Tendon chitosan tubes covalently coupled with synthesized laminin peptides facilitate nerve regeneration in vivo

We have developed tendon chitosan tubes having the ability to bind peptides covalently, and the effectiveness of laminin peptides coupled to these tubular wall on nerve regeneration was examined in vivo. Bridge graft implantation (15 mm) into the sciatic nerve of SD rats was carried out using chitosan tubes having a triangular cross section containing either covalently bound intact laminin or the laminin peptides CDPGYIGSR or CSRARKQAASIKVAVSAD or being nontreated (N = 20 in each group). As a control, isografting (N = 5) was carried out. Three rats in each experimental group were sacrificed for histology observations after 1, 2, 4, 6, and 8 weeks. The total area of regenerating tissue in the tube and the length of the area where regenerating tissue attached to the inner surface of the tube were measured. In five rats from each experimental and control group, the latency quotient between the implanted and the nontreated site was determined 12 weeks after implantation. Furthermore, the percentage of myelinated axon area was measured at a 10-mm distance from the distal anastomosed site. Histological findings suggest that the immobilized laminin, confirmed by immunostaining as long as 12 weeks postoperatively, as well as laminin oligopeptides may effectively assist nerve tissue extension. According to statistical analysis of the percentage neural tissue found in relation to evoked action potentials, the sequential treatments with YIGSR first followed by IKVAV matched the effectiveness of intact laminin in enhancing nerve regeneration. However, when compared with that after isografting, the enhancement of regenerated axon growth was less sufficient.     

Intracellular processing and immunogenicity of the envelope proteins of human T-cell leukemia virus type I that are expressed from recombinant vaccinia viruses

Two types of recombinant vaccinia viruses (VVs) expressing the env gene of the human T-cell leukemia virus type I (HTLV-I) were reported previously. One recombinant VV, WR-proenv1, synthesized the authentic env protein. In the other recombinant VV, WR-env17, the env gene was inserted within the signal sequence of the VV hemagglutinin (HA) gene, so that the reading frame for the env gene was in phase with that for the HA gene. Comparative studies were performed on the mode of expression and processing of the env proteins in relation to their immunogenicity. In WR-env17-infected cells, translation was initiated exclusively from the initiation methionine of the HA to produce nascently the chimeric env protein, including the altered HA signal peptide. Both this altered HA signal peptide and the internalized env signal peptide functioned as insertion signals for the endoplasmic reticulum. Although about half of the nascent chimeric protein was cleaved at the carboxyl terminus of the internalized env signal peptide to produce the authentic env protein, the other half was cleaved at the carboxyl terminus of the altered HA signal peptide alone to synthesize the chimeric protein. These events led to a less efficient transport of the env protein produced by WR-env17 from the rough endoplasmic reticulum to the Golgi apparatus than that of the authentic env protein synthesized by WR-proenv1. The efficiency of the processing and transport of the env protein affected the immunogenicity of these two recombinant VVs.     

USEFULNESS OF MULTI DETECTOR ROW COMPUTED TOMOGRAPHY FOR DETECTION OF FLAT AND DEPRESSED COLORECTAL CANCER

Background: Recently, the clinical usefulness of colorectal cancer screening by CT colonography has been reported in Europe and the USA. However, in Japan, the diagnosis of flat or depressed colorectal cancer lesions has been emphasized, and the question of whether CT colonography facilitates visualization of these lesions remains to be answered. In the present study, we compared the visualization of flat and depressed colorectal cancer lesions by CT colonography with that of protruding lesions. Methods: We investigated 33 Dukes A colorectal cancer lesions that had been examined by 3D‐CT, colonoscopy, and barium enema prior to surgery. In all patients, CT colonography was performed immediately after colonoscopy. Volume rendering was used for 3‐D rearrangement, and imaging findings were examined with respect to morphology, tumor diameter, and tumor height. Results: All (14/14) of the protruding‐type lesions were visualized by CT colonography, whereas 78.9% (15/19) of the flat and depressed‐type lesions were visualized. There was no significant difference in tumor diameter between protruding‐type lesions and flat and depressed‐type lesions. With respect to tumor height, 100% of the lesions measuring 2 mm or more in height were visualized, whereas only 42.9% of those measuring less than 2 mm in height were visualized; the difference was significant (P < 0.001). Conclusions: These results suggest that the visualization capacity of CT colonography is associated with tumor height, but not with tumor diameter. Currently, lesions measuring 2 mm or more in height can be visualized reliably by CT colonography.     

Effect of endothelin on gastric mucosal lesion in rats

Gastric mucosal blood flow and gastric mucosal prostaglandin E2 (PGE2) and prostacyclin (PGI2) were investigated in male Wistar rats intraarterially injected with endothelin (ET), an endothelium-derived vasoconstrictor peptide. Immediately following ET (4 nmol/kg) administration, gastric mucosal blood flow decreased. Then 30 min later, the blood flow reached the minimum, but PGE2 and PGI2 showed the highest value. PGE2 showed a tendency to decrease 90 min later, while PGI2 continued to show high value. There were redness and hemorrhagic damage in the gastric mucosa. Endogenous PGs were presumed to be relate to the regulation of the development of the mucosal damage owing to decrease in the blood flow after ET administration.     

Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis.

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a wide range of fungi. In the present study, we investigated the therapeutic effects of oral ER-30346 on experimental local infections caused by Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans and compared them with those of itraconazole and fluconazole. In experimental murine models of pulmonary aspergillosis, candidiasis, and cryptococcosis, ER-30346 reduced the numbers of CFU in the lungs significantly compared with the numbers of CFU in the lungs of the controls (P < 0.05). ER-30346 was as effective as or more effective than itraconazole against pulmonary aspergillosis. Against pulmonary candidiasis and cryptococcosis, ER-30346 was more effective than itraconazole and was as effective as fluconazole. ER-30346 was also effective against pulmonary candidiasis caused by fluconazole-resistant C. albicans. In mice with intracranial cryptococcosis, ER-30346 reduced the numbers of CFU in the brains significantly compared with the numbers of CFU in the brains of the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. In an experimental model of oral candidiasis in rats, ER-30346 reduced the numbers of CFU in oral swabs significantly compared with the numbers of CFU in oral swabs from the controls (P < 0.05) and was more effective than itraconazole and as effective as fluconazole. Thus, ER-30346 shows efficacy in murine aspergillosis, candidiasis, and cryptococcosis models. Further studies are needed to determine the potential of ER-30346 for use in the treatment of these infections.     

Hemodynamic changes in a patient with esophageal varices after endoscopic injection sclerotherapy evaluated by endoscopic color Doppler ultrasonography

A 46-year-old man with alcoholic cirrhosis was admitted to our hospital for treatment of high-risk esophageal varices in February 2000. Images of the esophageal varices, paraesophageal veins and palisade veins were obtained by endoscopic color Doppler ultrasonography (ECDUS) before endoscopic injection sclerotherapy (EIS). Prophylactic EIS was performed six times per week for esophageal varices, and EIS was continued until the esophageal varices were completely eradicated. In July 2002, endoscopy revealed esophageal varices graded as Cb, F1, Lm, and RC(−), and color flow images of the palisade veins (hepatofugal flow), esophageal varices, and a developed paraesophageal vein were obtained with ECDUS. In April 2003, endoscopy showed esophageal varices graded as Cb, F1, Lm, and RC(−), and color flow images of the palisade veins and esophageal varices were obtained using ECDUS. The blood in the palisade veins flowed in an alternate direction on color flow images, and pulsatile waves were delineated at the gastroesophageal junction. In January 2004, endoscopy revealed esophageal varices graded as F0 and RC(−), and pulsatile waves were delineated in the lower esophagus with ECDUS. However, the esophageal varices and palisade veins had disappeared from color flow images. In conclusion, ECDUS was useful for evaluating hemodynamic changes after EIS.     

In vitro evaluation of E1077, a new cephalosporin with a broad antibacterial spectrum.

E1077 is a novel parenteral cephalosporin with a wide spectrum of potent antibacterial activity against aerobic and anaerobic gram-positive and gram-negative bacteria. Against methicillin-susceptible Staphylococcus aureus, E1077 was twice as active as cefpirome, with an MIC for 90% of strains tested (MIC90) of 0.78 micrograms/ml. Methicillin-resistant S. aureus was moderately to highly resistant to E1077, but E1077 was at least twice as active as other beta-lactams tested. Against Enterococcus faecalis, E1077 was the most active of the cephalosporins tested (MIC90, 12.5 micrograms/ml) and was at least fourfold more active than cefpirome and ceftazidime. At concentrations of less than or equal to 0.78 micrograms/ml, E1077 inhibited 90% of streptococci and most of the members of the family Enterobacteriaceae tested, with the exceptions of Serratia marcescens and Proteus vulgaris, for which the MIC90s of E1077 were both 3.13 micrograms/ml. Against Pseudomonas aeruginosa, E1077 was two- to fourfold more active than cefpirome and ceftazidime. For the anaerobes, E1077 was as active against Bacteroides fragilis as was cefuzonam, and its activity was fourfold higher than those of cefpirome and ceftazidime. E1077 was at least as resistant as cefpirome to hydrolysis by various beta-lactamases, and these enzymes had a low affinity for E1077.     

Effects of graded mechanical compression of rabbit sciatic nerve on nerve blood flow and electrophysiological properties

Entrapment neuropathy is a frequent clinical problem that can be caused by, among other factors, mechanical compression; however, exactly how a compressive force affects the peripheral nerves remains poorly understood. In this study, using a rabbit model of sciatic nerve injury (n = 12), we evaluated the time-course of changes in intraneural blood flow, compound nerve action potentials, and functioning of the blood–nerve barrier during graded mechanical compression. Nerve injury was applied using a compressor equipped with a custom-made pressure transducer. Cessation of intraneural blood flow was noted at a mean compressive force of 0.457 ± 0.022 N (±SEM), and the compound action potential became zero at 0.486 ± 0.031 N. Marked extravasation of Evans blue albumin was noted after 20 min of intraneural ischemia. The functional changes induced by compression are likely due to intraneural edema, which could subsequently result in impairment of nerve function. These changes may be critical factors in the development of symptoms associated with nerve compression.