Phosphorus intake regulates intestinal function and polyamine metabolism in uremia

Phosphorus intake regulates intestinal function and polyamine metabolism in uremia. This study found that 5/6-nephrectomized uremic rats showed secondary hyperparathyroidism as reflected by an increase in their serum parathyroid hormone (PTH) level in association with a decrease in serum 1,25-dihydroxyvitamin D [1,25-(OH)2D]. These changes recovered partially upon phosphorus restriction. Calcium absorption and gene expression of calbindin-D9k were decreased in uremia and were also improved by phosphorus restriction. In uremia, intestinal spermidine/spermine N1-acetyl-transferase activity was decreased, while ornithine decarboxylase (ODC) activity and its gene expression were potentiated. Enhancement of c-fos and c-jun gene expressions was also observed in uremia. These phenomena suggest that the intestinal villus may proliferate in uremia. Phosphorus restriction prevented increases in the expression of ODC, c-fos and c-jun observed in uremia. Since phosphorus restriction caused a rise in the serum 1,25-(OH)2D level, the role of 1,25-(OH)2D in uremia-induced intestinal dysfunction was examined. A single injection of 1,25-(OH)2D3 to uremic rats caused an increase in the steady-state calbindin-D9k mRNA level, and decreases in steady state c-fos and ODC mRNA levels, suggesting that the deficiency of 1,25-(OH)2D3 is responsible for intestinal dysfunction in uremia. In conclusion, altered polyamine metabolism caused by 1,25-(OH)2D deficiency is intimately involved in intestinal dysfunction and the development of the proliferative state of the intestinal villus in uremia

Evaluation of pharmaceutical lifesaving skills training oriented pharmaceutical intervention

Background: Many pharmacists are participating in team-based medical care in emergency hospitals. Therefore, there is a desperate need to improve the education system. In the present study, we provided a “pharmaceutical lifesaving skills training” to the students in their fifth and sixth year of the pharmaceutical school and evaluated the program’s impact on the students’ learning and confidence in their ability to perform pharmaceutical interventions for emergency patients. Methods: We conducted a pharmaceutical lifesaving skills training program with 12 participants who were in their fifth and six year of pharmaceutical school. We prepared a fictional scenario in which a patient with cardiac arrest has been rushed into a hospital. We measured the participants’ level of knowledge of pharmaceutical lifesaving procedures and participants’ confidence to perform pharmaceutical interventions before and after the training session. Using the data obtained from type II quantification method, we examined what elements in the content of the pharmaceutical lifesaving skill training attended by pharmacy students will affect the students’ confidence to perform pharmaceutical interventions. In addition, using the correspondence structural analysis, we examined which sections of the content of the pharmaceutical lifesaving skill training should be improved in the future. Results: When we evaluated the level of knowledge acquired in pharmaceutical lifesaving skills training, the post-training overall correct answer rate was significantly higher than the pre-training overall correct answer rate. And also, level of participants' confidence to perform pharmaceutical interventions similarly increased after pharmaceutical lifesaving skill training. The influence degree graph indicates that the items likely to have a major impact on the participants’ confidence to perform pharmaceutical interventions was “Selecting medicine”. According to the correspondence structural analysis graph based on the questionnaire survey, one item identified as an improvement required was “Selecting medicine”. Conclusions: Our high-performance patient simulator-based lifesaving skills training program not only increased the participants’ understanding of the training content but also increased their confidence in their ability to perform pharmaceutical interventions. Therefore, the pharmaceutical lifesaving skills training program we developed will contribute to the education of emergency care pharmacists who can perform pharmaceutical interventions for emergency patients

Advantage of Insulin Glulisine Over Regular Insulin in Patients With Type 2 Diabetes and Severe Renal Insufficiency

ObjectivesTo compare the efficacy and safety of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency.SubjectsOur study included 18 patients with type 2 diabetes and a mean (range) estimated glomerular filtration rate of 13.2 mL/minute/1.73 m2 (5.8-27.6), which corresponds to stage 4-5 chronic kidney disease.DesignAfter titration of doses, regular insulin was administered thrice daily on Day 1, along with continuous glucose monitoring for 24 h starting at 7 am. Exactly equal doses of insulin glulisine were administered on Day 2. Area under the curve (AUC) for blood glucose level variation after breakfast (AUC-B 0-4), lunch (AUC-L 0-6), and dinner (AUC-D 0-6) were evaluated.ResultsAUC-B 0-4 and AUC-D 0-6 were significantly lower with insulin glulisine than with regular insulin (AUC-B 0-4: 3.3 ± 4.7 vs. 6.2 ± 5.4 × 102 mmol/L·minute, respectively, P = .028; AUC-D 0-6: 1.8 ± 7.3 vs. 6.5 ± 6.2 × 102 mmol/L·minute, respectively, P = .023). In contrast, AUC-L 0-6 was higher with insulin glulisine than with regular insulin (AUC-L 0-6: 7.6 ± 6.4 vs. 4.2 ± 8.7 × 102 mmol/L·minute, respectively, P = .099), suggesting a prolonged hypoglycemic action of regular insulin after lunch.ConclusionsInsulin glulisine effectively suppressed postprandial hyperglycemia, whereas regular insulin caused a prolonged hypoglycemic action. These findings support the effectiveness and safety of insulin glulisine in patients with type 2 diabetes and severe renal insufficiency

