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Sample records for kamchatka glare sglt

  1. Kamchatka

    OpenAIRE

    Alessandra Russo

    2005-01-01

    Photo prise de : http://cine.ciudad.com.ar/kamchatkalapelicula/castellano/fotos/fotos.htm « La péninsule du Kamchatka est située à l’extrême frontière orientale de la Fédération de Russie, au nord du Japon et au Sud-Ouest de l’Alaska. Celle-ci s’étire sur 1500 km du nord au sud et 470 km dans sa plus grande largeur entre les latitudes 50°51’N (hauteur de Bruxelles) et 64°50’N». Qu’est-ce que tout cela a à voir avec le déchaînement de la dictature argentine ? En 1976 une famille porteña se voi...

  2. Kamchatka

    Directory of Open Access Journals (Sweden)

    Alessandra Russo

    2005-02-01

    Full Text Available Photo prise de : http://cine.ciudad.com.ar/kamchatkalapelicula/castellano/fotos/fotos.htm « La péninsule du Kamchatka est située à l’extrême frontière orientale de la Fédération de Russie, au nord du Japon et au Sud-Ouest de l’Alaska. Celle-ci s’étire sur 1500 km du nord au sud et 470 km dans sa plus grande largeur entre les latitudes 50°51’N (hauteur de Bruxelles et 64°50’N». Qu’est-ce que tout cela a à voir avec le déchaînement de la dictature argentine ? En 1976 une famille porteña se voi...

  3. Temporal Glare

    DEFF Research Database (Denmark)

    Ritschel, Tobias; Ihrke, Matthias; Frisvad, Jeppe Revall

    2009-01-01

    Glare is a consequence of light scattered within the human eye when looking at bright light sources. This effect can be exploited for tone mapping since adding glare to the depiction of high-dynamic range (HDR) imagery on a low-dynamic range (LDR) medium can dramatically increase perceived contrast...... and attractive renderings of bright light sources. Based on the anatomy of the human eye, we propose a model that enables real-time simulation of dynamic glare on a GPU. This allows an improved depiction of HDR images on LDR media for interactive applications like games, feature films, or even by adding movement...... to initially static HDR images. By conducting psychophysical studies, we validate that our method improves perceived brightness and that dynamic glare-renderings are often perceived as more attractive depending on the chosen scene....

  4. Flying GLARE

    NARCIS (Netherlands)

    Beumler, T.

    2004-01-01

    At the end of the second millennium did the aircraft industry decide for the first time to apply the fiber metal laminate GLARE in a large quantity on a civil transport aircraft. It was focused on an application of the material on the pressurised fuselage, the decision driven by the demand for

  5. Subfossil chironomids from Kamchatka

    Directory of Open Access Journals (Sweden)

    Larisa Nazarova

    2014-12-01

    Full Text Available Chironomid head capsules from surface sediments in Kamchatka reflect a rich and diverse fauna. We observed a relatively high abundance of head capsules from the subfamily Diamesinae. An unknown morphotype of Tanytarsini, 'Tanytarsini type klein', was found in the lake sediments of two lakes from Central and southern Kamchatka.

  6. Discomfort Glare: What Do We Actually Know?

    Energy Technology Data Exchange (ETDEWEB)

    Clear, Robert D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-04-19

    We reviewed glare models with an eye for missing conditions or inconsistencies. We found ambiguities as to when to use small source versus large source models, and as to what constitutes a glare source in a complex scene. We also found surprisingly little information validating the assumed independence of the factors driving glare. A barrier to progress in glare research is the lack of a standardized dependent measure of glare. We inverted the glare models to predict luminance, and compared model predictions against the 1949 Luckiesh and Guth data that form the basis of many of them. The models perform surprisingly poorly, particularly with regards to the luminance-size relationship and additivity. Evaluating glare in complex scenes may require fundamental changes to form of the glare models.

  7. Interaction of the Sodium/Glucose Cotransporter (SGLT) 2 inhibitor Canagliflozin with SGLT1 and SGLT2.

    Science.gov (United States)

    Ohgaki, Ryuichi; Wei, Ling; Yamada, Kazunori; Hara, Taiki; Kuriyama, Chiaki; Okuda, Suguru; Ueta, Kiichiro; Shiotani, Masaharu; Nagamori, Shushi; Kanai, Yoshikatsu

    2016-07-01

    Canagliflozin, a selective sodium/glucose cotransporter (SGLT) 2 inhibitor, suppresses the renal reabsorption of glucose and decreases blood glucose level in patients with type 2 diabetes. A characteristic of canagliflozin is its modest SGLT1 inhibitory action in the intestine at clinical dosage. To reveal its mechanism of action, we investigated the interaction of canagliflozin with SGLT1 and SGLT2. Inhibition kinetics and transporter-mediated uptake were examined in human SGLT1- or SGLT2-expressing cells. Whole-cell patch-clamp recording was conducted to examine the sidedness of drug action. Canagliflozin competitively inhibited SGLT1 and SGLT2, with high potency and selectivity for SGLT2. Inhibition constant (Ki) values for SGLT1 and SGLT2 were 770.5 and 4.0 nM, respectively. (14)C-canagliflozin was suggested to be transported by SGLT2; however, the transport rate was less than that of α-methyl-d-glucopyranoside. Canagliflozin inhibited α-methyl-d-glucopyranoside-induced SGLT1- and SGLT2-mediated inward currents preferentially from the extracellular side and not from the intracellular side. Based on the Ki value, canagliflozin is estimated to sufficiently inhibit SGLT2 from the urinary side in renal proximal tubules. The Ki value for SGLT1 suggests that canagliflozin suppresses SGLT1 in the small intestine from the luminal side, whereas it does not affect SGLT1 in the heart and skeletal muscle, considering the maximal concentration of plasma-unbound canagliflozin. Similarly, SGLT1 in the kidney would not be inhibited, thereby aiding in the prevention of hypoglycemia. After binding to SGLT2, canagliflozin may be reabsorbed by SGLT2, which leads to the low urinary excretion and prolonged drug action of canagliflozin. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  8. 1952 Kamchatka Peninsula, Russia Images

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The tsunami was generated by a magnitude 9.0 (Mw) earthquake on Kamchatka where it caused severe damage. The tsunami then struck Midway (3,000 kilometers away), the...

  9. The immediate effects of glare and electrochromic glare-reducing mirrors in simulated truck driving.

    Science.gov (United States)

    Ranney, T A; Simmons, L A; Masalonis, A J

    2000-01-01

    In this experiment 12 experienced truck drivers drove a fixed-base driving simulator for three 8-h sessions under simulated nighttime driving conditions. Sessions included (a) no glare, (b) intermittent glare presented in the exterior rearview mirrors to simulate following vehicles, and (c) intermittent glare with electrochromic glare reduction. The driving task combined vehicle control on straight and curved road segments with detection of pedestrians appearing alongside the road and targets appearing in the rearview mirrors. The presence of glare slowed detection of pedestrians and, to a lesser extent, slowed the detection of targets appearing in mirrors. Glare was also associated with increased lane position variability, reduced speed on curves, and, most consistently, increased steering variability. We found only meager evidence that electrochromic glare reduction improved target detection performance and no evidence that glare reduction improved vehicle control, despite the fact that participants consistently voiced positive preferences for glare reduction. The results will aid decision making that requires incorporation of the benefits of electrochromic glare-reducing mirrors.

  10. The assessment of glare in street-lighting.

    NARCIS (Netherlands)

    Adrian, W. & Schreuder, D.A.

    1968-01-01

    Quantitative measures for glare restriction can be introduced only if a- both disability glare and discomfort glare are included; b- the glare of a full installation not of one single lantern only-can be assessed at the design stage; and c- the system under considerations allows simple and fast calc

  11. Consensus and new improvements of disability glare

    Directory of Open Access Journals (Sweden)

    Yu-Wei Zheng

    2014-12-01

    Full Text Available Patients with early cataract may have normal visual acuity(VAbut complain that they have problems in driving at night, like seeing things through a veil. This phenomenon is defined as disability glare which maybe caused by growing stray light. Patients with intraocular lens following cataract surgery may complain about glare, halos and shadows in visual field, which are also resulted from dysphotopia. Disability glare is the VA loss due to disturbing luminance in visual field. In other words, it's the retinal contrast sensitivity reduction because of the straylight. This article contains the consensus and new progress of disability glare. It provides solutions according to its effect factors and offers clues for further study.

  12. Glare suppression by coherence gated negation

    CERN Document Server

    Zhou, Edward Haojiang; Brake, Joshua; Ruan, Haowen; Yang, Changhuei

    2016-01-01

    Imaging of a weak target hidden behind a scattering medium can be significantly confounded by glare. We report a method, termed coherence gated negation (CGN), that uses destructive optical interference to suppress glare and allow improved imaging of a weak target. As a demonstration, we show that by permuting through a set range of amplitude and phase values for a reference beam interfering with the optical field from the glare and target reflection, we can suppress glare by an order of magnitude, even when the optical wavefront is highly disordered. This strategy significantly departs from conventional coherence gating methods in that CGN actively 'gates out' the unwanted optical contributions while conventional methods 'gate in' the target optical signal. We further show that the CGN method can outperform conventional coherence gating image quality in certain scenarios by more effectively rejecting unwanted optical contributions.

  13. SGLT inhibitors: a novel target for diabetes.

    Science.gov (United States)

    Kanwal, Abhinav; Banerjee, Sanjay K

    2013-01-01

    Inhibiting sodium-glucose co-transporters (SGLT1/SGLT2), which have a key role in the absorption of glucose in the kidney and/or GI tract has been proposed as a novel therapeutic strategy for diabetes. Thus, screening and patenting of chemical compounds for SGLT1/SGLT2 gets more importance in the development of new drugs in diabetes. Several companies are developing SGLT inhibitors, some of which are now in various stages of clinical development. Some molecules in the pipeline, including dapagliflozin, canagliflozin, ASP1941, BI10773, LX4211, RG7201 and TS071, are at various stages of drug development. This patent review presents the overall progress carried out in the development of SGLT inhibitors over the last decade with the active participation of various pharmaceutical companies. This class of drug is anticipated to have a large impact on diabetes field and predicting to attain a blockbuster status.

  14. On the cause of disability glare and its dependence on glare angle, age and ocular pigmentation

    NARCIS (Netherlands)

    Vos, J.J.

    2003-01-01

    Background: In the 1920s and 1930s, disability glare was a topic of great interest in the Commission Internationale de l'Éclairage (CIE). The Second World War prevented agreement being reached on a standard to quantify disability glare but the Stiles-Holladay formula was widely accepted as such. In

  15. On the cause of disability glare and its dependence on glare angle, age and ocular pigmentation

    NARCIS (Netherlands)

    Vos, J.J.

    2003-01-01

    Background: In the 1920s and 1930s, disability glare was a topic of great interest in the Commission Internationale de l'Éclairage (CIE). The Second World War prevented agreement being reached on a standard to quantify disability glare but the Stiles-Holladay formula was widely accepted as such. In

  16. SGLT inhibitors in management of diabetes.

    Science.gov (United States)

    Tahrani, Abd A; Barnett, Anthony H; Bailey, Clifford J

    2013-10-01

    The two main sodium-glucose cotransporters (SGLTs), SGLT1 and SGLT2, provide new therapeutic targets to reduce hyperglycaemia in patients with diabetes. SGLT1 enables the small intestine to absorb glucose and contributes to the reabsorption of glucose filtered by the kidney. SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors with varying specificities for these transporters (eg, dapagliflozin, canagliflozin, and empagliflozin) can slow the rate of intestinal glucose absorption and increase the renal elimination of glucose into the urine. Results of randomised clinical trials have shown the blood glucose-lowering efficacy of SGLT inhibitors in type 2 diabetes when administered as monotherapy or in addition to other glucose-lowering therapies including insulin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Effective SGLT2 inhibition needs adequate glomerular filtration and might increase risk of urinary tract and genital infection, and excessive inhibition of SGLT1 can cause gastro-intestinal symptoms. However, the insulin-independent mechanism of action of SGLT inhibitors seems to offer durable glucose-lowering efficacy with low risk of clinically significant hypoglycaemia at any stage in the natural history of type 2 diabetes. SGLT inhibition might also be considered in conjunction with insulin therapy in type 1 diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Evaluation of discomfort glare in the 50+ elderly: experimental study

    Directory of Open Access Journals (Sweden)

    Agnieszka Wolska

    2014-08-01

    Full Text Available Objectives: The aim of the study was to analyze discomfort glare sensation in subjects aged 50 years and more in comparison with younger subjects (i.e. younger than 35 years of age. Material and Methods: The experiments were performed on a computer workstation placed in controlled lighting environment where 2 discomfort glare conditions were modeled. Each participant performed for about 1 h specially designed visual tasks, including the tests with Landolt's rings presented on the screen by a computer program. The glare evaluation method consisted of subjective evaluation of discomfort glare on the semantic glare rating scale, tests of mesopic contrast and glare sensitivity, subjective assessment of lighting quality and asthenopic symptoms. The time needed to perform the task and the number of mistakes were also recorded. The subjective evaluation of glare was compared with the Unified Glare Rating (UGR index calculated by the DIALux simulation program. Results: A higher percentage of the younger group subjects assessed glare after the experimental session as uncomfortable and intolerable than in the 50+ group, who more often assessed glare as acceptable. The assessment of discomfort glare in the younger group corresponded to higher UGR value compared to UGR value calculated by DIALux. In the 50+ group, such correlation was found only for lower discomfort glare (UGR = 19. The results showed that younger participants more frequently suffered from visual fatigue and assessed lighting as less comfortable. However, the mesopic glare sensitivity increased significantly after the experiments only in the 50+ group under both glare conditions. Conclusions: The obtained results showed that discomfort glare sensation changes with age. The younger population seems to be more sensitive and demanding than the older one in relation to discomfort glare limiting, in spite of the lack of significant objective measures of fatigue. The exposure of the elderly to

  18. The effect of glare on eye movements when reading.

    Science.gov (United States)

    Glimne, S; Brautaset, R L; Seimyr, G Öqvist

    2015-01-01

    Glare is a very common source of image degradation when performing computer work. Since reading is a task that is very sensitive to image degradation induced disability glare affects reading performance. To assess the effect of different glare conditions on eye movements when reading on a computer screen. Glare conditions have an impact on reading. This observation is based on the results from a study where we investigated how reading eye movements were affected by glare. Sixteen subjects with normal vision participated in this study. In a balanced repeated-measurement study, all subjects performed equal near-vision reading tasks. In addition to the condition of no glare three controlled conditions of glare were used: direct light, indirect light, and desk luminary. The subjects read three texts under each condition: First a short standardized text (IReST), secondly a longer newspaper text, and finally an additional IReST text. The texts were read on a Tobii T120 eye tracker. The results show that glare does have a negative effect on reading performance. The more adverse the lighting condition was, the slower the reading speed became. The decrease was primarily a result of increased fixation durations. Both glare conditions of direct and indirect glare increased the fixation durations significantly (p < 0.05). This study shows that even moderate glare conditions can have an impact on reading. The results show that it is important to follow recommendations of lighting design in computer work environment in order to avoid disability glare.

  19. Holocene Lake Records on Kamchatka

    Science.gov (United States)

    Diekmann, Bernhard; Biskaborn, Boris; Chapligin, Bernhard; Dirksen, Oleg; Dirksen, Veronika; Hoff, Ulrike; Meyer, Hanno; Nazarova, Larisa

    2014-05-01

    The availibility of terrestrial records of Holocene palaeoenvironmental changes in eastern Siberia still is quite limited, compared to other regions on the northern hemisphere. In particular, the Kamchatka Peninsula as an important climate-sensitive region is very underrepresented. Situated at the border of northeastern Eurasia, the maritime-influenced terrestrial setting of Kamchatka offers the potential to pinpoint connections of environmental changes between the periglacial and highly continental landmasses of eastern Siberia and the sub-Arctic Pacific Ocean and Sea of Okhotsk. The study region lies at the eastern end-loop of the global thermohaline ocean conveyor belt and is strongly affected by atmospheric teleconnections. Volcanic, tectonic, and glacial processes overprint palaeoenvironmental changes in addition to primary climate forcing. In order to widen our understanding of plaeoclimate dynamics on Kamchatka, sediment cores from different lake systems and peat sections were recovered and analysed by a multi-proxy approach, using sedimentological and geochemical data as well as fossil bioindicators, such as diatoms, pollen, and chironomids. Chronostratigraphy of the studied records was achieved through radiocarbon dating and tephrostratigraphy. Sediment cores with complete Holocene sedimentary sequences were retrieved from Lake Sokoch, an up to six metre deep lake of proglacial origin, situated at the treeline in the Ganalsky Ridge of southern central Kamchatka (53°15,13'N, 157°45.49' E, 495 m a.s.l.). Lacustrine sediment records of mid- to late Holocene age were also recovered from the up to 30 m deep Two-Yurts Lake, which occupies a former proglacial basin at the eastern flank of the Central Kamchatka Mountain Chain, the Sredinny Ridge (56°49.6'N, 160°06.9'E, 275 m a.s.l.). In addition to sediment coring in the open and deep Two-Yurts Lake, sediment records were also recovered from peat sections and small isolated forest lakes to compare

  20. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.

    Science.gov (United States)

    Vrhovac, Ivana; Balen Eror, Daniela; Klessen, Dirk; Burger, Christa; Breljak, Davorka; Kraus, Ognjen; Radović, Nikola; Jadrijević, Stipe; Aleksic, Ivan; Walles, Thorsten; Sauvant, Christoph; Sabolić, Ivan; Koepsell, Hermann

    2015-09-01

    Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development.

  1. SGLT-2 inhibitors: the glucosuric antidiabetics

    OpenAIRE

    Rekha Thaddanee; Ajeet Kumar Khilnani; Gurudas Khilnani

    2013-01-01

    Despite availability of a number of oral antidiabetics, a sizeable population of diabetics remains uncontrolled. Thus there is growing need of new group of drugs for diabetic control. Understanding renal conservation of glucose by efficient reabsorption through sodium glucose cotransporter-2 (SGLT-2) has paved way for development of an entirely new group of drugs, the SGLT-2 inhibitors. These glucosuric antidiabetic agents have shown promise in early clinical studies. Canagliflozin is recentl...

  2. Eye movement and pupil size constriction under discomfort glare.

    Science.gov (United States)

    Lin, Yandan; Fotios, Steve; Wei, Minchen; Liu, Yihong; Guo, Weihong; Sun, Yaojie

    2015-01-29

    Involuntary physiological responses offer an alternative means to psychophysical procedures for objectively evaluating discomfort glare. This study examined eye movement and pupil size responses to glare discomfort using new approaches to analysis: relative pupil size and speed of eye movement. Participants evaluated glare discomfort using the standard de Boer rating scale under various conditions manipulated to influence glare discomfort. Eye movement was recorded using an electro-oculogram (EOG), and pupil size was recorded using Tobii glasses. Ten young (mean age: 24.5 years old) and 10 senior (mean age: 61 years old) participants were recruited for this experiment. Subjective evaluation of glare discomfort was highly correlated with eye movement (multiple correlation coefficient [R(2)] of >0.94, P < 0.001) and pupil constriction (R(2) = 0.38, P < 0.001). Severe glare discomfort increased the speed of eye movement and caused larger pupil constriction. Larger variations of eye movement were found among seniors. The two physiological responses studied here to characterize discomfort glare under various lighting conditions had significant correlation with the subjective evaluation. The correlation between discomfort glare and physiological responses suggests an objective way to characterize and evaluate discomfort glare that may overcome the problems of conventional subjective evaluation. It also offers an explanation as to why long-term exposure to discomfort glare leads to visual fatigue and eyestrain. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  3. A novel SGLT is expressed in the human kidney

    OpenAIRE

    Kothinti, Rajendra K.; Blodgett, Amy B.; North, Paula E.; Roman, Richard J.; Tabatabai, Niloofar M.

    2012-01-01

    Selective inhibitors of sodium-glucose cotransporter 2 (SGLT2)-mediated reabsorption of glucose in the proximal tubule of the kidney are being developed for the treatment of diabetes. SGLT2 shares high degree of homology with SGLT3; however, very little is known about the expression and functional role of SGLT3 in the human kidney. Indeed, the SGLT2 inhibitors that are currently in clinical trials might affect the expression and/or the activity of SGLT3. Therefore, the present study examined ...

  4. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia

    OpenAIRE

    Rieg, Timo; Masuda, Takahiro; Gerasimova, Maria; Mayoux, Eric; Platt, Kenneth; Powell, David R.; Thomson, Scott C.; Koepsell, Hermann; Vallon, Volker

    2013-01-01

    In the kidney, the sodium-glucose cotransporters SGLT2 and SGLT1 are thought to account for >90 and ∼3% of fractional glucose reabsorption (FGR), respectively. However, euglycemic humans treated with an SGLT2 inhibitor maintain an FGR of 40–50%, mimicking values in Sglt2 knockout mice. Here, we show that oral gavage with a selective SGLT2 inhibitor (SGLT2-I) dose dependently increased urinary glucose excretion (UGE) in wild-type (WT) mice. The dose-response curve was shifted leftward and the ...

  5. Evaluation of Glare at the Ivanpah Solar Electric Generating System

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Clifford K. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sims, Cianan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Christian, Joshua Mark [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-07-01

    The Ivanpah Solar Electric Generating System (ISEGS), located on I - 15 about 40 miles (60 km) south of Las Vegas, NV, consists of three power towers 459 ft (140 m) tall and over 170,000 reflective heliostats with a rated capacity of 390 MW. Reports of glare from the plant have been submitted by pilots and air traffic controllers and recorded by the Aviation Safety Reporting System and the California Energy Commission since 2013. Aerial and ground - based surveys of the glare were conducted in April, 2014, to identify the cause and to quantify the irradiance and potential ocular impact s of the glare . Results showed that the intense glare viewed from the airspace above ISEGS was caused by he liostats in standby mode that were aimed to the side of the receiver. Evaluation of the glare showed that the retinal irradiance and subtended source angle of the glare from the heliostats in standby were sufficient to cause significant ocular impact (pot ential for after - image) up to a distance of %7E6 miles (10 km), but the values were below the threshold for permanent eye damage . Glare from the receivers had a low potential for after - image at all ground - based monitoring locations outside of the site bound aries. A Letter to Airmen has been issued by the Federal Aviation Administration to notify pilots of the potential glare hazards. Additional measures to mitigate the potential impacts of glare from ISGES are also presented and discussed. This page intentionally left blank

  6. A novel SGLT is expressed in the human kidney.

    Science.gov (United States)

    Kothinti, Rajendra K; Blodgett, Amy B; North, Paula E; Roman, Richard J; Tabatabai, Niloofar M

    2012-09-05

    Selective inhibitors of sodium-glucose cotransporter 2 (SGLT2)-mediated reabsorption of glucose in the proximal tubule of the kidney are being developed for the treatment of diabetes. SGLT2 shares high degree of homology with SGLT3; however, very little is known about the expression and functional role of SGLT3 in the human kidney. Indeed, the SGLT2 inhibitors that are currently in clinical trials might affect the expression and/or the activity of SGLT3. Therefore, the present study examined the expression of SGLT3 mRNA and protein in human kidney and in a human proximal tubule HK-2 cell line. The results indicated that human SGLT3 (hSGLT3) message and protein are expressed both in vivo and in vitro. We also studied the activity of hSGLT3 protein following its over-expression in mammalian kidney-derived COS-7 cells and in HK-2 cells treated with the imino sugar deoxynojirimycin (DNJ), a potent agonist of hSGLT3. Over-expression of hSGLT3 in COS-7 cells increased intracellular sodium concentration by 3-fold without affecting glucose transport. Activation of hSGLT3 with DNJ (50μM) increased sodium uptake in HK-2 cells by 5.5 fold and this effect could be completely blocked with SGLT inhibitor phlorizin (50μM). These results suggest that SGLT3 is expressed in human proximal tubular cells where it serves as a novel sodium transporter. Up-regulation of the expression of SGLT3 in the proximal tubule in diabetic patients may contribute to the elevated sodium transport in this segment of the nephron that has been postulated to promote hyperfiltration and renal injury.

  7. Glare as a criterion for quality in street lighting.

    NARCIS (Netherlands)

    Boer, J.B. & Schreuder, D.A.

    1967-01-01

    A simple method is given for determining the degree of discomfort glare in street lighting installations. This method is derived from results obtained partly from new investigations and partly from previous tests. Results arrived at by this method are compared with the glare produced in existing

  8. Glare as a criterion for quality in street lighting.

    NARCIS (Netherlands)

    Boer, J.B. & Schreuder, D.A.

    1967-01-01

    A simple method is given for determining the degree of discomfort glare in street lighting installations. This method is derived from results obtained partly from new investigations and partly from previous tests. Results arrived at by this method are compared with the glare produced in existing lig

  9. An experimental investigation of glare and restructured fiber metal laminates

    Science.gov (United States)

    Benedict, Adelina Vanessa

    Fiber Metal Laminates (FMLs) are a group of materials fabricated by bonding glass/epoxy layers within metal layers. This class of materials can provide good mechanical properties, as well as weight savings. An FML known as Glass Laminate Aluminum Reinforced Epoxy (GLARE) was studied. An experimental investigation comprising of microscopy and tensile testing was carried out using different grades of GLARE. Microscopy revealed the construction details of GLARE, while tensile testing provided means of measuring and analyzing its stress-strain responses. Next, different metal surface pretreatment methods were explored. These included sandblasting, Phosphoric Acid Anodizing (PAA), and AC-130 Sol-Gel treatment. Woven S-2 glass, an epoxy adhesive, and aluminum alloy sheet metal were used to fabricate restructured FMLs using time and cost effective procedures. Additional microscopy and tensile testing allowed for comparisons with GLARE and aircraft grade aluminum alloys. The restructured FMLs showed similar behaviors to GLARE with potential significant improvements in fabrication efficiency.

  10. LP-925219 maximizes urinary glucose excretion in mice by inhibiting both renal SGLT1 and SGLT2

    OpenAIRE

    Powell, David R.; Smith, Melinda G; Doree, Deon D; Harris, Angela L; Xiong, Wendy W; Mseeh, Faika; Wilson, Alan; Gopinathan, Suma; Diaz, Damaris; Goodwin, Nicole C.; Harrison, Bryce; Strobel, Eric; Rawlins, David B.; Carson, Ken; Zambrowicz, Brian

    2015-01-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents that improve glycemic control by inhibiting SGLT2-mediated renal glucose reabsorption. Currently available agents increase urinary glucose excretion (UGE) to 50% of filtered glucose when SGLT2 is completely inhibited. This led us to test whether LP-925219, a small molecule dual SGLT1/SGLT2 inhibitor, increases UGE to maximal values in wild-type (WT) mice. We first tested LP-925219 inhibition of gluc...

  11. META-GLARE: a shell for CIG systems.

    Science.gov (United States)

    Bottrighi, Alessio; Rubrichi, Stefania; Terenziani, Paolo

    2015-01-01

    In the last twenty years, many different approaches to deal with Computer-Interpretable clinical Guidelines (CIGs) have been developed, each one proposing its own representation formalism (mostly based on the Task-Network Model) execution engine. We propose META-GLARE a shell for easily defining new CIG systems. Using META-GLARE, CIG system designers can easily define their own systems (basically by defining their representation language), with a minimal programming effort. META-GLARE is thus a flexible and powerful vehicle for research about CIGs, since it supports easy and fast prototyping of new CIG systems.

  12. Contrast and glare testing in keratoconus and after penetrating keratoplasty

    National Research Council Canada - National Science Library

    Pesudovs, K; Schoneveld, P; Seto, R J; Coster, D J

    2004-01-01

    To compare the performance of keratoconus, penetrating keratoplasty (PK), and control subjects on clinical tests of contrast and glare vision, to determine whether differences in vision were independent of visual acuity (VA...

  13. The mechanical behavior of GLARE laminates for aircraft structures

    Science.gov (United States)

    Wu, Guocai; Yang, J.-M.

    2005-01-01

    GLARE (glass-reinforced aluminum laminate) is a new class of fiber metal laminates for advanced aerospace structural applications. It consists of thin aluminum sheets bonded together with unidirectional or biaxially reinforced adhesive prepreg of high-strength glass fibers. GLARE laminates offer a unique combination of properties such as outstanding fatigue resistance, high specific static properties, excellent impact resistance, good residual and blunt notch strength, flame resistance and corrosion properties, and ease of manufacture and repair. GLARE laminates can be tailored to suit a wide variety of applications by varying the fiber/resin system, the alloy type and thickness, stacking sequence, fiber orientation, surface pretreatment technique, etc. This article presents a comprehensive overview of the mechanical properties of various GLARE laminates under different loading conditions.

  14. Practical assessment of veiling glare in camera lens system

    Directory of Open Access Journals (Sweden)

    Ivana Tomić

    2014-12-01

    Full Text Available Veiling glare can be defined as an unwanted or stray light in an optical system caused by internal reflections between elements of the camera lens. It leads to image fogging and degradation of both image density and contrast, diminishing its overall quality. Each lens is susceptible to veiling glare to some extent - sometimes it is negligible, but it most cases it leads to the visible defects in an image. Unlike the other flaws and errors, lens flare is not easy to correct. Hence, it is highly recommended to prevent it during the capturing phase, if possible. For some applications, it can also be useful to estimate the susceptibility to a lens glare i.e. the degree of a glare in the lens system. Few methods are usually used for this types of testing. Some of the methods are hard to implement and often do not lead to consistent results. In this paper, we assessed one relatively easy method for practical evaluation of veiling glare. Method contains three steps: creating an appropriate scene, capturing the target image and analyzing it. In order to evaluate its applicability, we tested four lenses for Nikon 700 digital camera. Lenses used were with the fixed focal length of 35 and 85 mm and differed by the coatings of their elements. Furthermore, we evaluated the influence of aperture on veiling glare value. It was shown that presented method is not applicable for testing the lenses with short focal length and that the new generation of lenses, equipped with Nano crystal coatings are less susceptible to veiling glare. Aperture did not affect veiling glare value significantly.

  15. A single amino acid change converts the sugar sensor SGLT3 into a sugar transporter.

    Directory of Open Access Journals (Sweden)

    Laura Bianchi

    Full Text Available BACKGROUND: Sodium-glucose cotransporter proteins (SGLT belong to the SLC5A family, characterized by the cotransport of Na(+ with solute. SGLT1 is responsible for intestinal glucose absorption. Until recently the only role described for SGLT proteins was to transport sugar with Na(+. However, human SGLT3 (hSGLT3 does not transport sugar but causes depolarization of the plasma membrane when expressed in Xenopus oocytes. For this reason SGLT3 was suggested to be a sugar sensor rather than a transporter. Despite 70% amino acid identity between hSGLT3 and hSGLT1, their sugar transport, apparent sugar affinities, and sugar specificity differ greatly. Residue 457 is important for the function of SGLT1 and mutation at this position in hSGLT1 causes glucose-galactose malabsorption. Moreover, the crystal structure of vibrio SGLT reveals that the residue corresponding to 457 interacts directly with the sugar molecule. We thus wondered if this residue could account for some of the functional differences between SGLT1 and SGLT3. METHODOLOGY/PRINCIPAL FINDINGS: We mutated the glutamate at position 457 in hSGLT3 to glutamine, the amino acid present in all SGLT1 proteins, and characterized the mutant. Surprisingly, we found that E457Q-hSGLT3 transported sugar, had the same stoichiometry as SGLT1, and that the sugar specificity and apparent affinities for most sugars were similar to hSGLT1. We also show that SGLT3 functions as a sugar sensor in a living organism. We expressed hSGLT3 and E457Q-hSGLT3 in C. elegans sensory neurons and found that animals sensed glucose in an hSGLT3-dependent manner. CONCLUSIONS/SIGNIFICANCE: In summary, we demonstrate that hSGLT3 functions as a sugar sensor in vivo and that mutating a single amino acid converts this sugar sensor into a sugar transporter similar to SGLT1.

  16. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury

    OpenAIRE

    Yoon-Kyung Chang; Hyunsu Choi; Jin Young Jeong; Ki-Ryang Na; Kang Wook Lee; Beom Jin Lim; Dae Eun Choi

    2016-01-01

    Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated wi...

  17. SGLT2 Inhibitors: Benefit/Risk Balance.

    Science.gov (United States)

    Scheen, André J

    2016-10-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin showed remarkable reductions in cardiovascular/all-cause mortality and in hospitalization for heart failure in patients with previous cardiovascular disease. Positive renal outcomes were also shown with empagliflozin. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. Concern about a risk of ketoacidosis and bone fractures has been recently raised, which deserves caution and further evaluation.

  18. Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Lu, Yasong; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  19. Use systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Yasong eLu; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  20. Use systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Yasong eLu; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  1. Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    OpenAIRE

    Lu, Yasong; Griffen, Steven C.; Boulton, David W.; Leil, Tarek A.

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control...

  2. Intestinal SGLT1 in metabolic health and disease.

    Science.gov (United States)

    Lehmann, Anders; Hornby, Pamela J

    2016-06-01

    The Na(+)-glucose cotransporter 1 (SGLT1/SLC5A1) is predominantly expressed in the small intestine. It transports glucose and galactose across the apical membrane in a process driven by a Na(+) gradient created by Na(+)-K(+)-ATPase. SGLT2 is the major form found in the kidney, and SGLT2-selective inhibitors are a new class of treatment for type 2 diabetes mellitus (T2DM). Recent data from patients treated with dual SGLT1/2 inhibitors or SGLT2-selective drugs such as canagliflozin (SGLT1 IC50 = 663 nM) warrant evaluation of SGLT1 inhibition for T2DM. SGLT1 activity is highly dynamic, with modulation by multiple mechanisms to ensure maximal uptake of carbohydrates (CHOs). Intestinal SGLT1 inhibition lowers and delays the glucose excursion following CHO ingestion and augments glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion. The latter is likely due to increased glucose exposure of the colonic microbiota and formation of metabolites such as L cell secretagogues. GLP-1 and PYY secretion suppresses food intake, enhances the ileal brake, and has an incretin effect. An increase in colonic microbial production of propionate could contribute to intestinal gluconeogenesis and mediate positive metabolic effects. On the other hand, a threshold of SGLT1 inhibition that could lead to gastrointestinal intolerability is unclear. Altered Na(+) homeostasis and increased colonic CHO may result in diarrhea and adverse gastrointestinal effects. This review considers the potential mechanisms contributing to positive metabolic and negative intestinal effects. Compounds that inhibit SGLT1 must balance the modulation of these mechanisms to achieve therapeutic efficacy for metabolic diseases. Copyright © 2016 the American Physiological Society.

  3. Discomfort glare with complex fenestration systems and the impact on energy use when using daylighting control

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Sabine; McNeil, Andrew; Lee, Eleanor S.; Kalyanam, Raghuram

    2015-11-03

    Glare is a frequent issue in highly glazed buildings. A modelling approach is presented that uses discomfort glare probability and discomfort glare index as metrics to determine occupants’ behaviour. A glare control algorithm that actuated an interior shade for glare protection based on the predicted perception was implemented in a building simulation program. A reference case with a state-of-the-art base glazing was compared to the same glazing but with five different complex fenestration systems, i.e., exterior shades. The windows with exterior shades showed significant variations in glare frequencies. Energy use intensity in a prototypical office building with daylighting controls was greatly influenced for the systems with frequent glare occurrence. While the base glazing could benefit from glare control, some of the exterior shades showed significantly greater energy use when discomfort glare-based operation of interior shades was considered.

  4. Use of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans.

    Science.gov (United States)

    Lu, Yasong; Griffen, Steven C; Boulton, David W; Leil, Tarek A

    2014-01-01

    In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control in patients with diabetes. Despite demonstrating high levels (in excess of 80%) of inhibition of glucose transport by SGLT2 in vitro, potent SGLT2 inhibitors, e.g., dapagliflozin and canagliflozin, inhibit renal glucose reabsorption by only 30-50% in clinical studies. Hypotheses for this apparent paradox are mostly focused on the compensatory effect of SGLT1. The paradox has been explained and the role of SGLT1 demonstrated in the mouse, but direct data in humans are lacking. To further explore the roles of SGLT1/2 in renal glucose reabsorption in humans, we developed a systems pharmacology model with emphasis on SGLT1/2 mediated glucose reabsorption and the effects of SGLT2 inhibition. The model was calibrated using robust clinical data in the absence or presence of dapagliflozin (DeFronzo et al., 2013), and evaluated against clinical data from the literature (Mogensen, 1971; Wolf et al., 2009; Polidori et al., 2013). The model adequately described all four data sets. Simulations using the model clarified the operating characteristics of SGLT1/2 in humans in the healthy and diabetic state with or without SGLT2 inhibition. The modeling and simulations support our proposition that the apparent moderate, 30-50% inhibition of renal glucose reabsorption observed with potent SGLT2 inhibitors is a combined result of two physiological determinants: SGLT1 compensation and residual SGLT2 activity. This model will enable in silico inferences and predictions related to SGLT1/2 modulation.

  5. Computation of glint, glare, and solar irradiance distribution

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Clifford Kuofei; Khalsa, Siri Sahib Singh

    2017-08-01

    Described herein are technologies pertaining to computing the solar irradiance distribution on a surface of a receiver in a concentrating solar power system or glint/glare emitted from a reflective entity. At least one camera captures images of the Sun and the entity of interest, wherein the images have pluralities of pixels having respective pluralities of intensity values. Based upon the intensity values of the pixels in the respective images, the solar irradiance distribution on the surface of the entity or glint/glare corresponding to the entity is computed.

  6. Volcanism and Subduction: The Kamchatka Region

    Science.gov (United States)

    Eichelberger, John; Gordeev, Evgenii; Izbekov, Pavel; Kasahara, Minoru; Lees, Jonathan

    The Kamchatka Peninsula and contiguous North Pacific Rim is among the most active regions in the world. Kamchatka itself contains 29 active volcanoes, 4 now in a state of semi-continuous eruption, and I has experienced 14 magnitude 7 or greater earthquakes since accurate recording began in 1962. At its heart is the uniquely acute subduction cusp where the Kamchatka and Aleutian Arcs and Emperor Seamount Chain meet. Volcanism and Subduction covers coupled magmatism and tectonics in this spectacular region, where the torn North Pacific slab dives into hot mantle. Senior Russian and American authors grapple with the dynamics of the cusp with perspectives from the west and east of it, respectively, while careful tephrostratigraphy yields a remarkably precise record of behavior of storied volcanoes such as Kliuchevskoi and Shiveluch. Towards the south, Japanese researchers elucidate subduction earthquake processes with unprecedented geodetic resolution. Looking eastward, new insights on caldera formation, monitoring, and magma ascent are presented for the Aleutians. This is one of the first books of its kind printed in the English language. Students and scientists beginning research in the region will find in this book a useful context and introduction to the region's scientific leaders. Others who wish to apply lessons learned in the North Pacific to their areas of interest will find the volume a valuable reference.

  7. A modification of the method for the appraisal of glare in street lighting.

    NARCIS (Netherlands)

    Adrian, W. & D.A. Schreuder

    1971-01-01

    Description of a modification of a method to appraise glare in street lighting. The alteration concerns the assessment of discomfort and disability glare if the photometrical and geometrical data the lantern and the installation are provided.

  8. Thioglycosides as inhibitors of hSGLT1 and hSGLT2: Potential therapeutic agents for the control of hyperglycemia in diabetes

    Directory of Open Access Journals (Sweden)

    Francisco Castaneda, Antje Burse, Wilhelm Boland, Rolf K-H. Kinne

    2007-01-01

    Full Text Available The treatment of diabetes has been mainly focused on maintaining normal blood glucose concentrations. Insulin and hypoglycemic agents have been used as standard therapeutic strategies. However, these are characterized by limited efficacy and adverse side effects, making the development of new therapeutic alternatives mandatory. Inhibition of glucose reabsorption in the kidney, mediated by SGLT1 or SGLT2, represents a promising therapeutic approach. Therefore, the aim of the present study was to evaluate the effect of thioglycosides on human SGLT1 and SGLT2. For this purpose, stably transfected Chinese hamster ovary (CHO cells expressing human SGLT1 and SGLT2 were used. The inhibitory effect of thioglycosides was assessed in transport studies and membrane potential measurements, using α-methyl-glucoside uptake and fluorescence resonance energy transfer, respectively. We found that some thioglycosides inhibited hSGLT more strongly than phlorizin. Specifically, thioglycoside I (phenyl-1'-thio-β-D-glucopyranoside inhibited hSGLT2 stronger than hSGLT1 and to a larger extent than phlorizin. Thioglycoside VII (2-hydroxymethyl-phenyl-1'-thio-β-D-galacto-pyranoside had a pronounced inhibitory effect on hSGLT1 but not on hSGLT2. Kinetic studies confirmed the inhibitory effect of these thioglycosides on hSGLT1 or hSGLT2, demonstrating competitive inhibition as the mechanism of action. Therefore, these thioglycosides represent promising therapeutic agents for the control of hyperglycemia in patients with diabetes.

  9. Veiling Glare and Perceived Black in High Dynamic Range Displays

    NARCIS (Netherlands)

    Murdoch, M.J.; Heynderickx, I.E.J.

    2012-01-01

    A perceptual experiment was conducted to measure the visibility of black-level differences in the proximity of a bright glare source. In a controlled viewing environment, visual difference thresholds were adaptively measured using dark, shadow-detail images shown on a high dynamic range liquid crys

  10. Evaluation on Glare Response to Car Headlight and Drivers' Visibility

    Institute of Scientific and Technical Information of China (English)

    Zhang Dianye; Wang Wuhong; Cao Qi

    1996-01-01

    This paper proposes an ideal setof glare rating scales,shows how it affects the vision legibility for driving, and simulates the situation in which cars are moving at the relative speed of 120 km/h and 180 km/h,and the light quantity change caused by the moving light sources affects vision legibility. It will offer quantitative vision data for engineers.

  11. Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus)

    Science.gov (United States)

    Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Ramesh, Naresh; Delgado, María Jesús; Valenciano, Ana Isabel; Unniappan, Suraj

    2017-01-01

    Glucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish. PMID:28338019

  12. Effect of Sodium Glucose Cotransporter 2 Inhibitors With Low SGLT2/SGLT1 Selectivity on Circulating Glucagon-Like Peptide 1 Levels in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Takebayashi, Kohzo; Inukai, Toshihiko

    2017-09-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1. Recent evidence shows that these SGLT2 inhibitors with low SGLT2/SGLT1 selectivity elevate the level of circulating glucagon like peptide-1 (GLP-1), an incretin hormone that promotes insulin secretion in pancreatic β cells. This effect probably occurs partly via inhibition of intestinal SGLT1, and the elevation of active GLP-1 levels is especially apparent when these drugs are co-administered with dipeptidyl peptidase 4 (DPP4) inhibitors. These findings suggest that a combination of canagliflozin or sotagliflozin and a DPP4 inhibitor can provide a beneficial effect associated with elevation of circulating active GLP-1 and may serve as a treatment for patients with type 2 diabetes.

  13. PARAMETERS OF KAMCHATKA SEISMICITY IN 2008

    Directory of Open Access Journals (Sweden)

    Vadim A. Saltykov

    2015-09-01

    Full Text Available The paper describes seismicity of Kamchatka for the period of 2008 and presents 2D distribution of background seismicity parameters calculated from data published in the Regional Catalogue of Kamchatka Earthquakes. Parameters under study are total released seismic energy, seismic activity A10, slope of recurrence graph γ, parameters of RTL, ΔS and Z-function methods, and clustering of earthquakes. Estimations of seismicity are obtained for a region bordered by latitude 50.5–56.5N, longitude 156E–167E, with depths to 300 km. Earthquakes of energy classes not less than 8.5 as per the Fedotov’s classification are considered. The total seismic energy released in 2008 is estimated. According to a function of annual seismic energy distribution, an amount of seismic energy released in 2008 was close to the median level (Fig. 1. Over 2/3 of the total amount of seismic energy released in 2008 resulted from three largest earthquakes (МW ≥ 5.9. About 5 percent of the total number of seismic events are comprised of grouped earthquakes, i.e. aftershocks and swarms. A schematic map of the largest earthquakes (МW ≥ 5.9 and grouped seismic events which occurred in 2008 is given in Fig. 2; their parameters are listed in Table 1. Grouped earthquakes are excluded from the catalogue. A map showing epicenters of independent earthquakes is given in Fig. 3. The slope of recurrence graph γ and seismic activity A10 is based on the Gutenberg-Richter law stating the fundamental property of seismic process. The recurrence graph slope is calculated from continuous exponential distribution of earthquakes by energy classes. Using γ is conditioned by observations that in some cases the slope of the recurrence graph decreases prior to a large earthquake. Activity A10 is calculated from the number of earthquakes N and recurrence graph slope γ. Average slopes of recurrence graph γ and seismic activity A10 for the area under study in 2008 are calculated; our

  14. Applying artificial intelligence to clinical guidelines: the GLARE approach.

    Science.gov (United States)

    Terenziani, Paolo; Montani, Stefania; Bottrighi, Alessio; Molino, Gianpaolo; Torchio, Mauro

    2008-01-01

    We present GLARE, a domain-independent system for acquiring, representing and executing clinical guidelines (GL). GLARE is characterized by the adoption of Artificial Intelligence (AI) techniques in the definition and implementation of the system. First of all, a high-level and user-friendly knowledge representation language has been designed. Second, a user-friendly acquisition tool, which provides expert physicians with various forms of help, has been implemented. Third, a tool for executing GL on a specific patient has been made available. At all the levels above, advanced AI techniques have been exploited, in order to enhance flexibility and user-friendliness and to provide decision support. Specifically, this chapter focuses on the methods we have developed in order to cope with (i) automatic resource-based adaptation of GL, (ii) representation and reasoning about temporal constraints in GL, (iii) decision making support, and (iv) model-based verification. We stress that, although we have devised such techniques within the GLARE project, they are mostly system-independent, so that they might be applied to other guideline management systems.

  15. Experimental investigation on impact performances of GLARE laminates

    Directory of Open Access Journals (Sweden)

    Chen Qi

    2015-12-01

    Full Text Available An experimental investigation was carried out on the damage resistance to a concentrated quasi-static indentation force and low-velocity impact of four kinds of glass-reinforced aluminum laminates (GLARE for short. Compared with the experimental results of the CFRP (Carbon Fiber Reinforced Plastics laminates, the performance of GLARE was determined. By means of concentrated quasi-static indentation force test, typical force–displacement response, the maximum contact force and dent depth were received. Through drop-weight low-velocity impact tests, impact force histories, indentation depths (through a new method and dissipated energy were obtained. The test results show that the force–displacement response of GLARE 4 laminates under the concentrated quasi-static indentation force has an obvious flat roof and the failure is instantaneous, which are different from CFRP laminates. The indention will be visible once the impact happens. C-scan results find that there is no delamination besides the impact area after both the concentrated quasi-static indentation and low-velocity impact. The dissipated energy approximately equals the impact energy.

  16. Experimental investigation on impact performances of GLARE laminates

    Institute of Scientific and Technical Information of China (English)

    Chen Qi; Guan Zhidong; Li Zengshan; Ji Zhaojie; Zhuo Yue

    2015-01-01

    An experimental investigation was carried out on the damage resistance to a concen-trated quasi-static indentation force and low-velocity impact of four kinds of glass-reinforced aluminum laminates (GLARE for short). Compared with the experimental results of the CFRP (Carbon Fiber Reinforced Plastics) laminates, the performance of GLARE was determined. By means of concentrated quasi-static indentation force test, typical force–displacement response, the maximum contact force and dent depth were received. Through drop-weight low-velocity impact tests, impact force histories, indentation depths (through a new method) and dissipated energy were obtained. The test results show that the force–displacement response of GLARE 4 laminates under the concentrated quasi-static indentation force has an obvious flat roof and the failure is instantaneous, which are different from CFRP laminates. The indention will be visible once the impact happens. C-scan results find that there is no delamination besides the impact area after both the concentrated quasi-static indentation and low-velocity impact. The dissipated energy approximately equals the impact energy.

  17. [Contributions of SGLT-2 and new drugs under investigation].

    Science.gov (United States)

    Mediavilla Bravo, J J

    2014-07-01

    DeFronzo spoke of the "ominous octet", in which he referred to the existence of distinct pathways and organs related to the physiopathology of type 2 diabetes mellitus (DM2). One of these key organs is the kidney, which plays an important role in regulating glucose metabolism through gluconeogenesis and through glomerular filtration and glucose reabsorption in the proximal convoluted tubules. Approximately 180 g of glucose are filtered to the renal tubule from the blood stream through the glomerulus. The filtrate is subsequently reabsorbed from the tubules to the peritubular capillaries through the action of sodium glucose cotransporters (SGLT). There are 2 main cotransporters in the kidney, SGLT1 and SGLT2, which reabsorb the glucose (10% and 90%, respectively) and return it to the blood. In persons with DM2, SGLT2 is increased, leading to greater renal absorption of glucose, which has adverse effects as it contributes to the maintenance of hyperglycemia. Selective pharmacological SGLT2 inhibition increases renal glucose excretion and secondarily reduces its plasma values. SGLT2 inhibitors act exclusively on the kidney, reduce glycosylated hemoglobin (HbA1c) by about 0.66%, decrease blood pressure, and induce a weight loss of approximately 1.8 kg. These drugs have a low risk of hypoglycemia but carry an increased risk of genitourinary infections. Several clinical trials have shown that dapagliflozin (10mg/day), the first SGLT2 inhibitor commercialized in Spain, produces a statistically significant reduction in HbA1c of 0.82-0.97%, both in monotherapy and in combination with metformin, glimepiride, pioglitazone, or insulin. Its use produces a weight loss of between 2 and 3 kg and reduces both systolic and diastolic blood pressure, while the risk of hypoglycemias is low.

  18. Functional characterisation of human SGLT-5 as a novel kidney-specific sodium-dependent sugar transporter.

    Science.gov (United States)

    Grempler, Rolf; Augustin, Robert; Froehner, Stefanie; Hildebrandt, Tobias; Simon, Eric; Mark, Michael; Eickelmann, Peter

    2012-02-03

    Sodium glucose cotransporters (SGLT) actively catalyse carbohydrate transport across cellular membranes. Six of the 12 known SGLT family members have the capacity to bind and/or transport monosaccharides (SGLT-1 to 6); of these, all but SGLT-5 have been characterised. Here we demonstrate that human SGLT-5 is exclusively expressed in the kidney. Four splice variants were detected and the most abundant SGLT-5-mRNA was functionally characterised. SGLT-5 mediates sodium-dependent [(14)C]-α-methyl-D-glucose (AMG) transport that can be inhibited by mannose, fructose, glucose, and galactose. Uptake studies using demonstrated high capacity transport for mannose and fructose and, to a lesser extent, glucose, AMG, and galactose. SGLT-5 mediated mannose, fructose and AMG transport was weakly (μM potency) inhibited by SGLT-2 inhibitors. In summary, we have characterised SGLT-5 as a kidney mannose transporter. Further studies are warranted to explore the physiological role of SGLT-5.

  19. Effects of SGLT2 Inhibition in Human Kidney Proximal Tubular Cells—Renoprotection in Diabetic Nephropathy?

    OpenAIRE

    Usha Panchapakesan; Kate Pegg; Simon Gross; Muralikrishna Gangadharan Komala; Harshini Mudaliar; Josephine Forbes; Carol Pollock; Amanda Mather

    2013-01-01

    Sodium/glucose cotransporter 2 (SGLT2) inhibitors are oral hypoglycemic agents used to treat patients with diabetes mellitus. SGLT2 inhibitors block reabsorption of filtered glucose by inhibiting SGLT2, the primary glucose transporter in the proximal tubular cell (PTC), leading to glycosuria and lowering of serum glucose. We examined the renoprotective effects of the SGLT2 inhibitor empagliflozin to determine whether blocking glucose entry into the kidney PTCs reduced the inflammatory and fib...

  20. Use systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans

    Directory of Open Access Journals (Sweden)

    Yasong eLu

    2014-12-01

    Full Text Available In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1 and 2 (SGLT2 along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibition of SGLT2 is a viable mechanism for removing glucose from the body and improving glycemic control in patients with diabetes. Despite demonstrating high levels (in excess of 80% of inhibition of glucose transport by SGLT2 in vitro, potent SGLT2 inhibitors, e.g., dapagliflozin and canagliflozin, inhibit renal glucose reabsorption by only 30-50% in clinical studies. Hypotheses for this apparent paradox are mostly focused on the compensatory effect of SGLT1. The paradox has been explained and the role of SGLT1 demonstrated in the mouse, but direct data in humans are lacking. To further explore the roles of SGLT1/2 in renal glucose reabsorption in humans, we developed a systems pharmacology model with emphasis on SGLT1/2 mediated glucose reabsorption and the effects of SGLT2 inhibition. The model was calibrated using robust clinical data in the absence or presence of dapagliflozin (DeFronzo et al. data (2013, and evaluated against clinical data from the literature (Mogensen, 1971;Wolf et al., 2009;Polidori et al., 2013. The model adequately described all four data sets. Simulations using the model clarified the operating characteristics of SGLT1/2 in humans in the healthy and diabetic state with or without SGLT2 inhibition. The modeling and simulations support our proposition that the apparent moderate, 30-50% inhibition of renal glucose reabsorption observed with potent SGLT2 inhibitors is a combined result of two physiological determinants: SGLT1 compensation and residual SGLT2 activity. This model will enable in silico inferences and predictions related to

  1. Colored Height and Shaded Relief, Kamchatka Peninsula

    Science.gov (United States)

    2002-01-01

    Russia's Kamchatka Peninsula, lying between the Sea of Okhotsk to the west and the Bering Sea and Pacific Ocean to the east, is one of the most active volcanic regions along the Pacific Ring of Fire. It covers an area about the size of Colorado but contains more than 100 volcanoes stretching across the 1000-kilometer-long (620-mile-long) land mass. A dozen or more of these have active vents, with the youngest located along the eastern half of the peninsula. This color-coded shaded relief image, generated with data from the Shuttle Radar Topography Mission (SRTM), shows Kamchatka's volcanic nature to dramatic effect.Kliuchevskoi, one of the most active and renowned volcanoes in the world, dominates the main cluster of volcanoes called the Kliuchi group, visible as a circular feature in the center-right of the image. The two other main volcanic ranges lie along northeast-southwest lines, with the older, less active range occupying the center and western half of Kamchatka. The younger, more active belt begins at the southernmost point of the peninsula and continues upward along the Pacific coastline.Two visualization methods were combined to produce this image: shading and color coding of topographic height. The shade image was derived by computing topographic slope in the north-south direction, so northern slopes appear bright and southern slopes appear dark. Color coding is directly related to topographic height, with green at the lower elevations, rising through yellow and brown to white at the highest elevations.The Shuttle Radar Topography Mission flew aboard the Space Shuttle Endeavour, launched on February 11, 2000. The mission used the same radar instrument that comprised the Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar that flew twice on the Space Shuttle Endeavour in 1994. The Shuttle Radar Topography Mission was designed to collect three-dimensional measurements of the Earth's surface. To collect the 3-D data, engineers added a 60-meter (200

  2. Holocene environmental change in Kamchatka: A synopsis

    Science.gov (United States)

    Brooks, S. J.; Diekmann, B.; Jones, V. J.; Hammarlund, D.

    2015-11-01

    We present a synthesis of the results of a multiproxy, multisite, palaeoecological study of Holocene environmental change in Kamchatka, Far East Russia, details of which are presented elsewhere in the volume. We summarise the results of the analyses of pollen, diatom, chironomid, and testate amoebae assemblages, together with stable isotopes of oxygen and carbon, and sediment characteristics from the sediments of five lakes and a peat succession on a latitudinal gradient of the Kamchatka Peninsula, to infer environmental change and establish the major climate forcers and climatic teleconnections. There are synchronous shifts in the assemblage composition of most of the biota and across most sites at 6.5-6.2 ka BP, 5.2 ka BP, 4.0 ka BP, and 3.5 ka BP, suggesting a response to strong regional climate forcing at these times. These dates correspond to the warmest part of the Holocene Thermal Maximum (HTM) (6.5-6.2 ka BP), the beginning of the Neoglacial cooling (5.2 ka BP), the coolest and wettest part of the Neoglacial (4.0 ka BP), and a switch to warmer and drier conditions at 3.5 ka BP. Our results provide evidence for the penetration and domination of different air masses at different periods during the Holocene. Cool and dry periods in winter (e.g., at 6.0 ka BP) were driven by a relatively weak pressure gradient between the Siberian High and the Aleutian Low, whereas cool, wet periods in winter (e.g., the Neoglacial and during the LIA) developed when these two systems increased in strength. Warm, dry, continental periods in summer (e.g., at 2.5 ka BP) were driven by a weakening of the Siberian High. We find that the timing of the HTM in Kamchatka is later than in the Eurasian arctic but similar to northern Europe and the sub-arctic part of eastern Siberia. This progressive onset of the HTM was due to the effects of postglacial ice-sheet decay that modulated the routes of westerly storm tracks in Eurasia. A major ecosystem driver was the Siberian dwarf pine Pinus

  3. Trait-Based Individual Differences on Discomfort Glare Rating Responses and Related Visual Contrast Sensitivity

    OpenAIRE

    Mekaroonreung, Haruetai

    2003-01-01

    This research was designed to investigate the relationship between Trait-based Individual differences (neuroticism and extraversion) and glare subjective responses as well as the actual contrast sensitivity when exposed to the same manipulated glare condition. In addition, the relationship between the glare subjective responses and actual contrast sensitivity was investigated. To examine the trait-based individual differences, the International Personality Item Pool (IPIP) was used while th...

  4. Efficient Fruit Defect Detection and Glare removal Algorithm by anisotropic diffusion and 2D Gabor filter

    OpenAIRE

    Katyal, Vini; Srivastava, Deepesh

    2012-01-01

    This paper focuses on fruit defect detection and glare removal using morphological operations, Glare removal can be considered as an important preprocessing step as uneven lighting may introduce it in images, which hamper the results produced through segmentation by Gabor filters .The problem of glare in images is very pronounced sometimes due to the unusual reflectance from the camera sensor or stray light entering, this method counteracts this problem and makes the defect detection much mor...

  5. Sodium glucose transporter 2 (SGLT2 inhibition and ketogenesis

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available Sodium glucose transporter 2 (SGLT2 inhibitors are a recently developed class of drug that have been approved for use in type 2 diabetes. Their unique extra-pancreatic glucuretic mode of action has encouraged their usage in type 1 diabetes as well. At the same time, reports of pseudo ketoacidosis and ketoacidosis related to their use have been published. No clear mechanism for this phenomenon has been demonstrated so far. This communication delves into the biochemical effects of SGLT2 inhibition, discusses the utility of these drugs and proposes steps to maximize safe usage of the molecules.

  6. Sodium glucose transporter 2 (SGLT2) inhibition and ketogenesis.

    Science.gov (United States)

    Kalra, Sanjay; Sahay, Rakesh; Gupta, Yashdeep

    2015-01-01

    Sodium glucose transporter 2 (SGLT2) inhibitors are a recently developed class of drug that have been approved for use in type 2 diabetes. Their unique extra-pancreatic glucuretic mode of action has encouraged their usage in type 1 diabetes as well. At the same time, reports of pseudo ketoacidosis and ketoacidosis related to their use have been published. No clear mechanism for this phenomenon has been demonstrated so far. This communication delves into the biochemical effects of SGLT2 inhibition, discusses the utility of these drugs and proposes steps to maximize safe usage of the molecules.

  7. The Kamchatka-Aleutian Collision Zone: Mother of All Cusps

    Science.gov (United States)

    Lees, J. M.

    2008-12-01

    The Kamchatka subduction zone represents a key to the understanding of volcanism, tectonics and mantle dynamics. The termination of the Pacific plate in the northern part of the Kamchatka slab is the prime location to investigate the cusp-ward shoaling of seismicity, the volumetrically spectacular production of magma with unusual geochemical signatures and slab edge ablation associated with mantle flow around the leading edge of the plate. In addition, the Kamchatka subduction zone is further complicated by the subduction of the aseismic ridge, the Meiji Seamounts. The three-dimensional structural configuration of the subducting pacific slab, the Komandorsky basin and the volcanic arc all suggest that absence of Pacific slab north of latitude. Tomographic analyses show a deep low velocity zone below Kliuchevskoi Volcano, suggesting a deep source near the crust-mantle interface. The intense volcanic production rates of the northern part of the Kamchatka Arc indicate that a prolific source feeds the surface expression of the cusp. Extensive heating at the exposed slab edge provides a source of heat for the Kliuchevskoi group. In this presentation I will review the critical observations and conclusions regarding cusp dynamics in Kamchatka and the Pacific Rim.

  8. Geyser Valley on the Kamchatka Peninsula

    Science.gov (United States)

    2007-01-01

    On June 2, a devastating mudslide in the world-renowned Geyser Valley on the Kamchatka Peninsula virtually obliterated the natural wonder, forcing the emergency evacuation of visitors and national park personnel. The site, which is the Kamchatka Peninsula's main tourist attraction, consists of some 200 thermal pools created by the area's intense volcanic activity, including about 90 geysers covering an area of four square kilometers (2.5 square miles). It is one of only five sites in the world where the impressive eruptions of steam and boiling-hot water can be found. According to witnesses, a powerful mudslide 1.5 kilometers (one mile) long and 200 meters (600 feet) wide buried more than two-thirds of the valley beneath tens of meters of snow, dirt, trees and boulders (right image), and created a temporary lake submerging more geysers. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet. ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra spacecraft. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products. The broad spectral coverage and high spectral resolution of ASTER provides scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and geology; and measuring surface heat balance. The U.S. science team is located at NASA's Jet

  9. Pattern glare: the effects of contrast and color

    Directory of Open Access Journals (Sweden)

    Laura eMonger

    2015-10-01

    Full Text Available Aim: To test a theory of visual stress by investigating the inter-relationships between (1 the threshold contrast/saturation at which individuals first report discomfort when viewing colored gratings of progressively increasing contrast and decreasing saturation; (2 the choice of a colored overlay for reading; (3 any increase in reading speed when the overlay is used. Method: Ninety-five young adults, with normal color vision, reported illusions from square-wave gratings (Pattern Glare Test, chose any colored overlays that improved clarity (Intuitive Color Overlays and read aloud randomly ordered common words (Wilkins Rate of Reading Test. This was followed by an automated choice of tints for text using various screen colors on a tablet, and a test of discomfort from patterns of progressively increasing contrast and decreasing saturation, using software developed for this study. All participants wore their optimal refractive correction throughout the procedure.Results: Fifty-eight participants chose a colored overlay and reported that it made text easier and more comfortable to read. On average, these individuals had a greater improvement in reading speed with their overlays (p=0.003, a lower contrast threshold at which discomfort from achromatic gratings was first reported (p=0.015, and a tendency to report more pattern glare (p=0.052, compared to the other participants. Participants who chose both a most and least preferred tint for text using the automated procedure reported discomfort from colored gratings at a significantly higher contrast with their most preferred color compared to their least preferred color (p=0.003. The choice of a colored tint was therefore moderately consistent across tests. The most and least preferred colors tended to be complementary.Conclusion: Colored tints that improved reading speed reduced pattern glare both in terms of the illusion susceptibility and in terms of discomfort contrast threshold, supporting a

  10. Boreal Forests of Kamchatka: Structure and Composition

    Directory of Open Access Journals (Sweden)

    Markus P. Eichhorn

    2010-09-01

    Full Text Available Central Kamchatka abounds in virgin old-growth boreal forest, formed primarily by Larix cajanderi and Betula platyphylla in varying proportions. A series of eight 0.25–0.30 ha plots captured the range of forests present in this region and their structure is described. Overall trends in both uplands and lowlands are for higher sites to be dominated by L. cajanderi with an increasing component of B. platyphylla with decreasing altitude. The tree line on wet sites is commonly formed by mono-dominant B. ermanii forests. Basal area ranged from 7.8–38.1 m2/ha and average tree height from 8.3–24.7 m, both being greater in lowland forests. Size distributions varied considerably among plots, though they were consistently more even for L. cajanderi than B. platyphylla. Upland sites also contained a dense subcanopy of Pinus pumila averaging 38% of ground area. Soil characteristics differed among plots, with upland soils being of lower pH and containing more carbon. Comparisons are drawn with boreal forests elsewhere and the main current threats assessed. These forests provide a potential baseline to contrast with more disturbed regions elsewhere in the world and therefore may be used as a target for restoration efforts or to assess the effects of climate change independent of human impacts.

  11. Observers' Judgments of the Effects of Glare on Their Visual Acuity for High and Low Contrast Stimuli.

    Science.gov (United States)

    Sewall, Ashley A Stafford; Borzendowski, Stephanie A Whetsel; Tyrrell, Richard A; Stephens, Benjamin R; Rosopa, Patrick J

    2016-07-01

    Disability glare refers to a reduction in the ability to discern a stimulus that is positioned near another stimulus that has a much higher luminance. While it is common for drivers to report that they have been "blinded" by oncoming headlights, it is unclear whether observers can accurately judge when they are visually disabled by glare. This experiment sought to quantify the accuracy with which observers can judge when a glare source reduces their visual acuity. Seventeen observers estimated their disability glare threshold (DGT)-the luminance of a glare source that would be just sufficient to impair their ability to discern the orientation of a Landolt C that was surrounded by the glare source. These estimated DGTs were compared to the participant's actual DGTs. Participants consistently underestimated the intensity of glare that was required to impair their acuity. On average, estimates of glare threshold were 88% lower than actual glare threshold intensities. Participants' judgments were affected by stimulus size but not stimulus contrast. These results suggest that observers can exaggerate the debilitating effects of glare and that they can fail to appreciate that high contrast stimuli are more robust to glare. A driver who believes that even the lowest intensities of headlight glare can visually impair an oncoming driver may be reluctant to use high beam headlamps, despite their significant visibility advantages.

  12. Implications of advanced warning messages on eliminating sun glare disturbances at signalized intersections

    Directory of Open Access Journals (Sweden)

    Qing Li

    2016-08-01

    Full Text Available Due to sun glare disturbances, drivers encounter fatal threats on roadways, particularly at signalized intersections. Many studies have attempted to develop applicable solutions, such as avoiding sun positions, applying road geometric re-directions, and wearing anti-glare glasses. None of these strategies have fully solved the problem. As one of the “Connected Vehicle” practices proposed by the U.S. Department of Transportation, advanced warning messages (AWMs are capable of providing wireless information about traffic controls. AWM acts as a supplement to conventional signs and signals, which can be blocked by obstacles or natural disturbances, such as sun glare. The drivers' smart advisory system (DSAS can provide drivers with AWM. Using a driving simulator this research explores the effects of DSAS messages on driving behaviors under sun glare disturbance. Statistical analyses were applied to assess (1 the negative impacts of sun glare, (2 the compensation of the DSAS AWM to sun glare effects, and (3 the improvement in driving performance due to DSAS AWM. Four performance indexes were measured, including (1 half kinetic energy speed, (2 mean approach speed, (3 brake response time, and (4 braking distance. The effects of the socio-demographic factors, such as gender, age, educational background, and driving experience were also studied. The analytical results illustrate that the DSAS can compensate for reduced visibility due to sun glare and improve driving performance to a normal visual situation, particularly for left turn and through movement.

  13. Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?

    OpenAIRE

    Liu, Jiwen; Lee, TaeWeon; DeFronzo, Ralph A.

    2012-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30–50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokineti...

  14. Becoming Aboriginal: Experiences of a European Woman in Kamchatka's Wilderness.

    Science.gov (United States)

    Churikova, Victoria

    2000-01-01

    A Russian woman describes how living in remote Kamchatka helped her develop an aboriginal perspective. Chopping wood, hauling water, gathering food, alternately homeschooling her children and sending them to an ecological school, and interacting with local aboriginal people taught her the importance of conserving natural resources and living in…

  15. Viruses in acidic geothermal environments of the Kamchatka Peninsula

    DEFF Research Database (Denmark)

    Bize, Ariane; Peng, Xu; Prokofeva, Maria

    2008-01-01

    Screening for viruses in samples taken from acidic hot springs of Kamchatka (Russia) revealed a collection of morphotypes, including linear, spherical and complex fusiform shapes, which show partial similarity to those found in acidic geothermal environments in other geographical locations. One...

  16. Cellular distribution and regulation of intestinal SGLT1

    OpenAIRE

    Sá, Carla M.; Azevedo, Marisa; Lima, Cristóvão F; Wilson, Cristina Pereira

    2011-01-01

    Diabetes is achieving epidemic proportions in many countries. In addiction to high blood glucose it is associated with increased intestinal expression of the sodium-glucose cotransporter (SGLT1). This transporter is located in brush-border membrane (BBM) of the enterocytes and is responsible for transporting glucose and galactose from the intestinal lumen into the cytosol, using the inward Na+ gradient maintained by the basolateral Na+/K+-ATPase. Our previous results show that the adaptive re...

  17. SGLT-2 inhibition in patients with kidney disease.

    Science.gov (United States)

    Gilbert, R E

    2014-12-01

    Accustomed to managing diabetes with agents that mostly act by modulating the secretion and actions of insulin, with the advent of sodium-glucose linked transporter-2 (SGLT-2) inhibitors, physicians are now aware that the kidney also needs to be considered in the spectrum of action of anti-hyperglycaemic agents. Though familiar with the need for dose adjustment when prescribing many of our current anti-hyperglycaemic drugs in the setting of kidney dysfunction, with the SGLT-2 inhibitors pharmacodynamic as well as pharmacokinetic aspects also need to be considered. Finally, through their ability to reduce intraglomerular pressure, systemic blood pressure and plasma uric acid concentration, the SGLT-2 inhibitors offers the possibility of kidney protection. An hypothesis that will need to be tested with long term studies that address changes in the kidney beyond albuminuria, assessing the rate of decline in glomerular filtration rate and 'hard'kidneyrelated endpoints such as the need for renal replacement therapy (dialysis, transplantation) will be important in this setting.

