Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction

In the focal infarction model of the rat middle cerebral artery (MCA), the thalamus of the occluded side becomes gradually atrophic, mainly because of retrograde degeneration. We determined whether basic fibroblast growth factor (bFGF) administered intracisternally could prevent this thalamic atrophy. We occluded the left MCA through a small cranial opening, and animals were then divided into two groups. One group received intracisternal injections of recombinant bFGF (1 microgram dissolved in 0.1 ml of saline with 2% rat serum) starting 1 day after occlusion and repeated once a week to a total dose of 4 micrograms by four injections. The other group received vehicle solution by the same schedule. The animals were perfused and fixed at 28 days after occlusion, and histological examination was made at the level of the caudoputamen and thalamus. In the bFGF-treated rats, the area of the posterior ventral thalamus of the occluded side was 93% of that of the contralateral side, i.e., significantly larger than in the normal saline-treated rats (75%, p less than 0.01). The infarction size was not statistically different in the two groups. Microscopic observation indicated that normal-saline-treated animals showed shrinkage and disappearance of thalamic neurons, whereas bFGF-treated groups showed preservation of thalamic neurons. Computerized analysis of the cell size substantiated this observation. To assess the effect of bFGF on astrocytes, bFGF or vehicle solution was injected into normal rats, and their histology was evaluated at 1, 2, and 4 weeks after injection. The bFGF-injected group showed a significant increase in glial fibrillary acidic protein-positive astrocytes in the brain tissue facing the ventriculocisternal system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavioral treatment for chronic insomnia]

The efficacy of non-pharmacological intervention for chronic insomnia has been proven by several meta-analytic reviews, an NIH report, an American Academy of Sleep Medicine review, and numerous clinical trials. Behavior therapy for chronic insomnia consists of relaxation, stimulus control, sleep restriction, cognitive restructuring and sleep hygiene education, which has produced reliable and durable changes in total sleep time, sleep onset latency, number and duration of awakening. These studies also showed that the post-treatment effect of behavior therapy is equal to that of hypnotic therapy, and that these effects were maintained for 6 months on follow-up assessment. Elderly insomniac patients would gain considerable benefit from behavioral treatments because there are no adverse physical effects as there are from pharmacological therapy. The authors present the basic theory, techniques of behavior therapy for insomnia, and the results of two important key meta-analytic reviews. Any behavioral approach such as convenient education, self-care enhancement by bibliotherapy, and individual face-to-face counseling, seem to be fruitful not only for American but also Japanese insomnia patients. Nonetheless, there are no currently actual intervention studies using behavior therapy in Japan. We have discussed the methodology of intervention study and published a behavioral self-help manual for people with sleep problems. Development of a behavioral approach to chronic insomnia seemed to be very beneficial and a useful contribution to mental health services.     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.     

Significance of lateral biopsy specimens during transrectal ultrasound-guided prostate biopsies in Japanese men

OBJECTIVES: Lateral biopsies are thought to have a better cancer detection rate compared with standard sextant biopsies. This study aimed to determine whether lateral peripheral zone biopsies in Japanese men who underwent transrectal ultrasound-guided prostate biopsies provided a significantly higher cancer detection rate than sextant biopsies. METHODS: Between 1999 and 2004, data were collected from 461 men who underwent prostate biopsy and had enough data regarding the performance of lateral biopsies for statistical analysis. There were two categories in this study: (i) patients who underwent sextant prostate biopsies; and (ii) patients who underwent sextant biopsies plus lateral biopsies. RESULTS: Prostate cancer was detected in 141 (30.6%) of 461 patients. It was detected in 24 (22.2%) of 108 patients who underwent sextant biopsies and 117 (33.1%) of 353 patients who underwent sextant plus lateral biopsies. Lateral biopsies were not associated with a statistically higher rate of positive biopsy findings; however, we found a significantly higher ratio of patients with positive findings in those with prostate specific antigen (PSA) levels 10 ng/mL (one of 71, 1.4%) among those who had positive cores only in lateral biopsy samples (P < 0.0001). CONCLUSIONS: Lateral biopsies did not show a significantly higher detection ratio of prostate cancer compared to sextant biopsies. However, lateral biopsies were more effective than sextant biopsies in patients with lower PSA levels. Our findings might be useful for the establishment of biopsy strategies to detect prostate cancer, especially in patients with lower PSA levels.     

Sudden death from metastatic esophageal cancer to the ventricular septum.

A 67-year-old man was admitted to our hospital due to esophageal cancer. Cancer existed at the lower esophagus and subtotal esophagectomy and lymphadenectomy was performed. The postoperative course was uneventful. Pathological findings revealed moderately differentiated squamous cell carcinoma that metastasized to the abdominal lymph nodes which include the paraaortic lymph nodes. He complained of anorexia three months after the operation and was found to have multiple liver and mediastinal lymph node metastases. He was admitted for chemotherapy. Before starting chemotherapy, he suddenly died without any sign of hemorrhage or respiratory disorder. Autopsy showed metastatic lesions to the heart and mediastinal lymph nodes, liver, thoracic vertebrae, kidney, adrenal gland and heart. Metastatic nodules in the heart were on the ventricular septum where the conducting system exists. No direct invasion from the pericardium was observed. Blockade of the conducting system of the heart was considered to have caused the severe arrhythmia and sudden cardiac arrest.