DHA supplementation prevent the progression of NASH via GPR120 signaling.

Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases involving chronic accumulation of fat and inflammation, often leading to advanced fibrosis, cirrhosis and carcinoma. However, the pathological mechanism for this is unknown. GPR120/FFAR4 has been recognized as a functional fatty acid receptor and an attractive therapeutic target for metabolic diseases. In this study, we investigated the involvement of GPR120/FFAR4 in the pathogenesis of NASH. Mice fed with a 0.1% methionine and choline deficient high-fat (CDAHF) diet showed a significant increase in plasma aspartate transaminase and alanine transaminase levels, fatty deposition, inflammatory cell infiltration, and mild fibrosis. Docosahexaenoic acid (DHA, GPR120/FFAR4 agonist) suppressed the inflammatory cytokines in the liver tissues and prevented fibrosis in the wild type (WT) mice fed CDAHF diet, but not GPR120/FFAR4 deficient (GPR120KO) mice. GPR120KO mice fed CDAHF diet showed increment of the number of crown like structures and the immunoreactivity for F4/80 positive cells, and increased TNF-α mRNA in the liver compared to WT mice fed CDAHF diet. GPR120 KO mice fed CDAHF diet showed more severe liver inflammation than that of WT mice fed CDAHF diet, but not fibrosis. Our findings suggest that DHA supplementation could be prevented the development of NASH via GPR120/FFAR4 signaling. Furthermore, decrease of GPR120/FFAR4 signaling could be facilitated an inflammatory response in the process of NASH progression.

Frequency of Acute Kidney Injury Caused by Tazobactam/Piperacillin in Patients with Pneumonia and Chronic Kidney Disease: A Retrospective Observational Study.

Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function. We studied a cohort of 57 patients with impaired renal function hospitalized with pneumonia and treated with TAZ/PIPC between January 2015 and November 2016. Patients were classified into four groups according to TAZ/PIPC dose: 2.25 g three times daily (Group A); 2.25 g four times daily (B); 4.5 g twice daily (C) and 4.5 g three times daily (D). We examined the frequency of acute kidney injury (AKI) and treatment effectiveness. In Groups A, B, C and D, AKI occurred in 5.6%, 0.0%, 25.0% and 38.5% of patient. In groups C and D, hydration and dose reduction were required to address early signs of impending AKI. Our findings suggest that the higher TAZ/PIPC dose of 4.5 g was responsible for the decline in renal function, even if the dose frequency was reduced.

Influence of hyperglycemia on liver inflammatory conditions in the early phase of non-alcoholic fatty liver disease in mice.

OBJECTIVES: A non-alcoholic fatty liver disease (NAFLD) has high prevalence and now important issue of public health. In general, there exists strong interaction between NAFLD and diabetes, but the detailed mechanism is unclear. In this study, we determined the effects of hyperglycemia on progression in the early phase of NAFLD in mice. METHODS: Male ddY mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) consisting of 60% of kcal from fat and 0.1% methionine by weight. Hyperglycemic condition was induced by streptozotocin (STZ) treatment. The assessment of liver function used serum AST and ALT levels, and histological analysis. Hepatic tumour necrosis factor (TNF)-α mRNA levels was estimated by qRT-PCR. KEY FINDINGS: During the 3-42 days that the mice were fed CDAHFD, the livers gradually caused accumulation of fat, and infiltration of inflammation cells gradually increased. Serum AST and ALT levels and significantly increased after being fed CDAHFD for 3 days and were exacerbated by the STZ-induced hyperglycemic condition. In addition, hepatic TNF-α mRNA also significantly increased. These phenomena reversed by insulin administration. CONCLUSIONS: The results showed that progression in the early phase of NAFLD may be exacerbated by hyperglycemia-induced exacerbation of inflammation.

The survey for pharmacist in community pharmacy concerning the usefullness of oral rehydration therapy (ORT) in self-medication and the state of sales of products for ORT.

The usefulness as one of the tools for self-medication of oral rehydration therapy (ORT), recommended as a safe and effective therapy for mild to moderate dehydration, was surveyed by questionnaire for pharmacists in community pharmacies. ORT products were sold in 112 pharmacies (61%), and the common product was OS-1(®). Approximately 50% of sellers answered that they had no particular difficulty in explaining ORT. Percentage to answer "hard to describe" is significantly higher in pharmacists who believe there is a need to consider underlying health conditions of customers or patients when implementing ORT. Around 77% of pharmacists considered ORT to be useful in patients as a method of self-medication. A significant number of pharmacists selling ORT products depends on the consultation from customers or patients and provide advice to them confirming that ORT was useful. From these results, it was suggested that further information concerning ORT, such as its use in patients with chronic disorders or signs for completion, and the initiative of pharmacists to participate are necessary for spread the efficacy of ORT for self-medication in patients.

