Ozonated Olive Oil Intake Attenuates Hepatic Steatosis in Obese db/db Mice.

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.

MHC-DRB alleles with amino acids Val11, Phe13, and the shared epitopes promote collagen-induced arthritis and a rapid IgG1 response in Filipino cynomolgus macaques.

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.

Hepatocellular Carcinoma in Non-Fibrotic Liver: A Narrative Review.

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.

Factors other than fibrosis that increase measured shear wave velocity.

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.

Spontaneous Resolution of Strangulated Small Bowel Obstruction in a Patient With Intestinal Tuberculosis After Starting Anti-tuberculosis Drugs: A Case Report.

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.

Ozonated Olive Oil Alleviates Hepatic Steatosis in Obese Zucker (fa/fa) Rats.

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.

One-day seminar for residents for implementing abdominal pocket-sized ultrasound.

Despite its proven high utility, integration of pocked-sized portable ultrasound (US) into internal medicine residency training remains inconsistent. For 10 years, we have held a 1-d seminar biannually, consisting of lecture (half-day) and hands-on training (half-day) on pocket-sized US of the abdomen and lungs. The lecture consists of training on US physics and clinical applications of pocket-sized US, followed by a lecture covering the basic anatomy of the abdomen and lungs and introducing the systemic scanning method. Given the simple structure of pocket-sized US devices, understanding the basic physics is sufficient yet necessary to operate the pocket-sized US device. It is important to understand the selection of probes, adjustment of B mode gain, adjustment of color gain, and acoustic impedance. Basic comprehension may have a significant positive impact on the overall utilization of pocket-sized US devices. The easiest and most reliable way to observe the whole abdomen and lungs is a combination of transverse, sagittal, and oblique scanning, pursuing the main vascular system from the center to the periphery of the organ in the abdomen and systemic scanning of the pleura. There is usually a marked change in knowledge and attitudes among the program participants, although skill gaps remain among them. We discuss the limitations and problems to this education system as well.

Refraction artifact on abdominal sonogram.

Ultrasonography (US) is the first-line diagnostic tool for observing the whole abdomen. Unfortunately, a wide spectrum of refraction-related artefactual images is very frequently encountered in routine US examinations. In addition, most practitioners currently perform abdominal US examinations without sufficient knowledge of refraction artifacts (RAs). This review article was designed to present many representative RA images seen in the clinical setting, with a brief explanation of the mechanism of these images, in certain cases through an analyzed and reconstructed method using computer simulation that supports clinical observations. RAs are encountered not only with B-mode US but also with Doppler US, contrast-enhanced US, and shear wave elastography. RAs change their appearance according to the situation, but they always have a significant effect on detailed interpretation of abdominal US images. Correct diagnosis of abdominal US relies on a deep understanding of each characteristic artifactual finding, which necessitates knowledge of basic US physics. When analyzing mass lesions, computer simulation analysis helps to reveal the global images of RAs around a lesion.

No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques.

Tumorigenicity of induced pluripotent stem cells (iPSCs) is anticipated when cells derived from iPSCs are transplanted. It has been reported that iPSCs formed a teratoma in vivo in autologous transplantation in a nonhuman primate model without immunosuppression. However, there has been no study on tumorigenicity in major histocompatibility complex (MHC)-matched allogeneic iPSC transplantation with immune-competent hosts. To examine the tumorigenicity of allogeneic iPSCs, we generated four iPSC clones carrying a homozygous haplotype of the MHC. Two clones were derived from female fibroblasts by using a retrovirus and the other two clones were derived from male peripheral blood mononuclear cells by using Sendai virus (episomal approach). The iPSC clones were transplanted into allogenic MHC-matched immune-competent cynomolgus macaques. After transplantation of the iPSCs into subcutaneous tissue of an MHC-matched female macaque and into four testes of two MHC-matched male macaques, histological analysis showed no tumor, inflammation, or regenerative change in the excised tissues 3 months after transplantation, despite the results that iPSCs formed teratomas in immune-deficient mice and in autologous transplantation as previously reported. The results in the present study suggest that there is no tumorigenicity of iPSCs in MHC-matched allogeneic transplantation in clinical application.

Diagnostic problems in two-dimensional shear wave elastography of the liver.

Two-dimensional shear wave elastography (2D-SWE) is used in the clinical setting for observation of the liver. Unfortunately, a wide spectrum of artifactual images are frequently encountered in 2D-SWE, the precise mechanisms of which remain incompletely understood. This review was designed to present many of the artifactual images seen in 2D-SWE of the liver and to analyze them by computer simulation models that support clinical observations. Our computer simulations yielded the following suggestions: (1) When performing 2D-SWE in patients with chronic hepatic disease, especially liver cirrhosis, it is recommended to measure shear wave values through the least irregular hepatic surface; (2) The most useful 2D-SWE in patients with focal lesion will detect lesions that are poorly visible on B-mode ultrasound and will differentiate true tumors from pseudo-tumors (e.g., irregular fatty change); and (3) Measurement of shear wave values in the area posterior to a focal lesion must be avoided.