Dietary soyasaponin attenuates 2,4-dinitrofluorobenzene-induced contact hypersensitivity via gut microbiota in mice.

Soyasaponins (SSs) are abundant in soybeans and display inhibitory activity against contact hypersensitivity (CHS), which is often used as a mouse model for allergic contact dermatitis (ACD); however, their therapeutic mechanisms remain unknown. Here, we attempted to clarify the role of gut microbiota in the inhibition of CHS by dietary soyasaponins. For antibiotic treatment, mice were administered a mixture of ciprofloxacin and metronidazole or vancomycin. These antibiotics and SSs were given to mice via drinking water 3-weeks prior to CHS induction with 2,4-dinitrofluorobenzene, and the mice were analysed for ear swelling, tissue oedema, infiltration of Gr-1-positive immune cells, the composition of faecal microbiota and regulatory T (Treg ) cells. The soyasaponin diets attenuated ear swelling and tissue oedema, and reduced the number of Gr-1-positive cells infiltrating ear tissues. CHS caused changes in the structure of the gut microbiota, but dietary SSs blocked the changes in the microbiota composition. Ciprofloxacin and metronidazole treatments significantly enhanced the severity of CHS symptoms, whereas vancomycin treatment blocked the suppressive effect of dietary SSs on CHS. These antibiotic treatments differed in their effects on the gut microbiota composition. Treg cells in auricular lymph node and spleen increased under SS-enriched diets, but this increase was blocked by vancomycin treatment. These results suggest that dietary SSs exert their inhibitory activity on CHS via the gut microbiota in mice, suggesting that dietary supplementation with SSs may have beneficial effects on ACD patients, but that the gut microbiota is a critical determinant of the therapeutic value of dietary SSs.

Impact of COVID-19 on the mental health of primary schoolchildren during the later phase of the pandemic: A case report of an 18-month longitudinal survey in a Japanese primary school.

Background: Drastic changes such as school closures and stay-at-home measures due to the global COVID-19 pandemic, may have long-term negative effects on children's mental health; however, longitudinal studies after 2021 are limited. This study aimed to observe the long-term effects of the COVID-19 pandemic on children's mental health by exploring changes in their mental health over a period of 18 months. Study design: We conducted a longitudinal study at Chiba Prefecture in Japan, focusing on schoolchildren's mental health changes. Methods: Data were obtained from the Strengths and Difficulties Questionnaire (SDQ) questionnaire conducted at single primary school three times from October 2021 to March 2023 which and included 183 participants. This study adopted a linear-mixed model to evaluate changes in children's SDQ scores, with sex and grade as the independent variables, and participants as a random effect. Results: Regarding changes in SDQ scores, there were no significant changes in the total difficulty scores or in each subscale; Emotional Symptoms, Conduct Problems, Hyperactivity/Inattention, Peer Problems, and Prosocial Behavior. There was no statistically significant interaction between changes in SDQ scores and sex. Conclusions: This report indicates that the impact of the COVID-19 pandemic on the mental health of Japanese primary schoolchildren was negligible in the later phase of the pandemic. However, the impact may differ from country to country owing to factors such as social restrictions during the COVID-19 pandemic.

Enumeration of micro-organisms in processed soy products with an automated most probable number method compared with standard plate method.

AIM: The automated TEMPO system (bioMerieux) is based on the most probable number (MPN) method for the enumeration of micro-organisms in foods. In this study, we evaluated the performance of the TEMPO system as a diagnostic tool in comparison with the standard method in processed soy products. METHODS AND RESULTS: A verification study was conducted using artificially contaminated soy product samples such as soy protein isolate, water-soluble soy polysaccharides, soy milk and processed soy food. Five types of micro-organisms were analysed using the automated MPN method (total aerobic bacteria, total coliforms, Enterobacteriaceae, yeast and mould and Staphylococcus aureus) vs the standard plate method. The results from each of the methods were highly correlated (r > 0·95). Naturally contaminated processed soy products on the market were also studied. There were no discrepancies observed between the respective methods. CONCLUSIONS: TEMPO methods were equivalent to the corresponding standard plate methods with very good rates of agreement. SIGNIFICANCE AND IMPACT OF THE STUDY: The automated MPN method is more practical and reliable for in-house microbiological testing in processed soy products.

Computed tomography appearance of Hem-o-lok clips in patients who have undergone laparoscopic nephrectomy or nephroureterectomy.