  18. Efficient Fruit Defect Detection and Glare removal Algorithm by anisotropic diffusion and 2D Gabor filter

    CERN Document Server

    Katyal, Vini

    2012-01-01

    This paper focuses on fruit defect detection and glare removal using morphological operations, Glare removal can be considered as an important preprocessing step as uneven lighting may introduce it in images, which hamper the results produced through segmentation by Gabor filters .The problem of glare in images is very pronounced sometimes due to the unusual reflectance from the camera sensor or stray light entering, this method counteracts this problem and makes the defect detection much more pronounced. Anisotropic diffusion is used for further smoothening of the images and removing the high energy regions in an image for better defect detection and makes the defects more retrievable. Our algorithm is robust and scalable the employability of a particular mask for glare removal has been checked and proved useful for counteracting.this problem, anisotropic diffusion further enhances the defects with its use further Optimal Gabor filter at various orientations is used for defect detection.

  19. High-cycle fatigue investigations of notched Glare under different stress ratio's in various environments

    National Research Council Canada - National Science Library

    Bhat, Sunil; Narayanan, Sockalingam

    2014-01-01

    Notched Glare 4A-3/2 laminates, comprising thin 2014-T6 aerospace aluminum alloy sheets alternately bonded with unidirectional E-glass fiber-based composite prepregs, are tested under tensile-tensile...

  20. Verification of simple illuminance based measures for indication of discomfort glare from windows

    DEFF Research Database (Denmark)

    Karlsen, Line Røseth; Heiselberg, Per Kvols; Bryn, Ida

    2015-01-01

    predictions of discomfort glare from windows already in the early design stage when decisions regarding the façade are taken. This study focus on verifying if simple illuminance based measures like vertical illuminance at eye level or horizontal illuminance at the desk are correlated with the perceived glare...... confirm that there is a statistically significant correlation between both vertical eye illuminance and horizontal illuminance at the desk and the occupants’ perception of glare in a perimeter zone office environment, which is promising evidence towards utilizing such simple measures for indication...... of discomfort glare in early building design. Further, the observed response indicate that the participants in the present study were more tolerant to low illuminance levels and more sensitive to high illuminance levels than the DGPs model would predict. More and larger studies are needed to confirm or enfeeble...

  1. Diabetes and kidney disease: the role of sodium-glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes.

    Science.gov (United States)

    Mende, Christian W

    2017-03-01

    Patients with type 2 diabetes (T2D) often have coexisting chronic kidney disease (CKD). However, healthy renal function is crucial in maintaining glucose homeostasis, assuring that almost all of the filtered glucose is reabsorbed by the sodium glucose cotransporters (SGLTs) SGLT-1 and SGLT-2. In diabetes, an increased amount of glucose is filtered by the kidneys and SGLT-2 is upregulated, leading to increased glucose absorption and worsening hyperglycemia. Prolonged hyperglycemia contributes to the development of CKD by inducing metabolic and hemodynamic changes in the kidneys. Due to the importance of SGLT-2 in regulating glucose levels, investigation into SGLT-2 inhibitors was initiated as a glucose-dependent mechanism to control hyperglycemia, and there are three agents currently approved for use in the United States: dapagliflozin, canagliflozin, and empagliflozin. SGLT-2 inhibitors have been shown to reduce glycated hemoglobin (A1C), weight, and blood pressure, which not only affects glycemic control, but may also help slow the progression of renal disease by impacting the underlying mechanisms of kidney injury. In addition, SGLT-2 inhibitors have shown reductions in albuminuria, uric acid, and an increase in magnesium. Caution is advised when prescribing SGLT-2 inhibitors to patients with moderately impaired renal function and those at risk for volume depletion and hypotension. Published data on slowing of the development, as well as progression of CKD, is a hopeful indicator for the possible renal protection potential of this drug class. This narrative review provides an in-depth discussion of the interplay between diabetes, SGLT-2 inhibitors, and factors that affect kidney function.

  2. Design of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: A History Driven by Biology to Chemistry.

    Science.gov (United States)

    Cai, Wenqing; Jiang, Linlin; Xie, Yafei; Liu, Yuqiang; Liu, Wei; Zhao, Guilong

    2015-01-01

    A brief history of the design of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors is reviewed. The design of O-glucoside SGLT2 inhibitors by structural modification of phlorizin, a naturally occurring O-glucoside, in the early stage was a process mainly driven by biology with anticipation of improving SGLT2/SGLT1 selectivity and increasing metabolic stability. Discovery of dapagliflozin, a pioneering C-glucoside SGLT2 inhibitor developed by Bristol-Myers Squibb, represents an important milestone in this history. In the second stage, the design of C-glycoside SGLT2 inhibitors by modifications of the aglycone and glucose moiety of dapagliflozin, an original structural template for almost all C-glycoside SGLT2 inhibitors, was mainly driven by synthetic organic chemistry due to the challenge of designing dapagliflozin derivatives that are patentable, biologically active and synthetically accessible. Structure-activity relationships (SAR) of the SGLT2 inhibitors are also discussed.

  3. Human-inspired lighting the intention control in robot systems with of glare avoidance%Human-inspired lighting the intention control in robot systems with of glare avoidance

    Institute of Scientific and Technical Information of China (English)

    Chen Shengyong; Guan Qiu; Liu Sheng; Bi Dexue

    2011-01-01

    This paper presents some human-inspired strategies for lighting control in a robot system for best scene interpretation, where the main intention is to avoid possible glares or highlights occurring in images. It firstly compares the characteristics of human eyes and robot eyes. Then some evaluation criteria are addressed to assess the lighting conditions. A bio-inspired method is adopted to avoid the visual glare which is caused by either direct illumination from large light sources or indirect illumination reflected by smooth surfaces. Appropriate methods are proposed to optimize the pose and optical parameters of the light source and the vision camera.

  4. Glare Recovery of a Two Dimensional Tracking Task with Respect to Various Colors

    Science.gov (United States)

    1976-04-01

    transparent, yellowish tinged crystalline material of complex bio-chemical structure. Yellowing of the lens will continue with age, and thus increase... headlamps to remain on for approximately five seconds. After the end of the five seconds the timer will 29 turn off the headlamps and recycle for the...Comparator button 104 is then pressed high which activates the glare source which consists of two automotive type headlights. The glare source is

  5. Review of Efforts to Develop a Low-Luminance-Level Disability Glare Tester

    Science.gov (United States)

    2009-09-01

    letter features would be discernable at 20 feet (ft) by an individual with 20/20 Snellen acuity. Notice that the chart has both high and low- contrast...no-glare acuity and the best acuity measured under the glare condition was 20/33 Snellen . Overall they concluded that there was a need for improved... Snellen acuity. Archives of Ophthalmology. 119: 1371-1373. Nakagawara, V. B., Montgomery, R. W., and Wood, K. J. 1994. The applicability of

  6. The dark side of photovoltaic — 3D simulation of glare assessing risk and discomfort

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Thomas; Wollert, Alexander

    2015-04-15

    Photovoltaic (PV) systems form an important force in the implementation of renewable energies, but as we all know, the force has always its dark side. Besides efficiency considerations and discussions about architectures of power distribution networks, the increasing numbers of installations of PV systems for implementing renewable energies have secondary effects. PV systems can generate glare due to optical reflections and hence might be a serious concern. On the one hand, glare could affect safety, e.g. regarding traffic. On the other hand, glare is a constant source of discomfort in vicinities of PV systems. Hence, assessment of glare is decisive for the success of renewable energies near municipalities and traffic zones for the success of solar power. Several courts decided on the change of PV systems and even on their de-installation because of glare effects. Thus, location-based assessments are required to limit potential reflections and to avoid risks for public infrastructure or discomfort of residents. The question arises on how to calculate reflections accurately according to the environment's topography. Our approach is founded in a 3D-based simulation methodology to calculate and visualize reflections based on the geometry of the environment of PV systems. This computational model is implemented by an interactive tool for simulation and visualization. Hence, project planners receive flexible assistance for adjusting the parameters of solar panels amid the planning process and in particular before the installation of a PV system. - Highlights: • Solar panels cause glare that impacts neighborhoods and traffic infrastructures. • Glare might cause disability and discomfort. • 3D environment for the calculation of glare • Interactive tool to simulate and visualize reflections • Impact assessment of solar power plant farms.

  7. Analysis of efficacy of SGLT2 inhibitors using semi-mechanistic model

    Directory of Open Access Journals (Sweden)

    Oleg eDemin Jr

    2014-10-01

    Full Text Available Renal sodium-dependent glucose co-transporter 2 (SGLT2 is one of the most promising targets for the treatment of type 2 diabetes. Two SGLT2 inhibitors, dapagliflozin and canagliflozin, have already been approved for use in USA and Europe; several additional compounds are also being developed for this purpose. Based on the in vitro IC50 values and plasma concentration of dapagliflozin measured in clinical trials, the marketed dosage of the drug was expected to almost completely inhibit SGLT2 function and reduce glucose reabsorption by 90%. However, the administration of dapagliflozin resulted in only 30–50% inhibition of reabsorption. This study was aimed at investigating the mechanism underlying the discrepancy between the expected and observed levels of glucose reabsorption. To this end, systems pharmacology models were developed to analyze the time profile of dapagliflozin, canagliflozin, ipragliflozin, empagliflozin, and tofogliflozin in the plasma and urine; their filtration and active secretion from the blood to the renal proximal tubules; reverse reabsorption; urinary excretion; and their inhibitory effect on SGLT2. The model shows that concentration levels of tofogliflozin, ipragliflozin, and empagliflozin are higher than levels of other inhibitors following administration of marketed SGLT2 inhibitors at labeled doses and non-marketed SGLT2 inhibitors at maximal doses (approved for phase 2/3 studies. All the compounds exhibited almost 100% inhibition of SGLT2. Based on the results of our model, two explanations for the observed low efficacy of SGLT2 inhibitors were supported: 1 the site of action of SGLT2 inhibitors is not in the lumen of the kidney’s proximal tubules, but elsewhere (e.g., the kidneys proximal tubule cells; and 2 there are other transporters that could facilitate glucose reabsorption under the conditions of SGLT2 inhibition (e.g., other transporters of SGLT family.

  8. Effects of SGLT2 inhibition in human kidney proximal tubular cells--renoprotection in diabetic nephropathy?

    Directory of Open Access Journals (Sweden)

    Usha Panchapakesan

    Full Text Available Sodium/glucose cotransporter 2 (SGLT2 inhibitors are oral hypoglycemic agents used to treat patients with diabetes mellitus. SGLT2 inhibitors block reabsorption of filtered glucose by inhibiting SGLT2, the primary glucose transporter in the proximal tubular cell (PTC, leading to glycosuria and lowering of serum glucose. We examined the renoprotective effects of the SGLT2 inhibitor empagliflozin to determine whether blocking glucose entry into the kidney PTCs reduced the inflammatory and fibrotic responses of the cell to high glucose. We used an in vitro model of human PTCs. HK2 cells (human kidney PTC line were exposed to control 5 mM, high glucose (HG 30 mM or the profibrotic cytokine transforming growth factor beta (TGFβ1; 0.5 ng/ml in the presence and absence of empagliflozin for up to 72 h. SGLT1 and 2 expression and various inflammatory/fibrotic markers were assessed. A chromatin immunoprecipitation assay was used to determine the binding of phosphorylated smad3 to the promoter region of the SGLT2 gene. Our data showed that TGFβ1 but not HG increased SGLT2 expression and this occurred via phosphorylated smad3. HG induced expression of Toll-like receptor-4, increased nuclear deoxyribonucleic acid binding for nuclear factor kappa B (NF-κB and activator protein 1, induced collagen IV expression as well as interleukin-6 secretion all of which were attenuated with empagliflozin. Empagliflozin did not reduce high mobility group box protein 1 induced NF-κB suggesting that its effect is specifically related to a reduction in glycotoxicity. SGLT1 and GLUT2 expression was not significantly altered with HG or empagliflozin. In conclusion, empagliflozin reduces HG induced inflammatory and fibrotic markers by blocking glucose transport and did not induce a compensatory increase in SGLT1/GLUT2 expression. Although HG itself does not regulate SGLT2 expression in our model, TGFβ increases SGLT2 expression through phosphorylated smad3.

  9. A portable inspection system to estimate direct glare of various LED modules

    Science.gov (United States)

    Chen, Po-Li; Liao, Chun-Hsiang; Li, Hung-Chung; Jou, Shyh-Jye; Chen, Han-Ting; Lin, Yu-Hsin; Tang, Yu-Hsiang; Peng, Wei-Jei; Kuo, Hui-Jean; Sun, Pei-Li; Lee, Tsung-Xian

    2015-07-01

    Glare is caused by both direct and indirect light sources and discomfort glare produces visual discomfort, annoyance, or loss in visual performance and visibility. Direct glare is caused by light sources in the field of view whereas reflected glare is caused by bright reflections from polished or glossy surfaces that are reflected toward an individual. To improve visual comfort of our living environment, a portable inspection system to estimate direct glare of various commercial LED modules with the range of color temperature from 3100 K to 5300 K was developed in this study. The system utilized HDR images to obtain the illumination distribution of LED modules and was first calibrated for brightness and chromaticity and corrected with flat field, dark-corner and curvature by the installed algorithm. The index of direct glare was then automatically estimated after image capturing, and the operator can recognize the performance of LED modules and the possible effects on human being once the index was out of expecting range. In the future, we expect that the quick-response smart inspection system can be applied in several new fields and market, such as home energy diagnostics, environmental lighting and UGR monitoring and popularize it in several new fields.

  10. Isotonic transport by the Na+-glucose cotransporter SGLT1 from humans and rabbit

    DEFF Research Database (Denmark)

    Zeuthen, T; Meinild, A K; Loo, D D;

    2001-01-01

    water transport was divided about equally between cotransport, osmosis across the SGLT1 and osmosis across the native oocyte membrane. 6. Coexpression of AQP1 with the SGLT1 increased the water permeability more than 10-fold and steady state isotonic transport was achieved after less than 2 s of sugar...

  11. Most recent fall deposits of Ksudach Volcano, Kamchatka, Russia

    Science.gov (United States)

    Bursik, M.; Melekestsev, I. V.; Brajtseva, O. A.

    1993-01-01

    Three of four Plinian eruptions from Ksudach Volcano are among the four largest explosive eruptions in southern Kamchatka during the past 2000 years. The earliest of the eruptions was voluminous and was accompanied by an ignimbrite and the fifth and most recent Cddera collapse event at Ksudach. The isopach pattern is consistent with a column height of 23 km. The three more recent and smaller eruptions were from the Shtyubel' Cone, within the fifth caldera. Using isopach and grain size isopleth patterns, column heights ranged from >10 to 22 kin. Although the oldest eruption may have produced a large acidity peak in the Greenland ice, the three Shtyubel' events may not be related to major acid deposition. Thus it is possible that few if any of the uncorrelated acidity peaks of the past 2000 years in Greenland ice cores result from eruptions in southern Kamchatka.

  12. MAP17 and SGLT1 protein expression levels as prognostic markers for cervical tumor patient survival.

    Directory of Open Access Journals (Sweden)

    Marco Perez

    Full Text Available MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types.

  13. Third International Volcanological Field School in Kamchatka and Alaska

    Science.gov (United States)

    Melnikov, D.; Eichelberger, J.; Gordeev, E.; Malcolm, J.; Shipman, J.; Izbekov, P.

    2005-12-01

    The Kamchatka State University, Institute of Volcanology and Seismology FEB RAS (Petropavlovsk-Kamchatsky, Russia) and University of Alaska Fairbanks have developed an international field school focused on explosive volcanism of the North Pacific. The concept of the field school envisages joint field studies by young Russian scientists and their peers from the United States and Japan. Beyond providing first-hand experience with some of Earth's most remarkable volcanic features, the intent is to foster greater interest in language study, cultures, and ultimately in international research collaborations. The students receive both theoretical and practical knowledge of active volcanic systems, as well experience in working productively in a harsh environment. Each year, the class is offered in both Alaska and Kamchatka. The Alaska session is held in the Valley of Ten Thousand Smokes, Katmai National Park, product of the greatest volcanic eruption of the 20th century. A highlight in 2005 was the discovery of a new 70-m crater atop Trident Volcano. Also this year, we added the Great Tolbachik Eruption of 1975-76 to the itinerary of the Kamchatka school. Day trips were conducted to summit craters of New Tolbachik volcanoes and Plosky Tolbachik, Tolbachik lava flows; fumarole fields of Mutnovsky volcano, and a geothermal area and 60 MWe power plant. Students who attended both the Alaska and Kamchatka sessions could ponder the implications of great lateral separation of active vents - 10 km at Katmai and 30 km at Tolbachik - with multiple magmas and non-eruptive caldera collapse at the associated stratocones. During the evenings and on days of bad weather, the school faculty conducted lectures on various topics of volcanology in either Russian or English, with translation. The field school is a strong stimulus for growth of young volcanologists and cooperation among Russia, USA and Japan, leading naturally to longer student exchange visits and to joint research projects.

  14. Cadmium down-regulation of kidney Sp1 binding to mouse SGLT1 and SGLT2 gene promoters: possible reaction of cadmium with the zinc finger domain of Sp1.

    Science.gov (United States)

    Kothinti, Rajendra K; Blodgett, Amy B; Petering, David H; Tabatabai, Niloofar M

    2010-05-01

    Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose transporters, SGLT1 and SGLT2 and that Sp1 from Cd-exposed cells displayed reduced binding to the GC boxes of the mouse SGLT1 promoter in vitro. Here, we identified a GC box upstream of mouse SGLT2 gene. ChIP assays on PMKC revealed that exposure to 5 microM Cd abolished Sp1 binding to SGLT1 GC box while it decreased Sp1 binding to SGLT2 GC sequence by 30% in vivo. The in vitro DNA binding assay, EMSA, demonstrated that binding of Sp1 from Cd (7.5 microM)-treated PMKC to the SGLT2 GC probe was 86% lower than in untreated cells. Sp1 is a zinc finger protein. Compared to PMKC exposed to 5 microM Cd alone, inclusion of 5 microM Zn restored SGLT1 and 2 mRNA levels by 15% and 30%, respectively. Cd (10 microM) decreased the binding of recombinant Sp1 (rhSp1) to SGLT1 and SGLT2 GC probes to 12% and 8% of untreated controls. Cd exerted no effect on GC-bound rhSp1. Co-treatment with Cd and Zn showed that added Zn significantly restored rhSp1 binding to the SGLT1 and SGLT2. Addition of Zn post Cd treatment was not stimulatory. We conclude that Cd can replace Zn in Sp1 DNA binding domain to reduce its binding to GC sites in mouse SGLT1 and SGLT2 promoters. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Visual Fatigue Evaluation: Improvement of Reflected Glare on Touch Screen for Nuclear Power Plant

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kang Hung; Yang, Chih Wei [Institute of Nuclear Energy Research, Atomic Energy Council, Longtan (China); Hwang, Sheue Ling [National Tsing Hua University, Longtan (China); Liou, Jin Liang [Taiwan Power Company, Longtan (China)

    2014-08-15

    The purpose of this research is to evaluate the visual fatigue of operators caused by glare problems in the main control room of nuclear power plant. Within the limitation in the main control room, reflectors were set under the light source which generates reflected glare on touch screens. Through avoiding the light directly shines on touch screens, reflected glare were eliminated. This research matched up the setting process of reflectors, evaluated the visual fatigue of operators, and collected user's opinions before reflector setting, after the first setting, and after the second setting. The design of reflectors could refer the result of evaluations and the collection of opinions. Nevertheless, the improvement of reflected glare on touch screens could be verified by this evaluations. The result showed that setting reflectors under the light source could eliminate reflected glare effectively, and the visual fatigue was reduced both on subject and object evaluations. However, the setting direction of reflectors has potential effect on operators' visual fatigue, so the real setting of reflectors still need to be evaluated completely. The near point accommodation could reflect the effect of visual fatigue caused by changes of lighting environment. Thus, the verification of new lighting environment according to the near point accommodation is suggested.

  16. Monitoring recreational impacts in wilderness of Kamchatka (on example of Kronotsky State Natural Biosphere Preserve)

    Science.gov (United States)

    Anya V. Zavadskaya

    2011-01-01

    This paper describes an assessment and monitoring program that was designed and initiated for monitoring recreational impacts in a wilderness in Kamchatka. The framework of the recreational assessment was tested through its application to a case study conducted during the summers of 2008 and 2009 in the Kronotsky State Natural Biosphere Preserve (Kamchatka peninsula,...

  17. MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2.

    Science.gov (United States)

    Coady, Michael J; El Tarazi, Abdulah; Santer, René; Bissonnette, Pierre; Sasseville, Louis J; Calado, Joaquim; Lussier, Yoann; Dumayne, Christopher; Bichet, Daniel G; Lapointe, Jean-Yves

    2017-01-01

    The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na(+)-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17-SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na(+)/H(+) exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters. Copyright © 2016 by the American Society of Nephrology.

  18. Conformational Dynamics of hSGLT1 during Na+/Glucose Cotransport

    DEFF Research Database (Denmark)

    Loo, D. D.; Hirayama, B. A.; Karakossian, M. H.

    2006-01-01

    . voltage (Q-V) and fluorescence vs. voltage ( F-V) relations (for medium and slow components) obeyed Boltzmann relations with similar parameters: z (apparent valence of voltage sensor) 1; and V0.5 (midpoint voltage) between -15 and -40 mV. Sugar induced an inward current (Na+/glucose cotransport......This study examines the conformations of the Na+/glucose cotransporter (SGLT1) during sugar transport using charge and fluorescence measurements on the human SGLT1 mutant G507C expressed in Xenopus oocytes. The mutant exhibited similar steady-state and presteady-state kinetics as wild-type SGLT1...

  19. SGLT1-mediated transport in Caco-2 cells is highly dependent on cell bank origin

    DEFF Research Database (Denmark)

    Steffansen, B; Pedersen, Maria; Laghmoch, A M

    2017-01-01

    The Caco-2 cell line is a well-established in vitro model for studying transport phenomena for prediction of intestinal nutrient and drug absorption. However, for substances depending on transporters such predictions are complicated due to variable transporter expression and limited knowledge about...... permeability (PSGLT1). Here, the objective was to characterize and compare SGLT1-mediated uptake in Caco-2 cells obtained from different cell banks. SGLT1-mediated uptake of the standard SGLT1 substrate, α-MDG, in Caco-2 cells was shown to be highly dependent on cell bank origin. The most robust and reliable...

  20. Mobile computing device configured to compute irradiance, glint, and glare of the sun

    Science.gov (United States)

    Gupta, Vipin P; Ho, Clifford K; Khalsa, Siri Sahib

    2014-03-11

    Described herein are technologies pertaining to computing the solar irradiance distribution on a surface of a receiver in a concentrating solar power system or glint/glare emitted from a reflective entity. A mobile computing device includes at least one camera that captures images of the Sun and the entity of interest, wherein the images have pluralities of pixels having respective pluralities of intensity values. Based upon the intensity values of the pixels in the respective images, the solar irradiance distribution on the surface of the entity or glint/glare corresponding to the entity is computed by the mobile computing device.

  1. Influence of dirt, age and poor aim on glare and illumination intensities of car headlamps in practice

    NARCIS (Netherlands)

    Alferdinck, J.W.A.M.; Padmos, P.

    1987-01-01

    Luminous intensities of dipped car headlamps in directions of the eyes of drivers of oncoming cars (glare intensity) and the right roadside (illumination intensity) were measured (404 cars). The often too high glare intensities are mainly due to dirt and lamp age; the often too low illumination inte

  2. The KISS Project - Exploring the magmatic system beneath Kamchatka's volcanoes

    Science.gov (United States)

    Luehr, Birger-G.; Shapiro, Nikolai; Abkadyrov, Ilyas; Sens-Schönfelder, Christoph; Koulakov, Ivan; Jakovlev, Andrey; Abramenkov, Sergey; Saltykov, Vadim A.; Heit, Benjamin; Weber, Michael; Gordeev, Evgeny I.; Chebrov, Victor N.

    2016-04-01

    In a joint initiative of GFZ with Russian (IPGG, IVS, KGBS) and a French partner (IPGP) a temporary seismological network has been installed around the Klyuchevskoy volcanic group in Central Kamchatka. The Klyuchevskoy volcanic group is an ensemble of 13 stratovolcanoes with very different compositions and eruption styles in a ~70km diameter area which produced at least 30 VEI≥2 episodes during the last 15 years. Latest activity of the highest volcano Klyuchevskoy (4754 m) was in spring 2015. The group is located right on the triple junction between Asian, Pacifc and North American plates where the Hawaiian-Emperor seamount chain separates the Aleutian and the Kuril-Kamchatka trenches. The complex setting presumably leads to processes like increased melting at slab edges and/or accelerated mantle flow which affect the volcanism and might be responsible for the unparalleled concentration of volcanic activity in the Klyuchevskoy group. Due to the difficult field conditions and special permitting regulations seismological investigations have been rare in Kamchatka. In this consortium we build strongly on the experience of the Kamchatkan partners for permitting and logistics. Installation was done to about 50% by helicopter. Funding was provided via a grant from the Russian Science Foundation (grant 14-47-00002) to the IVS/KBGS/IPGG, the GFZ, and the IPGP. 60 of the stations were provided by the GFZ instrument pool GIPP. Including the permanent stations operated by KGBS and temporary stations provided by the partners, the network consist of 98 stations and will record earthquakes volcanic signals and the ambient field over one year in an area of approximately 150 by 150km.

  3. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors for patients with Type 2 diabetes

    DEFF Research Database (Denmark)

    Røder, Michael Einar; Storgaard, Heidi; Rungby, Jørgen;

    2016-01-01

    problem. Extremely rare cases of ketoacidosis are reported, mostly in patients with Type 1 diabetes. One SGLT-2i, empagliflozin, has been shown to reduce cardiovascular mortality and progression of kidney disease in patients with Type 2 diabetes and cardiovascular disease. Outcome trials for other SGLT-2i......The sodium-glucose cotransporter 2 inhibitor (SGLT-2i)-class is efficacious as monotherapy and as add-on therapy with an expected lowering of the glycated haemoglobin (HbA1c) concentration of approximately 7 mmol/mol. Side effects relate to the mode of action, genital infections are the main...... are pending. SGLT-2i are now in guidelines as a possible second-line therapy or in case of metformin intolerance....

  4. The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing.

    Directory of Open Access Journals (Sweden)

    Pia V Röder

    Full Text Available Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are suggested to play an important role in intestinal glucose sensing and incretin secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of these transporters in intestinal glucose uptake after radiotracer glucose gavage and performed Western blot analysis for transporter abundance in apical membrane fractions in a comparative approach. Moreover, we examined the contribution of these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically reduced throughout the entire small intestine whereas GLUT2-deficient animals exhibited higher tracer contents in tissue samples than wild type animals. Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose-induced insulin but not incretin secretion was impaired. Western blot analysis revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration. SGLT1 is unequivocally the prime intestinal glucose transporter even at high luminal glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin secretion. Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

  5. Carcinogenicity in rats of the SGLT2 inhibitor canagliflozin.

    Science.gov (United States)

    De Jonghe, Sandra; Proctor, Jim; Vinken, Petra; Feyen, Bianca; Wynant, Inneke; Marien, Dirk; Geys, Helena; Mamidi, Rao N V S; Johnson, Mark D

    2014-12-05

    The carcinogenicity potential of canagliflozin, an inhibitor of SGLT2, was evaluated in a 2-year rat study (10, 30, and 100 mg/kg). Rats showed an increase in pheochromocytomas, renal tubular tumors, and testicular Leydig cell tumors. Systemic exposure multiples at the highest dose relative to the maximum clinical dose were 12- to 21-fold. Pheochromocytomas and renal tubular tumors were noted in both sexes at 100 mg/kg. Leydig cell tumors were observed in males in all dose groups and were associated with increased luteinizing hormone levels. Hyperplasia was increased in the adrenal medulla at 100 mg/kg, but only a limited increase in simple tubular hyperplasia was observed in the kidney of males at 100 mg/kg. Hyperostosis occurred and was accompanied by substantial effects on calcium metabolism, including increased urinary calcium excretion and decreased levels of calcium regulating hormones (1,25-dihydroxyvitamin D and parathyroid hormone). A separate study with radiolabeled calcium confirmed that increased urinary calcium excretion was mediated via increased calcium absorption from the gastrointestinal tract. It was hypothesized that, at high doses, canagliflozin might have inhibited glucose absorption in the intestine via SGLT1 inhibition that resulted in glucose malabsorption, which increased calcium absorption by stimulating colonic glucose fermentation and reducing intestinal pH. Pheochromocytomas and adrenal medullary hyperplasia were attributed to altered calcium homeostasis, which have a known relationship in the rat. In conclusion, Leydig cell tumors were associated with increased luteinizing hormone levels and pheochromocytomas were most likely related to glucose malabsorption and altered calcium homeostasis. Renal tubular tumors may also have been linked to glucose malabsorption. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. A simple method for the appraisal of glare in street lighting.

    NARCIS (Netherlands)

    Adrian, W. & D.A. Schreuder

    1970-01-01

    A graphical method for the quantitative assessment of discomfort and disability glare in street lighting is described. The method is based on two groups of experiments which were carried out independently of each other. The results, which show good agreement, reveal the relationship between discomfo

  7. Damage evolution in GLARE fibre-metal laminate under repeated low-velocity impact tests

    NARCIS (Netherlands)

    Morinière, F.D.; Alderliesten, R.C.; Tooski, M.Y.; Benedictus, R.

    2012-01-01

    An experimental study was performed on the repeated low-velocity impact behaviour of GLARE. Damage evolution in the material constituents was characterised with successive number of impacts. Records were correlated with visual inspection, ultrasound C-scan and chemical etching. The stiffness of the

  8. Session IV. Problem Solving. Vehicle lighting system. Four steps in glare reduction.

    NARCIS (Netherlands)

    Schreuder, D.A.

    1972-01-01

    A number of proposals are described that may help to reduce glare. The systems are either only a partial improvement, or they are expensive, or their introduction raises severe problems. One solution, already widely in use, is applica- tion of overhead lighting. In order to really improve the situa

  9. Laser glare in the cockpit: psychophysical estimates versus model predictions of veiling luminance distribution

    NARCIS (Netherlands)

    Blick, D.W.; Beer, J.M.A.; Kosnik, W.D.; Troxel, S.; Toet, A.; Walraven, J.; Mitchell, W.

    2001-01-01

    Two methods for estimating the visual effects of light scattered from a laser glare source were compared: (1) a veiling luminance (VL) model that convolves a radiometric scan of the corneal light distribution with a point-spread function to calculate the retinal distribution and (2) psychophysically

  10. SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Misra, Monika

    2013-03-01

    Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

  11. Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus

    OpenAIRE

    Vallon, Volker; Rose, Michael; Gerasimova, Maria; Satriano, Joseph; Platt, Kenneth A.; Koepsell, Hermann; Cunard, Robyn; Sharma, Kumar; Thomson, Scott C.; Rieg, Timo

    2012-01-01

    The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic drugs. We used gene-targeted Sglt2 knockout (Sglt2−/−) mice to elucidate the contribution of SGLT2 to blood glucose control, glomerular hyperfiltration, kidney growth, and markers of renal growth and injury at 5 wk and 4.5 mo after induction of low-dose streptozotocin (STZ) diabetes. The absence of SGLT2 did not affect renal mRNA expressi...

  12. Composition and pools of humus in natural and agrogenic soils of the Kamchatka Peninsula

    Science.gov (United States)

    Kiseleva, I. V.; Purtova, L. N.; Kostenkov, N. M.

    2016-06-01

    Differentiation of Kamchatka soils with respect to the composition and pools of humus is discussed. Very low and low pools of humus of the fulvate type are typical of the ocherous and stratified ocherous volcanic soils of the eastern coastal zone and the Central Kamchatka Depression. Ocherous volcanic soils of the Western Kamchatka Lowland are characterized by the low and moderate pools of the humate-fulvate humus. Agrogenic soils are characterized by the higher pools of humus in the upper 20 cm in comparison with their natural analogues, which is largely related to changes in the physical properties of the soils under the impact of tillage.

  13. Competitive inhibition of SGLT2 by tofogliflozin or phlorizin induces urinary glucose excretion through extending splay in cynomolgus monkeys.

    Science.gov (United States)

    Nagata, Takumi; Suzuki, Masayuki; Fukazawa, Masanori; Honda, Kiyofumi; Yamane, Mizuki; Yoshida, Ayae; Azabu, Hiroko; Kitamura, Hidekazu; Toyota, Naoto; Suzuki, Yoshiyuki; Kawabe, Yoshiki

    2014-06-15

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors showed a glucose lowering effect in type 2 diabetes patients through inducing renal glucose excretion. Detailed analysis of the mechanism of the glucosuric effect of SGLT2 inhibition, however, has been hampered by limitations of clinical study. Here, we investigated the mechanism of urinary glucose excretion using nonhuman primates with SGLT inhibitors tofogliflozin and phlorizin, both in vitro and in vivo. In cells overexpressing cynomolgus monkey SGLT2 (cSGLT2), both tofogliflozin and phlorizin competitively inhibited uptake of the substrate (α-methyl-d-glucopyranoside; AMG). Tofogliflozin was found to be a selective cSGLT2 inhibitor, inhibiting cSGLT2 more strongly than did phlorizin, with selectivity toward cSGLT2 1,000 times that toward cSGLT1; phlorizin was found to be a nonselective cSGLT1/2 inhibitor. In a glucose titration study in cynomolgus monkeys under conditions of controlled plasma drug concentration, both tofogliflozin and phlorizin increased fractional excretion of glucose (FEG) by up to 50% under hyperglycemic conditions. By fitting the titration curve using a newly introduced method that avoids variability in estimating the threshold of renal glucose excretion, we found that tofogliflozin and phlorizin lowered the threshold and extended the splay in a dose-dependent manner without significantly affecting the tubular transport maximum for glucose (TmG). Our results demonstrate the contribution of SGLT2 to renal glucose reabsorption (RGR) in cynomolgus monkeys and demonstrate that competitive inhibition of cSGLT2 exerts a glucosuric effect by mainly extending splay and lowering threshold without affecting TmG.

  14. The design and synthesis of novel SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties.

    Science.gov (United States)

    Guo, Cheng; Hu, Min; DeOrazio, Russell J; Usyatinsky, Alexander; Fitzpatrick, Kevin; Zhang, Zhenjun; Maeng, Jun-Ho; Kitchen, Douglas B; Tom, Susan; Luche, Michele; Khmelnitsky, Yuri; Mhyre, Andrew J; Guzzo, Peter R; Liu, Shuang

    2014-07-01

    The sodium glucose co-transporter 2 (SGLT2) has received considerable attention in recent years as a target for the treatment of type 2 diabetes mellitus. This report describes the design, synthesis and structure-activity relationship (SAR) of C-glycosides with benzyltriazolopyridinone and phenylhydantoin as the aglycone moieties as novel SGLT2 inhibitors. Compounds 5p and 33b demonstrated high potency in inhibiting SGLT2 and high selectivity against SGLT1. The in vitro ADMET properties of these compounds will also be discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nauck MA

    2014-09-01

    Full Text Available Michael A Nauck Department of Internal Medicine, Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany Abstract: The importance of the kidney's role in glucose homeostasis has gained wider understanding in recent years. Consequently, the development of a new pharmacological class of anti-diabetes agents targeting the kidney has provided new treatment options for the management of type 2 diabetes mellitus (T2DM. Sodium glucose co-transporter type 2 (SGLT2 inhibitors, such as dapagliflozin, canagliflozin, and empagliflozin, decrease renal glucose reabsorption, which results in enhanced urinary glucose excretion and subsequent reductions in plasma glucose and glycosylated hemoglobin concentrations. Modest reductions in body weight and blood pressure have also been observed following treatment with SGLT2 inhibitors. SGLT2 inhibitors appear to be generally well tolerated, and have been used safely when given as monotherapy or in combination with other oral anti-diabetes agents and insulin. The risk of hypoglycemia is low with SGLT2 inhibitors. Typical adverse events appear to be related to the presence of glucose in the urine, namely genital mycotic infection and lower urinary tract infection, and are more often observed in women than in men. Data from long-term safety studies with SGLT2 inhibitors and from head-to-head SGLT2 inhibitor comparator studies are needed to fully determine their benefit–risk profile, and to identify any differences between individual agents. However, given current safety and efficacy data, SGLT2 inhibitors may present an attractive option for T2DM patients who are failing with metformin monotherapy, especially if weight is part of the underlying treatment consideration. Keywords: anti-diabetes agents, efficacy, hyperglycemia, safety, sodium glucose co-transporter type 2 inhibitors, type 2 diabetes mellitus

  16. Changes of geoacoustic emission directivity at «Mikizha» site associated with earthquakes in Kamchatka

    Directory of Open Access Journals (Sweden)

    Marapulets Yuriy

    2016-01-01

    Full Text Available To investigate high frequency geoacoustic emission, a receiving system based on a compound vector receiver was installed in Kamchatka. It allows the authors to determine the direction of sound wave arrival. In the result of data analysis for the period from August 2008 to January 2016, it was determined that anomalies of geoacoustic emission directivity occur during the majority of the earthquakes with Ks > 9.0 in the South of Kamchatka.

  17. Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

    Science.gov (United States)

    Scheen, André J

    2015-07-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus. SGLT2 cotransporters are responsible for reabsorption of 90 % of the glucose filtered by the kidney. The glucuretic effect resulting from SGLT2 inhibition contributes to reduce hyperglycaemia and also assists weight loss and blood pressure reduction. Several SGLT2 inhibitors are already available in many countries (dapagliflozin, canagliflozin, empagliflozin) and in Japan (ipragliflozin, tofogliflozin). These SGLT2 inhibitors share similar pharmacokinetic characteristics with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites and a low renal elimination as a parent drug. Pharmacokinetic parameters are slightly altered in the case of chronic kidney disease (CKD). While no dose adjustment is required in the case of mild CKD, SGLT2 inhibitors may not be used or only at a lower daily dose in patients with moderate CKD. Furthermore, the pharmacodynamic response to SGLT2 inhibitors as assessed by urinary glucose excretion declines with increasing severity of renal impairment as assessed by a reduction in the estimated glomerular filtration rate. Nevertheless, the glucose-lowering efficacy and safety of SGLT2 inhibitors are almost comparable in patients with mild CKD as in patients with normal kidney function. In patients with moderate CKD, the efficacy tends to be dampened and safety concerns may occur. In patients with severe CKD, the use of SGLT2 inhibitors is contraindicated. Thus, prescribing information should be consulted regarding dosage adjustments or restrictions in the case of renal dysfunction for each SGLT2 inhibitor. The clinical impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy deserve attention because of preliminary favourable results

  18. Elements for Success in Managing Type 2 Diabetes With SGLT-2 Inhibitors: Role of the Kidney in Glucose Homeostasis: Implications for SGLT-2 Inhibition in the Treatment of Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Miller, Eden M

    2017-02-01

    The focus on the kidney as a therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) has led to the development of the sodium-glucose cotransporter-2 (SGLT-2) inhibitors, of which 3 are available in the United States. This article addresses the implications for SGLT-2 inhibition in the treatment of T2DM.

  19. Evolution and genesis of volcanic rocks from Mutnovsky Volcano, Kamchatka

    Science.gov (United States)

    Simon, A.; Yogodzinski, G. M.; Robertson, K.; Smith, E.; Selyangin, O.; Kiryukhin, A.; Mulcahy, S. R.; Walker, J. D.

    2014-10-01

    This study presents new geochemical data for Mutnovsky Volcano, located on the volcanic front of the southern portion of the Kamchatka arc. Field relationships show that Mutnovsky Volcano is comprised of four distinct stratocones, which have grown over that past 80 ka. The youngest center, Mutnovsky IV, has produced basalts and basaltic andesites only. The three older centers (Mutnovsky I, II, III) are dominated by basalt and basaltic andesite (60-80% by volume), but each has also produced small volumes of andesite and dacite. Across centers of all ages, Mutnovsky lavas define a tholeiitic igneous series, from 48-70% SiO2. Basalts and basaltic andesites have relatively low K2O and Na2O, and high FeO* and Al2O3 compared to volcanic rocks throughout Kamchatka. The mafic lavas are also depleted in the light rare earth elements (REEs), with chondrite-normalized La/Sm arc volcanic rocks worldwide. Radiogenic isotope ratios (Sr, Nd, Pb, Hf) are similar for samples from all four eruptive centers, and indicate that all samples were produced by melting of a similar source mixture. No clear age-progressive changes are evident in the compositions of Mutnovsky lavas. Mass balance and assimilation-fractional crystallization (AFC) modeling of major and rare earth elements (REEs) indicate that basaltic andesites were produced by FC of plagioclase, clinopyroxene and olivine from a parental basalt, combined with assimilation of a melt composition similar to dacite lavas present at Mutnovsky. This modeling also indicates that andesites were produced by FC of plagioclase from basaltic andesite, combined with assimilation of dacite. Dacites erupted from Mutnovsky I and II have low abundances of REEs, and do not appear to be related to mafic magmas by FC or AFC processes. These dacites are modeled as the products of dehydration partial melting at mid-crustal levels of a garnet-free, amphibole-bearing basaltic rock, which itself formed in the mid-crust by emplacement of magma that

  20. GlaRe, a GIS tool to reconstruct the 3D surface of palaeoglaciers

    Science.gov (United States)

    Pellitero, Ramón; Rea, Brice R.; Spagnolo, Matteo; Bakke, Jostein; Ivy-Ochs, Susan; Frew, Craig R.; Hughes, Philip; Ribolini, Adriano; Lukas, Sven; Renssen, Hans

    2016-09-01

    Glacier reconstructions are widely used in palaeoclimatic studies and this paper presents a new semi-automated method for generating glacier reconstructions: GlaRe, is a toolbox coded in Python and operating in ArcGIS. This toolbox provides tools to generate the ice thickness from the bed topography along a palaeoglacier flowline applying the standard flow law for ice, and generates the 3D surface of the palaeoglacier using multiple interpolation methods. The toolbox performance has been evaluated using two extant glaciers, an icefield and a cirque/valley glacier from which the subglacial topography is known, using the basic reconstruction routine in GlaRe. Results in terms of ice surface, ice extent and equilibrium line altitude show excellent agreement that confirms the robustness of this procedure in the reconstruction of palaeoglaciers from glacial landforms such as frontal moraines.

  1. Damage evolution in GLARE fibre-metal laminate under repeated low-velocity impact tests

    Science.gov (United States)

    Morinière, Freddy; Alderliesten, René; Tooski, Mehdi; Benedictus, Rinze

    2012-12-01

    An experimental study was performed on the repeated low-velocity impact behaviour of GLARE. Damage evolution in the material constituents was characterised with successive number of impacts. Records were correlated with visual inspection, ultrasound C-scan and chemical etching. The stiffness of the plate varied when cumulating the number of impacts. Damage accumulation was limited thanks to the synthesis of unidirectional composite and metal. The glass/epoxy plies with high elastic tensile strength could withstand several impacts before perforation despite delamination growth in the vicinity of the impacted area. The damage tolerant aluminium layers prevented the penetration of the projectile and avoided the expansion of delamination. This efficient mechanism preserved the structural integrity of GLARE until first aluminium cracking at the non-impacted side. Among the different failure modes, plate deformation absorbed most of the impact energy. The findings will support the development of a generic quasi-static analytical model and numerical methods.

  2. Measurement of stray light and glare: comparison of Nyktotest, Mesotest, stray light meter, and computer implemented stray light meter

    National Research Council Canada - National Science Library

    van Rijn, L J; Nischler, C; Gamer, D; Franssen, L; de Wit, G; Kaper, R; Vonhoff, D; Grabner, G; Wilhelm, H; Völker-Dieben, H J; van den Berg, T J T P

    2005-01-01

    To evaluate the properties of devices for measuring stray light and glare: the Nyktotest, Mesotest, "conventional" stray light meter and a new, computer implemented version of the stray light meter...

  3. A Review on the Relationship between SGLT2 Inhibitors and Cancer

    Directory of Open Access Journals (Sweden)

    Hao-Wen Lin

    2014-01-01

    Full Text Available Risk of increasing breast and bladder cancer remains a safety issue of SGLT2 (sodium glucose cotransporter type 2 inhibitors, a novel class of antidiabetic agent. We reviewed related papers published before January 29, 2014, through Pubmed search. Dapagliflozin and canagliflozin are the first two approved SGLT2 inhibitors for diabetes therapy. Although preclinical animal toxicology did not suggest a cancer risk of dapagliflozin and overall tumor did not increase, excess numbers of female breast cancer and male bladder cancer were noted in preclinical trials (without statistical significance. This concern of cancer risk hindered its approval by the US FDA in January, 2012. New clinical data suggested that the imbalance of bladder and breast cancer might be due to early diagnosis rather than a real increase of cancer incidence. No increased risk of overall bladder or breast cancer was noted for canagliflozin. Therefore, the imbalance observed with dapagliflozin treatment should not be considered as a class effect of SGLT2 inhibitors and the relationship with cancer for each specific SGLT2 inhibitor should be examined individually. Relationship between SGLT2 inhibition and cancer formation is still inconclusive and studies with larger sample size, longer exposure duration, and different ethnicities are warranted.

  4. SGLT-2 Inhibitors: Is There a Role in Type 1 Diabetes Mellitus Management?

    Science.gov (United States)

    Ahmed-Sarwar, Nabila; Nagel, Angela K; Leistman, Samantha; Heacock, Kevin

    2017-09-01

    The purpose of this review is to identify and evaluate disease management of patients with type 1 diabetes mellitus (T1DM) who were treated with a sodium-glucose cotransporter 2 (SGLT-2) inhibitor as an adjunct to insulin therapy. A PubMed (1969 to March 2017) and Ovid (1946 to March 2017) search was performed for articles published utilizing the following MESH terms: canagliflozin, empagliflozin, dapagliflozin, type 1 diabetes mellitus, insulin dependent diabetes, insulin, sodium-glucose transporter 2. There were no limitations placed on publication type. All English-language articles were evaluated for association of SGLT-2 inhibitors and type 1 diabetes. Further studies were identified by review of pertinent manuscript bibliographies. All 3 SGLT-2 inhibitors, when combined with insulin, resulted in an overall reduction of hemoglobin A1C (up to 0.49%), lower total daily insulin doses, and a reduction in weight (up to 2.7 kg). The combination therapy of insulin and SGLT-2 inhibitors also resulted in a lower incidence of hypoglycemia. Study duration varied from 2 to 18 weeks. A review of the identified literature indicated that there is a potential role for the combination of SGLT-2 inhibitors with insulin in T1DM for improving glycemic control without increasing the risk of hypoglycemia. The short duration and small sample sizes limit the ability to fully evaluate the incidences of diabetic ketoacidosis and urogenital infections. The risks associated with this combination of medications require further evaluation.

  5. Microstructured glazing for daylighting, glare protection, seasonal thermal control and clear view

    OpenAIRE

    Kostro, André Gabriel

    2015-01-01

    The appropriate choice of glazing in a facade depends on many factors. They include amongst other criteria: location, orientation, climatic condition, energetic efficiency, usage of the building, required user comfort, and the architectural concept. On the south facade of high-rise buildings in particular, it is a challenge to have simultaneously large glazed area, no glare, no excessive cooling loads, a clear view and sufficient natural light flux. In Switzerland, electric lighting, heating ...

  6. A new device for dynamic luminance mapping and glare risk assessment in buildings

    Science.gov (United States)

    Borisuit, Apiparn; Münch, Mirjam; Deschamps, Laurent; Kämpf, Jérôme; Scartezzini, Jean-Louis

    2012-10-01

    High dynamic range imaging has been shown to be a reliable tool to assess luminance maps and glare risk probability in buildings. However, there are some limitations of image capturing time, especially when dealing with highly dynamic and contrasted daylight situations. We used a newly developed prototype of a digital camera which contains a high dynamic range pixel array chip, with a logarithmic scale for encoding. This type of camera allows to effectively assessing luminance, contrast and contrast directions, by taking only a single image or by performing real time recordings. The device was equipped with a fisheye lens and V-lambda filters to adapt the camera's spectral sensitivity to the human eye. After spectral as well as photometric calibration and vignetting correction, the device was tested to perform luminance mapping of real scenes. The results showed that luminance maps of a room can be efficiently assessed under dynamic daylight and mixed day- and electric lighting conditions in a very short time (i.e. 100 ms), when compared to classical HDR imaging techniques. This allows us to calculate glare indexes of a scene simultaneously. The camera opens a variety of new applications as a useful tool for architects, building designers and lighting experts. The device can be used to easily monitor daylight availability and glare indexes in existing buildings and further developments for advanced (day-) lighting control can be envisaged.

  7. Molecular analysis of the SGLT2 gene in patients with renal glucosuria

    DEFF Research Database (Denmark)

    Santer, René; Kinner, Martina; Lassen, Christoph L.

    2003-01-01

    heterozygous for an SGLT2 mutation resulting in glucosuria in the range of 14.6 to 202 g/1.73 m(2)/d (81 - 1120 mmol/1.73 m(2)/d). Some, but not all, of their heterozygous family members had an increased glucose excretion of up to 4.4 g/1.73 m(2)/d (24 mmol/1.73 m(2)/d). Likewise, in index cases...... with glucosuria below 10 g/1.73 m(2)/d (55 mmol/1.73 m(2)/d) an SGLT2 mutation, if present, was always detected in the heterozygous state. We conclude that SGLT2 plays an important role in renal tubular glucose reabsorption. Inheritance of renal glucosuria shows characteristics of a codominant trait with variable...

  8. SGLT5 Reabsorbs Fructose in the Kidney but Its Deficiency Paradoxically Exacerbates Hepatic Steatosis Induced by Fructose

    Science.gov (United States)

    Fukuzawa, Taku; Fukazawa, Masanori; Ueda, Otoya; Shimada, Hideaki; Kito, Aki; Kakefuda, Mami; Kawase, Yosuke; Wada, Naoko A.; Goto, Chisato; Fukushima, Naoshi; Jishage, Kou-ichi; Honda, Kiyofumi; King, George L.; Kawabe, Yoshiki

    2013-01-01

    Although excessive fructose intake is epidemiologically linked with dyslipidemia, obesity, and diabetes, the mechanisms regulating plasma fructose are not well known. Cells transfected with sodium/glucose cotransporter 5 (SGLT5), which is expressed exclusively in the kidney, transport fructose in vitro; however, the physiological role of this transporter in fructose metabolism remains unclear. To determine whether SGLT5 functions as a fructose transporter in vivo, we established a line of mice lacking the gene encoding SGLT5. Sodium-dependent fructose uptake disappeared in renal brush border membrane vesicles from SGLT5-deficient mice, and the increased urinary fructose in SGLT5-deficient mice indicated that SGLT5 was the major fructose reabsorption transporter in the kidney. From this, we hypothesized that urinary fructose excretion induced by SGLT5 deficiency would ameliorate fructose-induced hepatic steatosis. To test this hypothesis we compared SGLT5-deficient mice with wild-type mice under conditions of long-term fructose consumption. Paradoxically, however, fructose-induced hepatic steatosis was exacerbated in the SGLT5-deficient mice, and the massive urinary fructose excretion was accompanied by reduced levels of plasma triglycerides and epididymal fat but fasting hyperinsulinemia compared with fructose-fed wild-type mice. There was no difference in food consumption, water intake, or plasma fructose between the two types of mice. No compensatory effect by other transporters reportedly involved in fructose uptake in the liver and kidney were indicated at the mRNA level. These surprising findings indicated a previously unrecognized link through SGLT5 between renal fructose reabsorption and hepatic lipid metabolism. PMID:23451068

  9. KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state.

    Science.gov (United States)

    Ogata, Hidetada; Seino, Yusuke; Harada, Norio; Iida, Atsushi; Suzuki, Kazuyo; Izumoto, Takako; Ishikawa, Kota; Uenishi, Eita; Ozaki, Nobuaki; Hayashi, Yoshitaka; Miki, Takashi; Inagaki, Nobuya; Tsunekawa, Shin; Hamada, Yoji; Seino, Susumu; Oiso, Yutaka

    2014-08-01

    Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic β-cells are glucose-responsive and equipped with a similar glucose-sensing apparatus that includes glucokinase and an ATP-sensitive K(+) (KATP) channel comprising KIR6.2 and sulfonylurea receptor 1. In absorptive epithelial cells and enteroendocrine cells, sodium glucose co-transporter 1 (SGLT1) is also known to play an important role in glucose absorption and glucose-induced incretin secretion. However, the glucose-sensing mechanism in K-cells is not fully understood. In this study, we examined the involvement of SGLT1 (SLC5A1) and the KATP channels in glucose sensing in GIP secretion in both normal and streptozotocin-induced diabetic mice. Glimepiride, a sulfonylurea, did not induce GIP secretion and pretreatment with diazoxide, a KATP channel activator, did not affect glucose-induced GIP secretion in the normal state. In mice lacking KATP channels (Kir6.2(-/-) mice), glucose-induced GIP secretion was enhanced compared with control (Kir6.2(+) (/) (+)) mice, but was completely blocked by the SGLT1 inhibitor phlorizin. In Kir6.2(-/-) mice, intestinal glucose absorption through SGLT1 was enhanced compared with that in Kir6.2(+) (/) (+) mice. On the other hand, glucose-induced GIP secretion was enhanced in the diabetic state in Kir6.2(+) (/) (+) mice. This GIP secretion was partially blocked by phlorizin, but was completely blocked by pretreatment with diazoxide in addition to phlorizin administration. These results demonstrate that glucose-induced GIP secretion depends primarily on SGLT1 in the normal state, whereas the KATP channel as well as SGLT1 is involved in GIP secretion in the diabetic state in vivo.

  10. Iridium anomaly in the Cretaceous section of the Eastern Kamchatka

    Science.gov (United States)

    Savelyev, Dmitry; Savelyeva, Olga

    2010-05-01

    The origin of iridium anomalies is widely discussed with regard to massive fauna and flora extinction at several geologic boundaries. Two hypotheses are most popular, cosmogenic and volcanogenic. Anomalies of iridium are known at many stratigraphic levels, both at the geologic series borders and within geologic series. Our studies revealed increased content of iridium in a section of Cretaceous oceanic deposits on the Kamchatsky Mys Peninsula (Eastern Kamchatka, Russia). The investigated section (56°03.353´N, 163°00.376´E) includes interbedded jaspers and siliceous limestones overlaying pillow-basalts. These deposits belong to the Smagin Formation of the Albian-Cenomanian age. In the middle and upper parts of the section two beds of black carbonaceous rocks with sapropelic organic matter were observed. Their formation marked likely episodes of oxygen depletion of oceanic intermediate water (oceanic anoxic events). Our geochemical studies revealed an enrichment of the carbonaceous beds in a number of major and trace elements (Al2O3, TiO2, FeO, MgO, K2O, P2O5, Cu, Zn, Ni, Cr, V, Mo, Ba, Y, Zr, Nb, REE, U, Au, Pt etc.) in comparison with associating jaspers and limestones. There are likely different sources which contributed to the enrichment. It is possible however to correlate the excess of Al, Ti, Zr, Nb with volcanogenic admixture, which is absent in limestones and jaspers. A possible source of the volcanogenic material was local volcanism as suggested by the close association of the investigated section with volcanic rocks (basaltic lavas and hyaloclastites). The basalts of the Smagin Formation were previously proposed to originate during Cretaceous activity of the Hawaiian mantle plume (Portnyagin et al., Geology, 2008). Neutron activation analysis indicated increased up to 9 ppb concentration of Ir at the bottom of the lower carbonaceous bed (inorganic part of the sample was analyzed comprising 46% of the bulk rock). In other samples Ir content was below

  11. Expression of Na+-d-glucose cotransporter SGLT2 in rodents is kidney-specific and exhibits sex and species differences

    OpenAIRE

    Sabolić, Ivan; Vrhovac, Ivana; Eror, Daniela Balen; Gerasimova, Maria; Rose, Michael; Breljak, Davorka; Ljubojević, Marija; Brzica, Hrvoje; Sebastiani, Anne; Thal, Serge C.; Sauvant, Christoph; Kipp, Helmut; Vallon, Volker; Koepsell, Hermann

    2012-01-01

    With a novel antibody against the rat Na+-d-glucose cotransporter SGLT2 (rSGLT2-Ab), which does not cross-react with rSGLT1 or rSGLT3, the ∼75-kDa rSGLT2 protein was localized to the brush-border membrane (BBM) of the renal proximal tubule S1 and S2 segments (S1 > S2) with female-dominant expression in adult rats, whereas rSglt2 mRNA expression was similar in both sexes. Castration of adult males increased the abundance of rSGLT2 protein; this increase was further enhanced by estradiol and pr...

  12. Glare disability and spherical aberration with five foldable intraocular lenses: a prospective randomized study.

    Science.gov (United States)

    Casprini, Fabrizio; Balestrazzi, Angelo; Tosi, Gian Marco; Miracco, Flavia; Martone, Gianluca; Cevenini, Gabriele; Caporossi, Aldo

    2005-02-01

    To compare differences in subjective glare and spherical aberration between five foldable intraocular lenses (IOLs) made of different materials and to different designs. This prospective study comprised 175 cataract patients who underwent phacoemulsification and were randomized to receive one of five types of foldable IOL (AcrySof MA30BA, Alcon; Sensar AR40, AMO; AcrySof SA30AL, Alcon; Sensar AR40e, AMO, and Tecnis Z9000, Pharmacia & Upjohn). All patients received a questionnaire investigating the incidence of subjective photic phenomena. Two months postoperatively, we collected data regarding subjective glare and evaluated pupil size, visual acuity and wavefront aberration of the cornea and eye. With regard to difficulty in performing ordinary activities under different light conditions and light and dark adaptation, the difference between the groups was not significant (p > 0.05, chi-squared test). With respect to difficulty in driving at night, the MA30BA group had a significant higher incidence of photic phenomena than the SA30AL, AR40e and Z9000 groups (p < 0.05, chi-squared test). Wavefront measurements revealed a significant difference between the Z9000, AR40e and SA30AL groups, which showed the lowest values, and the MA30BA group, which showed the highest value (p < 0.05, anova with Tamhane posthoc test). New generation IOLs such as the Pharmacia Z9000, AMO AR40e and AcrySof SA30AL have a lower incidence of glare and spherical aberrations; however, their impact on future IOL design should be conditioned by further data, especially regarding posterior capsule opacification.

  13. Evaluation of anti-glare applications for a tactical helmet-mounted display

    Science.gov (United States)

    Roll, Jason L.; Trew, Noel J. M.; Geis, Matthew R.; Havig, Paul R.

    2011-06-01

    Non see-through, monocular helmet mounted displays (HMDs) provide warfighters with unprecedented amounts of information at a glance. The US Air Force recognizes their usefulness, and has included such an HMD as part of a kit for ground-based, Battlefield Airmen. Despite their many advantages, non see-through HMDs occlude a large portion of the visual field when worn as designed, directly in front of the eye. To address this limitation, operators have chosen to wear it just above the cheek, angled up toward the eye. However, wearing the HMD in this position exposes the display to glare, causing a potential viewing problem. In order to address this problem, we tested several film and HMD hood applications for their effect on glare. The first experiment objectively examined the amount of light reflected off the display with each application in a controlled environment. The second experiment used human participants to subjectively evaluate display readability/legibility with each film and HMD hood covering under normal office lighting and under a simulated sunlight condition. In this test paradigm, participants had to correctly identify different icons on a map and different words on a white background. Our results indicate that though some applications do reduce glare, they do not significantly improve the HMD's readability/legibility compared with an uncovered screen. This suggests that these post-production modifications will not completely solve this problem and underscores the importance of employing a user-centered approach early in the design cycle to determine an operator's use-case before manufacturing an HMD for a particular user community.

  14. Potential energy savings with exterior shades in large office buildings and the impact of discomfort glare

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Sabine [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Lee, Eleanor [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-04-01

    Exterior shades are highly efficient for reducing solar load in commercial buildings. Their impact on net energy use depends on the annual energy balance of heating, cooling, fan and lighting energy. This paper discusses the overall energy use intensity of various external shading systems for a prototypical large office building split into the different types of energy use and for different orientations and window sizes. Lighting energy was calculated for a constant lighting power as well as for dimmed lighting fixtures (daylighting control). In Section 3, slat angles and solar cut-off angles were varied for fixed exterior slat shading systems. While the most light-blocking shades performed best for the case without daylighting controls, the optimum cut-off angle with daylighting controls was found to be 30 deg for the office building prototype used in Chicago and Houston. For large window-to-wall (WWR) ratios, window related annual energy use could be reduced by at least 70 % without daylighting control and by a minimum of 86 % with daylighting control in average over all orientations. The occurrence of discomfort glare was is considered in Section 4 of the paper, which looks at the performance of commercially available exterior shading systems when an interior shade is used in addition to the exterior shade during hours when occupants would experience discomfort glare. Glare control impacts overall energy use intensity significantly for exterior shades with high transmittance, especially when daylighting controls are used. In these cases, exterior shades are only beneficial for window-to-wall areas ≥ 45% in the hot Houston climate. For smaller windows and in a heating/cooling climate like Chicago, exterior shades can increase energy consumption

  15. Low-carbohydrate diet combined with SGLT2 inhibitor for refractory hyperglycemia caused by insulin antibodies.

    Science.gov (United States)

    Shigeno, Riyoko; Horie, Ichiro; Ando, Takao; Abiru, Norio; Kawakami, Atsushi

    2016-06-01

    A low-carbohydrate diet is effective to improve hyperglycemia via insulin-independent actions. We report here that a low-carbohydrate diet combined with an SGLT2 inhibitor was effective and safe to treat refractory hyperglycemia in the perioperative period in a type 2 diabetes patient complicated with a high titer of insulin antibodies.

  16. Lagrangian study of temporal changes of a surface flow through the Kamchatka Strait

    CERN Document Server

    Prants, S V; Uleysky, M Yu; Budyansky, M V

    2014-01-01

    Using Lagrangian methods we analyze a 20-year-long estimate of water flux through the Kamchatka Strait in the northern North Pacific based on AVISO velocity field. It sheds new light on the flux pattern and its variability on annual and monthly time scales. Strong seasonality in surface outflow through the strait could be explained by temporal changes in the wind stress over the northern and western Bering Sea slopes. Interannual changes in a surface outflow through the Kamchatka Strait correlate significantly with the Near Strait inflow and Bering Strait outflow. Enhanced westward surface flow of the Alaskan Stream across the $174^\\circ$ E section in the northern North Pacific is accompanied by an increased inflow into the Bering Sea through the Near Strait. In summer, the surface flow pattern in the Kamchatka Strait is determined by passage of anticyclonic and cyclonic mesoscale eddies. The wind stress over the Bering basin in winter - spring is responsible for eddy generation in the region.

  17. Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence.

    Science.gov (United States)

    Scheen, A J; Paquot, N

    2014-12-01

    Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Control of disability glare by means of electrochromic filtering glasses: A pilot study

    Directory of Open Access Journals (Sweden)

    Rosa Maria Coco-Martín

    2017-01-01

    Full Text Available Purpose: To evaluate the potential clinical usability of a new prototype of ophthalmic blue light filters developed by using electrochromic technology in pseudophakic patients complaining of glare. Methods: A prototype of electrochromic device was developed, with a specific frame that enclosed an electronic driver that allowed personalizing its function for each patient. A prospective, observational case series study was performed to test it. Five patients who had undergone cataract surgery with clear intraocular lenses and complaining of glare were included in the study. Main outcome measures were the results obtained in the satisfaction questionnaire that was delivered to patients. Then, visual acuity, contrast sensitivity, and reading ability data were evaluated with and without the prototype under different lighting conditions and different modes of the prototype after a complete month of use. Lens transmittance was also measured. Results: Visual acuity, contrast sensitivity and reading function did not change significantly with prototype use. The main activity for which the prototype was used was walking. Only one patient found that the dimming level was insufficient. No patients reported variable discomfort when passing tunnels, not sufficiently clear indoors, or put on and remove discomfort. The lenses slightly decreased their transmittance at the end of the study. Conclusion: Glasses based on electrochromic technology may be acceptable for outdoor/indoor use and for distance–near vision. Future studies with larger samples must be conducted to confirm the clinical usability of these glasses.

  19. Lycium barbarum L. Polysaccharide (LBP Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell

    Directory of Open Access Journals (Sweden)

    Huizhen Cai

    2017-02-01

    Full Text Available Lycium barbarum L. polysaccharide (LBP is prepared from Lycium barbarum L. (L. barbarum, which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1.

  20. [High glucose dialysate enhances peritoneal fibrosis through upregulating glucose transporters GLUT1 and SGLT1].

    Science.gov (United States)

    Hong, Mengqi; Nie, Zhenyu; Chen, Zhengyue; Yu, Xiongwei; Bao, Beiyan

    2016-05-25

    Objective: To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) in high glucose dialysate-induced peritoneal fibrosis. Methods: Thirty six male SD rats were randomly divided into 6 groups (6 in each):normal control group, sham operation group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorizin group (PD+Z group), PD+phloretin+phlorizin group (PD+T+Z group). Rat model of uraemia was established using 5/6 nephrotomy, and 2.5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1, SGLT1, TGF-β1 and connective tissue growth factor (CTGF) in peritoneum. Human peritoneal microvascular endothelial cells (HPECs) were divided into 5 groups:normal control group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group (PD+T+Z group). Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF in peritoneal membrane and HPECs. Results:In vivo, compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly increased (all P<0.05); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (all P<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-β1 and CTGF (all P<0.05). In vitro, the mRNA and protein expressions of GLUT1, SGLT1, TGF-β1

  1. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    OpenAIRE

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the...

  2. SGLT5 Reabsorbs Fructose in the Kidney but Its Deficiency Paradoxically Exacerbates Hepatic Steatosis Induced by Fructose

    OpenAIRE

    Taku Fukuzawa; Masanori Fukazawa; Otoya Ueda; Hideaki Shimada; Aki Kito; Mami Kakefuda; Yosuke Kawase; Naoko A Wada; Chisato Goto; Naoshi Fukushima; Kou-Ichi Jishage; Kiyofumi Honda; King, George L.; Yoshiki Kawabe

    2013-01-01

    Although excessive fructose intake is epidemiologically linked with dyslipidemia, obesity, and diabetes, the mechanisms regulating plasma fructose are not well known. Cells transfected with sodium/glucose cotransporter 5 (SGLT5), which is expressed exclusively in the kidney, transport fructose in vitro; however, the physiological role of this transporter in fructose metabolism remains unclear. To determine whether SGLT5 functions as a fructose transporter in vivo, we established a line of mic...

  3. Late Glacial to Holocene paleoenvironmental change on the northwestern Pacific seaboard, Kamchatka Peninsula (Russia)

    Science.gov (United States)

    Pendea, Ionel Florin; Ponomareva, Vera; Bourgeois, Joanne; Zubrow, Ezra B. W.; Portnyagin, Maxim; Ponkratova, Irina; Harmsen, Hans; Korosec, Gregory

    2017-02-01

    We used a new sedimentary record from a small kettle wetland to reconstruct the Late Glacial and Holocene vegetation and fire history of the Krutoberegovo-Ust Kamchatsk region in eastern Kamchatka Peninsula (Russia). Pollen and charcoal data suggest that the Late Glacial landscape was dominated by a relatively fire-prone Larix forest-tundra during the Greenland Interstadial complex (GI 1) and a subarctic steppe during the Younger Dryas (GS1). The onset of the Holocene is marked by the reappearance of trees (mainly Alnus incana) within a fern and shrub dominated landscape. The Holocene Thermal Maximum (HTM) features shifting vegetational communities dominated by Alnus shrubs, diverse forb species, and locally abundant aquatic plants. The HTM is further defined by the first appearance of stone birch forests (Betula ermanii) - Kamchatka's most abundant modern tree species. The Late Holocene is marked by shifts in forest dynamics and forest-graminoid ratio and the appearance of new non-arboreal taxa such as bayberry (Myrica) and meadow rue (Filipendula). Kamchatka is one of Earth's most active volcanic regions. During the Late Glacial and Holocene, Kamchatka's volcanoes spread large quantities of tephra over the study region. Thirty-four tephra falls have been identified at the site. The events represented by most of these tephra falls have not left evidence of major impacts on the vegetation although some of the thicker tephras caused expansion of grasses (Poaceae) and, at least in one case, forest die-out and increased fire activity.

