Renal insufficiency secondary to contrast administration remains a prevalent and debilitating complication of angiographic procedures. Contrast-induced nephropathy (CIN) is a common clinical problem ...for which there is no effective medical treatment. However, agmatine has been shown to be effective against ischemia/reperfusion-induced acute kidney injury in rats, a similar condition to CIN. Our aim was to examine the protective effects of agmatine in a rat model of CIN and, based on those results, in a rabbit model of CIN. CIN in the rat model was induced by intravenous administration of indomethacin (10 mg/kg), Nω-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) and iopamidol (OYPALOMIN, 7.4 g iodine/kg) at 2 weeks after a unilateral nephrectomy. CIN in the rabbit model was induced by intrarenal arterial injection of only iopamidol (BYSTAGE, 4.8 g iodine/kg). Intravenous injection of agmatine (0.1 and 0.3 mmol/kg) did not attenuate the CIN-induced renal insufficiency in the rat model. Intravenous injection of agmatine (0.3 mmol/kg) attenuated the CIN-induced renal insufficiency in the rabbit model such as increases in blood urea nitrogen and plasma creatinine levels. Renal histological damage was also improved by the agmatine administration. The difference in effects of agmatine injection between CIN rats and CIN rabbits was caused by indomethacin and L-NAME administrations. These results indicate that agmatine prevents the development of CIN-induced renal insufficiency in rabbits, and the effect is accompanied by activation of nitric oxide synthase and subsequent increase of blood flow.
•Observations at 1μs interval were carried out for laser ablation in water.•Laser-induced shock wave and cavitation bubble are dynamically observed.•Jet-like shadows are observed during LAL in water ...after multiple-pulse irradiation.•Cloudlike-shadow moving away from the irradiated copper surface was observed.
Laser ablation in liquid (LAL) is utilized in many applications, such as the fabrication of nanoparticles, laser cleaning and laser peening. We have developed a high-speed laser stroboscopic videography system that enables observations at intervals of 1μs. Using this imaging system, we investigated the dynamics of cavitation bubbles induced by LAL to elucidate the timing and location of nanoparticle formation and dispersion into the surrounding liquid. The initial bubble demonstrated a well-defined, smooth boundary during its growth and shrinkage. Although previous studies have reported the ejection of particles at the boundary of the bubble, this was not observed in our images. Intermixing between the gas phase of the bubble and the surrounding liquid occurred when the first bubble collapsed. Jet-like shadows were recorded during LAL in water after multiple-pulse irradiation, but were not observed in freshly filled water that had not yet been irradiated. These shadows disappeared within 10μs and are postulated to be micro-bubbles induced by interactions between nanoparticles suspended in the water and the incoming laser beam.
Hyperphosphatemia is a major risk for poor prognosis in patients with end-stage renal disease. However, the molecular mechanism behind this link remains elusive. We and others have demonstrated that ...serum phosphorus levels correlate positively with circulating levels of calciprotein particles (CPPs). CPPs are colloidal mineral-protein complexes containing insoluble calcium-phosphate precipitates and have been reported to induce calcification in cultured vascular smooth muscle cells and inflammatory responses in cultured macrophages. Hence, we hypothesize that CPPs may be responsible for disorders associated with hyperphosphatemia. Using hyperphosphatemic miniature pigs receiving hemodialysis, here we show that removal of CPPs from the blood with a newly developed CPP adsorption column improves survival and alleviates complications including coronary artery calcification, vascular endothelial dysfunction, metastatic pulmonary calcification, left ventricular hypertrophy, and chronic inflammation. The present study identifies CPPs as an effective therapeutic target and justifies clinical trials to determine whether the CPP adsorption column may be useful as a medical device for improving clinical outcomes of hemodialysis patients.