BACKGROUND AND OBJECTIVES: Hem-o-lok clips are safe and reliable for controlling the renal vasculature. We retrospectively evaluated the CT appearance of Hem-o-lok clips in patients who had undergone laparoscopic radical nephrectomy (LRN) or nephroureterectomy (LRU) as well as their appearance on ex vivo CT scans. METHODS: Between January 2006 and December 2006, 19 patients underwent LRN or LRU, and their CT images were reviewed within 5 postoperative months. The Hem-o-lok clips were radiopaque in all of the patients' CT images, and their radiodensity value was 222 Hounsfield Units (HU). To confirm that Hem-o-lok clips are radiopaque on CT images, an ex vivo CT scan was performed. RESULTS: We confirmed that these clips are radiopaque on CT images and that they have a radiodensity of 223 HU. CONCLUSION: We conclude that the Hem-o-lok clips are radiopaque on CT images. It is important for urologists and radiologists to be aware of the CT appearance of Hem-o-lok clips when following up patients who have undergone LRN or LRU.

The surface composition of asteroid 162173 Ryugu from Hayabusa2 near-infrared spectroscopy.

The near-Earth asteroid 162173 Ryugu, the target of the Hayabusa2 sample-return mission, is thought to be a primitive carbonaceous object. We report reflectance spectra of Ryugu's surface acquired with the Near-Infrared Spectrometer (NIRS3) on Hayabusa2, to provide direct measurements of the surface composition and geological context for the returned samples. A weak, narrow absorption feature centered at 2.72 micrometers was detected across the entire observed surface, indicating that hydroxyl (OH)-bearing minerals are ubiquitous there. The intensity of the OH feature and low albedo are similar to thermally and/or shock-metamorphosed carbonaceous chondrite meteorites. There are few variations in the OH-band position, which is consistent with Ryugu being a compositionally homogeneous rubble-pile object generated from impact fragments of an undifferentiated aqueously altered parent body.

Measurement of effect of electron cyclotron heating in a tandem mirror plasma using a semiconductor detector array and an electrostatic energy analyzer.

Temporally and spatially resolved soft x-ray and end-loss-electron analyses of the electron cyclotron heated plasmas are carried out by using a semiconductor detector array and an electrostatic energy analyzer in the GAMMA 10 tandem mirror. The flux and the energy spectrum of the end loss electrons are measured by a multi-grid energy analyzer. Recently, the electron cyclotron heating power modulation experiments have been started in order to generate and control the high heat flux and to make the edge localized mode-like intermittent heat load pattern for the divertor simulation studies by the use of these detectors for electron properties.

Prorenin processing and restricted endoproteolysis by mouse tissue kallikrein family enzymes (mK1, mK9, mK13, and mK22).

Four members of the tissue kallikrein family, mK1, mK9, mK13, and mK22, all of which exhibit extensive homology in amino acid sequence among themselves, were obtained from the submandibular gland of ICR mice and examined for their ability to cleave prorenin. Tissue kallikrein mK13 was confirmed to be a prorenin-converting enzyme; and mK9, which was earlier shown to be an EGF-binding protein, was found to cleave mouse Ren 2 prorenin specifically and convert it to mature renin with an activity of approximately 1/10 of that of mK13. With the same substrate, mK22 (beta-NGF endopeptidase) gave two products, renin and arginyl-renin; whereas mK1 (true tissue kallikrein) did not process it at all. The endoproteolytic activity of tissue kallikreins was examined with various peptide-MCA substrates. The substrates contained three key structures; X(Y)-Arg-Arg, X(Y)-Lys-Arg and X-Lys-Lys motifs (where X and Y are hydrophilic and hydrophobic amino acids, respectively). We found that mK1, mK9 and mK13 preferentially cleaved the former two types of substrate, except Y-Arg-Arg-MCA. The substrate X-Lys-Lys-MCA was hardly cleaved by these three tissue kallikreins but was preferentially cleaved by mK22. The four tissue kallikreins seem to have the ability to process precursor proteins containing a pair of basic amino acid residues; the specificities of three of the enzymes (mK1, mK9 and mK13) were similar to each other but were different from that of mK22.