  4. Epimeria abyssalis sp. n. from the Kuril-Kamchatka Trench (Crustacea, Amphipoda, Epimeriidae)

    Science.gov (United States)

    Shimomura, Michitaka; Tomikawa, Ko

    2016-01-01

    Abstract A new deep-sea epimeriid, Epimeria abyssalis is described from the Kuril-Kamchatka Trench, in the northwestern Pacific. This species differs from its congeners in having a short rostrum and a telson with deep and narrow Y-shaped excavation. Epimeria abyssalis is the deepest recorded Epimeria species. A key to the north Pacific species of Epimeria is provided. PMID:28174500

  5. Three Lyman-alpha Emitters at z approx 6: Early GMOS/Gemini Data from the GLARE Project

    CERN Document Server

    Stanway, E R; Bunker, A J; Abraham, R G; Hook, I; Rhoads, J; McCarthy, P J; Boyle, B; Colless, M; Crampton, D; Couch, W; Jorgensen, I; Malhotra, S; Murowinski, R; Roth, K; Savaglio, S; Tsvetanov, Z I; Stanway, Elizabeth R.; Glazebrook, Karl; Bunker, Andrew J.; Abraham, Roberto G.; Hook, Isobel; Rhoads, James; Carthy, Patrick J. Mc; Boyle, Brian; Colless, Matthew; Crampton, David; Couch, Warrick; J{\\o}rgensen, Inger; Malhotra, Sangeeta; Murowinski, Rick; Roth, Kathy; Savaglio, Sandra; Tsvetanov., Zlatan

    2004-01-01

    We report spectroscopic detection of three z \\sim 6 Lyman-alpha emitting galaxies, in the vicinity of the Hubble Ultra Deep Field, from the early data of the Gemini Lyman-alpha at Reionisation Era (GLARE) project. Two objects, GLARE#3001 (z =5.79) and GLARE#3011 (z =5.94), are new detections and are fainter in z' (z'_AB = 26.37 and 27.15) than any continuum-selected objects previously detected in Lyman-alpha. A third object, GLARE#1042 (z =5.83) has previously been detected in line emission from the ground; we report here a new spectroscopic continuum detection. Gemini/GMOS-S spectra of these objects, obtained using nod & shuffle, are presented together with a discussion of their photometric properties. All three objects were selected for spectroscopy via the i-drop Lyman Break technique, the two new detections from the GOODS v1.0 imaging data. The red i'-z' colors and high equivalent widths of these objects suggest a high-confidence z>5 Lyman-alpha identification of the emission lines. This brings the to...

  6. A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor

    Directory of Open Access Journals (Sweden)

    Chang Hee Jung

    2014-08-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2 inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.

  7. SGLT 2 Inhibitors: A New Therapeutic Target And Its Role In Current Clinical Practice

    Directory of Open Access Journals (Sweden)

    PV Shiji

    2015-10-01

    Full Text Available Diabetes, one of the major life style diseases, is associated with high morbidity and mortality owing to its microvascular and macrovascular complications. The chance of development of various complications can be effectively prevented by tight glycemic control. We have various groups of drugs like Biguanides, Sulfonyl ureas, Glitazones, Alpha-glucosidase inhibitors, Incretin based therapy, Insulin and Insulin analogues in the armamentarium to treat diabetes. But still, the number of patients attaining glycemic targets are relatively low and various adverse effect limit the use of some of these drugs, especially in special groups. Hence there is ongoing research to develop newer and newer drugs which provide sustained blood glucose reduction with minimal adverse effects. SGLT-2 inhibitors are a new group of drugs recently approved by FDA to treat Diabetes. In this review we discuss about mechanism of action, various adverse effects and the clinical role of various SGLT-2 Inhibitors.

  8. SGLT2 inhibition: a novel prospective strategy in treatment of diabetes mellitus.

    Science.gov (United States)

    Deshmukh, Aaishwarya B; Patel, Maharshi C; Mishra, Bharat

    2013-01-01

    The role of the kidney in glucose homeostasis and the potential of the kidney as a therapeutic target in type 2 diabetes is little appreciated. Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose re-absorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications, thus representing an innovative therapeutic strategy for the treatment of hyperglycemia and/or obesity in patients with type 1 or type 2 diabetes by enhancing glucose and energy loss through the urine. Sodium glucose co-transporter 2 (SGLT2) has a key role in re-absorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes.

  9. Rainbow glare after laser-assisted in situ keratomileusis: a review of literature

    Directory of Open Access Journals (Sweden)

    Moshirfar M

    2016-11-01

    Full Text Available Majid Moshirfar,1,2 Jordan D Desautels,3 Tyler S Quist,4 David F Skanchy,5 Mark T Williams,6 Ryan T Wallace7 1Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, 2HDR Research Center, Hoopes Vision, Draper, UT, 3Tufts University School of Medicine, Boston, MA, 4University of Utah School of Medicine, Salt Lake City, UT, 5McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 6University of California, San Francisco School of Medicine, San Francisco, CA, 7Brigham Young University, Provo, UT, USA Abstract: This article reviews the current literature pertaining to rainbow glare (RG, including incidence rate, clinical presentation, etiology, prognosis, and management. RG is a rare optical complication of femtosecond laser-assisted in situ keratomileusis that results in patients seeing an array of spectral bands surrounding point sources of light under mesopic and scotopic conditions. The mechanism is thought to be a consequence of the formation of a transmissive diffraction grating on the posterior surface of the corneal flap created by the FS laser. RG has a good prognosis and is usually self-limiting. Persistent RG with concomitant residual refractive error may warrant lifting the flap and photoablating the posterior surface of the flap. Patients with persistent RG and no residual refractive error should be considered candidates for phototherapeutic keratectomy on the posterior flap surface. Keywords: rainbow glare, femtosecond, LASIK, keratomileusis, phototherapeutic keratectomy

  10. Understanding controls on cirque floor altitudes: Insights from Kamchatka

    Science.gov (United States)

    Barr, Iestyn D.; Spagnolo, Matteo

    2015-11-01

    Glacial cirques reflect former regions of glacier initiation, and are therefore used as indicators of past climate. One specific way in which palaeoclimatic information is obtained from cirques is by analysing their elevations, on the assumption that cirque floor altitudes are a proxy for climatically controlled equilibrium-line altitudes (ELAs) during former periods of small scale (cirque-type) glaciation. However, specific controls on cirque altitudes are rarely assessed, and the validity of using cirque floor altitudes as a source of palaeoclimatic information remains open to question. In order to address this, here we analyse the distribution of 3520 ice-free cirques on the Kamchatka Peninsula (eastern Russia), and assess various controls on their floor altitudes. In addition, we analyse controls on the mid-altitudes of 503 modern glaciers, currently identifiable on the peninsula, and make comparisons with the cirque altitude data. The main study findings are that cirque floor altitudes increase steeply inland from the Pacific, suggesting that moisture availability (i.e., proximity to the coastline) played a key role in regulating the altitudes at which former (cirque-forming) glaciers were able to initiate. Other factors, such as latitude, aspect, topography, geology, and neo-tectonics seem to have played a limited (but not insignificant) role in regulating cirque floor altitudes, though south-facing cirques are typically higher than their north-facing equivalents, potentially reflecting the impact of prevailing wind directions (from the SSE) and/or variations in solar radiation on the altitudes at which former glaciers were able to initiate. Trends in glacier and cirque altitudes across the peninsula are typically comparable (i.e., values typically rise from both the north and south, inland from the Pacific coastline, and where glaciers/cirques are south-facing), yet the relationship with latitude is stronger for modern glaciers, and the relationship with

  11. Kamchatka Peninsula, Russia 3-D Perspective with Landsat Overlay

    Science.gov (United States)

    2000-01-01

    This three-dimensional perspective view, looking up the Tigil River, shows the western side of the volcanically active Kamchatka Peninsula, Russia. The image shows that the Tigil River has eroded down from a higher and differing landscape and now flows through, rather than around the large green-colored bedrock ridge in the foreground. The older surface was likely composed of volcanic ash and debris from eruptions of nearby volcanoes. The green tones indicate that denser vegetation grows on south facing sunlit slopes at the northern latitudes. High resolution SRTM elevation data will be used by geologists to study how rivers shape the landscape, and by ecologists to study the influence of topography on ecosystems.This image shows how data collected by the Shuttle Radar Topography Mission (SRTM) can be used to enhance other satellite images. Color and natural shading are provided by a Landsat 7 image acquired on January 31, 2000. Terrain perspective and shading were derived from SRTM elevation data acquired on February 12, 2000. Topography is exaggerated by about six times vertically. The United States Geological Survey's Earth Resources Observations Systems (EROS) DataCenter, Sioux Falls, South Dakota, provided the Landsat data.The Shuttle Radar Topography Mission (SRTM), launched on February 11,2000, uses the same radar instrument that comprised the Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR) that flew twice on the Space Shuttle Endeavour in 1994. The mission is designed to collect three-dimensional measurements of the Earth's surface. To collect the 3-D data, engineers added a 60-meter-long (200-foot) mast, an additional C-band imaging antenna and improved tracking and navigation devices. The mission is a cooperative project between the National Aeronautics and Space Administration (NASA), the National Imagery and Mapping Agency (NIMA) and the German (DLR) and Italian (ASI) space agencies. It is managed by NASA's Jet Propulsion

  12. The Role of the Kidney and SGLT2 Inhibitors in Type 2 Diabetes.

    Science.gov (United States)

    Katz, Pamela M; Leiter, Lawrence A

    2015-12-01

    Effective glycemic control reduces the risk for diabetes-related complications. However, the majority of patients with type 2 diabetes still do not achieve glycemic targets. Beyond metformin therapy, current practice guidelines for the management of type 2 diabetes recommend individualized treatment based on patient and agent characteristics. The sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a novel treatment strategy, independent of impaired beta-cell function and insulin resistance. SGLT2 inhibitors decrease renal glucose reabsorption, thereby increasing urinary glucose excretion with subsequent reduction in plasma glucose levels and glycosylated hemoglobin concentrations. Current evidence suggests that they are effective as monotherapy or as add-ons to metformin either alone, or in combination with other oral glucose-lowering agents or insulin. They are generally well tolerated, though rates of lower urinary tract and genital mycotic infections are slightly increased. The advantages of this class include modest reductions in body weight and blood pressure, and low risk for hypoglycemia. Long-term safety data and results of ongoing cardiovascular outcome studies are awaited so we can fully understand the role that SGLT2 inhibitors will play in the comprehensive management of type 2 diabetes.

  13. QSAR studies on triazole derivatives as sglt inhibitors via CoMFA and CoMSIA

    Science.gov (United States)

    Zhi, Hui; Zheng, Junxia; Chang, Yiqun; Li, Qingguo; Liao, Guochao; Wang, Qi; Sun, Pinghua

    2015-10-01

    Forty-six sodium-dependent glucose cotransporters-2 (SGLT-2) inhibitors with hypoglycemic activity were selected to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. A training set of 39 compounds were used to build up the models, which were then evaluated by a series of internal and external cross-validation techniques. A test set of 7 compounds was used for the external validation. The CoMFA model predicted a q2 value of 0.792 and an r2 value of 0.985. The best CoMSIA model predicted a q2 value of 0.633 and an r2 value of 0.895 based on a combination of steric, electrostatic, hydrophobic and hydrogen-bond acceptor effects. The predictive correlation coefficients of CoMFA and CoMSIA models were 0.872 and 0.839, respectively. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active sglt inhibitors, and on the basis of the models 8 new sglt inhibitors were designed and predicted.

  14. Influence of the Metal Volume Fraction on the permanent dent depth and energy absorption of GLARE plates subjected to low velocity impact

    Science.gov (United States)

    Bikakis, GSE; Savaidis, A.; Zalimidis, P.; Tsitos, S.

    2016-11-01

    Fiber-metal laminates are hybrid composite materials, consisting of alternating metal layers bonded to fiber-reinforced prepreg layers. GLARE (GLAss REinforced) belongs to this new family of materials. GLARE is the most successful fiber-metal laminate up to now and is currently being used for the construction of primary aerospace structures, such as the fuselage of the Airbus A380 air plane. Impact properties are very important in aerospace structures, since impact damage is caused by various sources, such as maintenance damage from dropped tools, collision between service cars or cargo and the structure, bird strikes and hail. The principal objective of this article is to evaluate the influence of the Metal Volume Fraction (MVF) on the low velocity impact response of GLARE fiber-metal laminates. Previously published differential equations of motion are employed for this purpose. The low velocity impact behavior of various circular GLARE plates is predicted and characteristic values of impact variables, which represent the impact phenomenon, are evaluated versus the corresponding MVF of the examined GLARE material grades. The considered GLARE plates are subjected to low velocity impact under identical impact conditions. A strong effect of the MVF on the maximum impact load and a significant effect on the maximum plate deflection of GLARE plates has been found.

  15. Influence of the Metal Volume Fraction on the maximum deflection and impact load of GLARE plates subjected to low velocity impact

    Science.gov (United States)

    Bikakis, GSE; Savaidis, A.; Zalimidis, P.; Tsitos, S.

    2016-11-01

    Fiber-metal laminates are hybrid composite materials, consisting of alternating metal layers bonded to fiber-reinforced prepreg layers. GLARE (GLAss REinforced) belongs to this new family of materials. GLARE is the most successful fiber-metal laminate up to now and is currently being used for the construction of primary aerospace structures, such as the fuselage of the Airbus A380 air plane. Impact properties are very important in aerospace structures, since impact damage is caused by various sources, such as maintenance damage from dropped tools, collision between service cars or cargo and the structure, bird strikes and hail. The principal objective of this article is to evaluate the influence of the Metal Volume Fraction (MVF) on the low velocity impact response of GLARE fiber-metal laminates. Previously published differential equations of motion are employed for this purpose. The low velocity impact behavior of various circular GLARE plates is predicted and characteristic values of impact variables, which represent the impact phenomenon, are evaluated versus the corresponding MVF of the examined GLARE material grades. The considered GLARE plates are subjected to low velocity impact under identical impact conditions. A strong effect of the MVF on the maximum impact load and a significant effect on the maximum plate deflection of GLARE plates has been found.

  16. Sodium-glucose co-transporter 2 (SGLT2 inhibitors: a growing class of anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Eva M Vivian

    2014-12-01

    Full Text Available Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM. The renal sodium-glucose co-transporter 2 (SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic agents. Treatment with SGLT2 inhibitors is associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a promising new treatment option for T2DM.

  17. Composition, structure and properties of sediment thermal springs of Kamchatka

    Science.gov (United States)

    Shanina, Violetta; Smolyakov, Pavel; Parfenov, Oleg

    2016-04-01

    The paper deals with the physical and mechanical properties sediment thermal fields Mutnovsky, Lower Koshelevo and Bannyh (Kamchatka). This multi-component soils, mineral and chemical composition of which depends on the formation factors (pH, temperature, salinity of water, composition and structure of the host volcanic rocks). Samples Lower Koshelevo sediment thermal sources differ in the following composition: smectite, kaolinite, kaolinite-smectite mixed-mineral. Samples of sediment thermal springs Mutnovsky volcano in accordance with the X-ray analysis has the following composition: volcanic glass, crystalline sulfur, plagioclase, smectite, illite-smectite mixed, illite, chlorite, quartz, cristobalite, pyrite, melanterite, kaolinite. Natural moisture content samples of sediment thermal springs from 45 to 121%, hygroscopic moisture content of 1.3 to 3.7%. A large amount of native sulfur (up to 92%) and the presence of amorphous material gives low values of density of solid particles (up to 2.1 g/cm3) samples Mutnovskii thermal field. The values of the density of solids sediment Koshelevo and Bannyh hot springs close to those of the main components of mineral densities (up to 2.6-3.0 g/cm3). The results of the particle size distribution and microaggregate analysis of sediment thermal springs Lower Koshelevo field shows that the predominance observed of particles with a diameter from 0.05 mm to 0.25 mm, the coefficient of soil heterogeneity heterogeneous. In the bottom sediments of the thermal springs of the volcano Mutnovsky poorly traced predominance of one faction. Most prevalent fraction with particle size 0.01 - 0.05 mm. When analyzing the content in the soil microaggregates their content is shifted towards particles with a diameter of 0.25 mm. The contents of a large number of large (1-10 mm), porous rock fragments, due to the deposition of pyroclastic material from the eruptions of the last century. Present in large amounts rounded crystals of native sulfur

  18. Spotlight on Canagliflozin 300: review of its efficacy and an indirect comparison to other SGLT-2 inhibitors and long-acting GLP-1 receptor agonists.

    Science.gov (United States)

    Singh, Awadhesh Kumar; Singh, Ritu

    2017-06-01

    Both sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been consistently found to lower blood glucose, body weight and systolic blood pressure (SBP) in patients with type 2 diabetes mellitus (T2DM). While all the SGLT-2Is inhibit glucose reabsorption by blocking SGLT-2 receptor in kidney, dose-dependently, the highest licensed dose of canagliflozin 300-mg has an additional ability to inhibit SGLT-1 receptor in intestine transiently, that may lead to additional inhibition of prandial glucose absorption, unlike other approved highly selective SGLT-2Is. Areas covered: An electronic search on studies with highest licensed dose of all approved SGLT-2Is and long-acting GLP-1RAs was made up to December 2016. We systemically reviewed the studies of canagliflozin 300-mg and compared its glucose, body weight and SBP lowering with other approved SGLT-2Is and GLP-1RAs in their highest approved doses. Expert commentary: From the available evidences, it appears that canagliflozin 300-mg may have the highest potential to improve gluco-metabolic profile in T2DM, amongst the SGLT-2Is class. While the highest approved dosage of GLP-1RAs lowered HbA1c better than canagliflozin 300-mg, weight and SBP lowering could be non-inferior or slightly better with the latter drug. Nonetheless, only head-to-head trial can conclusively answer these questions.

  19. New stands of species of the Paramecium aurelia complex (Ciliophora, Protista) in Russia (Siberia, Kamchatka).

    Science.gov (United States)

    Przyboś, Ewa; Rautian, Maria; Surmacz, Marta; Bieliavskaya, Alexandra

    2013-01-01

    New stands of P. primaurelia, P. biaurelia, and P. dodecaurelia were found in Russia. P. primaurelia was recorded in Tulun (Siberia, Irkutsk region) and in three stands situated on the Kamchatka peninsula: in Lake Chalaktyrskoye, in the Valley of Geysers, and Petropavlovsk Kamchatski. P. biaurelia was also found in Tulun and in two stands in the vicinity of Lake Baikal and the Buriatia region. P. dodecaurelia was recorded in Cheboksary in European Russia and in other stands situated in Asian Russia: Novosibirsk, the vicinity of Lake Baikal, Buriatia, Kamchatka (Petropavlovsk Kamchatski, Lake Chalaktyrskoye, and Nalychevo). These data extend the ranges of species of the P. aurelia complex in Russia, however, this large territory remains understudied.

  20. Late Holocene climate and environmental changes in Kamchatka inferred from the subfossil chironomid record

    Science.gov (United States)

    Nazarova, Larisa; de Hoog, Verena; Hoff, Ulrike; Dirksen, Oleg; Diekmann, Bernhard

    2013-05-01

    This study presents a reconstruction of the Late Holocene climate in Kamchatka based on chironomid remains from a 332 cm long composite sediment core recovered from Dvuyurtochnoe Lake (Two-Yurts Lake, TYL) in central Kamchatka. The oldest recovered sediments date to about 4500 cal years BP. Chironomid head capsules from TYL reflect a rich and diverse fauna. An unknown morphotype of Tanytarsini, Tanytarsus type klein, was found in the lake sediments. Our analysis reveals four chironomid assemblage zones reflecting four different climatic periods in the Late Holocene. Between 4500 and 4000 cal years BP, the chironomid composition indicates a high lake level, well-oxygenated lake water conditions and close to modern temperatures (˜13 °C). From 4000 to 1000 cal years BP, two consecutive warm intervals were recorded, with the highest reconstructed temperature reaching 16.8 °C between 3700 and 2800 cal years BP. Cooling trend, started around 1100 cal years BP led to low temperatures during the last stage of the Holocene. Comparison with other regional studies has shown that termination of cooling at the beginning of late Holocene is relatively synchronous in central Kamchatka, South Kurile, Bering and Japanese Islands and take place around 3700 cal years BP. From ca 3700 cal years BP to the last millennium, a newly strengthened climate continentality accompanied by general warming trend with minor cool excursions led to apparent spatial heterogeneity of climatic patterns in the region. Some timing differences in climatic changes reconstructed from chironomid record of TYL sediments and late Holocene events reconstructed from other sites and other proxies might be linked to differences in local forcing mechanisms or caused by the different degree of dating precision, the different temporal resolution, and the different sensitive responses of climate proxies to the climate variations. Further high-resolution stratigraphic studies in this region are needed to understand

  1. Structural evolution of the Kamchatka - Aleutian arc junction area in the Late Mesozoic and Tertiary

    Science.gov (United States)

    Alexeiev, D.; Gaedicke, C.; Tsukanov, N. V.; Freitag, R.; Harbert, W.

    2002-05-01

    Structural, sedimentological and paleomagnetic studies have been conducted within the Kamchatka - Aleutian junction area aiming to a reconstruction of the tectonic history of the region from the Late Cretaceous to the Miocene. Pre-Pliocene structures of the area are comprised of 1) Achaivayam -Valaginskiy (Olyutorskiy) arc, 2) Vetlovskiy terrane, 3) Kronotskiy arc, and 4) Tyushevka basin, which goes along the boundary between Vetlovskiy and Kronotskiy units. In the Late Cretaceous and Tertiary deformations within the area of study were controlled by the following processes: 1) Northward subduction of the Pacific and Kula plates underneath the Kronotskiy arc and accretion in the fore-arc wedge south of the arc from the Late Cretaceous to the Middle Eocene. 2) Collision of the Achaivayam - Valaginskiy arc against Eurasia during the Early and Middle Eocene. 3) Northwest directed subduction in Proto-Kamchatka subduction zone and development of the accretionary wedge within Vetlovskiy terrane in the Middle and Late Eocene. 4) Collision of the Kronotskiy arc against Kamchatka during the Late Eocene through the Middle Miocene. We reconstruct seven structural complexes with individual structural patterns, which document different episodes of the regional deformation history. Age of the Kronotskiy arc collision is constrained by that 1) the Tyushevka foreland basin developed during the Late Eocene (?), Oligocene, Early and Middle Miocene, and 2) the foreland basin discordantly crosses syn-collisional plunging folds within the Kronotskiy arc. Syn-collisional deformations were controlled by the northwest motion of the Kronotskiy arc as part of the Pacific plate, and by the simultaneous motion of the entire northeast Eurasia margin toward the South. This caused deflection of the western segment of the Kronotskiy arc toward the south; it's rotation up to 90o counterclockwise and the subsequent bent of the arc into a large knee-like structure. The eastern portion of the

  2. Plastic pollution of the Kuril-Kamchatka Trench area (NW pacific)

    Science.gov (United States)

    Fischer, Viola; Elsner, Nikolaus O.; Brenke, Nils; Schwabe, Enrico; Brandt, Angelika

    2015-01-01

    During the German-Russian expedition KuramBio (Kuril-Kamchatka Biodiversity Studies) to the northwest Pacific Kuril-Kamchatka Trench and its adjacent abyssal plain, we found several kinds and sizes of plastic debris ranging from fishing nets and packaging to microplastic in the sediment of the deep-sea floor. Microplastics were ubiquitous in the smaller fractions of the box corer samples from every station from depths between 4869 and 5766 m. They were found on the abyssal plain and in the sediments of the trench slope on both sides. The amount of microplastics differed between the stations, with lowest concentration of 60 pieces per m2 and highest concentrations of more than 2000 pieces per m2. Around 75% of the microplastics (defined here as particles marine fauna (Zenkevich, 1963). Yet we can only guess how these microplastics accumulated in the deep sea of the Kuril-Kamchatka Trench area and what consequences the microplastic itself and its adsorbed chemicals will have on this very special and rich deep-sea fauna. But we herewith present an evaluation of the different kinds of plastic debris we found, as a documentation of human impact into the deep sea of this region of the Northwest Pacific.

  3. A full holocene tephrochronology for the Kamchatsky Peninsula region: Applications from Kamchatka to North America

    Science.gov (United States)

    Ponomareva, Vera; Portnyagin, Maxim; Pendea, I. Florin; Zelenin, Egor; Bourgeois, Joanne; Pinegina, Tatiana; Kozhurin, Andrey

    2017-07-01

    Geochemically fingerprinted widespread tephra layers serve as excellent marker horizons which can directly link and synchronize disparate sedimentary archives and be used for dating various deposits related to climate shifts, faulting events, tsunami, and human occupation. In addition, tephras represent records of explosive volcanic activity and permit assessment of regional ashfall hazard. In this paper we report a detailed Holocene tephrochronological model developed for the Kamchatsky Peninsula region of eastern Kamchatka (NW Pacific) based on ∼2800 new electron microprobe analyses of single glass shards from tephra samples collected in the area as well as on previously published data. Tephra ages are modeled based on a compilation of 223 14C dates, including published dates for Shiveluch proximal tephra sequence and regional marker tephras; new AMS 14C dates; and modeled calibrated ages from the Krutoberegovo key site. The main source volcanoes for tephra in the region are Shiveluch and Kliuchevskoi located 60-100 km to the west. In addition, local tephra sequences contain two tephras from the Plosky volcanic massif and three regional marker tephras from Ksudach and Avachinsky volcanoes located in the Eastern volcanic front of Kamchatka. This tephrochronological framework contributes to the combined history of environmental change, tectonic events, and volcanic impact in the study area and farther afield. This study is another step in the construction of the Kamchatka-wide Holocene tephrochronological framework under the same methodological umbrella. Our dataset provides a research reference for tephra and cryptotephra studies in the northwest Pacific, the Bering Sea, and North America.

  4. The GLARE Survey II. Faint z=6 Ly-alpha Line Emitters in the HUDF

    CERN Document Server

    Stanway, Elizabeth R; Glazebrook, Karl; Abraham, Roberto G; Rhoads, James; Malhotra, Sangeeta; Crampton, David; Colless, Matthew; Chiu, Kuenley; 10.1111/j.1365-2966.2007.11469.x

    2008-01-01

    The galaxy population at z~6 has been the subject of intense study in recent years, culminating in the Hubble Ultra Deep Field (HUDF) -- the deepest imaging survey yet. A large number of high redshift galaxy candidates have been identified within the HUDF, but until now analysis of their properties has been hampered by the difficulty of obtaining spectroscopic redshifts for these faint galaxies. Our ''Gemini Lyman-Alpha at Reionisation Era'' (GLARE) project has been designed to undertake spectroscopic follow up of faint (z'5.5, and a further nine possible line emitters with detections at lower significance. We also place tight constraints on the equivalent width of Lyman-alpha emission for a further ten i'-drop galaxies and examine the equivalent width distribution of this faint spectroscopic sample of z~6 galaxies. We find that the fraction of galaxies with little or no emission is similar to that at z~3, but that the z~6 population has a tail of sources with high rest frame equivalent widths. Possible expla...

  5. Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

    Directory of Open Access Journals (Sweden)

    Masato Furuhashi

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP. Sodium-glucose cotransporter 2 (SGLT2 inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level.Canagliflozin (100 mg/day was administered to type 2 diabetic patients (n = 39 for 12 weeks. Serum FABP4 level was measured before and after treatment.At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008, though elevation of FABP4 level after treatment was observed in 26 (66.7% out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044, HbA1c (r = 0.329, P = 0.044 and noradrenaline (r = 0.329, P = 0.041 but was not significantly correlated with change in adiposity or other variables.Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.UMIN-CTR Clinical Trial UMIN000018151.

  6. Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

    Science.gov (United States)

    Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji

    2016-01-01

    Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. UMIN-CTR Clinical Trial UMIN000018151.

  7. Hot Topics in Primary Care: Role of the Kidney and SGLT-2 Inhibition in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Miller, Kevin; Miller, Eden M

    2015-12-01

    SGLT-2 inhibitors provide a complementary mechanism of glucose lowering and can be used as monotherapy or in combination with other medications, including insulin. In addition to improved glycemic control, which generally is maintained over 2 years, SGLT-2 inhibitors provide reductions in body weight and systolic blood pressure. Increases in LDL-C and HDL-C also have been observed. A requirement for adequate renal function is a limitation in patients with CKD. A low incidence of hypoglycemia, ability to promote weight loss, and availability as an oral formulation diminish common barriers to glucose-lowering therapy.

  8. Syntheses of isotope-labeled SGLT2 inhibitor canagliflozin (JNJ-28431754).

    Science.gov (United States)

    Lin, Ronghui; Hoerr, David C; Weaner, Larry E; Salter, Rhys

    2017-08-18

    Canagliflozin (Invokana, JNJ-28431754) is an orally bioavailable and selective SGLT2 (subtype 2 sodium-glucose transport protein) inhibitor approved for the treatment of type 2 diabetes. Herein, we report the synthesis of (13) C and (14) C-labeled canagliflozin. Stable isotope-labeled [(13) C6 ]canagliflozin was synthesized in 4 steps starting from [(13) C6 ]-labeled glucose. The [(14) C]-Labeled canagliflozin was synthesized by incorporation of [(14) C] into the benzylic position between the thiophene and benzene rings of the compound. Detailed synthesis of the isotope-labeled compounds is reported. Copyright © 2017 John Wiley & Sons, Ltd.

  9. International Volcanological Field School in Kamchatka and Alaska: Experiencing Language, Culture, Environment, and Active Volcanoes

    Science.gov (United States)

    Eichelberger, J. C.; Gordeev, E.; Ivanov, B.; Izbekov, P.; Kasahara, M.; Melnikov, D.; Selyangin, O.; Vesna, Y.

    2003-12-01

    The Kamchatka State University of Education, University of Alaska Fairbanks, and Hokkaido University are developing an international field school focused on explosive volcanism of the North Pacific. An experimental first session was held on Mutnovsky and Gorely Volcanoes in Kamchatka during August 2003. Objectives of the school are to:(1) Acquaint students with the chemical and physical processes of explosive volcanism, through first-hand experience with some of the most spectacular volcanic features on Earth; (2) Expose students to different concepts and approaches to volcanology; (3) Expand students' ability to function in a harsh environment and to bridge barriers in language and culture; (4) Build long-lasting collaborations in research among students and in teaching and research among faculty in the North Pacific region. Both undergraduate and graduate students from Russia, the United States, and Japan participated. The school was based at a mountain hut situated between Gorely and Mutnovsky Volcanoes and accessible by all-terrain truck. Day trips were conducted to summit craters of both volcanoes, flank lava flows, fumarole fields, ignimbrite exposures, and a geothermal area and power plant. During the evenings and on days of bad weather, the school faculty conducted lectures on various topics of volcanology in either Russian or English, with translation. Although subjects were taught at the undergraduate level, lectures led to further discussion with more advanced students. Graduate students participated by describing their research activities to the undergraduates. A final session at a geophysical field station permitted demonstration of instrumentation and presentations requiring sophisticated graphics in more comfortable surroundings. Plans are underway to make this school an annual offering for academic credit in the Valley of Ten Thousand Smokes, Alaska and in Kamchatka. The course will be targeted at undergraduates with a strong interest in and

  10. Historical and paleo-tsunami deposits on Kamchatka, Russia: long-term chronologies and long-distance correlations

    Directory of Open Access Journals (Sweden)

    T. K. Pinegina

    2001-01-01

    Full Text Available Along the eastern coast of Kamchatka, at a number of localities, we have identified and attempted to assign ages to deposits of both historic and prehistoric (paleo- tsunamis. These deposits are dated and correlated using tephrochronology from Holocene marker tephra and local volcanic ash layers. Because the historical record of earthquakes and tsunamis on Kamchatka is so short, these investigations can make important contributions to evaluating tsunami hazards. Moreover, because even the historical record is spotty, our work helps add to and evaluate tsunami catalogues for Kamchatka. Furthermore, tsunami deposits provide a proxy record for large earthquakes and thus are important paleoseismological tools. The combined, preserved record of tsunami deposits and of numerous marker tephra on Kamchatka offers an unprecedented opportunity to study tsunami frequency. Using combined stratigraphic sections, we can examine both the average frequency of events for each locality, and also changes in frequency through time. Moreover, using key marker tephra as time lines, we can compare tsunami frequency and intensity records along the Kamchatka subduction zone. Preliminary results suggest real variations in frequency on a millennial time scale, with the period from about 0 to 1000 A.D. being particularly active at some localities.

  11. From bed topography to ice thickness: GlaRe, a GIS tool to reconstruct the surface of palaeoglaciers

    Science.gov (United States)

    Pellitero, Ramon; Rea, Brice; Spagnolo, Matteo; Bakke, Jostein; Ivy-Ochs, Susan; Frew, Craig; Hughes, Philip; Ribolini, Adriano; Renssen, Hans; Lukas, Sven

    2016-04-01

    We present GlaRe, A GIS tool that automatically reconstructs the 3D geometry for palaeoglaciers given the bed topography. This tool utilises a numerical approach and can work using a minimum of morphological evidence i.e. the position of the palaeoglacier front. The numerical approach is based on an iterative solution to the perfect plasticity assumption for ice rheology, explained in Benn and Hulton (2010). The tool can be run in ArcGIS 10.1 (ArcInfo license) and later updates and the toolset is written in Python code. The GlaRe toolbox presented in this paper implements a well-established approach for the determination of palaeoglacier equilibrium profiles. Significantly it permits users to quickly run multiple glacier reconstructions which were previously very laborious and time consuming (typically days for a single valley glacier). The implementation of GlaRe will facilitate the reconstruction of large numbers of palaeoglaciers which will provide opportunities for such research addressing at least two fundamental problems: 1. Investigation of the dynamics of palaeoglaciers. Glacier reconstructions are often based on a rigorous interpretation of glacial landforms but not always sufficient attention and/or time has been given to the actual reconstruction of the glacier surface, which is crucial for the calculation of palaeoglacier ELAs and subsequent derivation of quantitative palaeoclimatic data. 2. the ability to run large numbers of reconstructions and over much larger spatial areas provides an opportunity to undertake palaeoglaciers reconstructions across entire mountain, ranges, regions or even continents, allowing climatic gradients and atmospheric circulation patterns to be elucidated. The tool performance has been evaluated by comparing two extant glaciers, an icefield and a cirque/valley glacier from which the subglacial topography is known with a basic reconstruction using GlaRe. Results from the comparisons between extant glacier surfaces and modelled

  12. Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as Potential Antidiabetic Agents

    Science.gov (United States)

    Sharma, Mukesh C.; Sharma, Smita

    2014-01-01

    A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential antidiabetic agents was performed with thirty-three compounds. Comparison of the obtained results indicated the superiority of the genetic algorithm over the simulated annealing and stepwise forward-backward variable method for feature selection. The best 2D QSAR model showed satisfactory statistical parameters for the data set (r2 = 0.8499, q2 = 0.8267, and pred_r2 = 0.7729) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution position improves the inhibitory activity. The good predictive 3D-QSAR models by k-nearest neighbor (kNN) method for molecular field analysis (MFA) have cross-validated coefficient q2 value of 0.7663 and predicted r2 value of 0.7386. The results have showed that thiophenyl groups are necessary for activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced the biological activity. These studies are promising for the development of novel SGLT2 inhibitor, which may have potent antidiabetic activity. PMID:25574393

  13. Canagliflozin: A novel SGLT2 inhibitor for type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Shaveta Kaushal

    2014-01-01

    Full Text Available Diabetes Mellitus continues to be a major non- communicable disease with global burden of 366 million at present and projected to increase to 439 to 552 million by 2030, India being the hub of diabetes. Sodium glucose transporter 2 (SGLT2 inhibitors presents a new class of anti-diabetic drugs having an insulin-independent mechanism that offers a considerable advantage of increasing urinary glucose excretion without inducing hypoglycemia and promoting weight loss due to loss of 300 to 400kcal/day, Canagliflozin being the 1 st successful candidate of this group and became the first SGLT2 inhibitor to be FDA approved on March 29, 2013. In various clinical trials, it has shown promising results in controlling glycemia, causing weight loss, reducing systolic and diastolic BP and cardiovascular risk. There are some safety concerns associated with its use e.g. genital mycotic infections, increased urination, urinary tract infection and hyperkalemia, which need to be carefully addressed while using this drug.

  14. Canagliflozin: A Novel SGLT2 Inhibitor for Type 2 Diabetes Mellitus

    Science.gov (United States)

    Kaushal, Shaveta; Singh, Harmanjit; Thangaraju, Pugazhenthan; Singh, Jasbir

    2014-01-01

    Diabetes Mellitus continues to be a major non- communicable disease with global burden of 366 million at present and projected to increase to 439 to 552 million by 2030, India being the hub of diabetes. Sodium glucose transporter 2 (SGLT2) inhibitors presents a new class of anti-diabetic drugs having an insulin-independent mechanism that offers a considerable advantage of increasing urinary glucose excretion without inducing hypoglycemia and promoting weight loss due to loss of 300 to 400kcal/day, Canagliflozin being the 1st successful candidate of this group and became the first SGLT2 inhibitor to be FDA approved on March 29, 2013. In various clinical trials, it has shown promising results in controlling glycemia, causing weight loss, reducing systolic and diastolic BP and cardiovascular risk. There are some safety concerns associated with its use e.g. genital mycotic infections, increased urination, urinary tract infection and hyperkalemia, which need to be carefully addressed while using this drug. PMID:24741548

  15. Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as Potential Antidiabetic Agents

    Directory of Open Access Journals (Sweden)

    Mukesh C. Sharma

    2014-01-01

    Full Text Available A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential antidiabetic agents was performed with thirty-three compounds. Comparison of the obtained results indicated the superiority of the genetic algorithm over the simulated annealing and stepwise forward-backward variable method for feature selection. The best 2D QSAR model showed satisfactory statistical parameters for the data set (r2=0.8499, q2=0.8267, and pred_r2=0.7729 with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution position improves the inhibitory activity. The good predictive 3D-QSAR models by k-nearest neighbor (kNN method for molecular field analysis (MFA have cross-validated coefficient q2 value of 0.7663 and predicted r2 value of 0.7386. The results have showed that thiophenyl groups are necessary for activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced the biological activity. These studies are promising for the development of novel SGLT2 inhibitor, which may have potent antidiabetic activity.

  16. Comparison of seismotomographic and thermogravitational models with distribution of the seismotectonic deformation orientations for Kamchatka region

    Science.gov (United States)

    Bushenkova, Natalia; Kuchay, Olga; Chervov, Victor; Koulakov, Ivan

    2016-04-01

    In this study we reveal the relationships between the structure of the lithosphere, the distribution of convective flows in the upper mantle and the character of seismotectonic deformations (STD) that is especially important for regions of active continental margins. We present a comprehensive analysis of seismotomographic and thermogravitational models together with the distribution of the STD principal axes orientations for the Kamchatka region, where crustal displacements are accompanied with seismic and volcanic activity. Our previous results have shown that: the variations of the lithosphere thickness significantly affect the structure of convective flows in the upper mantle [Chervov, Chernykh, 2014]; the pattern of these flows, in turn, correlate with the distribution and the orientations of STD principal axes (for the Altai-Sayan region with surrounding areas [Bushenkova, at al., 2014]). Based on the upper mantle seismic tomography model beneath Kamchatka and adjacent regions by Koulakov et al. (2011) and taking into account the variations of the lithosphere structure, we have calculated a numerical 3D model of thermal convection in the upper mantle. Also, we have estimated the distribution of orientations of the STD principal axes. We used the focal mechanisms of 511 earthquakes occurred in the period of 1976-2015 [www.isc.ac.uk/iscbulletin/search/fmechanisms] in the Kamchatka region. These focal mechanisms were transformed to the 3D STD distributions based on the Riznichenko's method (1985). In this case, the STD was determined as an average seismic moment tensor of all earthquakes in a unit volume for the selected time. We found that the STD principal axes distribution is inherited for different depth layers along the entire eastern coast of Kamchatka. Abrupt changes in the orientation of the principal axes of elongation and shortening, and a change of the direction of their dipping are observed in area zone of 53.0- 54.50 N. This zone coincides with an

  17. SGLT2 inhibitors – an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin

    Science.gov (United States)

    Seufert, Jochen

    2015-01-01

    Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM) are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These “concomitant effects” are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand the treatment options for patients at every stage of T2DM. The efficacy and tolerability of canagliflozin have been tested in an extensive clinical trial program

  18. SGLT2 inhibitors - an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin.

    Science.gov (United States)

    Seufert, Jochen

    2015-01-01

    Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM) are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These "concomitant effects" are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand the treatment options for patients at every stage of T2DM. The efficacy and tolerability of canagliflozin have been tested in an extensive clinical trial program

  19. Mantle temperature control on composition of arc magmas along the Central Kamchatka Depression

    Science.gov (United States)

    Portnyagin, Maxim; Constantin Manea, Vlad

    2008-07-01

    Abundant volcanism in the Central Kamchatka Depression (CKD)adjacent to the Kamchatka-Aleutian Arc junction occurswhere the Pacific slab edge is subducting beneath Kamchatka.Here we summarize published data on CKD rocks and demonstratea systematic south-to-north change of their compositions frommoderately fractionated basalt-andesite tholeiitic series tohighly fractionated basalt-rhyolite calc-alkaline series includinghigh-magnesian andesites near the slab edge. Localized slabmelting at the slab edge cannot explain these regional geochemicalvariations. Instead, we propose that the thermal state of themantle wedge can be the key factor governing the compositionof CKD magmas. We integrate the results from petrology and numericmodeling to demonstrate the northward decrease of the mantlewedge temperatures beneath CKD volcanoes, which correlates withdecreasing slab dip, length of mantle columns, and magma flux.We envision two petrogenetic models, which relate the compositionof erupted magmas to the subduction parameters beneath the CKD.The first model suggests that mantle temperature governs melt-peridotiteequilibria and favors generation of andesitic primary meltsin cold mantle regions above the shallowly subducting Pacificslab edge. Alternatively, mantle temperature may control magmaticproductivity along the CKD, which decreases sharply toward theslab edge and thus allows more extensive magma fractionationdeeper in the crust and mixing of highly evolved and mantle-derivedmagmas to generate Si-rich "primitive" magmas. These resultspoint to a possible casual link between deep mantle and shallowcrustal magmatic processes. Similar effects of mantle temperatureon the composition and productivity of arc magmatism are expectedelsewhere, particularly in volcanic regions associated withsignificant slab dip variation along the arc.

  20. Volcanic-glacial interactions: GIS applications to the assessment of lahar hazards (case study of Kamchatka)

    OpenAIRE

    2014-01-01

    On the Kamchatka peninsula, lahars or volcanogenic mudflows arise as a result of intensive snow melting caused by incandescent material ejected by volcanoes onto the surface. Such flows carrying volcanic ash and cinders together with lava fragments and blocks move with a speed up to 70 km/h that can result in significant destructions and even human victims. Formation of such water flows is possible during the whole year.Large-scale GIS «Hazards of lahars (volcanogenic mudflows)» has been deve...

  1. SGLT-2 inhibitors and their potential in the treatment of diabetes

    Directory of Open Access Journals (Sweden)

    Rosenwasser RF

    2013-11-01

    Full Text Available Rebecca F Rosenwasser,1 Senan Sultan,2 David Sutton,2 Rushab Choksi,1 Benjamin J Epstein3 1East Coast Institute for Research, Jacksonville, FL, USA; 2Northeast Florida Endocrine and Diabetes Associates, Jacksonville, FL, USA; 3Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA Abstract: Diabetes remains a burgeoning global problem, necessitating ongoing efforts on the part of pharmaceutical and device manufacturers, patients, and society to curb the frightening trends in morbidity and mortality attributable to the malady. Since 1835 when phlorizin was discovered, sodium glucose co-transporter 2 (SGLT-2 inhibitors have rested tantalizingly on the horizon, promising a more physiological approach to glucose control. These agents lower glucose by enhancing its excretion by blocking reabsorption in the renal tubules, thus eliminating glucose from the body along with the molecules' attendant effects on caloric balance, plasma osmolality, and lipids. Consequently, SGLT-2 inhibitors improve glucose control to an extent comparable to other hypoglycemic agents while simultaneously reducing body weight, blood pressure, and cholesterol – an admirable portfolio. One agent, canagliflozin, has recently been approved by the US Food and Drug Administration (FDA and two other agents have progressed through Phase III trials, including dapagliflozin and empagliflozin. Collectively, when used as monotherapy, these agents have demonstrated reductions in hemoglobin A1c (HbA1c, body weight, and blood pressure of –0.34% to –1.03%, –2.0 to -3.4 kg, and –1.7 to –6.4 mmHg/–0.3 to –2.6 mmHg (systolic blood pressure/diastolic blood pressure, respectively. SGLT-2 inhibitors have been well tolerated, with hypoglycemia (0.9% to 4.3% occurring infrequently in clinical trials. Safety signals related to breast and bladder cancer have arisen with dapagliflozin, though these are unsubstantiated

  2. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2015-01-01

    Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin

  3. Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin

    Science.gov (United States)

    Bader, Nimrah; Mirza, Lubna

    2016-01-01

    We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin. The clinical history, physical examination findings and laboratory values are described. Other causes of acidosis such as salicylate toxicity or alcohol intoxication were excluded. Ketoacidosis resolved after increasing dextrose and insulin doses supporting the hypothesis that SGLT-2 inhibitors may lead to hypoinsulinemia. Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. We recommend reserving SGLT2 inhibitor therapy to type 2 diabetics, discontinuing medication and treating patients presenting with ketoacidosis due to SGLT-2 inhibitors with higher concentrations of dextrose with appropriate doses of insulin to help resolve acidosis. PMID:27375734

  4. A New Choice for Combination Therapy with Insulin:Adding SGLT-2 Inhibitors to Basal Insulin%胰岛素联合治疗的新选择--基础胰岛素+SGLT-2抑制剂

    Institute of Scientific and Technical Information of China (English)

    郭琳; 李强

    2016-01-01

    Mechanism complementary, simple and effective treatment is important for decreasing the blood glucose level of type 2 diabetes patient. Aglycone SGLT2 inhibitors with competitive combined glucose transporters, effectively restrain the activity of renal proximal convoluted tubules SGLT-2, reduce renal tubular epithelial cells reabsorption of glucose, increase the excretion of urine glucose, thereby reducing the blood sugar level. Because the mechanism is not dependent on insulin secretion and insulin action of unique mechanism of action of SGLT2 inhibitor is especially suitable for as a choice for insulin combined treatment drugs. This paper reviews the basic evidence for insulin combined SGLT-2 inhibitor treatment in the following respects:starting time, patients and safety, to point out the combination therapy in the treatment of type 2 diabetes will have good application prospects.%机制互补且简单有效的治疗方案更利于2型糖尿病患者的血糖管理。S G LT-2抑制剂的糖苷配基通过与葡萄糖竞争性结合转运蛋白,有效抑制肾脏近曲小管S G LT-2的活性,减少肾小管上皮细胞对葡萄糖的重吸收,使尿葡萄糖排泄增加,从而降低血糖水平。由于其不依赖于胰岛素分泌和胰岛素作用的独特的作用机制,SGLT-2抑制剂特别适合作为胰岛素联合治疗的选择药物。本文综述了基础胰岛素联合SGLT-2抑制剂治疗的循证证据、起始时机、适应人群和安全性,指出这种联合治疗在2型糖尿病的治疗中将拥有良好的应用前景。

  5. Role of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Solini, Anna

    2016-12-01

    In the last ten years, knowledge on pathophysiology of type 2 diabetes (T2DM) has significantly increased, with multiple failures (decreased incretin effect, increased lipolysis, increased glucagon secretion, neurotransmitters dysfunction) recognized as important contributors, together with decreased insulin secretion and reduced peripheral glucose uptake. As a consequence, the pharmacologic therapy of T2DM has been progressively enriched by several novel classes of drugs, trying to overcome these defects. The last, intriguing compounds come into the market are SGLT2 inhibitors, framing the kidney in a different scenario, not as site of a harmful disease complication, but rather as the means to correct hyperglycemia and fight the disease. This review aims to offer a short, updated overview of the role of these compounds in the treatment of T2DM, focusing on efficacy, ancillary albeit relevant clinical effects, safety, potential cardiovascular protection, positioning in common therapeutic algorithms.

  6. Sodium-dependent reorganization of the sugar-binding site of SGLT1

    DEFF Research Database (Denmark)

    Hirayama, Bruce A; Loo, Donald D F; Díez-Sampedro, Ana

    2007-01-01

    of interactions between mutated residues and hydroxyls on the pyranose ring was assessed by comparing the affinities of deoxy sugars to those of glucose. We determined conformation-dependent accessibility to the mutated residues by both a traditional substituted cysteine accessibility method (SCAM) and a new......The sodium-dependent glucose cotransporter SGLT1 undergoes a series of voltage- and ligand-induced conformational changes that underlie the cotransport mechanism. In this study we describe how the binding of external Na changes the conformation of the sugar-binding domain, exposing residues...... that are involved in sugar recognition to the external environment. We constructed 15 individual Cys mutants in the four transmembrane helices (TMHs) that form the sugar binding and translocation domain. Each mutant was functionally characterized for transport kinetics and substrate specificity. Identification...

  7. Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin

    OpenAIRE

    Bader, Nimrah; Mirza, Lubna

    2016-01-01

    We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin. The clinical history, physical examination findings and laboratory values are described. Other causes of acidosis such as salicylate toxicity or alcohol intoxication were excluded. Ketoacidosis resolved after increasing dextrose and insulin doses supporting the hypothesis that SGLT-2 inhibitors may lead to hypoin...

  8. Genetic variation among major sockeye salmon populations in Kamchatka peninsula inferred from SNP and microsatellite DNA analyses

    DEFF Research Database (Denmark)

    Khrustaleva, A.M.; Limborg, Morten; Seeb, J. E.

    of the two northern Kamchatka rivers (Palana River and Pakhacha River) differed significantly from the other populations studied. We estimated the efficiency for both types of markers for individual assignment of fish taken in mixtures. Accuracy was generally higher for assignment with SNP data; however...

  9. Positive geothermal anomalies in oceanic crust of Cretaceous age offshore Kamchatka

    Directory of Open Access Journals (Sweden)

    G. Delisle

    2011-09-01

    Full Text Available Heat flow measurements were carried out in 2009 offshore Kamchatka during the German-Russian joint-expedition KALMAR. An area with elevated heat flow in oceanic crust of Cretaceous age – detected ~30 yr ago in the course of several Russian heat flow surveys – was revisited. One previous interpretation postulated anomalous lithospheric conditions or a connection between a postulated mantle plume at great depth (>200 km as the source for the observed high heat flow. However, the positive heat flow anomaly – as our bathymetric data show – is closely associated with the fragmentation of the western flank of the Meiji Seamount into a horst and graben structure initiated during descent of the oceanic crust into the subduction zone offshore Kamchatka. This paper offers an alternative interpretation, which connects high heat flow primarily with natural convection of fluids in the fragmented rock mass and, as a potential additional factor, high rates of erosion, for which evidence is available from our collected bathymetric image. Given high erosion rates, warm rock material at depth rises to nearer the sea floor, where it cools and causes temporary elevated heat flow.

  10. Oceanic, island arc, and back-arc remnants into eastern Kamchatka accretionary complexes

    Energy Technology Data Exchange (ETDEWEB)

    Fedorchuk, A.V.; Vishnevskaya, V.S.; Izvekov, I.N. (Institute of the Lithosphere, Moscow (USSR))

    1990-06-01

    The Kamchatsky Mts. accretionary complex in the Eastern Kamchatka orogenic belt was studied for identification of the oceanic and suprasubduction components into accretionary wedges. That complex is divided into two tectonic units. The Lower unit is formed sedimentary and tectonic melanges containing arc-related components (Late Senonian volcaniclastics and boninitic gabbro) and oceanic fragments (Fe-Ti-tholeiites, ocean island basalts, and pelagic sediments of Valanginian to Turonian age). The Upper unit consists of ductile deformed oceanic cumulates from troctolites to Fe-Ti-gabbro, 151 to 172 Ma, which are intruded MORB-like diabases with suprasubduction characteristics, 122 to 141 Ma, and are overlain by basalts similar to latter. The Lower and Upper units are separated by a SW-dipping thrust, which is related by an ophiolitoclastic olistostrome of Late Campanian to Early Maestrichtian age. Both units are covered by Paleocene authoclastic deposits. They are all thrusted over the early Neogene island arc complex, 16 to 20 Ma. The Lower unit of the Kamchatsky Mys accretionary complex was originated in a shear zone between a Late Cretaceous island arc and an Early Cretaceous oceanic plate. The Upper unit represents a Jurassic oceanic remnant that formed a basement of Early Cretaceous back-arc or fore-arc basin. Both units were superposed in the latest Cretaceous. The Kamchatsky Mys accretionary complex was emplaced into the Eastern Kamchatka orogenic belt during late Neogene by collision of the early Neogene island arc.

  11. Multiproxy records of climate variability for Kamchatka for the past 400 years

    Directory of Open Access Journals (Sweden)

    O. Solomina

    2006-11-01

    Full Text Available Tree rings, ice cores and glacial geologic histories for the past several centuries offer an opportunity to characterize climate variability and to identify the key climate parameters forcing glacier expansions. A newly developed larch ring-width chronology is presented for Kamchatka that is sensitive to past summer temperature variability. This record provides the basis to compare with other proxy records of inferred temperature and precipitation change from ice core and glacier records, and to characterize climate for the region over the past 400 years. Individual low growth years in the larch record are associated with several known and proposed volcanic events that have been observed in other proxy records from the Northern Hemisphere. Comparison of the tree-rings with an ice core record of melt feature index for Kamchatka's Ushkovsky volcano confirms a 1–3 year dating accuracy for this ice core series over the late 18th to 20th centuries. Decadal variations of low summer temperatures (tree-ring record and high annual precipitation (ice core record are broadly consistent with intervals of positive mass balance measured and estimated at several glaciers, and with moraine building, provides a basis to interpret geologic glacier records.

  12. Comparative estimates of Kamchatka territory development in the context of northern territories of foreign countries

    Directory of Open Access Journals (Sweden)

    Andrey Gennadyevich Shelomentsev

    2014-06-01

    Full Text Available The article promotes an approach to assess the prospects of regional development on the basis of the synthesis of comparative and historical methods of research. According to the authors, the comparative analysis of the similar functioning of the socio-economic systems forms deeper understanding what part factors and methods of state regulation play in regional development, and also their place in socio-economic and geopolitical space. The object of the research is Kamchatka territory as the region playing strategically important role in socio-economic development of Russia and also northern territories of the other countries comparable with Kamchatka on the bass if environmental conditions such as Iceland, Greenland, USA (Alaska, Canada (Yukon, and Japan (Hokkaido. On the basis of allocation of the general signs of regional socio-economic systems and creation of the regional development models forming the basis for comparative estimates, the article analyses the territories, which are comparable on the base of climatic, geographic, economic, geopolitical conditions, but thus significantly different due to the level of economic familiarity. The generalization of the extensive statistical material characterizing various spheres of activity at these territories, including branch structure of the economy, its infrastructure security, demographic situation, the budgetary and financial sphere are given. It allows defining the crucial features of the regional economy development models. In the conclusion, the authors emphasize that ignoring of the essential relations among the regional system elements and internal and external factors deprives a research of historical and socio-economic basis.

  13. RECREATION MONITORING OF RESOURCE CONDITIONS IN THE KRONOTSKY STATE NATURAL BIOSPHERE PRESERVE (KAMCHATKA: AN INITIAL ASSESSMENT

    Directory of Open Access Journals (Sweden)

    Anna Zavadskaya

    2011-01-01

    Full Text Available The paper describes assessment and monitoring program which has been designed and initiated for monitoring recreational impacts in some wildernesses areas of Kamchatka. The framework of the recreational assessment was tested through its application in a case study conducted during the summer 2008 in the Kronotsky State Natural Biosphere Preserve (the Kamchatka peninsula, Russia. The overall objective of the case study was to assess the existing campsite and trail recreation impacts and to establish a network of key sites for the subsequent long-term impact monitoring. The detailed assessment of different components of natural complexes of the Kronotsky State Natural Preserve and the obtained maps of their ecological conditions showed that some sites had been highly disturbed. The results of these works have given rise to a concern that the intensive use of these areas would make an unacceptable impact on the nature. Findings of our initial work corroborate the importance of founding wilderness management programs on knowledge about the trail and campsite impacts and emphasize the necessity of adopting the recreational assessment and monitoring framework to the practice of decision-making.

  14. Geophysical Observatory in Kamchatka region for monitoring of phenomena connected with seismic activity

    Directory of Open Access Journals (Sweden)

    S. Uyeda

    2001-01-01

    Full Text Available Regular monitoring of some geophysical parameters in association with seismicity has been carried out since last year at the Japan-Russian Complex Geophysical Observatory in the Kamchatka region. This observatory was organized in connection with the ISTC project in Russia and was motivated by the results of the FRONTIER/RIKEN and FRONTIER/NASDA research projects in Japan. The main purpose of the observations is to investigate the electromagnetic and acoustic phenomena induced by the lithosphere processes (especially by seismic activity. The seismicity of the Kamchatka area is analyzed and a description of the observatory equipment is presented. At present, the activity of the observatory includes the seismic (frequency range ∆F = 0.5 – 40 Hz and meteorological recordings, together with seismo-acoustic (∆F = 30 – 1000 Hz and electromagnetic observations: three-component magnetic ULF variations ( ∆F = 0.003 – 30 Hz, three-component electric potential variations ( ∆F 1.0 Hz, and VLF transmitter’s signal perturbations ( ∆F ~ 10 – 40 kHz.

  15. Occurrence and genetic typing of infectious hematopoietic necrosis virus in Kamchatka, Russia.

    Science.gov (United States)

    Rudakova, Svetlana L; Kurath, Gael; Bochkova, Elena V

    2007-03-29

    Infectious hematopoietic necrosis virus (IHNV) is a well known rhabdoviral pathogen of salmonid fish in North America that has become established in Asia and Europe. On the Pacific coast of Russia, IHNV was first detected in hatchery sockeye from the Kamchatka Peninsula in 2001. Results of virological examinations of over 10,000 wild and cultured salmonid fish from Kamchatka during 1996 to 2005 revealed IHNV in several sockeye salmon Oncorhynchus nerka populations. The virus was isolated from spawning adults and from juveniles undergoing epidemics in both hatchery and wild sockeye populations from the Bolshaya watershed. No virus was detected in 2 other watersheds, or in species other than sockeye salmon. Genetic typing of 8 virus isolates by sequence analysis of partial glycoprotein and nucleocapsid genes revealed that they were genetically homogeneous and fell within the U genogroup of IHNV. In phylogenetic analyses, the Russian IHNV sequences were indistinguishable from the sequences of North American U genogroup isolates that occur throughout Alaska, British Columbia, Washington, and Oregon. The high similarity, and in some cases identity, between Russian and North American IHNV isolates suggests virus transmission or exposure to a common viral reservoir in the North Pacific Ocean.

  16. SGLT2 inhibitors – an insulin-independent therapeutic approach for treatment of type 2 diabetes: focus on canagliflozin

    Directory of Open Access Journals (Sweden)

    Seufert J

    2015-11-01

    Full Text Available Jochen SeufertDepartment of Endocrinology and Diabetology, Clinic for Internal Medicine II, Freiburg University Hospital, Freiburg, GermanyAbstract: Despite the availability of a great variety of medications, a significant proportion of people with type 2 diabetes mellitus (T2DM are not able to achieve or maintain adequate glycemic control. Beyond improved glucose control, novel treatments would ideally provide a reduction of cardiovascular risk, with a favorable impact on excess weight, and a low intrinsic hypoglycemia risk, as well as a synergistic mechanism of action for broad combination therapy. With the development of sodium glucose cotransporter 2 (SGLT2 inhibitors, an antidiabetic pharmacologic option has recently become available that comes close to meeting these requirements. For the first time, SGLT2 inhibitors offer a therapeutic approach acting directly on the kidneys without requiring insulin secretion or action. Canagliflozin, dapagliflozin, and empagliflozin are the SGLT2 inhibitors approved to date. Taken once a day, these medications can be combined with all other antidiabetic medications including insulin, due to their insulin-independent mechanism of action, with only a minimal risk of hypoglycemia. SGLT2 inhibitors provide additional reductions in body weight and blood pressure due to the therapeutically induced excretion of glucose and sodium through the kidneys. These "concomitant effects" are particularly interesting with regard to the increased cardiovascular risk in T2DM. In many cases, T2DM treatment requires a multidimensional approach where the treatment goals have to be adapted to the individual patient. While there is a consensus on the use of metformin as a first-line drug therapy, various antidiabetics are used for treatment intensification. New mechanisms of action like that of SGLT2 inhibitors such as canagliflozin, which can be used both in early and late stages of diabetes, are a welcome addition to expand

  17. Simulated annealing reveals the kinetic activity of SGLT1, a member of the LeuT structural family.

    Science.gov (United States)

    Longpré, Jean-Philippe; Sasseville, Louis J; Lapointe, Jean-Yves

    2012-10-01

    The Na(+)/glucose cotransporter (SGLT1) is the archetype of membrane proteins that use the electrochemical Na(+) gradient to drive uphill transport of a substrate. The crystal structure recently obtained for vSGLT strongly suggests that SGLT1 adopts the inverted repeat fold of the LeuT structural family for which several crystal structures are now available. What is largely missing is an accurate view of the rates at which SGLT1 transits between its different conformational states. In the present study, we used simulated annealing to analyze a large set of steady-state and pre-steady-state currents measured for human SGLT1 at different membrane potentials, and in the presence of different Na(+) and α-methyl-d-glucose (αMG) concentrations. The simplest kinetic model that could accurately reproduce the time course of the measured currents (down to the 2 ms time range) is a seven-state model (C(1) to C(7)) where the binding of the two Na(+) ions (C(4)→C(5)) is highly cooperative. In the forward direction (Na(+)/glucose influx), the model is characterized by two slow, electroneutral conformational changes (59 and 100 s(-1)) which represent reorientation of the free and of the fully loaded carrier between inside-facing and outside-facing conformations. From the inward-facing (C(1)) to the outward-facing Na-bound configuration (C(5)), 1.3 negative elementary charges are moved outward. Although extracellular glucose binding (C(5)→C(6)) is electroneutral, the next step (C(6)→C(7)) carries 0.7 positive charges inside the cell. Alignment of the seven-state model with a generalized model suggested by the structural data of the LeuT fold family suggests that electrogenic steps are associated with the movement of the so-called thin gates on each side of the substrate binding site. To our knowledge, this is the first model that can quantitatively describe the behavior of SGLT1 down to the 2 ms time domain. The model is highly symmetrical and in good agreement with the

  18. The influence of volcanic activity on suspended sediment yield of rivers (Kamchatka, Russia)

    Science.gov (United States)

    Kuksina, Ludmila

    2014-05-01

    Kamchatka is specific region of suspended sediment yield formation. This fact is particularly connected with active volcanism in the territory. The influence of volcanism on suspended sediment yield characteristics was studied in various time scales - into-diurnal, seasonal and long-term ones. The study of spatial variability of these characteristics reveals the maximum values characterize river basins in zones of strong impact of volcanic eruptions, especially, rivers draining slopes and flanks of active volcanoes. Into-diurnal fluctuations were studied for rivers in volcanic areas. They are characterized by synchronous changes of water flow and turbidity. It's determined by weak erosion-preventive capacity of friable volcanic deposits and big slopes of channels (2.5 - 6.0 %). The maximum of water flow and turbidity is observed at the period between 12 and 6 pm. The air temperature reaches its maximum by that time, and consequently, the intensity of snow melting is also maximum one. The maximum of turbidity advances diurnal maximum of water flow a little, and it's connected with the features of flood wave moving and consecutive maximums of slopes, turbidity, velocity, water flow, and capacity of stream during flush. Into-diurnal fluctuations are determined by complicated and little-studied processes of mass transfer between stream and channel deposits. These processes are connected with into-diurnal changes of stream capacity and water transfer between channel and underflow. As the result water regime is pulsating. Rivers under the influence of volcanic eruptions transport the main amount of sediments during floods which usually occur in summer-autumn period (in the absence of extreme floods in winter-spring period during volcanic eruptions). Combination of maximum snow supply, significant precipitation in warm part of the year and weak erosion-preventive capacity of friable volcanic deposits on volcanoes slopes is the reason of the most intense erosion in this

  19. Research progress of SGLT-2 inhibitors --drugs in treatment of diabetes type 2%2型糖尿病治疗药物--SGLT-2抑制剂研究进展

    Institute of Scientific and Technical Information of China (English)

    赵晓娟; 赵永红; 刘秀菊

    2015-01-01

    Blood glucose levels lowered by sodium-glucose cotransporter 2 (SGLT-2) inhibitor that could reduced reabsorption of glucose by human kidney, increased urine glucose excretion, which was a new way to treat diabetes type 2. In recent years, SGLT-2 inhibitor has also been published to treat patients with diabetes type 2, and brought new hope to them.%钠-葡萄糖协同转运蛋白-2抑制剂通过减少人体肾脏对葡萄糖的重吸收,增加尿糖的排泄,达到降低血液中葡萄糖水平的目的,从而成为治疗2型糖尿病的新途径。近年来,SGLT-2抑制剂类药物也不断的问世,给2型糖尿病患者的治疗带来了新的希望。

  20. SY 10-2 THE ROLE OF SGLT2 INHIBITORS IN THE MANAGEMENT OF T2DM.

    Science.gov (United States)

    Jung, Chang Hee

    2016-09-01

    Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder and is a major global public health problem with a rapidly increasing prevalence. Although a wide range of pharmacotherapy for glycemic control in T2DM is now available, management of T2DM remains complex and challenging. The kidneys contribute to glucose homeostasis primarily by the glucose reabsorption from the glomerular filtrate. The sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of antidiabetes agents that inhibit glucose absorption from the kidney tubule independent of insulin, offer a unique opportunity to improve outcomes for patient with T2DM.In this session, I'd like to discuss several topics regarding SGLT2 inhibitors including their glucose lowering effects, recently issued adverse effects and long-term cardiovascular benefits from the perspectives of endocrinologist.

  1. Involvement of functional groups on the surface of carboxyl group-terminated polyamidoamine dendrimers bearing arbutin in inhibition of Na⁺/glucose cotransporter 1 (SGLT1)-mediated D-glucose uptake.

    Science.gov (United States)

    Sakuma, Shinji; Kanamitsu, Shun; Teraoka, Yumi; Masaoka, Yoshie; Kataoka, Makoto; Yamashita, Shinji; Shirasaka, Yoshiyuki; Tamai, Ikumi; Muraoka, Masahiro; Nakatsuji, Yohji; Kida, Toshiyuki; Akashi, Mitsuru

    2012-04-01

    A carboxyl group-terminated polyamidoamine dendrimer (generation: 3.0) bearing arbutin, which is a substrate of Na⁺/glucose cotransporter 1 (SGLT1), via a nonbiodegradable ω-amino triethylene glycol linker (PAMAM-ARB), inhibits SGLT1-mediated D-glucose uptake, as does phloridzin, which is a typical SGLT1 inhibitor. Here, since our previous research revealed that the activity of arbutin was dramatically improved through conjugation with the dendrimer, we examined the involvement of functional groups on the dendrimer surface in inhibition of SGLT1-mediated D-glucose uptake. PAMAM-ARB, with a 6.25% arbutin content, inhibited in vitro D-glucose uptake most strongly; the inhibitory effect decreased as the arbutin content increased. In vitro experiments using arbutin-free original dendrimers indicated that dendrimer-derived carboxyl groups actively participated in SGLT1 inhibition. However, the inhibitory effect was much less than that of PAMAM-ARB and was equal to that of glucose moiety-free PAMAM-ARB. Data supported that the glucose moiety of arbutin was essential for the high activity of PAMAM-ARB in SGLT1 inhibition. Analysis of the balance of each domain further suggested that carboxyl groups anchored PAMAM-ARB to SGLT1, and the subsequent binding of arbutin-derived glucose moieties to the target sites on SGLT1 resulted in strong inhibition of SGLT1-mediated D-glucose uptake.

  2. The flavanone homoeriodictyol increases SGLT-1-mediated glucose uptake but decreases serotonin release in differentiated Caco-2 cells

    Science.gov (United States)

    Hoi, Julia Katharina; Holik, Ann-Katrin; Geissler, Katrin; Hans, Joachim; Friedl, Barbara; Liszt, Kathrin; Krammer, Gerhard E.; Ley, Jakob P.; Somoza, Veronika

    2017-01-01

    Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM. The glucose uptake stimulating effect was sensitive to phloridzin, but not to phloretin, indicating an involvement of the sodium-coupled glucose transporter SGLT-1, but not of sodium-independent glucose transporters (GLUT). In addition, in contrast to the increased extracellular serotonin levels by stimulation with 500 mM D-(+)-glucose, treatment with 100 μM homoeriodictyol decreased serotonin release by –48.8 ± 7.57% in Caco-2 cells via a phloridzin-sensitive signaling pathway. Extracellular serotonin levels were also reduced by –57.1 ± 5.43% after application of 0.01 μM homoeriodictyol to human neural SH-SY5Y cells. In conclusion, we demonstrate that homoeriodictyol affects both the glucose metabolism and the serotonin system in Caco-2 cells via a SGLT-1-meditated pathway. Furthermore, the results presented here support the usage of Caco-2 cells as a model for peripheral serotonin release. Further investigations may address the value of homoeriodictyol in the treatment of anorexia and malnutrition through the targeting of SGLT-1. PMID:28192456

  3. Sodium Glucose Co-transporter Type 2 (SGLT2) Inhibitors: Targeting the Kidney to Improve Glycemic Control in Diabetes Mellitus

    OpenAIRE

    Bays, Harold

    2013-01-01

    Although hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes mellitus (T2DM), many patients experience sub-optimal glycemic control. Current glucose-lowering agents involve the targeting of various body organs. Sodium glucose co-transporter type 2 (SGLT2) inhibitors target the kidney, reduce renal glucose reabsorption, and increase urinary glucose elimination, thus lowering glucose blood levels. This review examines some of the key efficacy and safety d...

