Efficacy of a topical gelatin-thrombin hemostatic matrix, FLOSEAL®, in intracranial tumor resection.

BACKGROUND: Hemostasis plays an important role in safe brain tumor resection and also reduces the risk for surgical complications. This study aimed to evaluate the efficacy of FLOSEAL®, a topical hemostatic agent that contains thrombin and gelatin granules, in brain tumor resections. METHODS: We evaluated the hemostatic effect of FLOSEAL by scoring the intensity of bleeding from 1 (mild) to 4 (life threatening). We assessed the rate of success of hemostasis with 100 patients who underwent intracranial tumor resection. We also investigated the duration of the operation, the amount of intra- and postoperative bleeding, the number of hospital stays, and adverse events in patients who used FLOSEAL compared with those who did not use FLOSEAL. RESULTS: FLOSEAL was applied to a total of 109 bleeding areas in 100 patients. A total of 95 bleeding areas had a score of 1 and 91 (96%) showed successful hemostasis. Thirteen bleeding areas scored 2 and 8 (62%) showed hemostasis with the first application of FLOSEAL. The second application was attempted with five bleeding areas and four showed hemostasis. About 94% (103/109 areas) of bleeding points successfully achieved hemostasis by FLOSEAL. Moreover, FLOSEAL significantly decreased the amount of intraoperative bleeding and postoperative bleeding as assessed with computed tomography on 1 day postoperatively compared with no use of FLOSEAL. There were no adverse events related to FLOSEAL use. CONCLUSION: Our results indicate that FLOSEAL is a reliable, convenient, and safe topical hemostatic agent for intracranial tumor resection.

Identification of KLRC2 as a candidate marker for brain tumor-initiating cells.

Objective: Brain tumor-initiating cells are characterized by their features of self-renewal, multi-lineage differentiation, and tumorigenicity. We analyzed the gene expression of brain tumor-initiating cells to identify their novel cellular markers. Methods: We performed cDNA microarray, in silico expressed sequence tags (ESTs), RT-PCR, and q-PCR analyses. Results: We identified 10 genes that were more highly expressed in brain tumor-initiating cells than in neural stem cells. In addition, we identified 10 other genes that were more highly expressed in brain tumor-initiating cells than in glioma cell line cells from the cDNA microarray analysis. Using the EST database, we looked to see if the 20 genes were expressed more highly in gliomas, compared with normal adult brains. Among the 20 genes, five (KLRC2, HOXB2, KCNJ2, KLRC1, and COL20A1) were expressed more than twice in glioma samples, compared with normal adult brains, and, therefore, were referred for further evaluation. RT-PCR was conducted using cDNA samples obtained from neural stem cells, normal brain tissue, fetal brain tissue, glioma cell lines, and glioma tumor-initiating cell lines. KLRC2, a transmembrane activating receptor in natural killer cells, was expressed more highly in glioma-initiating cells than in neural stem cell lines or normal adult brain tissue. The q-PCR analysis revealed that expression of KLRC2 was significantly higher in brain tumor-initiating cells compared to normal brain controls. Conclusion: KLRC2 could be a novel cellular marker for brain tumor-initiating cells.

Endonasal Chiasmapexy Using Autologous Cartilage/Bone for Empty Sella Syndrome After Cabergoline Therapy for Prolactinoma.

BACKGROUND: Visual field deterioration caused by secondary empty sella after cabergoline therapy for prolactinoma is a rare event. Chiasmapexy is performed to treat empty sella syndrome. Although various materials have been used for the elevation of the optic chasm, the most appropriate material remains to be established. Here, we describe the efficiency of chiasmapexy for empty sella syndrome following dopamine agonist treatment and the utility of septal cartilage and sphenoidal sinus bone as materials for chiasmapexy. CASE DESCRIPTION: A 35-year-old male with a history of cabergoline therapy for prolactinoma presented with visual deterioration. His magnetic resonance imaging revealed optic chiasm herniation into the empty sella. Endoscopic endonasal transsphenoidal chiasmapexy was performed using septal cartilage and sphenoidal sinus bone as materials for elevating the chiasm. Visual function improved immediately after operation. CONCLUSIONS: Chiasmapexy is an effective surgical method for treating visual deterioration caused by empty sella after cabergoline treatment. Endoscopic endonasal chiasmapexy with septal cartilage and sphenoidal sinus bone is a considerable option because it is minimally invasive and involves decreased risk of infection.

Endoscopic Endonasal Removal of Large Calcified Pituitary Adenoma: Case Report and Review of the Literature.