Pulsatility of ascending aortic pressure waveform is a powerful predictor of restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: Because ascending aortic pressure has a greater effect on coronary perfusion during diastole than systole, we hypothesized that a high coronary diastolic-to-systolic pressure ratio prevents coronary lesions from restenosing after percutaneous transluminal coronary angioplasty (PTCA) and that ascending aortic pulsatility relative to mean pressure is higher in patients with restenosis than in those without restenosis. The purpose of this study was to evaluate prospectively whether the morphology of the ascending aortic pressure wave can be used to predict restenosis after PTCA. METHODS AND RESULTS: We measured the coronary artery diameter and the aortic pressure before PTCA. To quantify the relative magnitude of the pulsatile-to-mean aortic pressure, we normalized the pulse pressure to mean pressure and referred to this value as the fractional pulse pressure (PPf). We prospectively investigated the effect of PPf in relation to subsequent risk of restenosis after PTCA in patients with coronary artery disease. PPf was a powerful predictor of restenosis. Crude cumulative incidence rates of restenosis were 17.6% for the lowest, 33.3% for the middle, and 77. 8% for the highest tertile of PPf levels. After adjustments for age, smoking habits, systolic blood pressure, type 2 diabetes, hypercholesterolemia, old myocardial infarction, vessel location, vessel size, and sex, the odds ratio of restenosis was 33.5 (95% confidence interval, 2.04 to 550.6) for the highest tertile of the PPf level compared with the lowest tertile level. CONCLUSIONS: Pulsatility of the ascending aortic pressure is a predictive factor for restenosis after PTCA.

Hemodynamic status and treatment of aggressive dural arteriovenous fistulas.

In this study the hemodynamic status and treatment modality of aggressive dural arteriovenous fistulas (dAVFs) was evaluated. Of 145 intracranial dAVFs treated in our clinic, there were 38 aggressive lesions presenting with hemorrhage, infarction, seizures, and symptoms of increased intracranial pressure. They included 3 (5% of all cavernous sinus lesions) cavernous sinus, 24 (44%) transverse-sigmoid and superior sagittal sinus, and 11 (46%) direct cortical types of dAVFs. Of these 38 aggressive lesions, retrograde leptomeningeal venous drainage was disclosed in 35 lesions, and retrograde sinus drainage in 3. Eighteen cases were treated only with endovascular procedures, 7 with surgical interventions, and 13 with combined endovascular and surgical procedures. Angiographic results were complete obliteration in 66% of the cases, subtotal and partial obliteration in 34%. Clinical outcome was GR (good recovery) in 58% of cases, MD (moderate disability) in 18%, SD (severe disability) in 13%, VS (vegetative state) in 8%, and D (death) (due to acute cardiac infarction) in 3%. Symptomatic procedural complication occurred in 3 cases. In conclusion, aggressive dural AVF resulted from retrograde leptomeningeal venous drainage. Combined surgical and endovascular treatment played the leading part in the management of this aggressive type of lesion.

Daily alcohol consumption and the risk of type 2 diabetes in Japanese men: the Osaka Health Survey.

OBJECTIVE: To investigate the relationship between daily alcohol consumption and the risk of type 2 diabetes in a large Japanese cohort. RESEARCH DESIGN AND METHODS: We enrolled 6,362 Japanese men aged 35-61 years who did not have diabetes, impaired fasting glucose, hypertension, or liver cirrhosis at study entry. Type 2 diabetes was defined as a fasting plasma glucose (FPG) level > or =126 mg/dl or was diagnosed by a physician. Data on alcohol consumption were obtained from questionnaires. We confirmed 456 cases of type 2 diabetes during the 62,016 person-years of follow-up. RESULTS: The relationship between daily alcohol consumption and the risk of type 2 diabetes among lean men and among men with a higher BMI was paradoxical. Among lean men (BMI < or =22.0 kg/m2), heavy drinking was associated with an increased risk of type 2 diabetes. Men who consumed > or =50.1 ml/day of alcohol had a relative risk (RR) of 2.48 (95% CI 1.31-4.71) compared with nondrinkers after adjusting for age, BMI, regular physical exercise, parental history of diabetes, smoking habits, and FPG level. However, among men with a BMI > or =22.1 kg/m2, moderate drinking (29.1-50.0 ml/day) was associated with a decreased risk of type 2 diabetes. Daily moderate drinkers had a multiple adjusted RR of 0.58 (0.39-0.87) compared with nondrinkers. CONCLUSIONS: Among men with a BMI > or =22.1 kg/m2, moderate alcohol consumption was associated with a reduced risk of type 2 diabetes, but among lean men (BMI < or =22.0 kg/m2), heavy alcohol consumption was associated with an increased risk of type 2 diabetes.

Impaired fasting glucose and the risk of hypertension in Japanese men between the 1980s and the 1990s. The Osaka Health Survey.

