The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology

Respiratory activities are produced by medullary respiratory rhythm generators and are modulated from various sites in the lower brainstem, and which are then output as motor activities through premotor efferent networks in the brainstem and spinal cord. Over the past few decades, new knowledge has been accumulated on the anatomical and physiological mechanisms underlying the generation and regulation of respiratory rhythm. In this review, we focus on the recent findings and attempt to elucidate the anatomical and functional mechanisms underlying respiratory control in the lower brainstem and spinal cord.     

d-Sorbose inhibits disaccharidase activity and demonstrates suppressive action on postprandial blood levels of glucose and insulin in the rat

In an attempt to develop d-sorbose as a new sweetener that could help in preventing lifestyle-related diseases, we investigated the inhibitory effect of d-sorbose on disaccharidase activity, using the brush border membrane vesicles of rat small intestines. The inhibitory effect was compared with that of l-sorbose and other rare sugars, and the small intestinal disaccharidases in rats was compared with that of humans as well. In humans and the small intestines of rats, d-sorbose strongly inhibited sucrase activity and weakly inhibited maltase activity. Inhibition by d-sorbose of sucrase activity was similar to that of l-arabinose, and the K_i of d-sorbose was 7.5 mM. Inhibition by d-sorbose was very strong in comparison with that of l-sorbose (K_i, 60.8 mM), whereas inhibition of d-tagatose was between that of d-sorbose and l-sorbose. The inhibitory mode of d-sorbose for sucrose and maltase was uncompetitive, and that of l-sorbose was competitive. To determine a suppressive effect on postprandial blood levels of glucose and insulin via inhibition of sucrase activity, sucrose solution with or without d-sorbose was administered to rats. Increments in the blood levels of glucose and insulin were suppressed significantly after administration of sucrose solution with d-sorbose to rats, in comparison to administration of sucrose solution without d-sorbose. In contrast, the suppressive effect of l-sorbose on postprandial blood levels of glucose and insulin was very weak. These results suggest that d-sorbose may have an inhibitory effect on disaccharidase activity and could be used as a sweetener to suppress the postprandial elevation of blood levels of glucose and insulin. The use of d-sorbose as a sweetener may contribute to the prevention of lifestyle-related diseases, such as type 2 diabetes mellitus.     

Tumor specific cytotoxicity of β-glucosylceramide: structure–cytotoxicity relationship and anti-tumor activity in vivo

This study describes the structure–cytotoxicity relationship of β-glucosylceramide (β-GluCer) and its antitumor activity in vivo. Unglycosylated ceramide had no selective cytotoxicity which demonstrated that the sugar moiety plays a critical role for the expression of selective cytotoxicity by β-GluCer. β-Galactosylceramide also showed tumor specific cytotoxicity suggesting that the chemical structure of sugar group is not a factor for the selective toxicity. Similarly, unglycosylated ceramides of short acyl chain also selectively inhibited the growth of cancer cells. These findings in concert point to the importance of the hydrophilicity of the ceramide molecule rather than the chemical structure for the cyto-selectivity. Treatment of the cells with β-GluCer increased the concentration of reactive oxygen species leading to cell cycle arrest and necrosis. Intraperitoneal administration of β-GluCer significantly suppressed the growth of tumor implanted to the back of mice. β-GluCer also induced antitumor immunity via the activation of NKT cells in vivo, and decreased the tumor metastasis of lymphoma cells. The present study thus demonstrated the antitumor activity of β-GluCer in vivo, and discussed the mechanisms responsible for the growth inhibition. H. Oku and C. Li equally contributed to this study.     

Phenotypic spectrum of CHARGE syndrome with CHD7 mutations

CHD7 gene mutations were identified in 17 (71%) of 24 children clinically diagnosed to have CHARGE syndrome (C, coloboma of the iris or retina; H, heart defects; A, atresia of the choanae; R, retardation of growth and/or development; G, genital anomalies; and E, ear abnormalities). Colobomata, hearing loss, laryngomalacia, and vestibulo-cochlear defect were prevalent. Molecular testing for CHD7 enables an accurate diagnosis and provides health anticipatory guidance and genetic counseling to families with CHARGE syndrome.     