  4. Volcanic-glacial interactions: GIS applications to the assessment of lahar hazards (case study of Kamchatka

    Directory of Open Access Journals (Sweden)

    Ya. D. Muraviev

    2014-01-01

    Full Text Available On the Kamchatka peninsula, lahars or volcanogenic mudflows arise as a result of intensive snow melting caused by incandescent material ejected by volcanoes onto the surface. Such flows carrying volcanic ash and cinders together with lava fragments and blocks move with a speed up to 70 km/h that can result in significant destructions and even human victims. Formation of such water flows is possible during the whole year.Large-scale GIS «Hazards of lahars (volcanogenic mudflows» has been developed for some volcano group as well as for individual volcanoes on the peninsula in framework of the GIS «Volcanic hazard of the Kuril-Kamchatka island arc». Main components of this database are the following: physic-geographical information on region of active volcanism and adjacent areas, on human settlements; data on the mudflow activity; data on distribution of the snow and ice reserves. This database is aimed at mapping of surrounding territories and estimating a hazard of lahars.For illustration the paper presents a map of the lahar hazards, results of calculations of the distances of ejects and maximal area of ejected material spreading in dependence on a character and power of an eruption. In future we plan to perform operational calculations of maximal possible volumes of such flows and areas of their spreading. The calculations will be made on the basis of the GIS «Volcanic hazard of the Kuril-Kamchatka island arc».A volume of hard material carried by lahars onto slopes and down to foot of the Kluchevskaya volcanic massif is estimated on the basis of data on the snow and ice reserves on volcano slopes. On the average for many years, the snow accumulation in zones of the mudflow formations their volume often reaches 15–17 millions of cubic meters. Depending on the snowfall activity in different years this value may vary within 50% relative to the norm. Further on, calculations of maximal possible volume of such flows will be performed in a

  5. Preliminary evaluation of discomfort glare from organic light-emitting diode and edge-lit light-emitting diode lighting panels.

    Science.gov (United States)

    Mou, Xi; Freyssinier, Jean Paul; Narendran, Nadarajah; Bullough, John D

    2017-05-01

    The organic light-emitting diode (OLED) is an area light source, and its primary competing technology is the edge-lit light-emitting diode (LED) panel. Both technologies are similar in shape and appearance, but there is little understanding of how people perceive discomfort glare (DG) from area sources. The objective of this study was to evaluate the DG of these two technologies under similar operating conditions. Additionally, two existing DG models were compared to evaluate the correlation between predicted values and observed values. In an earlier study, we found no statistically significant difference in human response in terms of DG between OLED and edge-lit LED panels when the two sources produced the same luminous stimulus. The range of testing stimulus was expanded to test different panel luminances at three background illuminations. The results showed no difference in perceived glare between the panels, and, as the background illumination increased, the perceived glare decreased. In other words, both appeared equally glary beyond a certain luminance and background illumination. We then compared two existing glare models with the observed values and found that one model showed a good estimation of how humans perceive DG. That model was further modified to increase its power.

  6. Preliminary evaluation of discomfort glare from organic light-emitting diode and edge-lit light-emitting diode lighting panels

    Science.gov (United States)

    Mou, Xi; Freyssinier, Jean Paul; Narendran, Nadarajah; Bullough, John D.

    2017-05-01

    The organic light-emitting diode (OLED) is an area light source, and its primary competing technology is the edge-lit light-emitting diode (LED) panel. Both technologies are similar in shape and appearance, but there is little understanding of how people perceive discomfort glare (DG) from area sources. The objective of this study was to evaluate the DG of these two technologies under similar operating conditions. Additionally, two existing DG models were compared to evaluate the correlation between predicted values and observed values. In an earlier study, we found no statistically significant difference in human response in terms of DG between OLED and edge-lit LED panels when the two sources produced the same luminous stimulus. The range of testing stimulus was expanded to test different panel luminances at three background illuminations. The results showed no difference in perceived glare between the panels, and, as the background illumination increased, the perceived glare decreased. In other words, both appeared equally glary beyond a certain luminance and background illumination. We then compared two existing glare models with the observed values and found that one model showed a good estimation of how humans perceive DG. That model was further modified to increase its power.

  7. Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats.

    Science.gov (United States)

    O'Neill, Julie; Fasching, Angelica; Pihl, Liselotte; Patinha, Daniela; Franzén, Stephanie; Palm, Fredrik

    2015-08-01

    Early stage diabetic nephropathy is characterized by glomerular hyperfiltration and reduced renal tissue Po2. Recent observations have indicated that increased tubular Na(+)-glucose linked transport (SGLT) plays a role in the development of diabetes-induced hyperfiltration. The aim of the present study was to determine how inhibition of SLGT impacts upon Po2 in the diabetic rat kidney. Diabetes was induced by streptozotocin in Sprague-Dawley rats 2 wk before experimentation. Renal hemodynamics, excretory function, and renal O2 homeostasis were measured in anesthetized control and diabetic rats during baseline and after acute SGLT inhibition using phlorizin (200 mg/kg ip). Baseline arterial pressure was similar in both groups and unaffected by SGLT inhibition. Diabetic animals displayed reduced baseline Po2 in both the cortex and medulla. SGLT inhibition improved cortical Po2 in the diabetic kidney, whereas it reduced medullary Po2 in both groups. SGLT inhibition reduced Na(+) transport efficiency [tubular Na(+) transport (TNa)/renal O2 consumption (Qo2)] in the control kidney, whereas the already reduced TNa/Qo2 in the diabetic kidney was unaffected by SGLT inhibition. In conclusion, these data demonstrate that when SGLT is inhibited, renal cortex Po2 in the diabetic rat kidney is normalized, which implies that increased proximal tubule transport contributes to the development of hypoxia in the diabetic kidney. The reduction in medullary Po2 in both control and diabetic kidneys during the inhibition of proximal Na(+) reabsorption suggests the redistribution of active Na(+) transport to less efficient nephron segments, such as the medullary thick ascending limb, which results in medullary hypoxia.

  8. New insights into the abyssal sponge fauna of the Kurile-Kamchatka plain and Trench region (Northwest Pacific)

    Science.gov (United States)

    Downey, Rachel V.; Janussen, Dorte

    2015-01-01

    The under-explored abyssal depths of the Kurile-Kamchatka region have been re-examined during the KuramBio (Kurile-Kamchatka Biodiversity Study) expedition. Combining new KuramBio data with previous expedition data in this region has enhanced our understanding abyssal sponge fauna, in particular, the patchiness, rarity, and exceptional richness of the Cladorhizidae family. In total, 14 sponge species, from 7 genera, in 5 families, within two classes (Demospongiae and Hexactinellida) were collected. Of the 14 species, 29% (4 spp.) have been found previously in this region, 36% (5 spp.) were new to the regional abyssal fauna, and 21% (3 spp.) were new to science. The number of abyssal species in this region has now been increased by 26% (8 spp.) and genera by nearly 15% (2 genera). Rarity is a prominent feature of this abyssal fauna, with more than half of species only found at one station, and 83% (19 spp.) of species found previously in this region were not re-found during KuramBio. Cladorhizid sponges dominate demosponge species and genera richness in the abyssal Kurile-Kamchatka region; accounting for 87% (20 spp.) of all demosponge species, and accounting for over 60% (5 genera) of all demosponge genera. Sponge richness in this region is potentially aided by the productivity of the ocean waters, the geological age of the Pacific Ocean, low population densities, and the varied topographic features (ridges, trenches, and seamounts) found in this region. Unusually, the dominance of demosponges in the Kurile-Kamchatka sponge faunal composition is not replicated in other well-sampled abyssal regions, which tend to be richer in deep-sea hexactinellid fauna. Broad depth, latitudinal and longitudinal ranges in Kurile-Kamchatka abyssal fauna are a key characteristic of this faunal assemblage. Strong abyssal faunal connectivity is found between the Kurile-Kamchatka region and North Pacific abyssal fauna, with weaker faunal connections found with the adjacent semi

  9. A facile fabrication of light diffusing film with LDP/polyacrylates composites coating for anti-glare LED application

    Science.gov (United States)

    Song, Shisen; Sun, Yaojie; Lin, Yandan; You, Bo

    2013-05-01

    In this paper, we present a facile coating technique to fabricate the light diffusing film with hemispherical surface convex micro-structure. The coating was prepared by different ratio of light-diffusing particles (LDP)/polyacrylates composites via in situ radical polymerization, with the H2SO4 and vinyl triethoxysilane (A-151) pretreatment made the LDP better dispersed and incorporated with polyacrylate polymer chains. When the mass ratio (LDP/polyacrylate) was 0.5, the film obtained the highest light-diffusing effect and more than 90% transmittance due to the formation of hemispherical surface convex micro-structure. The light diffusing films have excellent anti-glare property if applied to LED light system.

  10. Cross-Correlation Earthquake Precursors in the Hydrogeochemical and Geoacoustic Signals for the Kamchatka Peninsula

    CERN Document Server

    Ryabinin, G V; Polyakov, Yu S; Timashev, S F

    2012-01-01

    We propose a new type of earthquake precursor based on the analysis of correlation dynamics between geophysical signals of different nature. The precursor is found using a two-parameter cross-correlation function introduced within the framework of flicker-noise spectroscopy, a general statistical physics approach to the analysis of time series. We consider an example of cross-correlation analysis for water salinity time series, an integral characteristic of the chemical composition of groundwater, and geoacoustic emissions recorded at the G-1 borehole on the Kamchatka peninsula in the time frame from 2001 to 2003, which is characterized by a sequence of three groups of significant seismic events. We found that cross-correlation precursors took place 27, 31, and 35 days ahead of the strongest earthquakes for each group of seismic events, respectively. At the same time, precursory anomalies in the signals themselves were observed only in the geoacoustic emissions for one group of earthquakes.

  11. June 03, 2007 Natural Disaster in the Valley of Geysers in Kamchatka

    Science.gov (United States)

    Gordeev, E. I.; Pinegina, T. K.; Droznin, V. A.; Dvigalo, V. N.; Melekestsev, I. V.

    2007-12-01

    The famous Valley of Geysers along with active volcanoes appears to be a beautiful visiting card of Kamchatka. It is well known in Russia and other countries as the most popular tourist place. Annually it is visited by thousands of Russian and foreign tourists. The Valley of Geysers is the most potentially hazardous area in Kamchatka because of intense development of landslides, avalanches and frequent mudflows occurring within its boundaries. June 03, 2007 landslide, followed by a mudflow, resulted in a north - west faced horse-shoe amphitheater consisting of two adjacent circuses. The height of north-eastern sub-vertical wall is 150 m with a length 800 m; the length of a flatly inclined bottom 400 - 600 m. Initially estimated volume of collapse and avalanche made up 8-15 millions cubic meters. Avalanching and formation of a dam at the Geysernaya River caused completion of some geysers and open thermal water discharge at sites blocked off by the avalanche and a dammed lake. However beyond the boundaries of the avalanche and the lake, the geysers are still operating. It is likely that some geysers could be brought back if water level in the lake decreases. Possibly new geysers could appear. Based on results of routine survey we estimated specific areas that nowadays pose a hazard as well as a possibility of new avalanches and landslides that may occur in the future. Estimation and forecast of new avalanches and landslides require continuous observations to be performed in the Valley of Geysers to monitor deformation and seismic processes.

  12. Gold recycling and enrichment beneath volcanoes: A case study of Tolbachik, Kamchatka

    Science.gov (United States)

    Zelenski, Michael; Kamenetsky, Vadim S.; Hedenquist, Jeffrey

    2016-03-01

    Magmas supply metals to hydrothermal ore deposits, although typical arc basalts may be unable to produce a gold-rich ore-forming fluid, as such basalts rarely exceed 5 ppb Au. Consistent with this, the occurrence of native gold of magmatic origin is extremely rare, and only a few finds of micron-sized gold particles in unaltered basalts have been documented. Surprisingly, some lava flows and scoria cones of the historic basaltic eruptions of Tolbachik volcano (Kamchatka) are unusually gold-rich. Tolbachik basalts contain up to 11.6 ppb Au based on whole rock analyses, nuggets of gold (electrum) up to 900 μm in size and native gold droplets up to 200 μm, plus numerous vapor-deposited gold crystals within fumarolic incrustations and directly on surfaces of basaltic lapilli. Our results demonstrate that the gold nuggets in Tolbachik basalt are of hydrothermal origin and were physically scavenged from epithermal veins hosted by country rocks during intrusion of mafic magmas. Depending on the melt temperature and/or time span of the melt-rock interaction, gold was ejected by the erupting volcano either in the form of abraded nuggets or liquid droplets, or was fully assimilated (dissolved) into the shallow long-lived magma chamber to provide a 4-fold increase in gold content over background concentration of 2.7 ppb Au, characteristic of mafic volcanic rocks in Kamchatka. Upon the end of the eruption, the continued discharge of volcanic vapors enriched in gold deposited abundant crystals of gold on cooling lava and scoria. Similar to Tolbachik, recycling of metals from prior accumulations (ore deposits) in the shallow crust may take place in other long-lived magma reservoirs, thus upgrading the gold and other metal contents and contributing to the ore-forming potential of a magma.

  13. Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent glucose transporter SGLT1.

    Directory of Open Access Journals (Sweden)

    Xin Jin

    Full Text Available Delphinidin-3-glucoside (Dp is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs. Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1. Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio. Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.

  14. Carbohydrate malabsorption mechanism for tumor formation in rats treated with the SGLT2 inhibitor canagliflozin.

    Science.gov (United States)

    Mamidi, Rao N V S; Proctor, Jim; De Jonghe, Sandra; Feyen, Bianca; Moesen, Esther; Vinken, Petra; Ma, Jing Ying; Bryant, Stewart; Snook, Sandra; Louden, Calvert; Lammens, Godelieve; Ways, Kirk; Kelley, Michael F; Johnson, Mark D

    2014-09-25

    Canagliflozin is an SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus. Studies were conducted to investigate the mechanism responsible for renal tubular tumors and pheochromocytomas observed at the high dose in a 2-year carcinogenicity study in rats. At the high dose (100mg/kg) in rats, canagliflozin caused carbohydrate malabsorption evidenced by inhibition of intestinal glucose uptake, decreased intestinal pH and increased urinary calcium excretion. In a 6-month mechanistic study utilization of a glucose-free diet prevented carbohydrate malabsorption and its sequelae, including increased calcium absorption and urinary calcium excretion, and hyperostosis. Cell proliferation in the kidney and adrenal medulla was increased in rats maintained on standard diet and administered canagliflozin (100mg/kg), and in addition an increase in the renal injury biomarker KIM-1 was observed. Increased cell proliferation is considered as a proximal event in carcinogenesis. Effects on cell proliferation, KIM-1 and calcium excretion were inhibited in rats maintained on the glucose-free diet, indicating they are secondary to carbohydrate malabsorption and are not direct effects of canagliflozin. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. [Canagliflozin (Invokana): kidney SGLT2 cotransporter inhibitor for treating type 2 diabetes].

    Science.gov (United States)

    Scheen, A J

    2014-12-01

    Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(1c)). Furthermore, canagliflozin promotes weight loss and lowers arterial (mainly systolic) blood pressure. Its efficacy is decreased in patients with renal insufficiency and the treatment should be stopped if estimated glomerular filtration rate is below 45 ml/min/1.73 m2. Both the efficacy and safety of canagliflozin have been investigated in 24 to 104-week controlled trials versus placebo or versus an active comparator (glimepiride or sitagliptin). The mean reduction in HbA(1c) averages 0.75% when added to other treatments, as compared to placebo. The 100 mg dose is as active as sitagliptin 100 mg while the 300 mg canagliflozin dose is even more efficacious. Adverse events are mostly mycotic genital infections and more rarely mild urinary tract infections. Caution is required in elderly patients and the risk of volume depletion should be checked (hypotension). Hypoglycaemia may occur only in patients already treated with an insulin-secreting agent or insulin. Canagliflozin is commercialized under the trade name Invokana, at the doses of 100 mg and 300 mg once daily, for the treatment of type 2 diabetes.

  16. 2010 Volcanic activity in Alaska, Kamchatka, and the Kurile Islands: summary of events and response of the Alaska Volcano Observatory

    Science.gov (United States)

    Neal, Christina A.; Herrick, Julie; Girina, O.A.; Chibisova, Marina; Rybin, Alexander; McGimsey, Robert G.; Dixon, Jim

    2014-01-01

    The Alaska Volcano Observatory (AVO) responded to eruptions, possible eruptions, volcanic unrest or suspected unrest at 12 volcanic centers in Alaska during 2010. The most notable volcanic activity consisted of intermittent ash emissions from long-active Cleveland volcano in the Aleutian Islands. AVO staff also participated in hazard communication regarding eruptions or unrest at seven volcanoes in Russia as part of an ongoing collaborative role in the Kamchatka and Sakhalin Volcanic Eruption Response Teams.

  17. Synthesis of novel l-rhamnose derived acyclic C-nucleosides with substituted 1,2,3-triazole core as potent sodium-glucose co-transporter (SGLT) inhibitors.

    Science.gov (United States)

    Putapatri, Siddamal Reddy; Kanwal, Abhinav; Banerjee, Sanjay K; Kantevari, Srinivas

    2014-03-15

    Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes by preventing renal glucose reabsorption. In our efforts to identify novel inhibitors of SGLT, we synthesized a series of l-rhamnose derived acyclic C-nucleosides with 1,2,3-triazole core. The key β-ketoester building block 4 prepared from l-rhamnose in five steps, was reacted with various aryl azides to produce the respective 1,2,3-triazole derivatives in excellent yields. Deprotection of acetonide group gave the desired acyclic C-nucleosides 7a-o. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using recently developed cell-based nonradioactive fluorescence glucose uptake assay. Among them, 7m with IC50: 125.9nM emerged as the most potent SGLT2 inhibitor. On the other hand compound 7d exhibited best selectivity for inhibition of SGLT2 (IC50: 149.1nM) over SGLT1 (IC50: 693.2nM). The results presented here demonstrated the utility of acyclic C-nucleosides as novel SGLT inhibitors for future investigations.

  18. Magmatic gas flux emissions from Gorelyi volcano, Kamchatka, and implications for volatile recycling in the NW Pacific

    Science.gov (United States)

    Aiuppa, A.; Bagnato, E.; Calabrese, S.; Giudice, G.; Liuzzo, M.; Tamburello, G.; Allard, P.; Chaplygin, I.; Taran, Y.

    2012-04-01

    The Kamchatka peninsula, in the north-western part of the Pacific 'Ring of Fire', is one of the most active volcanic realms on Earth, with 29 historically erupting volcanoes along its ~700 km-long Eastern Volcanic Belt (EVB). This notwithstanding, volatile input and output fluxes along this arc sector have remained poorly characterised until very recently. We here report on the very first assessment of volatile flux emissions from Gorelyi, a large (25 km3, 1830 m high) and most active shield-like Holocene volcano located on the southern segment of the Kamchatka EVB. By combing results from a variety of in situ and remote sensing techniques (MultiGAS, filter packs, and UV camera), we determine the bulk plume molar concentrations of major (H2O 93.5%, CO2 2.6%, SO2 2.2%, HCl 1.1%, HF 0.3%, H2 0.2%) to trace-halogens (Br, I) and trace-element volatile species, and we estimate a total gas release of ~11,000 t/day from Gorelyi during ~900°C non-eruptive degassing. Using this observation, we derive new constraints on the abundances and origins of volatiles in the subduction-modified mantle source feeding magmatism in Kamchatka.

  19. Drug-drug interactions with sodium-glucose cotransporters type 2 (SGLT2) inhibitors, new oral glucose-lowering agents for the management of type 2 diabetes mellitus.

    Science.gov (United States)

    Scheen, André J

    2014-04-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions (DDIs) regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure [assessed by peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC)] to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose-lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin. Some modest changes were not considered as clinically relevant. However, drugs that could specifically interfere with the metabolic pathways of SGLT2 inhibitors [rifampicin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase (UGT)] may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin. Potential DDIs in patients with type 2 diabetes receiving chronic treatment with an SGLT2 inhibitor deserve further attention, especially in individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

  20. Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2 inhibitor for the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Joshua J Neumiller

    2014-06-01

    Full Text Available Type 2 diabetes is increasing in prevalence worldwide, and hyperglycemia is often poorly controlled despite a number of therapeutic options. Unlike previously available agents, sodium-glucose co-transporter 2 (SGLT2 inhibitors offer an insulin-independent mechanism for improving blood glucose levels, since they promote urinary glucose excretion (UGE by inhibiting glucose reabsorption in the kidney. In addition to glucose control, SGLT2 inhibitors are associated with weight loss and blood pressure reductions, and do not increase the risk of hypoglycemia. Empagliflozin is a selective inhibitor of SGLT2, providing dose-dependent UGE increases in healthy volunteers, with up to 90 g of glucose excreted per day. It can be administered orally, and studies of people with renal or hepatic impairment indicated empagliflozin needed no dose adjustment based on pharmacokinetics. In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure. As add-on to basal insulin, empagliflozin not only improved HbA1c levels but also reduced insulin doses. Across studies, empagliflozin was generally well tolerated with a similar rate of hypoglycemia to placebo; however, patients had a slightly increased frequency of genital infections, but not urinary tract infections, versus placebo. Phase III studies have also reported a good safety profile along with significant improvements in HbA1c, weight and blood pressure, with no increased risk of hypoglycemia versus placebo. Based on available data, it appears that empagliflozin may be a useful option in a range of patients; however, clinical decisions will be better informed by the results of ongoing studies, in particular, a large cardiovascular outcome study (EMPA-REG OUTCOME™.

  1. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

    Science.gov (United States)

    Chino, Yukihiro; Samukawa, Yoshishige; Sakai, Soichi; Nakai, Yasuhiro; Yamaguchi, Jun-ichi; Nakanishi, Takeo; Tamai, Ikumi

    2014-01-01

    Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UEUA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UEUA, suggesting that SUA decreased as a result of the increase in the UEUA. The increase in UEUA was correlated with an increase in urinary d-glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UEUA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d-glucose. It was observed that the efflux of [14C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans-stimulated by 10 mm d-glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [14C]UA by oocytes was cis-inhibited by 100 mm d-glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UEUA could potentially be increased by luseogliflozin-induced glycosuria, with alterations of UA transport activity because of urinary glucose. PMID:25044127

  2. Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice.

    Science.gov (United States)

    Hatanaka, Takashi; Ogawa, Daisuke; Tachibana, Hiromi; Eguchi, Jun; Inoue, Tatsuyuki; Yamada, Hiroshi; Takei, Kohji; Makino, Hirofumi; Wada, Jun

    2016-08-01

    It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured. Expansion of the mesangial matrix, interstitial fibrosis, and macrophage infiltration in kidneys were evaluated by histology. Oxidative stress and apoptosis were evaluated in kidneys and cultured proximal tubular epithelial cells. Compared with nontreated mice, dapagliflozin and insulin decreased blood glucose and hemoglobin A1c levels equally. Urine volume and water intake increased significantly in the dapagliflozin-treated group compared with those in the insulin-treated group, but there were no differences in body weight or blood pressure between the two groups. Macrophage infiltration and fibrosis in renal interstitium improved significantly in the dapagliflozin group compared with the insulin group. Oxidative stress was attenuated by dapagliflozin, and suppression occurred in a dose-dependent manner. RNAi knockdown of SGLT2 resulted in reduced oxidative stress. Dapagliflozin ameliorates diabetic nephropathy by suppressing hyperglycemia-induced oxidative stress in a manner independent of hyperglycemia improvement in Akita mice. Our findings suggest that dapagliflozin may be a novel therapeutic approach for the treatment of diabetic nephropathy.

  3. First evidence of the Oceanic Anoxic Events in Cenomanian paleoceanic deposits of the Eastern Kamchatka

    Science.gov (United States)

    Savelyeva, Olga; Palechek, Tatiana; Savelyev, Dmitry

    2010-05-01

    They are a few stratigraphical levels corresponding to OAEs in the deep-water drilling sites in the Pacific ocean. Discoveries of ОАЕs evidences in fold-thrust belt of Pacific are important for correlation of Pacific ocean sections with well investigated sections of Europe. We studied Albian-Cenomanian paleoceanic carbonate-siliceous deposits of the Kamchatsky Mys Peninsula (Eastern Kamchatka, Russia). They are deposited in association with pillow-basalts and hyaloclastites. The thickness of the studied section (56°03.353´N, 163°00.376´E) is about 10 m. The deposits are represented mainly by rhythmical intercalation of red-brown radiolarian jaspers, pink nannoplancton limestones as well as siliceous limestones. In the middle and upper parts of the section there are two thin beds enriched by organic carbon. The thickness of the beds is about 2 cm and 5 cm. Such carbon-rich beds were also found in several other exposures. Near the carbonaceous beds jaspers and limestones lose red and pink colours and become gray and black (on the weathered surface almost white). The content of the mineral matter in the carbon-rich beds amounts 27-75%. It consists of biogenic silica and clay minerals (likely altered hyaloclactites). Carbonaceous beds contain pyrite, barite, phosphates in the form of pellets and fish bone detritus. Mo/Mn ratio in the mineral matter of carbon-rich beds corresponds to euxinic conditions. Total organic carbon contents change from 18 to 53%. The calculated values of the hydrogen and oxygen indexes indicate that the organic carbon originated from marine (sapropelic) organic matter. In studied section the curve of d13C (analyzed in limestones) is characterized by a clearly expressed positive shift at the level of the lower carbonaceous bed. Below it and in the overlapping stratum of siliceous limestone (1 cm thickness) d13C has the values of 1.9-2.1 pro mil, and above it d13C increases up to 2.5-3 pro mil. The radiolarian assemblages are dominated by

  4. [EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES].

    Science.gov (United States)

    Scheen, A J

    2015-09-01

    Empagliflozin is a new inhibitor of sodiumglucose cotransporters type 2 (SGLT2) for the treatment of type 2 diabetes mellitus (T2DM). Its specific action inhibits glucose reabsorption in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(Ic)), independently of insulin. Furthermore, calorie urinary loss promotes weight reduction and osmotic diuresis lowers arterial blood pressure. The efficacy of empagliflozin increases according to the level of hyperglycaemia but decreases in patients with renal insufficiency. In 24 to 104-week controlled trials versus placebo, empagliflozin reduces HbA(1c) (approximately 0.8%), without hypoglycaemia (except in patients already treated with insulin or sulphonylureas). This improvement in glucose control is rather similar to that observed with active comparators (metformin, glimepiride or sitagliptin), with the advantage for empagliflozin of reducing body weight (approximately 2 kg) and blood pressure (systolic approximately 4 mm Hg and diastolic approximately 2 mm Hg). Empagliflozin has shown a cardiovascular protection in the EMPA-REG OUTCOME trial. Mycotic genital infections occur more frequently, especially in women, while a negligible increase in mild urinary tract infections may be observed. The risk of hypotension and volume depletion is low, although it should be carefully checked in more fragile and at risk patients. Empagliflozin (Jardiance), which is commercialized at the doses of 10 mg and 25 mg once daily, is indicated for the treatment of T2DM and reimbursed in Belgium with conditions as add-on to a background glucose-lowering therapy.

  5. Constraining recent Shiveluch volcano eruptions (Kamchatka, Russia by means of dendrochronology

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    O. Solomina

    2008-10-01

    Full Text Available Shiveluch (N 56°38´, E 161°19´; elevation: active dome ~2500 m, summit of Old Shiveluch 3283 m is one of the most active volcanoes in Kamchatka. The eruptions of Shiveluch commonly result in major environmental damage caused by debris avalanches, hot pyroclastic flows, tephra falls and lahars. Constraining these events in time and space is important for the understanding and prediction of these natural hazards. The last major eruption of Shiveluch occurred in 2005; earlier ones, dated by instrumental, historical, 14C and tephrochronological methods, occurred in the last millennium around AD 1030, 1430, 1650, 1739, 1790–1810, 1854, 1879–1883, 1897–1898, 1905, 1927–1929, 1944–1950, and 1964. A lava dome has been growing in the 1964 crater since 1980, occasionally producing tephra falls and pyroclastic flows. Several Shiveluch eruptions (~AD 1050, 1650, 1854, 1964 may have been climatically effective and are probably recorded in the Greenland ice cores.

    Previously, most dates for eruptions before AD 1854 were obtained by tephrochronology and constrained by radiocarbon dating with an accuracy of several decades or centuries. In this paper we report tree-ring dates for a recent pyroclastic flow in Baidarnaia valley. Though the wood buried in these deposits is carbonized, fragile and poorly preserved, we were able to measure ring-width using standard tree-ring equipment or photographs and to cross-date these samples against the regional Kamchatka larch ring-width chronology. The dates of the outer rings indicate the date of the eruptions. In the Baidarnaia valley the eruption occurred shortly after AD 1756, but not later than AD 1758. This date coincides with the decrease of ring-width in trees growing near Shiveluch volcano in 1758–1763 in comparison with the control "non-volcanic" chronology. The pyroclastic flow in Kamenskaia valley, although similar in appearance to the one in Baidarnaia valley, definitively

  6. Holocene pollen record from Lake Sokoch, interior Kamchatka (Russia), and its paleobotanical and paleoclimatic interpretation

    Science.gov (United States)

    Dirksen, Veronika; Dirksen, Oleg; van den Bogaard, Christel; Diekmann, Bernhard

    2015-11-01

    A pollen record, obtained from sediments of Lake Sokoch in mountain interior of the Kamchatka Peninsula, covers the last ca. 9600 years (all ages are given in calibrated years BP). Variations in local components, including pollen, spores and non-pollen palynomorphs, and related changes in sedimentation document the lake development from initially seepage and shallow basin to deeper lake during the mid Holocene and then to the hydrologically open system during the late Holocene. The studies of volcanic ashes from the lake sediment core show their complex depositional histories. Lake Sokoch occupies a former proglacial basin between two terminal moraines of the LGM time. The undated basal part of record before ca. 9600 year BP, however, does not reflect properly cold conditions. At that time, although shrublands and tundra dominated, stone birch and white birch forests have already settled in surroundings; the presence of alder woodland indicates wet and maritime-like climate. The subsequent forest advance suggesting warmer conditions was interrupted by the ca. 8000-7600 year BP spell of cooler climate. The following culmination of warmth is bracketed by the evidence of the first maximal forest extent between ca. 7400 and 5100 year BP. During that time, dramatic retreat of alder forest suggests a turn from maritime-like to more continental climate conditions. The cool and wet pulse after ca. 5100 year BP was pronounced as forests retreat while shrublands, meadows and bogs extended. An expansion of white birch forest since ca. 3500 year BP reflected the onset of drier climate, strengthening continentality and seasonal contrast. The second maximum of forests dominated by both stone and white birches occurred between ca. 2200 and 1700 year BP and indicated warming in association with relatively dry and increasingly continental climate. The following period was wetter and cooler, and minor outbreak of alder forest around ca. 1500 year BP suggests a short-term return of

  7. Evaluation of Workpiece Temperature during Drilling of GLARE Fiber Metal Laminates Using Infrared Techniques: Effect of Cutting Parameters, Fiber Orientation and Spray Mist Application

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    Khaled Giasin

    2016-07-01

    Full Text Available The rise in cutting temperatures during the machining process can influence the final quality of the machined part. The impact of cutting temperatures is more critical when machining composite-metal stacks and fiber metal laminates due to the stacking nature of those hybrids which subjects the composite to heat from direct contact with metallic part of the stack and the evacuated hot chips. In this paper, the workpiece surface temperature of two grades of fiber metal laminates commercially know as GLARE is investigated. An experimental study was carried out using thermocouples and infrared thermography to determine the emissivity of the upper, lower and side surfaces of GLARE laminates. In addition, infrared thermography was used to determine the maximum temperature of the bottom surface of machined holes during drilling GLARE under dry and minimum quantity lubrication (MQL cooling conditions under different cutting parameters. The results showed that during the machining process, the workpiece surface temperature increased with the increase in feed rate and fiber orientation influenced the developed temperature in the laminate.

  8. Geochemistry of the Koshelev Volcano-Hydrothermal System, Southern Kamchatka, Russia

    Science.gov (United States)

    Taran, Y.; Kalacheva, E.

    2015-12-01

    Koshelev is the southernmost volcano of the Kamchatkan volcanic front where magmatic plumbing systems of the Kamchatkan subduction zone cross a thick layer of the oil-gas-bearing Neogene sedimentary strata of Western Kamchatka. The volcanic massive hosts a powerful hydrothermal system, which has been drilled in early 1980s. Deep wells tapped a hot (ca. 300ºC) saline solution (up to 40 g/L of Cl), whereas the upper part of the system is a typical steam cap with temperature close to 240ºC. Two hydrothermal fields of the volcano (Upper and Lower) discharge saturated or super-heated (up to 150ºC) steam and are characterized by numerous hot pools and low flow-rate springs of steam-heated waters enriched in boron and ammonia. There is also a small lateral group of warm Na-Ca-Cl-SO4 springs (40ºC). We report here our data and review the literature geochemical data on the chemical and isotopic composition of waters and hydrothermal vapours of the Koshelev system. Data on the gas composition include He and C isotopes, as well as the chemical and isotopic composition of light hydrocarbons. Water geochemistry includes literature data on water isotopes of the deep brine and trace elements and REE of steam-heated waters. A conceptual model of the system is presented and discussed.

  9. 3D Numeric modeling of slab-plume interaction in Kamchatka

    Science.gov (United States)

    Constantin Manea, Vlad; Portnyagin, Maxim; Manea, Marina

    2010-05-01

    Volcanic rocks located in the central segment of the Eastern Volcanic Belt of Kamchatka show a high variability, both in age as well as in the geochemical composition. Three principal groups have been identified, an older group (7-12 my) represented by rich alkaline and transitional basalts, a 7-8 my group exemplified by alkaline basalts of extreme plume type, and a younger group (3-8 my) characterized by calc-alkaline andesites and dacites rocks. Moreover, the younger group shows an adakitic signature. The magmas are assumed to originate from two principle sources: from a subduction modified Pacific MORB-type and from plume-type mantle. In this paper we study the interaction of a cold subducting slab and a hot plume by means of 3D numeric modeling integrated 30 my back in time. Our preliminary modeling results show a short episode of plume material inflowing into the mantle wedge at ~10 my consistent with the second rocks group (plume like). Also our models predict slab edge melting consistent with the youngest group.

  10. The Magma-Hydrothermal System at Mutnovsky Volcano, Kamchatka Peninsula, Russia

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    Alexey Kiryukhin

    2009-03-01

    Full Text Available What is the relationship between the kinds of volcanoes that ring the Pacific plate and nearby hydrothermal systems? A typical geometry for stratovolcanoes and dome complexes is summit fumaroles and hydrothermal manifestations on and beyond their flanks. Analogous subsurface mineralization is porphyry copper deposits flanked by shallow Cu-As-Au acid-sulfate deposits and base metal veins. Possible reasons for this association are (1 upward and outward flow of magmatic gas and heat from the volcano’s conduit and magma reservoir, mixing with meteoric water; (2 dikes extending from or feeding towards the volcano that extend laterally well beyond the surface edifice, heating a broad region; or (3 peripheral hot intrusions that are remnants of previous volcanic episodes, unrelated to current volcanism. These hypotheses are testable through a Mutnovsky Scientific Drilling Project (MSDP that was discussed in a workshop during the last week of September 2006 at a key example, the Mutnovsky Volcano of Kamchatka. Hypothesis (1 was regarded as the most likely. It is also the most attractive since it could lead to a new understanding of themagma-hydrothermal connection and motivate global geothermal exploration of andesitic arc volcanoes.

  11. Dendrogeomorphic reconstruction of lahar activity and triggers: Shiveluch volcano, Kamchatka Peninsula, Russia

    Science.gov (United States)

    Salaorni, E.; Stoffel, M.; Tutubalina, O.; Chernomorets, S.; Seynova, I.; Sorg, A.

    2017-01-01

    Lahars are highly concentrated, water-saturated volcanic hyperconcentrated flows or debris flows containing pyroclastic material and are a characteristic mass movement process on volcanic slopes. On Kamchatka Peninsula (Russian Federation), lahars are widespread and may affect remote settlements. Historical records of past lahar occurrences are generally sparse and mostly limited to events which damaged infrastructure on the slopes or at the foot of volcanoes. In this study, we present a tree-ring-based reconstruction of spatiotemporal patterns of past lahar activity at Shiveluch volcano. Using increment cores and cross sections from 126 Larix cajanderi trees, we document 34 events covering the period AD 1729-2012. Analyses of the seasonality of damage in trees reveal that 95% of all lahars occurred between October and May and thus point to the predominant role of the sudden melt of the snow cover by volcanic material. These observations suggest that most lahars were likely syn-eruptive and that lahar activity is largely restricted to periods of volcanic activity. By contrast, rainfall events do not seem to play a significant role in lahar triggering.

  12. Rapid glacial retreat on the Kamchatka Peninsula during the early 21st century

    Science.gov (United States)

    Lynch, Colleen M.; Barr, Iestyn D.; Mullan, Donal; Ruffell, Alastair

    2016-08-01

    Monitoring glacier fluctuations provides insights into changing glacial environments and recent climate change. The availability of satellite imagery offers the opportunity to view these changes for remote and inaccessible regions. Gaining an understanding of the ongoing changes in such regions is vital if a complete picture of glacial fluctuations globally is to be established. Here, satellite imagery (Landsat 7, 8 and ASTER) is used to conduct a multi-annual remote sensing survey of glacier fluctuations on the Kamchatka Peninsula (eastern Russia) over the 2000-2014 period. Glacier margins were digitised manually and reveal that, in 2000, the peninsula was occupied by 673 glaciers, with a total glacier surface area of 775.7 ± 27.9 km2. By 2014, the number of glaciers had increased to 738 (reflecting the fragmentation of larger glaciers), but their surface area had decreased to 592.9 ± 20.4 km2. This represents a ˜ 24 % decline in total glacier surface area between 2000 and 2014 and a notable acceleration in the rate of area loss since the late 20th century. Analysis of possible controls indicates that these glacier fluctuations were likely governed by variations in climate (particularly rising summer temperatures), though the response of individual glaciers was modulated by other (non-climatic) factors, principally glacier size, local shading and debris cover.

  13. Thermogladius calderae gen. nov., sp. nov., an anaerobic, hyperthermophilic crenarchaeote from a Kamchatka hot spring.

    Science.gov (United States)

    Kochetkova, Tatiana V; Kublanov, Ilya V; Toshchakov, Stepan V; Osburn, Magdalena R; Novikov, Andrei A; Bonch-Osmolovskaya, Elizaveta A; Perevalova, Anna A

    2016-01-21

    An obligately anaerobic, hyperthermophilic, organoheterotrophic archaeon, strain 1633T, was isolated from a terrestrial hot spring of the Uzon Caldera (Kamchatka Peninsula, Russia). Cells were regular cocci, 0.5-0.9 μm in diameter, with one flagellum. The temperature range for growth was 80-95°C, with an optimum at 84°C. Strain 1633T grew on yeast extract, beef extract, peptone, cellulose and cellobiose. No growth was detected on other sugars or carbohydrates, organic acids, or under autotrophic conditions. The only detected growth products were CO2, acetate, and H2. Growth rate was stimulated by elemental sulfur, which was reduced to hydrogen sulfide. In silico calculated G+C content of strain 1633T genomic DNA was 55.64 mol%. 16S rRNA gene sequence analysis placed the strain 1633T together with the non-validly published "Thermogladius shockii" strain WB1 in a separate genus-level cluster within the Desulfurococcaceae family. ANI results revealed 75.72% identity between 1633T and WB1. Based on these results we propose a novel genus and species, for which the name Thermogladius calderae gen. nov., sp. nov. (type strain 1633T=DSM 22663T=VKM B-2946T) is proposed.

  14. Metadynamics simulations reveal a Na+ independent exiting path of galactose for the inward-facing conformation of vSGLT.

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    Ina Bisha

    2014-12-01

    Full Text Available Sodium-Galactose Transporter (SGLT is a secondary active symporter which accumulates sugars into cells by using the electrochemical gradient of Na+ across the membrane. Previous computational studies provided insights into the release process of the two ligands (galactose and sodium ion into the cytoplasm from the inward-facing conformation of Vibrio parahaemolyticus sodium/galactose transporter (vSGLT. Several aspects of the transport mechanism of this symporter remain to be clarified: (i a detailed kinetic and thermodynamic characterization of the exit path of the two ligands is still lacking; (ii contradictory conclusions have been drawn concerning the gating role of Y263; (iii the role of Na+ in modulating the release path of galactose is not clear. In this work, we use bias-exchange metadynamics simulations to characterize the free energy profile of the galactose and Na+ release processes toward the intracellular side. Surprisingly, we find that the exit of Na+ and galactose is non-concerted as the cooperativity between the two ligands is associated to a transition that is not rate limiting. The dissociation barriers are of the order of 11-12 kcal/mol for both the ion and the substrate, in line with kinetic information concerning this type of transporters. On the basis of these results we propose a branched six-state alternating access mechanism, which may be shared also by other members of the LeuT-fold transporters.

  15. A Medical Literature Review on Canagliflozin and Dapagliflozin and the Role of SGLT2 inhibitors in Diabetic Management

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    Deepu Daniel

    2015-04-01

    Full Text Available Diabetes is one of the most common diseases encountered in both the outpatient and inpatient settings. According to data from the 2011 National Diabetes Fact Sheet, approximately 8.3% (25.8 million of the entire American population have diabetes. Of this population, about 72.9% (18.8 million have been clinically diagnosed while an estimated 27.1% (7.0 million remain undiagnosed. According to the study Economic Costs of Diabetes in the U.S. in 2012, the total national cost of diagnosed diabetes, including direct medical cost and reduced productivity was nearly $245 billion. Extensive research efforts have gone into developing new pharmacologic agents to treat diabetes. The newest medications recently approved by the FDA are the SGLT2 inhibitors. This article will explain the mechanism of the action of this class of drugs along with their specific role in diabetic management. This article will focus on canagliflozin and dapagliflozin, the two most well researched and studied drugs of SGLT2 inhibitors, both of which have been approved for use by the Food and Drug Administration. Some of the major trials concerning both of these drugs will be presented in this article.

  16. Targeting renal glucose reabsorption for the treatment of type 2 diabetes mellitus using the SGLT2 inhibitor dapagliflozin.

    Science.gov (United States)

    Jabbour, Serge A; Whaley, Jean M; Tirmenstein, Mark; Poucher, Simon M; Reilly, Timothy P; Boulton, David W; Saye, Joanne; List, James F; Parikh, Shamik

    2012-07-01

    Sodium-glucose co-transporter 2 (SGLT2) plays a key role in glucose homeostasis as the key transporter responsible for most renal glucose reabsorption in the proximal tubules of the kidney. Dapagliflozin is a potent, selective, and reversible inhibitor of SGLT2 that lowers blood glucose levels in an insulin-independent fashion. This novel agent has been studied extensively in patients with type 2 diabetes mellitus (T2DM). In these clinical trials, dapagliflozin significantly decreased glycated hemoglobin and fasting plasma glucose levels when administered alone or as add-on treatment in patients who were already receiving metformin, a sulfonylurea (glimepiride), pioglitazone, or insulin. Moreover, dapagliflozin decreased body weight when taken as monotherapy or in combination with metformin, a sulfonylurea, or insulin, and mitigated weight gain in patients receiving pioglitazone. Consistent with preclinical toxicology studies, dapagliflozin has a manageable adverse event profile that is largely predictable from its mechanism of action. While there are no clinically significant negative effects on renal function or electrolytes, dapagliflozin treatment is associated with increased frequencies of urinary tract infections and vulvovaginitis/balanitis. With a mechanism of action that is distinct from and complementary to that of existing antihyperglycemic therapies, dapagliflozin is an effective antihyperglycemic agent that is well tolerated and may enhance weight loss. As such, dapagliflozin promises to become an important adjunctive therapy for comprehensive treatment of T2DM.

  17. SGLT1 protein expression in plasma membrane of acinar cells correlates with the sympathetic outflow to salivary glands in diabetic and hypertensive rats.

    Science.gov (United States)

    Sabino-Silva, Robinson; Alves-Wagner, Ana B T; Burgi, Katia; Okamoto, Maristela M; Alves, Adilson S; Lima, Guilherme A; Freitas, Helayne S; Antunes, Vagner R; Machado, Ubiratan F

    2010-12-01

    Salivary gland dysfunction is a feature in diabetes and hypertension. We hypothesized that sodium-glucose cotransporter 1 (SGLT1) participates in salivary dysfunctions through a sympathetic- and protein kinase A (PKA)-mediated pathway. In Wistar-Kyoto (WKY), diabetic WKY (WKY-D), spontaneously hypertensive (SHR), and diabetic SHR (SHR-D) rats, PKA/SGLT1 proteins were analyzed in parotid and submandibular glands, and the sympathetic nerve activity (SNA) to the glands was monitored. Basal SNA was threefold higher in SHR (P acinar cells were regulated in parallel to the SNA. Electrical stimulation of the sympathetic branch to salivary glands increased (∼30%, P acinar cells. Taken together, our results show highly coordinated regulation of sympathetic activity upon PKA activity and plasma membrane SGLT1 content in salivary glands. Furthermore, the present findings show that diabetic- and/or hypertensive-induced changes in the sympathetic activity correlate with changes in SGLT1 expression in basolateral membrane of acinar cells, which can participate in the salivary glands dysfunctions reported by patients with these pathologies.

  18. 2009 Volcanic activity in Alaska, Kamchatka, and the Kurile Islands: summary of events and response of the Alaska Volcano Observatory

    Science.gov (United States)

    McGimsey, Robert G.; Neal, Christina A.; Girina, Olga A.; Chibisova, Marina; Rybin, Alexander

    2014-01-01

    The Alaska Volcano Observatory (AVO) responded to eruptions, possible eruptions, volcanic unrest, and reports of unusual activity at or near eight separate volcanic centers in Alaska during 2009. The year was highlighted by the eruption of Redoubt Volcano, one of three active volcanoes on the western side of Cook Inlet and near south-central Alaska's population and commerce centers, which comprise about 62 percent of the State's population of 710,213 (2010 census). AVO staff also participated in hazard communication and monitoring of multiple eruptions at ten volcanoes in Russia as part of its collaborative role in the Kamchatka and Sakhalin Volcanic Eruption Response Teams.

  19. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx.

    Science.gov (United States)

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette; Holst, Jens Juul

    2015-06-15

    Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans, but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide, which causes hyperpolarization, eliminated the response. Luminal inhibition of the sodium-glucose cotransporter 1 (SGLT1) (by phloridzin) eliminated glucose-stimulated release as well as secretion stimulated by luminal methyl-α-D-glucopyranoside (20% wt/vol), a metabolically inactive SGLT1 substrate, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct KATP channel closure by sulfonylureas stimulated secretion. Therefore, glucose stimulates NT secretion by uptake through SGLT1 and GLUT2, both causing depolarization either as a consequence of sodium-coupled uptake (SGLT1) or by closure of KATP channels (GLUT2 and SGLT1) secondary to the ATP-generating metabolism of glucose.

  20. Expression of Na+/glucose co-transporter 1 (SGLT1) is enhanced by supplementation of the diet of weaning piglets with artificial sweeteners.

    Science.gov (United States)

    Moran, Andrew W; Al-Rammahi, Miran A; Arora, Daleep K; Batchelor, Daniel J; Coulter, Erin A; Daly, Kristian; Ionescu, Catherine; Bravo, David; Shirazi-Beechey, Soraya P

    2010-09-01

    In an intensive livestock production, a shorter suckling period allows more piglets to be born. However, this practice leads to a number of disorders including nutrient malabsorption, resulting in diarrhoea, malnutrition and dehydration. A number of strategies have been proposed to overcome weaning problems. Artificial sweeteners, routinely included in piglets' diet, were thought to enhance feed palatability. However, it is shown in rodent models that when included in the diet, they enhance the expression of Na+/glucose co-transporter (SGLT1) and the capacity of the gut to absorb glucose. Here, we show that supplementation of piglets' feed with a combination of artificial sweeteners saccharin and neohesperidin dihydrochalcone enhances the expression of SGLT1 and intestinal glucose transport function. Artificial sweeteners are known to act on the intestinal sweet taste receptor T1R2/T1R3 and its partner G-protein, gustducin, to activate pathways leading to SGLT1 up-regulation. Here, we demonstrate that T1R2, T1R3 and gustducin are expressed together in the enteroendocrine cells of piglet intestine. Furthermore, gut hormones secreted by the endocrine cells in response to dietary carbohydrates, glucagon-like peptides (GLP)-1, GLP-2 and glucose-dependent insulinotrophic peptide (GIP), are co-expressed with type 1 G-protein-coupled receptors (T1R) and gustducin, indicating that L- and K-enteroendocrine cells express these taste elements. In a fewer endocrine cells, T1R are also co-expressed with serotonin. Lactisole, an inhibitor of human T1R3, had no inhibitory effect on sweetener-induced SGLT1 up-regulation in piglet intestine. A better understanding of the mechanism(s) involved in sweetener up-regulation of SGLT1 will allow the identification of nutritional targets with implications for the prevention of weaning-related malabsorption.

  1. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis

    Science.gov (United States)

    Chen, Jiao; Fan, Fang; Wang, J. Y.; Long, Yang; Gao, C. L.; Stanton, R. C.; Xu, Yong

    2017-01-01

    To assess the efficacy and safety of the SGLT-2 inhibitors as adjunct therapy to insulin in T1DM, clinical trials indexed in PubMed, Cochrane Library, EMbase from inception through April 5, 2016. A meta-analysis was conducted on trials of SGLT-2 inhibitors in patients with T1DM on insulin therapy using RevMan 5.3 software. Of the 371 articles identified, ten met eligibility criteria. Seven clinical trials including four randomized controlled trials and 581 patients were included. Compared with the control group, SGLT-2 inhibitors group had significantly reduced fasting plasma glucose by 0.69 mmol/L [1.32; 0.07], glycosylated hemoglobin A1C by 0.37% [0.54; 0.20], body weight by 2.54 kg [3.48; 1.60] and total daily insulin dose by 6.22 IU [8.04; 4.40]. The total incidence of adverse events (AEs), hypoglycemia, and genital and urinary infections were also similar to placebo, while an increased incidence of diabetic ketoacidosis (DKA) (n = 16) was seen in SGLT-2 inhibitors group. The present study demonstrates that SGLT-2 inhibitors are effective as adjunct therapy to insulin in T1DM, heralding improved glycemic control, reduced body weight and total daily insulin dose without an increase in total AEs, hypoglycemia, or genital and urinary infections. However, the risk of DKA should be carefully monitored in future clinical trials. PMID:28276512

  2. Sediment transport in headwaters of a volcanic catchment—Kamchatka Peninsula case study

    Science.gov (United States)

    Chalov, Sergey R.; Tsyplenkov, Anatolii S.; Pietron, Jan; Chalova, Aleksandra S.; Shkolnyi, Danila I.; Jarsjö, Jerker; Maerker, Michael

    2017-09-01

    Due to specific environmental conditions, headwater catchments located on volcanic slopes and valleys are characterized by distinctive hydrology and sediment transport patterns. However, lack of sufficient monitoring causes that the governing processes and patterns in these areas are rarely well understood. In this study, spatiotemporal water discharge and sediment transport from upstream sources was investigated in one of the numerous headwater catchments located in the lahar valleys of the Kamchatka Peninsula Sukhaya Elizovskaya River near Avachinskii and Koryakskii volcanoes. Three different subcatchments and corresponding channel types (wandering rivers within lahar valleys, mountain rivers within volcanic slopes and rivers within submountain terrains) were identified in the studied area. Our measurements from different periods of observations between years 2012-2014 showed that the studied catchment was characterized by extreme diurnal fluctuation of water discharges and sediment loads that were influenced by snowmelt patterns and high infiltration rates of the easily erodible lahar deposits. The highest recorded sediment loads were up to 9•104 mg/L which was related to an increase of two orders of magnitude within a one day of observations. Additionally, to get a quantitative estimate of the spatial distribution of the eroded material in the volcanic substrates we applied an empirical soil erosion and sediment yield model-modified universal soil loss equation (MUSLE). The modeling results showed that even if the applications of the universal erosion model to different non-agricultural areas (e.g., volcanic catchments) can lead to irrelevant results, the MUSLE model delivered might be acceptable for non-lahar areas of the studied volcanic catchment. Overall the results of our study increase our understanding of the hydrology and associated sediment transport for prediction of risk management within headwater volcanic catchments.

  3. Abrupt transition from fractional crystallization to magma mixing at Gorely volcano (Kamchatka) after caldera collapse

    Science.gov (United States)

    Gavrilenko, Maxim; Ozerov, Alexey; Kyle, Philip R.; Carr, Michael J.; Nikulin, Alex; Vidito, Christopher; Danyushevsky, Leonid

    2016-07-01

    A series of large caldera-forming eruptions (361-38 ka) transformed Gorely volcano, southern Kamchatka Peninsula, from a shield-type system dominated by fractional crystallization processes to a composite volcanic center, exhibiting geochemical evidence of magma mixing. Old Gorely, an early shield volcano (700-361 ka), was followed by Young Gorely eruptions. Calc-alkaline high magnesium basalt to rhyolite lavas have been erupted from Gorely volcano since the Pleistocene. Fractional crystallization dominated evolution of the Old Gorely magmas, whereas magma mixing is more prominent in the Young Gorely eruptive products. The role of recharge-evacuation processes in Gorely magma evolution is negligible (a closed magmatic system); however, crustal rock assimilation plays a significant role for the evolved magmas. Most Gorely magmas differentiate in a shallow magmatic system at pressures up to 300 MPa, ˜3 wt% H2O, and oxygen fugacity of ˜QFM + 1.5 log units. Magma temperatures of 1123-1218 °C were measured using aluminum distribution between olivine and spinel in Old and Young Gorely basalts. The crystallization sequence of major minerals for Old Gorely was as follows: olivine and spinel (Ol + Sp) for mafic compositions (more than 5 wt% of MgO); clinopyroxene and plagioclase crystallized at ˜5 wt% of MgO (Ol + Cpx + Plag) and magnetite at ˜3.5 wt% of MgO (Ol + Cpx + Plag + Mt). We show that the shallow magma chamber evolution of Old Gorely occurs under conditions of decompression and degassing. We find that the caldera-forming eruption(s) modified the magma plumbing geometry. This led to a change in the dominant magma evolution process from fractional crystallization to magma mixing. We further suggest that disruption of the magma chamber and accompanying change in differentiation process have the potential to transform a shield volcanic system to that of composite cone on a global scale.

  4. Anaerobic transformation of carbon monoxide by microbial communities of Kamchatka hot springs.

    Science.gov (United States)

    Kochetkova, Tatiana V; Rusanov, Igor I; Pimenov, Nikolay V; Kolganova, Tatyana V; Lebedinsky, Alexander V; Bonch-Osmolovskaya, Elizaveta A; Sokolova, Tatyana G

    2011-05-01

    Carbon monoxide (CO) is one of the common gaseous compounds found in hot volcanic environments. It is known to serve as the growth substrate for a number of thermophilic prokaryotes, both aerobic and anaerobic. The goal of this work was to study the process of anaerobic transformation of CO by microbial communities inhabiting natural thermal environments: hot springs of Uzon Caldera, Kamchatka. The anaerobic microbial community of Treshchinny Spring (80°C, pH 6.5) was found to exhibit two peaks of affinity for CO (K (S1) = 54 nM and K (S2) = 1 μM). The actual rate of anaerobic CO transformation by the microbial community of this spring, calculated after obtaining the concentration dependence curve and extrapolated to the natural concentration of CO dissolved in the hot spring water (20 nM), was found to be 120 μmol l(-1) of sediment day(-1). In all the hot springs studied, more than 90% of the carbon of (14)CO upon anaerobic incubation was recovered as (14)CO(2). From 1 to 5% of (14)CO was transformed to volatile fatty acids (VFA). The number of microorganisms capable of anaerobic CO oxidation determined by dilution-to-extinction method reached 10(6) cells ml(-1) of sediment. CO-transforming anaerobic thermophilic microorganisms isolated from the springs under study exhibited hydrogenogenic type of CO oxidation and belonged to the bacterial genera Carboxydocella and Dictyoglomus. These data suggest a significant role of hydrogenogenic carboxydotrophic prokaryotes in anaerobic CO transformation in Uzon Caldera hot springs.

  5. Sediment transport in headwaters of a volcanic catchment—Kamchatka Peninsula case study

    Science.gov (United States)

    Chalov, Sergey R.; Tsyplenkov, Anatolii S.; Pietron, Jan; Chalova, Aleksandra S.; Shkolnyi, Danila I.; Jarsjö, Jerker; Maerker, Michael

    2017-01-01

    Due to specific environmental conditions, headwater catchments located on volcanic slopes and valleys are characterized by distinctive hydrology and sediment transport patterns. However, lack of sufficient monitoring causes that the governing processes and patterns in these areas are rarely well understood. In this study, spatiotemporal water discharge and sediment transport from upstream sources was investigated in one of the numerous headwater catchments located in the lahar valleys of the Kamchatka Peninsula Sukhaya Elizovskaya River near Avachinskii and Koryakskii volcanoes. Three different subcatchments and corresponding channel types (wandering rivers within lahar valleys, mountain rivers within volcanic slopes and rivers within submountain terrains) were identified in the studied area. Our measurements from different periods of observations between years 2012-2014 showed that the studied catchment was characterized by extreme diurnal fluctuation of water discharges and sediment loads that were influenced by snowmelt patterns and high infiltration rates of the easily erodible lahar deposits. The highest recorded sediment loads were up to 9•104 mg/L which was related to an increase of two orders of magnitude within a one day of observations. Additionally, to get a quantitative estimate of the spatial distribution of the eroded material in the volcanic substrates we applied an empirical soil erosion and sediment yield model-modified universal soil loss equation (MUSLE). The modeling results showed that even if the applications of the universal erosion model to different non-agricultural areas (e.g., volcanic catchments) can lead to irrelevant results, the MUSLE model delivered might be acceptable for non-lahar areas of the studied volcanic catchment. Overall the results of our study increase our understanding of the hydrology and associated sediment transport for prediction of risk management within headwater volcanic catchments.

  6. Determination of the Na(+)/glucose cotransporter (SGLT1) turnover rate using the ion-trap technique.

    Science.gov (United States)

    Longpré, Jean-Philippe; Lapointe, Jean-Yves

    2011-01-05

    The Na(+)/glucose cotransporter (SGLT1) is a membrane protein that couples the transport of two Na(+) ions and one glucose molecule using the so-called alternating access mechanism. According to this principle, each cotransporter molecule can adopt either of two main conformations: one with the binding sites accessible to the extracellular solution and one with the binding sites facing the intracellular solution. The turnover rate (TOR) is the number of complete cycles that each protein performs per second. Determination of the TOR has important consequences for investigation of the cotransport mechanism, as none of the rate constants involved in mediating transport in a given direction (conformational changes and binding and unbinding reactions) can be slower than the TOR measured under the same conditions. In addition, the TOR can be used to estimate the number of cotransporter molecules involved in generating a given ensemble activity. In this study, we obtain an independent estimation of the TOR for human SGLT1 expressed in Xenopus laevis oocytes applying the ion-trap technique. This approach detects the quantity of ions released in or taken up from the restricted space existing between the oocyte plasma membrane and the tip of a large ion-selective electrode. Taking advantage of the fact that hSGLT1 in the absence of Na(+) can cotransport glucose with protons, we used a pH electrode to determine a TOR of 8.00 ± 1.3 s⁻¹ in the presence of 35 mM α-methyl-glucose at -150 mV (pH 5.5). For the same group of oocytes, a TOR of 13.3 ± 2.4 s⁻¹ was estimated under near-V(max) conditions, i.e., in the presence of 90 mM Na(+) and 5 mM α-methyl-glucose. Under these circumstances, the average cotransport current was -1.08 ± 0.61 μA (n = 14), and this activity was generated by an average of 3.6 ± 0.7 × 10¹¹ cotransporter molecules/oocyte. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Determination of the Na+/Glucose Cotransporter (SGLT1) Turnover Rate Using the Ion-Trap Technique

    Science.gov (United States)

    Longpré, Jean-Philippe; Lapointe, Jean-Yves

    2011-01-01

    The Na+/glucose cotransporter (SGLT1) is a membrane protein that couples the transport of two Na+ ions and one glucose molecule using the so-called alternating access mechanism. According to this principle, each cotransporter molecule can adopt either of two main conformations: one with the binding sites accessible to the extracellular solution and one with the binding sites facing the intracellular solution. The turnover rate (TOR) is the number of complete cycles that each protein performs per second. Determination of the TOR has important consequences for investigation of the cotransport mechanism, as none of the rate constants involved in mediating transport in a given direction (conformational changes and binding and unbinding reactions) can be slower than the TOR measured under the same conditions. In addition, the TOR can be used to estimate the number of cotransporter molecules involved in generating a given ensemble activity. In this study, we obtain an independent estimation of the TOR for human SGLT1 expressed in Xenopus laevis oocytes applying the ion-trap technique. This approach detects the quantity of ions released in or taken up from the restricted space existing between the oocyte plasma membrane and the tip of a large ion-selective electrode. Taking advantage of the fact that hSGLT1 in the absence of Na+ can cotransport glucose with protons, we used a pH electrode to determine a TOR of 8.00 ± 1.3 s−1 in the presence of 35 mM α-methyl-glucose at −150 mV (pH 5.5). For the same group of oocytes, a TOR of 13.3 ± 2.4 s−1 was estimated under near-Vmax conditions, i.e., in the presence of 90 mM Na+ and 5 mM α-methyl-glucose. Under these circumstances, the average cotransport current was −1.08 ± 0.61 μA (n = 14), and this activity was generated by an average of 3.6 ± 0.7 × 1011 cotransporter molecules/oocyte. PMID:21190656

  8. Multiparameter monitoring of short-term earthquake precursors and its physical basis. Implementation in the Kamchatka region

    Directory of Open Access Journals (Sweden)

    Pulinets Sergey

    2016-01-01

    Full Text Available We apply experimental approach of the multiparameter monitoring of short-term earthquake precursors which reliability was confirmed by the Lithosphere-Atmosphere-Ionosphere Coupling (LAIC model created recently [1]. A key element of the model is the process of Ion induced Nucleation (IIN and formation of cluster ions occurring as a result of the ionization of near surface air layer by radon emanating from the Earth's crust within the earthquake preparation zone. This process is similar to the formation of droplet’s embryos for cloud formation under action of galactic cosmic rays. The consequence of this process is the generation of a number of precursors that can be divided into two groups: a thermal and meteorological, and b electromagnetic and ionospheric. We demonstrate elements of prospective monitoring of some strong earthquakes in Kamchatka region and statistical results for the Chemical potential correction parameter for more than 10 years of observations for earthquakes with M≥6. As some experimental attempt, the data of Kamchatka volcanoes monitoring will be demonstrated.

  9. Satellite thermal monitoring of the 2010 - 2013 eruption of Kizimen volcano (Kamchatka) using MIROVA hot-spot detection system

    Science.gov (United States)

    Massimetti, Francesco; Coppola, Diego; Laiolo, Marco; Cigolini, Corrado

    2017-04-01

    After 81 years of rest, the Holocenic stratovolcano of Kizimen (Kamchatka, Russia) began a new eruptive phase on December 2010. The eruption was preceded by a year-long seismic unrest and fumarole activity, and persisted for 3 years showing a transition from explosive to effusive style. The initial explosive phase caused the partial disruption of the volcano summit and was followed by the effusion of andesitic lava flow along the eastern side of the edifice. Here we used an automatic hot-spot detection system named MIROVA (Middle InfraRed Observation of Volcanic Activity), in order to track the thermal evolution of the eruption and to understand the eruptive dynamic. MIROVA is based on the analysis IR images acquired by the MODIS sensor (Moderate Resolution Imaging Spectroradiometer) and is able to provide thermal maps (1 km resolution) and Volcanic Radiative Power (VRP, in Watt) time series in near real time (1-4 hours from satellite overpass). Each image with a thermal alert has been classified, distinguishing different quality level of the data based on cloud cover, viewing geometry and coherence with the VRP trend. The analysis of VRP variation show different thermal phases that have been correlated with independent observations of KVERT (Kamchatka Volcanic Eruption Response Team). Finally, we show that the relation between total thermal energy radiated (VRE, in Joule) and erupted lava volume is consistent with the typical radiant density of an intermediate-silicic lava flow (Coppola et al., 2013).

  10. The Influence of Features of Aluminium Alloys 2024, 6061 and 7075 on the Properties of Glare-Type Composites / Wpływ Właściwości Stopów Aluminium 2024, 6061, 7075 Na Cechy Kompozytu Typu Glare

    Directory of Open Access Journals (Sweden)

    Wilk M.S.

    2015-12-01

    Full Text Available The above paper presents the assumptions and results of the research whose aim was to determine the influence of 2024, 6061 and 7075 aluminum alloys on the final properties of GLARE-type composites. GLARE 3 2/1 type composites, made of two layers of the epoxy prepreg, reinforced with unidirectional glass fibers, arranged in the direction of 0°/90°, and two sheets of aluminum with a thickness of 0.4 mm, were investigated. Composites of various stacking configurations of alloy layers, made of one type of aluminum alloy (so-called ‘homogeneous composites’, and two different alloys (mixed composites, were analyzed. The properties of the composites were evaluated with the use of the mixing rule and compared with the test results.

  11. Oat β-glucan depresses SGLT1- and GLUT2-mediated glucose transport in intestinal epithelial cells (IEC-6).

    Science.gov (United States)

    Abbasi, Nazanin N; Purslow, Peter P; Tosh, Susan M; Bakovic, Marica

    2016-06-01

    Oat β-glucan consumption is linked to reduced risk factors associated with diabetes and obesity by lowering glycemic response and serum level of low-density lipoproteins. The purpose of this study was to identify the mechanism of action of oat β-glucan at the interface between the gut wall and the lumen responsible for attenuating glucose levels. We proposed that viscous oat β-glucan acts as a physical barrier to glucose uptake in normally absorptive gut epithelial cells IEC-6 by affecting the expression of intestinal glucose transporters. Concentration and time-dependent changes in glucose uptake were established by using a nonmetabolizable glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose. The effectiveness of nutrient transport in IEC-6 cells was shown by significant differences in glucose uptake and corresponding transporter expression. The expressions of glucose transporters sodium-glucose-linked transport protein 1 (SGLT1) and glucose transporter 2 (GLUT2) increased with time (0-60 minutes) and glucose levels (5-25 mmol/L). The suppression of glucose uptake and SGLT1 and GLUT2 expression by increasing concentrations (4-8 mg/mL) of oat β-glucan demonstrated a direct effect of the physical properties of oat β-glucan on glucose transport. These results affirmed oat β-glucan as a dietary agent for minimizing postprandial glucose and showed that modulating the activity of the key intestinal glucose transporters with oat β-glucan could be an effective way of lowering blood glucose levels in patients with diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Geochemical evolution of Bolshaya Udina, Malaya Udina, and Gorny Zub Volcanoes, Klyuchevskaya Group (Kamchatka)

    Science.gov (United States)

    Churikova, Tatiana; Gordeychik, Boris; Wörner, Gerhard; Flerov, Gleb; Hartmann, Gerald; Simon, Klaus

    2017-04-01

    The Klyuchevskaya group of volcanoes (KGV) located in the northern part of Kamchatka has the highest magma production rate for any arc worldwide and several of its volcanoes have been studied in considerable detail [e.g. Kersting & Arculus, 1995; Pineau et al., 1999; Dorendorf et al., 2000; Ozerov, 2000; Churikova et al., 2001, 2012, 2015; Mironov et al., 2001; Portnyagin et al., 2007, 2015; Turner et al., 2007]. However, some volcanoes of the KGV including Late-Pleistocene volcanoes Bolshaya Udina, Malaya Udina, Ostraya Zimina, Ovalnaya Zimina, and Gorny Zub were studied only on a reconnaissance basis [Timerbaeva, 1967; Ermakov, 1977] and the modern geochemical studies have not been carried out at all. Among the volcanoes of KGV these volcanoes are closest to the arc trench and may hold information on geochemical zonation with respect to across arc source variations. We present the first major and trace element data on rocks from these volcanoes as well as on their basement. All rocks are medium-calc-alkaline basaltic andesites to dacites except few low-Mg basalts from Malaya Udina volcano. Phenocrysts are mainly olivine, pyroxene, plagioclase and magnetite, Hb-bearing andesites and dacites are rarely found only in subvolcanic intrusions at Bolshaya Udina volcano. Lavas are geochemically similar to the active Bezymianny volcano, however, individual variations for each volcano exist in both major and trace elements. Trace element geochemistry is typical of island arc volcanism. Compared to KGV lavas all studied rocks form very narrow trends in all major element diagrams, which almost do not overlap with the fields of other KGV volcanoes. The lavas are relatively poor in alkalis, TiO2, P2O5, FeO, Ni, Zr, and enriched in SiO2 compared to other KGV volcanics and show greater geochemical and petrological evidence of magmatic differentiation during shallow crustal processing. Basement samples of the Udinskoe plateau lavas to the east of Bolshaya Udina volcano have

  13. Gas flux measurements of episodic bimodal eruptive activity at Karymsky volcano (Kamchatka, Russia)

    Science.gov (United States)

    Arellano, S.; Galle, B.; Melnikov, D.