BACKGROUND: Large calcified intrasellar masses, called pituitary stones, have been reported as calcified pituitary adenomas in the literature. Although relatively rare, calcified pituitary adenomas appear in various formations. Thus, whether the lesion is removable-and, if so, which approach is appropriate-mainly depends on its formation and quality. CASE DESCRIPTION: A 46-year-old woman presented with visual loss and amenorrhea. Although computed tomography showed a uniformly calcified sellar tumor, magnetic resonance imaging displayed heterogenous intensity on T2-weighted images and mild gadolinium enhancement, suggesting that the lesion was a mixture of pituitary adenoma and fine calcification. Thus, we undertook tumor resection via an endoscopic endonasal approach, which resulted in total removal. The pathological diagnosis was a pituitary adenoma with rich calcification. CONCLUSIONS: We report a rare case of a large pituitary stone that was successfully removed via an endoscopic endonasal approach. This could therefore be a feasible, effective technique for the removal of pituitary stones, although careful analysis of preoperative magnetic resonance imaging is required.

Pros and cons of using ORBEYE™ for microneurosurgery.

OBJECTIVE: To evaluate the pros and cons of using a newly developed microscope, ORBEYE™, during microneurosurgery. PATIENTS AND METHODS: ORBEYE™ use in 14 microneurosurgical procedures was retrospectively assessed by nine neurosurgeons after the procedure. A questionnaire comprising 20 questions was designed and used for evaluation. RESULTS: Compared with the current gold standard, the binocular microscope, ease of setting up the equipment was scored the highest, whereas ease of conducting surgery in a position of an assistant was scored the lowest. Among characteristics of ORBEYE™ itself, the space-saving feature was scored the highest and was followed by the ability to perform procedures in a comfortable position. The only characteristic that was rated below average was ease of operation in a position of an assistant. Neurosurgeons with greater experience (more than five procedures using ORBEYE™) provided significantly higher scores (p = 0.0196) for characteristics of ORBEYE™ itself compared with neurosurgeon with fewer ORBEYE™ experience. CONCLUSIONS: The main benefits of the ORBEYETM are its compact size and freedom from focusing through the eye lens of a conventional binocular microscope. However, it appears to be disadvantageous for operating in a position of an assistant because the surgical field has a rotated view on the monitor from a position of an assistant. Nonetheless, because of certain advantages, we believe the ORBEYE™ could be of additional help to use of conventional binocular microscope at the moment and will facilitate microneurosurgery in the future.

Multiple Approaches to the Investigation of Cell Assembly in Memory Research-Present and Future.

In this review article we focus on research methodologies for detecting the actual activity of cell assemblies, which are populations of functionally connected neurons that encode information in the brain. We introduce and discuss traditional and novel experimental methods and those currently in development and briefly discuss their advantages and disadvantages for the detection of cell-assembly activity. First, we introduce the electrophysiological method, i.e., multineuronal recording, and review former and recent examples of studies showing models of dynamic coding by cell assemblies in behaving rodents and monkeys. We also discuss how the firing correlation of two neurons reflects the firing synchrony among the numerous surrounding neurons that constitute cell assemblies. Second, we review the recent outstanding studies that used the novel method of optogenetics to show causal relationships between cell-assembly activity and behavioral change. Third, we review the most recently developed method of live-cell imaging, which facilitates the simultaneous observation of firings of a large number of neurons in behaving rodents. Currently, all these available methods have both advantages and disadvantages, and no single measurement method can directly and precisely detect the actual activity of cell assemblies. The best strategy is to combine the available methods and utilize each of their advantages with the technique of operant conditioning of multiple-task behaviors in animals and, if necessary, with brain-machine interface technology to verify the accuracy of neural information detected as cell-assembly activity.

Characteristics of diabetic osteopenia in KK-Ay diabetic mice.

We examined the bone mineral density (BMD) of the proximal region and the mid-diaphysis of the femur using dual energy X-ray absorption (DXA), the blood osteocalcin level and the blood glucose level every five weeks from 8 to 23 weeks old in KK-Ay diabetic mice. The BMD of the proximal region after 18 weeks old was significantly lower when compared with that at 8 weeks old (p<0.05), whereas there was no significant difference in the BMD of the mid-diaphysis at each week. The BMD of the proximal region at 18 weeks old was significantly lower than that in ddY mice, used as controls (p<0.05). The blood osteocalcin level at 18 weeks old was significantly lower than that at 8 weeks old and that in 18-week-old ddY mice (p<0.05). There was significant negative correlation between the blood glucose level and the BMD of the proximal region (r=-0.64, p<0.05). These results suggest that type 2 diabetes exerts an influence only on spongy bone, not on cortical bone, and that the BMD in the proximal region of the femur seems to be affected by blood glucose level, parallel with the progression of diabetes, through the blood osteocalcin level. In the present study, we show the characteristics of diabetic osteopenia in KK-Ay mice, an animal model of type 2 diabetes.

Effect of corosolic acid on dietary hypercholesterolemia and hepatic steatosis in KK-Ay diabetic mice.