Evaluation of O-[18F]fluoromethyl-d-tyrosine as a radiotracer for tumor imaging with positron emission tomography

O-[¹⁸F]Fluoromethyl-d-tyrosine (d-[¹⁸F]FMT) has been reported as a potential tumor-detecting agent for positron emission tomography (PET). However, the reason why d-[¹⁸F]FMT is better than l-[¹⁸F]FMT is unclear. To clarify this point, we examined the mechanism of their transport and their suitability for tumor detection. The stereo-selective uptake and release of enantiomerically pure d- and l-[¹⁸F]FMT by rat C6 glioma cells and human cervix adenocarcinoma HeLa cells were examined. The results of a competitive inhibition study using various amino acids and a selective inhibitor for transport system L suggested that d-[¹⁸F]FMT, as well as l-[¹⁸F]FMT, was transported via system L, the large neutral amino acid transporter, possibly via LAT1. The in vivo distribution of both [¹⁸F]FMT and [¹⁸F]FDG in tumor-bearing mice and rats was imaged with a high-resolution small-animal PET system. In vivo PET imaging of d-[¹⁸F]FMT in mouse xenograft and rat allograft tumor models showed high contrast with a low background, especially in the abdominal and brain region. The results of our in vitro and in vivo studies indicate that l-[¹⁸F]FMT and d-[¹⁸F]FMT are specifically taken up by tumor cells via system L. d-[¹⁸F]FMT, however, provides a better tumor-to-background contrast with a tumor/background (contralateral region) ratio of 2.741 vs. 1.878 with the l-isomer, whose difference appears to be caused by a difference in the influence of extracellular amino acids on the uptake and excretion of these two isomers in various organs. Therefore, d-[¹⁸F]FMT would be a more powerful tool as a tumor-detecting agent for PET, especially for the imaging of a brain cancer and an abdominal cancer.     

Optic cup enlargement followed by reduced optic nerve head circulation after optic nerve stimulation.

PURPOSE: To investigate changes in optic nerve head (ONH) circulation, visual evoked potentials (VEPs), and ONH cupping after stimulation of the optic nerve. METHODS: Electrodes were fixed above the optic chiasma in rabbits under general anesthesia. Screw-type electrodes for VEP recording were fixed on the dura. ONH circulation, intraocular pressure (IOP), and blood pressure (BP) were measured after the passage of a current of 0.1 mA for 0.1 second (weak stimulation), 1 mA for 1 second (moderate), 5 mA for 10 seconds (strong), or 25 mA for 10 seconds (severe). Normalized blur (NB), indicative of tissue blood flow and velocity, was measured in the ONH after each stimulation, by using a laser speckle circulation analyzer. Changes in VEP and ocular fundus were also recorded. The ratio of cup area (CA) to disc area (DA) was measured before and 4 weeks after stimulation. After all experiments, the ONH was histologically examined. RESULTS: Weak stimulation increased NB in ONH for 10 minutes, whereas strong or severe stimulation significantly decreased NB for a longer time, in a dose-dependent manner. BP showed no significant change, except with severe stimulation. IOP was not significantly changed. VEP amplitude was reduced 30 minutes after strong stimulation. The CA-to-DA ratio was significantly increased 4 weeks after strong stimulation. In some rabbits, disc hemorrhage occurred, followed by enlargement of disc cupping, with slight gliosis. CONCLUSIONS: Electrical stimulation of the optic nerve changed ONH circulation and VEPs and increased disc cupping. This technique warrants further investigation as an experimental model for normal-tension glaucoma.     

Quantitative pediatric surgical skill assessment using a rapid-prototyped chest model

Introduction: Though minimally invasive pediatric surgery has become more widespread, pediatric-specific surgical skills have not been quantitatively assessed. Material and methods: As a first step toward the quantification of pediatric-specific surgical skills, a pediatric chest model comprising a three-dimensional rapid-prototyped pediatric ribcage with accurate anatomical dimensions, a suturing skin model with force-sensing capability, and forceps with motion-tracking sensors were developed. A skill assessment experiment was conducted by recruiting 16 inexperienced pediatric surgeons and 14 experienced pediatric surgeons to perform an endoscopic intracorporeal suturing and knot-tying task in both the pediatric chest model setup and the conventional box trainer setup. Results: The instrument motion measurement was successful in only 20 surgeons due to sensor failure. The task completion time, total path length of instruments, and applied force were compared between the inexperienced and experienced surgeons as well as between the box trainer and chest model setups. The experienced surgeons demonstrated better performance in all parameters for both setups, and the pediatric chest model was more challenging due to the pediatric features replicated by the model. Conclusion: The pediatric chest model was valid for pediatric skill assessment, and further analysis of the collected data will be conducted to further investigate pediatric-specific skills.     

Microsurgical robotic system for vitreoretinal surgery

Purpose  

Robotics may improve vitreoretinal surgery by steadying hand motion, thereby reducing negative outcomes. This study aimed to develop a microsurgical robot for vitreoretinal surgery and to perform clinical procedures using robot-assisted interventions.