Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT)

<p>Abstract</p> <p>Background</p> <p>Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice.</p> <p>Methods</p> <p>Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT.</p> <p>Results</p> <p>Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (<it>P </it>< 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both <it>P </it>< 0.05). Serum levels of high-sensitivity C-reactive protein (<it>P </it>= 0.067) and interleukin-6 (<it>P </it>= 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (<it>P </it>= 0.016).</p> <p>Conclusions</p> <p>These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.</p

Divergence in Sex Steroid Hormone Signaling between Sympatric Species of Japanese Threespine Stickleback

Sex steroids mediate the expression of sexually dimorphic or sex-specific traits that are important both for mate choice within species and for behavioral isolation between species. We investigated divergence in sex steroid signaling between two sympatric species of threespine stickleback (Gasterosteus aculeatus): the Japan Sea form and the Pacific Ocean form. These sympatric forms diverge in both male display traits and female mate choice behaviors, which together contribute to asymmetric behavioral isolation in sympatry. Here, we found that plasma levels of testosterone and 17β-estradiol differed between spawning females of the two sympatric forms. Transcript levels of follicle-stimulating hormone-β (FSHβ) gene were also higher in the pituitary gland of spawning Japan Sea females than in the pituitary gland of spawning Pacific Ocean females. By contrast, none of the sex steroids examined were significantly different between nesting males of the two forms. However, combining the plasma sex steroid data with testis transcriptome data suggested that the efficiency of the conversion of testosterone into 11-ketotestosterone has likely diverged between forms. Within forms, plasma testosterone levels in males were significantly correlated with male body size, a trait important for female mate choice in the two sympatric species. These results demonstrate that substantial divergence in sex steroid signaling can occur between incipient sympatric species. We suggest that investigation of the genetic and ecological mechanisms underlying divergence in hormonal signaling between incipient sympatric species will provide a better understanding of the mechanisms of speciation in animals

Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA

Distinct families of multipotent heart progenitors play a central role in the generation of diverse cardiac, smooth muscle and endothelial cell lineages during mammalian cardiogenesis. The identification of precise paracrine signals that drive the cell-fate decision of these multipotent progenitors, and the development of novel approaches to deliver these signals in vivo, are critical steps towards unlocking their regenerative therapeutic potential. Herein, we have identified a family of human cardiac endothelial intermediates located in outflow tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of Isl1 and CD144/vWF. By comparing angiocrine factors expressed by the human OFT-ECs and non-cardiac ECs, vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, and clonal assays documented its ability to drive endothelial specification of human embryonic stem cell (ESC)-derived Isl1+ progenitors in a VEGF receptor-dependent manner. Human Isl1-ECs (endothelial cells differentiated from hESC-derived ISL1+ progenitors) resemble OFT-ECs in terms of expression of the cardiac endothelial progenitor- and endocardial cell-specific genes, confirming their organ specificity. To determine whether VEGF-A might serve as an in vivo cell-fate switch for human ESC-derived Isl1-ECs, we established a novel approach using chemically modified mRNA as a platform for transient, yet highly efficient expression of paracrine factors in cardiovascular progenitors. Overexpression of VEGF-A promotes not only the endothelial specification but also engraftment, proliferation and survival (reduced apoptosis) of the human Isl1+ progenitors in vivo. The large-scale derivation of cardiac-specific human Isl1-ECs from human pluripotent stem cells, coupled with the ability to drive endothelial specification, engraftment, and survival following transplantation, suggest a novel strategy for vascular regeneration in the heart

Terrestrial invasion of pomatiopsid gastropods in the heavy-snow region of the Japanese Archipelago

