The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin’s osmotic diuresis mechanism, patients’ serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=−0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e’ tended to decrease (β1=−0.382, p=0.13, LRA). Compared to the baseline, E/e’ was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e’ group (E/e’≥10, n=34), E/e’ decreased significantly (β1=−0.63, p<0.05, LRA). ΔE/e’ was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e’ in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function

Hepatitis C Virus Induced a Novel Apoptosis-Like Death of Pancreatic Beta Cells through a Caspase 3-Dependent Pathway

Epidemiological and experimental studies have suggested that Hepatitis C virus (HCV) infection is associated with the development of type 2 diabetes. Pancreatic beta cell failure is central to the progression of type 2 diabetes. Using virus infection system, we investigate the influence of HCV infection on the fate of the insulinoma cell line, MIN6. Our experiments demonstrate that the HCV virion itself is indispensable and has a dose- and time-dependent cytopathic effect on the cells. HCV infection inhibits cell proliferation and induces death of MIN6 cells with apoptotic characteristics, including cell surface exposure of phosphatidylserine, decreased mitochondrial membrane potential, activation of caspase 3 and poly (ADP-ribose) polymerase, and DNA fragmentation in the nucleus. However, the fact that HCV-infected cells exhibit a dilated, low-density nucleus with intact plasma and nuclear membrane indicates that a novel apoptosis-like death occurs. HCV infection also causes endoplasmic reticulum (ER) stress. Further, HCV RNA replication was detected in MIN6 cells, although the infection efficiency is very low and no progeny virus particle generates. Taken together, our data suggest that HCV infection induces death of pancreatic beta cells through an ER stress-involved, caspase 3-dependent, special pathway

Auditory enhancement of visual searches for event scenes

Increasing research has revealed that uninformative spatial sounds facilitate the early processing of visual stimuli. This study examined the crossmodal interactions of semantically congruent stimuli by assessing whether the presentation of event-related characteristic sounds facilitated or interfered with the visual search for corresponding event scenes in pictures. The search array consisted of four images: one target and three non-target pictures. Auditory stimuli were presented to participants in synchronization with picture onset using three types of sounds: a sound congruent with a target, a sound congruent with a distractor, or a control sound. The control sound varied across six experiments, alternating between a sound unrelated to the search stimuli, white noise, and no sound. Participants were required to swiftly localize a target position while ignoring the sound presentation. Visual localization resulted in rapid responses when a sound that was semantically related to the target was played. Furthermore, when a sound was semantically related to a distractor picture, the response times were longer. When the distractor-congruent sound was used, participants incorrectly localized the distractor position more often than at the chance level. These findings were replicated when the experiments ruled out the possibility that participants would learn picture-sound pairs during the visual tasks (i.e., the possibility of brief training during the experiments). Overall, event-related crossmodal interactions occur based on semantic representations, and audiovisual associations may develop as a result of long-term experiences rather than brief training in a laboratory

Goal-directed facilitation by sounds in the search for dynamic action scenes

Research on search tasks has shown that there are crossmodal interactions between visually and auditorily congruent stimuli. While a goal-directed strategy typically improves target localization, the presence of distractor sounds can delay visual search time for action scene images when the event name is provided beforehand. This study aims to investigate the role of goal-directed control in these semantically crossmodal interactions. The experiments involved a search array comprising four different video stimuli played simultaneously, with one of three types of sounds accompanying the onset of the search array: a sound congruent with the target, a sound congruent with a distractor, or a control sound. Participants were tasked with localizing a target among the four videos while ignoring the others. Across all three experiments, the results indicated the absence of auditory interference, suggesting that semantically distractor-congruent sounds did not significantly impact search performance. These findings differ from previous studies on action scene search, which reported the presence of auditory interference. The contrasting results observed in this study may be attributed to the use of action scene videos, which contain inherent spatiotemporal variations of actions. The activation of goal-directed control is likely more pronounced when identifying discrete scene features such as physical movements rather than static and isolated single-frame information. Other factors, such as the synchronization of audiovisual stimuli and experience with audiovisual stimuli, may also influence goal-directed control in semantically crossmodal interactions

Synergistic effects of pCO2 and iron availability on nutrient consumption ratio of the Bering Sea phytoplankton community

