Dietary Gamma-Aminobutyric Acid (GABA) Induces Satiation by Enhancing the Postprandial Activation of Vagal Afferent Nerves

Gamma-aminobutyric acid (GABA) is present in the mammalian brain as the main inhibitory neurotransmitter and in foods. It is widely used as a supplement that regulates brain function through stress-reducing and sleep-enhancing effects. However, its underlying mechanisms remain poorly understood, as it is reportedly unable to cross the blood–brain barrier. Here, we explored whether a single peroral administration of GABA affects feeding behavior as an evaluation of brain function and the involvement of vagal afferent nerves. Peroral GABA at 20 and 200 mg/kg immediately before refeeding suppressed short-term food intake without aversive behaviors in mice. However, GABA administration 30 min before refeeding demonstrated no effects. A rise in circulating GABA concentrations by the peroral administration of 200 mg/kg GABA was similar to that by the intraperitoneal injection of 20 mg/kg GABA, which did not alter feeding. The feeding suppression by peroral GABA was blunted by the denervation of vagal afferents. Unexpectedly, peroral GABA alone did not alter vagal afferent activities histologically. The coadministration of a liquid diet and GABA potentiated the postprandial activation of vagal afferents, thereby enhancing postprandial satiation. In conclusion, dietary GABA activates vagal afferents in collaboration with meals or meal-evoked factors and regulates brain function including feeding behavior.     

First case of a bloodstream infection caused by the genus Brachybacterium

An 83-year-old previously self-sufficient man was referred to our hospital for a fever, severe tenderness over the lumbar spine, and elevated C-reactive protein levels. Computed tomography revealed fluid collection in the intervertebral space of L3/4. Gram-positive, short rod-shaped bacteria were isolated from two sets of blood cultures. A 16S rRNA sequence analysis of an isolate showed a similarity of 98.1% to the nearest type strain Brachybacterium squillarum JCM 16464^T. Biochemical characteristics of the presently isolated strain differed from those of the most closely related species of the genus Brachybacterium. The patient was successfully discharged on day 73 of admission with antimicrobial therapies and showed no recurrence during outpatient visits. Brachybacterium spp. have mainly been isolated from the environment, and human Brachybacterium infections have rarely been documented to date. To our knowledge, this is the first clinical isolation of Brachybacterium sp. as a causative pathogen of bloodstream infection.     

Late giant coronary aneurysm associated with a fracture of sirolimus eluting stent: a case report

A 73-year-old female underwent percutaneous coronary intervention (PCI) because of stable angina. An elective PCI for the RCA lesion was first performed with deploying sirolimus eluting stents (SES). Three weeks later, PCI was also provided in the residual LAD lesion. Eight months later, she presented with new angina. CAG revealed an in-stent restenosis in the mid LAD and a large eccentric saccular coronary aneurysm (17 mm x 9 mm) at the proximal RCA. Intravascular ultrasound (IVUS) showed absence of stent struts around the orifice of aneurysm, which suggested a fracture of SES stent. The entry of coronary aneurysm was finally sealed with a polytetrafluoroethylene-covered stent. This report documented a rare case of late giant coronary artery aneurysm associated with a fracture of SES.     

Ezetimibe alone or in combination with pitavastatin prevents kidney dysfunction in 5/6 nephrectomized rats fed high-cholesterol

We attempted to elucidate the relationship between cholesterol absorption and kidney damage by investigating the renoprotective effect of ezetimibe, a cholesterol absorption inhibitor, in 5/6 nephrectomized rats (Nx). The Nx or sham-operated rats (Sham) were fed 1% high-cholesterol diet (HC) containing ezetimibe (10 mg/[kg d]), pitavastatin (3 mg/[kg d]), or both for 8 weeks. Pathological changes, endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA), and oxidative stress were assessed in the kidney. The Sham fed HC exhibited hypercholesterolemia and glomerulosclerosis with macrophage infiltration in the kidney, and ezetimibe attenuated these changes. The Nx exhibited hypercholesterolemia, increased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), glomerulosclerosis with macrophage infiltration and interstitial fibrosis, and downregulation of eNOS mRNA. The HC increased cholesterol further and worsened the kidney damage with increased 8-OHdG. Ezetimibe attenuated the hypercholesterolemia, kidney dysfunction, and pathological changes. The beneficial effects of ezetimibe were significantly associated with reduced 8-OHdG (P < .01). Pitavastatin did not reduce cholesterol or 8-OHdG, but it did significantly suppress the kidney damage with upregulated eNOS mRNA by 2.5-fold (P < .02). The combination of ezetimibe and pitavastatin synergistically ameliorated the kidney damage. The kidney dysfunction and pathological changes were significantly associated with cholesterol, markers of cholesterol absorption (campesterol and cholestanol), and 8-OHdG (P < .001-.05). Multiple regression analysis revealed that the markers of cholesterol absorption were independently associated with the kidney damage. Ezetimibe confers renoprotective effects by inhibiting cholesterol absorption, which in turn reduces oxidative stress; and pitavastatin additively ameliorates kidney damage by increasing NO production via mechanisms independent of cholesterol reduction.     

Adverse Effects of High Temperature On Mammary Alveolar Development In Vitro

Journal of Mammary Gland Biology and Neoplasia - In the mammary glands during pregnancy, the alveolar buds are first branched from the mammary ducts after which they form the alveolar luminal...     

Prevention by parenteral aspirin of indomethacin-induced gastric lesions in rats: mediation by salicylic acid

Nonsteroidal antiinflammatory drugs (NSAIDs) produce gastric damage in experimental animals, irrespective of the route of administration. However, aspirin (ASA) causes damage only when it is given orally. In the present study, we examined the gastric ulcerogenic effect of subcutaneously administered ASA in rats, in comparison with various NSAIDs, and investigated the reason why ASA does not cause damage in the stomach, in relation to its metabolite salicylic acid (SA). Since the antiinflammatory action of SA is known to be mediated, partly, by endogenous adenosine (AD), we also examined the possible involvement of AD in the protective action of SA. Various NSAIDs (indomethacin, flurbiprofen, naproxen, diclrofenac, ASA, SA) were administered subcutaneously, and the gastric mucosa was examined macroscopically 4 hr later. All NSAIDs tested, except ASA and SA, caused hemorrhagic lesions in the stomach, with a marked gastric hypermotility and a decrease of mucosal PGE₂ contents. These ulcerogenic and motility responses caused by NSAIDs were blocked by pretreatment with atropine or PGE₂. ASA, although inhibiting PGE₂ generation, caused neither hypermotility nor damage in the stomach. On the other hand, SA alone inhibited basal gastric motility without any effect on mucosal PGE₂ contents, and this agent, when given together with indomethacin, prevented gastric hypermotility and lesion formation in response to indomethacin, without affecting the reduced PGE₂ contents. Likewise, ASA inhibited these responses to indomethacin, yet the effects appeared later than those of SA. Following administration of ASA, the blood SA levels reached a peak within 30 min and remained elevated for 4 hr. In addition, the protective effect of SA was not significantly influenced by either the AD deaminase or the AD-receptor antagonists. These results suggest that the failure of parenteral ASA to induce gastric damage may be explained by a protective action of SA metabolized from ASA. SA has a cytoprotective action against NSAID-induced gastric lesions, and this action is not mediated by endogenous AD but may be functionally associated with inhibition of the gastric motility response.