<p>Abstract</p> <p>Background</p> <p>Gastropod mollusks are one of the most successful animals that have diversified in the fully terrestrial habitat. They have evolved terrestrial taxa in more than nine lineages, most of which originated during the Paleozoic or Mesozoic. The rissooidean gastropod family Pomatiopsidae is one of the few groups that have evolved fully terrestrial taxa during the late Cenozoic. The pomatiopsine diversity is particularly high in the Japanese Archipelago and the terrestrial taxa occur only in this region. In this study, we conducted thorough samplings of Japanese pomatiopsid species and performed molecular phylogenetic analyses to explore the patterns of diversification and terrestrial invasion.</p> <p>Results</p> <p>Molecular phylogenetic analyses revealed that Japanese Pomatiopsinae derived from multiple colonization of the Eurasian Continent and that subsequent habitat shifts from aquatic to terrestrial life occurred at least twice within two Japanese endemic lineages. Each lineage comprises amphibious and terrestrial species, both of which are confined to the mountains in heavy-snow regions facing the Japan Sea. The estimated divergence time suggested that diversification of these terrestrial lineages started in the Late Miocene, when active orogenesis of the Japanese landmass and establishment of snowy conditions began.</p> <p>Conclusions</p> <p>The terrestrial invasion of Japanese Pomatiopsinae occurred at least twice beside the mountain streamlets of heavy-snow regions, which is considered the first case of this event in the area. Because snow coverage maintains stable temperatures and high humidity on the ground surface, heavy-snow conditions may have paved the way for these organisms from freshwater to land via mountain streamlets by preventing winter desiccation in mountain valleys. The fact that the terrestrialization of Pomatiopsidae occurred only in year-round wet environments, but not in seasonally dried regions, provides new insight into ancient molluscan terrestrialization.</p

トクシマシ イシカイ ノ トウニョウビョウ タイサク

Tokushima City Medical Association has founded the committee for the means to prevent diabetesmellitus, because the mortality rate by diabetes mellitus in Tokushima Prefecture remainedranked first for 14 years from 1993 to 2006. It has enlightened a large number of people, such asdiabetic patients and candidates for diabetes, and also healthy citizens in Tokushima for preventingdiabetes mellitus. For this aim, Tokushima City Medical Association has made the home pagenamed Tokushima City Diabetic Network to show clearly the means to prevent diabetes mellitusfor the citizens. By this Web site, the citizens can get a correct knowledge about diabetes mellitus,a useful information about the treatments including exercises, diets and medications, and an informationabout medical institutions by utilizing the search page to receive a proper diabetic treatment.Tokushima City Medical Association held several events, such as Tokushima citizens’extension courses and diabetes forums for the citizens to understand diabetes mellitus clearly.Fortunately, in 2007, Tokushima got out of the first rank of diabetic mortality rate. TokushimaCity Medical Association will continue efforts to prevent diabetes mellitus by approaching the citizensof all ages from various aspects

ラット肝臓の虚血前処置 : 肝虚血再潅流障害に対する耐性増強における熱ショックタンパク質誘導の効果に関する研究

京都大学0048新制・課程博士博士(医学)甲第7719号医博第2072号新制||医||706(附属図書館)UT51-99-G313京都大学大学院医学研究科外科系専攻(主査)教授 田中 紘一, 教授 今村 正之, 教授 山岡 義生学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Effect of Goreisan, a traditional Japanese Kampo medicine, on postoperative nausea and vomiting in gynecological patients

Abstract Background Goreisan, a traditional Japanese Kampo medicine, may prevent postoperative nausea and vomiting (PONV). The purpose of this study was to evaluate the effect of Goreisan on PONV in a high-risk population in a randomized, double-blind, placebo-controlled manner. Findings Patients undergoing gynecological surgery were randomly allocated to the Goreisan and the control groups. General anesthesia was induced with propofol and remifentanil. After endotracheal intubation, anesthesia was maintained with sevoflurane, fentanyl, and remifentanil. Goreisan 7.5 g dissolved in water (Goreisan group) or water (control group) in a volume of 20 ml was administered through a nasogastric tube approximately 1 h before completion of surgery. The primary outcome of this study was the incidence of PONV during the first 2 h after extubation. In the interim analysis, it was apparent that Goreisan has no effect. Therefore, we discontinued recruiting patients and present results based on data from 83 patients. The incidence of PONV during the first 2 h after extubation was 45% in the Goreisan group (n = 40) and 46.5% in the control group (n = 43) (p = 0.89). There was no significant difference in PONV incidence or severity during the first 24 h post-extubation. Conclusion Goreisan has little potency in preventing PONV in high-risk patients