    2012-04-01

    Volcanoes of intermediate magmatic composition commonly exhibit episodes of intermittent gas and ash emission of variable duration. Due to the multiple conditions present at each system, different mechanisms have been proposed to account for the observed activity, and without key measurements at hand, a definite understanding of the situation might not be singled out. Karymsky, the most active volcano of Central Kamchatka, has presented a remarkably stable pattern of bimodal eruption since a few weeks after its violent reactivation in 1996. Periods of quasi-periodic explosive emissions with typical recurrence intervals of 3-10 min are alternated with episodes of semi-continuous discharge which intensity has a typical modulation at a frequency of 1 Hz. Geophysical studies at Karymsky have identified the main visual, seismic and acoustic features of these two eruption modalities. From these observations, the time scales of the processes have been defined and relevant models have been formulated, according to which the two modes are controlled by the rheological properties of an intruding gas-saturated magma batch and a shallow gas-depleted magma plug. Explosions are explained as the consequence of the formation of temporary sealing, overpressure buildup and vent clearance. Clearly, direct measurements of the gas emission rate are the key parameter to test such models. In this work, we report on the results of a field campaign for SO2 gas measurements carried out at Karymsky during 10-14 September 2011. We deployed 2 NOVAC-type, scanning DOAS systems as well as 1 rapid wide-Field of View mini-DOAS plume tracker. With this setup, we derived time-resolved SO2 flux, plume height, direction and speed, and detected pulses of increasing emission with high temporal resolution. We observed phases of explosive and quiescent degassing with variable amounts of ash emission and detected intensity changes of the associated acoustic signals. The repose time intervals between these

  14. Petrological and geochemical evolution of the Tolbachik volcanic massif, Kamchatka, Russia

    Science.gov (United States)

    Churikova, Tatiana G.; Gordeychik, Boris N.; Iwamori, Hikaru; Nakamura, Hitomi; Ishizuka, Osamu; Nishizawa, Tatsuji; Haraguchi, Satoru; Miyazaki, Takashi; Vaglarov, Bogdan S.

    2015-12-01

    Data on the geology, petrography, and geochemistry of Middle-Late-Pleistocene rocks from the Tolbachik volcanic massif (Kamchatka, Klyuchevskaya group of volcanoes) are presented and compared with rocks from the neighboring Mount Povorotnaya, Klyuchevskaya group basement, and Holocene-historical Tolbachik monogenetic cones. Two volcanic series of lavas, middle-K and high-K, are found in the Tolbachik massif. The results of our data analysis and computer modeling of crystallization at different P-T-H2O-fO2 conditions allow us to reconstruct the geochemical history of the massif. The Tolbachik volcanic massif started to form earlier than 86 ka based on K-Ar dating. During the formation of the pedestal and the lower parts of the stratovolcanoes, the middle-K melts, depleted relative to NMORB, fractionated in water-rich conditions (about 3% of H2O). At the Late Pleistocene-Holocene boundary, a large fissure zone was initiated and the geodynamical regime changed. Upwelling associated with intra-arc rifting generated melting from the same mantle source that produced magmas more enriched in incompatible trace elements and subduction components; these magmas are high-K, not depleted relative to N-MORB melts with island arc signatures and rift-like characteristics. The fissure opening caused degassing during magma ascent, and the high-K melts fractionated at anhydrous conditions. These high-K rocks contributed to the formation of the upper parts of stratovolcanoes. At the beginning of Holocene, the high-K rocks became prevalent and formed cinder cones and associated lava fields along the fissure zone. However, some features, including 1975-1976 Northern Breakthrough, are represented by middle-K high-Mg rocks, suggesting that both middle-K and high-K melts still exist in the Tolbachik system. Our results show that fractional crystallization at different water conditions and a variably depleted upper mantle source are responsible for all observed variations in rocks within

  15. The Holocene environmental history of a small coastal lake on the north-eastern Kamchatka Peninsula

    Science.gov (United States)

    Solovieva, N.; Klimaschewski, A.; Self, A. E.; Jones, V. J.; Andrén, E.; Andreev, A. A.; Hammarlund., D.; Lepskaya, E. V.; Nazarova, L.

    2015-11-01

    A radiocarbon and tephra-dated sediment core from Lifebuoy Lake, located on the north-east coast of Kamchatka Peninsula, was analysed for pollen, spores, diatoms, chironomids and tephra in order to uncover regional environmental history. The 6500-year environmental history of Lifebuoy Lake correlates with the broad regional patterns of vegetation development and climate dynamics with both diatoms and chironomids showing near-synchronous changes. Between ca. 6300 and 3900 cal yr BP, the lake ecosystem was naturally enriched, with several Stephanodiscus species dominating the diatom plankton. This natural eutrophication state is likely to be due to a combination of the base-rich catchment geology, the fertilisation effect of several fires in the catchment, silica input from tephra layers and, possibly, nitrogen input from seabirds. The substantial tephra deposit at about 3850 cal yr BP might have stopped sedimentary phosphorus from entering the lake water thus decreasing the trophic state of the lake and facilitating the shift in diatom composition to a benthic Fragiliariaceae complex. Both diatoms and chironomids showed simultaneous compositional changes, which are also reflected by statistically significant changes in their rates of change 300-400 years after the arrival of Pinus pumila in the lake catchment. The rapid increase in both total diatom concentration and the percentage abundance of the large heavy species, Aulacoseira subarctica might be a response to the change in timing and intensity of lake spring turn-over due to the changes in the patterns of North Pacific atmospheric circulation, most notably westward shift of the Aleutian Low. The two highest peaks in A. subarctica abundance at Lifebouy Lake occurred during opposite summer temperature inferences: the earlier peak (3500-2900 cal yr BP) coincided with warm summers and the latter peak (300 cal yr BP-present) occurred during the cold summer period. These imply that A. subarctica shows no direct

  16. High-Mg# andesitic lavas of the Shisheisky Complex, Northern Kamchatka: implications for primitive calc-alkaline magmatism

    Science.gov (United States)

    Bryant, J. A.; Yogodzinski, G. M.; Churikova, T. G.

    2011-05-01

    Primitive arc magmatism and mantle wedge processes are investigated through a petrologic and geochemical study of high-Mg# (Mg/Mg + Fe > 0.65) basalts, basaltic andesites and andesites from the Kurile-Kamchatka subduction system. Primitive andesitic samples are from the Shisheisky Complex, a field of Quaternary-age, monogenetic cones located in the Aleutian-Kamchatka junction, north of Shiveluch Volcano, the northernmost active composite volcano in Kamchatka. The Shisheisky lavas have Mg# of 0.66-0.73 at intermediate SiO2 (54-58 wt%) with low CaO (3.0 wt%) and K2O (>1.0 wt%). Olivine phenocryst core compositions of Fo90 appear to be in equilibrium with whole-rock `melts', consistent with the sparsely phyric nature of the lavas. Compared to the Shisheisky andesites, primitive basalts from the region (Kuriles, Tolbachik, Kharchinsky) have higher CaO (>9.9 wt%) and CaO/Al2O3 (>0.60), and lower whole-rock Na2O (andesites. The absence of plagioclase phenocrysts from the primitive andesitic lavas contrasts the plagioclase-phyric basalts, indicating relatively high pre-eruptive water contents for the primitive andesitic magmas compared to basalts. Estimated temperature and water contents for primitive basaltic andesites and andesites are 984-1,143°C and 4-7 wt% H2O. For primitive basalts they are 1,149-1,227°C and 2 wt% H2O. Petrographic and mineral compositions suggest that the primitive andesitic lavas were liquids in equilibrium with mantle peridotite and were not produced by mixing between basalts and felsic crustal melts, contamination by xenocrystic olivine, or crystal fractionation of basalt. Key geochemical features of the Shisheisky primitive lavas (high Ni/MgO, Na2O, Ni/Yb and Mg# at intermediate SiO2) combined with the location of the volcanic field above the edge of the subducting Pacific Plate support a genetic model that involves melting of eclogite or pyroxenite at or near the surface of the subducting plate, followed by interaction of that melt with

  17. Holocene environmental changes in southern Kamchatka, Far Eastern Russia, inferred from a pollen and testate amoebae peat succession record

    Science.gov (United States)

    Klimaschewski, A.; Barnekow, L.; Bennett, K. D.; Andreev, A. A.; Andrén, E.; Bobrov, A. A.; Hammarlund, D.

    2015-11-01

    High resolution palaeoenvironmental records in Far-Eastern Russia are rare, and the Kamchatka Peninsula is among the least studied areas of the region. This paper describes a record spanning the last ca. 11,000 yr, obtained from a bog in the southern part of Kamchatka. The radiocarbon dated core was analysed for pollen, testate amoebae, charcoal and loss-on-ignition (LOI). The vegetation during the early Holocene was dominated by grasses (Poaceae), birch (Betula) and heath (Ericaceae p. p.). Around 10,300 cal yr BP there was a substantial change in the vegetation cover to shrub alder (Alnus viridis s.l.) stands with sedges and ferns (Polypodiophyta) as well as herbs such as meadow rue (Thalictrum) in the understory. In the surroundings of Utka peatlands started to form. The variations in the vegetation cover were most probably caused by climatic changes. At the beginning of sediment accumulation, before 10,300 cal yr BP, the composition of the vegetation points to cooler summers and/or decreased annual precipitation. Around 10,300 cal yr BP, changes in vegetation occurred due to rising temperatures and/or changed water regimes. Increased abundancies of dry indicating testate amoebae after 9100 cal yr BP point to intermediate to dry soil conditions. Between 8600 and 7700 cal yr BP tree alder (Alnus incana) was widely spread at the site which probably indicates optimal environmental conditions. The tephra layer at 381-384.5 cm (ca. 8500 cal yr BP) produces a strong impact on the testate amoebae assemblages. At 7700 cal yr BP there was a sudden drop of A. incana in the local vegetation. From this time on, A. incana and also A. viridis decrease continuously whereas Betula gradually increases. The upper part of the sequence (after 6300 cal yr BP) shows higher abundancies of meadowsweet (Filipendula) and sweet gale (Myrica) pollen. After 6300 cal yr BP, changes in testate amoebae demonstrate variable soil moisture conditions at the site. Between 3700 and 1800 cal yr BP

  18. Early Holocene volcanism in CKD (Kamchatka) as a mechanical probe of the stress level in the crust.

    Science.gov (United States)

    Simakin, Alexander; Shaposhnikova, Olga

    2016-04-01

    The last (late Pleistocene) glaciation in Kluychevskaya group of volcanoes (KGV) can be considered as a large scale mechanical experiment allowing evaluation of the level of the global geodynamic stresses in the crust of North Kamchatka. KGV is located in the Central Kamchatka depression (CKD). Formation of the CKD can be connected with accretion of Kronotsky paleoarc to the Kamchatka edge c.a. 5 Mys ago. At the compression stage zone of the contact was thickened so that lower part can reach PT parameters of basalt-eclogite transition. Suggested carbonates contamination of the mantle wedge during accretion (Simakin et al., 2015) can became a source of CO2 facilitating eclogite formation. Dense eclogitic keel and trench retreat following accretion can be the driving forces of the CKD rift formation. Extension is partially accommodated (several mm/yr eastward motion) on the eastern border of CKD in the zone of the normal faulting (Kozhurin et al., 2006). And partially extension is accommodated by the formation of the series of dykes of submeridional direction marked by monogenic cones on the surface. At the last phase of the Pleistocene glaciation KGV was covered by the ice cap with 80 km diameter and above 1000 m maximum thickness on the slopes. After the fast deglaciation surface uplift has produced horizontal compression (Simakin and Muravyev, 2015; Pagli and Sigmundsson, 2008). Addition of the deglacial compression to the geodynamic extension turns s1 direction to the horizontal latitudinal one. Due to the horizontal compression areal of eruptions was expanded towards edges of the former glacier. Numerical modeling demonstrates that maximum level of the glacial stress is proportional to the ice gravity load and is estimated to be 5.8-7.5 MPa. Initially principle compressive stress due to the deglaciation was higher than geodynamic one abs(s1,glac) > abs(s1,geod). Time of the volcanism return to the basic submeridional direction marked the moment of viscous

  19. Design, synthesis and in vivo anti-hyperglycemic activity of gem-dimethyl-bearing C-glucosides as SGLT2 inhibitors

    Institute of Scientific and Technical Information of China (English)

    Wen Jing Zhao; Yong Heng Shi; Gui Long Zhao; Yu Li Wang; Hua Shao; Li Da Tang; Jian Wu Wang

    2011-01-01

    A series of gem-dimethyl-bearing C-glucosides were designed and synthesized as SGLT2 inhibitors, with anhydrous aluminum chloride-mediated Friedel-Crafts alkylation to construct the gem-dimethyl functionality being the key step. The in vivo anti-hyperglycemic activity was evaluated with mice oral glucose tolerance test (OGTT), and all the synthesized compounds showed significant but less potent anti-hyperglycemic activity than the positive control dapagliflozin.

  20. 2008 Volcanic activity in Alaska, Kamchatka, and the Kurile Islands: Summary of events and response of the Alaska Volcano Observatory

    Science.gov (United States)

    Neal, Christina A.; McGimsey, Robert G.; Dixon, James P.; Cameron, Cheryl E.; Nuzhdaev, Anton A.; Chibisova, Marina

    2011-01-01

    The Alaska Volcano Observatory (AVO) responded to eruptions, possible eruptions, and volcanic unrest or suspected unrest at seven separate volcanic centers in Alaska during 2008. Significant explosive eruptions at Okmok and Kasatochi Volcanoes in July and August dominated Observatory operations in the summer and autumn. AVO maintained 24-hour staffing at the Anchorage facility from July 12 through August 28. Minor eruptive activity continued at Veniaminof and Cleveland Volcanoes. Observed volcanic unrest at Cook Inlet's Redoubt Volcano presaged a significant eruption in the spring of 2009. AVO staff also participated in hazard communication regarding eruptions or unrest at nine volcanoes in Russia as part of a collaborative role in the Kamchatka and Sakhalin Volcanic Eruption Response Teams.

  1. International Studies of Hazardous Groundwater/Surface Water Exchange in the Volcanic Eruption and Tsunami Affected Areas of Kamchatka

    Science.gov (United States)

    Kontar, Y. A.; Gusiakov, V. K.; Izbekov, P. E.; Gordeev, E.; Titov, V. V.; Verstraeten, I. M.; Pinegina, T. K.; Tsadikovsky, E. I.; Heilweil, V. M.; Gingerich, S. B.

    2012-12-01

    During the US-Russia Geohazards Workshop held July 17-19, 2012 in Moscow, Russia the international research effort was asked to identify cooperative actions for disaster risk reduction, focusing on extreme geophysical events. As a part of this recommendation the PIRE project was developed to understand, quantify, forecast and protect the coastal zone aquifers and inland water resources of Kamchatka (Russia) and its ecosystems affected by the November 4, 1952 Kamchatka tsunami (Khalatyrka Beach near Petropavlovsk-Kamchatskiy) and the January 2, 1996 Karymskiy volcano eruption and the lake tsunami. This project brings together teams from U.S. universities and research institutions located in Russia. The research consortium was briefed on recent technical developments and will utilize samples secured via major international volcanic and tsunami programs for the purpose of advancing the study of submarine groundwater discharge (SGD) in the volcanic eruption and tsunami affected coastal areas and inland lakes of Kamchatka. We plan to accomplish this project by developing and applying the next generation of field sampling, remote sensing, laboratory techniques and mathematical tools to study groundwater-surface water interaction processes and SGD. We will develop a field and modeling approach to define SGD environment, key controls, and influence of volcano eruption and tsunami, which will provide a framework for making recommendations to combat contamination. This is valuable for politicians, water resource managers and decision-makers and for the volcano eruption and tsunami affected region water supply and water quality of Kamchatka. Data mining and results of our field work will be compiled for spatial modeling by Geo-Information System (GIS) using 3-D Earth Systems Visualization Lab. The field and model results will be communicated to interested stakeholders via an interactive web site. This will allow computation of SGD spatial patterns. In addition, thanks to the

  2. Deciphering petrogenic processes using Pb isotope ratios from time-series samples at Bezymianny and Klyuchevskoy volcanoes, Central Kamchatka Depression

    Science.gov (United States)

    Kayzar, Theresa M.; Nelson, Bruce K.; Bachmann, Olivier; Bauer, Ann M.; Izbekov, Pavel E.

    2014-10-01

    The Klyuchevskoy group of volcanoes in the Kamchatka arc erupts compositionally diverse magmas (high-Mg basalts to dacites) over small spatial scales. New high-precision Pb isotope data from modern juvenile (1956-present) erupted products and hosted enclaves and xenoliths from Bezymianny volcano reveal that Bezymianny and Klyuchevskoy volcanoes, separated by only 9 km, undergo varying degrees of crustal processing through independent crustal columns. Lead isotope compositions of Klyuchevskoy basalts-basaltic andesites are more radiogenic than Bezymianny andesites (208Pb/204Pb = 37.850-37.903, 207Pb/204Pb = 15.468-15.480, and 206Pb/204Pb = 18.249-18.278 at Bezymianny; 208Pb/204Pb = 37.907-37.949, 207Pb/204Pb = 15.478-15.487, and 206Pb/204Pb = 18.289-18.305 at Klyuchevskoy). A mid-crustal xenolith with a crystallization pressure of 5.2 ± 0.6 kbars inferred from two-pyroxene geobarometry and basaltic andesite enclaves from Bezymianny record less radiogenic Pb isotope compositions than their host magmas. Hence, assimilation of such lithologies in the middle or lower crust can explain the Pb isotope data in Bezymianny andesites, although a component of magma mixing with less radiogenic mafic recharge magmas and possible mantle heterogeneity cannot be excluded. Lead isotope compositions for the Klyuchevskoy Group are less radiogenic than other arc segments (Karymsky—Eastern Volcanic Zone; Shiveluch—Northern Central Kamchatka Depression), which indicate increased lower-crustal assimilation beneath the Klyuchevskoy Group. Decadal timescale Pb isotope variations at Klyuchevskoy demonstrate rapid changes in the magnitude of assimilation at a volcanic center. Lead isotope data coupled with trace element data reflect the influence of crustal processes on magma compositions even in thin mafic volcanic arcs.

  3. Isolation, characterization and molecular cloning of Duplex-Specific Nuclease from the hepatopancreas of the Kamchatka crab

    Directory of Open Access Journals (Sweden)

    Vagner Laura L

    2008-05-01

    Full Text Available Abstract Background Nucleases, which are key components of biologically diverse processes such as DNA replication, repair and recombination, antiviral defense, apoptosis and digestion, have revolutionized the field of molecular biology. Indeed many standard molecular strategies, including molecular cloning, studies of DNA-protein interactions, and analysis of nucleic acid structures, would be virtually impossible without these versatile enzymes. The discovery of nucleases with unique properties has often served as the basis for the development of modern molecular biology methods. Thus, the search for novel nucleases with potentially exploitable functions remains an important scientific undertaking. Results Using degenerative primers and the rapid amplification of cDNA ends (RACE procedure, we cloned the Duplex-Specific Nuclease (DSN gene from the hepatopancreas of the Kamchatka crab and determined its full primary structure. We also developed an effective method for purifying functional DSN from the crab hepatopancreas. The isolated enzyme was highly thermostable, exhibited a broad pH optimum (5.5 – 7.5 and required divalent cations for activity, with manganese and cobalt being especially effective. The enzyme was highly specific, cleaving double-stranded DNA or DNA in DNA-RNA hybrids, but not single-stranded DNA or single- or double-stranded RNA. Moreover, only DNA duplexes containing at least 9 base pairs were effectively cleaved by DSN; shorter DNA duplexes were left intact. Conclusion We describe a new DSN from Kamchatka crab hepatopancreas, determining its primary structure and developing a preparative method for its purification. We found that DSN had unique substrate specificity, cleaving only DNA duplexes longer than 8 base pairs, or DNA in DNA-RNA hybrids. Interestingly, the DSN primary structure is homologous to well-known Serratia-like non-specific nucleases structures, but the properties of DSN are distinct. The unique substrate

  4. Effect of BSA-induced ER stress on SGLT protein expression levels and alpha-MG uptake in renal proximal tubule cells.

    Science.gov (United States)

    Lee, Yu Jin; Suh, Han Na; Han, Ho Jae

    2009-06-01

    Recent studies demonstrated that endoplasmic reticulum (ER) stress regulates glucose homeostasis and that ER stress preconditioning which induces an adaptive, protective unfolded protein response (UPR) offers cytoprotection against nephrotoxins. Thus the aim of the present study was to use renal proximal tubule cells (PTCs) to further elucidate the link between the BSA-induced ER stress and alpha-methyl-d-glucopyranoside (alpha-MG) uptake and to identify related signaling pathways. Among ER stress inducers such as high glucose, BSA, H2O2, or tumicamycin, BSA pretreatment ameliorated the reduction of Na(+)-glucose cotransporter (SGLT) expression and alpha-MG uptake by gentamicin or cyclosporine A. Immunofluorescence studies revealed that BSA (10 mg/ml) stimulated the expression of glucose-regulated protein 78 (GRP78), an ER stress biomarker. In addition, BSA increased levels of GRP78 protein expression and eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation in a time-dependent manner. Furthermore, transfection with a GRP78-specific small interfering RNA (siRNA) inhibited BSA-stimulated SGLT expression and alpha-MG uptake. In experiments designed to unravel the mechanisms underlying BSA-induced ER stress, BSA stimulated the production of cellular reactive oxygen species (ROS), and antioxidants such as ascorbic acid or N-acetylcysteine (NAC) blocked BSA-induced increases in GRP78 activation, eIF2alpha phosphorylation, SGLT expression, and alpha-MG uptake. Moreover, the cells upregulated peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA levels in response to BSA or troglitazone (a PPARgamma agonist), but BSA was ineffective in the presence of GW9662 (a PPARgamma antagonist). In addition, both BSA and troglitazone stimulated GRP78 and eIF2alpha activation, SGLT expression, and alpha-MG uptake, whereas GW9662 inhibited the effects of BSA. BSA also stimulated phosphorylation of JNK and NF-kappaB, and GW9662 or GRP78 siRNA attenuated this

  5. Glucosamine-induced Sp1 O-GlcNAcylation ameliorates hypoxia-induced SGLT dysfunction in primary cultured renal proximal tubule cells.

    Science.gov (United States)

    Suh, Han Na; Lee, Yu Jin; Kim, Mi Ok; Ryu, Jung Min; Han, Ho Jae

    2014-10-01

    The aim of this study is to determine whether GlcN could recover the endoplasmic reticulum (ER) stress-induced dysfunction of Na(+) /glucose cotransporter (SGLT) in renal proximal tubule cells (PTCs) under hypoxia. With the rabbit model, the renal ischemia induced tubulointerstitial abnormalities and decreased SGLTs expression in tubular brush-border, which were recovered by GlcN. Thus, the protective mechanism of GlcN against renal ischemia was being examined by using PTCs. Hypoxia decreased the level of protein O-GlcNAc and the expression of O-GlcNAc transferase (OGT) while increased O-GlcNAcase (OGA) and these were reversed by GlcN. Hypoxia also decreased the expression of SGLTs (SGLT1 and 2) and [(14) C]-α-methyl-D-glucopyranoside (α-MG) uptake which were recovered by GlcN and PUGNAc (OGA inhibitor). Hypoxia enhanced reactive oxygen species (ROS) and then ER stress proteins, glucose-regulated protein 78 (GRP78), and C/EBP-homologous protein (CHOP). However, the expression of GRP78 increased till 6 h and then decreased whereas CHOP increased gradually. Moreover, decreased GRP78 and increased CHOP were reversed by NAC (antioxidant) and GlcN. GlcN ameliorated hypoxia-induced decrease of O-GlcNAc modification of Sp1 but OGT or Sp1 siRNAs blocked the recovery effect of GlcN on SGLT expression and α-MG uptake. In addition, hypoxia-decreased GRP78 and HIF-1α expression was reversed by GlcN but OGT siRNA or Sp1 siRNA ameliorated the effect of GlcN. When PTCs were transfected with GRP78 siRNA or HIF-1α siRNA, SGLT expression and α-MG uptake was decreased. Taken together, these data suggest that GlcN-induced O-GlcNAc modified Sp1 with stimulating GRP78 and HIF-1α activity ameliorate hypoxia-induced SGLT dysfunction in renal PTCs. J. Cell. Physiol. 229: 1557-1568, 2014. © 2014 Wiley Periodicals, Inc.

  6. The First Result of the Precursors Observation in Karymshina Observatory (Kamchatka, Russia) for Moderate Earthquakes

    Science.gov (United States)

    Gordeev, E.; Uyeda, S.; Nagao, T.; Molchanov, O.; Hattori, K.; Lutikov, A.; Gladyshev, V.; Schekotov, A.; Chebrov, V.

    2001-12-01

    In 1999 the complex geophysical observatory was created in Kamchatka, Russia under mutual Russian-Japanese scientific project. The main purpose of this project is to investigate electromagnetic and other phenomena in connection with earthquakes. The observatory is sited in the place without any sources of industrial noise. The seismic waveforms, acoustic emission, telluric currents, magnetic pulsation and chemical composition of underground water are measured continuously. The measurements of three components of ground displacement velocity is realized by seismometer in the frequency band 0.5-40 Hz with sensitivity threshold 10-8 m/s and dynamic range of 90 dB. Triaxial induction magnetometer measures geomagnetic pulsations in the frequency range 0.003-30 Hz with sensitivity threshold 20 pT/Hz1/2 at frequency 0.01 Hz and 0.02 pT/Hz1/2 at frequencies higher than 10 Hz. Dynamic range of the magnetometer is 90 dB. Measurements of NS and EW components of telluric currents with maximum distance between electrodes of about 500 m are carried out. The acoustic emission receiver (high-frequency seismometer) based on mechanical pendulum with ceramic transducer is installed in 30 m borehole. The output signals are filtered by 4 filters with central frequencies equal to 30, 160, 500 and 1000 Hz. In the same borehole was installed high-frequency seismic noise (HFSN) piezoceramic sensor with very narrow band around 30 Hz and sensitivity threshold 10-12 m. The chemical components Cl, HCO3, SO4, Na, K, Ca, H3BO3, H4SiO4, gases CH4, N2, O2, CO2, Ar, He, H2 and hydrocarbonates C2H6, C2H4, C3H8, C3H6, C4H10, C4H10i are analysed in a few wells nearby the observatory. The atmospheric pressure, direction and velocity of the wind, humidity, precipitation, air and ground temperature are measured using meteorological station installed at observatory. Since June 2000 CGO Karymshina has started regular simultaneous monitoring of the above-mentioned parameters. Processing and analysis of the

  7. Microbial metabolism and the geochemistry of bioactive gases in Kamchatka and Lassen hot springs

    Science.gov (United States)

    He, B.; Robb, F. T.; Colman, A. S.

    2013-12-01

    Thermophilic and hyperthermophilic metabolisms include several pathways that involve dissolved gases as carbon sources, energy sources, and/or waste products. In hot springs, dissolved gas concentrations are often compared with concentrations predicted based upon equilibration with free phase gases bubbling up in the same springs. This comparison guides the inference of metabolic modes in the subsurface, spring vents, and outflow channels. Supersaturation is invoked as a signal of a biogenic source for the gas, while undersaturation is interpreted to indicate microbial consumption. However, these conventional interpretations of disequilibria between dissolved and free phase gases can be misleading. They ignore the decoupling of water and free phase gas transport in terrestrial hot springs and the effects on gas solubility of thermal and pressure gradients that exist as fluids travel from depth to vent. We have surveyed two significant geothermal regions: Lassen Volcanic National Park (LVNP), California, USA (July, 2009), and Uzon Caldera, Kamchatka, Russia (August, 2010) in past years. We collected and analyzed both free phase and dissolved gas composition from a number of hot springs in each region. We used Henry's Law to calculate apparent saturation state of the dissolved gases with respect to the free phases gases bubbling up in the springs. We then constructed a 1-D gas exchange-transport model to examine the thermodynamic drivers and potential kinetic hindrances to gas exchange and equilibration in water and gases ascending continental hot spring systems. Specifically, this model takes into account: (1) the vertical gradient in temperature and pressure, (2) interaction between the bioactive gases via water gas shift reaction, and (3) fluid transport from subsurface to vent. We have modeled several end-member transport-exchange scenarios: (1) gas and spring water co-ascend in a closed system, with instantaneous equilibration between free phase and dissolved

  8. Pre-eruption deformation and seismic anomalies in 2012 in Tolbachik volcanic zone, Kamchatka

    Science.gov (United States)

    Kugaenko, Yulia; Saltykov, Vadim; Titkov, Nikolay

    2014-05-01

    Tolbachik volcanic zone (active volcano Plosky Tolbachik, dormant volcano Ostry Tolbachik and Tolbachik zone of cinder cones) is situated in the south part of Klyuchevskaya group of volcanoes in Kamchatka. All historical fissure eruptions of Tolbachik volcanic zone (1740, 1941, 1975-76 and 2012-13) were connected with one or another activity of Plosky Tolbachik volcano. In 1941 the fissure vent was occurred during the completion of 1939-41 terminal eruption of Plosky Tolbachik. In 1975 the Large Tolbachik Fissure Eruption (LTFE) was forestalled by Plosky Tolbachik terminal activity of the Hawaiian type and then was accompanied by the catastrophic collapse in the crater of Plosky Tolbachik. What events took place in the vicinity of Plosky Tolbachik in 2012 before the 2012-13 fissure eruption? In contrast of the 1975-76 LTFE the eruption 2012-13 was not preceded by intensive seismic preparation. Nowadays Klyuchevskaya group of volcanoes is under monitoring by 12 seismic stations, so we can investigate seismicity in details on the lower energy level then forty years ago. We analyzed seismicity of Plosky Tolbachik using regional catalogue 1999-2012. Anomalies of low-energy (M≥1.5) seismicity parameters (increase of seismicity rate and seismic energy) were discovered. This is evidence of seismic activization covered the whole Plosky Tolbachik volcano. The significance of this anomaly was estimated by distribution function of emitted seismic energy. Statistically significant transition of seismicity from background level to high and extremely high levels was revealed. It corresponds to multiple growth of earthquake number and seismic energy in 2012, July-November (five months before the eruption). The seismicity transition from background level to high level was happen in August 2012. During last three weeks before fissure eruption seismicity of analyzed seismoactive volume was on extremely high level. Earthquakes from fissure site directly appeared only on November 27

  9. Initial H2O content and conditions of parent magma origin for Gorely volcano (Southern Kamchatka) estimated by trace element thermobarometry

    Science.gov (United States)

    Nazarova, D. P.; Portnyagin, M. V.; Krasheninnikov, S. P.; Mironov, N. L.; Sobolev, A. V.

    2017-01-01

    The formation conditions of the parental magmas of Gorely volcano, which is located behind a volcanic front in Southern Kamchatka, have been evaluated using the modern methods of micro-element thermobarometry. These magmas contained 1.7 ± 0.8 (2σ) wt % of H2O, the majority (82%) of which has been lost from inclusions. They crystallized at 1121 ± 17°C and an oxygen fugacity of ΔQFM 1.2 ± 0.2, and could have been produced by about 11% melting of an enriched MORB source (E-DMM) at a temperature of about 1270°C, and a pressure of about 1.5 GPa. A distinctive feature of Gorely volcano, compared with frontal volcanoes of Kamchatka, is the unusually high temperature (925 ± 20°C) of formation of the subduction component corresponding to the region of existence of water-bearing melts.

  10. Draft Genome Sequence of Geobacillus icigianus Strain G1w1T Isolated from Hot Springs in the Valley of Geysers, Kamchatka (Russian Federation).

    Science.gov (United States)

    Bryanskaya, Alla V; Rozanov, Aleksey S; Logacheva, Maria D; Kotenko, Anastasia V; Peltek, Sergey E

    2014-10-23

    The Geobacillus icigianus G1w1(T) strain was isolated from sludge samples of unnamed vaporing hydrothermal (97°С) outlets situated in a geyser in the Troinoy region (Valley of Geysers, Kronotsky Nature Reserve, Kamchatka, Russian Federation; 54°25'51.40″N, 160°7'41.40″E). The sequenced and annotated genome is 3,457,810 bp and encodes 3,342 genes.

  11. Progress in Synthesis of C-Aryl Glucosides Sodium Glucose Co-Transporter 2 Inhibitors%C-芳基糖苷类SGLT2抑制剂的合成研究进展

    Institute of Scientific and Technical Information of China (English)

    杜铁奇; 郑亿; 朱灵龙; 钟为慧

    2015-01-01

    Sodium glucose Co-transporter 2 (SGLT2) has been a hot spot of research on the treatment for type II diabetes. Inhibiting SGLT2, which works in the kidney specially, can reduce renal glucose reab-sorption, excrete excess glucose through the urine and lower the plasma glucose. This paper briefly reviews the synthetic routes to the C-aryl glucosides sodium glucose Co-transporter 2 inhibitors on the market, such as Ipragliflozin, Empagliflozin.%钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂是目前Ⅱ型糖尿病药物研究的热点之一。通过抑制这种在肾脏特异性表达的钠-葡萄糖协同转运蛋白2(SGLT2),可以减少肾脏对葡萄糖的重吸收,增加葡萄糖在尿中的排泄,从而降低血糖。本文将针对已上市的C-芳基糖苷类SGLT2抑制剂伊格列净和恩格列净的合成路线进行简要评述。

  12. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin.

    Science.gov (United States)

    Katsuda, Yoshiaki; Sasase, Tomohiko; Tadaki, Hironobu; Mera, Yasuko; Motohashi, Yu; Kemmochi, Yusuke; Toyoda, Kaoru; Kakimoto, Kochi; Kume, Shinichi; Ohta, Takeshi

    2015-01-01

    The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats.

  13. Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin

    Science.gov (United States)

    KATSUDA, Yoshiaki; SASASE, Tomohiko; TADAKI, Hironobu; MERA, Yasuko; MOTOHASHI, Yu; KEMMOCHI, Yusuke; TOYODA, Kaoru; KAKIMOTO, Kochi; KUME, Shinichi; OHTA, Takeshi

    2015-01-01

    The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats. PMID:25736710

  14. Predicted radionuclide release from reactor-related unenclosed solid objects dumped in the Sea of Japan and the Pacific Ocean, east coast of Kamchatka

    Energy Technology Data Exchange (ETDEWEB)

    Mount, M.E. [Lawrence Livermore National Lab., CA (United States); Lynn, N.M.; Warden, J.M. [Royal Naval Coll., Greenwich (United Kingdom)

    1996-06-01

    Between 1978 and 1991 reactor-related solid radioactive waste was dumped by the former Soviet Union as unenclosed objects in the Pacific Ocean, east coast of Kamchatka, and the Sea of Japan. This paper presented estimates for the current (1994) inventory of activation and corrosion products contained in the reactor-related unenclosed solid objects. In addition, simple models derived for prediction of radionuclide release from marine reactors dumped in the Kara Sea are applied to certain of the dumped objects to provide estimates of radionuclide release to the Pacific Ocean, east coast of Kamchatka, and Sea of Japan environments. For the Pacific Ocean, east coast of Kamchatka, total release rates start below 0.01 GBq yr{sup -1} and over 1,000 years, fall to 100 Bq yr{sup -1}. In the Sea of Japan, the total release rate starts just above 1 GBq yr{sup - 1}, dropping off to a level less than 0.1 GBq yr{sup -1}, extending past the year 4,000.

  15. Taxonomy of the early life stages of arrowtooth flounder (Atheresthes stomias) and Kamchatka flounder (A. evermanni) in the eastern Bering Sea, with notes on distribution and condition

    Science.gov (United States)

    De Forest, Lisa; Duffy-Anderson, J. T.; Heintz, R. A.; Matarese, A. C.; Siddon, E. C.; Smart, T. I.; Spies, I. B.

    2014-11-01

    Arrowtooth flounder (Atheresthes stomias) and Kamchatka flounder (A. evermanni) are closely related flatfish species that co-occur in the eastern Bering Sea. As adults, arrowtooth flounder can be distinguished from Kamchatka flounder; however, larvae and early juveniles can only be indentified to the genus level due to morphological similarities. This has precluded studies of ecology for the early life stages of both species in the eastern Bering Sea. In this study, we developed a genetic technique to identify the larvae and early juveniles of the two species using mtDNA cytochrome oxidase subunit I (COI). Genetically identified specimens were then examined to determine a visual identification method based on pigment patterns and morphology. Specimens 6.0-12.0 mm SL and≥18.0 mm SL can be identified to the species level, but species identification of individuals 12.1-17.9 mm SL by visual means alone remains elusive. The distribution of larvae (larvae and juveniles of each species by analyzing lipid content (%) and energy density (kJ/g dry mass). Kamchatka flounder larvae on average had higher lipid content than arrowtooth flounder larvae, but were also larger on average than arrowtooth flounder larvae in the summer. When corrected for length, both species had similar lipid content in the larval and juvenile stages.

  16. 基于视觉仿真的飞机座舱风挡眩光分布影响研究%Cockpit Windshield Glare Analysis Based on Optical Simulation

    Institute of Scientific and Technical Information of China (English)

    邓金萍; 李闻; 俞金海; 陈迎春

    2012-01-01

    Cockpit interior lighting, integrated displays, and other light-emitting display units have been found increased application in the modern cockpit. As a result the optical environment within the cockpit becomes more complicated. Inappropriate lighting and furnishing design or cockpit spatial layout generates glare and af fects flight safety. The effects of center pedestal control display unit (CDU) orientation and position changes on resultant windshield glare are analyzed. It is found that, for curved windshield, CDU orientation has limited in fluence on glare distribution while CDU position has a pronounced impact on glare distribution. Hence in CDU position changes are effective for alleviating or eliminating glare.%现代飞机座舱内照明灯具、综合显示器以及其他发光显示器件的大量应用,使得座舱内光学环境越来越复杂。不合理的照明和内饰设计,或者不合适的舱内空间布局,将会导致各种有害光的出现,影响飞行安全。采用视觉仿真方法,从操纵台控制显示装置的布置角度、布置位置等方面对其在前风挡形成的有害光进行分析,结果表明:针对大弧度曲面造型风挡,调整控制显示装置布置角度对有害光分布的影响有限,调整布置位置对有害光分布的影响显著,可以大大改善或避免眩光对飞行员的影响。

  17. Kamchatka and North Kurile Volcano Explosive Eruptions in 2015 and Danger to Aviation

    Science.gov (United States)

    Girina, Olga; Melnikov, Dmitry; Manevich, Alexander; Demyanchuk, Yury; Nuzhdaev, Anton; Petrova, Elena

    2016-04-01

    There are 36 active volcanoes in the Kamchatka and North Kurile, and several of them are continuously active. In 2015, four of the Kamchatkan volcanoes (Sheveluch, Klyuchevskoy, Karymsky and Zhupanovsky) and two volcanoes of North Kurile (Alaid and Chikurachki) had strong and moderate explosive eruptions. Moderate gas-steam activity was observing of Bezymianny, Kizimen, Avachinsky, Koryaksky, Gorely, Mutnovsky and other volcanoes. Strong explosive eruptions of volcanoes are the most dangerous for aircraft because they can produce in a few hours or days to the atmosphere and the stratosphere till several cubic kilometers of volcanic ash and aerosols. Ash plumes and the clouds, depending on the power of the eruption, the strength and wind speed, can travel thousands of kilometers from the volcano for several days, remaining hazardous to aircraft, as the melting temperature of small particles of ash below the operating temperature of jet engines. The eruptive activity of Sheveluch volcano began since 1980 (growth of the lava dome) and is continuing at present. Strong explosive events of the volcano occurred in 2015: on 07, 12, and 15 January, 01, 17, and 28 February, 04, 08, 16, 21-22, and 26 March, 07 and 12 April: ash plumes rose up to 7-12 km a.s.l. and extended more 900 km to the different directions of the volcano. Ashfalls occurred at Ust'-Kamchatsk on 16 March, and Klyuchi on 30 October. Strong and moderate hot avalanches from the lava dome were observing more often in the second half of the year. Aviation color code of Sheveluch was Orange during the year. Activity of the volcano was dangerous to international and local aviation. Explosive-effusive eruption of Klyuchevskoy volcano lasted from 01 January till 24 March. Strombolian explosive volcanic activity began from 01 January, and on 08-09 January a lava flow was detected at the Apakhonchich chute on the southeastern flank of the volcano. Vulcanian activity of the volcano began from 10 January. Ashfalls

  18. Effects of the SGLT2 inhibitor dapagliflozin on HDL cholesterol, particle size, and cholesterol efflux capacity in patients with type 2 diabetes: a randomized placebo-controlled trial.

    Science.gov (United States)

    Fadini, Gian Paolo; Bonora, Benedetta Maria; Zatti, Giancarlo; Vitturi, Nicola; Iori, Elisabetta; Marescotti, Maria Cristina; Albiero, Mattia; Avogaro, Angelo

    2017-04-04

    Sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce glucose levels, body weight, and blood pressure, possibly resulting in cardiovascular protection. In phase III trials, SGLT2i were shown to increase HDL cholesterol. We aimed to evaluate whether the SGLT2i dapagliflozin affects HDL function in a randomized placebo-controlled trial. Thirty-three type 2 diabetic patients were randomized to receive dapagliflozin 10 mg or placebo for 12 weeks on top of their glucose lowering medications. The primary end-point was the change in cholesterol efflux capacity (CEC) from macrophages at study end versus baseline. Secondary endpoints were changes in: distribution of HDL subfractions, lipid profile, activity of enzymes that mediate HDL antioxidant properties (PON1 and ARE) and cholesterol metabolism (CETP), HbA1c, body weight and composition. Thirty-one patients completed the study, n = 16 in the placebo group and n = 15 in the dapagliflozin group. Patients randomized to dapagliflozin were older and had lower adiposity indexes, although these differences disappeared after correction for multiple testing. Therapy with dapagliflozin reduced HbA1c by 0.9% and body weight by 3.1 kg, mainly attributable to reduction of body water and lean mass. As compared to placebo, dapagliflozin reduced CEC (-6.7 ± 2.4 versus 0.3 ± 1.8%; p = 0.043), but this effect was no longer significant after adjusting for age and BMI. No change was detected in HDL cholesterol, HDL subfractions, activity of PON1, ARE, and CETP. Despite improvements in glucose control and reduction in body weight, therapy with dapagliflozin exerted no significant effect on HDL cholesterol levels and HDL functionality. Trial registration EudraCT 2014-004270-42; NCT02327039.

  19. Explosive eruptions at Bezymianny Volcano (Kamchatka, Russia) from 2000-2009: warning system, prediction and risk assessment

    Science.gov (United States)

    Senyukov, S.

    2010-12-01

    for population centers, were released to the Kamchatka Branch of the Russian Advisory Council. The copies of these documents were sent to participants of the KVERT (Kamchatka Volcano Eruption Response Team) project, uniting scientists Alaska Volcano Observatory, Institute of Volcanology and Seismology and KBGS. One explosive eruption was missed and only one false prediction (due to incorrect data) was made during this time period. Seismic precursors of sixteen explosive eruptions of Bezymianny were investigated using seismic data from both Bezymianny and nearby Kluchevskoy Volcano to improve risk assessment. It was determined that the successful prediction of a Bezymianny eruption depends strongly on the activity at Kluchevskoy.

  20. Assessment of geomorphic risks and attractiveness to recreational systems: a case of Nalychevo Nature Park (Kamchatka, Russia).

    Science.gov (United States)

    Blinova, I.; Bredikhin, A.

    2012-04-01

    Attractiveness of relief, diversity and rareness were always the basic features of overall recreational attractiveness of a territory. Mountainous regions with high geomorphic diversity served as model for first recreation and tourism researches. The above features often favoured sustainability of touristic system. Unique relief forms are commonly referred to natural sites. They differ from the others in structure or have some morphological and morphometric characteristics not found in other forms of the earth's surface. Such monuments form the main natural functional kernel for a recreation system which is created and exists around them. In general, functions of geomorphological sites in recreation can be divided into socio-cultural and economic. Socio-cultural function is the principal function of recreation. It responds to the cultural or spiritual needs of people such as the knowledge in the broader sense, knowledge of the world and their place in it. The economic function is to create consumer demand for goods and services, and sometimes an entire economy sector. Natural sites are particularly vulnerable to dangerous occurrence of endogenous and exogenous processes as guarantee of environmental stability is an essential condition for a proper system functioning. This requires a comprehensive study of relief dynamics, monitoring and forecasting its evolution in recreation areas. Nowadays educational and environmental tourism in Russia develop rapidly. The unique tectonic position of Kamchatka Peninsula (the active geodynamic area dedicated to the subduction zone) formed a variety of landscapes, attracting visitors from all over the world. Recreational development of this region is slow due to remoteness and poor transport accessibility. However, there are 3 state federal reserves and one federal wildlife sanctuary, 4 natural parks of regional significance, 23 nature preserves of regional significance, and 105 natural monuments officially marked in this region

  1. Overview of the precursors and dynamics of the 2012-13 basaltic fissure eruption of Tolbachik Volcano, Kamchatka, Russia

    Science.gov (United States)

    Belousov, Alexander; Belousova, Marina; Edwards, Benjamin; Volynets, Anna; Melnikov, Dmitry

    2015-12-01

    We present a broad overview of the 2012-13 flank fissure eruption of Plosky Tolbachik Volcano in the central Kamchatka Peninsula. The eruption lasted more than nine months and produced approximately 0.55 km3 DRE (volume recalculated to a density of 2.8 g/cm3) of basaltic trachyandesite magma. The 2012-13 eruption of Tolbachik is one of the most voluminous historical eruptions of mafic magma at subduction related volcanoes globally, and it is the second largest at Kamchatka. The eruption was preceded by five months of elevated seismicity and ground inflation, both of which peaked a day before the eruption commenced on 27 November 2012. The batch of high-Al magma ascended from depths of 5-10 km; its apical part contained 54-55 wt.% SiO2, and the main body 52-53 wt.% SiO2. The eruption started by the opening of a 6 km-long radial fissure on the southwestern slope of the volcano that fed multi-vent phreatomagmatic and magmatic explosive activity, as well as intensive effusion of lava with an initial discharge of > 440 m3/s. After 10 days the eruption continued only at the lower part of the fissure, where explosive and effusive activity of Hawaiian-Strombolian type occurred from a lava pond in the crater of the main growing scoria cone. The discharge rate for the nine month long, effusion-dominated eruption gradually declined from 140 to 18 m3/s and formed a compound lava field with a total area of ~ 36 km2; the effusive activity evolved from high-discharge channel-fed 'a'a lavas to dominantly low-discharge tube-fed pahoehoe lavas. On 23 August, the effusion of lava ceased and the intra-crater lava pond drained. Weak Strombolian-type explosions continued for several more days on the crater bottom until the end of the eruption around 5 September 2013. Based on a broad array of new data collected during this eruption, we develop a model for the magma storage and transport system of Plosky Tolbachik that links the storage zones of the two main genetically related magma

  2. Protective effects of SGLT2 inhibitor luseogliflozin on pancreatic β-cells in obese type 2 diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Okauchi, Seizo, E-mail: okauchi@med.kawasaki-m.ac.jp; Shimoda, Masashi; Obata, Atsushi; Kimura, Tomohiko; Hirukawa, Hidenori; Kohara, Kenji; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki

    2016-02-12

    It is well known that Sodium-Glucose Co-transporter 2 (SGLT2) inhibitors, new hypoglycemic agents, improve glycemic control by increasing urine glucose excretion, but it remained unclear how they exert protective effects on pancreatic β-cells. In this study, we examined the effects of SGLT2 inhibitor luseogliflozin on β-cell function and mass using obese type 2 diabetic db/db mice. Ten-week-old male diabetic db/db mice were treated with luseogliflozin 0.0025% or 0.01% in chow (Luse 0.0025% or Luse 0.01%) or vehicle (control) for 4 weeks. Urinary glucose excretion was increased in Luse groups (0.0025% and 0.01%) compared to control mice 3 days after the intervention. Fasting blood glucose levels were significantly lower in mice treated with Luse compared to control mice. Fasting serum insulin concentrations were significantly higher in mice treated with Luse compared to control mice. Triglyceride levels tended to be lower in Luse groups compared to control mice. In immunohistochemical study using pancreas tissues, β-cell mass was larger in Luse groups compared to control group which was due to the increase of β-cell proliferation and decrease of β-cell apoptosis. Furthermore, in gene analysis using isolated islets, insulin 1, insulin 2, MafA, PDX-1 and GLUT2 gene expression levels were significantly higher in Luse groups compared to control group. In contrast, expression levels of fibrosis-related gene such as TGFβ, fibronectin, collagen I and collagen III were significantly lower in Luse groups. In conclusion, SGLT2 inhibitor luseogliflozin ameliorates glycemic control and thus exerts protective effects on pancreatic β-cell mass and function. - Highlights: • SGLT2 inhibitor luseogliflozin ameliorates glycemic control in db/db mice. • Luseogliflozin increases β-cell proliferation and decreases β-cell apoptosis. • Luseogliflozin preserves various β-cell-specific gene expression. • Luseogliflozin decreases various fibrosis-related factors in db

  3. Testing and Adapting a Daytime Four Band Satellite Ash Detection Algorithm for Eruptions in Alaska and the Kamchatka Peninsula, Russia

    Science.gov (United States)

    Andrup-Henriksen, G.; Skoog, R. A.

    2007-12-01

    Volcanic ash is detectable from satellite remote sensing due to the differences in spectral signatures compared to meteorological clouds. Recently a new global daytime ash detection algorithm was developed at University of Madison, Wisconsin. The algorithm is based on four spectral bands with the central wavelengths 0.65, 3.75, 11 and 12 micrometers that are common on weather satellite sensors including MODIS, AVHRR, GOES and MTSAT. The initial development of the algorithm was primarily based on MODIS data with global coverage. We have tested it using three years of AVHRR data in Alaska and the Kamchatka Peninsula, Russia. All the AVHRR data have been manually analyzed and recorded into an observational database during the daily monitoring performed by the remote sensing group at the Alaska Volcano Observatory (AVO). By taking the manual observations as accurate we were able to examine the accuracy of the four-channel algorithm for daytime data. The results were also compared to the current automated ash alarm used by AVO, based on the reverse absorption technique, also known as the split window method, with a threshold of -1.7K. This comparison indicates that the four- banded technique has a higher sensitivity to volcanic ash, but a greater number of false alarms. The algorithm was modified to achieve a false alarm rate comparable to current ash alarm while still maintaining increased sensitivity.

  4. Phase equilibria constraints on pre-eruptive magma storage conditions for the 1956 eruption of Bezymianny Volcano, Kamchatka, Russia

    Science.gov (United States)

    Shcherbakov, Vasily D.; Neill, Owen K.; Izbekov, Pavel E.; Plechov, Pavel Yu.

    2013-08-01

    Phase equilibria experiments were performed on andesites from the catastrophic 1956 eruption of Bezymianny Volcano, Kamchatka, Russia, to determine pre-eruptive magma storage conditions. Fifteen experiments were conducted under water-saturated conditions, with oxygen fugacity equal to the Ni-NiO oxygen buffer, at temperatures between 775 and 1100 °C and pressures between 50 and 200 MPa. Simultaneous amphibole and plagioclase crystallization is reproduced at ≤ 850 °C and ≥ 200 MPa. The simultaneous crystallization temperature range of the plagioclase-clinopyroxene-orthopyroxene-Fe-Ti oxide assemblage increases with decreasing pressure, from 840 to 940 °C at 150 MPa to 940-1020 °C at 50 MPa. Melt inclusion compositions in plagioclase phenocrysts and matrix glass match experimental melt compositions reproduced at 50-100 MPa and ≤ 50 MPa, respectively. Presence of the silica phase in groundmass and mature amphibole breakdown rims suggests that magma has been stored at ca. 3 km depth prior to the final ascent for at least 40 days. Syn-eruptive ascent led to decompression-driven crystallization, which caused a temperature increase from 850-900 °C to 950-1000 °C.

  5. Triticella minini - a new ctenostome bryozoan from the abyssal plain adjacent to the Kuril-Kamchatka Trench

    Science.gov (United States)

    Grischenko, Andrei V.; Chernyshev, Alexei V.

    2015-01-01

    A new species of ctenostome bryozoan, Triticella minini sp. nov., is described from the abyssal plain adjacent to the Kuril-Kamchatka Trench, based on material collected by the Russian-German deep-sea expedition KuramBio 2012. Colonies of T. minini sp. nov. were found attached to the oral spines of irregular sea urchin Echinosigra (Echinogutta) amphoraMironov, 1974 by means of rhizoid fibers that penetrated the substratum through circular borings. The specimens were examined by light microscopy, scanning electron microscopy, and confocal laser scanning microscopy with phalloidin and nuclear labeling. The description of T. minini sp. nov. combines a general taxonomic description with a description of the anatomy of the muscular system. The new species differs from congeners in lacking a stolon. It has an intertentacular organ. T. minini sp. nov. is the eleventh species described in the genus TriticellaDalyell, 1848, and the first record for this genus from the northwestern Pacific. The new species is the fifth ctenostome bryozoan known to occur in 5001-5500 m depth interval worldwide, and the deepest record reported for Triticella.

  6. Promising Diabetes Therapy Based on the Molecular Mechanism for Glucose Toxicity: Usefulness of SGLT2 Inhibitors as well as Incretin-Related Drugs.

    Science.gov (United States)

    Kaneto, Hideaki; Obata, Atsushi; Shimoda, Masashi; Kimura, Tomohiko; Hirukawa, Hidenori; Okauchi, Seizo; Matsuoka, Taka-Aki; Kaku, Kohei

    2016-01-01

    Pancreatic β-cell dysfunction and insulin resistance are the main characteristics of type 2 diabetes. Chronic exposure of β-cells to hyperglycemia leads to the deterioration of β-cell function. Such phenomena are well known as pancreatic β-cell glucose toxicity. MafA, a strong transactivator of insulin gene, is particularly important for the maintenance of mature β-cell function, but its expression level is significantly reduced under diabetic conditions which is likely associated with β-cell failure. Reduction of incretin receptor expression level in β-cells in diabetes is also likely associated with β-cell failure. On the other hand, incretin-related drugs and sodium-glucose co-transporter 2 (SGLT2) inhibitors are promising diabetes therapy based on the mechanism for pancreatic β-cell glucose toxicity. Indeed, it was shown that incretin-related drugs exerted protective effects on β-cells through the augmentation of IRS-2 expression especially in the presence of pioglitazone. It was also shown that incretin-related drug and/or pioglitazone exerted more protective effects on β-cells at the early stage of diabetes compared to the advanced stage. SGLT2 inhibitors, new hypoglycemic agents, also exert beneficial effects for the protection of pancreatic β-cells as well as for the reduction of insulin resistance in various insulin target tissues. Taken together, it is important to select appropriate therapy based on the molecular mechanism for glucose toxicity.

  7. Assessing the Altitude and Dispersion of Volcanic Plumes Using MISR Multi-angle Imaging from Space: Sixteen Years of Volcanic Activity in the Kamchatka Peninsula, Russia

    Science.gov (United States)

    Flower, Verity J. B.; Kahn, Ralph A.

    2017-01-01

    Volcanic eruptions represent a significant source of atmospheric aerosols and can display local, regional and global effects, impacting earth systems and human populations. In order to assess the relative impacts of these events, accurate plume injection altitude measurements are needed. In this work, volcanic plumes generated from seven Kamchatka Peninsula volcanoes (Shiveluch, Kliuchevskoi, Bezymianny, Tolbachik, Kizimen, Karymsky and Zhupanovsky), were identified using over 16 years of Multi-angle Imaging SpectroRadimeter (MISR) measurements. Eighty-eight volcanic plumes were observed by MISR, capturing 3-25% of reported events at individual volcanoes. Retrievals were most successful where high intensity events persisted over a period of weeks to months. Compared with existing ground and airborne observations, and alternative satellite-based reports compiled by the Global Volcanism Program (GVP), MISR plume height retrievals showed general consistency; the comparison reports appear to be skewed towards the region of highest concentration observed in MISR-constrained vertical plume extent. The report observations display less discrepancy with MISR toward the end of the analysis period, with improvements in the suborbital data likely the result of the deployment of new instrumentation. Conversely, the general consistency of MISR plume heights with conventionally reported observations supports the use of MISR in the ongoing assessment of volcanic activity globally, especially where other types of volcanic plume observations are unavailable. Differences between the northern (Shiveluch, Kliuchevskoi, Bezymianny and Tolbachik) and southern (Kizimen, Karymsky and Zhupanovsky) volcanoes broadly correspond to the Central Kamchatka Depression (CKD) and Eastern Volcanic Front (EVF), respectively, geological sub-regions of Kamchatka distinguished by varying magma composition. For example, by comparison with reanalysis-model simulations of local meteorological conditions

  8. Accumulation reconstruction and water isotope analysis for 1736-1997 of an ice core from the Ushkovsky volcano, Kamchatka, and their relationships to North Pacific climate records

    Science.gov (United States)

    Sato, T.; Shiraiwa, T.; Greve, R.; Seddik, H.; Edelmann, E.; Zwinger, T.

    2014-02-01

    An ice core was retrieved in June 1998 from the Gorshkov crater glacier at the top of the Ushkovsky volcano, in central Kamchatka. This ice core is one of only two recovered from Kamchatka so far, thus filling a gap in the regional instrumental climate network. Hydrogen isotope (δD) analyses and past accumulation reconstructions were conducted for the top 140.7 m of the core, spanning 1736-1997. Two accumulation reconstruction methods were developed and applied with the Salamatin and the Elmer/Ice firn-ice dynamics models, revealing a slightly increasing or nearly stable trend, respectively. Wavelet analysis shows that the ice core records have significant decadal and multi-decadal variabilities at different times. Around 1880 the multi-decadal variability of δD became lost and its average value increased by 6‰. The multi-decadal variability of reconstructed accumulation rates changed at around 1850. Reconstructed accumulation variations agree with ages of moraines in Kamchatka. Ice core signals were significantly correlated with North Pacific sea surface temperature (SST) and surface temperature (2 m temperature). δD correlates with the North Pacific Gyre Oscillation (NPGO) index after the climate regime shift in 1976/1977, but not before that. Therefore, our findings imply that the ice core record contains various information on the local, regional and large-scale climate variability in the North Pacific region. Understanding all detailed mechanisms behind the time-dependent connections between these climate patterns is challenging and requires further efforts towards multi-proxy analysis and climate modelling.

  9. Characteristics of a crater glacier at Ushkovsky volcano, Kamchatka, Russia, as revealed by the physical properties of ice cores and borehole thermometry

    OpenAIRE

    Shiraiwa, Takayuki; Murav'yev, Yaroslav D.; Kameda,Takao; Nishio,Fumihiko; Toyama, Yoko; Takahashi, Akiyoshi; Ovsyannikov, Alexander A.; Salamatin, Andrey N.; YAMAGATA, Kotaro

    2001-01-01

    A glacier at the summit of Ushkovskyvolcano, Kamchatka peninsula, Russia, was studied in order to obtain information about the physical characteristics of a glacier that fills a volcanic crater. The glacier has a gentle surface and a concave basal profile with a maximum measured depth of 240 m at site K2. The annual accumulation rate was 0.54 m a-1 w.e., and the 10 m depth temperature was -15.8°C. A 211.70 m long ice core drilled at K2 indicates that (1) the site is categorized as a percolati...

  10. Velocity structure of the crust and upper mantle at the northern group of Kamchatka volcanoes (Based on the travel time of P-waves from volcanic earthquakes)

    Science.gov (United States)

    Slavina, L. B.; Pivovarova, N. B.; Senyukov, S. L.

    2012-12-01

    The results of a calculation of the P-wave ( V P ) velocity fields are presented on the basis of the method of the reversible wave and the TAU parameter characterizing the V P / V S ratio of seismic waves from the local volcanic earthquakes that occurred at the northern group of Kamchatka volcanoes in 2005-2007. The 3D velocity cross sections were constructed along the SW-NE-trending volcanic group from the Ploskii Tolbachik volcano in the southwest up to the Shiveluch volcano in the northeast. The change of velocity field in time and depth is found. The problems of relating these changes to volcanic activity is reviewed.

  11. Glycemic control with ipragliflozin, a novel selective SGLT2 inhibitor, ameliorated endothelial dysfunction in streptozotocin-induced diabetic mouse

    Directory of Open Access Journals (Sweden)

    Hotimah Masdan Salim

    2016-10-01

    Full Text Available Background: Endothelial dysfunction caused by increased oxidative stress is a critical initiator of macro- and micro-vascular disease development in diabetic patients. Ipragliflozin, a selective sodium glucose co-transporter 2 (SGLT2 inhibitor, offers a novel approach for the treatment of diabetes by enhancing urinary glucose excretion. The aim of the present study was to examine whether ipragliflozin attenuates endothelial dysfunction in diabetic mice.Methods: Eight-week-old male C57BL/6 mice were treated with streptozotocin (150 mg/kg by a single intraperitoneal injection to induce diabetes mellitus. At three days of injection, ipragliflozin (3 mg/kg/day was administered via gavage for 3 weeks. Vascular function was assessed by isometric tension recording. Human umbilical endothelial cells (HUVEC were used for in vitro experiments. RNA and protein expression were examined by quantitative RT-PCR (qPCR and western blot, respectively. Oxidative stress was determined by measuring urine 8-hydroxy-2'-deoxyguanosine (8-OHdG level.Results: Ipragliflozin administration significantly reduced blood glucose level (P<0.01 and attenuated the impairment of endothelial function in diabetic mice, as determined by acetylcholine-dependent vasodilation (P<0.001. Ipragliflozin did not alter metabolic parameters such as body weight and food intake. Ipragliflozin administration ameliorated impaired phosphorylation of Akt and eNOSSer1177 in the abdominal aorta and reduced reactive oxygen species generation as determined by urinary excretion of 8-OHdG in diabetic mice. Furthermore, qPCR analyses demonstrated that ipragliflozin decreased the expression of inflammatory molecules (e.g.; MCP-1, VCAM-1 and ICAM-1 in the abdominal aorta (P<0.05, respectively. In in vitro studies, incubation with methylglyoxal, one of the advanced glycation end products, significantly impaired phosphorylation of Akt and eNOSSer1177 (P<0.01, respectively and increased the expression of MCP-1

  12. Effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Lubin Xu

    2017-06-01

    Full Text Available Aim To evaluate the effects of sodium-glucose co-transporter 2 (SGLT2 inhibition on renal function and albuminuria in patients with type 2 diabetes. Methods We conducted systematic searches of PubMed, Embase and Cochrane Central Register of Controlled Trials up to June 2016 and included randomized controlled trials of SGLT2 inhibitors in adult type 2 diabetic patients reporting estimated glomerular filtration rate (eGFR and/or urine albumin/creatinine ratio (ACR changes. Data were synthesized using the random-effects model. Results Forty-seven studies with 22,843 participants were included. SGLT2 inhibition was not associated with a significant change in eGFR in general (weighted mean difference (WMD, −0.33 ml/min per 1.73 m2, 95% CI [−0.90 to 0.23] or in patients with chronic kidney disease (CKD (WMD −0.78 ml/min per 1.73 m2, 95% CI [−2.52 to 0.97]. SGLT2 inhibition was associated with eGFR reduction in short-term trials (WMD −0.98 ml/min per 1.73 m2, 95% CI [−1.42 to −0.54], and with eGFR preservation in long-term trials (WMD 2.01 ml/min per 1.73 m2, 95% CI [0.86 to 3.16]. Urine ACR reduction after SGLT2 inhibition was not statistically significant in type 2 diabetic patients in general (WMD −7.24 mg/g, 95% CI [−15.54 to 1.06], but was significant in patients with CKD (WMD −107.35 mg/g, 95% CI [−192.53 to −22.18]. Conclusions SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes, likely resulting from a mixture of an initial reduction of eGFR and long-term renal function preservation. SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD.

  13. Multilocus sequence analysis of Thermoanaerobacter isolates reveals recombining, but differentiated, populations from geothermal springs of the Uzon Caldera, Kamchatka, Russia

    Science.gov (United States)

    Wagner, Isaac D.; Varghese, Litty B.; Hemme, Christopher L.; Wiegel, Juergen

    2013-01-01

    Thermal environments have island-like characteristics and provide a unique opportunity to study population structure and diversity patterns of microbial taxa inhabiting these sites. Strains having ≥98% 16S rRNA gene sequence similarity to the obligately anaerobic Firmicutes Thermoanaerobacter uzonensis were isolated from seven geothermal springs, separated by up to 1600 m, within the Uzon Caldera (Kamchatka, Russian Far East). The intraspecies variation and spatial patterns of diversity for this taxon were assessed by multilocus sequence analysis (MLSA) of 106 strains. Analysis of eight protein-coding loci (gyrB, lepA, leuS, pyrG, recA, recG, rplB, and rpoB) revealed that all loci were polymorphic and that nucleotide substitutions were mostly synonymous. There were 148 variable nucleotide sites across 8003 bp concatenates of the protein-coding loci. While pairwise FST values indicated a small but significant level of genetic differentiation between most subpopulations, there was a negligible relationship between genetic divergence and spatial separation. Strains with the same allelic profile were only isolated from the same hot spring, occasionally from consecutive years, and single locus variant (SLV) sequence types were usually derived from the same spring. While recombination occurred, there was an “epidemic” population structure in which a particular T. uzonensis sequence type rose in frequency relative to the rest of the population. These results demonstrate spatial diversity patterns for an anaerobic bacterial species in a relative small geographic location and reinforce the view that terrestrial geothermal springs are excellent places to look for biogeographic diversity patterns regardless of the involved distances. PMID:23801987

  14. Climatic Seesaws Across The North Pacific As Revealed By High-Mountain Ice Cores Drilled At Kamchatka And Wrangell-St. Elias Mountains

    Science.gov (United States)

    Shiraiwa, T.; Goto-Azuma, K.; Kanamori, S.; Matoba, S.; Benson, C. S.; Muravyev, Y. D.; Salamatin, A. N.

    2004-12-01

    We drilled ca. 210-m deep ice cores at Mt. Ushkovsky (Kamchatka: 1998), King Col of Mt. Logan (2002) and Mt. Wrangell (2004). Thanks to the high accumulation rates up to 2 m per year in these mountains, the ice cores are expected to unveil the climate and atmospheric changes in the northern North Pacific during the last several centuries. The reconstructed annual accumulation rates time-series of Mt. Ushkovsky showed, for example, decadal to interdecadal oscillations which were closely correlated to the Pacific Decadal Oscillations (PDO). Comparison between the reconstructed accumulation rates between the Ushkovsky and our two ice cores from Wrangell-St. Elias mountains suggests that the PDO played an important role in determining the precipitation at both side of the northern North Pacific: positive PDO supplied high precipitation in the Pacific North America and the negative PDO did high in Kamchatka during the last two centuries. Beside the significance of the climate proxy signals, the physical properties of the ice cores and the related glaciological features at the three mountains provided unique feature of glaciers developing on high mountains with complicated topographies and high accumulation rates. It was shown that careful treatment of dynamic behavior in these high mountain glaciers are indispensable for the precise reconstruction of past accumulation time-series.

  15. Mapping resource use over a Russian landscape: an integrated look at harvesting of a non-timber forest product in central Kamchatka

    Science.gov (United States)

    Hitztaler, Stephanie K.; Bergen, Kathleen M.

    2013-12-01

    Small-scale resource use became an important adaptive mechanism in remote logging communities in Russia at the onset of the post-Soviet period in 1991. We focused on harvesting of a non-timber forest product, lingonberry (Vaccinium vitis-idaea), in the forests of the Kamchatka Peninsula (Russian Far East). We employed an integrated geographical approach to make quantifiable connections between harvesting and the landscape, and to interpret these relationships in their broader contexts. Landsat TM images were used for a new classification; the resulting land-cover map was the basis for linking non-spatial data on harvesters’ gathering behaviors to spatial data within delineated lingonberry gathering sites. Several significant relationships emerged: (1) mature forests negatively affected harvesters’ initial choice to gather in a site, while young forests had a positive effect; (2) land-cover type was critical in determining how and why gathering occurred: post-disturbance young and maturing forests were significantly associated with higher gathering intensity and with the choice to market harvests; and (3) distance from gathering sites to villages and main roads also mattered: longer distances were significantly correlated to more time spent gathering and to increased marketing of harvests. We further considered our findings in light of the larger ecological and social dynamics at play in central Kamchatka. This unique study is an important starting point for conservation- and sustainable development-based work, and for additional research into the drivers of human-landscape interactions in the Russian Far East.

  16. Radioactive contamination of the soil-plant cover at certain locations of Primorsky Krai, Sakhalin Island and Kamchatka Peninsula: Assessment of the Fukushima fallout.

    Science.gov (United States)

    Mikhailovskaya, L N; Molchanova, I V; Pozolotina, V N; Zhuravlev, Yu N; Timofeeva, Ya O; Burdukovsky, M L

    2017-06-01

    The contamination densities of soil-plant cover at certain locations within the Primorsky Krai, Sakhalin Island and Kamchatka Peninsula attributable to (90)Sr, (137)Cs and (239,240)Pu were 500-1390 Bq m(-2), 980-2300 Bq m(-2) and 37-74 Bq m(-2), respectively. These values do not exceed average global background levels, typical for mid-latitudes of the Northern Hemisphere. The spatial distribution of radionuclides depends on the climatic conditions of the region. A positive dependence of the (90)Sr and (137)Cs contamination densities, as well as additional (137)Cs from NPP "Fukushima" in the soil, was determined based on the sum of annual atmospheric precipitation within the study areas. No trends in the spatial distribution of Pu isotopes were observed. The (137)Cs contribution from the "Fukushima" NPP constitutes 11-300 Bq m(-2) in the Primorsky Krai, Sakhalin Island and at the Kamchatka peninsula, i.e., 1-22% of the total amount of radionuclides in the soil. The contribution of this radionuclide to the contamination of moss-lichen vegetation ranged from 7 to 42%. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Chlorinated, brominated, and perfluorinated compounds, polycyclic aromatic hydrocarbons and trace elements in livers of sea otters from California, Washington, and Alaska (USA), and Kamchatka (Russia)

    Science.gov (United States)

    Kannan, K.; Moon, H.-B.; Yun, S.-H.; Agusa, T.; Thomas, N.J.; Tanabe, S.

