Mirabegron causes vesical and urethral relaxation in rats with spinal cord injury

The effects of solifenacin and mirabegron on vesical and urethral function were compared in rats with or without spinal cord injury (SCI). Isovolumetric cystometry and urethral pressure recording were initially performed in intact rats. Then, the bladder neck was ligated under urethane anesthesia, after which a catheter was inserted through the bladder dome for isovolumetric cystometry and another catheter was inserted into the urethra to measure urethral pressure. Solifenacin (0.03–3 mg/kg) or mirabegron (0.03–3 mg/kg) was injected intravenously, and bladder and urethral activity were recorded. To create rats with SCI, the spinal cord was transected at the lower thoracic level under isoflurane anesthesia. After 2 weeks, a catheter was inserted through the bladder dome for single cystometry and bladder activity was recorded without anesthesia following intravenous injection of solifenacin or mirabegron. Isovolumetric cystometry revealed a larger decrease in maximum bladder contraction pressure after injection of solifenacin, whereas prolongation of the interval between bladder contractions was greater with mirabegron. In SCI rats, single cystometry showed that solifenacin and mirabegron both increased bladder volume at the first non‐voiding bladder contraction and decreased the maximum bladder contraction pressure. Mirabegron also increased the voided volume and decreased the percentage residual volume without altering bladder capacity. Solifenacin and mirabegron both inhibited bladder contractility, and mirabegron possibly also induced urethral relaxation. Mirabegron may be suitable for patients with overactive bladder and residual urine.     

Clinical Benefit of the Change of Dialysate Calcium Concentration From 3.0 to 2.75 mEq/L

Because active vitamin D preparations and calcimimetics have been widely used to treat secondary hyperparathyroidism, maintenance of acceptable serum calcium and phosphate levels is important. A 2.75 mEq/L dialysate calcium product, which may bring the calcium balance closer to 0, has recently been launched, and we had an opportunity to examine its possible benefits. We performed a 6‐month retrospective review after switching from 3.0 mEq/L to 2.75 mEq/L calcium dialysate in 85 outpatients undergoing chronic hemodialysis. We evaluated blood biochemical parameters, including predialysis and postdialysis serum calcium and phosphate levels, predialysis intact parathyroid hormone (iPTH) levels; dialysis dose (Kt/V); and doses of concomitant active vitamin D preparations, calcimimetics, phosphate binder, and erythropoiesis‐stimulating agents. Postdialysis calcium levels were significantly lower and predialysis corrected calcium levels significantly decreased. The change in calcium levels before and after dialysis was smaller after switching of the dialysate than before. iPTH levels significantly increased 1 month after switching of the dialysate. No remarkable changes were observed in phosphate levels or Kt/V. The dose of alfacalcidol, one of the concomitant drugs, somewhat increased, and no remarkable changes in dosage were observed for other concomitant drugs. These results were favorable in terms of calcium balance. However, there may be limitations in interpreting the results, but the resultant calcium levels suggest that switching to 2.75 mEq/L calcium dialysate may improve the control of calcium levels. In addition, it is hoped that the treatment choice of secondary hyperparathyroidism is extended.     

Organization and cellular arrangement of two neurogenic regions in the adult ferret (Mustela putorius furo) brain

In the adult mammalian brain, two neurogenic regions have been characterized, the subventricular zone (SVZ) of the lateral ventricle (LV) and the subgranular zone (SGZ) of the dentate gyrus (DG). Despite remarkable knowledge of rodents, the detailed arrangement of neurogenic regions in most mammals is poorly understood. In this study, we used immunohistochemistry and cell type‐specific antibodies to investigate the organization of two germinal regions in the adult ferret, which belongs to the order Carnivora and is widely used as a model animal with a gyrencephalic brain. From the SVZ to the olfactory bulb, doublecortin‐positive cells tended to organize in chain‐like clusters, which are surrounded by a meshwork of astrocytes. This structure is homologous to the rostral migratory stream (RMS) described in other species. Different from rodents, the horizontal limb of the RMS emerges directly from the LV, and the anterior region of the LV extends rostrally and reached the olfactory bulb. In the DG, glial fibrillary acidic protein‐positive cells with long radial processes as well as doublecortin‐positive cells are oriented in the SGZ. In both regions, doublecortin‐positive cells showed characteristic morphology and were positive for polysialylated‐neural cell adhesion molecule, beta‐III tubulin, and lamin B1 (intense staining). Proliferating cells were detected in both regions using antibodies against proliferating cell nuclear antigen and phospho‐histone H3. These observations demonstrate that the two neurogenic regions in ferrets have a similar cellular composition as those of other mammalian species despite anatomical differences in the brain. J. Comp. Neurol. 522:1818–1838, 2014. © 2013 Wiley Periodicals, Inc.     

Patterns of tooth agenesis in Japanese subjects with bilateral agenesis of mandibular second premolars

The aim of this study was to explore the patterns of tooth agenesis in Japanese orthodontic patients with bilateral agenesis of mandibular second premolars. A total of 80 Japanese orthodontic patients with 2 congenitally missing mandibular second premolars were selected as the subjects of this study (experimental group). Another 80 individuals without bilateral agenesis of mandibular second premolars were collected for comparison (control group). The 2 groups were matched with regard to sex. Radiographs, dental casts and records of medical and/or dental treatment were used to identify tooth agenesis. The Chi-square test, odds ratio, and test for equality were used to make statistical comparisons. The prevalence rates of other types of tooth agenesis were significantly higher in the experimental group than in the control group. The occurrence of agenesis of maxillary and mandibular lateral incisors and third molars, and maxillary second premolars was also significantly higher in the experimental group than in the control group. Significantly increased prevalence rates of symmetrical tooth agenesis, with third molars included, and oligodontia were observed in the experimental group. Japanese subjects with bilateral agenesis of mandibular second premolars are at significantly high risk of agenesis of other types of permanent teeth, symmetrical tooth agenesis and oligodontia.     

Enhancement of Hemocompatibility of the MERA Monopivot Centrifugal Pump: Toward Medium‐Term Use

The MERA monopivot centrifugal pump has been developed for use in open‐heart surgery, circulatory support, and bridge‐to‐decision for up to 4 weeks. The pump has a closed‐type, 50‐mm diameter impeller with four straight paths. The impeller is supported by a monopivot bearing and is driven by a radial‐flux magnet‐coupling motor. Because flow visualization experiments have clarified sufficient pivot wash and stagnation at the sharp corner of the pivot support was suggested, sharp corners were removed in the design stage. The index of hemolysis of the pump operating at more than 200 mm Hg was found to be lower than that of a commercial pump. Four‐week animal tests were then conducted two times; improvement of thrombus formation was seen in the female pivot through modification of female pivot geometry. Overall antithrombogenicity was also recorded. Finally, to assure mid‐term use, an additional 4‐week durability test revealed that the rate of the axial pivot wear was as small as 1.1 µm/day. The present in vitro and in vivo studies revealed that the MERA monopivot centrifugal pump has sufficient hemocompatibility and durability for up to 4 weeks.