OBJECTIVE: To determine whether impaired fasting glucose (IFG) increased the risk for hypertension in two large Japanese cohorts during the different time periods. RESEARCH DESIGN AND METHODS: We prospectively investigated two Japanese cohorts: a 1980s population, comprising 4,130 normotensive and nondiabetic men aged 35-60 years entered between 1981 and 1983, and a 1990s population, comprising 4,319 normotensive and nondiabetic men aged 35-60 years entered between 1991 and 1992. Data on lifestyle factors were obtained from questionnaires. IFG was defined as a fasting plasma glucose level > or = 110 and < 126 mg/dl. RESULTS: During the 4-year observation period, 708 cases of hypertension were confirmed in the 1980s and 848 cases were confirmed in the 1990s. In both the 1980s and 1990s populations, IFG was associated with the risk of hypertension. The frequency of IFG in men in the 1990s group was twice as high as that in the 1980s group. The multivariate-adjusted odds ratio (OR) of hypertension was 1.54 (95% CI, 1.01-2.34) for men with IFG in the 1980s population and 1.73 (1.31-2.29) in the 1990s population, compared with those without IFG in the two populations. In the 1990s population, among lean men with a BMI < or = 23 kg/m2, men with IFG had a multivariate-adjusted OR of hypertension of 2.31 (1.46-3.65) compared with those without IFG. CONCLUSIONS: This study demonstrated direct correlation between IFG and hypertension and greater incidence of this hypertension in the 1990s group than in the 1980s group.

High normal blood pressure, hypertension, and the risk of type 2 diabetes in Japanese men. The Osaka Health Survey.

OBJECTIVE: To investigate the relationship between high normal blood pressure or hypertension and the risk of developing type 2 diabetes in a large Japanese cohort. RESEARCH DESIGN AND METHODS: We enrolled 7,594 Japanese men aged 35-60 years who did not have diabetes or impaired fasting glucose at study entry. Type 2 diabetes was defined as a fasting plasma glucose level of > or = 126 mg/dl or a 2-h postload plasma glucose level of > or = 200 mg/dl. High normal blood pressure was defined as no history of hypertension and a systolic blood pressure of > or = 130 and < 140 mmHg or a diastolic blood pressure of > or = 85 and < 90 mmHg. Subjects were considered to have hypertension if they had a systolic blood pressure > or = 140 mmHg, if they had a diastolic blood pressure > or = 90 mmHg, or if they were taking anti-hypertensive medications. RESULTS: We confirmed 600 cases of type 2 diabetes during the 72,946 person-years of follow-up. Both high normal blood pressure and hypertension were associated with the risk of type 2 diabetes. Compared with normotensive men, men with high normal blood pressure had a multiple adjusted relative risk (RR) of 1.39 (95% CI 1.14-1.69), and men with hypertension had a multiple adjusted RR of 1.76 (1.43-2.16). Even among lean men (BMI < 22.7 kg/m2), men with high normal blood pressure had a multiple adjusted RR of 1.71 (1.20-2.42), and men with hypertension had a multiple adjusted RR of 2.02 (1.34-3.05) compared with normotensive men. CONCLUSIONS: High normal blood pressure and hypertension are associated with an increased risk of developing type 2 diabetes.

The antihypertensive effect of calcitonin gene-related peptide in rats with norepinephrine- and angiotensin II-induced hypertension.

To investigate the role of calcitonin gene-related peptide (CGRP) in blood pressure regulation, we used rats with hypertension, induced by the chronic infusion of norepinephrine or angiotensin II, and examined changes in the systemic hemodynamics using the radioactive microspheres method. CGRP (0.05 micrograms/kg per min) administered simultaneously with norepinephrine (1.8 mg/kg per day) significantly reduced the systolic blood pressure of conscious rats compared with norepinephrine infusion alone. Similarly CGRP given with angiotensin II (0.9 mg/kg per day) significantly reduced the systolic blood pressure compared with angiotensin II alone. The antihypertensive effect of CGRP was sustained for 6 days. CGRP infusion decreased the total peripheral resistance but caused no change in cardiac output compared with rats given only pressor substances. Thus, a subdepressor dose of CGRP can modulate the vasopressor effects of norepinephrine and angiotensin II. CGRP may be involved in the regulation of blood pressure via an effect on peripheral vascular resistance.

Pulsatility of brachial artery pressure is associated with an increased risk of coronary artery disease in men.

