Long-term clinical effect of nilvadipine in patients with chronic heart failure: A double-blind placebo-controlled study

Summary The long-term effect of calcium channel blockers on chronic heart failure is disappointing, probably because of reflex sympathetic activation through arterial vasodilation. However, nilvadipine may be beneficial for treatment of chronic heart failure since this drug has minimal effects on sympathetic activation. In this study, the effects of 12-week administration of nilvadipine or placebo on symptoms of heart failure and cardiac function were investigated in 23 patients with mild-to-moderate chronic heart failure in a double-blind trial. The patients were randomly assigned to either a nilvadipine group (16 mg daily) or a placebo group. Intergroup comparisons did not show significant differences in any parameters. Serious adverse effects were not observed during the study. Thus, this study failed to show any beneficial effect of nilvadipine in the long-term treatment of patients with chronic heart failure. We conclude that the long-term administration of nilvadipine (16 mg daily) is neither effective nor harmful in the treatment of patients with chronic heart failure.Other members are listed in the appendix.     

Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151

CD151, one of the tetraspanins, forms a stable complex with integrin alpha3beta1, the major laminin receptor on the cell surface. We found that 8C3, an anti-CD151 mAb obtained by screening for reactivity with integrin alpha3beta1-CD151 complexes, was capable of dissociating CD151 from integrin alpha3beta1, thereby allowing us to deplete CD151 from purified integrin alpha3beta1-CD151 complexes. The CD151-free integrin alpha3beta1 thus obtained showed a significant reduction in its ability to bind to laminin-10/11, a high-affinity ligand for integrin alpha3beta1, with a concomitant reduction in its reactivity with mAb AG89, which recognizes activated beta1-containing integrins. These results raised the possibility that the association of integrin alpha3beta1 with CD151 potentiates the ligand-binding activity of the integrin through sustaining its activated conformation. In support of this possibility, the ligand-binding activity was restored when CD151-free integrin alpha3beta1 was reassociated with purified CD151. 8C3-induced dissociation of CD151 from integrin alpha3beta1 was also demonstrated on the surface of living cells by fluorescent resonance energy transfer imaging, accompanied by a concomitant reduction in the cell adhesion to laminin-10/11-coated substrates. CD151 knock-down by RNA interference also resulted in a reduction in the adhesive activity of the cells. Taken together, these results indicate that CD151 association modulates the ligand-binding activity of integrin alpha3beta1 through stabilizing its activated conformation not only with purified proteins but also in a physiological context.     

Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis: possible involvement of osteopontin in bone destruction in arthritis

OBJECTIVE: To investigate the involvement of osteopontin (OPN) in bone destruction in a murine experimental arthritis model of collagen-induced arthritis (CIA). METHODS: The expression of OPN was examined at both the messenger RNA (mRNA) and protein levels in various arthritic lesions in mice with CIA by in situ hybridization and immunohistochemistry, respectively. In addition, the expression of alpha(v)beta3 integrin, a receptor for OPN, the ligation of which is thought to be essential for bone resorption by osteoclasts, was examined by immunohistochemistry. Plasma concentrations of OPN were measured at different time points in the course of CIA by enzyme-linked immunosorbent assay. RESULTS: OPN mRNA was detected mainly at sites of bone erosion in arthritic lesions, where activated osteoclasts were present; OPN protein was also detected at sites of bone erosion. In the arthritic synovium, OPN was predominantly expressed in the synovial lining layer, but not in lymphoid aggregates. In addition, alpha(v)beta3 integrin was detected coincident with OPN at sites of bone erosion (bone-pannus junction). Plasma OPN levels were markedly elevated at the time points that corresponded to arthritis flares, and higher levels were maintained during the progression of arthritis. CONCLUSION: OPN may mediate bone resorption by osteoclasts in arthritis through ligation with its receptor, alpha(v)beta3 integrin. OPN may be a useful therapeutic target molecule in the prevention of bone destruction in arthritis.     

