Automatic irrigation system with a fiber-optic pressure sensor regulating intrapelvic pressure for flexible ureteroscopy.

Increased intrapelvic pressure (IPP) due to irrigation during flexible ureteroscopy (f-URS) can pose a risk of postoperative severe urinary tract infection associated with pyelovenous backflow. An automatic regulation system for maintaining safe IPP levels could enable surgeons to perform f-URS safely without postoperative complications. This study aimed to assess the measurement accuracy of an ultra-miniature fiber-optic pressure sensor incorporated into a small-caliper ureteroscope for assessing IPP and to develop an automatic irrigation system linked to this sensor. A porcine kidney was used for the ex vivo experiment. The nephrostomy catheter, connected to the conventional pressure transducer, was placed on the renal pelvis to evaluate the actual IPP (a-IPP). For measuring IPP using the fiber-optic pressure sensor (fo-IPP) built into the f-URS, a diaphragm pressure sensor of Φ250 µm was used. To establish an irrigation system, the optimal proportional-integral-derivative (PID) controller was explored to accurately adjust the irrigation pump flow rate. A high correlation between a-IPP and fo-IPP was confirmed across irrigation pressure values of 60-180 mbar (all, r ≥ 0.7, p < 0.001). When performing bolus irrigation, although fo-IPP showed relatively a higher peak value than a-IPP, the response time of fo-IPP was equivalent to that of a-IPP. After PID parameter optimization, our automatic irrigation system based on fo-IPP smoothly and accurately regulated the intended IPP set in the 5-20 mmHg range without overshooting. We successfully developed and demonstrated an automatic irrigation system regulating IPP based on the PID controller for f-URS, utilizing a fiber-optic pressure sensor. Further research, including in vivo studies, will be needed to assess clinical feasibility.

Development of modified laser Doppler flowmetry device for real-time monitoring of esophageal mucosal blood flow: a preclinical assessment with an animal model.

This study aimed to modify a laser Doppler flowmeter designed and assembled at our institute. After measuring sensitivity evaluation in ex vivo experiments, we confirmed the efficacy of this new device for monitoring real-time esophageal mucosal blood flow changes after thoracic stent graft implantation by simulating various clinical situations in an animal model. Thoracic stent graft implantation was performed in a swine model (n = 8). Esophageal mucosal blood flow decreased significantly from baseline (34.1 ± 18.8 ml/min/100 g vs. 16.7 ± 6.6 ml/min/100 g, P < 0.05) in the lower esophagus (Th6-Th8) where the stent graft covered the aorta. In the hemorrhagic shock model (shock index ≥ 1.0), esophageal mucosal blood flow showed a remarkable change from baseline in the upper esophagus (Th1-Th3), where the stent graft did not cover the aorta (20.8 ± 9.8 ml/min/100 g vs. 12.9 ± 8.6 ml/min/100 g, P < 0.01); however, it returned to the baseline value within a 30-min period. Mucosal blood flow remained stable in the esophagus, where the stent graft did not cover the aorta. After elevating the mean blood pressure to > 70 mmHg with continuous intravenous noradrenaline infusion, esophageal mucosal blood flow increased significantly in both regions; however, the reaction was different between the two regions. Our newly developed laser Doppler flowmeter could measure real-time esophageal mucosal blood flow changes in various clinical situations during thoracic stent graft implantation in a swine model. Hence, this device can be applied in many medical fields by downsizing it.

Estimation of daily intake of food additives by Japanese young children using the market basket method in 2018.

To estimate the daily intake of food additives by young children aged 1-6 years in Japan, an intake survey was conducted in 2018 using the market basket method for food additives, including twelve types of colourants, three kinds of preservatives, three kinds of sweeteners and two kinds of food manufacturing agents. A list of the daily consumption of processed foods was prepared based on a special survey (MHLW 2011) and used for the estimation. The results of the survey showed that the food additives with the highest daily intake were phosphorus compounds (phosphoric acid and its salts; 11.2 mg/kg bw/day, expressed as phosphorus), followed by propylene glycol (0.80 mg/kg bw/day). The daily intake of other food additives ranged from 0 to 0.20 mg/kg bw/day. The estimated daily intake of each food additives by young children was compared with the acceptable daily intake (ADI) or maximum tolerable daily intake (MTDI). The highest ratio of the estimated daily intake to ADI was 3.2% for propylene glycol, whereas the ratios of the estimated daily intake to ADI for colourants, preservatives and sweeteners ranged from 0 to 1.1% (benzoic acid). The ratio of the estimated daily intake to MTDI for phosphorus compounds was 16%.

