Axons in the adult mammalian central nervous system (CNS) exhibit little regeneration after injury. It has been suggested that several axonal growth inhibitors prevent CNS axonal regeneration. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration. We identified a strong and selective inhibitor of Sema3A, SM-216289, from the fermentation broth of a fungal strain. To examine the effect of SM-216289 in vivo, we transected the spinal cord of adult rats and administered SM-216289 into the lesion site for 4 weeks. Rats treated with SM-216289 showed substantially enhanced regeneration and/or preservation of injured axons, robust Schwann cell-mediated myelination and axonal regeneration in the lesion site, appreciable decreases in apoptotic cell number and marked enhancement of angiogenesis, resulting in considerably better functional recovery. Thus, Sema3A is essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (SCI). These results support the possibility of using Sema3A inhibitors in the treatment of human SCI.

We previously reported that brain-derived neurotrophic factor (BDNF) regulates both food intake and blood glucose metabolism in rodent obese diabetic models such as C57BL/KsJ-lepr N eurotrophins are important regulators in the embryogenesis, development, and functioning of nervous systems (1,2). At present, four neurotrophins are known: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, and NT-4 / N T-5 (3-6) in mammals. BDNF, discovered long after NGF, enhances the survival and differentiation of several classes of neurons in the central and peripheral nervous systems, including motoneurons and sensory neurons. BDNF and its receptor, TrkB, are widely expressed in a variety of neurons through the embryonic, postnatal, and adult stages (7-10). These results and the many activities of BDNF described in in vitro cell cultures and lesioned animal studies (11,12) indicate that BDNF is likely to have multiple functions.In addition to the efficacy of BDNF in neurological disorders, we previously found that BDNF reduces food intake and blood glucose concentration in rodent obese diabetic models, such as C57BL/KsJ-d b/d b mice (13,14). To eliminate the effect of reduced food intake on the regulation of glucose metabolism, we evaluated the hypoglycemic effect of BDNF in d b/d b mice using the conventional pair-feeding protocol in which the amount of food provided to each pair-fed mouse was the same as the average amount of food eaten by the BDNF-treated mice during the preceding 24-h period (13,14). H o w e v e r, because such hyperphagic diabetic mice given a vehicle ate all of the food over a period of several hours, leaving them in a fasting condition until the next feeding, this protocol was inappropriate to study the effect of antidiabetic agents on glucose metabolism by mechanisms other than appetite alteration.In this study, to overcome these drawbacks, we designed a novel pellet pair-feeding apparatus and evaluated the effect of Received for publication 28 April 1999 and accepted in revised form 1 8 November 1999. B D N F, brain-derived neurotrophic factor; ELISA, enzyme-linked immunosorbent assay; NGF, nerve growth factor; NT, neurotrophin; PBS, phosphate-buffered saline; PPA R-, peroxisome proliferator-a c t i v a t e d r e c e p t o r-; STZ, streptozotocin.

No abstract

The use of PGA sheets and fibrin glue after esophageal ESD is a novel method that radically decreases the incidence of esophageal stricture and the number of EBD sessions subsequently required. University Hospital Medical Network Clinical Trial Registry (UMIN000011058).

BackgroundDespite the marked increase of diverticulosis, its risk factors have not been adequately elucidated. We therefore aim to identify significantly associated factors with diverticulosis. We also aim to investigate the present state of diverticulosis in Japan.MethodsWe reviewed the medical records from 1990 to 2010 that included the data of consecutive 62,503 asymptomatic colonoscopy examinees from the general population in Japan. Most recent 3,327 examinees were analyzed with 16 background factors.ResultsAmong the 62,503 subjects (47,325 men and 15,178 women; 52.1 ± 9.2 years old), diverticulosis was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0% (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than the former in all age groups and for both genders. Considering the anatomical locations of colorectal diverticula, left-sided ones have markedly increased with age but not significantly changed with times. Univariate analyses of the 3,327 subjects showed significant association of diverticulosis with four basic factors (age, sex, body mass index, blood pressure), three life style-related factor (smoking, drinking, severe weight increase in adulthood), and two blood test values (triglyceride, HbA1c). The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that age (β = 0.217-0.674, OR = 1.24-1.96), male gender (β = 0.185, OR = 1.20), smoking (β = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (β = 0.153, OR = 1.17), HbA1c (β = 0.136, OR = 1.15), drinking (β = 0.109, OR = 1.11), and serum triglyceride (β = 0.098, OR = 1.10) showed significantly positive association with diverticulosis whereas body mass index and blood pressure did not.ConclusionsThe large-scale data of asymptomatic colonoscopy examinees from the general population from 1990 to 2010 indicated that the prevalence of diverticulosis is still increasing in Japan. Age, male gender, smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum triglyceride showed significant positive association with diverticulosis.