Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-α-induced optic nerve degeneration

Brain-derived neurotrophic factor (BDNF) is a potent survival and developmental factor that is regulated by cyclic AMP-response element binding protein (CREB) and has a protective effect against retinal ganglion cell (RGC) death. However, the effect of BDNF on the optic nerve axonal degeneration remains to be examined. In this study, we show that intravitreal injection of tumor necrosis factor (TNF)-α induces transient increases in phosphorylated-CREB (p-CREB) and BDNF expression in the optic nerve. Administration of exogenous BDNF further increased the p-CREB and endogenous BDNF level and exerted a neuroprotective effect against TNF-α-induced axonal loss. The increases in BDNF mRNA and protein induced by TNF-α were inhibited significantly by a CRE decoy oligonucleotide. The protective effect of exogenous BDNF on axons was also inhibited by the CRE decoy oligonucleotide. These results suggest that the protective effect of exogenous BDNF may be associated with increases in CREB phosphorylation and endogenous BDNF in the optic nerve.     

Elental prevented and reduced oral mucositis during chemotherapy in patients esophageal cancer

Stomatitis is a side effect caused frequently by chemotherapy in patients with esophageal cancer, but a standard treatment for it has not been established. Reactive oxygen species are known to be among the causes of stomatitis induced by chemotherapy or radiotherapy, and some reports suggest that their influences might be reduced by the oral supplementation of glutamine. Elental? is one of the widely-used nutritional supplements, and its pack contains 1, 932 mg of L-glutamine (an especially high amount.). Therefore, we examined the preventive or reducing effects Elental? mey have on oral mucositis. Fifteen patients with esophageal cancer received chemotherapy, six of whom had grade one oral mucositis. All of those six patients entered the investigation, and seven courses of Elental? were administered. After seven courses, all six patients oral mucositis declined from grade 1 to grade 0. This result suggests that Elental? has preventive or reducing effects on oral mucositis.     

A case of intractable hepatic encephalopathy successfully treated by oral administration of vancomycin hydrochloride, with subsequent improvement of hepatic function reserve enabling transcatheter arterial chemoembolization against hepatocellular carcinoma

We report a case of an 80-year-old male who suffered from intractable hepatic encephalopathy and hepatocellular carcinoma( HCC), associated with hepatitis type C-related liver cirrhosis. He was unable to receive HCC treatment due to the deterioration of his liver. His hepatic encephalopathy was resistant to oral administration of laxatives, lactulose, and kanamycin sulfate, etc. His blood ammonia concentration averaged about 130 mg/dL, and often exceeded 200 mg/dL(normal range: <80 mg/dL). Later, an oral administration of vancomycin hydrochloride, 0. 5 g once every 3 days, was initiated. Soon after ward, his blood ammonia concentration declined to the normal range(about 50 mg/dL), and the clinical symptoms of hepatic encephalopathy showed a remarkable improvement. By the continuation of vancomycin administration, the normalization of his state of consciousness was achieved, improving his quality of life, and his activities of daily living. Three months after beginning treatment, he was able to receive transcatheter arterial chemoembolization for the treatment of HCC, because his liver function reserve improved(Child-Pugh score decreased from 10 to 7).     

Gallates of isoorientin and (2S)-1,2-propanediol glucoside from the leaves of Schoepfia jasminodora

From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Schoepfia jasminodora collected from Okinawa Island, two new galloyl esters and 15 known compounds were isolated. The structures of the new compounds were elucidated by spectroscopic analysis to be isoorientin 4″-O-gallate and (2S)-1,2-propanediol 1-O-β-D: -glucopyranoside 6'-O-gallate. The compounds possessing galloyl or cathechol moieties showed equal radical scavenging activity.     

Chronopharmacological assessment identified GLUT4 as a factor responsible for the circadian variation of the hypoglycemic effect of tolbutamide in rats

The circadian relationship between the pharmacokinetics and pharmacodynamics of tolbutamide in rats was analyzed using a compartment model. The basal concentration of plasma glucose had a circadian rhythm with the acrophase at 15:19 h. After intravenous administration of tolbutamide at 06:00, 14:00, or 18:00 h, the hypoglycemic effect showed a circadian variation, with the greatest effect at 18:00 h and the lowest effect at 06:00 h. The time courses of unbound tolbutamide concentration in plasma after intravenous administration were predicted using the model-estimated total concentration of tolbutamide and the albumin concentration and resulted in profiles that did not vary with the time of administration. Significant low insulin resistance was observed at 18:00 h to i.v. glucose and insulin loads. There was no obvious time dependency in the expression of glucose transporter 4 (GLUT4) in epididymal adipocytes. The hypoglycemic rate estimated from the plasma glucose concentration was described by the conventional pharmacokinetic-pharmacodynamic model with an effect compartment. The time courses of theoretical signals in the effect compartment described the observed circadian changes in the increased expression profile of GLUT4 normalized by the increased plasma insulin (IRI) concentration (ΔGLUT4/ΔIRI) after dosing. Thus, the time dependency in glucose uptake is responsible for the circadian variation of the hypoglycemic effect of tolbutamide.     

The expressions of claudin‐1 and E‐cadherin in junctional epithelium

Fujita T, Hayashida K, Shiba H, Kishimoto A, Matsuda S, Takeda K, Kawaguchi H, Kurihara H. The expressions of claudin‐1 and E‐cadherin in junctional epithelium. J Periodont Res 2010; 45: 579–582. © 2010 John Wiley & Sons A/S Background and Objective: The epithelium provides an important barrier against microbial invasion. Tight junction structural proteins called claudins are known to contribute to the epithelial cell barrier. Junctional epithelium is located at a strategically important interface between gingival sulcus and is interconnected by desmosomes and gap junctions, but not by tight junctions. Although claudins are tight junction‐associated proteins, they are also expressed in the epithelium despite its lack of tight junctions in invertebrates. Therefore, claudins may play an important role in junctional epithelium without tight junctions. E‐cadherin is a key molecule in the formation of adherence junctions and desmosomes. In the present study, we aimed to investigate the expressions of claudin‐1,claudin‐3, claudin‐7 and E‐cadherin in the junctional epithelium of Fischer 344 rats. Material and Methods: Gingival tissues from Fischer 344 rats were analyzed by immunohistochemical staining for claudin‐1, claudin‐3, claudin‐7, and E‐cadherin. Results: Intense staining for claudin‐1 and E‐cadherin were observed in the junctional epithelium. In contrast to claudin‐1, claudin‐3 was mainly expressed in oral gingival epithelium and claudin‐7 could not be detected on immunohistochemical analysis of the rat gingiva. Conclusion: These data suggest that claudin‐1 and E‐cadherin exist in the junctional epithelium and may play an important role in epithelial barrier function.