Design and kinematics of a tube-shaped multidirectional bending robotic device using slackened SMA wires for transurethral ureterolithotripsy.

PURPOSE: The complex and elaborate structure of the urinary system presents surgeons with difficulty in using a ureteroscope with a fixed optical fiber to reach the targeted calculus. To address this challenge, a robotic device is required to control the direction of laser irradiation position independently in ureteroscopes. METHOD: A continuum robotic device was designed and fabricated. The device is constructed with three slackened shape memory alloy (SMA) wires to control the laser irradiation position of the optical fiber combined with the view of the camera on the tip of the ureteroscope. Kinematics analysis and experimental evaluation reveal the capability of the device. RESULTS: The structure of the device is the same as a single-joint continuum robot. This device is unique because of the tiny diameter of 1.1 mm which can be used inside the ureteroscope through a Ø1.2 mm inner channel into the kidney for transurethral ureterolithotripsy. Kinematic analysis revealed the relationship among space coordinates, angles of bending, and direction and SMA wires length. The maximum bending angle was around 25° when the current value was 350 mA on a single SMA wire. The device could achieve multi-directional bending by allocating the values of current on SMA wires, separately. CONCLUSION: This device offers a major advancement in small size and dexterity in medical robotics. Combined with a proper control system, this device could simplify the operation and improve the efficiency of the transurethral ureterolithotripsy.

Focused Ultrasound PC-6 Stimulation Effects on Blood Flow Volume, Skin Temperature, and Coldness of the Finger and Toe.

INTRODUCTION: Focused ultrasound can stimulate a specific point of tissue and can be a noninvasive method for acupoint stimulation. The aim of this study was to clarify the effects of acupoint stimulation by focused ultrasound on blood flow volume and coldness of the fingers and toes. MATERIALS AND METHODS: Forty healthy volunteers were included in this experiment. The blood flow volume and the skin temperature of a finger and toe were measured before and after stimulation of the pericardium 6 acupuncture point (PC-6) by focused ultrasound. Subjective coldness of the fingers and toes was also assessed using a visual analog scale (VAS) before and after stimulation. RESULTS: The maximum blood flow volumes of the finger and toe were significantly larger (p < 0.01) than those before stimulation. The maximum skin surface temperatures of the fingers were significantly higher (p < 0.01) than those before stimulation. The VAS scores for subjective coldness of the toes after stimulation were significantly higher (p < 0.01). CONCLUSION: The blood flow volume and skin temperature tended to increase after PC-6 stimulation. The VAS scores also indicated a tendency toward a warmer sensation in the toes after stimulation.

Lactate and glucose measurement in subepidermal tissue using minimally invasive microperfusion needle.

Knowing the concentrations of biological substances can help ascertain physiological and pathological states. In the present study, a minimally invasive microperfusion needle was developed for measuring the concentrations of biological substances in subepidermal tissue. The microperfusion needle has a flow channel with a perforated membrane through which biological substances from subepidermal tissue are extracted. Since this device uses a thin steel acupuncture needle as the base substrate, it has sufficient rigidity for insertion through the skin. The efficacy of the needle was examined by measuring lactate and glucose concentrations in mice. Lactate was injected intraperitoneally, and changes in lactate concentrations in subepidermal tissue over time were measured using the device. Lactate concentrations of blood were also measured as a reference. Lactate was successfully collected using the microperfusion needle, and the lactate concentration of perfused saline was significantly correlated with blood lactate concentration. Glucose solution was administered orally, and the glucose concentration of perfused saline was also correlated with blood glucose concentration. The newly developed microperfusion needle can be used for minimally invasive monitoring of the concentrations of biological substances.

Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.

OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. The authors developed a new ultrasound-facilitated drug delivery (UFD) system that enables the application of ultrasound at the infusion site. The purpose of this study was to demonstrate the efficacy of the UFD system and to examine effective ultrasound profiles. METHODS The authors fabricated a steel bar-based device that generates ultrasound and enables infusion of the aqueous drug from one end of the bar. The volume of distribution (Vd) after infusion of 10 ml of 2% Evans blue dye (EBD) into rodent brain was tested with different frequencies and applied voltages: 252 kHz/30 V; 252 kHz/60 V; 524 kHz/13 V; 524 kHz/30 V; and 524 kHz/60 V. In addition, infusion of 5 mM gadopentetate dimeglumine (Gd-DTPA) was tested with 260 kHz/60 V, the distribution of which was evaluated using a 7-T MRI unit. In a nonhuman primate (Macaca fascicularis) study, 300 µl of 1 mM Gd-DTPA/EBD was infused. The final distribution was evaluated using MRI. Two-sample comparisons were made by Student t-test, and 1-way ANOVA was used for multiple comparisons. Significance was set at p < 0.05. RESULTS After infusion of 10 µl of EBD into the rat brain using the UFD system, the Vds of EBD in the UFD groups were significantly larger than those of the control group. When a frequency of 252 kHz was applied, the Vd of the group in which 60 V was applied was significantly larger than that of the group in which 30 V was used. When a frequency of 524 kHz was applied, the Vd tended to increase with application of a higher voltage; however, the differences were not significant (1-way ANOVA). The Vd of Gd-DTPA was also significantly larger in the UFD group than in the control group (p < 0.05, Student t-test). The volume of Gd-DTPA in the nonhuman primate used in this study was 1209.8 ± 193.6 mm(3). This volume was much larger than that achieved by conventional CED (568.6 ± 141.0 mm(3)). CONCLUSIONS The UFD system facilitated the distribution of EBD and Gd-DTPA more effectively than conventional CED. Lower frequency and higher applied voltage using resonance frequencies might be more effective to enlarge the Vd. The UFD system may provide a new treatment approach for CNS disorders.

Brief effect of acupoint stimulation using focused ultrasound.

BACKGROUND: Acupuncture is used worldwide in medical treatment. However, needle insertion damages the skin and patients sometimes feel pain. To avoid such drawbacks, an acupoint stimulation device using focused ultrasound has been developed. Ultrasound stimulation does not damage the skin like acupuncture does because ultrasound can deliver vibration energy to soft tissues noninvasively. OBJECTIVES: The aim of this study was to clarify the effect of acupoint stimulation using focused ultrasound. SUBJECTS: Fifty (50) healthy volunteers (40 males and 10 females) were included in this experiment. DESIGN: Subjects were randomly assigned to two groups. LR-3 was stimulated bilaterally for 36 seconds by focused ultrasound and conventional acupuncture. Brachial artery blood flow volume was monitored by an ultrasound with an echo-tracking system. The hemodynamic parameters were measured before, during, and 30, 60, 180 seconds after stimulation. RESULTS: During stimulation, the blood flow volume of the acupuncture stimulation group decreased significantly (p<0.05) compared with resting value, but that of the focused ultrasound stimulation group did not decrease. Blood flow volume of both groups increased gradually and showed significant increase at 180 seconds after stimulation (p<0.05). CONCLUSIONS: Blood flow volume was increased significantly by both focused ultrasound stimulation and conventional acupuncture. Although a significant decrease of blood flow volume during acupuncture stimulation was observed, no such decrease was observed during ultrasound stimulation. Findings of the present study show that noninvasive stimulation of acupoints by focused ultrasound is as effective as conventional acupuncture in blood flow volume of the brachial artery.

Blocking effect of NIP-142 on the KCNQ1/KCNE1 channel current expressed in HEK293 cells.

We examined the effect of NIP-142, a benzopyran compound with terminating effect on experimental atrial arrhythmia, on the KCNQ1/KCNE1 channel, which underlies the slow component of the cardiac delayed rectifier potassium channel (I(Ks)). NIP-142, as well as chromanol 293B, showed concentration-dependent blockade of the current expressed in HEK293 cells; the EC(50) value of NIP-142 and chromanol 293B for the inhibition of tail current was 13.2 µM and 4.9 µM, respectively. These results indicate that NIP-142 has blocking effect on the KCNQ1/KCNE1 channel current.

Hepatic protection by glycyrrhizin and inhibition of iNOS expression in concanavalin A-induced liver injury in mice.

OBJECTIVE AND DESIGN: In this study, the possible protective effect of glycyrrhizin (GL), an active compound derived from licorice root, was examined on T cell-mediated liver injury in mice. MATERIALS AND METHODS: Mice were subjected to liver injury by intravenous injection of concanavalin A (Con A). They had been treated with GL (i.p.) 30 min before the injection. Liver injury was estimated by measuring serum levels of alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST), and by examining liver sections with hematoxylin-eosin staining. Expression of inducible nitric oxide synthase (iNOS) mRNA and protein in the liver was determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: Serum transaminases and hepatic iNOS levels increased with time after Con A treatment. Expression of iNOS mRNA in the liver was elevated for up to 8 h, and at 8 h, GL (ED(50): 10.5 mg/kg) suppressed the increases in AST and ALT in response to Con A. An increase in iNOS mRNA expression and protein was inhibited by treatment with GL. Furthermore, GL inhibited cell infiltration and the degeneration of hepatocytes in the liver of Con A-treated mice. CONCLUSION: The present study suggests that the prevention by GL of Con A-induced hepatitis is due partly to the modulation of hepatic iNOS induction and of degeneration of hepatocytes.