In an acute treatment experiment, metformin (150, 300 mg/kg, per os (p.o.)) markedly reduced the consumption of a high-fat diet (HFD) (45 kcal% fat-containing diet) for 2 h after the HFD was given to ...the fasted male C57BL/6J (B6) mice. In addition, metformin at a higher dose increased plasma active glucagon-like peptide-1 (GLP-1) levels at 1 h after the HFD was given. On the other hand, pioglitazone (12 mg/kg, p.o.) slightly increased the food intake but did not affect active GLP-1 levels when given at 6 and 12 mg/kg, p.o. In a long-team experiment for 9 weeks, metformin treatment (0.25, 0.5% in the HFD) resulted in reduction of body weight gain and HFD intake. When wet weights of various body fat pads of each mouse were measured at 9 weeks after treatment, metformin markedly decreased these weights. However, pioglitazone treatment (0.01, 0.02% in the HFD) did not have obvious effects on these parameters. Oral glucose tolerance test was carried out after 20-h fasting at 4 weeks post-treatment. Whereas metformin treatment (0.25, 0.5%) markedly improved glucose intolerance, pioglitazone treatment (0.02%) slightly improved this parameter. At 9 weeks, both metformin and pioglitazone markedly improved hyperglycemia and hyperinsulinemia. Metformin treatment also improved hyperleptinemia, whereas pioglitazone was ineffective. These results indicate that metformin reduces body weight gain and improves glucose intolerance in HFD-induced obese diabetic B6 mice.
In July 2007, the Neonatal Cardiopulmonary Resuscitation (NCPR) program in Japan was launched to ensure that all staff involved in perinatal and neonatal medicine can learn and practice NCPR based on ...the Consensus on Science with Treatment Recommendations developed by the International Liaison Committee on Resuscitation. In 1978 in North America, a working group on pediatric resuscitation was formed by the American Heart Association Emergency Cardiac Care Committee and concluded that the resuscitation of newborns required a different strategy than the resuscitation of adults. The original first edition of the Neonatal Resuscitation Program textbook was published in 1987. The NCPR program consists of three courses for health-care providers and two courses for instructors. A course and B course are for newly certified health-care providers and course S is for health-care providers who are renewing their certification. As of 31 March 2019, 3,227 advanced instructors (I instructor) and 1,877 basic instructors (J instructor) were trained to teach A, B, and S courses to health-care providers on the basis of their license. In total 7,075 A courses and 4,012 B courses were held; 131 651 people attended A course or B course of the NCPR program, and 77 367 were certified. A total of 1,865 S courses, which were developed in 2015, were held and 12 875 people attended this course. Here, we introduce the background, purpose, history, and content of the development of the NCPR program in Japan.
Early enteral nutrition using reliable biomarkers of intestinal function must be established to improve neurodevelopmental outcomes in very low birth weight infants (VLBWIs). Serum citrulline levels ...reflect the intestinal function in adults. To elucidate the relationship among antenatal growth, postnatal enteral nutrition, and blood citrulline levels, a retrospective single-center observational study was conducted on 248 VLBWIs born between April 2014 and March 2021. A mixed effect model and post hoc simple slope analysis were used to estimate the correlations between clinical variables and citrulline levels at Early (day 5.1) and Late (day 24.3) postnatal ages. Greater gestational age, birth weight, and amount of enteral nutrition at the time of blood sampling were associated with lower citrulline levels at the Early postnatal age and higher citrulline levels at the Late postnatal age. Provided that Early citrulline levels predominantly reflect the consequence of antenatal citrulline metabolism, it is suggested that fetal growth and maturation are likely to promote citrulline catabolism in utero and its synthesis after birth. With additional insights into the temporal transition point wherein the maturation-dependent balance of citrulline metabolism shifts from catabolism-dominant to synthesis-dominant, citrulline emerges as a potential biomarker for assessing intestinal function and gastrointestinal disorders.
