Hypothalamic brain-derived neurotrophic factor regulates glucagon secretion mediated by pancreatic efferent nerves.

Understanding the molecular mechanism of the regulation of glucagon secretion is critical for treating the dysfunction of α cells observed in diabetes. Glucagon-like peptide (GLP)-1 analogues reduce plasma glucagon and are assumed to contribute to their action to lower blood glucose. It has previously been demonstrated that the central administration of brain-derived neurotrophic factor (BDNF) improves glucose metabolism by a mechanism independent of feeding behaviour in obese subjects. Using male rats, we examined whether BDNF influences glucagon secretion from α cells via the the central nervous system. We investigate whether: (i) the central infusion of BDNF stimulates glucagon and/or insulin secretion via the pancreatic efferent nerve from the hypothalamus; (ii) the intraportal infusion of GLP-1 regulates glucose metabolism via the central and peripheral nervous system; and (iii) BDNF receptor and/or BDNF-positive fibres are localised near α cells of islets. The portal glucagon level decreased with the central administration of BDNF (n = 6, in each; P < 0.05); in contrast, there was no significant change in portal insulin, peripheral glucagon and insulin levels with the same treatment. This reduction of glucagon secretion was abolished by pancreatic efferent denervation (n = 6, in each; P < 0.05). In an immunohistochemical study, pancreatic α cells were stained specifically with BDNF and tyrosine-related kinase B, a specific receptor for BDNF, and α cells were also co-localised with BDNF. Moreover, intraportal administration of GLP-1 decreased glucagon secretion, as well as blood glucose, whereas it increased the BDNF content in the pancreas; these effects were inhibited with the central infusion of BDNF antibody (n = 6, in each; P < 0.05). BDNF and GLP-1 affect glucose metabolism and modulate glucagon secretion from pancreatic α cells via the central and peripheral nervous systems.

Effect of supplementation of dry cat food with D,L-methionine and ammonium chloride on struvite activity product and sediment in urine.

Feeding dry foods supplemented with urine acidifier (D,L-methionine (Met) or ammonium chloride) decreased urinary pH and struvite activity product in clinically normal cats. As a result, the number of struvite crystals in urine was greatly reduced. Supplementation with 3% Met but not 1% Met caused decrease in the urinary concentration of sediment, which resulted from a reduction in the HCl-soluble fraction. The concentration of HCl-insoluble sediment was not affected by supplementation with the urine acidifier.

Enhanced antitumor activity in mice after administration of thermosensitive liposome encapsulating cisplatin with hyperthermia.

The antitumor effect of cisplatin-(CDDP)-encapsulated thermosensitive large unilamellar liposome (ThLip) administration with hyperthermia (HT) was examined in mice bearing Meth A fibrosarcoma. The tumor Pt levels after ThLip administration were increased in response to HT. The targeting index was approximately 3. The antitumor activity of ThLip + HT, as measured by tumor growth delay or tumor weight inhibition, was larger than that of ThLip without HT or a solution with or without HT. The CDDP dose in ThLip + HT to give equivalent tumor growth delay in solution (40 micrograms/mouse) + HT was about 10 micrograms/mouse, and therefore the targeted drug delivery enhancement ratio was about 4. The ratio correlates with the targeting index. The blood urea nitrogen level, as an indicator of CDDP nephrotoxicity, was increased 7 days after the administration of ThLip (40 micrograms CDDP/mouse) with HT. However, this blood urea nitrogen level rise was independent of the activity enhancement by the liposome. These findings suggest that the HT combined CDDP delivery system using ThLip can decrease the effective CDDP dose, thereby increasing its therapeutic index.

[A case of myonephropathic metabolic syndrome treated with limb washout using a roller pump and cell saver].

We operated on a 65 year old male for the saddle embolism presenting the signs of MNMS. Before the reperfusion of the ischemic limbs which were successfully embolectomized with the use of Fogarty catheter, we performed limb washout using roller pump and cell saver. The washout was done in the high flow and large volume by the roller pump. The red blood cells in the efflux were saved using cell saver and retransfused to the patient. The patient recovered without deterioration of MNMS. The limb washout was effective for the prevention of the deterioration of MNMS.