    2008-01-01

    Concentrations of organochlorine pesticides (DDTs, HCHs, and chlordanes), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), perfluorinated compounds (PFCs), and 20 trace elements were determined in livers of 3- to 5-year old stranded sea otters collected from the coastal waters of California, Washington, and Alaska (USA) and from Kamchatka (Russia). Concentrations of organochlorine pesticides, PCBs, and PBDEs were high in sea otters collected from the California coast. Concentrations of DDTs were 10-fold higher in California sea otters than in otters from other locations; PCB concentrations were 5-fold higher, and PBDE concentrations were 2-fold higher, in California sea otters than in otters from other locations. Concentrations of PAHs were higher in sea otters from Prince William Sound than in sea otters from other locations. Concentrations of several trace elements were elevated in sea otters collected from California and Prince William Sound. Elevated concentrations of Mn and Zn in sea otters from California and Prince William Sound were indicative of oxidative stress-related injuries in these two populations. Concentrations of all of the target compounds, including trace elements, that were analyzed in sea otters from Kamchatka were lower than those found from the US coastal locations. ?? The Royal Society of Chemistry.

  18. Deep-sea epibiotic hydroids from the abyssal plain adjacent to the Kuril-Kamchatka Trench with description of Garveia belyaevi sp. nov. (Hydrozoa, Bougainvilliidae)

    Science.gov (United States)

    Stepanjants, Sofia D.; Chernyshev, Alexey V.

    2015-01-01

    Examination of material collected by the German-Russian KuramBio Deep-Sea Expedition to the abyssal plain adjacent to the Kuril-Kamchatka Trench revealed about 17 hydroid species, including two species presumably new to science. Before the KuramBio Expedition only fragments of the unidentified hydroids and Cryptolaria sp. were collected in the Kuril-Kamchatka Trench from depths exceeding 3000 m. Descriptions of three species of epibiotic hydroids (including one new species, Garveia belyaevi sp. nov.) are presented herein. A colony of G. belyaevi sp. nov. (the third deep-sea and deepest species of the wide distributed genus Garveia) was attached to the spines of unidentified irregular sea urchins from depths 5217 to 5229 m. Нalitholus (?) sp. (Hydrozoa, Anthoathecata) colonized the skin of spoon worms (Echiura) but could not be identified to species level because the mature medusa stage was absent in the material. An unidentified juvenile polyp (Pandeidae) was found on the bryozoan Tricitella minini attached to spines of irregular sea urchins Echinosigra amphora. Colonial sedentary organisms inhabiting abyssal plains with soft bottoms may colonize invertebrates which are seldom used as substrates for epibiota in shallow waters. Epibiosis among abyssal colonial invertebrates, though extremely poorly studied, appears to be rather frequent.

  19. [Karyological differences of the Northern Dolly Varden Salvelinus malma malma and the white char Salvelinus albus from the Kamchatka River basin].

    Science.gov (United States)

    Frolov, S V

    2001-03-01

    The karyotypes of northern Dolly Varden and white char, sympathrically inhabiting the Kamchatka River basin, were studied. The karyotype of Dolly Varden was stable: 2n = 78 and NF = 98 + 2, while in white char, polymorphism and mosaicism for the chromosome number were revealed: 2n = 76-79, NF = 98 + 2. Using a routine chromosome staining technique, the karyotype of white char (2n = 78) was shown to be identical to that of Dolly Varden. In both karyotypes, similar sets of marker chromosomes were present: two pairs of submetacentric (SM), one pair of submeta-subtelocentric (SM-ST), one pair of large acrocentric (A), and one pair of large sub-telocentric (ST) chromosomes. However, the karyotypes of Dolly Varden and white char differed in the number and location of nucleolus organizer regions (NORs). In Dolly Varden, single NORs located in the telomeric regions of the marker SM-ST chromosomes were observed. In white char, NORs were multiple and located both in the telomeric regions of the marker SM-ST chromosomes and on the short and long arms of large ST chromosomes. The identical marker chromosomes indicate considerable phylogenetic relatedness between Dolly Varden and white char from the Kamchatka River basin. Variation in NORs provides evidence for the reproductive isolation of these chars and their species status.

  20. Unexpectedly higher metazoan meiofauna abundances in the Kuril-Kamchatka Trench compared to the adjacent abyssal plains

    Science.gov (United States)

    Schmidt, Christina; Martínez Arbizu, Pedro

    2015-01-01

    We studied meiofauna standing stocks and community structure in the Kuril-Kamchatka Trench and its adjacent abyssal plains in the northwestern Pacific Ocean. In general, the Nematoda were dominant (93%) followed by the Copepoda (4%). Nematode abundances ranged from 87% to 96%; those of copepods from 2% to 7%. The most diverse deployment yielded 17 taxa: Acari, Amphipoda, Annelida, Bivalvia, Coelenterata, Copepoda, Cumacea, Gastrotricha, Isopoda, Kinorhyncha, Loricifera, Nematoda, Ostracoda, Priapulida, Tanaidacea, Tantulocarida, and Tardigrada. Nauplii were also present. Generally, the trench slope and the southernmost deployments had the highest abundances (850-1392 individuals/cm2). The results of non-metric multidimensional scaling indicated that these deployments were similar to each other in meiofauna community structure. The southernmost deployments were located in a zone of higher particulate organic carbon (POC) flux (g Corg m-2 yr-1), whereas the trench slope should have low POC flux due to depth attenuation. Also, POC and abundance were significantly correlated in the abyssal plains. This correlation may explain the higher abundances at the southernmost deployments. Lateral transport was also assumed to explain high meiofauna abundances on the trench slope. Abundances were generally higher than expected from model results. ANOSIM revealed significant differences between the trench slope and the northern abyssal plains, between the central abyssal plains and the trench slope, between the trench slope and the southern abyssal plains, between the central and the southern abyssal plains, and between the central and northern deployments. The northern and southern abyssal plains did not differ significantly. In addition, a U-test revealed highly significant differences between the trench-slope and abyssal deployments. The taxa inhabited mostly the upper 0-3 cm of the sediment layer (Nematoda 80-90%; Copepoda 88-100%). The trench-slope and abyssal did not differ

  1. First data on magma ascent and residence times retrieved from Fe-Mg and trace element zonation in olivine phenocrysts from Kamchatka basalts

    Science.gov (United States)

    Gordeychik, Boris; Churikova, Tatiana; Kronz, Andreas; Simakin, Alexander; Wörner, Gerhard

    2016-04-01

    Compositional zonation in olivine phenocrysts and diffusion modelling have been used in the last ten years to estimate magma residence times and the duration of magma ascent. The fundamental assumption is that mixing with newly injected magma into a reservoir triggers diffusional exchange between mafic olivine crystals and more evolved magma and that this magma mixing eventually triggers eruption. If depth of mixing is known, this translates to ascent rates of magmas to the surface. We applied this approach to a series of different arc basalt lavas from Kamchatka to constrain the rates of magma ascent and magma resident in what is one of the most active subduction zones in the world that is also dominated by an abundance of unusually mafic magmas. Our sample collection cover the principal modes of arc magmatism in Kamchatka: from different volcanic complexes (stratovolcano, dikes, summit eruptions, monogenetic cones), of different age (from Late-Pleistocene to Holocene and recent eruptions), from different magmatic regimes (long-lived volcanoes vs. monogenetic eruptions) and different major element composition (from basalt to basaltic andesite of different geochemical character including LILE enrichments). We analyzed and modelled zonation profiles for a range of elements with different diffusivities (e.g. Mg-Fe, Ca, Ni, Mn, Cr) to assess the role of variable diffusivities as a function of major and trace elements in the olivines from different P-T conditions. First data were obtained on samples from the Klyuchevskoy, Shiveluch and Tolbachik, including recent most eruption in 2012/2013. These data show that for some samples the zonation patterns are much more complex than is usually observed: high-Mg olivines at different volcanoes have very different zonation patterns, including normally, reversely zoned grains or even show highly complex repetitive zonation that indicate large compositional changes in the surrounding magma at very short time scales (years). Thus

  2. How to Avoid Headlight Glare

    Science.gov (United States)

    ... such an inspection, take your vehicle to an auto mechanic, dealer or other properly equipped repair shop at least once a year for a headlight checkup. Your properly aligned headlights will help you see better, and will help other drivers ...

  3. Late Cretaceous paleomagnetism of the East Ranges island arc complex, Kamchatka: Implications for terrane movements and kinematics of the northwest Pacific

    Science.gov (United States)

    Levashova, Natalia M.; Bazhenov, Mikhail L.; Shapiro, Mikhail N.

    1997-11-01

    A Campanian-lower Paleocene island arc complex was sampled for paleomagnetic studies at 12 sites in the East Ranges tectonic zone of Kamchatka. After thermal demagnetization, a reversed polarity characteristic remanent magnetization (ChRM) was isolated from most volcanoclastic and basaltic units as well as from lava debris from intraformational conglomerates. The fold and conglomerate tests are positive, and the ChRM in the studied rocks is likely primary. The formation-mean inclination of 66.3°±3.7° corresponds to a paleolatitude of 48.7°±5.0°N which is about 20° lower than the Late Cretaceous North American reference values. Because northward displacement of the studied terrane is indicated by the paleomagnetic data, we examine several models of intraoceanic transport with the Pacific and/or Kula plates and coastwise transport after terrane accretion, far to the south of the present-day position of Kamchatka. Our preferred interpretation is that the studied island arc complex accumulated at about 83-79 Ma; the island arc, to which the studied terrane had originally belonged, was active between this time and 65-60 Ma. According to geological data, the docking time nearly coincided with cessation of volcanic activity, and northward movement of the island arc took place simultaneously with the volcanic activity. The absolute motion of a subduction zone should have the same direction as the overriding plate; therefore, the subduction zone related to the East Ranges island arc is inferred to have moved northward with the Kula plate or with the Kula and Pacific plates, successively, consuming either the oceanic periphery of a continental plate or some unknown minor oceanic plate. This process went on until 65-55 Ma when the island arc and related subduction zone approached the continental margin and became extinct. The proposed models also place additional constraints on kinematics of the Kula-Pacific transform plate boundary.

  4. New deep-sea large free-living nematodes from macrobenthos in the Kuril-Kamchatka Trench (the North-Western Pacific)

    Science.gov (United States)

    Fadeeva, Natalia; Mordukhovich, Vladimir; Zograf, Julia

    2015-01-01

    The composition of deep-sea nematode assemblages of the North-Western (NW) Pacific is poorly-studied. According to the available literature data more than 700 valid species of nematodes were reported from the depth of 400 m and deeper, out of that only 6 species were registered in the NW Pacific: 2 species from the coast of the Japanese Islands and 4 from the Sea of Japan. Ecological studies of the deep-sea nematode communities of this region are scanty and represent very scarce and fragmentary information. The first recent study of free-living nematodes collected from the abyssal plain adjacent to the Kuril-Kamchatka Trench has revealed more than 50 species of nematodes in macrobenthic samples. Families Anticomidae, Comesomatidae, Desmodoridae, Leptosomatidae, Oncholaimidae, Oxystominidae, Phanodermatidae, Siphonolaimidae and Thoracostomopsidae were the most abundant and diverse. Such taxonomic composition differs greatly from previously described meiobenthical nematode communities of NW Pacific and even World Ocean and similar to macrofaunal nematode assemblages of the Atlantic and Arctic regions. Several genera of nematodes can be considered as new records for the NW Pacific region. Micoletzkyia kamchatika sp. nov., Metaphanoderma improvisa sp. nov., and Phylloncholaimus palmaris sp. nov. are described from the Kuril-Kamchatka Trench. Micoletzkyia kamchatika sp. nov. is particularly characterized by a developed cuticular cephalic capsule underlying amphids, relatively small amphids, and the shape of the gubernaculum. Metaphanoderma improvisa sp. nov. is particularly characterized by a developed cuticular cephalic capsule, relatively large amphids, and the absence of pigmented eye spots. Phylloncholaimus palmaris sp. nov. is similar to the type species in many measurements but may be differentiated from that by the smaller amphid, shape of spicules and gubernaculums and by large precloacal papillae with four setae.

  5. Carbon isotope curve and iridium anomaly in the Albian-Cenomanian paleoceanic deposits of the Eastern Kamchatka

    Science.gov (United States)

    Savelyev, D. P.; Savelyeva, O. L.; Palechek, T. N.; Pokrovsky, B. G.

    2012-04-01

    We studied Albian-Cenomanian paleoceanic carbonate-siliceous deposits of the Kamchatsky Mys Peninsula (Eastern Kamchatka, Russia). They are deposited in association with pillow-basalts and hyaloclastites. The thickness of the studied section is about 10 m. The deposits are represented mainly by rhythmical intercalation of red-brown radiolarian jaspers, pink nannoplankton limestones as well as siliceous limestones. In the middle and upper parts of the section there are two beds enriched by organic carbon. The largest organic matter contents in this beds amount to 68%. The calculated values of the hydrogen and oxygen indexes indicate that the carbonaceous beds consist of marine organic matter. The accumulation of the carbonaceous beds reflects oxygen depletion in intermediate oceanic waters (ocean anoxic events, OAE). The structure of the studied section emphasizes its similarity to the contemporary deposits recovered by ODP and DSDP sites on Hess and Shatsky Rises. Two orders of rhythmicity were observed in the section. The rhythmicity of the first order (average thickness of a rhythm is 5-7 cm) is an alternation of reddish brown radiolarian jaspers and pink nannofossil limestones. The rhythmicity of the second order is characterized by an increase in thickness of the jasper or limy layer in every 4th-5th rhythm of the first order and marked by an elevation of the silica content in calcareous layers. The rhythmicity formation can be attributed to fluctuation of astronomical parameters (Milankovitch cycles) with periods of 21 and 100 kyr. The character of atmospheric circulation and ocean currents served as transmission link. The section was sampled layerwise and more than 100 samples were taken. The radiolarians were extracted from the samples of jaspers and siliceous limestones lying between carbonaceous beds. The educed radiolarian complexes allowed us to define the age of the deposits as Cenomanian. For more detailed dating of members of the section we have

  6. Geochemical Similarities Between the Pre-Caldera and Modern Evolutionary Series of Eruptive Products from Gorely Volcano, Kamchatka

    Science.gov (United States)

    Gavrilenko, M.; Ozerov, A.

    2010-12-01

    Gorely volcano, in southern Kamchatka, is a large, long-lived shield-type volcano that is currently in an eruptive phase. Prior eruptions occurred in 1980 and 1984. It is comprised of three structural units: Pra-Gorely volcano; thick ignimbrite complex, associated with a caldera forming eruption; modern edifice named ‘Young Gorely’. An integrated mineralogical-geochemical have been conducted on all structural units of the Gorely volcanic edifice to determine their genetic conditions. After geochemical analysis two evolution series were found. First, Pra-Gorely volcano is represented by a suite of compositions ranging from basalt to rhyolite, with in this series, high-Mg basalts were discovered. Second, Young Gorely edifice is composed of only basalt, andesite and dacite. The reconstruction of chemical evolution trends shows that both volcanic series of Gorely volcano share the same genetic history with similar evolutionary stages. We suggest fractionation of an upper mantle peridotite as a common means to produce both volcanic series as a result of which the evolution of all rocks was generated. The magmatic series of Pra-Gorely and Young Gorely volcanoes were formed under different geodynamic conditions. Between these two series was a powerful stage of caldera formation, during which 100 km3 of ignimbrites were emplaced. The 12-km diameter caldera collapse was the catalyst for large-scale reorganization of the volcanic feeding system. Nevertheless following caldera collapse, Young Gorely was formed by activity inside the caldera and shows very similar evolutionary trends to that of Pra-Gorely. It can be confidently stated that crustal components are practically absent in the evolution of the series, and the compositional range is attributed directly to the evolution of the magmatic melts of Gorely volcano. Microprobe analyses conducted on olivine and pyroxene phenocrysts of Gorely volcano lavas, show that there were at least two stages of crystallization

  7. Characterization and petrophysical properties of hydrothemally altered lacustrine volcanistic rock in Geyser Valley (Kamchatka) and its transformation by weathering

    Science.gov (United States)

    Gvozdeva, Irina; Zerkal, Oleg; Samarin, Evgeny

    2013-04-01

    Work is devoted to the study of volcano sedimentary hydrothermally altered rocks in Geyser Valley (Kamchatka peninsula, Russia). The Geyser Valley is one of the most unique nature objects in Russia. There are quite large geyser fields. The valley of the river is part of the Uson-Geysernaya depression, where hydrothermal activity is very high. Besides geysers here are hot springs, mud pots and fumarols. In the late Pleistocene (about 45-35 thousand years ago) the lake was located in the site of the modern valley of the Geysernaya river, where sediments accumulated intensively. Sedimentary material came from several sources in the form of pyroclastic flows, ash falls, was supplied by permanent and temporary water streams. The total deposit thickness reached several hundred meters. In the late Pleistocene there was breakthrough of reservoir and further conditions for the lacustrine deposits formation did not arose. Later the rocks were intensively processed by thermal water. In 2007 large landslide was formed in lower part of the Geysernaya River on their left slope. Deposits of Geysernaya (Q34grn) series and Pemsovaya (Q34pmz) series were involved in landslide displacement. The headscarp was formed up to 100 m and a length of 800 m, exposing the volcano-sedimentary section of hydrothermally altered rocks - a unique opportunity for sampling and subsequent laboratory study. Thickness of lake sediments is interbedding of coarse-grain, medium-grain, fine-grain tuffites predominantly acidic composition. The study of thin sections revealed that all samples are lithoclastic and vitroclastic hydrothermally altered tuffits. Currently, the primary minerals and volcanic glass is largely replaced by clay minerals of the smectite group. Pores and cracks are made zeolites (heulandite and clinoptilolite). All this points to the low-temperature (weathered to clayey state tuffites inherit structural and textural features of the primary species. The composition also varies: increased

  8. Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus.

    Science.gov (United States)

    Hemmingsen, Bianca; Krogh, Jesper; Metzendorf, Maria-Inti; Richter, Bernd

    2016-04-21

    Sodium-glucose cotransporter (SGLT) 2 inhibitors were recently approved as glucose-lowering interventions in people with type 2 diabetes mellitus (T2DM). Potential beneficial or harmful effects of SGLT 2 inhibitors in people at risk for the development of T2DM are unknown. To assess the effects of SGLT 2 inhibitors focusing on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose or moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of ongoing for information about additional trials. The date of the last search of all databases was January 2016. Randomised controlled trials (RCTs) of any duration comparing SGLT 2 inhibitors with any glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these. Two review authors read all abstracts, assessed quality and extracted data independently. We resolved discrepancies by consensus or the involvement of a third author. We could not include any RCT in this systematic review. One trial was published in two abstracts, but did not provide separate information of the participants with impaired glucose tolerance, impaired fasting glucose or both. We identified two ongoing trials, both evaluating the effects of dapagliflozin (and metformin) in people at risk for the development of type 2 diabetes and a follow-up of 24 to 26 weeks. Both trials will mainly report on surrogate outcome measures with some data on adverse effects and health

  9. EFFECTS OF SOYBEAN OLIGOSACCHARIDES ON DEVELOPMENT OF SMALL INTESTINE AND EXPRESSION OF SGLT1 AND GLUT2 IN WEANED HUANJIANG MINI-PIGLETS%大豆寡糖对断奶环江香猪小肠发育及SGLT1和GLUT2表达的影响

    Institute of Scientific and Technical Information of China (English)

    周笑犁; 孔祥峰; 张珍珍; 印遇龙

    2013-01-01

    Ojective To investigate the effects of soybean oligosaccharides (SBOS) on development of small intestine and absorption in weaned piglets. Method Twelve Huanjiang mini-piglets weaned at age 21 d were randomly allocated into two groups with six replicates in the feeding trial. The piglets were fed 0% or 0.5% SBOS- supplemented diet for 14 d. The plasma was collected at the end of this trail and used for measuring blood glucose. The jejunum and ileum were collected for histological analysis. The mRNA expression abundances of sodiuml glucose cotransporter (SGLT1) and glucose transporfer (GLUT2) in jejunum and ileum were determined by relative quantitative RT-PCR respectively. Results The mRNA expression of SGLT1 and GLUT2 in SBOS group had intestinal space position specificity, and their expression levels in the jejunum were higher (P<0.05) than those in ileum, as well as than the control group. SBOS increased (.P<0.05) the ratio of villus height and fossae depth of small intestine. Conclusion SBOS can promote development and nutrient absorption of small intestine in mini-piglets.%目的 研究大豆寡糖(SBOS)对小肠发育及其吸收功能的影响.方法 选用21d龄断奶的环江香猪12头,随机分为2组,每组6头,分别饲喂添加0.5% SBOS的日粮和基础日粮,试验期14d.试验结束后采集血液,肝素抗凝,离心分离血浆,测定血糖浓度;放血处死后取空、回肠组织各两份,另一份采用于组织固定,进行形态学观察;一份利用荧光定量RT-PCR法,测定葡萄糖转运载体SGLT1和GLUT2 mRNA的表达.结果 与基础日粮组相比,SBOS组葡萄糖转运载体的表达具有肠道空间位置特异性,空肠SGLT1和GLUT2 mRNA的表达量显著高于回肠(P<0.05);并显著高于基础日粮组空肠的表达量(P<0.05);SBOS显著提高了仔猪小肠绒毛高度与隐窝深度的比值(P<0.05).结论 SBOS能促进小肠发育,提高肠道对营养物质的吸收.

  10. SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Gurgle HE

    2016-06-01

    Full Text Available Holly E Gurgle, Karen White, Carrie McAdam-Marx Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA Abstract: Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium–glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM. This review summarizes comparative evidence for providers who are determining which of the two classes may be the most appropriate for a specific patient. Keywords: type 2 diabetes mellitus, GLP-1 receptor agonist, SGLT2 inhibitor, A1c, weight loss, adverse effect

  11. SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O-β-d-Glucoside in Rats.

    Science.gov (United States)

    Shi, Jian; Zheng, Haihui; Yu, Jia; Zhu, Lijun; Yan, Tongmeng; Wu, Peng; Lu, Linlin; Wang, Ying; Hu, Ming; Liu, Zhongqiu

    2016-03-01

    Hydrolysis by lactase-phloridzin hydrolase (LPH) is the first and critical step in the absorption of isoflavonoid glucosides. However, the absorption characteristics of calycosin-7-O-β-d-glucoside (CG) slightly differ from other isoflavonoid glucosides. In this study, we used the rat intestinal perfusion model and performed pharmacokinetic studies and in vitro experiments to determine the factors influencing CG absorption and disposition. After oral administration of isoflavonoid glucosides, LPH was found to play minimal or no role on the hydrolysis of CG, in contrast to that of daidzin. CG was mainly transported into the small intestinal cells by sodium-dependent glucose transporter 1 (SGLT-1) as intact. This pathway could be the main mechanism underlying the high permeability of CG in the small intestine. CG was likely to be hydrolyzed in enterocytes to its aglycone calycosin by broad-specific β-glucuronides (BSβG) and glucocerebrosidase or rapidly metabolized. Calycosin was also rapidly and extensively metabolized to 3'-glucuronide in the enterocytes and liver, and the glucuronidation rates of calycosin and CG were much higher in the former. The metabolites were also transported into lumen by breast cancer resistance protein and multidrug resistance-associated protein 2. In conclusion, the enterocytes could be an important site for CG absorption, deglycosylation, and metabolism in rats. This study could contribute to the theoretical foundation and mechanism of absorption and disposition of flavonoid compounds.

  12. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice.

    Science.gov (United States)

    Gallo, Linda A; Ward, Micheal S; Fotheringham, Amelia K; Zhuang, Aowen; Borg, Danielle J; Flemming, Nicole B; Harvie, Ben M; Kinneally, Toni L; Yeh, Shang-Ming; McCarthy, Domenica A; Koepsell, Hermann; Vallon, Volker; Pollock, Carol; Panchapakesan, Usha; Forbes, Josephine M

    2016-05-26

    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

  13. Chlorine Stable Isotopes to reveal contribution of magmatic chlorine in subduction zones: the case of the Kamchatka-Kuril and the Lesser Antilles Volcanic Arcs

    Science.gov (United States)

    Agrinier, Pierre; Shilobreeva, Svetlana; Bardoux, Gerard; Michel, Agnes; Maximov, Alexandr; Kalatcheva, Elena; Ryabinin, Gennady; Bonifacie, Magali

    2015-04-01

    By using the stable isotopes of chlorine (δ 37Cl), we have shown that magmatic chlorine (δ 37Cl ≤ -0.6 ‰ [1]) is different from surface chlorine (δ 37Cl ≈ 0 ‰ [1]) in hydrothermal system of Soufrière and Montagne Pelé from the young arc volcanic system of Lesser Antilles. First measurements on condensed chlorides from volcanic gases (e.g. [2], [3]) did not permitted to get sensible δ 37Cl values on degassed chlorine likely because chlorine isotopes are fractionated during the HClgas - chloride equilibrium in the fumaroles or during sampling artifacts. Therefore we have developed an alternative strategy based on the analysis of chloride in thermal springs, streams, sout{f}lowing on the flanks of the volcanoes. Due to the highly hydrophilic behavior of Cl, we hypothesize that thermal springs incorporate chlorine without fractionation of chlorine isotopes and might reflect the chlorine isotopic composition degassed by magmas [1]. Indeed Thermal spring with low δ 37Cl chlorides (≤ -0.6 perthousand{}) are linked with magmatic volatiles characters (3He ratio at 5 Ra at and δ 13C CO2 quad ≈ -3 perthousand{}). To go further in the potentiality of using the Chlorine isotopes to reveal contribution of magmatic chlorine in volcanic systems, we have started the survey of thermal springs and wells waters in the Kamchatka-Kuril volcanic mature Arc (on sites Mutnovsky, Paratunka, Nalychevsky, Khodutkinsky, Paramushir Island, identified by Taran, 2009 [4] for concentrations of chloride). Preliminary results show δ 37Cl values ranging from 0.5 to -0.2 ‰ and generally higher chloride concentrations. The δ 37Cl values are higher than the value recorded for the young arc volcanic system of lesser Antilles. At present moment very few negative δ 37Cl have been measured in the Kamchatka-Kuril volcanic mature Arc. [1] Li et al., 2015 EPSL in press. [2] Sharp et al. 2010 GCA. [3] Rizzo et al., 2013, EPSL, 371, 134. [4] Taran, 2009, GCA, 73, 1067

  14. N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population

    Directory of Open Access Journals (Sweden)

    Mark A Babizhayev

    2008-10-01

    Full Text Available Mark A Babizhayev1, Leslie Burke2, Philip Micans3, Stuart P Richer4,51Innovative Vision Products, Inc., County of New Castle, Delaware, USA; 2Wise Choice Products LLC, London, England, United Kingdom; 3IAS Group, Sark, United Kingdom; 4Eye Clinic DVA Medical Center, North Chicago, Illinois, USA; 5Department of Family and Preventive Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USABackground: Innovative Vision Products, Inc. (IVP’s scientists developed the lubricant eye drops (Can-C™ designed as 1% N-acetylcarnosine (NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops.Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance, and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years.Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9

  15. The impact of SGLT2 inhibitors, compared with insulin, on diabetic bone disease in a mouse model of type 1 diabetes.

    Science.gov (United States)

    Thrailkill, Kathryn M; Nyman, Jeffry S; Bunn, R Clay; Uppuganti, Sasidhar; Thompson, Katherine L; Lumpkin, Charles K; Kalaitzoglou, Evangelia; Fowlkes, John L

    2017-01-01

    Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9weeks with: 1) oral canagliflozin (CANA, dose range ~10-16mg/kg/day), an inhibitor of the renal sodium-dependent glucose co-transporter type 2 (SGLT2); 2) subcutaneous insulin, via minipump (INS, 0.125units/day); 3) co-therapy (CANA+INS); or 4) no treatment (STZ, without therapy). These groups were also compared to non-diabetic control groups. Untreated diabetic mice experienced increased bone resorption and significant deficits in cortical and trabecular bone that contributed to structural weakness of the femur mid-shaft and the lumbar vertebra, as determined by three-point bending and compression tests, respectively. Treatment with either canagliflozin or insulin alone only partially rectified hyperglycemia and the diabetic bone phenotype. However, when used in combination, normalization of glycemic control was achieved, and a prevention of the DM-related deterioration in bone microarchitecture and bone strength occurred, due to additive effects of canagliflozin and insulin. Nevertheless, CANA-treated mice, whether diabetic or non-diabetic, demonstrated an increase in urinary calcium loss; FGF23 was also increased in CANA-treated DM mice. These findings could herald ongoing bone mineral losses following CANA exposure, suggesting that certain CANA-induced skeletal consequences might detract from therapeutic improvements in glycemic control, as they

  16. Contamination status and accumulation profiles of organotins in sea otters (Enhydra lutris) found dead along the coasts of California, Washington, Alaska (USA), and Kamchatka (Russia).

    Science.gov (United States)

    Murata, Satoko; Takahashi, Shin; Agusa, Tetsuro; Thomas, Nancy J; Kannan, Kurunthachalam; Tanabe, Shinsuke

    2008-04-01

    Organotin compounds (OTs) including mono- to tri-butyltins, -phenyltins, and -octyltins were determined in the liver of adult sea otters (Enhydra lutris) found dead along the coasts of California, Washington, and Alaska in the USA and Kamchatka, Russia. Total concentrations of OTs in sea otters from California ranged from 34 to 4100ng/g on a wet weight basis. The order of concentrations of OTs in sea otters was total butyltins>total octyltins> or = total phenyltins. Elevated concentrations of butyltins (BTs) were found in some otters classified under 'infectious-disease' mortality category. Concentrations of BTs in few of these otters were close to or above the threshold levels for adverse health effects. Total butyltin concentrations decreased significantly in the livers of California sea otters since the 1990s. Based on the concentrations of organotins in sea otters collected from 1992 to 2002, the half-lives of tributyltin and total butyltins in sea otters were estimated to be approximately three years.

  17. The nexus of soil radon and hydrogen dynamics and seismicity of the northern flank of the Kuril-Kamchatka subduction zone

    Directory of Open Access Journals (Sweden)

    O. P. Malysheva

    2007-06-01

    Full Text Available The comparison of kinematics and dynamic parameters of radon and molecular hydrogen concentration in subsoil air on the stations network at the Petropavlovsk-Kamchatsky geodynamic proving ground with seismicity of the northern flank of the Kuril-Kamchatka subduction zone was fulfilled in the period from July till August 2004. On the basis of correlation analysis of the regional seismicity and variations of radon flux density calculated using the data of gas-discharge counters of STS-6 type and SSNTDs it was shown that the radon mass transfer abnormal variations are conditioned by both regional seismicity in total and the subduction zone of proving ground. The azimuths of «geodeformation waves» coming to the registration points are calculated during clearly expressed anomaly beginnings, which coincide with directions to earthquake epicenters taking place at the same time. The geochemical anomalies recorded are presumptively deformative by nature and can be conditioned by processes of «quasi-viscous» flow of the lithosphere during rearrangement of tectonic stress fields of the subduction zone. The short-term (predicted time ? <14 days precursor of the earthquakes swarm was revealed in hydrogen dynamics on August, 4-5 (four earthquakes had M?5.3 and epicentral distance about 130 km from the Paratunka base station.

  18. Evolutionary relationships among sympatric life history forms of Dolly Varden inhabiting the landlocked Kronotsky Lake, Kamchatka, and a neighboring anadromous population

    Science.gov (United States)

    Ostberg, C.O.; Pavlov, S.D.; Hauser, L.

    2009-01-01

    We investigated the evolutionary relationships among five sympatric morphs of Dolly Varden Salvelinus malma (white, Schmidti, longhead, river, and dwarf) inhabiting landlocked Kronotsky Lake on the Kamchatka Peninsula, Russia, and an anadromous population below the barrier waterfall on the outflowing Kronotsky River. Morphological analyses indicated phenotypic differentiation corresponding to preferred habitat, the longhead (a limnetic piscivorous morph) having a fusiform body, long jaw, and short fins and the Schmidti (a benthic morph) having a robust body, small jaw, and long fins. Analysis of molecular variance among the Kronotsky Lake morphs indicated that contemporary gene flow is restricted both among morphs within locations and among locations within morphs. Gene flow from Kronotsky Lake into the anadromous population also appears to be restricted. Our findings indicate that there are two divergent evolutionary lineages, one consisting of the white, Schmidti, river, and dwarf morphs and the other of the longhead morph and the anadromous population, which suggests that Kronotsky Lake was subject to separate waves of immigration. The Kronotsky Lake Dolly Varden morphs may represent an example of ecological speciation in progress, and we present a working hypothesis for the diversification of morphs within Kronotsky Lake.

  19. Accumulation reconstruction and water isotope analysis for 1735–1997 of an ice core from the Ushkovsky volcano, Kamchatka, and their relationships to North Pacific climate records

    Directory of Open Access Journals (Sweden)

    T. Sato

    2013-04-01

    Full Text Available To investigate past climate change in the Northwest Pacific region, an ice core was retrieved in June 1998 from the Gorshkov crater glacier at the top of the Ushkovsky volcano, in central Kamchatka. Hydrogen isotope (δD analysis and past accumulation reconstructions were conducted to a depth of 140.7 m, dated to 1735. Two accumulation reconstruction methods were applied with the Salamatin and the Elmer/Ice ice flow models. Reconstructed accumulation rates and δD were significantly correlated with North Pacific surface temperature. This, and a significant correlation of δD with the North Pacific Gyre Oscillation (NPGO index implies that NPGO data is contained in this record. Wavelet analysis shows that the ice core records have significant multi-decadal power spectra up to the late 19th century. The multi-decadal periods of reconstructed accumulation rates change at around 1850 in the same way as do Northeast Pacific ice core and tree ring records. The loss of multi-decadal scale power spectra of δD and the 6‰ increase in its average value occurred around 1880. Thus the core record confirms that the periodicity of precipitation for the entire North Pacific changed between the end of the Little Ice Age through the present due to changes in conditions in the North Pacific Ocean.

  20. Geochemistry and Microbiology of Hot Springs in Kamchatka,Russia%俄罗斯勘察加半岛热泉的地球化学和微生物学

    Institute of Scientific and Technical Information of China (English)

    赵为东; Christopher S. Romanek; Gary Mills; Juergen Wiegel; 张传伦

    2005-01-01

    Kamchatka is one of the most active regions of volcanism in the world because it is located in the transitional zone where the Eurasian plate, North American plate and Pacific plates meet. As a result, Kamchatka has numerous hydrothermal systems, which constantly release geothermal gases and fluids out to the earth surface. Geothermal gases such as N2 and CO2 may prevail in the outflows but H2, CH4 and H2S occur frequently. Hot spring waters in Kamchatka may have multiple origins including meteoric and magmatic water. The temperature of these hot springs ranges from ~20 ℃ to greater than 90 ℃. Water chemistry also varies dramatically with pH ranging from 3.1 to 9.8. Hydrothermal fluids are sodium chloride water dominant and may contain various dissolved constituents including K+, H3BO3, H4SiO4, Ca2+, and SO42-. Volcanic ore-formation prevails in the high thermal activity regions in Kamchatka and precipitates may be dominated by silica crusts, sulfur and Hg-Sb-As-FeS deposits. Oils are also generated in the region and dominated by n-alkanes.More than 24 novel thermophilic microorganisms have been isolated from hot springs in Kamchatka. Most of these isolates are heterotrophs; however, autotrophs may be equally abundant depending on the spring conditions. Collectively, these organisms may play important roles in biogeochemical cycling of carbon, sulfur and iron in the hydrothermal system. Culture-independent approaches and quantitative methods are now employed to enhance our understanding of the ecology and biogeochemical functions of microorganisms in Kamchatka hot springs.%勘察加半岛位于欧洲板块、北美板块和太平洋板块交汇的过渡带上,是世界火山活动最活跃的地区之一.其众多的热液系统不断的向地表释放地热气体和流体.以N2和CO2为主的地热气体也经常含有高浓度的H2,CH4和H2S.大气水和熔岩水构成了勘察加热泉水的主要源,水体温度从20 ℃到>90 ℃不等.水化学性质

  1. Comparison of GLUT1, GLUT2, GLUT4 and SGLT1 mRNA Expression in the Salivary Glands and Six Other Organs of Control, Streptozotocin-Induced and Goto-Kakizaki Diabetic Rats

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    Cedric Jurysta

    2013-01-01

    Full Text Available Background/Aims: The expression and localization of several distinct glucose transporters (GLUT1, GLUT2, GLUT4, and SGLT1 was recently characterized in the parotid gland of normal rats by quantitative real-time PCR analysis, immunohistochemistry and Western blotting. The major aims of the present study was to compare the mRNA expression of these glucose transporters in both the parotid gland and submaxillary gland of control rats, streptozotocin-induced diabetic rats and hereditarily diabetic Goto-Kakizaki rats. Methods: Quantitative real-time PCR analysis was performed in the parotid and submaxillary salivary glands and, for purpose of comparison, also in the heart, kidney, liver, lung, muscle and pancreas from control animals and either streptozotocin-treated or Goto-Kakizaki rats. Results: The expression of GLUT4, but not GLUT1 or SGLT1, mRNA was decreased in the diabetic rats. The results also allow comparing both the mRNA expression level of the four glucose transporters in salivary glands and six other organs, and the diabetes-induced changes in such an expression in distinct locations. Conclusion: The mRNA expression of the insulin-dependent GLUT4 transporter was the sole to be significantly decreased in the salivary glands of diabetic animals. The possible consequence of such a decrease in terms of the control of salivary glucose concentration requires further investigation.

  2. 钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)在治疗2型糖尿病中的有效性和安全性%Efficacy and safety of sodium glucose co-transporter 2 inhibitors(SGLT2i) in the treatment of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    张波; 杨文英

    2016-01-01

    [Summary] As of 2014, an estimated 387 million people have diabetes mellitus ( DM) worldwide, which represents 8.3%of the adult population.China Noncommunicable Disease Surveillance in 2010 shows that the overall prevalence of DM is estimated to be 11.6%(approximately 113.9 million) in the Chinese adult population, with the prevalence among men of 12.1%and women of 11.0%, respectively.Control of blood glucose is fundamental to DM management.Despite the availability of several antihyperglycemic agents, only 53%of patients with DM achieve the recommended goals for DM care of HbA1C<7.0%.According to the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System Survey during the period of 10 years in the United States, 33.4%to 48.7%of persons with DM still have not met the targets for glycemic control, blood pressure or lipid level.In order to improve glycemic control, there is a need for new therapeutic options with innovative mechanisms of action and acceptable safety profiles.As a newly developed class of oral antidiabetic drugs, sodium-glucose co-transporter 2 inhibitors(SGLT2i) have recently been approved for the treatment of patients with type 2 diabetes mellitus, including canagliflozin, dapagliflozin, and empagliflozin.Evidence from clinical trials has suggested promising efficacy and safety of SGLT2i when used as monotherapy or in combination with other antihyperglycemic medications.SGLT2i significantly reduce HbA1C and fasting plasma glucose, and are well tolerated in general with a low intrinsic propensity to cause hypoglycemia, as well as rare severe renal or cardiovascular adverse events reported.%2014年全球确诊糖尿病患者共3.87亿例,患病率8.3%。2010年中国慢病监测暨糖尿病专题调查显示,中国成人糖尿病患病率为11.6%(约1.139亿例),男性和女性分别为12.1%和11.0%。血糖控制对2型糖尿病的治疗管理至关重要。

  3. Neural network approach to the prediction of seismic events based on low-frequency signal monitoring of the Kuril-Kamchatka and Japanese regions

    Directory of Open Access Journals (Sweden)

    Irina Popova

    2013-08-01

    Full Text Available Very-low-frequency/ low-frequency (VLF/LF sub-ionospheric radiowave monitoring has been widely used in recent years to analyze earthquake preparatory processes. The connection between earthquakes with M ≥5.5 and nighttime disturbances of signal amplitude and phase has been established. Thus, it is possible to use nighttime anomalies of VLF/LF signals as earthquake precursors. Here, we propose a method for estimation of the VLF/LF signal sensitivity to seismic processes using a neural network approach. We apply the error back-propagation technique based on a three-level perceptron to predict a seismic event. The back-propagation technique involves two main stages to solve the problem; namely, network training, and recognition (the prediction itself. To train a neural network, we first create a so-called ‘training set’. The ‘teacher’ specifies the correspondence between the chosen input and the output data. In the present case, a representative database includes both the LF data received over three years of monitoring at the station in Petropavlovsk-Kamchatsky (2005-2007, and the seismicity parameters of the Kuril-Kamchatka and Japanese regions. At the first stage, the neural network established the relationship between the characteristic features of the LF signal (the mean and dispersion of a phase and an amplitude at nighttime for a few days before a seismic event and the corresponding level of correlation with a seismic event, or the absence of a seismic event. For the second stage, the trained neural network was applied to predict seismic events from the LF data using twelve time intervals in 2004, 2005, 2006 and 2007. The results of the prediction are discussed.

  4. Geochemistry of the late Holocene rocks from the Tolbachik volcanic field, Kamchatka: Quantitative modelling of subduction-related open magmatic systems

    Science.gov (United States)

    Portnyagin, Maxim; Duggen, Svend; Hauff, Folkmar; Mironov, Nikita; Bindeman, Ilya; Thirlwall, Matthew; Hoernle, Kaj

    2015-12-01

    We present new major and trace element, high-precision Sr-Nd-Pb (double spike), and O-isotope data for the whole range of rocks from the Holocene Tolbachik volcanic field in the Central Kamchatka Depression (CKD). The Tolbachik rocks range from high-Mg basalts to low-Mg basaltic trachyandesites. The rocks considered in this paper represent mostly Late Holocene eruptions (using tephrochronological dating), including historic ones in 1941, 1975-1976 and 2012-2013. Major compositional features of the Tolbachik volcanic rocks include the prolonged predominance of one erupted magma type, close association of middle-K primitive and high-K evolved rocks, large variations in incompatible element abundances and ratios but narrow range in isotopic composition. We quantify the conditions of the Tolbachik magma origin and evolution and revise previously proposed models. We conclude that all Tolbachik rocks are genetically related by crystal fractionation of medium-K primary magmas with only a small range in trace element and isotope composition. The primary Tolbachik magmas contain ~ 14 wt.% of MgO and ~ 4% wt.% of H2O and originated by partial melting (~ 6%) of moderately depleted mantle peridotite with Indian-MORB-type isotopic composition at temperature of ~ 1250 °C and pressure of ~ 2 GPa. The melting of the mantle wedge was triggered by slab-derived hydrous melts formed at ~ 2.8 GPa and ~ 725 °C from a mixture of sediments and MORB- and Meiji-type altered oceanic crust. The primary magmas experienced a complex open-system evolution termed Recharge-Evacuation-Fractional Crystallization (REFC). First the original primary magmas underwent open-system crystal fractionation combined with periodic recharge of the magma chamber with more primitive magma, followed by mixing of both magma types, further fractionation and finally eruption. Evolved high-K basalts, which predominate in the Tolbachik field, and basaltic trachyandesites erupted in 2012-2013 approach steady-state REFC

  5. Lava emplacements at Shiveluch volcano (Kamchatka) from June 2011 to September 2014 observed by TanDEM-X SAR-Interferometry

    Science.gov (United States)

    Heck, Alexandra; Kubanek, Julia; Westerhaus, Malte; Gottschämmer, Ellen; Heck, Bernhard; Wenzel, Friedemann

    2016-04-01

    As part of the Ring of Fire, Shiveluch volcano is one of the largest and most active volcanoes on Kamchatka Peninsula. During the Holocene, only the southern part of the Shiveluch massive was active. Since the last Plinian eruption in 1964, the activity of Shiveluch is characterized by periods of dome growth and explosive eruptions. The recent active phase began in 1999 and continues until today. Due to the special conditions at active volcanoes, such as smoke development, danger of explosions or lava flows, as well as poor weather conditions and inaccessible area, it is difficult to observe the interaction between dome growth, dome destruction, and explosive eruptions in regular intervals. Consequently, a reconstruction of the eruption processes is hardly possible, though important for a better understanding of the eruption mechanism as well as for hazard forecast and risk assessment. A new approach is provided by the bistatic radar data acquired by the TanDEM-X satellite mission. This mission is composed of two nearly identical satellites, TerraSAR-X and TanDEM-X, flying in a close helix formation. On one hand, the radar signals penetrate clouds and partially vegetation and snow considering the average wavelength of about 3.1 cm. On the other hand, in comparison with conventional InSAR methods, the bistatic radar mode has the advantage that there are no difficulties due to temporal decorrelation. By interferometric evaluation of the simultaneously recorded SAR images, it is possible to calculate high-resolution digital elevation models (DEMs) of Shiveluch volcano and its surroundings. Furthermore, the short recurrence interval of 11 days allows to generate time series of DEMs, with which finally volumetric changes of the dome and of lava flows can be determined, as well as lava effusion rates. Here, this method is used at Shiveluch volcano based on data acquired between June 2011 and September 2014. Although Shiveluch has a fissured topography with steep slopes

  6. Recognizing subtle evidence for silicic magma derivation from petrochemically-similar arc crust: Isotopic and chemical evidence for the bimodal volcanic series of Gorely Volcanic Center, Kamchatka, Russia

    Science.gov (United States)

    Seligman, A. N.; Bindeman, I. N.; Ellis, B. S.; Ponomareva, V.; Leonov, V.

    2012-12-01

    The Kamchatka Peninsula is home to some of the most prolific subduction related volcanic activity in the world. Gorely caldera and its central volcano are located in the rear of its currently active Eastern Volcanic Front. Recent work determined the presence of explosive ignimbrite eruptions sourced from Gorely volcano during the Pleistocene. We studied 32 eruptive units, including tephrochronologically-dated Holocene tephra, stratigraphically-arranged ignimbrites, as well as pre- and post-caldera lavas. We analyzed oxygen isotope ratios of pyroxene and plagioclase grains by laser fluorination, and major and trace element compositions of whole rocks. In addition, we determined 87Sr/86Sr and 143Nd/144Nd ratios of caldera-forming ignimbrite eruptions. Chemical compositions show that Gorely eruptive units range from basalt to basaltic andesite in the "Pra-Gorely" stages prior to caldera formation and the modern Gorely stages forming its current edifice. In contrast, eruptive material from earlier ignimbrites exposed at Opasny Ravine consists primarily of dacite. Whole rock analyses for Gorely indicate that silicic rocks and ignimbrites volumetrically dominate all other products, forming separate bimodal peaks in our SiO2-frequency diagram. In addition, trace element concentrations and ratios define two trends, one for more silicic and another for more mafic material. δ18Omelt values range from a low of 4.85 up to 6.22‰, where the lowest value was found in the last caldera forming eruption, suggesting incorporation of hydrothermally-altered material from earlier eruptions. 87Sr/86Sr and 143Nd/144Nd ratios range from 0.70328 to 0.70351 and from 0.51303 to 0.51309 respectively, with higher and more diverse values being characteristic of earlier ignimbrite units; again suggesting incorporation of surrounding crustal material. In contrast to these results, MELTS modeling using a variety of likely primitive basalts from Gorely shows it is possible to obtain silicic

  7. Chlorine and fluorine partition coefficients and abundances in sub-arc mantle xenoliths (Kamchatka, Russia): Implications for melt generation and volatile recycling processes in subduction zones

    Science.gov (United States)

    Bénard, A.; Koga, K. T.; Shimizu, N.; Kendrick, M. A.; Ionov, D. A.; Nebel, O.; Arculus, R. J.

    2017-02-01

    We report chlorine (Cl) and fluorine (F) abundances in minerals, interstitial glasses, and melt inclusions in 12 andesite-hosted, spinel harzburgite xenoliths and crosscutting pyroxenite veins exhumed from the sub-arc lithospheric mantle beneath Avacha volcano in the Kamchatka Arc (NE Russia). The data are used to calculate equilibrium mineral-melt partition coefficients (D mineral / melt) for Cl and F relevant to subduction-zone processes and unravel the history of volatile depletion and enrichment mechanisms in an arc setting. Chlorine is ∼100 times more incompatible in pyroxenes (DClmineral/melt = 0.005-0.008 [±0.002-0.003]) than F (DFmineral/melt = 0.50-0.57 [±0.21-0.24]), which indicates that partial melting of mantle sources leads to strong depletions in Cl relative to F in the residues. The data set in this study suggests a strong control of melt composition on DCl,Fpyroxene/melt, in particular H2O contents and Al/(Al + Si), which is in line with recent experiments. Fluorine is compatible in Ca-amphibole in the 'wet' sub-arc mantle (DFamphibole/melt = 3.5-3.7 [±1.5]) but not Cl (DClamphibole/melt = 0.03-0.05 [±0.01-0.03]), indicating that amphibole may fractionate F from Cl in the mantle wedge. The inter-mineral partition coefficients for Cl and F in this study are consistent amongst different harzburgite samples, whether they contain glass or not. In particular, disseminated amphibole hosts much of the Cl and F bulk rock budgets of spinel harzburgites (DClamphibole/pyroxene up to 14 and DFamphibole/pyroxene up to 40). Chlorine and fluorine are variably enriched (up to 1500 ppm Cl and 750 ppm F) in the parental arc picrite and boninite melts of primitive pyroxenite veins (and related melt inclusions) crosscutting spinel harzburgites. Based on the data in this study, the main inferences on the behaviour of Cl and F during melting and metasomatic processes in the sub-arc mantle are as follow: (i) Melting models show that most depleted mantle protoliths

  8. Steklite, KAl(SO4)2: A finding at the Tolbachik Volcano, Kamchatka, Russia, validating its status as a mineral species and crystal structure

    Science.gov (United States)

    Murashko, M. N.; Pekov, I. V.; Krivovichev, S. V.; Chernyatyeva, A. P.; Yapaskurt, V. O.; Zadov, A. E.; Zelensky, M. E.

    2013-12-01

    Steklite KAl(SO4)2 has been found in sublimates of the Yadovitaya (Poisonous) fumarole at the second cinder cone of the northern breach of the Great Fissure Tolbachik Eruption, Tolbachik volcano, Kamchatka Peninsula, Russia. Steklite was approved as a valid mineral species by the Commission on New Minerals, Nomenclature, and Mineral Classification of the International Mineralogical Association on June 2, 2011 (IMA no. 2011-041). The name steklite is left for this mineral, as it was named by Chesnokov et al. (1995) for its technogenic analog from a burnt dump of coal mine no. 47 at Kopeisk, the Southern Urals, Russia. It is named after the Russian word steklo, meaning glass, in allusion to the visual similarity of its lamellae to thin glass platelets. At Tolbachik, steklite is associated with alumoklyuchevskite, langbeinite, euchlorine, fedotovite, chalcocyanite, hematite, and lyonsite. It occurs as hexagonal or irregular-shaped lamellar crystals with the major form {001} reaching 30 μm in thickness and 0.2 mm (occasionally up to 1 mm) in width. The crystals are frequently split. They are combined into openwork aggregates or thin crusts up to 1.5 × 2.5 cm in area. Steklite is transparent and colorless, with vitreous luster. The cleavage is perfect, parallel to (001). The mineral is brittle. The Mohs' hardness is 2.5. D calc is 2.797 g/cm3. Steklite is optically uniaxial, (-), ω = 1.546(2), ɛ = 1.533(3). The chemical composition (wt %, electron-microprobe data) is as follows: 0.09 Na2O, 18.12 K2O, 0.08 CaO, 0.03 MnO, 2.02 Fe2O3, 18.18 Al2O3, 61.80 SO3. The total is 100.37. The empirical formula calculated on the basis of eight O atoms is: (K0.997Na0.008Ca0.004)Σ1.009(Al0.925Fe{0.066/3+}Mg0.003Mn0.001)Σ0.995S2.01O8. Steklite is trigonal, space group P321, a = 4.7281(3), c = 7.9936(5) Å, V = 154.76(17)Å3, Z =1. The strongest reflections in the X-ray powder diffraction pattern ( d, Å- I[ hkl]) are: 8.02-34[001], 4.085-11[100], 3.649-100[011, 101], 2

  9. New volcanogenic-eruptive genetic type of diamond occurrence (based on studying the 2012-2013 Fissure Tolbachik Eruption in Kamchatka)

    Science.gov (United States)

    Karpov, Gennady; Anikin, Leonid; Filatov, Stanislav; Silaev, Valery; Petrovsky, Vitaly; Zolotarev, Andrey; Dunin-Barkovsky, Romuald; Volynets, Anna

    2014-05-01

    the instance considered. The above can indicate that Tolbachik diamonds were never affected by mantle anneal. Generally, by their spectroscopic properties, Kamchatka diamonds correspond to the Ib-type whose occurrence among natural diamonds does not exceed 2%. Reported are isolated twinned crystals. Tiny grains of blue moissanite, single grains of pink garnet and pink and blue corundum were found within the association accompanying diamonds (commonly in basalt pores). Often found are thin laminae and filaments of native elements (Fe, Al, Cu), blades or lumpy grains of Cu-Sn (Zn) alloy. Tolbachik diamonds bear no evidence of magmatic corrosion. Data obtained allow us to state the discovery of a new genetic type of diamond occurrence that we suggest to call "volcanogenic-eruptive", or Tolbachik type.

  10. New Paleoclimate Records from the Russian Far East: Carbon Accumulation Rates and Ecological Change Over the Last 13,000 Years from Western and Central Kamchatka

    Science.gov (United States)

    Bochicchio, C. J.; Loisel, J.; Yu, Z.; Beilman, D.; Dirksen, V.; Dirksen, O.; Nichols, J. E.

    2014-12-01

    The Kamchatka peninsula lies along the confluence of the Pacific Ocean, and the Bering and Okhotsk Seas (OS). Its location is ideal to record shifts in regional ocean and atmospheric circulation and contains vast stores of carbon-rich peatlands, yet paleoclimate records from this area are scarce. This research aims to provide new paleo-proxy records that document carbon dynamics, precipitation, and temperature over the Holocene. We focus on site C4 (54.02 N, 156.13 E) located 18 km from OS coast at 91 m elevation and draw comparisons with site C1 (54.91 N, 156.60 E) which is 62 km from the coast at 256 m elevation, both in the Western Lowland (WL) region. Cores C1 and C4 are 450 and 375 cm in length, respectively. C4 and C1 were analyzed for organic matter (OM) content; while C4 received additional δ-deuterium (δD), plant macrofossil, and fossil pollen analysis. Both cores cover the last 13,000 years from the Western Lowlands (WL); prior to this study no such records existed from the WL or the eastern OS coastline. Chronologies are based on radiocarbon dating of fine fraction bulk peat and Sphagnum plant macrofossils. At both sites, peat accumulation began 11 ka (1 ka = 1000 calibrated years before present), is continuous to the surface, interlayered with tephra, and overlays a clay unit with 20% OM. OM density measured at 1 cm intervals show similar means of 0.1 g cm-3 over the last 11 ka and, despite the close proximity of the sites (103 km), they show two opposing OM trends: Period 1) From 5.8 to 3.5 ka, C1 OM density decreased ~0.10 to 0.06 g cm-3 while C4 increased from ~0.10 to 0.19 g cm-3, and Period 2) from 3.5 to 0.9 ka, C1 OM density increased to ~0.18 g cm-3 while C4 decreased to ~0.11 cm-3. Peat carbon accumulation rate (PCAR) is similar for both periods in C1 and C4 at 20.1 and 14.1 g m-2 yr-1, respectively. Prior to 5.8 ka PCAR in C1 and C4 is ~30 g m-2 yr-1 in the early Holocene, decreasing to 19 g m-2 yr-1 in the Mid- Late Holocene. C4 shows large

  11. A validated LC-MS/MS method for the determination of canagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, in a lower volume of rat plasma: application to pharmacokinetic studies in rats.

    Science.gov (United States)

    Kobuchi, Shinji; Yano, Kyoka; Ito, Yukako; Sakaeda, Toshiyuki

    2016-10-01

    Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of canagliflozin in a lower volume of rat plasma (0.1 mL) was established and applied to a pharmacokinetic study in rats. Following liquid-liquid extraction by tert-butyl methyl ether, chromatographic separation of canagliflozin was performed on a Quicksorb ODS (2.1 mm i.d. × 150 mm, 5 µm size) using acetonitrile-0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.2 mL/min. The detection was carried out using an API 3200 triple-quadrupole mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z = 462.0 [M + NH4 ](+)  → 191.0 for canagliflozin and m/z = 451.2 [M + H](+)  → 71.0 for empagliflozin (internal standard) were obtained. The validation of the method was investigated, and it was found to be of sufficient specificity, accuracy and precision. Canagliflozin in rat plasma was stable under the analytical conditions used. This validated method was successfully applied to assess the pharmacokinetics of canagliflozin in rats using 0.1 mL rat plasma. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. SOME RESULTS OF THE THIRD COMPLEX MULTIDISCIPLINARY EXPEDITION OF THE RUSSIAN GEOGRAPHICAL SOCIETY FOR MONITORING OF THE RADIATION SITUATION IN THE KURIL-KAMCHATKA AREA OF THE PACIFIC OCEAN, 2014

    Directory of Open Access Journals (Sweden)

    A. M. Biblin

    2015-01-01

    Full Text Available The Third complex multidisciplinary expedition of the Russian Geographic Society for monitoring of the radiation situation in the Kuril-Kamchatka area of the Pacific Oceantook place in September – October 2014. The purposes of the expedition were monitoring of the radiation situation and assessment of the impact of the accident at the nuclear power plant “Fukushima-1”on radioactive contamination of the marine environment near the Russian coasts. This paper presents results on the activity measurements of the cesium and strontium radionuclides in the hydrobionts collected during the expedition in the Seas of Japan and Okhotsk. Nine samples of the sea hydrobionts including one species of invertebrates and four species of fish have been analysed. Determination of activity concentrations of radionuclides of cesium (separately 134Cs and 137Cs were carried out by the gammaspectrometry method using a high-resolution semiconductor detector. Activity concentrations of 90Sr were quantified with a radiochemical method. The activity concentrations of 90Sr and the total activity concentrations of both cesium radioisotopes for all the samples analyzed did not exceed 1 Bq kg–1 (wet weight. This value is much lower than the safe levels of 130 Bq kg–1 (radiocesium and 100 Bq kg–1 (radiostrontium for the fish consumption inRussia. The study demonstrates that theFukushima accident has no considerable impact on radioactive contamination of the selected species of hydrobiota in Russian waters of theJapanSea andOkhotskSea.

  13. Centennial to millennial climate variability in the far northwestern Pacific (off Kamchatka and its linkage to the East Asian monsoon and North Atlantic from the Last Glacial Maximum to the early Holocene

    Directory of Open Access Journals (Sweden)

    S. A. Gorbarenko

    2017-08-01

    Full Text Available High-resolution reconstructions based on productivity proxies and magnetic properties of core LV63-41-2 (off Kamchatka reveal prevailing centennial productivity/climate variability in the northwestern (NW Pacific from the Last Glacial Maximum (LGM to the early Holocene (EH. The age model of the core is established by AMS 14C dating and by projections of AMS 14C data of the nearby core SO-201-12KL through correlation of the productivity proxies and relative paleomagnetic intensity. The resulting sequence of centennial productivity increases/climate warming events in the NW Pacific occurred synchronously with the East Asian summer monsoon (EASM sub-interstadials during the LGM (four events, Heinrich Event 1 (HE1 (four events, Bølling–Allerød (B/A warming (four events, and over the EH (four events. Remarkable similarity of the sequence of the NW Pacific increased-productivity events with the EASM sub-interstadials over the LGM-HE1 implies that the Siberian High is a strong and common driver. The comparison with the δ18O record from Antarctica suggests that another mechanism associated with the temperature gradient in the Southern Hemisphere may also be responsible for the EASM/NW Pacific centennial events over the LGM-HE1. During the B/A warming and resumption of the Atlantic Meridional Overturning Circulation (AMOC, clear synchronicity between the NW Pacific, EASM and Greenland sub-interstadials was mainly controlled by changes in the atmospheric circulation. During the EH the linkages between solar forcing, ocean circulation, and climate changes likely control the synchronicity of abrupt climate changes in the NW Pacific and North Atlantic. The sequence of centennial events recorded in this study is a persistent regional feature during the LGM-EH, which may serve as a template in high-resolution paleoceanography and sediment stratigraphy in the NW Pacific.

  14. 断奶仔猪日粮添加人工甜味剂可提高钠/葡萄糖共转运载体的表达%The Effect of Artificial Sweetener for Early Weaned Piglets on the SGLT1 Expression

    Institute of Scientific and Technical Information of China (English)

    Andrew W Moran; Miran A Al-Rammahi; David Bravo; Soraya P Shirazi-Beechey; 张津校

    2010-01-01

    在当今集约化养殖日益突出的环境下,缩短仔猪断奶日龄可以提高母猪的年产仔猪数量.然而,这种人为干预会导致小猪出现营养吸收紊乱,表现出腹泻、营养不良和脱水等症状.为了预防这些症状,研究人员提出了很多解决方案.人工合成的甜味剂由于能够改善日粮的适口性而被广泛应用于仔猪日粮中.本研究证明了在仔猪日粮中添加含人工合成甜味剂糖精钠和新橙皮苷二氢查耳酮(NHDC)的产品能够提高SGLT1的表达以及肠道对葡萄糖的转运能力,T1R2、T1R3和味导素在仔猪肠道内分泌细胞中共同表达生成,并且一些肠道内分泌激素与日粮的碳水化合物、类胰高血糖素肽(GLP1和GLP2)、萄萄糖依赖促胰岛素肽(GIP)相互作用且和Ⅰ型GTP结合蛋白耦联受体(T1R)以及味导素等在肠道共表达,仅仅很少数目的L-型和K-型内分泌细胞能够表达这些味觉因子且与Ⅰ型GTP结合蛋白耦联受体和5-羟色胺共同表达释放.此外,本研究亦证明了人T1R3的抑制剂(Lactisole)不能抑制仔猪肠道SGLT1的表达.总之,通过对甜味剂上调SGLT1机理的深入研究有助于营养学家更深入地了解如何更好地预防仔猪断奶相关的营养吸收不良等问题的发生.

  15. Bolstering your armamentarium with SGLT2 inhibitors.

    Science.gov (United States)

    Novak, Lucia M; Kruger, Davida F

    2017-10-18

    Sodium-glucose cotransporter-2 inhibitors have a unique mechanism of action in the kidneys that causes glucosuria, which lowers plasma glucose. They are also associated with reduced body weight and BP, and a low incidence of hypoglycemia. This article reviews the pharmacologic profiles and clinical implications of canagliflozin, dapagliflozin, and empagliflozin.

  16. Composition, volatile components, and trace elements in andesitic melts of the Kurile-Kamchatka region%俄罗斯Kurile-Kamchatka地区安山质熔体的成分、挥发分组成和微量元素

    Institute of Scientific and Technical Information of China (English)

    M.L.Tolstykh; V.B.Naumov; A.D.Babansky

    2007-01-01

    Melt inclusions in minerals from some volcanoes of the Kurile-Kamchatka region were examined. The studied basaltic andesites and andesites were sampled from volcanoes of the Central Kamchatka depression ( Shiveluch and Bezymyannyi), Eastern Kamchatka volcanic belt (Avachinskii and Karymskii), and Iturup Island, Southern Kuriles (Kudryavyi). Basalts of the 1996 eruption of the Karymskii volcanic center and dacites of Dikii Greben' volcano, Southern Kamchatka were also studied. More than 260 melt inclusions from 31 rock samples were homogenized, and quenched glasses were analyzed using electron and ion microprobes. The compositions of melt inclusions in andesitic phenocrysts vary in silica contents from 56 to 80wt%. Al2O3 , FeO, MgO, CaO decrease and Na2O and K2O increase with increasing SiO2. Many inclusions ( about 80% ) are dacitic or rhyolitic. However, the compositions of silicic glasses ( >65wt% SiO2 ) in andesites significantly differ in TiO2 , FeO, MgO, CaO, and K2O contents from those in dacites and rhyolites. High-potassium melts (K2O 3.8 ~6.8wt% ) with various SiO2 from 51.4 to 77.2wt% were found in minerals of all volcanoes studied. This indicates a contribution of a component selectively enriched in potassium to magmas of the whole region. A great compositional diversity of melt inclusions in plagioclase phenocrysts from the Bezymyannyi andesites suggests a complex history of plagioclase crystallization and magma evolution in the andesite formation. Melts from different volcanoes strongly vary in volatile contents. The highest H2O contents are found in the melts from Shiveluch (3.0 ~7.2wt%, 4.7wt% on average) and Avachinskii (4.7 ~4.8wt% ); while those are lower in melts of Kudryavyi (0.1 ~ 2.6wt% ), Dikii Greben' (0.4 ~ 1.8wt% ), and Bezymyannyi ( < 1wt% ). Chlorine contents are also variable. The lowest values are found in the Bezymyannyi melts (0.09wt% on average), the highest Cl contents are typical of melt inclusions in minerals from

  17. Comparison of contrast sensitivity and glare contrast sensitivity following implantation of photochromic, blue-light filtering ,and conventional clear intraocular lenses%光变色IOL、蓝光滤过IOL和普通IOL植入术后对比敏感度、眩光对比敏感度对比分析

    Institute of Scientific and Technical Information of China (English)

    陈琛; 韦秋红; 刘超; 杜卫静

    2012-01-01

    Objective To compare contrast sensitivity (CS) and glare CS following implantation of photochromic, blue-light filtering and conventional clear intraocular lenses. Methods Sixty senile cataract patients (60 eyes) were randomly divided into 3 groups according to the type of IOL. Group A was implanted MATRITM 400,group B was implanted Acrysof Natural SN60AT,and group C was implanted LENSTEC SofTec I. The CS and glare CS were measured with CSV-1000E at 3 months after surgery. Results Preoperative best corrected vision were 0. 27 ±0. 10 in group A,0. 27 ± 0. 09 in group B ,0.27 ± 0. 09 in group C, and postoperative best corrected vision were 0. 75 ± 0.08 in group A.0.70 ±0.09 in group B,0.70 ±0.09 in group C. There was no statisticaldifference among three groups preoperatively and postoperatively ( all P > 0. 05). But there were statistical differences in each group about the corrected vision between pre-operation and post-operation (all P 0.05). Compared with CS,the glare CS was improved in group A at each spatial frequency (all P 0.05). The CS curve was at normal value in group A, but lower than that of normal people in group B and group C. Conclusion Photochromic MATRIX? 400 intraocular lens has better visual quality than that with blue-light filtering Acrysof Natural SN60AT or conventional clear intraocular lens LENSTEC SofTec I.%目的 观察光变色人工晶状体( intraocular lens,IOL)、蓝光滤过IOL和普通非蓝光滤过IOL植入术后的对比敏感度( contrast sensitivity,CS)和眩光CS的差异.方法 60例老年性白内障随机分为3组,均行白内障超声乳化吸出联合IOL植入术,分别植入光变色MATRIXTM400型IOL(A组)、Acrysof Nutural SN60AT蓝光滤过IOL(B组)、不具有光线滤过功能的LEN-STEC SofTec Ⅰ普通折叠IOL(C组),术后3个月对3组患者进行最佳矫正视力、CS和眩光CS检查.结果 术前A组最佳矫正视力为0.27±0.10,B组为0.27±0.09,C组为0.27±0.09,术后分别为0.75±0.08、0.70±0

  18. Determination of laser energy density threshold leading to glare-induced blindness by pattern visual evoked potential in guinea pigs%图形视觉诱发电位在豚鼠眩光致盲激光能量密度阈值检测中的作用

    Institute of Scientific and Technical Information of China (English)

    李振峰; 熊聪; 殷浩; 夏峰; 安晶; 张磊; 张作明

    2012-01-01

    Objective To explore the application of pattern visual evoked potential (PVEP) in examination of energy density threshold of laser beam that may lead to glare-induced blindness in guinea pigs. Methods Stainless steel bolts (5mm in length, 1.2mm in diameter), as reference electrode and recording electrode for the PVEP measurement, were implanted into skulls of 27 guinea pigs, located in 6mm proximal to bregma and 10mm distal to bregma. These guinea pigs were randomly divided into three groups with 9(18 eyes) for each group, and they were exposed to laser beam at wave length of 63Snm, 660nm and 690nm, respectively. The PVEP was recorded in each group before and immediately after laser irradiation, and also on day 2 and day 4 after laser irradiation in guinea pigs blinded immediately after laser exposure. The latency and amplitude of P wave in PVEP before irradiation was considered as control value for each group. When PVEP could not be recorded instantly after laser irradiatibn, the intensity of electric current applied at that time was considered as threshold value of each laser beam. The power of electricity(P) values was then calculated, and energy density threshold that led to glare-induced blindness was figured out according to current-power curve (P-I curve). On day 2 and day 4 after irradiation, PVEP was additionally recorded, and latency and amplitude of Pwave were compared with that of control values to examine the recovery of visual function of the blind guinea pigs. Results The energy density thresholds of the three laser beams at wave length of 635nm, 660nm, 690nm respectively were 356.36×10-9J/cm2, 349.58×10-9 J/cm and 343.93 x 10 J/cm . In guinea pigs became blind after exposure to laser beams at wave length of 635nm, 660nm, 690nm, the latencies of P wave recorded 2 days after blindness were not significantly different with control value of each group(t= -0.356, P=0.729;t=0.492, P=0.633; t= - 0.445, P=0.666), while the difference in amplitudes was

  19. Automatic Laser Glare Suppression in Electro-Optical Sensors

    Directory of Open Access Journals (Sweden)

    Gunnar Ritt

    2015-01-01

    Full Text Available Progress in laser technology has led to very compact but nevertheless powerful laser sources. In the visible and near infrared spectral region, lasers of any wavelength can be purchased. Continuous wave laser sources pose an especially serious threat to the human eye and electro-optical sensors due to their high proliferation and easy availability. The manifold of available wavelengths cannot be covered by conventional safety measures like absorption or interference filters. We present a protection concept for electro-optical sensors to suppress dazzling in the visible spectral region. The key element of the concept is the use of a digital micromirror device (DMD in combination with wavelength multiplexing. This approach allows selective spectral filtering in defined regions of interest in the scene. The system offers the possibility of automatic attenuation of dazzling laser radiation.

