Prognostic value of the liver fibrosis marker fibrosis-5 index in patients with severe isolated tricuspid regurgitation: comparison with fibrosis-4 index

The fibrosis-4 index (FIB4), a liver fibrosis maker, has been shown to be associated with the prognosis in patients with severe isolated tricuspid regurgitation (TR). Recent study showed that the fibrosis-5 index (FIB5), which was calculated by albumin, alkaline phosphatase, aspartate transaminase, alanine aminotransferase and platelet count, had better prognostic value than FIB4 in patients with heart failure. The aim of this study was to evaluate the usefulness of FIB5 index for predicting prognosis in patients with severe isolated TR and compare the prognostic value between the FIB4 and the FIB5 in those patients. This was a dual-center, retrospective study. 113 consecutive outpatients with severe isolated TR (mean age, 65.8 years; 47.8% male) were analyzed. Major adverse cardiovascular events (MACEs) were defined as the composite of cardiovascular death, hospitalization for heart failure, myocardial infarction, and stroke. During a median follow-up of 3.0 years, 41 MACEs occurred. Patients with MACEs had a lower the FIB5 than patients without MACEs. The multivariate Cox analysis revealed that the FIB5 < -4.30 was significantly associated with higher incidence of MACEs after adjusted by confounding factors. Receiver-operating characteristic curve analyses showed that prognostic values did not differ between the FIB5 and the FIB4 in whole patients and in patients aged ≥ 70 years; while, in patients aged < 70 years, the FIB5 had better prognostic value than the FIB4. The FIB5 may be a useful predictor of MACEs in patients with severe isolated TR

Preventive Effect of Proglumide on Erosive Gastritis in the Rat

The purpose of this study is to determine whether or not proglumide has a preventive effect on the erosive gastritis induced by sodium salt of taurocholic acid (TCA) in the rat. Its effect on the formation of gastric erosions, serum gastrin levels and secretion of acid and pepsin were also studied. The rats were given standard feed containing 0.25% proglumide and water containing 5mM TCA (experimental E group). The control rats were given standard feed and water containing 5mM TCA (TCA group). All rats were killed at the end of the 3 months. The tissue specimens of the resected gastric mucosa were stained with hematoxylin eosin for histopathology and with azan for evaluation of fibrous ploriferation. From microscopic observation of the stained specimens, the following results were obtained. TCA-group showed long mucosal surface injury (erosion), inflammatory cell infiltration, a reduction in the number of parietal cells, a decrease of mucosal thickness, and proliferation of collagenous fiber. In contrast, in the E group, these morphological and morphoquantitative changes were significantly small. The length of erosion and inflammatory cell infiltration were significantly reduced in the E group when compared with the TCA group. Furthermore, mucosal thickness was almost normal and fibrous proliferation was significantly scarce in the E group. Proglumide had an insignificant effect on pH on the mucosa, volume and pH of gastric juice, serum gastrin levels and tetragastrin-induced secretion of acid and pepsin. It is, thus, evident that proglumide has a preventive effect on the induction of erosive gastritis caused by TCA in the rats. Since it is difficult to explain its mechanism for the prevention of gastritis from only the already known facts that it has protective action on gastric mucosa and an inhibitory effect on secretion of acid and pepsin, unknown mechanisms are suspected to be involved

A Galanin-Like Peptide in the Colon of the Golden Hamster

Galanin-like immunoreactive peptide was studied in the colonic wall of the golden hamster using the immunoflurescent technique. Galanin-like immunoreactivity was observed mainly in cell bodies of the myenteric plexus and in fibers in the lamina propria mucosae and in the circular muscle layer. The submucosal plexus and submucosal connective tissue, however, contained very little galanin-like immunoreactive peptide. This peptide appears to be instrinsic mainly to the colon. The presence of the peptide indicates some possible biological roles in the colonic function

Compound auroral micromorphology: ground-based high-speed imaging

Auroral microphysics still remains partly unexplored. Cutting-edge ground-based optical observations using scientific complementary metal-oxide semiconductor (sCMOS) cameras recently enabled us to observe the fine-scale morphology of bright aurora at magnetic zenith for a variety of rapidly varying features for long uninterrupted periods. We report two interesting examples of combinations of fine-scale rapidly varying auroral features as observed by the sCMOS cameras installed at Poker Flat Research Range (PFRR), Alaska, in February 2014. The first example shows that flickering rays and pulsating modulation simultaneously appeared at the middle of a surge in the pre-midnight sector. The second example shows localized flickering aurora associated with growing eddies at the poleward edge of an arc in the midnight secto

Existence of VIP and PHI-Like Immunoreactivities in the Amphibian Gut

The present paper provides the first definitive evidence on the presence and possible co-existence of VIP- and PHI-like peptides in the peripheral nervous system of the amphibian (bullfrog) gut wall. The possibility of co-existence of the peptides suggests that VIP- and PHI-like peptide may be synthesized from the same precursor protein in the amphibian

Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil

Transplantation of human neural stem/progenitor cells (hNSPCs) is a promising method to regenerate tissue from damage and recover function in various neurological diseases including brain ischemia. Galectin-1(Gal1) is a lectin that is expressed in damaged brain areas after ischemia. Here, we characterized the detailed Gal1 expression pattern in an animal model of brain ischemia. After brain ischemia, Gal1 was expressed in reactive astrocytes within and around the infarcted region, and its expression diminished over time. Previously, we showed that infusion of human Gal1 protein (hGal1) resulted in functional recovery after brain ischemia but failed to reduce the volume of the ischemic region. This prompted us to examine whether the combination of hNSPCs-transplantation and stable delivery of hGal1 around the ischemic region could reduce the ischemic volume and promote better functional recovery after brain ischemia. In this study, we transplanted hNSPCs that stably overexpressed hGal1 (hGal1-hNSPCs) in a model of unilateral focal brain ischemia using Mongolian gerbils. Indeed, we found that transplantation of hGal1-hNSPCs both reduced the ischemic volume and improved deficits in motor function after brain ischemia to a greater extent than the transplantation of hNSPCs alone. This study provides evidence for a potential application of hGal1 with hNSPCs-transplantation in the treatment of brain ischemia

Gastrin and Somatostatin in Patients with Hyperchlorhydric Duodenal Ulcer

Hormonal and morphological studies were conducted to ascertain the role played by gastrin and somatostatin in the pathophysiology of duodenal ulcer, in particular hyperchlorhydric duodenal ulcer, using 35 patients with duodenal ulcer, of whom 15 were hyperchlorhydric and 20 were normochlorhydric. Twenty normal subjects with normochlorhydria were used as a control. In patients with hyperchlorhydric duodenal ulcer following significant findings were observed: 1. Basal and stimulated hyperchlorhydria, 2. Parietal cell hyperplasia, 3. Basal hypergastrinemia, 4. Increased concentration of gastrin and large number of G cells (G cell hyperplasia) in the antral mucosa. 5. Mucosal concentration of somatostatin and D cells in the antrum was reduced, but the former in patients with hyperchlorhydric duodenal ulcer was not different from that in patients with normoacidic duodenal ulcer. 6. A significant correlation in mucosal concentration was demonstrated between gastrin and somatostatin in control subjects but not in patients with duodenal ulcer. 7. There was a significant correlation in maximal acidity in gastric secretion and mucosal concentration of antral somatostatin in control subjects but not in patients with duodenal ulcer. 8. Concentration of plasma somatostatin in patients with duodenal ulcer was not different from that in control subjects. These findings indicate that gastrin and somatostatin may participate in the pathophysiology of duodenal ulcer, at least in the subgroup of duodenal ulcer associated with hyperchlorhydria, and the subgroup of duodenal ulcer may be an endocrine disorder

Disturbance in the protein landscape of cochlear perilymph in an Alzheimer’s disease mouse model

Fukuda M., Okanishi H., Ino D., et al. (2024) Disturbance in the protein landscape of cochlear perilymph in an Alzheimer’s disease mouse model. PLoS ONE 19, e0303375. https://doi.org/10.1371/journal.pone.0303375.Hearing loss is a pivotal risk factor for dementia. It has recently emerged that a disruption in the intercommunication between the cochlea and brain is a key process in the initiation and progression of this disease. However, whether the cochlear properties can be influenced by pathological signals associated with dementia remains unclear. In this study, using a mouse model of Alzheimer’s disease (AD), we investigated the impacts of the AD-like amyloid β (Aβ) pathology in the brain on the cochlea. Despite little detectable change in the age-related shift of the hearing threshold, we observed quantitative and qualitative alterations in the protein profile in perilymph, an extracellular fluid that fills the path of sound waves in the cochlea. Our findings highlight the potential contribution of Aβ pathology in the brain to the disturbance of cochlear homeostasis

Characterisation of N-glycans in the epithelial-like tissue of the rat cochlea

Nonomura Y., Sawamura S., Hanzawa K., et al. Characterisation of N-glycans in the epithelial-like tissue of the rat cochlea. Scientific Reports 9, 1551 (2019); https://doi.org/10.1038/s41598-018-38079-0.Membrane proteins (such as ion channels, transporters, and receptors) and secreted proteins are essential for cellular activities. N-linked glycosylation is involved in stability and function of these proteins and occurs at Asn residues. In several organs, profiles of N-glycans have been determined by comprehensive analyses. Nevertheless, the cochlea of the mammalian inner ear, a tiny organ mediating hearing, has yet to be examined. Here, we focused on the stria vascularis, an epithelial-like tissue in the cochlea, and characterised N-glycans by liquid chromatography with mass spectrometry. This hypervascular tissue not only expresses several ion transporters and channels to control the electrochemical balance in the cochlea but also harbours different transporters and receptors that maintain structure and activity of the organ. Seventy-nine N-linked glycans were identified in the rat stria vascularis. Among these, in 55 glycans, the complete structures were determined; in the other 24 species, partial glycosidic linkage patterns and full profiles of the monosaccharide composition were identified. In the process of characterisation, several sialylated glycans were subjected sequentially to two different alkylamidation reactions; this derivatisation helped to distinguish α2,3-linkage and α2,6-linkage sialyl isomers with mass spectrometry. These data should accelerate elucidation of the molecular architecture of the cochlea

Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus

Background Effects of sodium‐glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium‐glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF. Methods and Results We performed a multicenter, open‐label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B‐type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, −9.0% versus −1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78–1.10; P=0.26). Conclusion In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose