Evaluation of the Effects of Cultured Bone Marrow Mesenchymal Stem Cell Infusion on Hepatocarcinogenesis in Hepatocarcinogenic Mice With Liver Cirrhosis.

OBJECTIVES: Liver transplantation remains the only curative therapy for decompensated liver cirrhosis. However, it has several limitations, and not all patients can receive liver transplants. Therefore, liver regenerative therapy without liver transplantation is considered necessary. In this study, we attempted minimally invasive liver regenerative therapy by peripheral vein infusion of bone marrow-derived mesenchymal stem cells (BMSCs) cultured from a small amount of autologous bone marrow fluid and evaluated the effects of BMSCs on hepatocarcinogenesis in a mouse model. METHODS: C57BL/6 male mice were injected intraperitoneally with N-nitrosodiethylamine once at 2 weeks of age, followed by carbon tetrachloride twice a week from 6 weeks of age onwards, to create a mouse model of highly oncogenic liver cirrhosis. From 10 weeks of age, mouse isogenic green fluorescent protein-positive BMSCs (1.0 × 106/body weight) were infused once every 2 weeks, for a total of 5 times, and the effects of frequent BMSC infusion on hepatocarcinogenesis were evaluated. RESULTS: In the histologic evaluation, no significant differences were observed between the controls and BMSC-administered mice in terms of incidence rate, number, or average size of foci and tumors. However, significant suppression of fibrosis and liver injury was confirmed in the group that received BMSC infusions. DISCUSSION: Considering that BMSC infusion did not promote carcinogenesis, even in the state of highly oncogenic liver cirrhosis, autologous BMSC infusion might be a safe and effective therapy for human decompensated liver cirrhosis.

High resolution optical mapping of cardiac action potentials in freely beating rabbit hearts.

UNLABELLED: Optical mapping of action potentials (APs) has become important tools for the cardiac electrophysiology. However, cardiac contraction unavoidably produces motion artifacts (MA) in optical signal. We developed a method to suppress motion artifacts without arresting the hearts. METHODS: Using a dual-wavelength optical mapping system, APs were recorded on the surface of an isolated rabbit heart. Transmembrane APs were simultaneously recorded using glass microelectrodes. We eliminated MA in a frontal plane by a motion tracking technique. Subsequently, a dual-wavelength ratiometric method was used to remove MA in a vertical direction to a frontal plane. RESULTS: MA were effectively removed from optical signals. Action potential duration measured from optical signals corresponded with those measured from microelectrodes (r2=0.9677). Our method enables us to map action potentials in freely beating hearts.

The laryngeal tube compared with the laryngeal mask: insertion, gas leak pressure and gastric insufflation.

BACKGROUND: We have compared the laryngeal tube and laryngeal mask in 22 patients for the success rate of insertion, gas leak pressure and the incidence of gastric insufflation. METHOD: In a randomized, crossover design, the laryngeal tube and laryngeal mask were inserted in turn after induction of anaesthesia and neuromuscular block. The cuffs were inflated until the intracuff pressure reached 60 cm H(2)O. We measured adequacy of ventilation and the minimum airway pressure at which gas leaked around the cuff. The presence or absence of gastric insufflation was studied at an inflation pressure of 20 cm H(2)O. RESULTS: It was possible to ventilate through the laryngeal tube in 21 patients and through the laryngeal mask in 21 patients. The mean leak pressure for the laryngeal tube (26 (SD 5) cm H(2)O) was significantly greater than that for the laryngeal mask (19 (4) cm H(2)O) (P<0.01; 95% confidence intervals for mean difference: 5.3-10.2 cm H(2)O). Gastric insufflation did not occur when the laryngeal tube was used and was noted in three patients when the laryngeal mask was used. CONCLUSION: The laryngeal tube provides a better seal in the oropharynx than the laryngeal mask.

Efficacy of catheter needles with safeguard mechanisms.

