Partially hydrolyzed guar gum attenuates non-alcoholic fatty liver disease in mice through the gut-liver axis

BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.

Coronary spasm: It's common, but it's still unsolved

Coronary spasm is caused by a transient coronary nar -rowing due to the constriction of epicardial coronary artery, which leads to myocardial ischemia. More than 50 years have passed since the first recognition of coronary spasm, and many findings on coronary spasm have been reported. Coronary spasm has been considered as having pivotal roles in the cause of not only rest angina but also exertional angina, acute coronary syndrome, and heart failure. In addition, several new findings of the mechanism of coronary spasm have emerged recently. The diagnosis based mainly on coronary angiography and spasm provo-cation test and the mainstream treatment with a focus on a calcium-channel blocker have been established. At a glance, coronary spasm or vasospastic angina(VSA) has become a common disease. On the contrary, there are several uncertain or unsolved problems regarding coronary spasm, including the presence of medically refractory coronary spasm(intractable VSA), or an appropriate use of implantable cardioverter defibrillator in patients with cardiac arrest who have been confirmed as having coronary spasm. This editorial focused on coronary spasm, including recent topics and unsolved problems.

Case of angina pectoris at rest and during effort due to coronary spasm and myocardial bridging

We present a case of a 71-year-old male who hadchest symptoms at rest and during effort. He had felt chest oppression during effort for 1 year,and his chest symptoms had recently worsened. One month before admission he felt chest squeezing at rest in the early morning. He presented at our institution to evaluate his chest symptoms. Electrocardiography and echocardiography failed to show any specific changes. Because of the possibility that his chest symptoms were due to myocardial ischemia,he was admitted to our institution for coronary angiography(CAG). An initial CAG showed mild atherosclerotic changes in the proximal segment of the left anterior descending coronary artery(LAD) and mid-segment of the left circumflex coronary artery. Subsequent spasm provocation testing using acetylcholine revealed a bilateral coronary vasospasm,which was relieved after the intracoronary infusion of nitroglycerin. Finally,a CAG showed myocardial bridging(MB) of the mid-distal segments of the LAD. Fractional flow reserve using the intravenous administration of adenosine triphosphate was positive at 0.77,which jumped up to 0.90 through the myocardial bridging segments when the pressure wire was pulled back. Thus,coronary vasospasm and MB might have contributed to his chest symptoms at rest and during effort. Interventional cardiologists should consider the presence of MB as a potential cause of myocardial ischemia.

Increased frequency of angina attacks caused by switching a brand-name vasodilator to a generic vasodilator in patients with vasospastic angina:Two case reports

It is well known that calcium channel blockers(CCBs) are the first line of therapy for vasospastic angina(VSA). Here, we report two cases of VSA with an increase in the frequency of angina attacks after switching from a brand-name to a generic CCB. In both cases, angina recurred upon switching from a brand-name CCB to a generic CCB during follow-up. The patients' condition improved upon switching back to the original CCB. Both cases involved a high severity of VSA, based on the results of spasm provocation testing. These findings suggest that, in some patients with severe VSA, the frequency of angina attacks increases when switching from a brand-name CCB to a generic CCB. Cardiologists should consider this factor when prescribing drugs for angina.

Influences of Diamines on the Morphologies and the Chemical, Thermal, and Mechanical Properties of Polyurethane-Imide Elastomers

Polyurethane-imide elastomers (PUIEs) are formed from isocyanate, polyol, acid anhydride, and diamine by liquid polymerization. Unfortunately, many of the diamines have rarely been applied to the formation of PUIEs. Hence, investigating the effect of diamines on PUIEs remains a challenge in polymer chemistry. Herein, PUIEs prepared from 4,4'-diphenylmethane diisocyanate (MDI), polytetramethylene glycol (Mw: 1000), pyromellitic dianhydride, and aromatic diamines (such as p-phenylene diamine, 4,4'-oxydianiline, and 1,3-bis(4-aminophenoxy)benzene), and aliphatic diamines (such as 1,2-ethylene diamine, 1,6-hexamethylene diamine, and 1,12-dodecamethylene diamine) were synthesized by liquid polymerization. The morphologies and the chemical, thermal, and mechanical properties of the various PUIEs were investigated. The obtained elastomeric sheets were characterized in terms of the following tests and methods: solubility and swelling tests, X-ray diffraction and differential scanning calorimetry, dynamic mechanical analysis and thermogravimetric analysis, tensile tests, nuclear magnetic resonance spectroscopy, infrared spectroscopy, atomic force microscopy, contact angle microscopy, and scanning electron

Synthesis and Properties of Novel Polyurethane-Imide Elastomers

Novel polyurethane-imide elastomers were prepared from isocyanates (hexamethylene, and 4,4’-dicyclohexyl diisocyanates), polytetramethylene glycol (PTMG1000, Mw = 1000), pyromellitic dianhydride, and 4,4’-diphenylmethane diamine. The formation of PUIEs was confirmed by Fourier transform infrared spectroscopy. The resultant films were studied through X-ray diffraction analysis, contact angle measurement, atomic force microscopy, solubility and swelling tests, tensile test, differential scanning calorimetry, dynamic mechanical analysis, and thermogravimetric analysis.

Importance of a second spasm provocation test:Four cases with an initial negative spasm provocation test

The spasm provocation test(SPT) is an important test in the diagnosis of vasospastic angina(VSA). In many cases, this test is performed as the gold standard test, and VSA is considered not present if the SPT is negative. However, some patients continue to experience chest symptoms despite a negative SPT. In this study, we report four cases in which SPT was repeated to evaluate chest symptoms despite the negative results of the first SPT. Two men in their 70 s, one woman in her 60 s, and one woman in her 70 s, all with chest symptoms, underwent a second SPT at 4, 3, 2, and 3 years, respectively, after the first SPT, which was negative. Three patients had positive results in the second SPT(75%). In conclusion, even when SPT is negative, the diagnosis of VSA should be made with clinical symptoms in consideration. In some cases, a second SPT may be required to confirm the diagnosis of VSA.

Thermoplasticity in Polyurethane-Imide Elastomers

Polyurethane-imide elastomers (PUIEs) are formed from isocyanates, polyols, diamines, and acid anhydrides through liquid polymerization. However, thermoplastic PUIEs have rarely been reported because the synthesis of thermoplastic PUIEs remains a challenge in polymer chemistry. In this study, PUIEs were prepared from 4,4'-diphenylmethane diisocyanate, polyols (polytetramethylene glycol (Mw = 1000), polycaprolactone diol (Mw = 1000), and polycarbonate diol (Mw = 1000)), 4,4'-oxydianiline, and acid anhydrides (pyromellitic dianhydride and 4,4'-oxydiphtaric anhydride). The thermoplasticities of the resultant PUIEs were investigated, and only PUIEs synthesized using 4,4'-oxydiphtaric anhydride expressed thermoplasticity.