  20. Tensile and Interlaminar Properties of GLARE (Trade Name) Laminates

    Science.gov (United States)

    1991-09-01

    10 Aossnston For DTIC TAB Unannomum& ( JQs% t I rcat i-. _. DLatrlbuttoni wall oand/or VLa th 3p~elal III ,v I I i NAM-910874,0 FIGURES Figure...is good. This is particlarly eident when the GIARE results are ocupared to the peel strength of ARAU,-4 tested at the same peel rate. The very low...for Code 12; S. Fishman) Office of Naval Research ..................................... ........ 1 800 N. Quincy Street Arlington, VA 22217-5000 (1 for

  1. Pale Glares of Dark Matter in Quantum Spacetime

    CERN Document Server

    Doplicher, Sergio; Morsella, Gerardo; Pinamonti, Nicola

    2016-01-01

    A U(1) gauge theory turns, on physically motivated models of Quantum Spacetime, into a U($\\infty$) gauge theory, hence free classical electrodynamics is no longer free and neutral fields may have electromagnetic interactions. We discuss the last point for scalar fields, possibly describing dark matter; we have in mind the gravitational collapse of binary systems or future applications to self gravitating Bose-Einstein condensates as possible sources of evidence of quantum gravitational phenomena. The effects so far considered, however, seem too faint to be detectable at present.

  2. Bearing Strength Characteristics of Standard and Steel Reinforced GLARE

    NARCIS (Netherlands)

    Van Rooijen, R.G.J.

    2006-01-01

    Fibre Metal Laminates (FMLs) are hybrid materials, which consist of thin metal sheets bonded together with alternating unidirectional fibre layers. This material concept has resulted in superior fatigue characteristics with respect to the metallic counterpart. Several static characteristics are howe

  3. Modeling study of the Pauzhetsky geothermal field, Kamchatka, Russia

    Energy Technology Data Exchange (ETDEWEB)

    Kiryukhin, A.V. [Institute of Volcanology, Kamchatsky (Russian Federation); Yampolsky, V.A. [Kamchatskburgeotermia State Enterprise, Elizovo (Russian Federation)

    2004-08-01

    Exploitation of the Pauzhetsky geothermal field started in 1966 with a 5 MW{sub e} power plant. A hydrogeological model of the Pauzhetsky field has been developed based on an integrated analysis of data on lithological units, temperature, pressure, production zones and natural discharge distributions. A one-layer 'well by well' model with specified vertical heat and mass exchange conditions has been used to represent the main features of the production reservoir. Numerical model development was based on the TOUGH2 code [Pruess, 1991. TOUGH2 - A General Purpose Numerical Simulator for Multiphase Fluid and Heat Flow, Lawrence Berkeley National Laboratory Report, Berkeley, CA; Pruess et al., 1999. TOUGH2 User's Guide, Version 2.0, Report LBNL-43134, Lawrence Berkeley National Laboratory, Berkeley, CA] coupled with tables generated by the HOLA wellbore simulator [Aunzo et al., 1991. Wellbore Models GWELL, GWNACL, and HOLA, Users Guide, Draft, 81 pp.]. Lahey Fortran-90 compiler and computer graphical packages (Didger-3, Surfer-8, Grapher-3) were also used to model the development process. The modeling study of the natural-state conditions was targeted on a temperature distribution match to estimate the natural high-temperature upflow parameters: the mass flow-rate was estimated at 220 kg/s with enthalpy of 830-920 kJ/kg. The modeling study for the 1964-2000 exploitation period of the Pauzhetsky geothermal field was targeted at matching the transient reservoir pressure and flowing enthalpies of the production wells. The modeling study of exploitation confirmed that 'double porosity' in the reservoir, with a 10-20% active volume of 'fractures', and a thermo-mechanical response to reinjection (including changes in porosity due to compressibility and expansivity), were the key parameters of the model. The calibrated model of the Pauzhetsky geothermal field was used to forecast reservoir behavior under different exploitation scenarios for the central part of the field. The basic scenario assumes that the wellhead pressures of the eight exploitation wells and the injection rates of the three reinjection wells are maintained at the same conditions as of December 2000. In the base case, the model predicts a 12% decline in steam production rate (at 2.7 bar) during the next 30 years, even as the steam supply for the 5 MW{sub e} power plant is maintained. The modeling study confirmed that 30-60 kg/s is an optimal reinjection rate. An increase in the exploitation load has no significant effect on steam production from the central section of the Pauzhetsky field during the 30-year exploitation period; load doubling (eight additional exploitation wells) leads to a mere 16-27% increase in steam production. (author)

  4. Volcanic structure and composition of Old Shiveluch volcano, Kamchatka

    Science.gov (United States)

    Gorbach, Natalia; Portnyagin, Maxim; Tembrel, Igor

    2013-08-01

    This paper reports results of a new comprehensive geological mapping of the Late Pleistocene Old Shiveluch volcano. The mapping results and geochemical data on major and trace element composition of the volcanic rocks are used to characterize spatial distribution, eruptive sequence and volumetric relationships between different rock types of the volcano. Old Shiveluch volcano had been constructed during two main stages: initial explosive and subsequent effusive ones. Pyroclastic deposits of the initial stage are represented by agglomerate and psephytic tuffs with very few lava flows and form at least 60% of volume of the Old Shiveluch edifice. The deposits of the second stage are dominantly lava flows erupted from four vents: Central, Western, Baidarny and Southern, reconstructed from the field relationships of their lava flows. About 75% of the Old Shiveluch edifice, both pyroclastic deposits and lava, are composed of magnesian andesites (SiO2 = 57.3-63.8 wt.%, Mg# = 0.53-0.57). The most abundant andesitic lavas were coevally erupted from the Central and Western vents in the central part of the edifice. Less voluminous high-Al basaltic andesites (SiO2 = 53.5-55.7 wt.%, Mg# = 0.52-0.56) were produced by the Western, Baidarny and Southern vents situated in the south-western sector. Small volume high-Mg basaltic andesites (SiO2 = 53.9-55.0 wt.%, Mg# = 0.59-0.64) occur in the upper part of the pyroclastic deposits. Andesites of Old and Young Shiveluch Volcanoes have similar compositions, whereas Old Shiveluch basaltic andesites are compositionally distinctive from those of the Young Shiveluch by having lower Mg#, SiO2, Cr and Ni, and higher Al2O3, FeOT, CaO, TiO2, and V contents at given MgO. Geochemical modeling suggests that the compositions of the intermediate Old Shiveluch magmas can be reasonably explained by simple fractional crystallization of olivine, clinopyroxene, plagioclase and magnetite (± hornblende) from water-bearing (~ 3 wt.% H2O) high-Mg# basaltic parental magma at intermediate to shallow crustal depths ( 60 wt.%, Mg# 0.65) played a relatively minor role in creating the compositional diversity of the Old Shiveluch magmas compared to the Young Shiveluch ones. The pronounced change in the Shiveluch magma compositions could have been related to adjustments of the magma plumbing system beneath Old Shiveluch following the large scale sector collapse in the Late Pleistocene that enabled a common mixing of evolved and primitive magmas on the later, Holocene stage of the volcano evolution.

  5. Unaccompanied refugee children and adolescents: the glaring contrast between a legal and a psychological perspective.

    Science.gov (United States)

    Derluyn, Ilse; Broekaert, Eric

    2008-01-01

    Unaccompanied refugee children and adolescents are a vulnerable group: they live not only in a relatively difficult situation as minor refugees staying in another country, but also face other risks due to the absence of their parents, such as traumatic experiences, exploitation or abuse. The difficult living situation of these unaccompanied refugee children and adolescents might therefore threaten their emotional well-being, resulting in important emotional and behavioural problems. This 'psychological' perspective shows the necessity of a strongly elaborated reception and care system for these children and adolescents in order to meet their specific situation and needs. Nevertheless, the case study of unaccompanied refugee minors living in Belgium, as explored in this paper, shows that the legal perspective on these youths - considering them as 'refugees' and 'migrants', not as 'children' - is predominantly the starting point to build the care system on. Moreover, this legal perspective contrasts sharply with the psychological perspective, as such that these children and adolescents do not receive appropriate support and care as they need.

  6. Evaluation of Anti-Glare Applications for a Tactical Helmet-Mounted Display

    Science.gov (United States)

    2012-03-01

    participants wore a hat or head covering that would shield the projected light. After instruction, the participant was given a color blindness test...using a series of pseudoisochromatic plates. If the participant passed the color blindness test, they continued on to a second vision test that

  7. Hydrogen-bonded structures and interaction energies in two forms of the SGLT-2 inhibitor sotagliflozin.

    Science.gov (United States)

    Gelbrich, Thomas; Adamer, Verena; Stefinovic, Marijan; Thaler, Andrea; Griesser, Ulrich J

    2017-09-01

    The sotagliflozin molecule exhibits two fundamentally different molecular conformations in form 1 {systematic name: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(methylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol, C21H25ClO5S, (I)} and the monohydrate [C21H25ClO5S·H2O, (II)]. Both crystals display hydrogen-bonded layers formed by intermolecular interactions which involve the three -OH groups of the xyloside fragment of the molecule. The layer architectures of (I) and (II) contain a non-hydrogen-bonded molecule-molecule interaction along the short crystallographic axis (a axis) whose total PIXEL energy exceeds that of each hydrogen-bonded molecule-molecule pair. The hydrogen-bonded layer of (I) has the topology of the 4-connected sql net and that formed by the water and sotagliflozin molecules of (II) has the topology of a 3,7-connected net.

  8. Efficacy, safety and regulatory status of SGLT2 inhibitors: focus on canagliflozin

    Science.gov (United States)

    Haas, B; Eckstein, N; Pfeifer, V; Mayer, P; Hass, M D S

    2014-01-01

    Prevalence of diabetes mellitus is inc6reasing, with a burden of 382 million patients worldwide at present (more than the entire US population). The International Diabetes Federation anticipates an increase up to 592 million patients by 2035. Another major problem arises from the fact that just 50% of patients with type 2 diabetes mellitus are at target glycaemic control with currently available medications. Therefore, a clear need for new therapies that aim to optimize glycaemic control becomes evident. Renal sodium-linked glucose transporter 2 inhibitors are new antidiabetic drugs with an insulin-independent mechanism of action. They pose one remarkable advantage compared with already established antidiabetics: increasing urinary glucose excretion without inducing hypoglycaemia, thereby promoting body weight reduction due to loss of ~300 kcal per day. This review focuses on canagliflozin, which was the first successful compound of this class to be approved by both the US Food and Drug Administration and the European Medicines Agency in 2013. Clinical trials showed promising results: enhancing glycaemic control was paralleled by reducing body weight and systolic and diastolic blood pressure. Nevertheless, some safety concerns remain, such as genital mycotic infections, urinary tract infections and cardiovascular risks in vulnerable patients, which will be closely monitored in several post-authorization safety studies. PMID:25365416

  9. Peering through the glare: using dual-energy CT to overcome the problem of metal artefacts in bone radiology

    Energy Technology Data Exchange (ETDEWEB)

    Coupal, Tyler M. [McMaster University, Michael G. DeGroote School of Medicine, Hamilton, ON (Canada); Mallinson, Paul I.; McLaughlin, Patrick; Nicolaou, Savvas; Munk, Peter L.; Ouellette, Hugue [Vancouver General Hospital, Radiology Department, Vancouver, BC (Canada)

    2014-05-15

    Imaging of patients with large metal implants remains one of the most difficult endeavours for radiologists. This article reviews the theory of dual-energy CT (DECT) and its ability to reduce metal artefact, thus enhancing the diagnostic value of musculoskeletal imaging. The strengths, weaknesses, and alternative applications of DECT, as well as areas requiring further research, will also be reviewed. Currently, DECT stands as the frontier for metal artefact reduction in musculoskeletal imaging. DECT requires no additional radiation and provides significantly enhanced image acquisition. When considered along with its other capabilities, DECT is a promising new tool for musculoskeletal and trauma radiologists. (orig.)

  10. IMPACT OF CYCLONES OVER KAMCHATKA ON ELECTRON DISTRIBUTION IN THE IONOSPHERE

    Directory of Open Access Journals (Sweden)

    Bogdanov, V.V.

    2016-11-01

    Full Text Available The paper presents the results of investigation of cyclone impact on ionosphere parameters. Ionosphere state was observed by the automatic sounding equipment applying low-orbital navigational spacecrafts in the conditions of low seismicity

  11. Inverse modeling and forecasting for the exploitation of the Pauzhetsky geothermal field, Kamchatka, Russia

    Energy Technology Data Exchange (ETDEWEB)

    Finsterle, Stefan; Kiryukhin, A.V.; Asaulova, N.P.; Finsterle, S.

    2008-04-01

    A three-dimensional numerical model of the Pauzhetsky geothermal field has been developed based on a conceptual hydrogeological model of the system. It extends over a 13.6-km2 area and includes three layers: (1) a base layer with inflow; (2) a geothermal reservoir; and (3) an upper layer with discharge and recharge/infiltration areas. Using the computer program iTOUGH2 (Finsterle, 2004), the model is calibrated to a total of 13,675 calibration points, combining natural-state and 1960-2006 exploitation data. The principal model parameters identified and estimated by inverse modeling include the fracture permeability and fracture porosity of the geothermal reservoir, the initial natural upflow rate, the base-layer porosity, and the permeabilities of the infiltration zones. Heat and mass balances derived from the calibrated model helped identify the sources of the geothermal reserves in the field. With the addition of five makeup wells, simulation forecasts for the 2007-2032 period predict a sustainable average steam production of 29 kg/s, which is sufficient to maintain the generation of 6.8 MWe at the Pauzhetsky power plant.

  12. Microbial Diversity and Biochemical Potential Encoded by Thermal Spring Metagenomes Derived from the Kamchatka Peninsula

    Directory of Open Access Journals (Sweden)

    Bernd Wemheuer

    2013-01-01

    Full Text Available Volcanic regions contain a variety of environments suitable for extremophiles. This study was focused on assessing and exploiting the prokaryotic diversity of two microbial communities derived from different Kamchatkian thermal springs by metagenomic approaches. Samples were taken from a thermoacidophilic spring near the Mutnovsky Volcano and from a thermophilic spring in the Uzon Caldera. Environmental DNA for metagenomic analysis was isolated from collected sediment samples by direct cell lysis. The prokaryotic community composition was examined by analysis of archaeal and bacterial 16S rRNA genes. A total number of 1235 16S rRNA gene sequences were obtained and used for taxonomic classification. Most abundant in the samples were members of Thaumarchaeota, Thermotogae, and Proteobacteria. The Mutnovsky hot spring was dominated by the Terrestrial Hot Spring Group, Kosmotoga, and Acidithiobacillus. The Uzon Caldera was dominated by uncultured members of the Miscellaneous Crenarchaeotic Group and Enterobacteriaceae. The remaining 16S rRNA gene sequences belonged to the Aquificae, Dictyoglomi, Euryarchaeota, Korarchaeota, Thermodesulfobacteria, Firmicutes, and some potential new phyla. In addition, the recovered DNA was used for generation of metagenomic libraries, which were subsequently mined for genes encoding lipolytic and proteolytic enzymes. Three novel genes conferring lipolytic and one gene conferring proteolytic activity were identified.

  13. A novel thermophilic methane-oxidizing bacteria from thermal springs of Uzon volcano caldera, Kamchatka

    Science.gov (United States)

    Dvorianchikova, E.; Kizilova, A.; Kravchenko, I.; Galchenko, V.

    2012-04-01

    Methane is a radiatively active trace gas, contributing significantly to the greenhouse effect. It is 26 times more efficient in absorbing and re-emitting infrared radiation than carbon dioxide. Methanotrophs play an essential role in the global carbon cycle by oxidizing 50-75% of the biologically produced methane in situ, before it reaches the atmosphere. Methane-oxidizing bacteria are isolated from the various ecosystems and described at present. Their biology, processes of methane oxidation in fresh-water, marsh, soil and marine habitats are investigated quite well. Processes of methane oxidation in places with extreme physical and chemical conditions (high or low , salinity and temperature values) are studied in much smaller degree. Such ecosystems occupy a considerable part of the Earth's surface. The existence of aerobic methanotrophs inhabiting extreme environments has been verified so far by cultivation experiments and direct detection of methane monooxygenase genes specific to almost all aerobic methanotrophs. Thermophilic and thermotolerant methanotrophs have been isolated from such extreme environments and consist of the gammaproteobacterial (type I) genera Methylothermus, Methylocaldum, Methylococcus and the verrucomicrobial genus Methylacidiphilum. Uzon volcano caldera is a unique area, where volcanic processes still happen today. Hydrothermal springs of the area are extreme ecosystems which microbial communities represent considerable scientific interest of fundamental and applied character. A thermophilic aerobic methane-oxidising bacterium was isolated from a sediment sample from a hot spring (56.1; 5.3) of Uzon caldera. Strain S21 was isolated using mineral low salt medium. The headspace gas was composed of CH4, Ar, CO2, and O2 (40:40:15:5). The temperature of cultivation was 50, pH 5.5. Cells of strain S21 in exponential and early-stationary phase were coccoid bacilli, about 1 μm in diameter, and motile with a single polar flagellum. PCR and molecular cloning of a pmoA gene fragment have shown that strain S21 was moderately related to the genus Methylothermus; the closest organism is Methylothermus subterraneus. The further studying of strain S21 will expand our knowledge of this group of organisms, important from the ecological point of view.

  14. Overview of the 2012-13 basaltic fissure eruption of Tolbachik, Kamchatka, Russia

    Science.gov (United States)

    Belousov, Alexander; Belousova, Marina; Edwards, Benjamin; Volynetz, Anna; Melnikov, Dmitry; Senyukov, Sergey

    2014-05-01

    On 27 November 2012 a short-lived swarm of shallow (cinder cone. While explosive activity was rather mild, initial discharge of lava was very high (up to 400 m3/s) and by the end of December 'a'a lava flows had travelled up to 17 km from the vent. SiO2 concentrations for the plagioclase-phyric lava were 54 wt.%, but then decreased to 52 wt.%. In January 2013 lava was transported through a system of lava tubes 1 km long and up to 5 m wide. From tube exit points it propagated in the form of channelized lava streams (velocities 1-3 m/s; discharge rates 30-50 m3/s); on lower slopes of the volcano it propagated mostly as 'a'a flows. Lava channels were frequently dammed by floating clinker and accretionary lava balls, which caused flooding of proximal areas by ropy/shelly/slabby pahoehoe lavas. Locally small volumes of lava were extruded through the upper surfaces and lateral levees of 'a'a lava to form very slowly inflating entrail pahoehoe lava lobes. Starting in mid-February the average intensity of the eruption gradually declined, with sporadic bursts in February and April. By May discharge rates of lava had decreased to approximately 15 m3/s and most of lava started to flow as entrail pahoehoe. By the beginning of June the volume of erupted products (dominantly lavas) reached 0.52km3. The effusion of lava continued until the end of August, when the lava lake in the crater of the active cinder cone became inactive. Weak strombolian outbursts from 1-3 small vents on the bottom of the crater continued until September 5, 2013. Total volume of the erupted products reached approximately 0.7 km3, which is ~0.3 km3 less than estimates for the total eruptive volume from the previous eruption at Tolbachik in 1975-76.

  15. ANOMALOUS CHANGES OF THE GEOMAGNETIC FIELD VERTICAL COMPONENT IN KAMCHATKA

    Directory of Open Access Journals (Sweden)

    Smirnov, S.E.

    2016-11-01

    Full Text Available Statistical estimates of the effect in the electric field of the surface layer of the atmosphere parameters, such as time of the beginning, time of a maximum, its intensity and duration, were obtained. It was shown experimentally that the diurnal variation maximum of atmospheric electric field intensity is associated with air temperature height distribution. Power spectra of time variations of electric field intensity in the near ground atmosphere and of the horizontal component of geomagnetic field were under study. It was shown that there are oscillations with the periods of T _ 2, 0–2,5 hours in the power spectra of these parameters during a day. A possible mechanism of generation of these oscillations was proposed. It is associated with vortex motion of convective cells arising during the sunrise in the atmosphere exchange layer.

  16. Geochemistry of volcanic gas at the 2012-13 New Tolbachik eruption, Kamchatka

    Science.gov (United States)

    Chaplygin, I. V.; Lavrushin, V. Y.; Dubinina, E. O.; Bychkova, Y. V.; Inguaggiato, S.; Yudovskaya, M. A.

    2016-09-01

    We report measurements of the chemical and isotopic composition of gas emitted from the lava flow at the 2012-13 New Tolbachik eruption. Gas and condensate samples were taken from two vents over a lava tube in May 2013. The 1030 °C gas sample was collected in evacuated Giggenbach bottle from a periodically pumping-to-venting outlet above active lava flow ~ 300 m from Naboko cone. Concentrations of major components in the 1030 °C gas sample are (mol%): 95.5 H2O, 0.47 CO2, 2.01 SO2, 1.18 HCl, 0.34 HF that are within a range of gas compositions for subduction zone volcanoes. Isotopic analysis of He gives a corrected to atmosphere R/Ra ratio = 7.24 (He/Ne ratio = 1.41) that is close to MORB values. The 1030 °C condensate contained 9.7 ppm Cu, 2.5 ppm Zn, 1.5 ppm Tl, 20 ppb Re and 3 ppb Au, and can be considered as a representative sample for the metal composition of exsolved magmatic gases at the 2012-13 Tolbachik eruption. Isotopic data on the 1030 °C condensate (δ18O = 6.4‰, δD = - 32‰) indicate a magmatic source. Another condensate sample taken at 690 °C was found to be drastically different from the magmatic 1030 °C condensate. We suggest that the disproportional enrichment in trace elements of this 690 °C condensate as compared to the 1030 °C condensate could result from evaporation at forced pumping during sampling and possible dissolution of earlier precipitated sublimates in the gas conduit. Unusual isotopic composition of the 690 °C condensate (δ18O = 18.9‰, δD = - 68.5‰) can be explained by the isotopic exchange between volcanic vapor and atmospheric O2 (δ18O = 23.5‰).

  17. Chemical composition and metal capacity of magmatic gases of Gorelyi volcano, Kamchatka

    Science.gov (United States)

    Chaplygin, I. V.; Taran, Yu. A.; Dubinina, E. O.; Shapar, V. N.; Timofeeva, I. F.

    2015-07-01

    The high-temperature (865°C according to data of an IR-camera) gases and the crater lake water of Gorelyi volcano were sampled in September 2011. The gas and condensate were collected from the active crater in bocca, which was formed in June 2010. The chemical composition and the δ18O and δD values of the condensate and lake water were analyzed. In comparison with the isotopic data on volcanic condensates of the adjacent Mutnovskii volcano, the data points of samples from Gorelyi volcano fall to the mixing line of meteoric and magmatic water. The isotopic characteristics of the water component of the fluid mostly correspond to the high-temperature equilibrium with silicate rocks or melts; the portion of local meteoric water is ~25%. The high metal content of gases of the volcano is determined. The total removal of Cu, Zn, Pb, Mo, Cd, In, Sn, Tl, and Bi by gases of Gorelyi volcano (~30 t/year) comparable to that of the Kudryavyi volcano (20-80 t/year) indicates the high ore-bearing capacity of the volcanic gas fluids.

  18. Recent and emerging therapeutic medications in type 2 diabetes mellitus: incretin-based, Pramlintide, Colesevelam, SGLT2 Inhibitors, Tagatose, Succinobucol.

    Science.gov (United States)

    Lo, Margaret C; Lansang, M Cecilia

    2013-01-01

    Nearly 285 million people worldwide, with 10% being Americans, suffer from diabetes mellitus and its associated comorbidities. This is projected to increase by 6.5% per year, with 439 million inflicted by year 2030. Both morbidity and mortality from diabetes stem from the consequences of microvascular and macrovascular complications. Of the 285 million with diabetes, over a quarter of a million die per year from related complications, making diabetes the fifth leading cause of death in high-income countries. These startling statistics illustrate the therapeutic failure of current diabetes drugs to retard the progression of diabetes. These statistics further illustrate the continual need for further research and development of alternative drugs with novel mechanisms to slow disease progression and disease complications. The treatment algorithm updated in 2008 by American Diabetes Association and the European Association for the Study of Diabetes currently recommends the traditional medications of metformin, either as monotherapy or in combination with sulfonylurea or insulin, as the preferred choice in the tier 1 option. The algorithm only suggests addition of alternative medications such as pioglitazone and incretin-based drugs as second-line agents in the tier 2 "less well-validated" option. However, these traditional medications have not proven to delay the progressive course of diabetes as evidence of increasing need over time for multiple drug therapy to maintain sufficient glycemic control. Because current diabetes medications have limited efficacy and untoward side effects, the development of diabetes mellitus drugs with newer mechanisms of action continues. This article will review the clinical data on the newly available incretin-based drugs on the market, including glucagon-like peptide agonists and of dipeptidyl peptidase type-4 inhibitors. It will also discuss 2 unique medications: pramlintide, which is indicated for both type and type-2 diabetes, and colesevelam, which is approved by the United States Food and Drug Administration for both type-2 diabetes and hyperlipidemia. It will further review the clinical data on the novel emerging agents of sodium-glucose cotransporter-2 inhibitors, tagatose, and succinobucol, all currently in phase III clinical trials. This review article can serve as an aid for clinicians to identify clinical indications in which these new agents can be applied in the treatment algorithm.

  19. Native gold from volcanic gases at Tolbachik 1975-76 and 2012-13 Fissure Eruptions, Kamchatka

    Science.gov (United States)

    Chaplygin, Ilya; Yudovskaya, Marina; Vergasova, Lidiya; Mokhov, Andrey

    2015-12-01

    Aggregates and euhedral crystals of native gold were found in sublimates formed during New Tolbachik Fissure Eruption in 2012-2013 (NTFE). Gold-bearing sublimate samples were taken from a red-hot (690 °C) degassing fracture in the roof of an active lava tunnel 1.5 km from active Naboko cinder cone in May 2013. The gas condensate collected at 690 °C in this site contains 16 ppb Au, 190 ppb Ag and 1180 ppm Cu compared to 3 ppb Au, 39 ppb Ag and 9.7 ppm Cu in the condensate of pristine magmatic gas sampled at 1030 °C. The 690 °C volcanic gas is most likely a mix of magmatic gas and local snow buried under the lava flows as indicated by oxygen and hydrogen isotope compositions of the condensate. The lower-temperature gas enrichment in gold, copper and chlorine is resulted from evaporation of the 690 °C condensate during forced gas pumping at sampling. Native gold was also found in fumarolic encrustations collected from caverns in basalt lava flows with temperature up to 600 °C in June 2014, in a year after eruption finished. The native gold precipitation in newly formed Cu-rich sublimates together with the well known gold occurrences in cinder cones of 1975-1976 Large Tolbachik Fissure Eruption manifest a transport capability of oxidized volcanic gas.

  20. Pyroclastic surges and flows from the 8-10 May 1997 explosive eruption of Bezymianny volcano, Kamchatka, Russia

    Science.gov (United States)

    Belousov, Alexander; Voight, Barry; Belousova, Marina; Petukhin, Anatoly

    2002-07-01

    The 8-10 May 1997 eruption of Bezymianny volcano began with extrusion of a crystallized plug from the vent in the upper part of the dome. Progressive gravitational collapses of the plug caused decompression of highly crystalline magma in the upper conduit, leading at 13:12 local time on 9 May to a powerful, vertical Vulcanian explosion. The dense pyroclastic mixture collapsed in boil-over style to generate a pyroclastic surge which was focused toward the southeast by the steep-walled, 1956 horseshoe-shaped crater. This surge, with a temperature 30 km2 with deposits as much as 30 cm thick and extending 7 km from the vent. The surge deposits comprised massive to vaguely laminated, gravelly sand (Md -1.2 to 3.7φ sorting 1.2 to 3φ) of poorly vesiculated andesite (mean density 1.82 g cm-3 vesicularity 30 vol% SiO2 content 58.0 wt%). The deposits, with a volume of 5-15×106 m3, became finer grained and better sorted with distance; the maximal diameter of juvenile clasts decreased from 46 to 4 cm. The transport and deposition of the surge over a snowy landscape generated extensive lahars which traveled >30 km. Immediately following the surge, semi-vesiculated block-and-ash flows were emplaced as far as 4.7 km from the vent. Over time the juvenile lava in clasts of these flows became progressively less crystallized, apparently more silicic (59.0 to 59.9 wt% SiO2) and more vesiculated (density 1.64 to 1.12 g cm-3 vesicularity 37 to 57 vol%). At this stage the eruption showed transitional behavior, with mass divided between collapsing fountain and buoyant column. The youngest pumice-and-ash flows were accompanied by a sustained sub-Plinian eruption column 14 km high, from which platy fallout clasts were deposited ( 59.7% SiO2; density 1.09 g cm-3 vesicularity 58 vol%). The explosive activity lasted about 37 min and produced a total of 0.026 km3 dense rock equivalent of magma, with an average discharge of 1.2×104 m3 s-1. A lava flow 200 m long terminated the eruption. The evolutionary succession of different eruptive styles during the explosive eruption was caused by vertical gradients in crystallization and volatile content of the conduit magma, which produced significant changes in the properties of the erupting mixture.

  1. Comparative analysis of the lux operons in Aliivibrio logei KCh1 (a Kamchatka Isolate) and Aliivibrio salmonicida.

    Science.gov (United States)

    Manukhov, Ilya V; Khrul'nova, Svetlana A; Baranova, Ancha; Zavilgelsky, Gennadii B

    2011-08-01

    Here we provide a molecular description of a new psychrophilic strain, KCh11, of marine luminescent bacteria classified as Aliivibrio logei. We sequenced the entire lux operon of A. logei KCh1 and showed that it is substantially similar to the lux operon of Aliivibrio salmonicida. It was demonstrated that the reduced production of bioluminescence in A. salmonicida is most likely defined by a specific defect in its luxD gene.

  2. Modeling and observations of geyser activity in relation to catastrophic landslides-mudflows (Kronotsky nature reserve, Kamchatka, Russia)

    Science.gov (United States)

    Kiryukhin, Alexey

    2016-09-01

    This study reports and interprets observational data of geyser cycling in the Valley of Geysers and Uzon hydrothermal systems between 2007 and 2015. The monitoring of the Velikan and Bolshoy Geysers after the catastrophic landslide on 3.06.2007 (which dammed and created Podprudnoe Lake, drowning some geysers) and before a mudflow on 3.01.2014 (which destroyed the dam and almost completely drained Podprudnoe Lake) shows that the interval between eruptions (IBE) of the Bolshoy Geyser decreased from 108 to 63 min and that the IBE of the Velikan Geyser slowly declined over three years from 379 min to 335 min. The seasonal hydrological cycle of the Velikan Geyser shows an increase in the IBE during winter (average of 41 min). The dilution of the chloride deep components of the Bolshoy (- 23%) and Velikan Geysers (- 12%) is also observed. A local TOUGH2 model of the Velikan Geyser is developed. This model is used to describe the transient thermal hydrodynamic and CO2 changes in a Velikan Geyser conduit during the entire cycling process by using cyclic, time-dependent boundary mass flow conditions (major eruption discharge and sub-cyclically assigned CO2 mass flow recharge into the base of the geyser conduit and water recharge at the mid-height of the geyser conduit) and a constant mass flow of water into the geyser at depth. This model also indicates a seepage element at the conduit's top to allow pre-eruptive discharge and a buffering isothermal reservoir below to compensate for pressure declines from major eruptions at earlier times. A local TOUGH2 model is successfully calibrated against temperature observations at both the mid-height and base of the conduit of the Velikan Geyser, which shows the essential role of the above parameters in describing the functionality of the geyser. A reservoir model of shallow production geysers is also developed. This 2D model is used to describe changes in the thermal hydrodynamic state and evolving chloride concentrations in the areas of most prominent discharge, both at steady state and when perturbed by cold water injection from Podprudnoe Lake and other cold water sources (after 3.06.2007). A "well on deliverability" option is used to model the geyser discharge features in the model. The modeled increases in geyser discharge that is caused by an increase in the reservoir pressure from cold water injection reasonably matches observations of IBE decreases in the Bolshoy (~ 58%) and Velikan Geysers (~ 9%). The modeling also shows the possibility of chloride dilution in the Velikan Geyser but no dilution in the Bolshoy Geyser. The latter observation is attributed to the presence of direct cold water inflow into the Bolshoy Geyser conduit.

  3. Complete genome sequence of Desulfurococcus fermentans, a hyperthermophilic cellulolytic crenarchaeon isolated from a freshwater hot spring in Kamchatka, Russia.

    Science.gov (United States)

    Susanti, Dwi; Johnson, Eric F; Rodriguez, Jason R; Anderson, Iain; Perevalova, Anna A; Kyrpides, Nikos; Lucas, Susan; Han, James; Lapidus, Alla; Cheng, Jan-Fang; Goodwin, Lynne; Pitluck, Sam; Mavrommatis, Konstantinos; Peters, Lin; Land, Miriam L; Hauser, Loren; Gopalan, Venkat; Chan, Patricia P; Lowe, Todd M; Atomi, Haruyuki; Bonch-Osmolovskaya, Elizaveta A; Woyke, Tanja; Mukhopadhyay, Biswarup

    2012-10-01

    Desulfurococcus fermentans is the first known cellulolytic archaeon. This hyperthermophilic and strictly anaerobic crenarchaeon produces hydrogen from fermentation of various carbohydrates and peptides without inhibition by accumulating hydrogen. The complete genome sequence reported here suggested that D. fermentans employs membrane-bound hydrogenases and novel glycohydrolases for hydrogen production from cellulose.

  4. Complete Genome Sequence of Desulfurococcus fermentans, a Hyperthermophilic Cellulolytic Crenarchaeon Isolated from a Freshwater Hot Spring in Kamchatka, Russia

    Energy Technology Data Exchange (ETDEWEB)

    Susanti, Dwi [Virginia Polytechnic Institute and State University (Virginia Tech); Johnson, Eric F [Virginia Polytechnic Institute and State University (Virginia Tech); Rodriquez, Jason [Virginia Polytechnic Institute and State University (Virginia Tech); Anderson, Iain [U.S. Department of Energy, Joint Genome Institute; Perevalova, Anna [Virginia Polytechnic Institute and State University (Virginia Tech); Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Han, James [U.S. Department of Energy, Joint Genome Institute; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Peters, Lin [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Gopapan, Venkay [Ohio State University; Chan, Patricia [University of California, Santa Cruz; Atomi, Haruyuki [Kyoto University, Japan; Bonch-Osmolovskaya, Elizaveta [Russian Academy of Sciences, Moscow; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Mukhopadhyay, Biswarup [Virginia Polytechnic Institute and State University (Virginia Tech)

    2012-01-01

    Desulfurococcus fermentans is the first known cellulolytic archaeon. This hyperthermophilic and strictly anaerobic crenarchaeon produces hydrogen from fermentation of various carbohydrates and peptides without inhibition by accumulating hydrogen. The complete genome sequence reported here suggested that D. fermentans employs membrane-bound hydrogenases and novel glycohydrolases for hydrogen production from cellulose.

  5. Research of Dealing Method to Glare in SS7 System%SS7系统中继同抢处理新方法的研究

    Institute of Scientific and Technical Information of China (English)

    孙素霞

    2007-01-01

    介绍了中继同抢现象的两种新的处理方法,一种是增加等本端业务层IAM消息的定时器,如果定时内没有收到业务侧的IAM消息则把发生同抢的中继作入中继使用.另一种是不论是否发生在主控中继上本端都要做同抢处理,处理方法是把对端来的呼叫直接接续,本端进行重复试呼.这种方法实现比较简单,同样可以达到解决中继同抢的目的.

  6. The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Wit, H.M. de; Groen, M.; Rovers, M.M.; Tack, C.J.J.

    2016-01-01

    AIMS: The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP-1

  7. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Belhage, Bo; Zeuthen, Emil

    2005-01-01

    and osmosis at the membrane with diffusion in the cytoplasm. The combination of high resolution measurements and precise modelling showed that water transport across the membrane can be explained by cotransport of water in the membrane proteins and that intracellular unstirred layers effects are minute....

  8. Glucose Stimulates GLP-1 Secretion from Isolated Perfused Rat Small Intestine by SGLT1 and GLUT2 Mediated Uptake, Causing V-gated Calcium Channel Activation

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Frost, Charlotte Rasmussen; Svendsen, Berit

    2014-01-01

    substrate, α-MGP, stimulated release (15.7 ± 0.5 vs. 29.4 ± 0.7 pM, P presence of the SGTL1 inhibitor phloridzin (10 μM) (P > 0.05). However, glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2...

  9. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2 leading to cell depolarization and calcium influx

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Hartmann, Bolette

    2015-01-01

    , but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways...

  10. Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy-an emerging problem and solutions offered by diabetes technology

    DEFF Research Database (Denmark)

    Pfützner, A; Klonoff, D; Heinemann, Lars

    2017-01-01

    and without any indicative hyperglycemia. In consequence, patients on sodium-glucose cotransporter2 inhibitors are recommended to perform regular blood ketone tests since they are not alerted to incipient diabetic ketoacidosis by glucose testing alone. This option is offered by several blood glucose meters...... that can also measure ketones with a separate ketone strip or in one case by an automatic parallel ketone assessment from the same strip. The need for extra testing and the associated costs may be a barrier to patient acceptance of this risk mitigation procedure. However, patients who are at risk...

  11. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats.

    Science.gov (United States)

    Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Jaiwongkam, Thidarat; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-10-15

    Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks. At week 13, the HFD-fed rats were divided into four subgroups (n=8/subgroup) to receive either a vehicle, vildagliptin (3mg/kg/day) dapagliflozin (1mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The transport mechanism of the human sodium/myo-inositol transporter 2 (SMIT2/SGLT6), a member of the LeuT structural family.

    Science.gov (United States)

    Sasseville, Louis J; Longpré, Jean-Philippe; Wallendorff, Bernadette; Lapointe, Jean-Yves

    2014-09-01

    The sodium/myo-inositol transporter 2 (SMIT2) is a member of the SLC5A gene family, which is believed to share the five-transmembrane segment inverted repeat of the LeuT structural family. The two-electrode voltage-clamp (TEVC) technique was used to measure the steady-state and the pre-steady-state currents mediated by human SMIT2 after expression in Xenopus laevis oocytes. Phlorizin is first shown to be a poor inhibitor of pre-steady-state currents for depolarizing voltage pulse. From an up to threefold difference between the apparent ON and OFF transferred charges during a voltage pulse, we also show that a fraction of the transient current recorded for very negative potentials is not a true pre-steady-state current coming from the cotransporter conformational changes. We suggest that this transient current comes from a time-dependent leak current that can reach large amplitudes when external Na(+) concentration is reduced. A kinetic model was generated through a simulated annealing algorithm. This algorithm was used to identify the optimal connectivity among 19 different kinetic models and obtain the numerical values of the associated parameters. The proposed 5-state model includes cooperative binding of Na(+) ions, strong apparent asymmetry of the energy barriers, a rate-limiting step that is likely associated with the translocation of the empty transporter, and a turnover rate of 21 s(-1). The proposed model is a proof of concept for a novel approach to kinetic modeling of electrogenic transporters and allows insight into the transport mechanism of members of the LeuT structural family at the millisecond timescale.

  13. Alternative Agents in Type 1 Diabetes in Addition to Insulin Therapy: Metformin, Alpha-Glucosidase Inhibitors, Pioglitazone, GLP-1 Agonists, DPP-IV Inhibitors, and SGLT-2 Inhibitors.

    Science.gov (United States)

    DeGeeter, Michelle; Williamson, Bobbie

    2016-04-01

    Insulin is the mainstay of current treatment for patients with type 1 diabetes mellitus (T1DM). Due to increasing insulin resistance, insulin doses are often continually increased, which may result in weight gain for patients. Medications currently approved for the treatment of type 2 diabetes offer varying mechanisms of action that can help to reduce insulin resistance and prevent or deter weight gain. A MEDLINE search was conducted to review literature evaluating the use of metformin, alpha-glucosidase inhibitors, pioglitazone, glucagon-like peptide 1 agonists, dipeptidyl peptidase, and sodium-dependent glucose transporter 2 inhibitors, in patients with T1DM. Varying results were found with some benefits including reductions in hemoglobin A1c, decreased insulin doses, and favorable effects on weight. Of significance, a common fear of utilizing multiple therapies for diabetes treatment is the risk of hypoglycemia, and this review displayed limited evidence of hypoglycemia with multiple agents.

  14. Regulation of SGLT expression and localization through Epac/PKA-dependent caveolin-1 and F-actin activation in renal proximal tubule cells.

    Science.gov (United States)

    Lee, Yu Jin; Kim, Mi Ok; Ryu, Jung Min; Han, Ho Jae

    2012-04-01

    This study demonstrated that exchange proteins directly activated by cAMP (Epac) and protein kinase A (PKA) by 8-bromo (8-Br)-adenosine 3',5'-cyclic monophosphate (cAMP) stimulated [(14)C]-α-methyl-D-glucopyranoside (α-MG) uptake through increased sodium-glucose cotransporters (SGLTs) expression and translocation to lipid rafts in renal proximal tubule cells (PTCs). In PTCs, SGLTs were colocalized with lipid raft caveolin-1 (cav-1), disrupted by methyl-β-cyclodextrin (MβCD). Selective activators of Epac or PKA, 8-Br-cAMP, and forskolin stimulated expressions of SGLTs and α-MG uptake in PTCs. In addition, 8-Br-cAMP-induced PKA and Epac activation increased phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB), which were involved in expressions of SGLTs. Furthermore, 8-Br-cAMP stimulated SGLTs translocation to lipid rafts via filamentous actin (F-actin) organization, which was blocked by cytochalasin D. In addition, cav-1 and SGLTs stimulated by 8-Br-cAMP were detected in lipid rafts, which were blocked by cytochalasin D. Furthermore, 8-Br-cAMP-induced SGLTs translocation and α-MG uptake were attenuated by inhibition of cav-1 activation with cav-1 small interfering RNA (siRNA) and inhibition of F-actin organization with TRIO and F-actin binding protein (TRIOBP). In conclusion, 8-Br-cAMP stimulated α-MG uptake via Epac and PKA-dependent SGLTs expression and trafficking through cav-1 and F-actin in PTCs.

  15. Targeting the kidney and glucose excretion with dapagliflozin: preclinical and clinical evidence for SGLT2 inhibition as a new option for treatment of type 2 diabetes mellitus

    OpenAIRE

    Whaley JM; Tirmenstein M; Reilly TP; Poucher SM; Saye J; Parikh S.; List JF

    2012-01-01

    Jean M Whaley,1 Mark Tirmenstein,2 Timothy P Reilly,2 Simon M Poucher,3 JoAnne Saye,4 Shamik Parikh,5 James F List61Bristol-Myers Squibb, Metabolic Disease Discovery Biology, Research and Development, Princeton, NJ, USA; 2Bristol-Myers Squibb, Drug Safety Evaluation, Research and Development, New Brunswick and Princeton, NJ, USA; 3AstraZeneca, Cardiovascular and Gastrointestinal Innovative Medicines Science Unit, Alderley Park, Macclesfield, Cheshire, UK; 4AstraZeneca, Global Safety Assessmen...

  16. Variations in electric and meteorological parameters in the near-Earth's atmosphere at Kamchatka during the solar events in October 2003

    Science.gov (United States)

    Smirnov, S. E.; Mikhailova, G. A.; Kapustina, O. V.

    2014-03-01

    The diurnal variations in the electric conductivity, electric-field strength, and meteorological parameters in the near-Earth's atmosphere during the solar events in October 21-31, 2003, have been studied. It has been indicated that the conductivity and electric-field strength strongly depend on the air temperature and humidity. It has been found that the conductivity increased for 2 days before the geomagnetic storm on October 29-30 as a result of the effect of solar cosmic rays and decreased during a Forbush decrease in galactic cosmic rays, which was accompanied by a corresponding increase in the electric-field strength. It has been found that the air temperature and humidity anomalously increased in the process of solar activity, which resulted in the formation of different clouds, including thunderclouds accompanied by thunderstorm processes and showers. Simultaneous disturbances of the regular meteorological processes, solar flare series, and emission intensification in the near ultraviolet band, and visible and infrared spectral regions make it possible to consider these processes as a source of additional energy inflow into the lower atmosphere.

  17. Atmospheric anomalies and anomalies of electricity in the near-surface atmosphere before the Kamchatka earthquake of January 30, 2016, based on the data from the Paratunka Observatory

    Science.gov (United States)

    Bychkov, V. V.; Korsunova, L. P.; Smirnov, S. E.; Hegai, V. V.

    2017-07-01

    The 15-min data of vertical ionosphere sounding and 10-min data from measurements of the vertical component ( Ez) of the near-surface quasistatic atmospheric electrical field and the respective values of electrical conductance of near-surface air at the Paratunka complex geophysical observatory in the period from January 28 to January 30, 2016 have been analyzed to reveal the possible anomalies preceding the M = 7.2 earthquake that occurred on January 30, 2016, at 0325 UT. The distance between the observatory and epicenter was 117 km. These anomalies have been revealed, and the majority of them, in our opinion, may be related to the processes of earthquake preparation.

  18. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus : Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications

    NARCIS (Netherlands)

    Heerspink, Hiddo J. L.; Perkins, Bruce A.; Fitchett, David H.; Husain, Mansoor; Cherney, David Z. I.

    2016-01-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and

  19. The effect of combined treatment with canagliflozin and teneligliptin on glucose intolerance in Zucker diabetic fatty rats

    National Research Council Canada - National Science Library

    Oguma, Takahiro; Kuriyama, Chiaki; Nakayama, Keiko; Matsushita, Yasuaki; Yoshida, Kumiko; Kiuchi, Satoko; Ikenaga, Yuka; Nakamaru, Yoshinobu; Hikida, Kumiko; Saito, Akira; Arakawa, Kenji; Oka, Kozo; Ueta, Kiichiro; Shiotani, Masaharu

    2015-01-01

    ... inhibitor, on glucose intolerance was investigated in Zucker diabetic fatty (ZDF) rats. Canagliflozin potently inhibited human and rat SGLT2 and moderately inhibited human and rat SGLT1 activities but did not affect DPP4 activity...

  20. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus : Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications

    NARCIS (Netherlands)

    Heerspink, Hiddo J. L.; Perkins, Bruce A.; Fitchett, David H.; Husain, Mansoor; Cherney, David Z. I.

    2016-01-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and na

  1. The effect of combined treatment with canagliflozin and teneligliptin on glucose intolerance in Zucker diabetic fatty rats

    OpenAIRE

    Takahiro Oguma; Chiaki Kuriyama; Keiko Nakayama; Yasuaki Matsushita; Kumiko Yoshida; Satoko Kiuchi; Yuka Ikenaga; Yoshinobu Nakamaru; Kumiko Hikida; Akira Saito; Kenji Arakawa; Kozo Oka; Kiichiro Ueta; Masaharu Shiotani

    2015-01-01

    To assess the impact of concomitant inhibition of sodium-glucose cotransporter (SGLT) 2 and dipeptidyl peptidase IV (DPP4) for the treatment of type 2 diabetes mellitus (T2DM), the effect of combined treatment with canagliflozin, a novel SGLT2 inhibitor, and teneligliptin, a DPP4 inhibitor, on glucose intolerance was investigated in Zucker diabetic fatty (ZDF) rats. Canagliflozin potently inhibited human and rat SGLT2 and moderately inhibited human and rat SGLT1 activities but did not affect ...

  2. Diabetic Ketoacidosis in a Patient with Type 2 Diabetes After Initiation of Sodium-Glucose Cotransporter 2 Inhibitor Treatment

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Bagger, Jonatan I; Knop, Filip K

    2016-01-01

    Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were recently introduced for the treatment of type 2 diabetes (T2D). SGLT2i lower plasma glucose by inhibiting the renal reuptake of glucose leading to glucosuria. Generally, these drugs are considered safe to use. However, recently, SGLT2i have...

  3. EFFECT OF OVERLOAD ON CRACK GROWTH IN FIBER REINFORCED METAL LAMINATES

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    This paper is concerned with fatigue behavior of glass fiber reinforced aluminium laminates (GLARE) under overload fatigue loading. The effect of single overload on the crack growth rates in GLARE was investigated, and the mechanism of the retardation of crack growth determined. Crack growth retardation by overload was observed in GLARE, but much smaller than monolithic metals. The retardation of crack growth in GLARE is only controlled by the effective stress intensity factor experienced by the constituent metals at crack tips.

  4. 钠-葡萄糖协同转运蛋白与糖尿病%Sodium-glucose cotransporters and diabetes

    Institute of Scientific and Technical Information of China (English)

    朱蕾; 杨怡

    2011-01-01

    Sodium-glucose cotransporters (SGLTs) are carrier proteins which can help glucose to enter eukaryotic cells.Among them,the SGLT1 and SGLT2 are the most important ones and play major roles in dietary glucose absorption and renal glucose reabsorption respectively.In the state of diabetes,increased expression of SGLT1 in the intestine will enhance the glucose absorption and therefore accelerate hyperglycemia.Through decreasing salivary secretion,increased expression of SGLT1 in salivary glands will promote the development of diabetic oral complications.Meanwhile the expression of SGLT1 and SGLT2 in kidney are also increased which will enhance the glucose reabsorption and therefore accelerate hyperglycemia and deteriorate dial.tic nephropathy.At present,selective inhibitor of SGLT2 is becoming a new drug for diabetes.%钠-葡萄糖协同转运蛋白(SGLTs)在葡萄糖的跨细胞转运中发挥重要作用,其中SGLT1负责膳食葡萄糖的吸收,SGLT2负责肾脏中葡萄糖的重吸收.在糖尿病状态下,肠道SGLT1表达的增加将促进葡萄糖的吸收,从而加重了高血糖,而涎腺导管SGLT1表达的增加则使唾液分泌减少,促进了口腔并发症的发生;肾脏SGLT2和SGLT1表达的增加使葡萄糖的重吸收增加,加重了高血糖,并促进了糖尿病肾病的进展.目前,选择性SLGT2抑制剂已经成为新型的抗糖尿病药物.

  5. Effects of isoleucine on glucose uptake through the enhancement of muscular membrane concentrations of GLUT1 and GLUT4 and intestinal membrane concentrations of Na+/glucose co-transporter 1 (SGLT-1) and GLUT2.

    Science.gov (United States)

    Zhang, Shihai; Yang, Qing; Ren, Man; Qiao, Shiyan; He, Pingli; Li, Defa; Zeng, Xiangfang

    2016-08-01

    Knowledge of regulation of glucose transport contributes to our understanding of whole-body glucose homoeostasis and human metabolic diseases. Isoleucine has been reported to participate in regulation of glucose levels in many studies; therefore, this study was designed to examine the effect of isoleucine on intestinal and muscular GLUT expressions. In an animal experiment, muscular GLUT and intestinal GLUT were determined in weaning pigs fed control or isoleucine-supplemented diets. Supplementation of isoleucine in the diet significantly increased piglet average daily gain, enhanced GLUT1 expression in red muscle and GLUT4 expression in red muscle, white muscle and intermediate muscle (P<0·05). In additional, expressions of Na+/glucose co-transporter 1 and GLUT2 were up-regulated in the small intestine when pigs were fed isoleucine-supplemented diets (P<0·05). C2C12 cells were used to examine the expressions of muscular GLUT and glucose uptake in vitro. In C2C12 cells supplemented with isoleucine in the medium, cellular 2-deoxyglucose uptake was increased (P<0·05) through enhancement of the expressions of GLUT4 and GLUT1 (P<0·05). The effect of isoleucine was greater than that of leucine on glucose uptake (P<0·05). Compared with newborn piglets, 35-d-old piglets have comparatively higher GLUT4, GLUT2 and GLUT5 expressions. The results of this study demonstrated that isoleucine supplementation enhanced the intestinal and muscular GLUT expressions, which have important implications that suggest that isoleucine could potentially increase muscle growth and intestinal development by enhancing local glucose uptake in animals and human beings.

  6. Ipragliflozin: A novel sodium-glucose cotransporter 2inhibitor developed in Japan

    Institute of Scientific and Technical Information of China (English)

    Tsuyoshi Ohkura

    2015-01-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitioninduces glucosuria and decreases blood glucose levelsin diabetic patients and lowers hypoglycemic risk.SGLT1 is expressed in the kidney and intestine; SGLT1inhibition causes abdominal symptoms such as diarrheaand reduces incretin secretion. Therefore, SGLT2selectivity is important. Ipragliflozin is highly selectivefor SGLT2. In type 2 diabetes mellitus (T2DM), urinaryglucose excretion increased to 90 g/24 h after 28 d oftreatment with ipragliflozin 300 mg/d. Twelve weeksof ipragliflozin 50 mg/d vs placebo reduced glycatedhemoglobin and body weight by 0.65% and 0.66kg, respectively, in Western T2DM patients, and by1.3% and 1.89 kg, respectively, in Japanese patients.Ipragliflozin (highly selective SGLT2 inhibitor) improvesglycemic control and reduces body weight andlowers hypoglycemic risk and abdominal symptoms.Ipragliflozin can be a novel anti-diabetic and antiobesityagent.

  7. In vitro characterization of luseogliflozin, a potent and competitive sodium glucose co-transporter 2 inhibitor: Inhibition kinetics and binding studies.

    Science.gov (United States)

    Uchida, Saeko; Mitani, Akiko; Gunji, Emi; Takahashi, Teisuke; Yamamoto, Koji

    2015-05-01

    In this study, we evaluated an inhibition model of luseogliflozin on sodium glucose co-transporter 2 (SGLT2). We also analyzed the binding kinetics of the drug to SGLT2 protein using [(3)H]-luseogliflozin. Luseogliflozin competitively inhibited human SGLT2 (hSGLT2)-mediated glucose uptake with a Ki value of 1.10 nM. In the absence of glucose, [(3)H]-luseogliflozin exhibited a high affinity for hSGLT2 with a Kd value of 1.3 nM. The dissociation half-time was 7 h, suggesting that luseogliflozin dissociates rather slowly from hSGLT2. These profiles of luseogliflozin might contribute to the long duration of action of this drug.

  8. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    OpenAIRE

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or c...

  9. Sodium-glucose cotransport

    Science.gov (United States)

    Poulsen, Søren Brandt; Fenton, Robert A.; Rieg, Timo

    2017-01-01

    Purpose of review Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs. Recent findings Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways. Summary SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2. PMID:26125647

  10. 钠葡萄糖协同转运子2抑制剂:糖尿病治疗的新选择%Sodium glucose co-transporter 2 inhibitors: A novel option for the treatment of diabetes

    Institute of Scientific and Technical Information of China (English)

    袁璐; 李倩; 高谷; 马建华

    2010-01-01

    钠葡萄糖协同转运子2(SGLT2)是几乎仅在近曲小管表达的跨膜蛋白,介导了90%滤过葡萄糖的重吸收,SGLT2抑制剂可特异性抑制肾小管对滤过葡萄糖的重吸收,增加尿糖排泄,发挥降糖作用.SGLT2抑制剂还具有促进体重下降,间接改善肥胖的作用.根皮苷作为人类最早发现的SGLT2抑制剂,研究较为局限,随着T-1095、serglilozin、dapagliflozin等新型SGLT2抑制剂的开发,SCLT2抑制剂在治疗糖尿病上的有效性和安全性得到了进一步论证,为糖尿病治疗提供了新选择.%The sodium glucose co-transporter 2 ( SGLT2 ) located in the plasma membrane of cells lining the proximal tubule mediates 90 percent of renal glucose reabsorption from the tubular fluid. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, which can lower the elevated blood glucose levels in patients with diabetes. The SGLT2 inhibitors also play roles in weight loss,which can improve the obesity. As the earliest SGLT2 inhibitor,the research of phlorizin are limited. With the development of novel SGLT2 inhibitors,such as T-1095, serglilozin and dapagliflozin, the efficacy and safety of SGLT2 inhibitors in the terms of treating diabetes has been further confirmed,so the SGLT2 inhibitors provide new approaches to the treatment of diabetes mellitus.

  11. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    OpenAIRE

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or c...

  12. Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models

    OpenAIRE

    Yin Liang; Kenji Arakawa; Kiichiro Ueta; Yasuaki Matsushita; Chiaki Kuriyama; Tonya Martin; Fuyong Du; Yi Liu; June Xu; Bruce Conway; Jamie Conway; David Polidori; Kirk Ways; Keith Demarest

    2012-01-01

    BACKGROUND: Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). METHODS: (14)C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; (3)H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose e...

  13. The German-Russian deep-sea expedition KuramBio (Kurile Kamchatka biodiversity studies) on board of the RV Sonne in 2012 following the footsteps of the legendary expeditions with RV Vityaz

    Science.gov (United States)

    Brandt, Angelika; Malyutina, Marina V.

    2015-01-01

    The deep sea is the largest but least explored environment on Earth. The oceans occupy 71% of Earth's surface and 90% of this area is deep sea (Raupach et al., 2009; Ramirez-Llodra et al., 2010). Thus its inhabiting fauna represents the most typical life forms on the planet (Gage and Tyler, 1991). Recent investigations discovered a high biodiversity in the deep sea, preliminary estimates are ranging between 0.5 and 10 million species for the macrofauna (Brandt et al., 2004, 2007a, 2007b, 2007c; Grassle and Machiolek, 1992; Sanders and Hessler, 1969); estimates go as high as 20-30 million for the meiofauna (Adrianov, 2004). Global biodiversity has been estimated to hold 8.7 million species of which 2.2 million are marine (Mora et al., 2011). These authors extrapolate that 91% of species in the ocean still await description. Therefore, major aims of recent deep-sea investigations are still describe and explain patterns of benthic biodiversity in different deep-sea areas (Brandt et al., 2004; Sanders and Hessler, 1969). For example, for all waters surrounding Japan a total of 33,629 species have been reported (Fujikura et al., 2010). The CeDAMar expeditions in the framework of the Census of Marine Life documented that deep-sea biodiversity is very unevenly distributed in the different oceans and ocean basins (e.g. Ramirez-Llodra et al., 2010). Some mechanisms, however, were already identified that cause high local species concentrations (productivity and isolation) (e.g. Brandt et al., 2007b; Levin et al., 2001; Snelgrove and Smith, 2002).

  14. Ginsenosides, ingredients of the root of Panax ginseng, are not substrates but inhibitors of sodium-glucose transporter 1.

    Science.gov (United States)

    Gao, Shengli; Kushida, Hirotaka; Makino, Toshiaki

    2017-01-01

    Recent pharmacokinetic studies have revealed that ginsenosides, the major ingredients of ginseng (the roots of Panax ginseng), are present in the plasma collected from subjects receiving ginseng, and speculated that ginsenosides might be actively transported via glucose transporters. We evaluated whether ginsenosides Rb1 and Rg1, and their metabolites from enteric bacteria act as substrates of sodium-glucose cotransporter (SGLT) 1, the major glucose transporter expressed on the apical side of intestinal epithelial cells. First, we evaluated the competing effects of ginseng extract and ginsenosides on the uptake of [(14)C]methyl-glucose, a substrate of SGLT1, by SGLT1-overexpressing HEK293 cells. A boiling water extract of ginseng inhibited SGLT1 in a concentration-dependent manner with an IC50 value of 0.85 mg/ml. By activity-guided fractionation, we determined that the fraction containing ginsenosides displayed an inhibitory effect on SGLT1. Of the ginsenosides evaluated, protopanaxatriol-type ginsenosides were not found to inhibit SGLT1, whereas protopanaxadiol-type ginsenosides, including ginsenosides Rd, Rg3, Rh2, F2 and compound K, exhibited significant inhibitory effects on SGLT1, with ginsenoside F2 having the highest activity with an IC50 value of 23.0 µM. Next, we measured the uptake of ginsenoside F2 and compound K into Caco-2 cells, a cell line frequently used to evaluate the intestinal absorption of drugs. The uptake of ginsenoside F2 and compound K into Caco-2 cells was not competitively inhibited by glucose. Furthermore, the uptake of ginsenoside F2 and compound K into SGLT1-overexpressing HEK293 cells was not significantly higher than into mock cells. Ginsenoside F2 and compound K did not appear to be substrates of SGLT1, although these compounds could inhibit SGLT1. Ginsenosides might be absorbed by passive diffusion through the intestinal membrane or actively transported via unknown transporters other than SGLT1.

  15. 2型糖尿病治疗靶点钠-葡萄糖共转运蛋白2抑制剂研究进展%Research progress of sodium-glucose co-transporter 2 inhibitors for treatment of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    万惠新; 沈竞康

    2012-01-01

    Sodium-glucose co-transporters are a family of glucose transporter found in the intestinal mucosa of the small intestine (SGLT-2) and the proximal tubule of the nephron (SGLT-1 and SGLT-2). They contribute to renal glucose reabsorption and most of renal glucose (about 90%) is reabsorbed by SGLT-2 located in the proximal renal tubule. Selectively inhibiting activity of SGLT-2 is an innovative therapeutic strategy for treatment of type 2 diabetes by enhancing urinary glucose excretion from the body. Therefore SGLT-2 inhibitors are considered to be potential antidiabetic drugs with an unique mechanism. This review will highlight some recent advances and structure-activity relationships in the discovery and development of SGLT-2 inhibitors including O-glycoside, C-glycoside, C, 0-spiro glycoside and non glycosides.%钠—葡萄糖共转运蛋白2 (sodium-glucose co-transporter2,SGLT-2)分布在肾脏近曲小管S1部位,负责肾脏中约90%葡萄糖的重吸收,抑制SGLT-2可以促进糖尿病患者尿糖的排出,因此SGLT-2抑制剂被认为是一种新型的具有独特作用机制的抗糖尿病药物.本文按照化合物的结构特征分类,重点介绍O-芳基糖苷类、C-芳基糖苷类、O,C-螺环芳基糖苷类、N-芳基糖苷类以及非糖苷类SGLT-2抑制剂的构效关系以及最新研究进展.

  16. Histomorphology and small intestinal sodium-dependent glucose transporter 1 gene expression in piglets fed phytic acid and phytase-supplemented diets.

    Science.gov (United States)

    Woyengo, T A; Rodriguez-Lecompte, J C; Adeola, O; Nyachoti, C M

    2011-08-01

    An experiment was conducted to determine the effect of dietary phytic acid (PA) and phytase supplementation on small intestinal histomorphology and Na-dependent glucose transporter 1 (SGLT1) gene expression in piglets. Twenty-four piglets with an average initial BW of 7.60 ± 0.73 kg were randomly assigned to 3 experimental diets, to give 8 piglets per diet. The diets were a casein-cornstarch-based diet that was supplemented with 0 or 2% PA, or 2% PA (as Na phytate) plus an Escherichia coli-derived phytase at 500 phytase units/kg. The basal diet was formulated to meet the 1998 NRC energy, digestible AA, mineral, and vitamin requirements for piglets. After 10 d of feeding, the piglets were killed to determine small intestinal histomorphology and small intestinal SGLT1 gene expression. Phytic acid supplementation did not affect (P > 0.1) villus height (VH) and the VH-to-crypt depth (CD) ratio, but did decrease (P 0.1) VH, CD, and the VH-to-CD ratio. Phytic acid supplementation reduced SGLT1 gene expression in the duodenum, jejunum, and ileum by 1.1-, 5.4-, and 2.4-fold, respectively. Phytase supplementation increased SGLT1 gene expression in the jejunum by 2.6-fold, but reduced SGLT1 gene expression in the duodenum and ileum by 2.0- and 4.0-fold, respectively. In conclusion, PA reduced CD in the jejunum and SGLT1 gene expression in the duodenum, jejunum, and ileum, whereas phytase supplementation increased the expression of SGLT1 in the jejunum. The reduced SGLT1 gene expression by PA implies that PA reduces nutrient utilization in pigs partly through reduced expression of SGLT1, which is involved in glucose and Na absorption. The increased expression of SGLT1 in the jejunum by phytase supplementation implies that phytase alleviated the negative effects of PA partly through increased expression of SGLT1.

  17. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes

    NARCIS (Netherlands)

    Heerspink, H. J. Lambers; de Zeeuw, D.; Wie, L.; Leslie, B.; List, J.

    2013-01-01

    Aims: Sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-l

  18. Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs

    DEFF Research Database (Denmark)

    Kosiborod, Mikhail; Cavender, Matthew A; Fu, Alex Z

    2017-01-01

    for Germany. RESULTS: After propensity matching, there were 309 056 patients newly initiated on either SGLT-2i or other glucose-lowering drugs (154 528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42%, and 5% of the total exposure time in the SGLT-2i...

  19. Efficacy and Safety of Canagliflozin in Patients with Type 2 Diabetes and Stage 3 Nephropathy

    NARCIS (Netherlands)

    Yamout, Hala; Perkovic, Vlado; Davies, Melanie; Woo, Vincent; de Zeeuw, Dick; Mayer, Cristiana; Vijapurkar, Ujjwala; Kline, Irina; Usiskin, Keith; Meininger, Gary; Bakris, George

    2014-01-01

    Background/Aims: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of >= 45 ml/mm/1.73 m(2). The efficacy and safety of canagliflozin, an approved SGLT(2)

  20. Efficacy and Safety of Canagliflozin in Patients with Type 2 Diabetes and Stage 3 Nephropathy

    NARCIS (Netherlands)

    Yamout, Hala; Perkovic, Vlado; Davies, Melanie; Woo, Vincent; de Zeeuw, Dick; Mayer, Cristiana; Vijapurkar, Ujjwala; Kline, Irina; Usiskin, Keith; Meininger, Gary; Bakris, George

    2014-01-01

    Background/Aims: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of >= 45 ml/mm/1.73 m(2). The efficacy and safety of canagliflozin, an approved SGLT(2) inhibit

  1. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes

    NARCIS (Netherlands)

    Heerspink, H. J. Lambers; de Zeeuw, D.; Wie, L.; Leslie, B.; List, J.

    2013-01-01

    Aims: Sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-l

  2. Nanostructured Super-Black Optical Materials Project

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA faces difficulties in imaging and characterizing faint astrophysical objects within the glare of brighter stellar sources. Achieving a very low background...

  3. Physiologically based pharmacokinetic-pharmacodynamic modeling to predict concentrations and actions of sodium-dependent glucose transporter 2 inhibitor canagliflozin in human intestines and renal tubules.

    Science.gov (United States)

    Mori, Kazumi; Saito, Ryuta; Nakamaru, Yoshinobu; Shimizu, Makiko; Yamazaki, Hiroshi

    2016-11-01

    Canagliflozin is a recently developed sodium-glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic-pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized. Therefore, a physiologically based pharmacokinetic (PBPK) model of canagliflozin was developed based on clinical data from healthy volunteers and it was used to simulate luminal concentrations in intestines and renal tubules. In small intestine simulations, the inhibition ratios for SGLT1 were predicted to be 40%-60% after the oral administration of clinical doses (100-300 mg/day). In contrast, inhibition ratios of canagliflozin for renal SGLT2 and SGLT1 were predicted to be approximately 100% and 0.2%-0.4%, respectively. These analyses suggest that canagliflozin only inhibits SGLT2 in the kidney. Using the simulated proximal tubule luminal concentrations of canagliflozin, the urinary glucose excretion rates in canagliflozin-treated diabetic patients were accurately predicted using the renal glucose reabsorption model as a PD model. Because the simulation of canagliflozin pharmacokinetics was successful, this PBPK methodology was further validated by successfully simulating the pharmacokinetics of dapagliflozin, another SGLT2 inhibitor. The present results suggest the utility of this PBPK/PD model for predicting canagliflozin concentrations at target sites and help to elucidate the pharmacological effects of SGLT1/2 inhibition in humans. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal Tubule.

    Science.gov (United States)

    Ghezzi, Chiara; Yu, Amy S; Hirayama, Bruce A; Kepe, Vladimir; Liu, Jie; Scafoglio, Claudio; Powell, David R; Huang, Sung-Cheng; Satyamurthy, Nagichettiar; Barrio, Jorge R; Wright, Ernest M

    2017-03-01

    Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[(18)F]fluoro-dapagliflozin (F-Dapa). We detected prominent binding of intravenously injected F-Dapa in the kidney cortexes of rats and wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding. Furthermore, imaging revealed only low levels of F-Dapa in the urinary bladder, even after displacement of kidney binding with dapagliflozin. Microscopic ex vitro autoradiography of kidney showed F-Dapa binding to the apical surface of early proximal tubules. Notably, in vivo imaging did not show measureable specific binding of F-Dapa in heart, muscle, salivary glands, liver, or brain. We propose that F-Dapa is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubule, and is subsequently reabsorbed into blood. The high density of functional SGLT2 transporters detected in the apical membrane of the proximal tubule but not detected in other organs likely accounts for the high kidney specificity of SGLT2 inhibitors. Overall, these data are consistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of action of these drugs. Copyright © 2017 by the American Society of Nephrology.

  5. Intestinal Sodium Glucose Cotransporter 1 Inhibition Enhances Glucagon-Like Peptide-1 Secretion in Normal and Diabetic Rodents.