There has been considerable interest in using safeguarded needles to reduce needlestick injury. In a randomised design, we studied the efficacy and safety of two such needles (the Insyte AutoGuard and the Protective Acuvance), by comparing them with a conventional catheter needle (Insyte), for intravenous cannulation (18 G) in 150 patients and for intra-arterial cannulation in another 150 patients (20 G). For intravenous cannulation, the success rates were similar in the three groups but insertion of the AutoGuard or Acuvance catheter was significantly more difficult than the conventional catheter. For the Acuvance, the back-flow of blood into the chamber was sometimes too slow. For intra-arterial cannulation, insertion of the AutoGuard was significantly more difficult than the other two devices, mainly because the backflow chamber of the AutoGuard was too short so that the chamber often filled with blood before cannulation. Insertion of the Acuvance was significantly more difficult than the conventional catheter. For both intravenous and intra-arterial insertion, handling of the withdrawn needle was judged significantly safer in the AutoGuard group than the other two groups, whereas there was no significant difference in the safety between the Acuvance and conventional groups. In five subjects from the AutoGuard group, blood splashed on retraction of the needle. Blood contamination during needle withdrawal occurred frequently in the control and Acuvance groups, but rarely occurred in the AutoGuard group. Therefore, the AutoGuard needle is more suitable for intravenous cannulation, and the Acuvance is more suitable for intra-arterial cannulation.

Noise-enhanced heart rate and sympathetic nerve responses to oscillatory lower body negative pressure in humans.

By injecting noise into the carotid sinus baroreceptors, we previously showed that heart rate (HR) responses to weak oscillatory tilt were enhanced via a mechanism known as "stochastic resonance." It remains unclear, however, whether the same responses would be observed when using oscillatory lower body negative pressure (LBNP), which would unload the cardiopulmonary baroreceptors with physically negligible effects on the arterial system. Also, the vasomotor sympathetic activity directly controlling peripheral resistance against hypotensive stimuli was not observed. We therefore investigated the effects of weak (0 to approximately -10 mmHg) oscillatory (0.03 Hz) LBNP on HR and muscle sympathetic nerve activity (MSNA) while adding incremental noise to the carotid sinus baroreceptors via a pneumatic neck chamber. The signal-to-noise ratio of HR, cardiac interbeat interval, and total MSNA were all significantly improved by increasing noise intensity, while there was no significant change in the arterial blood pressure in synchronized with the oscillatory LBNP. We conclude that the stochastic resonance, affecting both HR and MSNA, results from the interaction of noise with the signal in the brain stem, where the neuronal inputs from the arterial and cardiopulmonary baroreceptors first come together in the nucleus tractus solitarius. Also, these results indicate that the noise could induce functional improvement in human blood pressure regulatory system in overcoming given hypotensive stimuli.

Behavioral-independent features of complex heartbeat dynamics.

We test whether the complexity of the cardiac interbeat interval time series is simply a consequence of the wide range of scales characterizing human behavior, especially physical activity, by analyzing data taken from healthy adult subjects under three conditions with controls: (i) a "constant routine" protocol where physical activity and postural changes are kept to a minimum, (ii) sympathetic blockade, and (iii) parasympathetic blockade. We find that when fluctuations in physical activity and other behavioral modifiers are minimized, a remarkable level of complexity of heartbeat dynamics remains, while for neuroautonomic blockade the multifractal complexity decreases.

Functional stochastic resonance in the human brain: noise induced sensitization of baroreflex system.

We demonstrate experimentally that noise can enhance the homeostatic function in the human blood pressure regulatory system. The results show that the compensatory heart rate response to the weak periodic signal introduced at the venous blood pressure receptor is optimized by adding noise to the arterial blood pressure receptor. We conclude that this functional stochastic resonance most likely results from the interaction of noise with signal in the brain stem, where the neuronal inputs from these two different receptors first join together.

Analysis of respiratory sinus arrhythmia with respect to respiratory phase.

