The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops

In the present study, two experiments were performed to investigate the influence of OPC-31260 on experimentally induced endolymphatic hydrops in guinea pigs and the regulation of aquaporin-2 (AQP2) mRNA expression in the rat inner ear. In morphological studies, the increases in the ratios of the length of Reissner's membrane (IR-L) and the cross-sectional area of the scala media (IR-S) were quantitatively assessed among normal guinea pigs (normal ears) and three groups with hydropic ears: hydropic ears with no infusion (non-infusion hydropic ears), hydropic ears with an infusion of physiological saline into the scala tympani (saline-infused hydropic ears) and hydropic ears with infusion of 0.3% OPC-31260 into the scala tympani (OPC-infused hydropic ears). IR-Ls in the experimental groups were markedly larger than in the normal ear group, but there was no significant difference among the groups of non-infusion hydropic ears, saline-infused hydropic ears and OPC-infused hydropic ears. The IR-Ss of non-infusion hydropic ears and saline-infused hydropic ears (48.8-49.3%) were statistically different from that of normal ears (6.5%) (Dunnet multiple comparison test, P<0.01). However, IR-S of the OPC-infused hydropic ears (-14.8%) was significantly smaller than those of non-infusion hydropic ears and saline-infused hydropic ears (one-way ANOVA, P<0.01). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (MAQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in MAQP2/Mbeta-actin both in the cochlea and in the endolymphatic sac (t-test, P<0.001). These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease.     

Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization

Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.     

Safety and Feasibility of Laparoscopic Intersphincteric Resection for Very Low Rectal Cancer

Background

Laparoscopic surgery has been reported to be one of the approaches for total mesorectal excision (TME) in rectal cancer surgery. Intersphincteric resection (ISR) has been reported as a promising method for sphincter-preserving operation in selected patients with very low rectal cancer.

Methods

From July 2005 to December 2008, 35 patients with very low rectal cancer underwent laparoscopic TME with ISR. The results were compared retrospectively with those of previous open TME with ISR.

Results

Conversion to open surgery was necessary in one (3%) patient. The median operation time was 293 min and median estimated blood loss was 40 ml. The pelvic plexus was completely preserved in 32 patients. There was no mortality. Postoperative complications occurred in three (9%) patients. The median length of postoperative hospital stay was 17 days. Macroscopic complete mesorectal excision was achieved in all cases. Complete resection (R0) was achieved in 34 patients. Clinical lymph node stage, operation time, and blood loss were significantly different between the laparoscopic group and open group, but the differences of other factors were not statistically significant.

Conclusions

Laparoscopic TME with ISR is technically feasible and a safe alternative to laparotomy with favorable short-term postoperative outcomes.     

Ductal adenocarcinoma of the prostate associated with prostatic multilocular cyst.

A case is reported here of ductal adenocarcinoma of the prostate forming a multilocular cyst, which responded well to androgen deprivation therapy.     

Perivalvular leakage 25 years after initial mitral valve replacement with a Björk-Shiley prosthesis

An 80-year-old woman had undergone initial mitral valve replacement using a Björk-Shiley mechanical valve owing to mitral stenosis 25 years earlier. Suddenly, she had anemia and an increased lactic dehydrogenase (LDH) level. Transesophageal echography (TEE) showed perivalvular leakage. In a redo operation, two side-by-side stitches of the valve on the posterior annulus were loosened without cutting and the sewing cuff at that site was floated over the annulus, leading to the perivalvular leakage. The valve was easily removed; and round, hard, degenerative calcified tissue composed of remnant mitral valve in the suture site during the initial operation was found just under the sewing cuff. After resection of this calcified round tissue, a 25-mm bioprosthesis was put in place. Her postoperative recovery was uneventful, and 47 days after surgery she was discharged without perivalvular leakage or anemia.     