ABSTRACT Introduction: Retrolaminar blocks (RLBs) are effective, easy to perform, and safer than paravertebral blocks (PVBs). However, the pharmacokinetics of RLBs is not well understood. We compared ...changes in the plasma concentrations of levobupivacaine following a single-shot thoracic PVB or RLB. Methods: The study protocol was approved by the ethics committee of Tokyo National Medical Center (R15-135), and the trial was registered in the UMIN Clinical Trials Registry (UMIN000021759). The primary outcome was comparison of plasma levobupivacaine concentrations following single-shot thoracic PVB and RLB. A total of 46 women undergoing partial mastectomy were randomly allocated to receive either a thoracic PVB or RLB. In both groups, 2 mg kg-1 levobupivacaine (0.5%) was administered, and blood samples were collected at 5, 10, 20, 60, and 120 min after the injection. Results: Forty-two patients were analyzed for plasma levobupivacaine concentration, and 30 patients were assessed for pain. The maximum plasma concentration and time to reach the maximum concentration were determined using nonlinear regression analysis and were 1.32 μg ml-1 and 9 min in the thoracic PVB group, respectively, and 1.47 μg ml-1 and 5.5 min in the RLB group, respectively. The intraoperative opioid consumption did not differ between groups, but the time to the first request for analgesics was significantly shorter for the RLB group (p = 0.0318). Conclusions: The plasma concentration of levobupivacaine peaked earlier in the RLB group than in the thoracic PVB group. Therefore, local anesthetic toxicity should be avoided when performing RLB.
Supraglottic airway devices such as laryngeal masks and i-gels are useful for airway management. The i-gel is a relatively new device that replaces the air-inflated cuff of the laryngeal mask with a ...gel-filled cuff. It remains unclear which device is more effective for neonatal resuscitation. We aimed to evaluate the dependence of successful airway management in neonatal simulators on the device type and providers' backgrounds. Ninety-one healthcare providers performed four attempts at airway management using a laryngeal mask and i-gel in two types of neonatal manikins. The dependence of successful insertions within 16.7 s (75th percentile of all successful insertions) on the device type and providers' specialty, years of healthcare service, and completion of the neonatal resuscitation training course was assessed. Successful insertion (
= 0.001) and insertion time (
= 0.003) were associated with using the i-gel vs. laryngeal mask. The providers' backgrounds were not associated with the outcome. Using the i-gel was associated with more successful airway management than laryngeal masks using neonatal manikins. Considering the limited effect of the provider's specialty and experience, using the i-gel as the first-choice device in neonatal resuscitation may be advantageous. Prospective studies are warranted to compare these devices in the clinical setting.
Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We ...searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole‐exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in KIF5B encoding kinesin‐1 heavy chain: two with c.272A>G:p.(Lys91Arg), one with c.584C>A:p.(Thr195Lys), and the other with c.701G>T:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity‐related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous KIF5B deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.
Genetic and radiographic features of KIF5B‐kyphomelic dysplasia. KIF5B variants occured de novo and are located in or close to the highly conserved ATPase activity‐related motifs in the catalytic motor domain. Radiographic features include brachycephaly, narrow chest, iliac flaring, platyspondyly, bowing and bone spur in limb bones, normal metacarpal bones, and osteoporosis with age.
Sacrococcygeal teratoma (SCT) is the most common extragonadal germ cell tumor in neonates and infants. Although most cases of infantile SCT are benign tumors by nature, some develop into extremely ...large lesions, leading to massive bleeding, high-output heart failure, disseminated intravascular coagulation, and even fatal outcomes during the neonatal period. In addition, some patients may present with tumor recurrence, malignant transformation, long-term sequelae (including bladder and bowel dysfunction) and lower leg palsy during the long-term follow up. SCT, however, is very rare, and there are few opportunities to encounter this disease, therefore general physicians without expert credentials currently lack information relevant to clinical practice. For this reason, the research project committee has compiled guidelines concerning SCT.
The purpose of these guidelines was to share information concerning the treatment and follow up of infantile SCT. The guidelines were developed using the methodologies in the Medical Information Network Distribution System. A comprehensive search of the English- and Japanese-language articles in PubMed and Ichu-Shi Web identified only case reports or case series, and the recommendations were developed through a process of informal consensus.
The clinical questions addressed the risk factors, the efficacy of cesarean section, the initial devascularization of tumor feeding vessels, interventional radiology, recommended clinical studies for follow up and possible long-term complications.
These are the first guidelines for SCT to be established in Japan, and they may have huge clinical value and significance in terms of developing therapeutic strategies and follow up, potentially contributing to the improvement of the prognosis and quality of life of SCT patients.