Clinical Significance of Cytoplasmic IgE-Positive Mast Cells in Eosinophilic Chronic Rhinosinusitis

Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (Fc epsilon RI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. Fc epsilon RI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis

Excessive daytime napping independently associated with decreased insulin sensitivity in cross-sectional study – Hyogo Sleep Cardio-Autonomic Atherosclerosis cohort study

BackgroundAlthough excessive daytime napping has been shown to be involved in diabetes occurrence, its impact on insulin secretion and sensitivity has not been elucidated. It is speculated that excessive napping disrupts the sleep-wake rhythm and increases sympathetic nerve activity during the day, resulting in decreased insulin sensitivity, which may be a mechanism leading to development of diabetes. We previously conducted a cross-sectional study that showed an association of autonomic dysfunction with decreased insulin sensitivity, though involvement of autonomic function in the association between napping and insulin sensitivity remained unclear. Furthermore, the effects of napping used to supplement to short nighttime sleep on insulin secretion and sensitivity are also unknown. In the present cross-sectional study, we examined the relationships of daytime nap duration and autonomic function with insulin secretion and sensitivity in 436 subjects enrolled in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Cohort Study who underwent a 75-g oral glucose tolerance test (75-g OGTT), after excluding those already diagnosed with diabetes.MethodsDaytime nap duration was objectively measured using actigraphy, with the subjects divided into the short (≤1 hour) and long (>1 hour) nap groups. Insulin secretion and sensitivity were determined using 75-g OGTT findings. Standard deviation of normal to normal R-R interval (SDNN), a measure of autonomic function, was also determined based on heart rate variability. Subgroup analysis was performed for the associations of napping with insulin secretion and sensitivity, with the results stratified by nighttime sleep duration of less or greater than six hours.ResultsSubjects in the long nap group exhibited lower insulin sensitivity parameters (QUICKI: β=-0.135, p<0.01; Matsuda index: β=-0.119, p<0.05) independent of other clinical factors. In contrast, no associations with insulin secretion were found in either group. Furthermore, the association of long nap duration with insulin sensitivity was not confounded by SDNN. Specific subgroup analyses revealed more prominent associations of long nap habit with lower insulin sensitivity in subjects with a short nighttime sleep time (β=-0.137, p<0.05).ConclusionLong daytime nap duration may be a potential risk factor for decreased insulin sensitivity

Environmental impact on star-forming galaxies in a z∼0.9z \sim 0.9 cluster during course of galaxy accretion

Galaxies change their properties as they assemble into clusters. In order to understand the physics behind that, we need to go back in time and observe directly what is occurring in galaxies as they fall into a cluster. We have conducted a narrow-band and $J$-band imaging survey on a cluster CL1604-D at $z=0.923$ using a new infrared instrument SWIMS installed at the Subaru Telescope. The narrow-band filter, NB1261, matches to H$\alpha$ emission from the cluster at $z=0.923$. Combined with a wide range of existing data from various surveys, we have investigated galaxy properties in and around this cluster in great detail. We have identified 27 H$\alpha$ emitters associated with the cluster. They have significant overlap with MIPS 24$\mu$m sources and are located exclusively in the star forming regime on the rest-frame $UVJ$ diagram. We have identified two groups of galaxies near the cluster in the 2D spatial distribution and the phase-space diagram, which are likely to be in-falling to the cluster main body. We have compared various physical properties of star forming galaxies, such as specific star formation rates (burstiness) and morphologies (merger) as a function of environment; cluster center, older group, younger group, and the field. As a result, a global picture has emerged on how the galaxy properties are altered as they assemble into a denser region. This includes the occurrence of mergers, enhancement of star formation activity, excursion to the dusty starburst phase, and eventual quenching to a passive phase.Comment: 19 pages, 15 figures. Accepted for publication in ApJ. Error bars in Table 2 correcte

Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis

マイクロRNA-33bの阻害は非アルコール性脂肪肝炎を改善する --核酸医薬による治療応用へ--. 京都大学プレスリリース. 2023-06-13.Nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma in their advanced stages; however, there are currently no approved therapies. Here, we show that microRNA (miR)-33b in hepatocytes is critical for the development of NASH. miR-33b is located in the intron of sterol regulatory element–binding transcription factor 1 and is abundantly expressed in humans, but absent in rodents. miR-33b knock-in (KI) mice, which have a miR-33b sequence in the same intron of sterol regulatory element–binding transcription factor 1 as humans and express miR-33b similar to humans, exhibit NASH under high-fat diet feeding. This condition is ameliorated by hepatocyte-specific miR-33b deficiency but unaffected by macrophage-specific miR-33b deficiency. Anti-miR-33b oligonucleotide improves the phenotype of NASH in miR-33b KI mice fed a Gubra Amylin NASH diet, which induces miR-33b and worsens NASH more than a high-fat diet. Anti-miR-33b treatment reduces hepatic free cholesterol and triglyceride accumulation through up-regulation of the lipid metabolism–related target genes. Furthermore, it decreases the expression of fibrosis marker genes in cultured hepatic stellate cells. Thus, inhibition of miR-33b using nucleic acid medicine is a promising treatment for NASH