The efficacy of incretin therapy in patients with type 2 diabetes undergoing hemodialysis

BACKGROUND: Although incretin therapy is clinically available in patients with type 2 diabetes undergoing hemodialysis, no study has yet examined whether incretin therapy is capable of maintaining glycemic control in this group of patients when switched from insulin therapy. In this study, we examined the efficacy of incretin therapy in patients with insulin-treated type 2 diabetes undergoing hemodialysis. METHODS: Ten type 2 diabetic patients undergoing hemodialysis received daily 0.3 mg liraglutide, 50 mg vildagliptin, and 6.25 mg alogliptin switched from insulin therapy on both the day of hemodialysis and the non-hemodialysis day. Blood glucose level was monitored by continuous glucose monitoring. After blood glucose control by insulin, patients were treated with three types of incretin therapy in a randomized crossover manner, with continuous glucose monitoring performed for each treatment. RESULTS: During treatment with incretin therapies, severe hyperglycemia and ketosis were not observed in any patients. Maximum blood glucose and mean blood glucose on the day of hemodialysis were significantly lower after treatment with liraglutide compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. The standard deviation value, a marker of glucose fluctuation, on the non-hemodialysis day was significantly lower after treatment with liraglutide compared with treatment with insulin and alogliptin (p < 0.05), but not with vildagliptin. Furthermore, the duration of hyperglycemia was significantly shorter after treatment with liraglutide on both the hemodialysis and non-hemodialysis days compared with treatment with alogliptin (p < 0.05), but not with vildagliptin. CONCLUSIONS: The data presented here suggest that patients with type 2 diabetes undergoing hemodialysis and insulin therapy could be treated with incretin therapy in some cases

Effects of clozapine and N-desmethylclozapine on synaptic transmission at hippocampal inhibitory and excitatory synapses

Clozapine is the first atypical antipsychotic, and improves positive and negative symptoms of many patients with schizophrenia resistant to treatment with other antipsychotic agents. Clozapine induces minimal extrapyramidal side effects, but is more often associated with seizures. A large number of studies have been conducted to elucidate pharmacological profiles of clozapine and its major active metabolite, N-desmethylclozapine (NDMC). However, there are only a limited number of electrophysiological studies examining their effects on synaptic transmission. In this study, we examined effects of clozapine and NDMC on synaptic transmission by measuring inhibitory and excitatory postsynaptic currents in rat cultured hippocampal neurons. We found that clozapine and NDMC have qualitatively similar actions. They depressed the inhibitory transmission at 1-30 μM, and the excitatory transmission at 30 μM, the former being much more sensitive. The depression of IPSCs by 30 μM of these drugs was associated with an increase in the paired-pulse ratio. The GABA-induced currents were suppressed by these drugs, but less sensitive than IPSCs. The AMPA-induced currents were slightly potentiated by these drugs at 30 μM. At 30 μM, clozapine and NDMC slightly suppressed Ca2+ and Na+ channels. These results strongly suggest that clozapine and NMDC depress the inhibitory synaptic transmission mainly by antagonizing postsynaptic GABAA receptors, but at higher concentrations additionally by acting on presynaptic site, possibly in part through inhibition of presynaptic Ca2+ and Na+ channels. Preferential depression of inhibitory synaptic transmission by clozapine and NDMC might contribute to therapeutic actions and/or side-effects of clozapine. © 2011 Elsevier B.V. All rights reserved

Two times lowering of lake water at around 48 and 38 ka, caused by possible earthquakes, recorded in the Paleo-Kathmandu lake, central Nepal Himalaya

Sedimentary facies and micro-fossil analyses, and AMS[14]C dating were performed in order to reveal the water-level fall events and draining process of the lake (Paleo-Kathmandu Lake) that existed in the past in the Central Nepal Himalaya. The sedimentary facies change from the lacustrine Kalimati Formation to the deltaic Sunakothi Formation in the southern and central Kathmandu basin, and the abrupt and prominent increase of phytoliths Bambusoideae and Pediastrum, and contemporaneous decrease of sponge spicule and charcoal grains around 48 and 38 ka support the lowering of water level at these times. According to the pollen analysis, both events occurred under rather warm and wet climate, thus supporting that they were triggered by tectonic cause and not by climate change. The first event might be linked to a possible occurrence of a large earthquake with an epicenter in the vicinity of the Paleo-Kathmandu Lake. The occurrence of a mega landslide in Langtang area close to the north of the Kathmandu Valley producing pseudotachylite dated at 51 ± 13 ka could be linked to this earthquake. Finally, the water was completely drained out from the remnant lake at the central part of the Kathmandu basin by ca.12 ka