We evaluated the respiratory modulation of heart rate, i.e., respiratory sinus arrhythmia (RSA), with respect to respiratory phase derived from an analytic signal from the lung volume curve, during spontaneous breathing and paced breathing with different patterns. The magnitudes and waveforms of RSA in the phase domain were similar regardless of breathing pattern, even including spontaneous breathing. An examination of the occurrence of heart beats with respect to the respiratory phase revealed that synchronized patterns recently reported in the literature (Nature 392: 239, 1998) were observed during paced breathing with breath holding periods whereby the respiratory phase advanced more slowly. It was concluded that the phase domain approach might be useful in extracting RSA during spontaneous breathing and for elucidating detailed mechanisms for RSA. However, the use of this technique for studies investigating cardio-respiratory coupling should be approached cautiously, as the results may be influenced by breathing patterns.

Taste responses to amino acids from facial nerve branches innervating oral and extra-oral taste buds in the channel catfish, Ictalurus punctatus.

Electrophysiological recordings were obtained from two branches of the facial nerve innervating oral and extra-oral taste receptive fields, respectively, in the channel catfish, Ictalurus punctatus. The results indicate that taste buds innervated by the ramus ophthalmicus superficialis (ros), innervating taste buds on the nasal barbel, and the ramus palatinus (rp), innervating taste buds on the anterior palate, have similar chemical specificities for amino acids. Among the amino acids tested, the most stimulatory compounds for both the ros and rp were L-alanine and L-arginine, having estimated electrophysiological thresholds of approximately 10(-9) M. Dose-response functions for amino acid stimuli recorded from both the ros and rp were power functions extending over 5 log units of stimulus concentrations. The general similarity in the nature of the taste input from spatially distinct gustatory areas supports a chemotactic role of the facial taste system in the channel catfish.

Mechanical sensitivity of the facial nerve fibers innervating the anterior palate of the puffer, Fugu pardalis, and their central projection to the primary taste center.

Mechanical and chemical sensitivity of the palatine nerve, ramus palatinus facialis, innervating the anterior palate of the puffer, Fugu pardalis, and their central projection to the primary taste center were investigated. Application of horseradish peroxidase (HRP) to the central cut end of the palatine nerve resulted in retrogradely labeled neurons in the geniculate ganglion but no such neurons in the trigeminal ganglion, suggesting that the palatine nerve is represented only by the facial component. Tracing of the facial sensory root in serial histological sections of the brain stem suggested that the facial sensory nerve fibers project only to the visceral sensory column of the medulla. Peripheral recordings from the palatine nerve bundle showed that both mechanical and chemical stimuli caused marked responses. Mechanosensitive fibers were rather uniformly distributed in the nerve bundle. Intra-cranial recordings from the trigeminal and facial nerves at their respective roots revealed that tactile information produced in the anterior palate was carried by the facial nerve fibers. Elimination of the sea water current over the receptive field also caused a marked response in the palatine nerve bundle or facial nerve root while this did not cause any detectable responses in the trigeminal nerve root. Single fiber analyses of the mechanical responsiveness of the palatine nerve were performed by recording unit responses of 106 single fibers to mechanical stimuli (water flow), HCl (0.005 M), uridine-5'-monophosphate (UMP, 0.001 M), proline (0.01 M), CaCl2 (0.5 M), and NaSCN (0.5 M). All these fibers responded well to one of the above stimuli; however, most taste fibers did not respond well to the inorganic salts. The palatine fibers (n = 36), identified as mechanosensitive, never responded to any of the chemical stimuli, whereas chemosensitive fibers (n = 70) did not respond to mechanical stimuli at all. The chemosensitive units showed a high specificity to the above stimuli: they tended to respond selectively to hydrochloric acid, UMP, or proline. The responses of the mechanosensitive units consisted of phasic and tonic impulse trains and the sensitivity of the units varied considerably. The results reveal that the facial nerve fibers innervating the anterior palate of the puffer contain two kinds of afferent fibers, chemosensory and mechanosensory respectively, and suggest that the convergence of the tactile and gustatory information first occurs in the neurons of the primary gustatory center in the medulla.