Whole-body vibration training improves the walking ability of a moderately impaired child with cerebral palsy: a case study

[Purpose] Strength training is recommended for children with cerebral palsy. However, it is difficult for moderately impaired children with cerebral palsy, who require crutches for ambulation, to participate in this type of training. The purpose of this study was to investigate whether whole-body vibration training is an effective method of strengthening in a moderately impaired child with cerebral palsy. [Subject and Methods] This report describes an 8-year-old Japanese boy with cerebral palsy, who was ambulatory with crutches. The subject participated in physical therapy twice a week for 5 weeks. Whole-body vibration training was selected to complement the standing practice. The patient’s crutch-walking ability, gross motor function, and spasticity were evaluated. [Results] The number of steps and walking duration were reduced in a 5-m walk test with crutches and gross motor function was improved. Further, the spasticity was reduced. [Conclusion] Whole-body vibration training is an effective physical therapy intervention in moderately impaired children with cerebral palsy, who are unable to walk without crutches.Key words: Cerebral palsy, Whole-body vibration, Walking ability     

Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseases

Liver tissue engineering using hepatocyte transplantation has been proposed as an alternative to whole-organ transplantation or liver-directed gene therapy to correct various types of hepatic insufficiency. Hepatocytes are not sustained when transplanted under the kidney capsule of syngeneic mice. However, when we transplanted hepatocytes with the extracellular matrix components extracted from Engelbreth-Holm-Swarm cells, hepatocytes survived for at least 140 days and formed small liver tissues. Liver engineering in hemophilia A mice reconstituted 5% to 10% of normal clotting activity, enough to reduce the bleeding time and have a therapeutic benefit. Conversely, the subcutaneous space did not support the persistent survival of hepatocytes with Engelbreth-Holm-Swarm gel matrix. We hypothesized that establishing a local vascular network at the transplantation site would reduce graft loss. To test this idea, we provided a potent angiogenic agent before hepatocyte transplantation into the subcutaneous space. With this procedure, persistent survival was achieved for the length of the experiment (120 days). To establish that these engineered liver tissues also retained their native regeneration potential in vivo, we induced two different modes of proliferative stimulus to the naive liver and confirmed that hepatocytes within the extrahepatic tissues regenerated with activity similar to that of naive liver. In conclusion, our studies indicate that liver tissues can be engineered and maintained at extrahepatic sites, retain their capacity for regeneration in vivo, and used to successfully treat genetic disorders.     

Laparoscopy-assisted and open distal gastrectomies for early gastric cancer at a general hospital in Japan

BACKGROUND/AIMS: At general hospitals in Japan, laparoscopic surgery for early gastric cancer is not yet popular. The benefits and feasibility of this procedure remain to be established. The aim of this study was to evaluate the surgical outcome of laparoscopy-assisted distal gastrectomy (LADG) in comparison with open distal gastrectomy (ODG) in a general hospital. METHODOLOGY: We performed LADG in 20 patients with early gastric cancer between 2000 and 2001. Clinicopathologic data, blood analyses, clinical course and financial cost of treating patients with LADG were compared with 22 patients treated with ODG between 1998 and 1999. RESULTS: All patients were treated successfully by LADG. Neither reduced operative curability nor increased complications were found with this procedure. Although LADG required a significantly longer operation time than ODG, blood loss was lower in LADG than in ODG. The leukocyte count on day 1 and day 3, and serum C-reactive protein levels on day 1 were significantly lower after LADG than after ODG. There was no significant difference between LADG and ODG in the period and volume of analgesics required. High body temperature continued longer after ODG than after LADG. The first walking, passage of flatus and oral diet initiation were significantly earlier in patients with LADG than in those with ODG. LADG required a significantly shorter hospital stay and less total hospital charge than ODG. CONCLUSIONS: Laparoscopy-assisted distal gastrectomy offered faster recovery of gastrointestinal function, a shorter hospital stay, and consequently less financial cost when compared with open surgery. Therefore, LADG may be a safe and recommendable procedure for patients with early gastric cancer at general hospitals in Japan.     

Secondary pouchitis in a post-operative patient with ulcerative colitis, successfully treated by salvage surgery

We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion in the ileal reservoir provoked by pouch-related complication following total colectomy and pouch anal anastomosis, which was successfully treated by salvage surgery- A 20-year-old woman with ulcerative colitis developed acute severe bloody diarrhea following proctocolectomy, ileal pouch-anal anastomosis and diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly caused by a peripouch abscess and partly concerned with the abnormal pouch formation. The remnant rectum and ileal pouch were excised and ileal pouch-anal anastomosis and diverting ileostomy were constructed. The postoperative course was uneventful with no sign of pouchitis. Salvage surgery may be indicated to treat secondary pouchitis when caused by surgery-related complications.