Syndrome of inappropriate secretion of antidiuretic hormone associated with angiotensin-converting enzyme inhibitor administration.

Angiotensin-converting enzyme inhibitors (ACEI's) are an important medication in the treatment of congestive heart failure. However, ACEIs may cause harmful side effects, such as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), which is a rare but important side effect. We describe here a case of SIADH associated with ACEI administration in a 6-year-old boy with restrictive cardiomyopathy. After recovery from acute exacerbation of congestive heart failure by tolvaptan administration, an ACEI (cilazapril) was started to decrease the production of angiotensin II, which upregulates serum antidiuretic hormone secretion. The patient's heart failure symptoms worsened, including accumulation of right pleural effusion and ascites, after the initiation of ACEI administration. Cessation of ACEI administration dramatically improved his symptoms. Because it is difficult to distinguish SIADH associated with ACEI from worsening congestive heart failure, the possibility of fluid retention due to ACEI administration should always be considered when this agent is administered to patients with heart failure.

[Evaluation of cerebral oxygenation changes with clamping of the left superior vena cava by near-infrared spectroscopy].

OBJECTIVE: The left superior vena cava (LSVC) is often complicated with congenital heart defect. Although we simply clamp LSVC during cardio-pulmonary bypass (CPB), appropriateness of this technique has not been clarified. We noninvasively evaluate cerebral tissue oxygenation while the clamping of LSVC under CPB by near-infrared spectroscopy (NIRS). METHODS: Six children (3 male and 3 female; aged 1.0 +/- 0.6 year) undergoing open heart surgery were studied. The NIRO 300 was incorporated into an established multimodal monitoring system. Tissue oxygenation index (TOI), oxyhemoglobin (O2Hb), and deoxyhemoglobin (HHb) changes were assessed and compared with LSVC pressure. RESULTS: There were no significant changes in cerebral oxygen delivery after LSVC clamp. LSVC pressure increased from 7.3 +/- 1.8 mmHg to 20.1 +/- 2.6 just after LSVC clamp, but gradually decreased without any maneuver. CONCLUSION: These data demonstrated that LSVC could be safely clamped when LSVC pressure was under 30 mmHg.

Volume measurement of the left ventricle in children using real-time three-dimensional echocardiography: comparison with ventriculography.

OBJECTIVES: Recently, a real-time three-dimensional echocardiography (RT3DE) volume scanning technique was developed and used clinically. For precise ventricular volumetry, independent of mathematical assumptions, imaging techniques such as three-dimensional echocardiography are required in children with heart disease. This study evaluated whether RT3DE is suitable for left ventricular volumetry in children, and whether left ventricular volumes measured by RT3DE correlate sufficiently well with those measured by left ventriculography (LVG). METHODS: Twenty-five children with heart disease, 17 boys and 8 girls aged from 8 months to 18 years (mean age 5.9 +/- 5.3 years), underwent cardiac catheterization at our institution. RT3DE was performed within 30 min after LVG using the Philips SONOS 7500 ultrasound system with an electronic sector probe consisting of a X 4 matrix phased array transducer (center frequency of 2-4 MHz). Ultrasound images of the ventricle were calculated offline using TomTec 4D Cardio-View RT 1.2 software. Left ventricular volumes by LVG were calculated using Siemens Hicor T.O.P. Finally, the left ventricular volumes by RT3DE and LVG were compared. RESULTS: Left ventricular volumes measured by RT3DE correlated and agreed well with those measured by LVG(r = 0.996, Y = 0.566 + 0.964 X, mean difference -0.29 +/- 1.90ml; left ventricular end-systolic volume, r = 0.979, Y=-0.187 + 0.897 X, mean difference -6.76 +/- 10.58ml; left ventricular end-diastolic volume). CONCLUSIONS: RT3DE is suitable for left ventricular volumetry in children. There was a good correlation between RT3DE and LVG, but the volume of left ventricular end-diastolic volume estimated by RT3DE was smaller than that by LVG.

Elevated CSF IL-6 in a patient with respiratory syncytial virus encephalopathy.

The patient was an 11-month-old boy who developed encephalopathy associated with respiratory syncytial virus bronchiolitis. Right hemispheric encephalopathy was indicated by left hemiparesis and a diffuse right hemispheric lesion detected with magnetic resonance imaging. Elevated levels of interleukin-6 in the cerebrospinal fluid during the acute phase suggested the involvement of increased production of one or more cytokines in the pathogenesis of viral related encephalopathy, similarly to that proposed for influenza encephalopathy.