Association between lumber bone mineral density and vascular stiffness as assessed by pulse wave velocity in postmenopausal women

Recent studies have showed a significant correlation between vascular calcification and bone mineral density (BMD). Therefore, an investigation was carried out on the association between arterial stiffness, lumbar BMD and bone metabolic markers in Japanese postmenopausal women. Brachial-ankle PWV (baPWV) and BMD of the lumbar spine and serum bone-specific alkaline phosphatase (BAP) levels in 143 postmenopausal women were measured, where there was a significant negative correlation between baPWV and BMD (r = −0.21; P = 0.0135). An additional analysis included the remaining 75 subjects, but excluded subjects with hypertension and obesity. Here, a more negative correlation between baPWV and BMD (r = −0.315; P = 0.006), and a positive correlation between baPWV and BAP (r = 0.248; P = 0.032) were also significant. A group analysis, where the women were age matched and stratified into three groups of different bone density, i.e., normal BMD, osteopenic and osteoporotic, were further made. This showed lower PWV values in the normal BMD group than in the other two groups. A study also showed that the tertile with the highest BAP was associated with significantly higher PWV values than the other tertiles. However, when the multiple linear regression analysis was carried out, there was no correlation between PWV and BAP values. Low BMD and arterial stiffness show some correlation, suggesting that BAP may reflect the degree of arterial stiffness present.     

Biological fixation of the graft within bone after anterior cruciate ligament reconstruction in rabbits: effects of the duration of postoperative immobilization

To investigate the effects of the duration of postoperative immobilization on the biological fixation of the graft within bone after anterior cruciate ligament (ACL) reconstruction, we performed ACL reconstruction in 27 rabbits, which were divided into five groups — no immobilization and 1-, 2-, 4-, and 6-week immobilization. All animals were killed 6 weeks postoperatively, and the graft-bone tunnel interface was examined biomechanically and histologically. In the groups with immobilization, in tensile failure tests, most specimens failed through the intraarticu-lar portion of the grafts. There was no significant difference in the maximum load between these groups. In the no-immobilization group, all specimens failed through pulling of the grafts out of the femoral tunnel, with a lower maximum load than in the other groups. Histologically, new bone formation and occasional collagen fiber continuity were observed at the interface; which consisted of a fibrous tissue. In the no-immobilization group, the graft was partly separated from the fibrous tissue covering the bony wall. It is concluded that no immobilization delays the biological fixation process in the bone tunnel after ACL reconstruction, and that a certain period of immobilization is necessary for the fixation to proceed smoothly. Received for publication on Oct. 26, 1998; accepted on July 9, 1999     

Occurrence of Antifouling Biocides and Fluorinated Alkyl Compounds in Sediment Core from Deep Sea: Suruga Bay,Tosa Bay,and Nankai Tough,Japan

Contamination profiles of antifouling biocides were investigated in a deep-sea environment in Suruga Bay Japan. Significant differences in the tributyltin (TBT) and triphenyltin (TPT) concentrations in subsurface sediment between 850 and 800 m of water depth were not observed (p < 0.05). Organotin (OT) concentrations in sediment core of 0–30.5 cm from a water depth of 800 m were investigated. The butyltins (BTs) and phenyltins (PTs) concentrations were constant between 0 and 15 cm, and, subsequently, the concentration of these compounds increased. The peaks of the BTs and PTs concentrations were observed between 18 and 19 cm. The concentrations of Irgarol 1051 decreased until a core depth of 9 cm, and, the values then became near the detection limit under the 10 cm of core depth. Perfluorooctane sulfonate (PFOS) and perfluorooctanic acid (PFOA) were detected in the sediment core (0–30.5 cm) of Suruga Bay. The concentration of PFOS was high in the 0–5-cm core depth and then decreased. The concentrations of PFOA, however, were at the values near the detection limit throughout the sediment core. The BTs and PTs concentrations in surface sediment from Tosa Bay decreased with water depth. Although Irgarol 1051 was the only alternative compound detected, the value was near the detection limit. PFOS and PFOA were detected in sediment core from Tosa Bay. The concentrations of PFOS became low as the water depth became deeper. TBT, TPT, Sea Nine 211, Diuron and Irgarol 1051 were detected in sediment core (core depth: 10 cm) from the Nankai trough (water depth: 4010 m).