OBJECTIVES: The purpose of this study was to evaluate whether the pulsatility of brachial artery pressure is related to an increased risk of coronary artery disease (CAD). On the basis of vascular mechanics, we recently reported that relative pulse pressure can predict the occurrence of restenosis after percutaneous transluminal coronary angioplasty. We also hypothesized that relative pulse pressure of the brachial arterial pressure waveform is associated with an increased risk of CAD. DESIGN: A cross-sectional study. PATIENTS: We enrolled 172 men who had the same cardiac performances. MAIN OUTCOME MEASURES: We measured their brachial artery pressures with a sphygmomanometer. To quantify the relative magnitude of the pulsatility to diastolic pressure, we made use of the ratio of pulse pressure to diastolic pressure (PP/DP). We investigated the effects of the PP/DP in relation to the risk of CAD. RESULTS: PP/DP was associated with an increased risk of CAD. The prevalence rates of significant stenosis were 28.1% for the lowest, 43.1% for the middle and 49.1% for the highest tertile of PP/DP levels. The age-adjusted odds ratio of CAD was 2.23 (95% confidence interval 0.98-5.04) for the middle tertile of the PP/DP level and 2.55 (1.10-5.93) for the highest tertile compared with the lowest tertile. CONCLUSIONS: The pulsatility of the brachial artery pressure was associated with an increased risk of CAD.

Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey.

OBJECTIVE: To investigate the association of serum uric acid level with the risk for hypertension and Type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Work site in Osaka, Japan. PARTICIPANTS: A total of 6,356 Japanese men, aged 35-60 years with systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, normal glucose intolerance, and no history of hypertension or diabetes at baseline. MAIN OUTCOME MEASURES: Blood pressure was measured by standard techniques, using 160/95 mmHg for diagnosis of hypertension. Type 2 diabetes was defined as a fasting plasma glucose level > or = 126 mg/dl or a 2 h post-loaded plasma glucose level > or = 200 mg/dl. RESULTS: During the 61,716 person-years follow-up period, we confirmed 639 cases of hypertension and 454 cases of Type 2 diabetes. Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes. After adjustment for known risk factors, including daily alcohol consumption, the serum uric acid level was associated with an increased risk for hypertension; the relative risks for hypertension were 1.00 for quintile 1 of the serum uric acid level, 1.24 [95% confidence interval (CI), 0.94-1.65] for quintile 2, 1.34 (CI, 1.03-1.76) for quintile 3, 1.76 (CI, 1.35-2.29) for quintile 4, and 2.01 (CI, 1.56-2.60) for quintile 5 (P for trend < 0.001). Even among both non-drinkers and lean subjects, serum uric acid level was associated with an increased risk for hypertension. CONCLUSIONS: Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes.

Electrocardiogram is very useful for predicting acute heart failure following myeloablative chemotherapy with hematopoietic stem cell transplantation rescue.

A prospective study was conducted in 71 evaluable patients who received myeloablative hematopoietic stem cell transplantation (HSCT) at our facility from 1995 to 2002, to find a sensitive marker for post-transplant heart failure, including echocardiographic systolic and diastolic markers and QTc interval. QTc was found to be an independent and significant risk factor for acute heart failure (AHF) on multivariate logistic regression analysis (OR 1.5, P=0.01, 95% confidence interval (CI) 1.1-2.0), while no significant differences between patients with AHF and those without AHF were found in age, sex, treatment history, type of conditioning regimen, and echocardiographic systolic and diastolic markers. On further analysis, post-transplant risk of AHF appeared to be increased as QTc was prolonged. The post-transplant risk of AHF in the group with longest QTc on multivariate logistic regression analysis was found to be 9.8 times that in the group with shortest QTc (P=0.04, 95% CI 1.0-100). These results suggest that echocardiographic markers are less valuable predictors of post-transplant AHF, but that prolongation of the QTc, an ECG marker, before HSCT is strongly associated with onset of AHF after HSCT.

Chronic parathyroid hormone administration reverses the antihypertensive effect of calcium loading in young spontaneously hypertensive rats.