Corosolic acid (CA), contained in the leaves of the banaba plant (Lagerstroemia speciosa L.), is a pentacyclic triterpene, and has hypoglycemic effects. The effects of CA on dietary hypercholesterolemia and hepatic steatosis were assessed in KK-Ay mice, an animal model of type 2 diabetes. Two kinds of high cholesterol diet with or without 0.023% CA, were prepared for the study. KK-Ay mice were fed a normal diet (controls), the high cholesterol diet with CA (CA-mice) or that without CA (HC-mice) for 10 weeks. CA inhibited the mean blood cholesterol level by 32% (P<0.05) and the liver cholesterol content by 46% (P<0.05) compared with those of HC-mice 10 weeks after the start of dietary intake. Acutely, CA inhibited the mean blood cholesterol level 4 h after the administration of a high-cholesterol cocktail in an oral cholesterol-loading test, compared with that of control mice (P<0.05). These results suggest that CA has some direct effects on the cholesterol absorption process in the small intestine. CA may inhibit the activity of cholesterol acyltransferase, which acts in the re-esterification of cholesterol in the small intestine, in type 2 diabetes.

Effect of corosolic acid on the hydrolysis of disaccharides.

The banaba leaf (Lagerstroemia speciosa L.) has been used in traditional Oriental medicine to treat diabetes in the Philippines. It contains corosolic acid (CA), a compound which has a hypoglycemic effect. We examined the effect of CA on blood glucose levels and the hydrolysis of disaccharides in the small intestine in mice. CA (10 mg/kg body weight) improved hyperglycemia after an oral administration of sucrose, and significantly reduced the hydrolysis of sucrose in the small intestine. These results suggest that the hypoglycemic activity of CA is derived, at least in part, due to the inhibition of the hydrolysis of sucrose.

Neuropathological alteration of aquaporin 1 immunoreactive enteric neurons in the streptozotocin-induced diabetic rats.

Long-term diabetic patients exhibit major clinical gastrointestinal problems, such as diarrhea and constipation. In recent years, water channel protein, aquaporin 1 (AQP1) has been identified in the enteric nervous system (ENS). We have examined the pathological changes in AQP1 immunoreactive (IR) neurons in streptozotocin-induced (STZ) diabetic rats. Eight-week-old Wistar rats were injected with streptozotocin, and artificial diabetes was induced. Sixteen-week-old STZ rats were then examined with double immunofluorescence staining and ABC immunohistochemical staining. AQP1-IR neurons in STZ rats were significantly increased compared with control rats (p<0.01). The ratio of AQP1 vs. HuC/D in STZ rats was also clearly increased as compared with control rats (p<0.05). It was apparent that thick AQP1-IR fibers were frequently observed in the secondary and tertiary myenteric plexus of STZ rats. The AQP1-IR fibers of STZ rats conspicuously showed many swollen varicosities. These swollen varicose fibers were also observed in the longitudinal and circular muscle layers. Streptozotocin-induced diabetic rats showed pathological changes in AQP1-IR neurons of the ENS. The alteration of AQP1-IR neurons may be possible contribute to diabetic gastrointestinal dysfunction in streptozotocin-induced diabetic rats.

Sex differentiation and pubertal development of gonads in the viviparous mosquitofish, Gambusia affinis.

The ontogenetic development of gonads from embryo to adult was observed histologically in the viviparous teleost, Gambusia affinis. Primordial germ cells (PGCs) appeared in the subendodermal space of the embryo 14 days before birth, and then transferred to the dorsal mesentery to form paired genital ridges 12 days before birth. The PGCs proliferated in the genital ridge, forming gonadal primordia 10 days before birth. All gonadal primordia differentiated to the ovary containing oocytes 2 days before birth, but then redifferentiated to the ovary and testis just after birth. This indicates that the mosquitofish is a juvenile hermaphroditic species. The characteristics of gonadal sex differentiation just after birth were enlargement of the oocytes in females, and invasion of somatic cells from the hilar region to an inner portion of the gonad in males. The paired ovary fused at the basal area 5 days after birth, then on the ventral and dorsal portions, developing into a single ovary 10 days after birth. During this time a single ovarian cavity was formed on the dorsal portion of the ovary. The paired testes fused only at the basal area and became a single testis having two main lobes 10 days after birth. The oocytes gradually developed and began vitellogenesis 100 days after birth, but did not reach maturation until 110 days after birth. Spermatogenic cells formed cysts at 20 days, began meiosis at 70 days, and matured to form sperm balls 90 days after birth. The male fish sexually matured earlier than the female.

Antidiabetic effect of nitobegiku in KK-Ay diabetic mice.

In the past, nitobegiku (the herb of Tithonia diversifolia (Hemsl) A. Gray) has been used as a medicinal plant for diabetes. Antidiabetic effect of the water extract of Nitobegiku (NG) was investigated in KK-Ay-mice--one of the animal models of type 2 diabetes. NG (1,500 mg/kg body weight) reduced the blood glucose of KK-Ay mice from 509 +/- 22 mg/dl to 340 +/- 14 mg/dl (p < 0.001) and also lowered the plasma insulin (p < 0.05) 7 hours after single oral administration. No change in blood glucose of NG-treated normal mice (ddY) was seen. These results support that NG improve glucose metabolism by reducing insulin resistance. Therefore, NG may be useful for treatment of type 2 diabetes.