confirmed the safety of Oz-Olive administration in normal mice and its ability to alleviate hepatic steatosis by inhibiting fatty acid synthesis and inflammation in obese mice. more...

Hepatocellular carcinoma (HCC) in a non-fibrotic liver (F0) is considered to be rare, and there is a marked paucity of studies in the literature on this HCC type. A review of the literature shows some important clinical and tumor characteristics: (a) it occurs mainly in young female and elder male patients; (b) clinically, under normal hepatic function, alpha-fetoprotein level is often normal, and there are no risk factors; (c) associated with metabolic disease; (d) macroscopically, single large lesions are noted; and (e) microscopically, the lesions are well-differentiated and encapsulated. Radiological imaging results are straightforward, showing arterial hyperenhancement and later wash-out. The combined use of B-mode and contrast-enhanced (CE) ultrasound (US) is the most reliable and cost-effective diagnostic method. Few peri-and post-operative complications are noted and 5-year survival is not inferior to patients with HCC on fibrosis liver despite the lesion's large size. Most clinicians believe that HCC is unlikely to occur if patients have no symptoms and normal hepatic function. Although detailed clinical data are very limited, we expect that this review will help to improve the clinical management of HCC in non-fibrotic livers., Competing Interests: The authors declare no conflicts of interest. more...

Shear wave elastography (SWE) is now becoming an indispensable diagnostic tool in the routine examination of liver diseases. In particular, accuracy is required for shear wave propagation velocity measurement, which is directly related to diagnostic accuracy. It is generally accepted that the liver shear wave propagation velocity reflects the degree of fibrosis, but there are still few reports on other factors that increase the shear wave propagation velocity. In this study, we reviewed such factors in the literature and examined their mechanisms. Current SWE measures propagation velocity based on the assumption that the medium has a homogeneous structure, uniform density, and is purely elastic. Otherwise, the measurement is subject to error. The other (confounding) factors that we routinely experience are primarily: (1) Conditions that appear to increase the viscous component; and (2) Conditions that appear to increase tissue density. Clinically, the former includes acute hepatitis, congested liver, biliary obstruction, etc , and the latter includes diffuse infiltration of malignant cells, various storage diseases, tissue necrosis, etc . In any case, it is important to evaluate SWE in the context of the entire clinical picture., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.) more...

Intestinal tuberculosis can cause strangulated small bowel obstruction. Strangulated small bowel obstruction usually requires surgery. We report a case of a patient with intestinal tuberculosis, who developed a spontaneously resolving strangulated small bowel obstruction after the commencement of anti-tuberculosis drugs. A 72-year-old woman presented with abdominal pain and ascites was noticed on abdominal ultrasonography. Contrast-enhanced computed tomography (CT) revealed a 50-mm tumor in the ileocecal region that was darkly contrasted, along with peritoneal thickening and ascites. A malignant tumor and carcinomatous peritonitis were suspected. Colonoscopy showed an ulcerative lesion in the terminal ileum, and the acid-fast bacillus culture was positive; therefore, the patient was diagnosed with intestinal tuberculosis and was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. After commencing treatment, improvement in peritoneal thickening and ascites was confirmed using abdominal ultrasonography; therefore, we concluded that the ascites was due to tuberculous peritonitis. Six weeks after the initiation of treatment, the patient visited our facility with complaints of abdominal pain. Contrast-enhanced CT revealed unenhanced small intestinal walls, and a diagnosis of strangulated small bowel obstruction was made; however, her symptoms improved naturally. Strangulated small bowel obstruction was presumed to be due to the presence of bands as anti-tuberculosis therapy could promote fibrosis. In this case, abdominal ultrasonography was useful in the evaluation of the effects of treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Nakagawa et al.) more...

Excessive lipid accumulation in organs and adipocytes results in chronic inflammation. This causes irreversible organ dysfunction and the development of metabolic syndrome, atherosclerosis, and cancer. Ozonated olive oil shows anti-inflammatory effects when applied directly to the skin; however, there are no reports on its effects on lipid metabolism through its oral administration in rats. Hence, this study investigates the effects of oral ingestion of ozonated olive oil on the pathologies of obese model rats. Obese model Zucker (fa/fa) rats were fed one of the following AIN-76 diets for four weeks: control diet: 6.5% corn oil + 0.5% olive oil, low ozonated oil diet: 6.5% corn oil + 0.45% olive oil + 0.05% ozonated olive oil, high ozonated oil diet: 6.5% corn oil + 0.5% ozonated olive oil. Control diet fed-Zucker lean rats were used as the reference. Growth parameters, hepatic lipids, hepatic enzyme activities, and serum parameters were determined. As the results, there was a dose-dependent improvement of hepatomegaly, fatty liver and elevated levels of hepatic injury markers in Zucker (fa/fa) rat upon ozonated olive oil consumption. Activities of hepatic enzymes related to lipid synthesis and lipid degradation were not affected by ozonated olive oil intake. On the other hand, there was a dose-dependent elimination of hepatic lipid secretion deficiency and suppression of inflammatory factors upon ozonated olive oil consumption. In conclusion, ozonated olive oil intake by Zucker (fa/fa) rats alleviates hepatic steatosis through the inhibition of triglyceride accumulation in the liver and suppression of inflammatory factors. more...