To investigate the role of parathyroid hormone (PTH) in the development of hypertension, the long-term administration of human PTH (hPTH) was performed in 7-week-old male spontaneously hypertensive rats maintained on a standard calcium diet (1.1% calcium) or a high calcium diet (2.8% calcium). The hPTH was infused subcutaneously at 0.9 U/h over 2 weeks using a minipump. Two weeks after minipump implantation, rat PTH (rPTH) and 1,25-dihydroxy vitamin D (1,25-D) levels were measured and the pressor response to norepinephrine (NE) was examined. Calcium loading both attenuated the development of hypertension and reduced the pressor response to norepinephrine. Chronic hPTH administration accelerated the development of hypertension and increased the pressor response to norepinephrine in rats fed a high calcium diet, but did not affect either parameter in rats fed a standard calcium diet. The serum concentrations of rat PTH and 1,25-D were significantly lower in rats fed a high calcium diet than in those fed a standard calcium diet (rat PTH: 351 +/- 16 v 430 +/- 1 pmol/L; 1,25-D: 125 +/- 19 v 206 +/- 31 pg/mL). Chronic administration of hPTH increased the serum 1,25-D concentration in rats fed a high calcium diet (186 +/- 35 pg/mL), but did not affect that of rats fed a standard calcium diet (165 +/- 16 pg/mL). It is concluded that PTH prevented the antihypertensive effect of calcium loading in young SHR, perhaps by enhancing blood pressure reactivity through causing an increase of 1,25-D.

Pulsatility of ascending aortic blood pressure waveform is associated with an increased risk of coronary heart disease.

BACKGROUND: Although it was reported that pulse pressure of the peripheral artery could differentiate patients with coronary heart disease (CHD) from those without CHD, it is not known whether pulsatility of the ascending aortic pressure waveform differentiates patients with CHD from those without CHD. The purpose of this study was to evaluate whether the pulsatility of ascending aortic pressure is associated with an increased risk of CHD. METHODS: For this study, we enrolled 293 subjects who had chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. To quantify the relative magnitude of the pulsatile to mean artery pressure, we normalized the pulse pressure to the mean pressure and referred to this value as the fractional pulse pressure (PPf). We investigated the association between the PPf and the risk of CHD. RESULTS: The PPf of the ascending aorta was associated with an increased risk of CHD. The multiple-adjusted odds ratio of CHD was 2.93 (95% CI, 1.44 to 5.94) for the middle tertile of the PPf level and was 3.93 (95% CI, 1.74 to 8.85) for the highest tertile compared with the lowest tertile. CONCLUSION: Ascending aortic pulsatility is related to an increased risk of CHD.

Expression of an allozyme of prorenin-converting enzyme in the submandibular gland of DBA/2N mice.

A protein product of the tissue kallikrein gene family was isolated from the submandibular gland of DBA/2N mice. Amino acid sequencing showed this protein to be highly homologous to two tissue kallikreins, mK13 and mK26, also known as prorenin-converting enzymes PRECE and PRECE-2, respectively. The cDNA corresponding to the present enzyme was cloned, and its complete nucleotide sequence was determined. The cloned cDNA was different in 6 and 12 bases out of 783 nucleotides from those of mK1k-13 and mK1k-26 cDNAs, respectively, the homologies being 99.2 and 98.5% (nucleotide), or 98.3 and 96.2% (amino acid). Upon incubation with either bovine kininogens or mouse Ren 2 prorenin, this tissue kallikrein generated bradykinin and renin, respectively, as judged by Western blotting and protein sequence analysis. Isoelectric focusing analysis of the submandibular gland tissue kallikreins suggested that the present enzyme was not expressed in CD-1 or ICR mice and that no mK13 protein was present in DBA/2N mice. These data suggest that the enzyme is an allozyme of mK13, a prorenin-converting enzyme highly expressed in the submandibular gland of DBA/2N mice. The mK1k-13 gene in mice is therefore suggested to be polymorphic, having at least two allelic forms with a high sequence homology. The designation mK13(b) and mK1k-13(b) for the protein and gene of this tissue kallikrein is proposed.

Experimentally induced acute hyperinsulinemia stimulates endogenous nitric oxide production in humans: detection using urinary NO2-/NO3-excretion.

Insulin-mediated glucose metabolism in skeletal muscle is associated with a proportional increase in muscle perfusion. The vasodilatory effect of insulin is thought to be mediated in part by endothelium-derived nitric oxide (NO). The present study was performed to determine whether acute hyperinsulinemia has any stimulatory effect on endogenous NO production in humans. Bolus intravenous injection of insulin (0.1 IU/kg body weight) caused a significant increase in urinary excretion of NO2-/NO3- together with a significant decrease in blood pressure, whereas saline infusion alone had no effect on these parameters. The increased NO response to insulin was almost comparable to that obtained with infusion of 30 g L-arginine. The acute effect of hyperinsulinemia on endogenous NO formation supports the concept that NO may mediate the vasodilatory action of insulin in humans.