    Science.gov (United States)

    Oguma, Takahiro; Nakayama, Keiko; Kuriyama, Chiaki; Matsushita, Yasuaki; Yoshida, Kumiko; Hikida, Kumiko; Obokata, Naoyuki; Tsuda-Tsukimoto, Minoru; Saito, Akira; Arakawa, Kenji; Ueta, Kiichiro; Shiotani, Masaharu

    2015-09-01

    The sodium glucose cotransporter (SGLT) 1 plays a major role in glucose absorption and incretin hormone release in the gastrointestinal tract; however, the impact of SGLT1 inhibition on plasma glucagon-like peptide-1 (GLP-1) levels in vivo is controversial. We analyzed the effects of SGLT1 inhibitors on GLP-1 secretion in normoglycemic and hyperglycemic rodents using phloridzin, CGMI [3-(4-cyclopropylphenylmethyl)-1-(β-d-glucopyranosyl)-4-methylindole], and canagliflozin. These compounds are SGLT2 inhibitors with moderate SGLT1 inhibitory activity, and their IC50 values against rat SGLT1 and mouse SGLT1 were 609 and 760 nM for phloridzin, 39.4 and 41.5 nM for CGMI, and 555 and 613 nM for canagliflozin, respectively. Oral administration of these inhibitors markedly enhanced and prolonged the glucose-induced plasma active GLP-1 (aGLP-1) increase in combination treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, in normoglycemic mice and rats. CGMI, the most potent SGLT1 inhibitor among them, enhanced glucose-induced, but not fat-induced, plasma aGLP-1 increase at a lower dose compared with canagliflozin. Both CGMI and canagliflozin delayed intestinal glucose absorption after oral administration in normoglycemic rats. The combined treatment of canagliflozin and a DPP4 inhibitor increased plasma aGLP-1 levels and improved glucose tolerance compared with single treatment in both 8- and 13-week-old Zucker diabetic fatty rats. These results suggest that transient inhibition of intestinal SGLT1 promotes GLP-1 secretion by delaying glucose absorption and that concomitant inhibition of intestinal SGLT1 and DPP4 is a novel therapeutic option for glycemic control in type 2 diabetes mellitus. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  6. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Science.gov (United States)

    Reed, James W

    2016-01-01

    SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM). These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP) lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin) on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose control. PMID:27822054

  7. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Directory of Open Access Journals (Sweden)

    Reed JW

    2016-10-01

    Full Text Available James W Reed Morehouse School of Medicine, Atlanta, GA, USA Abstract: SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM. These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose

  8. Leading Causes of Blindness | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... had cataract surgery. Common symptoms are: Blurry vision Colors that seem faded Glare Not being able to see well at night Double vision Frequent prescription changes in your eye wear Treatment with new glasses, brighter lighting, anti-glare sunglasses, or magnifying lenses ...

  9. Cataracts and Other Common Eye Diseases | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... had cataract surgery. Common symptoms are: Blurry vision Colors that seem faded Glare Not being able to see well at night Double vision Frequent prescription changes in your eyewear At first new glasses, brighter lighting, anti-glare sunglasses, or magnifying lenses ...

  10. Neodymium:YAG treatment of interlenticular opacification in a secondary piggyback case.

    Science.gov (United States)

    Gayton, J L; Van der Karr, M; Sanders, V

    2001-09-01

    Interlenticular opacification (ILO) developed 7 months after secondary acrylic piggyback lens implantation in which the anterior lens was placed in the bag. This resulted in glare and a hyperopic shift. Treating the ILO with the neodymium:YAG laser successfully reduced the glare and corrected the hyperopic shift.

  11. Ocular Straylight with Different Multifocal Contact Lenses

    NARCIS (Netherlands)

    Łabuz, Grzegorz; López-Gil, Norberto; van den Berg, Thomas J T P; Vargas-Martín, Fernando

    2017-01-01

    PURPOSE: Multifocal contact lenses have been growing in popularity as a modality to correct presbyopic eyes, although visual side effects such as disability glare have been reported. The objective of this study was to investigate the effect of multifocal contact lenses on disability glare by means

  12. Characterisation of fibre metal laminates under thermomechanical loadings

    NARCIS (Netherlands)

    Hagenbeek, M.

    2005-01-01

    Fibre metal laminates, such as Arall or Glare, can offer improved properties compared to monolithic materials. Glare for example shows improved fatigue, residual strength, burn-through, impact and corrosion properties with respect to aluminium 2024, together with a considerable weight reduction and

  13. Characterisation of fibre metal laminates under thermomechanical loadings

    NARCIS (Netherlands)

    Hagenbeek, M.

    2005-01-01

    Fibre metal laminates, such as Arall or Glare, can offer improved properties compared to monolithic materials. Glare for example shows improved fatigue, residual strength, burn-through, impact and corrosion properties with respect to aluminium 2024, together with a considerable weight reduction and

  14. Development of fibre-metal laminates for improved impact performance

    NARCIS (Netherlands)

    Morinière, F.D.; Alderliesten, R.C.; Benedictus, R.

    2012-01-01

    An analytical and experimental investigation into the low-velocity behaviour of GLARE Fibre-Metal Laminates (FMLs) has been performed. A quasi-static approach was developed to estimate the perforation energy absorbed between the constituents of GLARE. The analysis considered contact area increase du

  15. Degradation Behavior of Epoxy Resins in Fibre Metal Laminates Under Thermal Conditions

    NARCIS (Netherlands)

    Zhu, G.; Xiao, Y.; Yang, Y.; Wang, J.; Sun, B.; Boom, R.

    2012-01-01

    GLARE (glass fibre/epoxy reinforced aluminum laminate) is a member of the fiber metal laminate (FML) family, and is built up of alternating metal and fiber layers. About 500m2 GLARE is employed in each Airbus A380 because of the superior mechanical properties over the monolithic aluminum alloys, suc

  16. Employees with Myasthenia Gravis

    Science.gov (United States)

    ... the workstation Allow a flexible work schedule and flexible use of leave time Allow work from home Provide a scooter or other mobility aid if walking cannot be reduced Vision Impairment: Provide large print material or screen reading software Control glare by adding a glare ...

  17. The effect of combined treatment with canagliflozin and teneligliptin on glucose intolerance in Zucker diabetic fatty rats.

    Science.gov (United States)

    Oguma, Takahiro; Kuriyama, Chiaki; Nakayama, Keiko; Matsushita, Yasuaki; Yoshida, Kumiko; Kiuchi, Satoko; Ikenaga, Yuka; Nakamaru, Yoshinobu; Hikida, Kumiko; Saito, Akira; Arakawa, Kenji; Oka, Kozo; Ueta, Kiichiro; Shiotani, Masaharu

    2015-04-01

    To assess the impact of concomitant inhibition of sodium-glucose cotransporter (SGLT) 2 and dipeptidyl peptidase IV (DPP4) for the treatment of type 2 diabetes mellitus (T2DM), the effect of combined treatment with canagliflozin, a novel SGLT2 inhibitor, and teneligliptin, a DPP4 inhibitor, on glucose intolerance was investigated in Zucker diabetic fatty (ZDF) rats. Canagliflozin potently inhibited human and rat SGLT2 and moderately inhibited human and rat SGLT1 activities but did not affect DPP4 activity. In contrast, teneligliptin inhibited human and rat DPP4 activities but not SGLT activities. A single oral treatment of canagliflozin and teneligliptin suppressed plasma glucose elevation in an oral glucose tolerance test in 13 week-old ZDF rats. This combination of agents elevated plasma active GLP-1 levels in a synergistic manner, probably mediated by intestinal SGLT1 inhibition, and further improved glucose intolerance. In the combination-treated animals, there was no pharmacokinetic interaction of the drugs and no further inhibition of plasma DPP4 activity compared with that in the teneligliptin-treated animals. These results suggest that the inhibition of SGLT2 and DPP4 improves glucose intolerance and that combined treatment with canagliflozin and teneligliptin is a novel therapeutic option for glycemic control in T2DM. Copyright © 2015 Mitsubishi Tanabe Pharma Corporation. Production and hosting by Elsevier B.V. All rights reserved.

  18. The effect of combined treatment with canagliflozin and teneligliptin on glucose intolerance in Zucker diabetic fatty rats

    Directory of Open Access Journals (Sweden)

    Takahiro Oguma

    2015-04-01

    Full Text Available To assess the impact of concomitant inhibition of sodium-glucose cotransporter (SGLT 2 and dipeptidyl peptidase IV (DPP4 for the treatment of type 2 diabetes mellitus (T2DM, the effect of combined treatment with canagliflozin, a novel SGLT2 inhibitor, and teneligliptin, a DPP4 inhibitor, on glucose intolerance was investigated in Zucker diabetic fatty (ZDF rats. Canagliflozin potently inhibited human and rat SGLT2 and moderately inhibited human and rat SGLT1 activities but did not affect DPP4 activity. In contrast, teneligliptin inhibited human and rat DPP4 activities but not SGLT activities. A single oral treatment of canagliflozin and teneligliptin suppressed plasma glucose elevation in an oral glucose tolerance test in 13 week-old ZDF rats. This combination of agents elevated plasma active GLP-1 levels in a synergistic manner, probably mediated by intestinal SGLT1 inhibition, and further improved glucose intolerance. In the combination-treated animals, there was no pharmacokinetic interaction of the drugs and no further inhibition of plasma DPP4 activity compared with that in the teneligliptin-treated animals. These results suggest that the inhibition of SGLT2 and DPP4 improves glucose intolerance and that combined treatment with canagliflozin and teneligliptin is a novel therapeutic option for glycemic control in T2DM.

  19. Sodium-Glucose Linked Transporter-2 Inhibitors in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    L. Zanoli

    2015-01-01

    Full Text Available SGLT2 inhibitors are new antihyperglycaemic agents whose ability to lower glucose is directly proportional to GFR. Therefore, in chronic kidney disease (CKD the blood glucose lowering effect is reduced. Unlike many current therapies, the mechanism of action of SGLT2 inhibitors is independent of insulin action or beta-cell function. In addition, the mechanism of action of SGLT2 inhibitors is complementary and not alternative to other antidiabetic agents. SGLT2 inhibitors could be potentially effective in attenuating renal hyperfiltration and, consequently, the progression of CKD. Moreover, the reductions in intraglomerular pressure, systemic blood pressure, and uric acid levels induced by SGLT inhibition may potentially be of benefit in CKD subjects without diabetes. However, at present, only few clinical studies were designed to evaluate the effects of SGLT2 inhibitors in CKD. Consequently, safety and potential efficacy beyond blood glucose lowering should be better clarified in CKD. In this paper we provide an updated review of the use of SGLT2 inhibitors in clinical practice, with particular attention on subjects with CKD.

  20. 3D Finite Element Modelling of Cutting Forces in Drilling Fibre Metal Laminates and Experimental Hole Quality Analysis

    Science.gov (United States)

    Giasin, Khaled; Ayvar-Soberanis, Sabino; French, Toby; Phadnis, Vaibhav

    2017-02-01

    Machining Glass fibre aluminium reinforced epoxy (GLARE) is cumbersome due to distinctively different mechanical and thermal properties of its constituents, which makes it challenging to achieve damage-free holes with the acceptable surface quality. The proposed work focuses on the study of the machinability of thin ( 2.5 mm) GLARE laminate. Drilling trials were conducted to analyse the effect of feed rate and spindle speed on the cutting forces and hole quality. The resulting hole quality metrics (surface roughness, hole size, circularity error, burr formation and delamination) were assessed using surface profilometry and optical scanning techniques. A three dimensional (3D) finite-element (FE) model of drilling GLARE laminate was also developed using ABAQUS/Explicit to help understand the mechanism of drilling GLARE. The homogenised ply-level response of GLARE laminate was considered in the FE model to predict cutting forces in the drilling process.

  1. 3D Finite Element Modelling of Cutting Forces in Drilling Fibre Metal Laminates and Experimental Hole Quality Analysis

    Science.gov (United States)

    Giasin, Khaled; Ayvar-Soberanis, Sabino; French, Toby; Phadnis, Vaibhav

    2016-07-01

    Machining Glass fibre aluminium reinforced epoxy (GLARE) is cumbersome due to distinctively different mechanical and thermal properties of its constituents, which makes it challenging to achieve damage-free holes with the acceptable surface quality. The proposed work focuses on the study of the machinability of thin (~2.5 mm) GLARE laminate. Drilling trials were conducted to analyse the effect of feed rate and spindle speed on the cutting forces and hole quality. The resulting hole quality metrics (surface roughness, hole size, circularity error, burr formation and delamination) were assessed using surface profilometry and optical scanning techniques. A three dimensional (3D) finite-element (FE) model of drilling GLARE laminate was also developed using ABAQUS/Explicit to help understand the mechanism of drilling GLARE. The homogenised ply-level response of GLARE laminate was considered in the FE model to predict cutting forces in the drilling process.

  2. Chronic and selective inhibition of basolateral membrane Na-K-ATPase uniquely regulates brush border membrane Na absorption in intestinal epithelial cells

    Science.gov (United States)

    Manoharan, Palanikumar; Gayam, Swapna; Arthur, Subha; Palaniappan, Balasubramanian; Singh, Soudamani; Dick, Gregory M.

    2015-01-01

    Na-K-ATPase, an integral membrane protein in mammalian cells, is responsible for maintaining the favorable intracellular Na gradient necessary to promote Na-coupled solute cotransport processes [e.g., Na-glucose cotransport (SGLT1)]. Inhibition of brush border membrane (BBM) SGLT1 is, at least in part, due to the diminished Na-K-ATPase in villus cells from chronically inflamed rabbit intestine. The aim of the present study was to determine the effect of Na-K-ATPase inhibition on the two major BBM Na absorptive pathways, specifically Na-glucose cotransport and Na/H exchange (NHE), in intestinal epithelial (IEC-18) cells. Na-K-ATPase was inhibited using 1 mM ouabain or siRNA for Na-K-ATPase-α1 in IEC-18 cells. SGLT1 activity was determined as 3-O-methyl-d-[3H]glucose uptake. Na-K-ATPase activity was measured as the amount of inorganic phosphate released. Treatment with ouabain resulted in SGLT1 inhibition at 1 h but stimulation at 24 h. To further characterize this unexpected stimulation of SGLT1, siRNA silencing was utilized to inhibit Na-K-ATPase-α1. SGLT1 activity was significantly upregulated by Na-K-ATPase silencing, while NHE3 activity remained unaltered. Kinetics showed that the mechanism of stimulation of SGLT1 activity was secondary to an increase in affinity of the cotransporter for glucose without a change in the number of cotransporters. Molecular studies demonstrated that the mechanism of stimulation was not secondary to altered BBM SGLT1 protein levels. Chronic and direct silencing of basolateral Na-K-ATPase uniquely regulates BBM Na absorptive pathways in intestinal epithelial cells. Specifically, while BBM NHE3 is unaffected, SGLT1 is stimulated secondary to enhanced affinity of the cotransporter. PMID:25652450

  3. Skeletal muscle sodium glucose co-transporters in older adults with type 2 diabetes undergoing resistance training

    Directory of Open Access Journals (Sweden)

    Francisco Castaneda, Jennifer E. Layne, Carmen Castaneda

    2006-01-01

    Full Text Available We examined the expression of the sodium-dependent glucose co-transporter system (hSGLT3 in skeletal muscle of Hispanic older adults with type 2 diabetes. Subjects (65±8 yr were randomized to resistance training (3x/wk, n=13 or standard of care (controls, n=5 for 16 weeks. Skeletal muscle hSGLT3 and GLUT4 mRNA transcript levels were determined by real time RT-PCR. hSGLT3 transcripts increased by a factor of ten following resistance training compared to control subjects (0.10, P=0.03. There were no differences in GLUT4 mRNA expression levels between groups. Protein expression levels of these transporters were confirmed by immunohistochemistry and Western blotting. hSGLT3 after resistance exercise was found not to be co-localized with the nicotinic acetylcholine receptor. The change in hSGLT3 transcript levels in the vastus lateralis muscle was positively correlated with glucose uptake, as measured by the change in muscle glycogen stores (r=0.53, P=0.02; and with exercise intensity, as measured by the change in muscle strength (r=0.73, P=0.001. Group assignment was be the only independent predictor of hSGLT3 transcript levels, explaining 68% of its variability (P=0.01. Our data show that hSGLT3, but not GLTU4, expression was enhanced in skeletal muscle after 16 weeks of resistance training. This finding suggests that hSGLT3, an insulin-independent glucose transporter, is activated with exercise and it may play a significant role in glycemic control with muscle contraction. The hSGLT3 exact mechanism is not well understood and requires further investigation. However its functional significance regarding a reduction of glucose toxicity and improvement of insulin resistance is the subject of ongoing research.

  4. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic)

    DEFF Research Database (Denmark)

    Birkeland, Kåre I; Jørgensen, Marit E; Carstensen, Bendix

    2017-01-01

    BACKGROUND: In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed......% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors...

  5. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect

    Science.gov (United States)

    Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A. G.

    2016-01-01

    This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a “good person,” who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production. PMID:27730088

  6. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect.

    Science.gov (United States)

    Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A G

    2016-01-01

    This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

  7. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2 inhibition: Calorie restriction mimicry (CRM and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

  8. Sodium-glucose cotransporter 2 inhibitor use: A pharmaco-ergonomic qualification tool

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2017-01-01

    Full Text Available Pharmaco-ergonomics implies tailoring the drug therapy to an individual patient's requirement(s. The development of sodium-glucose cotransporter 2 inhibitor (SGLT2-i agents has impelled multiple clinical considerations, in the management of type-2 diabetes. This paper attempts to summarize the pharmaco-ergonomic considerations for these agents, in the form of an SGLT2-i qualification tool, based on a clinical score. This tool may serve as a simple and inexpensive practical guide, to optimize the risk-benefit considerations for SGLT2-i agents.

  9. The distribution and status of sea otters in Alaska

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The original distribution of sea otters, Enhydra lutris (L), included the coastal area of the North Pacific Ocean and Bering Sea from Kamchatka south to Hokkaido...

  10. 77 FR 73471 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-10

    ...-transporter 2 (SGLT2) inhibitors, and was developed as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FDA intends to make background material available to...

  11. 76 FR 34085 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-06-10

    ...-transporter 2 (SGLT2) inhibitors, developed as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FDA intends to make background material available to the public...

  12. Clinical Implications of Canagliflozin Treatment in Patients With Type 2 Diabetes

    Science.gov (United States)

    Hinnen, Deborah

    2015-01-01

    IN BRIEF Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycemic agents that lower blood glucose levels in patients with type 2 diabetes. SGLT2 inhibitors have an insulin-independent mechanism of action, acting to inhibit the reabsorption of glucose in the kidney, which leads to increases in urinary glucose excretion in individuals with elevated blood glucose levels. This article provides an overview of the role of the kidney in type 2 diabetes, describes the rationale for renal SGLT2 as a new target for glycemic control, and focuses on the clinical implications of incorporating the SGLT2 inhibitor canagliflozin into type 2 diabetes treatment regimens based on data from phase 3 studies. PMID:25653467

  13. Anti sense and sensibility : renal and skin effects of (antisense) oligonucleotides

    NARCIS (Netherlands)

    Meer, van L.

    2017-01-01

    This thesis describes the clinical investigation of a novel treatment strategy for type 2 diabetes mellitus (t2dm) using an antisense oligonucleotide(aon)to inhibit the sglt2 receptor. Furthermore it describes skin effects of oligonucleotides

  14. An unusual cause of glycosuria in a 5-year-old child

    African Journals Online (AJOL)

    for glucose.1 Another urine sample was therefore requested, with similar results ... a low-affinity Na+/glucose co-transporter (SGLT2) is kidney specific. ... commonest type of diabetes, where the absence of insulin ... 1. Sacks D. Carbohydrates.

  15. The effects of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Gluud, Lise Lotte; Christensen, Mikkel

    2014-01-01

    to the knowledge regarding the beneficial and harmful effects of SGLT-2i in patients with type 2 diabetes. We plan to publish the study irrespective of the results. RESULTS: The study will be disseminated by peer-review publication and conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014008960......INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) increase urinary glucose excretion through a reduced renal glucose reabsorption. We plan to perform a systematic review of SGLT-2i for treatment of type 2 diabetes. METHODS AND ANALYSIS: A systematic review with meta......-analyses of randomised clinical trials on SGLT-2i versus placebo, other oral glucose lowering drugs or insulin for patients with type 2 diabetes will be performed. The primary end point will be the glycated haemoglobin. Secondary end points will include changes in body weight, body mass index, fasting plasma glucose...

  16. Structural and functional significance of water permeation through cotransporters

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Gorraitz, Edurne; Her, Ka

    2016-01-01

    and mutated residues lining the sugar transport pathway to cysteine. The mutants were expressed in Xenopus oocytes, and the unitary water and urea permeabilities were determined before and after modifying the cysteine side chain with reversible methanethiosulfonate reagents. The results demonstrate that water......Membrane transporters, in addition to their major role as specific carriers for ions and small molecules, can also behave as water channels. However, neither the location of the water pathway in the protein nor their functional importance is known. Here, we map the pathway for water and urea...... through the intestinal sodium/glucose cotransporter SGLT1. Molecular dynamics simulations using the atomic structure of the bacterial transporter vSGLT suggest that water permeates the same path as Na+ and sugar. On a structural model of SGLT1, based on the homology structure of vSGLT, we identified...

  17. Passive water and ion transport by cotransporters

    DEFF Research Database (Denmark)

    Loo, D D; Hirayama, B A; Meinild, A K

    1999-01-01

    1. The rabbit Na+-glucose (SGLT1) and the human Na+-Cl--GABA (GAT1) cotransporters were expressed in Xenopus laevis oocytes, and passive Na+ and water transport were studied using electrical and optical techniques. Passive water permeabilities (Lp) of the cotransporters were determined from...... the changes in oocyte volume in response to osmotic gradients. The specific SGLT1 and GAT1 Lp values were obtained by measuring Lp in the presence and absence of blockers (phlorizin and SKF89976A). In the presence of the blockers, the Lp values of oocytes expressing SGLT1 and GAT1 were indistinguishable from...... the Lp of control oocytes. Passive Na+ transport (Na+ leak) was obtained from the blocker-sensitive Na+ currents in the absence of substrates (glucose and GABA). 2. Passive Na+ and water transport through SGLT1 were blocked by phlorizin with the same sensitivity (inhibitory constant (Ki), 3-5 micro...

  18. Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate diet

    Science.gov (United States)

    Hayami, Tomohide; Kato, Yoshiro; Kamiya, Hideki; Kondo, Masaki; Naito, Ena; Sugiura, Yukako; Kojima, Chika; Sato, Sami; Yamada, Yuichiro; Kasagi, Rina; Ando, Toshihito; Noda, Saeko; Nakai, Hiromi; Takada, Eriko; Asano, Emi; Motegi, Mikio; Watarai, Atsuko; Kato, Koichi; Nakamura, Jiro

    2015-01-01

    We present a case of a 32-year-old diabetic woman with Prader–Willi syndrome who developed severe ketoacidosis caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents, during a strict low-carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was relatively low, though laboratory evaluations showed severe ketoacidosis. This is the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to not only pay attention when using a SGLT2 inhibitor in patients following a low-carbohydrate diet, but also to start a low-carbohydrate diet in patients treated with a SGLT2 inhibitor because of a high risk for developing ketoacidosis. PMID:26417418

  19. SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine

    National Research Council Canada - National Science Library

    Rym Aouameur; Sandra Da Cal; Pierre Bissonnette; Michael J. Coady; Jean-Yves Lapointe

    2007-01-01

    ...; rabbit intestine appears to lack apical transport of MI. Other sugar transport systems known to be present in apical membranes, such as SGLT1 or GLUT5, lacked any significant contribution to MI uptake...

  20. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Kim Y

    2012-08-01

    Full Text Available Yoojin Kim, Ambika R BabuDivision of Endocrinology, John Stroger Jr Hospital of Cook County and Rush University, Chicago, IL, USABackground: The kidney plays an important role in glucose metabolism, and has been considered a target for therapeutic intervention. The sodium-glucose cotransporter type 2 (SGLT2 mediates most of the glucose reabsorption from the proximal renal tubule. Inhibition of SGLT2 leads to glucosuria and provides a unique mechanism to lower elevated blood glucose levels in diabetes. The purpose of this review is to explore the physiology of SGLT2 and discuss several SGLT2 inhibitors which have clinical data in patients with type 2 diabetes.Methods: We performed a PubMed search using the terms "SGLT2" and "SGLT2 inhibitor" through April 10, 2012. Published articles, press releases, and abstracts presented at national and international meetings were considered.Results: SGLT2 inhibitors correct a novel pathophysiological defect, have an insulin-independent action, are efficacious with glycosylated hemoglobin reduction ranging from 0.5% to 1.5%, promote weight loss, have a low incidence of hypoglycemia, complement the action of other antidiabetic agents, and can be used at any stage of diabetes. They are generally well tolerated. However, due to side effects, such as repeated urinary tract and genital infections, increased hematocrit, and decreased blood pressure, appropriate patient selection for drug initiation and close monitoring after initiation will be important. Results of ongoing clinical studies of the effect of SGLT2 inhibitors on diabetic complications and cardiovascular safety are crucial to determine the risk-benefit ratio. A recent decision by the Committee for Medicinal Products for Human Use of the European Medicines Agency has recommended approval of dapagliflozin for the treatment of type 2 diabetes as an adjunct to diet and exercise, in combination with other glucose-lowering medicinal products, including

  1. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    OpenAIRE

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

    The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the a...

  2. Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium–glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents

    OpenAIRE

    Takahiro Oguma; Chiaki Kuriyama; Keiko Nakayama; Yasuaki Matsushita; Kumiko Hikida; Minoru Tsuda-Tsukimoto; Akira Saito; Kenji Arakawa; Kiichiro Ueta; Masabumi Minami; Masaharu Shiotani

    2016-01-01

    We investigated whether structurally different sodium–glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors—1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin—were examined to assess the effect of chemical structure. Oral treatment...

  3. The Na+ glucose co-transporter inhibitor canagliflozin activates AMP-activated protein kinase by inhibiting mitochondrial function and increasing cellular AMP levels

    OpenAIRE

    Hawley, Simon A.; Ford, Rebecca J.; Smith, Brennan K.; Gowans, Graeme J.; Mancini, Sarah; Pitt, Ryan D.; Day, Emily A.; Salt, Ian P.; Steinberg, Gregory R.; Hardie, D. Grahame

    2016-01-01

    Canagliflozin, dapagliflozin and empagliflozin, all recently approved for treatment of Type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose re-uptake by SGLT2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMP-activated protein kinase (AMPK), an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with da...

  4. Sodium-glucose cotransporter 2 inhibitors with insulin in type 2 diabetes: Clinical perspectives

    OpenAIRE

    Mathew John; Deepa Gopinath; Rejitha Jagesh

    2016-01-01

    The treatment of type 2 diabetes is a challenging problem. Most subjects with type 2 diabetes have progression of beta cell failure necessitating the addition of multiple antidiabetic agents and eventually use of insulin. Intensification of insulin leads to weight gain and increased risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antihyperglycemic agents which act by blocking the SGLT2 in the proximal tubule of the kidney. They have potential benefits in...

  5. Canagliflozin-Induced Diabetic Ketoacidosis

    OpenAIRE

    Jessica Turner MSIV; Tahmina Begum MD; Roger D. Smalligan MD, MPH

    2016-01-01

    Introduction: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are relatively new antihyperglycemic agents that lower renal glucose reabsorption. They are used as adjunctive therapy to standard diabetes treatment. Case Report: We present the case of a 62-year-old woman with a past medical history of type 2 diabetes mellitus and sudden-onset diabetic ketoacidosis (DKA). Use of canagliflozin, a SGLT-2 inhibitor, was determined to be the cause of the DKA. The patient ultimately recovered afte...

  6. Relationship between cerebral sodium-glucose transporter and hyperglycemia in cerebral ischemia.

    Science.gov (United States)

    Yamazaki, Yui; Harada, Shinichi; Tokuyama, Shogo

    2015-09-14

    Post-ischemic hyperglycemia exacerbates the development of cerebral ischemia. To elucidate this exacerbation mechanism, we focused on sodium-glucose transporter (SGLT) as a mediator that lead hyperglycemia to cerebral ischemia. SGLT transport glucose into the cell, together with sodium ion, using the sodium concentration gradient. We have previously reported that suppression of cerebral SGLT ameliorates cerebral ischemic neuronal damage. However, detail relationship cerebral between SGLT and post-ischemic hyperglycemia remain incompletely defined. Therefore, we examined the involvement of cerebral SGLT on cerebral ischemic neuronal damage with or without hyperglycemic condition. Cell survival rate of primary cultured neurons was assessed by biochemical assay. A mouse model of focal ischemia was generated using a middle cerebral artery occlusion (MCAO). Neuronal damage was assessed with histological and behavioral analyses. Concomitant hydrogen peroxide/glucose treatment exacerbated hydrogen peroxide alone-induced cell death. Although a SGLT family-specific inhibitor, phlorizin had no effect on developed hydrogen peroxide alone-induced cell death, it suppressed cell death induced by concomitant hydrogen peroxide/glucose treatment. α-MG induced a concentration-dependent and significant decrease in neuronal survival. PHZ administered on immediately after reperfusion had no effect, but PHZ given at 6h after reperfusion had an effect. Our in vitro study indicates that SGLT is not involved in neuronal cell death in non-hyperglycemic condition. We have already reported that post-ischemic hyperglycemia begins to develop at 6h after MCAO. Therefore, current our in vivo study show post-ischemic hyperglycemic condition may be necessary for the SGLT-mediated exacerbation of cerebral ischemic neuronal damage.

  7. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

    OpenAIRE

    Peters, Anne L.; Buschur, Elizabeth O.; Buse, John B.; Cohan, Pejman; Diner, Jamie C.; Hirsch, Irl B.

    2015-01-01

    OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 d...

  8. Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Gluud, Lise L; Bennett, Cathy

    2016-01-01

    OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND STUDY...... increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias....

  9. Sodium-glucose cotransporter 2 inhibitors with insulin in type 2 diabetes: Clinical perspectives

    Directory of Open Access Journals (Sweden)

    Mathew John

    2016-01-01

    Full Text Available The treatment of type 2 diabetes is a challenging problem. Most subjects with type 2 diabetes have progression of beta cell failure necessitating the addition of multiple antidiabetic agents and eventually use of insulin. Intensification of insulin leads to weight gain and increased risk of hypoglycemia. Sodium-glucose cotransporter 2 (SGLT2 inhibitors are a class of antihyperglycemic agents which act by blocking the SGLT2 in the proximal tubule of the kidney. They have potential benefits in terms of weight loss and reduction of blood pressure in addition to improvements in glycemic control. Further, one of the SGLT2 inhibitors, empagliflozin has proven benefits in reducing adverse cardiovascular (CV outcomes in a CV outcome trial. Adding SGLT2 inhibitors to insulin in subjects with type 2 diabetes produced favorable effects on glycemic control without the weight gain and hypoglycemic risks associated with insulin therapy. The general risks of increased genital mycotic infections, urinary tract infections, volume, and osmosis-related adverse effects in these subjects were similar to the pooled data of individual SGLT2 inhibitors. There are subsets of subjects with type 2 diabetes who may have insulin deficiency, beta cell autoimmunity, or is prone to diabetic ketoacidosis. In these subjects, SGLT2 inhibitors should be used with caution to prevent the rare risks of ketoacidosis.

  10. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects

    Directory of Open Access Journals (Sweden)

    Atsuo Tahara

    2016-03-01

    Full Text Available The sodium-glucose cotransporter (SGLT 2 offer a novel approach to treating type 2 diabetes by reducing hyperglycaemia via increased urinary glucose excretion. In the present study, the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six SGLT2 inhibitors commercially available in Japan were investigated and compared. Based on findings in normal and diabetic mice, the six drugs were classified into two categories, long-acting: ipragliflozin and dapagliflozin, and intermediate-acting: tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. Long-acting SGLT2 inhibitors exerted an antihyperglycemic effect with lower variability of blood glucose level via a long-lasting increase in urinary glucose excretion. In addition, ipragliflozin and luseogliflozin exhibited superiority over the others with respect to fast onset of pharmacological effect. Duration and onset of the pharmacologic effects seemed to be closely correlated with the pharmacokinetic properties of each SGLT2 inhibitor, particularly with respect to high distribution and long retention in the target organ, the kidney. While all six SGLT2 inhibitors were significantly effective in increasing urinary glucose excretion and reducing hyperglycemia, our findings suggest that variation in the quality of daily blood glucose control associated with duration and onset of pharmacologic effects of each SGLT2 inhibitor might cause slight differences in rates of improvement in type 2 diabetes.

  11. Heart failure hospitalization risk associated with use of two classes of oral antidiabetic medications: an observational, real-world analysis.

    Science.gov (United States)

    Gautam, Santosh; Agiro, Abiy; Barron, John; Power, Thomas; Weisman, Harry; White, Jeff

    2017-07-31

    Newer oral antidiabetic drug classes are expanding treatment options for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was to assess relative risk of heart failure hospitalization of sodium-glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM patients. This retrospective observational study used a national commercially insured claims database. Adults (>18 years) with T2DM newly starting SGLT2 or DPP4 medication between April 2013 and December 2014 were included. Depending on their index fill, patients were grouped into either SGLT2 or DPP4 medication class cohorts. The primary outcome was hospitalization for heart failure and the risk was assessed using Cox regression models. Propensity score matching (1:2 ratio) was used to adjust for potential confounders. Analyses were also stratified by the presence of baseline diabetes complication and age (heart failure hospitalization was lower among SGLT2 users in comparison with matched DPP4 users (2.0% SGLT2 vs 3.1% DPP4; adjusted hazard ratio [aHR] 0.68; 95% confidence interval [CI] 0.54-0.86; p = .001). However, the stratified analyses revealed no risk difference among the majority of the analyzed patients, i.e., those aged heart failure was significantly lower for patients initiating an SGLT2 compared with a DPP4 medication, specifically among older patients and those with diabetes complication.

  12. An investigation on dysphotopsia of a sigma-edged intraocular lens

    Institute of Scientific and Technical Information of China (English)

    Zhishan Gao; Meimei Kong; Xinhua Li; Lei Chen; Rihong Zhu

    2006-01-01

    @@ A sigma-edged design of intraocular lens (IOL) is proposed to minimize the reflected glare images associated with the edge. The optimal sigma inverse edge is investigated when pupil diameter is 5.0 mm by the established Escudero-Sanz's wide angle model. The non-sequential ray tracing program of Zemax-EE (Zemax Development Corp., San Diego, USA) is used to investigate the sigma edge of reducing the potential for edge glare phenomena. The results show that sigma-edged design can significantly reduce the reflected glare intensity on retina if the angle of its inverse edge is taken from 20 to 70 degrees.

  13. An overview of the effect of sodium glucose cotransporter 2 inhibitor monotherapy on glycemic and other clinical laboratory parameters in type 2 diabetes patients

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-07-01

    Full Text Available Yaowen Wang,1 Xueting Hu,2 Xueying Liu,3 Zengqi Wang2 1Department of Clinical Laboratory, Weifang People’s Hospital, 2Department of Clinical Laboratory, Weifang Traditional Chinese Hospital, Weifang, 3Department of Clinical Laboratory, The Third Hospital of Jinan, Jinan, People’s Republic of China Objectives: We aimed to determine the effect of sodium glucose cotransporter 2 (SGLT2 inhibitor monotherapy on glycemic and other clinical laboratory parameters versus other antidiabetic medications or placebo therapy in patients with type 2 diabetes mellitus. In addition, we aimed to investigate the risk of diabetic ketoacidosis associated with SGLT2 inhibitor therapy and evaluate its weight-sparing ability. Design: Meta-analysis. Materials and methods: PubMed and MEDLINE were searched to identify eligible studies up to December 2015. Randomized controlled trials that assessed the efficacy and safety of SGLT2 inhibitor monotherapy versus placebo therapy or active control were considered. The Cochrane Collaboration Risk of Bias Tool was used to evaluate quality and bias. The mean ­difference was used to evaluate the glycemic and other clinical laboratory parameters for SGLT2 inhibitor intervention versus control by drugs or placebo. Similarly, the risk ratio was used to assess adverse events, and the I2 was used to evaluate heterogeneity. Results: SGLT2 inhibitors significantly decreased glycated hemoglobin (HbA1c (P<0.001, weight (P<0.001, and the low-density lipoprotein/high-density lipoprotein ratio (P=0.03 compared with placebo therapy. No statistically significant changes were found in fasting plasma glucose, 2-hour postprandial glucose, or lipid parameters. Significant changes in the uric acid level were found for SGLT2 inhibitors versus placebo therapy (P=0.005 or active control (P<0.001. Although no significant change in levels of ketones occurred (P=0.93, patients receiving SGLT2 inhibitors were at greater risk of increased ketone bodies

  14. functional and psychological outcome of cataract surgeries in platea

    African Journals Online (AJOL)

    Perpetua

    cause of blindness, is the leading cause of blindness and low vision worldwide. .... (includes light/dark adaptation, colour discrimination and glare disability), a ..... are dissatisfied could have the opposite effect, and fear of a poor outcome may ...

  15. Preliminary Assessment of the Energy-Saving Potential of Electrochromic Windows in Residential Buildings

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, D. R.

    2009-12-01

    Electrochromic windows provide variable tinting that can help control glare and solar heat gain. We used BEopt software to evaluate their performance in prototypical energy models of a single-family home.

  16. Eldercare at Home: Communication Problems

    Science.gov (United States)

    ... not interfering with the person's vision. While bright light often helps, it also can create glare that interferes with vision. Eliminate background noise. Turn off the TV and radio. Turn off the TV and radio. ...

  17. Urban Planning, Downstream Petroleum Industry and Human Health

    African Journals Online (AJOL)

    DELL

    space, congestion, squalor, pollution and attendant environmental and health challenges. A glaring ... petrol station controls and regulations if the nation is to avert mass mortality in the near future. ..... International Cooperation in National.

  18. in Preventing Rise of Intraocular Pressure (Iop)

    African Journals Online (AJOL)

    tulyasys

    vision, increased glare and interference in the day to day activities of ... Materials and Methods: A randomized, single-blinded, parallel group study conducted in ... Precapsulotomy baseline IOP, Slitlamp examination and grading of. PCO was ...

  19. Perang dalam Perspektif Agama

    National Research Council Canada - National Science Library

    Daniel Ronda

    2005-01-01

    Tulisan di majalah TIME 24 Februari 2003 oleh Joe Klein, "The Blinding Glare of His Certainty" mempertanyakan antara iman kepercayaan Bush dengan keinginannya yang menggebu-gebu untuk menyerang Irak...

  20. Dartmouth Atlas of Health Care

    Data.gov (United States)

    U.S. Department of Health & Human Services — For more than 20 years, the Dartmouth Atlas Project has documented glaring variations in how medical resources are distributed and used in the United States. The...

  1. Nanostructured Super-Black Optical Materials Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Need: NASA faces challenges in imaging and characterizing faint astrophysical objects within the glare of brighter stellar sources. Achieving a very low background...

  2. Cataract

    Science.gov (United States)

    ... to the other. Common symptoms are Blurry vision Colors that seem faded Glare - headlights, lamps or sunlight ... the cloudy lens and replacing it with an artificial lens. Wearing sunglasses and a hat with a ...

  3. Safety of Sodium-Glucose Co-Transporter 2 Inhibitors during Ramadan Fasting: Evidence, Perceptions and Guidelines

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    Salem A. Beshyah

    2016-06-01

    Full Text Available Sodium-glucose co-transporter 2 (SGLT2 inhibitors are a new glucose-lowering therapy for T2DM with documented benefits on blood glucose, hypertension, weight reduction and long term cardiovascular benefit. They have an inherent osmotic diuretic effect and lead to some volume loss and possible dehydration. There is some concern about the safety of using SGLT2 inhibitors in Muslim type 2 diabetes mellitus (T2DM patients during the fast during Ramadan. Currently, there is a dearth of research data to help guide physicians and reassure patients.  One study confirmed good glycemic control with less risk of hypoglycemia and no marked volume depletion. Data in the elderly and in combination with diuretics are reassuring of their safe to use in Ramadan in general. SGLT2 inhibitor-related diabetic ketoacidosis has not been reported during Ramadan and is unlikely to be relevant. Survey of physicians revealed that the majority felt that SGLT2 inhibitors are generally safe in T2DM patients during Ramadan fasting but should be discontinued in certain high risk patients. Some professional groups with interest in diabetes and Ramadan fasting included SGLT2 inhibitors in their guidelines on management of diabetes during Ramadan. They acknowledged the lack of trial data, recommended caution in high risk groups, advised regular monitoring and emphasized pre-Ramadan patients’ education. In conclusion, currently, knowledge, data and experience with SGLT2 inhibitors in Ramadan are limited. Nonetheless, stable patients with normal kidney function and low risk of dehydration may safely use the SGLT2 inhibitors therapy. Higher risk patients should be observed carefully and managed on individual basis.

  4. Post-oral appetite stimulation by sugars and nonmetabolizable sugar analogs.

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    Zukerman, Steven; Ackroff, Karen; Sclafani, Anthony

    2013-10-01

    Post-oral sugar actions enhance the intake of and preference for sugar-rich foods, a process referred to as appetition. Here, we investigated the role of intestinal sodium glucose cotransporters (SGLTs) in sugar appetition in C57BL/6J mice using sugars and nonmetabolizable sugar analogs that differ in their affinity for SGLT1 and SGLT3. In experiments 1 and 2, food-restricted mice were trained (1 h/day) to consume a flavored saccharin solution [conditioned stimulus (CS-)] paired with intragastric (IG) self-infusions of water and a different flavored solution (CS+) paired with infusions of 8 or 12% sugars (glucose, fructose, and galactose) or sugar analogs (α-methyl-D-glucopyranoside, MDG; 3-O-methyl-D-glucopyranoside, OMG). Subsequent two-bottle CS+ vs. CS- choice tests were conducted without coinfusions. Infusions of the SGLT1 ligands glucose, galactose, MDG, and OMG stimulated CS+ licking above CS- levels. However, only glucose, MDG, and galactose conditioned significant CS+ preferences, with the SGLT3 ligands (glucose, MDG) producing the strongest preferences. Fructose, which is not a ligand for SGLTs, failed to stimulate CS+ intake or preference. Experiment 3 revealed that IG infusion of MDG+phloridzin (an SGLT1/3 antagonist) blocked MDG appetition, whereas phloridzin had minimal effects on glucose-induced appetition. However, adding phloretin (a GLUT2 antagonist) to the glucose+phloridzin infusion blocked glucose appetition. Taken together, these findings suggest that humoral signals generated by intestinal SGLT1 and SGLT3, and to a lesser degree, GLUT2, mediate post-oral sugar appetition in mice. The MDG results indicate that sugar metabolism is not essential for the post-oral intake-stimulating and preference-conditioning actions of sugars in mice.

  5. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice.

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    Muralikrishna Gangadharan Komala

    Full Text Available BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2 is the main luminal glucose transporter in the kidney. SGLT2 inhibition results in glycosuria and improved glycaemic control. Drugs inhibiting this transporter have recently been approved for clinical use and have been suggested to have potential renoprotective benefits by limiting glycotoxicity in the proximal tubule. We aimed to determine the renoprotective benefits of empagliflozin, an SGLT2 inhibitor, independent of its glucose lowering effect. RESEARCH DESIGN AND METHODS: We induced diabetes using a low dose streptozotocin protocol in 7-8 week old endothelial nitric oxide (eNOS synthase knockout mice. We measured fasting blood glucose on a monthly basis, terminal urinary albumin/creatinine ratio. Renal histology was assessed for inflammatory and fibrotic changes. Renal cortical mRNA transcription of inflammatory and profibrotic cytokines, glucose transporters and protein expression of SGLT2 and GLUT1 were determined. Outcomes were compared to diabetic animals receiving the angiotensin receptor blocker telmisartan (current best practice. RESULTS: Diabetic mice had high matched blood glucose levels. Empagliflozin did not attenuate diabetes-induced albuminuria, unlike telmisartan. Empagliflozin did not improve glomerulosclerosis, tubular atrophy, tubulointerstitial inflammation or fibrosis, while telmisartan attenuated these. Empagliflozin did not modify tubular toll-like receptor-2 expression in diabetic mice. Empagliflozin did not reduce the upregulation of macrophage chemoattractant protein-1 (MCP-1, transforming growth factor β1 and fibronectin mRNA observed in the diabetic animals, while telmisartan decreased transcription of MCP-1 and fibronectin. Empagliflozin increased GLUT1 mRNA expression and telmisartan increased SGLT2 mRNA expression in comparison to untreated diabetic mice. However no significant difference was found in protein expression of GLUT1 or SGLT2 among the

  6. Impact Resistance of Lightweight Hybrid Structures for Gas Turbine Engine Fan Containment Applications

    Science.gov (United States)

    Hebsur, Mohan G.; Noebe, Ronald D.; Revilock, Duane M.

    2003-01-01

    The ballistic impact resistance of hybrid composite sandwich structures was evaluated with the ultimate goal of developing new materials or structures for potential gas turbine engine fan containment applications. The sandwich structures investigated consisted of GLARE-5 laminates as face sheets with lightweight cellular metallic materials such as honeycomb, foam, and lattice block as a core material. The impact resistance of these hybrid sandwich structures was compared to GLARE-5 laminates and 2024-T3 Al sheet, which were tested as a function of areal weight (material thickness). The GLARE-5 laminates exhibited comparable impact properties to that of 2024-T3 Al at low areal weights, even though there were significant differences in the static tensile properties of these materials. The GLARE-5, however, did have a greater ballistic limit than straight aluminum sheet at higher areal weights. Furthermore, there is up to a 25% advantage in ballistic limit for the GLARE-5/foam sandwich structures compared to straight 2024-T3 Al. But no advantage in ballistic limit was observed between any of the hybrid sandwich structures and thicker versions of GLARE-5. Recommendations for future work are provided, based on these preliminary data.

  7. Slab mantle dehydrates beneath Kamchatka—Yet recycles water into the deep mantle

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    Konrad-Schmolke, Matthias; Halama, Ralf; Manea, Vlad C.

    2016-08-01

    The subduction of hydrated slab mantle is the most important and yet weakly constrained factor in the quantification of the Earth's deep geologic water cycle. The most critical unknowns are the initial hydration state and the dehydration behavior of the subducted oceanic mantle. Here we present a combined thermomechanical, thermodynamic, and geochemical model of the Kamchatka subduction zone that indicates significant dehydration of subducted slab mantle beneath Kamchatka. Evidence for the subduction of hydrated oceanic mantle comes from across-arc trends of boron concentrations and isotopic compositions in arc volcanic rocks. Our thermodynamic-geochemical models successfully predict the complex geochemical patterns and the spatial distribution of arc volcanoes in Kamchatka assuming the subduction of hydrated oceanic mantle. Our results show that water content and dehydration behavior of the slab mantle beneath Kamchatka can be directly linked to compositional features in arc volcanic rocks. Depending on hydration depth of the slab mantle, our models yield water recycling rates between 1.1 × 103 and 7.4 × 103 Tg/Ma/km corresponding to values between 0.75 × 106 and 5.2 × 106 Tg/Ma for the entire Kamchatkan subduction zone. These values are up to one order of magnitude lower than previous estimates for Kamchatka, but clearly show that subducted hydrated slab mantle significantly contributes to the water budget in the Kamchatkan subduction zone.

  8. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    Science.gov (United States)

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

  9. Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium–glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents

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    Takahiro Oguma

    2016-12-01

    Full Text Available We investigated whether structurally different sodium–glucose cotransporter (SGLT 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4 inhibitors, could enhance glucagon-like peptide-1 (GLP-1 secretion during oral glucose tolerance tests (OGTTs in rodents. Three different SGLT inhibitors—1-(β-d-Glucopyranosyl-4-chloro-3-[5-(6-fluoro-2-pyridyl-2-thienylmethyl]benzene (GTB, TA-1887, and canagliflozin—were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1 elevation and suppressed glucose excursions in both normal and diabetic rodents. In DPP4-deficient rats, GTB enhanced glucose-induced aGLP-1 elevation without affecting the basal level, whereas metformin, previously reported to enhance GLP-1 secretion, increased both the basal level and glucose-induced elevation. Oral treatment with canagliflozin and TA-1887 also enhanced glucose-induced aGLP-1 elevation when co-administered with either teneligliptin or sitagliptin. These data suggest that structurally different SGLT2 inhibitors enhance plasma aGLP-1 elevation and suppress glucose excursions during OGTT when co-administered with DPP4 inhibitors, regardless of the difference in chemical structure. Combination treatment with DPP4 inhibitors and SGLT2 inhibitors having moderate SGLT1 inhibitory activity may be a promising therapeutic option for improving glycemic control in patients with type 2 diabetes mellitus.

  10. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors: Part 2. Antidiabetic effects in type 2 diabetic mice

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    Atsuo Tahara

    2016-07-01

    Full Text Available Previously we investigated the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six sodium-glucose cotransporter (SGLT 2 inhibitors commercially available in Japan using normal and diabetic mice. We classified the SGLT2 inhibitors with respect to duration of action as either long-acting (ipragliflozin and dapagliflozin or intermediate-acting (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin. In the present study, antidiabetic effects of repeated administration of these SGLT2 inhibitors in type 2 diabetic mice were investigated. When repeatedly administered for 4 weeks, all SGLT2 inhibitors significantly exhibited antihyperglycemic, antihyperinsulinemic, and pancreas-protective effects, as well as insulin resistance-improving effects. When compared at doses producing comparable reduction in hyperglycemia across all drugs, the antidiabetic effects of ipragliflozin and dapagliflozin were more potent than those of the other four drugs, but these differences among the six drugs were not statistically significant. Further, an oral glucose tolerance test performed after repeated administration demonstrated significant improvement in glucose tolerance only with ipragliflozin and dapagliflozin, implying improved insulin resistance and secretion. Taken together, these findings demonstrate that, although all SGLT2 inhibitors exert antidiabetic effects in type 2 diabetic mice, these pharmacologic effects might be slightly superior with the long-acting drugs, which are able to provide favorable blood glucose control throughout the day.

  11. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study.

    Science.gov (United States)

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R

    2013-08-01

    Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, (3)H-glucose, (14)C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0-2h] reductions of 35% and 43%, respectively; P Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition.

  12. Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

    Science.gov (United States)

    Ampudia-Blasco, Francisco Javier; Romera, Irene; Ariño, Bernat; Gomis, Ramón

    2017-01-01

    Background The recently published cardiovascular outcomes data for the first sodium–glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. Main text Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. Conclusion There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a “class effect”, which is also attributable to dapagliflozin and canagliflozin. PMID:28144158

  13. Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters

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    Lihong Chen

    2016-01-01

    Full Text Available The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na+/glucose cotransporter (SGLT1, although glucose transporter type 2 (GLUT2 may also play a role. The membrane potential of small intestinal epithelial cells (IEC is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca2+]cyt can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca2+ in IEC are regulated by cation channels and transporters, such as Ca2+ channels, K+ channels, Na+/Ca2+ exchangers, and Na+/H+ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes.

  14. Identification of a second substrate-binding site in solute-sodium symporters.

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    Li, Zheng; Lee, Ashley S E; Bracher, Susanne; Jung, Heinrich; Paz, Aviv; Kumar, Jay P; Abramson, Jeff; Quick, Matthias; Shi, Lei

    2015-01-02

    The structure of the sodium/galactose transporter (vSGLT), a solute-sodium symporter (SSS) from Vibrio parahaemolyticus, shares a common structural fold with LeuT of the neurotransmitter-sodium symporter family. Structural alignments between LeuT and vSGLT reveal that the crystallographically identified galactose-binding site in vSGLT is located in a more extracellular location relative to the central substrate-binding site (S1) in LeuT. Our computational analyses suggest the existence of an additional galactose-binding site in vSGLT that aligns to the S1 site of LeuT. Radiolabeled galactose saturation binding experiments indicate that, like LeuT, vSGLT can simultaneously bind two substrate molecules under equilibrium conditions. Mutating key residues in the individual substrate-binding sites reduced the molar substrate-to-protein binding stoichiometry to ~1. In addition, the related and more experimentally tractable SSS member PutP (the Na(+)/proline transporter) also exhibits a binding stoichiometry of 2. Targeting residues in the proposed sites with mutations results in the reduction of the binding stoichiometry and is accompanied by severely impaired translocation of proline. Our data suggest that substrate transport by SSS members requires both substrate-binding sites, thereby implying that SSSs and neurotransmitter-sodium symporters share common mechanistic elements in substrate transport.

  15. Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters.

    Science.gov (United States)

    Chen, Lihong; Tuo, Biguang; Dong, Hui

    2016-01-14

    The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na⁺/glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca(2+)]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca(2+) in IEC are regulated by cation channels and transporters, such as Ca(2+) channels, K⁺ channels, Na⁺/Ca(2+) exchangers, and Na⁺/H⁺ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes.

  16. Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition

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    Resham Raj Poudel

    2013-01-01

    Full Text Available The kidneys play a major role in glucose homeostasis through its utilization, gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs. The defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2, plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential of this approach. These studies indicate that inducing glycosuria by suppressing SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Because the mechanism of SGLT2 inhibition is independent of insulin secretion and sensitivity, these agents can be combined with other antidiabetic agents, including exogenous insulin. This class represents a novel therapeutic approach with potential for the treatment of both type 2 and type 1 diabetes.

  17. Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease.

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    Yanling Zhang

    Full Text Available Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2 leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally nephrectomised rats, a model of progressive chronic kidney disease (CKD that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.

  18. Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Raskin, Philip

    2013-07-01

    Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.

  19. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

    Science.gov (United States)

    Buschur, Elizabeth O.; Buse, John B.; Cohan, Pejman; Diner, Jamie C.; Hirsch, Irl B.

    2015-01-01

    OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication. RESEARCH DESIGN AND METHODS Cases identified incidentally are described. RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers. CONCLUSIONS SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes. PMID:26078479

  20. Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin: rationale and evidences.

    Science.gov (United States)

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    Sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are recently approved class of anti-hyperglycaemic agents for the treatment of type 2 diabetes mellitus (T2DM). SGLT-2I inhibits renal glucose reabsorption, thereby ensuing urinary glucose excretion in a dose-dependent manner. This caloric loss and osmotic diuresis, secondary to increased urinary glucose excretion, has a unique potential to counter insulin induced weight gain and fluid retention, with little potential of hypoglycemic exacerbation. Also, as these agents act independently of insulin secretion or action, they are effective even in long-standing diabetes with depleted β-cell reserve. Improvement in insulin sensitivity, as observed with SGLT-2I can also facilitate insulin action. Furthermore, significant reduction in total daily insulin dosage and reduction of body weight as observed during combination therapy renders SGLT-2I, a near-ideal partner to insulin. This review aims to evaluate the safety and efficacy of currently used SGLT-2I as an add-on to insulin therapy in the treatment of T2DM.

  1. Contrast sensitivity and higher-order aberrations in patients with astigmatism

    Institute of Scientific and Technical Information of China (English)

    ZHENG Guang-ying; ZHANG Wei-xia; DU Jun; ZHANG Jin-song; LIU Su-bing; NIE Xiao-li; ZHU Xiao-hong; TANG Xiu-xia; XIN Bao-li; MAI Zhi-bin

    2007-01-01

    Background Astigmatism is one of the most significant obstacles for achieving satisfactory visual function. This study was to evaluate the influence of astigmatism on contrast sensitivity (CS) and higher-order aberrations.Methods CS, accommodation response and wavefront aberration were measured in 113 patients with astigmatism,aged 18-36 years. Both single and binocular visual performance were examined under four lighting conditions: photopia,photopia with glare, scotopia and scotopia with glare respectively. Accommodation response was classified as normal,abnormal and low. The contribution of the power and axis of astigmatism to CS, accommodation response and wavefront aberration was analyzed.Results As the dioptric power of astigmatism increased, the loss of CS spatial frequency changed from high to intermediate, and then to low frequency. CS scores varied at different illuminance levels, descending in the following sequence: photopia, photopia with glare, scotopia, and scotopia with glare. However, the normal accommodation group showed better CS values under photopia with glare than without glare. The range of influenced direction of sine-wave gratings remained mostly at the meridian line of high dioptric power, which would be expanded when optical accommadation attenuated. The patients with symmetrical astigmatism got higher CS scores with binoculus vision than with dominant eye vision, while the patients with asymmetrical astigmatism did this only at scotopia with glare. Among higher-order aberrations, coma aberration, secondary coma aberration and the total higher order aberration were influenced by astigmatism, all of which rising with the power of astigmatism increased.Conclusions Reducing astigmatism might improve the performance of visual function. Not only the power of astigmatism should be cut down, but also the binocular axes should be made symmetrically.

  2. Canagliflozin-Induced Diabetic Ketoacidosis

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    Jessica Turner MSIV

    2016-08-01

    Full Text Available Introduction: Sodium-glucose co-transporter 2 (SGLT-2 inhibitors are relatively new antihyperglycemic agents that lower renal glucose reabsorption. They are used as adjunctive therapy to standard diabetes treatment. Case Report: We present the case of a 62-year-old woman with a past medical history of type 2 diabetes mellitus and sudden-onset diabetic ketoacidosis (DKA. Use of canagliflozin, a SGLT-2 inhibitor, was determined to be the cause of the DKA. The patient ultimately recovered after 5 days in the intensive care unit. She was changed to long- and short-acting insulins and instructed to avoid canagliflozin. Conclusion: Although SGLT-2 inhibitors are effective at lowering a patient’s hemoglobin A1C, physicians must be aware of the rare but dangerous potential adverse effect of inducing DKA. This article reports an illustrative case and presents a review of the literature.

  3. Addressing unmet medical needs in type 2 diabetes: a narrative review of drugs under development.

    Science.gov (United States)

    Mittermayer, Friedrich; Caveney, Erica; De Oliveira, Claudia; Gourgiotis, Loukas; Puri, Mala; Tai, Li-Jung; Turner, J Rick

    2015-01-01

    The global burden of type 2 diabetes is increasing worldwide, and successful treatment of this disease needs constant provision of new drugs. Twelve classes of antidiabetic drugs are currently available, and many new drugs are under clinical development. These include compounds with known mechanisms of action but unique properties, such as once-weekly DPP4 inhibitors or oral insulin. They also include drugs with new mechanisms of action, the focus of this review. Most of these compounds are in Phase 1 and 2, with only a small number having made it to Phase 3 at this time. The new drug classes described include PPAR agonists/modulators, glucokinase activators, glucagon receptor antagonists, anti-inflammatory compounds, G-protein coupled receptor agonists, gastrointestinal peptide agonists other than GLP-1, apical sodium-dependent bile acid transporter (ASBT) inhibitors, SGLT1 and dual SGLT1/SGLT2 inhibitors, and 11beta- HSD1 inhibitors.

  4. Canagliflozin-Induced Diabetic Ketoacidosis

    Science.gov (United States)

    Turner, Jessica; Begum, Tahmina; Smalligan, Roger D.

    2016-01-01

    Introduction: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are relatively new antihyperglycemic agents that lower renal glucose reabsorption. They are used as adjunctive therapy to standard diabetes treatment. Case Report: We present the case of a 62-year-old woman with a past medical history of type 2 diabetes mellitus and sudden-onset diabetic ketoacidosis (DKA). Use of canagliflozin, a SGLT-2 inhibitor, was determined to be the cause of the DKA. The patient ultimately recovered after 5 days in the intensive care unit. She was changed to long- and short-acting insulins and instructed to avoid canagliflozin. Conclusion: Although SGLT-2 inhibitors are effective at lowering a patient’s hemoglobin A1C, physicians must be aware of the rare but dangerous potential adverse effect of inducing DKA. This article reports an illustrative case and presents a review of the literature. PMID:27635409

  5. Canagliflozin: a novel and lsquo;glucuretic' approach for the treatment of type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ravindra S. Beedimani

    2014-06-01

    Full Text Available Canagliflozin is the first in a new class of glucose-lowering drugs, an oral inhibitor of sodium glucose cotransporter 2 (SGLT2. SGLT2, the transporter is responsible for reabsorbing the majority of glucose filtered by the kidney. SGLT2 inhibitors are a new class of oral drugs indicated only for the treatment of type 2 diabetes mellitus in conjunction with exercise and a healthy diet. They inhibit glucose re-absorption in the proximal renal tubules providing an insulin independent mechanism to lower blood glucose. Their use in clinical studies is associated with improved glycemic control, weight loss, and a low risk of hypoglycemia. They have been studied alone and with other medications including sulfonylureas, sitagliptin, and insulin. [Int J Basic Clin Pharmacol 2014; 3(3.000: 578-580

  6. Molecular Mechanisms of Glucose-Stimulated GLP-1 Secretion From Perfused Rat Small Intestine

    DEFF Research Database (Denmark)

    Kuhre, Rune E.; Frost, Charlotte R.; Svendsen, Berit;

    2015-01-01

    Glucose is an important stimulus for glucagon-like peptide 1 (GLP-1) secretion, but the mechanisms of secretion have not been investigated in integrated physiological models. We studied glucose-stimulated GLP-1 secretion from isolated perfused rat small intestine. Luminal glucose (5% and 20% w...... (20%) of the nonmetabolizable sodium-glucose transporter 1 (SGLT1) substrate, methyl-α-d-glucopyranoside (α-MGP), stimulated release, whereas the SGLT1 inhibitor phloridzin (luminally) abolished responses to α-MGP and glucose. Furthermore, in the absence of luminal NaCl, luminal glucose (20%) did...... not stimulate a response. Luminal glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (phloretin), but in contrast to SGLT1 inhibition, phloretin did not eliminate the response, and luminal glucose (20%) stimulated larger GLP-1 responses than luminal α-MGP in matched concentrations...

  7. Intestinal glucose absorption in calves as affected by different carbohydrate sources.

    Science.gov (United States)

    Klinger, S; Noci, B; Müller, K; Breves, G

    2013-04-01

    From numerous recent studies, it has been demonstrated that the development of the forestomach system in ruminants and thus microbial carbohydrate fermentation do not exclude the potential of the small intestines for enzymatic carbohydrate digestion and subsequent monosaccharide absorption. However, the role of regulatory nutritional factors is still under discussion. Therefore, we investigated the kinetic parameters of intestinal Na(+) -dependent glucose absorption and SGLT1 expression using isolated brush border membrane vesicles (BBMV) from the jejunum of 10-week-old calves kept on either hay, concentrate or corn silage-based diets in addition to milk replacer. While the maximal transport capacity was significantly higher for concentrate and corn silage-fed animals, SGLT1 protein expression was highest in BBMV isolated from hay-fed animals. This observation differs from the prevalent conception that induction of Na(+) -dependent glucose uptake via SGLT1 is based on an increased number of transporters at the brush border membrane.

  8. Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

    Directory of Open Access Journals (Sweden)

    Ampudia-Blasco FJ

    2017-01-01

    Full Text Available Francisco Javier Ampudia‑Blasco,1 Irene Romera,2 Bernat Ariño,3 Ramón Gomis4 1Endocrinology and Nutrition Department, Clinic University Hospital Valencia, Valencia, Spain; 2Eli Lilly and Company España, Madrid, Spain; 3Boehringer Ingelheim España, Barcelona, Spain; 4Endocrinology Department, Hospital Clinic Barcelona, Barcelona, Spain Background: The recently published cardiovascular outcomes data for the first sodium–glucose cotransporter 2 (SGLT2 inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. Main text: Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. Conclusion: There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a “class effect”, which is also attributable to dapagliflozin and canagliflozin. Keywords: cardiovascular, outcome studies, SGLT2 inhibitors, empagliflozin, dapagliflozin, canagliflozin

  9. Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients

    Directory of Open Access Journals (Sweden)

    Eugenio Cersosimo

    2014-03-01

    Full Text Available The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2, became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties (“second-generation” were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors. Conclusion: Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.

  10. Use of sodium-glucose cotransporter 2 inhibitors in older patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kambara, Takahiro; Shibata, Rei; Osanai, Hiroyuki; Nakashima, Yoshihito; Asano, Hiroshi; Sakai, Kazuyoshi; Murohara, Toyoaki; Ajioka, Masayoshi

    2017-09-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. The mean age of the patients was 73.7 ± 10.0 years. During the follow-up period (mean 289.3 days), there was no event associated with oral administration of SGLT2 inhibitors. These drugs significantly lowered fasting blood glucose and glycosylated hemoglobin levels at 6 months, and did not affect the creatinine level, blood urea nitrogen/creatinine ratio or estimated glomerular filtration rate during treatment. Although the treatment significantly increased hemoglobin and hematocrit levels, it did not affect the ultrasonographically determined diameter of the inferior vena cava, and no signs of intravascular collapse were observed. Changes in brain natriuretic peptide levels during the follow-up period were assessed in 78 patients with a brain natriuretic peptide level exceeding the normal upper limit before treatment with SGLT2 inhibitors. The brain natriuretic peptide levels significantly decreased after 6 months of treatment. In older Japanese patients with diabetes, treatment with SGLT2 inhibitors for 6 months exerted a favorable hypoglycemic effect, while no sign of dehydration was observed. Geriatr Gerontol Int 2017; ••: ••-••. © 2017 Japan Geriatrics Society.

  11. Emerging roles of sodium-glucose cotransporter 2 inhibitors in cardiology.

    Science.gov (United States)

    Tanaka, Atsushi; Node, Koichi

    2017-03-01

    The ultimate goal of treatment in people with diabetes mellitus is to prevent development of cardiovascular (CV) disease, resulting in prolongation of healthy life expectancy. Although impaired glycemic metabolism has a central role in its pathology, a number of studies have demonstrated that remedy for its imbalance cannot necessarily be accomplished as a therapeutic goal. A comprehensive medical approach against multi-factorial pathologies in diabetes, such as insulin resistance, obesity, hypertension, and dyslipidemia, in addition to diet and exercise therapy should be rather performed in the routine clinical setting. Along with such conceptual transition, what is required in anti-diabetes agents has also changed, and several anti-diabetes agents have been newly placed on the market in this decade. Such agents are required to undergo global pre- or post-marketing clinical trials assessing CV safety. A growing body of clinical evidence from those trials is now accumulating, and empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has first demonstrated significant risk reduction, relative to placebo, in CV death, overall mortality, and hospitalization for worsened heart failure in high-risk patients with diabetes mellitus. An SGLT2 inhibitor is a unique glucose-lowering agent and at the same time has multifaceted effects on hemodynamic and metabolic parameters beyond glycemic control. A major mode of action of SGLT2 inhibitors appears to be 'glycosuria' and 'natriuresis,' leading to amelioration of systemic glycemic homeostasis and potential cardio-renal protection. However, the precise mechanisms by which SGLT2 inhibitors affect benefits on the CV systems are yet to be fully elucidated. Thus, although we are now facing several unanswered concerns lurking behind the successful trial, SGLT2 inhibitors surely play several important roles in high-quality management of not only diabetes, but also CV medicine. This review summarizes our current

  12. Sodium-glucose cotransporter-2 inhibition and the insulin: Glucagon ratio: Unexplored dimensions

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available The sodium-glucose cotransporter 2 (SGLT-2 inhibitors are a novel class of glucose-lowering drugs which act by inhibiting the reabsorption of filtered glucose from the kidneys. Their effect on insulin and glucagon levels has recently been studied but is not fully explained. This communication proposes various hypotheses: A direct effect of SGLT-2 inhibition on the alpha cell receptors, a paracrine or intra-islet mediated effect on alpha cell sensitivity to glucose, and a calorie restriction mimetic action, to explain the impact of these drugs on the insulin glucagon ratio.

  13. Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin.

    Science.gov (United States)

    Adachi, Junichiro; Inaba, Yuusuke; Maki, Chisato

    2017-01-01

    Diabetic ketoacidosis is characterized by hyperglycemia, anion-gap acidosis, and increased plasma ketones. After the resolution of hyperglycemia, persistent diuresis is rare. We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia. Physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with SGLT2 inhibitors.

  14. Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin

    Science.gov (United States)

    Adachi, Junichiro; Inaba, Yuusuke; Maki, Chisato

    2017-01-01

    Diabetic ketoacidosis is characterized by hyperglycemia, anion-gap acidosis, and increased plasma ketones. After the resolution of hyperglycemia, persistent diuresis is rare. We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia. Physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with SGLT2 inhibitors. PMID:28090050

  15. Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate diet

    OpenAIRE

    Hayami, Tomohide; KATO, Yoshiro; Kamiya, Hideki; Kondo, Masaki; Naito, Ena; Sugiura, Yukako; Kojima, Chika; Sato, Sami; Yamada, Yuichiro; Kasagi, Rina; Ando, Toshihito; Noda, Saeko; Nakai, Hiromi; Takada, Eriko; Asano, Emi

    2015-01-01

    We present a case of a 32-year-old diabetic woman with Prader–Willi syndrome who developed severe ketoacidosis caused by a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a novel class of antihyperglycemic agents, during a strict low-carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was relatively low, though laboratory evaluations showed severe ketoacidosis. This is the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to not only pay attention whe...

  16. Invokana (Canagliflozin) as a dual inhibitor of acetylcholinesterase and sodium glucose co-transporter 2: advancement in Alzheimer's disease- diabetes type 2 linkage via an enzoinformatics study.

    Science.gov (United States)

    Rizvi, Syed M D; Shakil, Shahnawaz; Biswas, Deboshree; Shakil, Shazi; Shaikh, Sibhghatulla; Bagga, Paramdeep; Kamal, Mohammad A

    2014-04-01

    Acetylcholinesterase (AChE) is a primary target for Alzheimer's therapy while recently sodium glucose cotransporter 2 (SGLT2) has gained importance as a potential target for Type 2 Diabetes Mellitus (T2DM) therapy. The present study emphasizes the molecular interactions between a new Food and Drug Administration (FDA) approved antidiabetic drug 'Invokana' (chemically known as Canagliflozi