TNF-alpha has been demonstrated to modulate angiogenesis, possibly via the inhibition of endothelial cell proliferation, in vivo. The effect of TNF-alpha blockage on the ischemic limb, however, has yet to be fully elucidated. In this study we examined whether TNF-alpha contributes to the recovery of blood perfusion in an ischemic hindlimb model of TNF-alpha knockout (KO) mice. Hindlimb ischemia was induced in 10- to 12-week-old male Balb/c Wild type (WT) and KO mice. After the femoral artery was exposed, the proximal end and the distal portion of the femoral artery were ligated, and the femoral artery was excised. Hindlimb blood perfusion was measured before and just after surgery and 1, 2, 4 weeks after surgery using a laser Doppler perfusion imager (LDPI) system. The results were expressed as the ratio of perfusion at each week versus the presurgical value. The blood perfusion of the ischemic hindlimb measured by LDPI gradually recovered in both mice, but the recovery rate in the KO mice was higher at the distal site at 2 weeks (p< 0.01) and significantly higher at both sites at 4 weeks (p< 0.005) . Both the capillary density (p< 0.05) and arteriole density (p< 0.005) were greater in KO mice than in WT mice at 4 weeks. The numbers of cells positive for Mac-3 (p< 0.0001) and positive for TUNEL staining (p< 0.0001) were significantly higher in WT mice than in KO mice at 4 weeks. The serum TNF-alpha concentration was increased transiently at 1 week in WT mice (p< 0.05) . The serum VEGF (vascular endothelial growth factor) concentration was significantly higher in KO mice than in WT mice at 4 weeks (p< 0.001) . We conclude that the deficiency of TNF-alpha improves blood perfusion recovery from hindlimb ischemia in KO mice by promoting angiogenesis and reducing inflammation and apoptosis.

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Androgen deprivation therapy (ADT) decreases bone mineral density (BMD) and increases the risk of fracture in men with prostate cancer. Smith has stated that prostate cancer patients show a degradation of BMD prior to ADT. We, therefore, studied the bone dynamics in Japanese prostate cancer patients prior toADT. BMD of the total hip, femoral neck, lumbar spine and forearm were measured by dual-energy x-ray absorptiometry (DEXA) before treatment in 53 prostate cancer patients without bone metastasis and in 16 patients with bone metastasis. Bone metabolism measurements of serum NTX and serum BAP were also carried out before treatment in 62 prostate cancer patients without bone metastasis and 22 patients with bone metastasis. Measurements in the total hip of nine of the 53 patients without bone metastasis indicated osteoporosis. Measurements of the femoral neck in eleven of the 53 patients indicated osteoporosis. Results show that Japanese prostate cancer patients without bone metastasis do not suffer from bone density degradation prior to ADT; only the Z score of the forearm showed a minus value. Serum NTX and BAP were significantly elevated in prostate cancer patients with bone metastasis compared with those without bone metastasis. No screening guidelines currently exist; however, patients at risk of decreased BMD should be screened and treated to prevent consequent fractures. Serum NTX and BAP monitoring of prostate cancer patients might facilitate the timely diagnosis of bone metastasis.

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The aim of this study was to evaluate the correlation between seminal inhibin-B and testicular function and to access the usefulness of seminal inhibin-B as a sensitive marker of spermatogenesis. This study included 81 infertile patients of which 13 had azoospermia, 33 had oligozoospermia, and 35 had normal sperm counts. Serum Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), testosterone, inhibin-B, seminal inhibin-B, and transferrin were measured. Semen analyses were performed, and the total sperm count and sperm density were used for analyses. The mean serum inhibin-B concentration was 149.4±83.42 pg/ml, the seminal inhibin-B concentration was 1111±1665 pg/ml, and the seminal transferrin concentration was 86.88 ± 99.87 mg/l. The mean serum inhibin B, seminal inhibin-B, and seminal transferrin concentrations were significantly different between patients with azoospermia, those with oligozoospermia, and those with normal sperm density (p < 0.001) . Serum inhibin-B significantly correlated with total sperm count (r=0.330), sperm density (r=0.451), serum LH (r=-0.434), serum FSH (r=-0.580), and seminal transferrin (r=0.370) . Seminal inhibin-B significantly correlated with sperm density (r=0.395), serum FSH (r=-0259) . and seminal transferrin (r=0.647) . Thus, seminal inhibin-B showed a stronger correlation with seminal transferrin than serum inhibin-B, but seminal inhibin-B correlated more weakly with sperm density and serum FSH than serum inhibin-B. Our study shows that seminal inhibin-B reflects spermatogenesis. However, seminal inhibin-B may be less sensitive to evaluate spermatogenesis than serum inhibin-B.

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Case 1. A 25-year-old woman, who had been performed appendectomy as initial diagnosis of acute appendicitis, presented entero-cutaneous fistula at a site of postoperative drainage. She was diagnosed as Crohn disease by re-evaluation of the lower gastrointestinal tract thereafter. The fistula was closed by triple infusion of infliximab at dose of 5mg/kg. Case 2. A 38-year-old man had been performed operation of resection of bowel and stoma because of fistulating Crohn disease in 2000. The abscess developed beside the stoma on Jan 2005 and it was revealed to be originated from the fistula at the sigmoid colon in the stoma. The fistula was successfully treated by triple infusion of infliximab at dose of 5 mg kg after drainage of the abscess. However, the fistula recurred on Jun 2005 and since the infliximab has been given bimonthly as a maintenance therapy. Imfliximab was new treatment for Crohn disease. We should observe the treatment because of the recurrence of fistula.

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