Photochemical control of membrane raft organization

Controllable membrane phase separation through the action of a synthetic photoresponsive amphiphile is reported. We studied multi-component giant vesicles formed from a ternary lipid mixture of saturated and unsaturated phospholipid and cholesterol together with the photoresponsive amphiphile. A change in the conformation of the photoresponsive amphiphile can switch membrane lateral segregation in a reversible manner. Cis-isomerization induces lateral phase separation in one-phase membranes or produces additional lateral domains in two-phase membranes. Membranes that are close to miscibility boundary show high photo-responsiveness. This is the first report on the reversible control of membrane lateral segregation triggered by a conformational change in a membrane-constituting molecule. These findings may lead to new methods for controlling membrane self-organization such as raft engineering

Observations of schooling behaviour in the oval squid Sepioteuthis lessoniana in coastal waters of Okinawa Island

The schooling behaviour of the oval squid Sepioteuthis lessoniana was observed over 4 summers at 3 observation sites in the coastal waters of Okinawa Island, Ryukyu Archipelago, Japan. During this field study, 3 static appearances (belt, ball and sheet shape) and 2 transitional appearances (high and low density) were noted, recorded and described. In addition to formations, a member of S. lessoniana schools also displayed particular and repeated behavioural patterns such as vanguard and intimidating display. The 3 observation sites were tropical coral reefs near the coastline at a depth of 1 to 15 m on an average. All participating observers snorkelled and were equipped with various underwater digital video and photographic cameras. The schools observed consisted of 8 to over 100 members with a wide range of body sizes. Despite these biological and locational differences, both static and transitional appearances were consistently observed with equally consistent individual behavioural patterns. There have been studies on related species, Sepioteuthis sepioidea, at the San Blas Islands along the Caribbean coast of eastern Panama, and the same species, S. lessoniana, at a different geographical location, Casuarina Beach on Lizard Island, Australia. The findings of this study are consistent with those reported previously, with some notable differences

Photochemical control on morphologies of a cell-sized synthetic vesicle

By using a synthetic photosensitive amphiphile containing azobenzene (KAON12), we developed a method for the photo-manipulation of lipid membrane morphology, in which the shape of a vesicle can be switched by light. Cell-sized liposomes are prepared from KAON12 and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We conducted real-time observations of vesicular transformation in the photo-sensitive liposome by phase-contrast microscopy, and found that membrane budding transitions could be controlled by light. These transformations can be interpreted in terms of the change in the effective membrane surface area due to photoisomerization of the constituent molecules. We discuss the mechanism by considering the elastic free energy of the membranes

Comparison of analgesia and akinesia between sub-Tenon’s capsule anesthesia and trans-Tenon’s capsule retrobulbar anesthesia in vitrectomy

Objectives: We compared the effects of sub-Tenon’s capsule anesthesia (STA) and trans-Tenon’s capsule retrobulbar anesthesia (TTRBA) in 68 patients with epiretinal membrane. Methods: Either STA or TTRBA was induced with 3 mL of lidocaine (2%) before vitrectomy combined with phacoemulsification and aspiration (phacovitrectomy). Akinesia was evaluated by range of eye movement (ROEM) in upward, downward, nasal, and temporal directions at 4, 10, and 30 minutes after injection. Analgesia was evaluated with a visual analogue pain score, which ranged from 0 to 10. Results: The mean cumulative ROEMs were 1.44±1.02 corneal diameters (CDs) at 4 minutes, 0.55±0.76 CDs at 10 minutes, and 0.26±0.33 CDs at 30 minutes in patients who received STA; these values were 0.39±0.35 CDs at 4 minutes, 0.22±0.30 CDs at 10 minutes, and 0.13±0.29 CDs at 30 minutes in patients who received TTRBA. At both 4 and 10 minutes, the cumulative ROEMs in all directions, as well as the temporal ROEMs, were significantly larger in patients who received STA than in patients who received TTRBA. Pain scores did not significantly differ between groups at any time point. Conclusions: STA and TTRBA produced identical degrees of analgesia, but akinesia was slower in patients who received STA. TTRBA might be preferable for patients undergoing brief vitrectomy