Analysis of arrhythmogenic profile in a canine model of chronic atrioventricular block by comparing in vitro effects of the class III antiarrhythmic drug nifekalant on the ventricular action potential indices between normal heart and atrioventricular block heart.

The chronic atrioventricular block dog is a useful model for predicting the future onset of drug-induced long QT syndrome in clinical practice. To better understand the arrhythmogenic profile of this model, we recorded the action potentials of the isolated ventricular tissues in the presence and absence of the class III antiarrhythmic drug nifekalant. The action potential durations of the Purkinje fiber and free wall of the right ventricle were longer in the chronic atrioventricular block dogs than in the dogs with normal sinus rhythm. Nifekalant in concentrations of 1 and 10 microM prolonged the action potential durations of Purkinje fiber and the free wall in a concentration-dependent manner. The extent of prolongation was greater in the chronic atrioventricular block dogs than in the normal dogs. However, increase of temporal dispersion of ventricular repolarization including early afterdepolarization was not detected by nifekalant in either group of dogs, indicating lack of potential to trigger arrhythmias in vitro. These results suggest that the ventricular repolarization delay in the chronic atrioventricular block model by nifekalant may largely depend on the decreased myocardial repolarization reserve, whereas the trigger for lethal arrhythmia was not generated in the in vitro condition in contrast to the in vivo experiment.

Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action potential shortening and GIRK1/4 channel.

Mechanisms for the atria-specific action potential-prolonging action of NIP-142 ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4-methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound that terminates experimental atrial arrhythmia, was examined. In isolated guinea-pig atrial tissue, NIP-142 reversed the shortening of action potential duration induced by either carbachol or adenosine. These effects were mimicked by tertiapin, but not by E-4031. NIP-142 concentration-dependently blocked the human G protein-coupled inwardly rectifying potassium channel current (GIRK1/4 channel current) expressed in HEK-293 cells with an EC50 value of 0.64 microM. At higher concentrations, NIP-142 blocked the human ether a go-go related gene (HERG) channel current with an EC50 value of 44 microM. In isolated guinea-pig papillary muscles, NIP-142 had no effect on the negative inotropic effect of carbachol under beta-adrenergic stimulation, indicating lack of effect on the muscarinic receptor and Gi protein. These results suggest that NIP-142 directly inhibits the acetylcholine-activated potassium current.

Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium.

NIP-142 is a novel benzopyran compound that was shown to prolong the atrial effective refractory period and terminate experimental atrial fibrillation in the dog. In the present study, we examined the effects of NIP-142 on isolated guinea pig myocardium and on the G-protein-coupled inwardly rectifying potassium channel current (acetylcholine-activated potassium current; I(KACh)) expressed in Xenopus oocytes. NIP-142 (10 and 100 microM) concentration-dependently prolonged the refractory period and action potential duration in the atrium but not in the ventricle. E-4031 and 4-aminopyridine prolonged action potential duration in both left atrium and right ventricle. Prolongation by NIP-142 of the atrial action potential duration was observed at stimulation frequencies between 0.5 and 5 Hz. In contrast, the prolongation by E-4031 was not observed at higher frequencies. Tertiapin, a blocker of I(KACh), prolonged action potential duration in the atrium but not in the ventricle. NIP-142 completely reversed the carbachol-induced shortening of atrial action potential duration. NIP-142 (1 to 100 microM), as well as tertiapin (0.1 to 100 nM), concentration-dependently blocked I(KACh) expressed in Xenopus oocytes; the blockade by NIP-142 was not affected by membrane voltage. In conclusion, NIP-142 was shown to prolong atrial refractory period and action potential duration through blockade of I(KACh) which may possibly explain its previously described antiarrhythmic activity. NIP-142 has pharmacological properties that are different from classical class III antiarrhythmic agents such as atria specificity and lack of reverse frequency dependence, and thus appears promising for the treatment of supraventricular arrhythmia.