Little is known concerning the effect of CO2 on phytoplankton ecophysiological processes under nutrient and trace element-limited conditions, because most CO2 manipulation experiments have been conducted under elements-replete conditions. To investigate the effects of CO2 and iron availability on phytoplankton ecophysiology, we conducted an experiment in September 2009 using a phytoplankton community in the iron limited, high-nutrient, low-chlorophyll (HNLC) region of the Bering Sea basin. Carbonate chemistry was controlled by the bubbling of the several levels of CO2 concentration (180, 380, 600, and 1000 ppm) controlled air, and two iron conditions were established, one with and one without the addition of inorganic iron. We demonstrated that in the iron-limited control conditions, the specific growth rate and the maximum photochemical quantum efficiency (F-v/F-m) of photosystem (PS) II decreased with increasing CO2 levels, suggesting a further decrease in iron bioavailability under the high-CO2 conditions. In addition, biogenic silica to particulate nitrogen and biogenic silica to particulate organic carbon ratios increased from 2.65 to 3.75 and 0.39 to 0.50, respectively, with an increase in the CO2 level in the iron-limited controls. By contrast, the specific growth rate, F-v/F-m values and elemental compositions in the iron-added treatments did not change in response to the CO2 variations, indicating that the addition of iron canceled out the effect of the modulation of iron bioavailability due to the change in carbonate chemistry. Our results suggest that high-CO2 conditions can alter the biogeochemical cycling of nutrients through decreasing iron bioavailability in the iron-limited HNLC regions in the future

Phytoplankton community response to Fe and temperature gradients in the NE (SERIES) and NW (SEEDS) subarctic Pacific Ocean

Ship-board iron enrichment bottle experiments were carried out with samples collected at the mesoscale iron fertilization experimental site (SERIES) in the subarctic NE Pacific in the summer of 2002. Samples were collected on Day 14 of the experiment outside the patch that was in a typical high nitrate and low chlorophyll (HNLC) condition. The iron concentration in the incubation bottles ranged from 0.1 to 2.0 nM by adding FeCl3 solution. The increase in chlorophyll-a (chl-a) in the micro (>10 μm) and nano-sized (2–10 μm) fraction was observed as a function of the added iron. Chl-a in the pico-sized fraction (0.7–2 μm) showed no increase with time. Nitrate and silicate were exhausted in the Fe-amended bottles, while those in the control bottle remained at the end of incubation. The relative consumption ratio of silicate to nitrate for the control bottles was significantly higher than that for the Fe-amended bottles. As a hyperbolic relation was found between iron concentration and the rate of increase in Chl-a (specific growth rate) for the micro and nano-sized fraction, the Monod equation was fit to obtain a maximum growth rate (μmax) and a half-saturation constant for iron (KFe). The μmax values were 0.72 and 0.48 d−1 for the micro and nano-sized fraction, respectively. The KFe values were 0.10 and 0.08 nM for the micro and nano-sized fraction, respectively. The μmax agreed with the rate of increase in Chl-a observed in situ for the mesoscale iron fertilization experiment. The μmax value for micro-sized fraction at 12 °C was half of that in the western subarctic Pacific Ocean (SEEDS experiment in 2001), indicating the Chl-a increase rate (potential growth rate) after iron enrichment was much higher in SEEDS than that in SERIES. The KFe values were much lower than that in SEEDS, suggesting that the phytoplankton community in the NE subarctic Pacific Ocean acclimates to a lower ambient Fe concentration. This difference in KFe between SERIES (NE) and SEEDS (NW) may reflect the previously suggested gradient in Fe flux to the subarctic Pacific Ocean. A temperature gradient was also applied to investigate the effect of temperature on the growth response of the phytoplankton community. No obvious effect of temperature increase to 16 °C was found in SERIES, while μmax and KFe changed significantly with temperature in SEEDS

Impacts of elevated CO2 on particulate and dissolved organic matter production: microcosm experiments using iron-deficient plankton communities in open subarctic waters

Response of phytoplankton to increasing CO2 in seawater in terms of physiology and ecology is key to predicting changes in marine ecosystems. However, responses of natural plankton communities especially in the open ocean to higher CO2 levels have not been fully examined. We conducted CO2 manipulation experiments in the Bering Sea and the central subarctic Pacific, known as high nutrient and low chlorophyll regions, in summer 2007 to investigate the response of organic matter production in iron-deficient plankton communities to CO2 increases. During the 14-day incubations of surface waters with natural plankton assemblages in microcosms under multiple pCO2 levels, the dynamics of particulate organic carbon (POC) and nitrogen (PN), and dissolved organic carbon (DOC) and phosphorus (DOP) were examined with the plankton community compositions. In the Bering site, net production of POC, PN, and DOP relative to net chlorophyll-a production decreased with increasing pCO2. While net produced POC:PN did not show any CO2-related variations, net produced DOC:DOP increased with increasing pCO2. On the other hand, no apparent trends for these parameters were observed in the Pacific site. The contrasting results observed were probably due to the different plankton community compositions between the two sites, with plankton biomass dominated by large-sized diatoms in the Bering Sea versus ultra-eukaryotes in the Pacific Ocean. We conclude that the quantity and quality of the production of particulate and dissolved organic matter may be altered under future elevated CO2 environments in some iron-deficient ecosystems, while the impacts may be negligible in some systems