Investigation of SO3 absorption line for in situ gas detection inside combustion plants using a 4-µm-band laser source.

We have investigated 4-µm-band SO3 absorption lines for in situSO3 detection using a mid-infrared laser source based on difference frequency generation in a quasi-phase-matched LiNbO3 waveguide. In the wavelength range of 4.09400-4.10600 µm, there were strong SO3 absorption lines. The maximum absorption coefficient at a concentration of 170 ppmv was estimated to be about 3.2×10-5 cm-1 at a gas temperature of 190°C. In coexistence with H2O, the reduction of the SO3 absorption peak height was observed, which was caused by sulfuric acid formation. We discuss a method of using an SO3 equilibrium curve to derive the total SO3 molecule concentration.

[Candida mediastinitis after double closure technique for repairing ventricular septal perforation].

A 69-year-old man was referred to our hospital due to acute myocardial infarction. Systolic heart murmur was first noted on the 23rd day after the onset, but no cardiac shunt flow was detected by echocardiography at that time. Six days later, cardiac function deteriorated rapidly, followed by oliguria and shock. Re-do echocardiography showed ventricular septal perforation. Emergency operation was performed, and septal perforation was seen on the anterior portion of the septum. In addition to infarct-exclusion-technique (Komeda-David method) with the equine pericardial patch, direct closure of the septal defect was performed (double closure technique). Fibrin glue was applied between the ventricular septum and the patch. After surgery, he suffered from Candida mediastinitis and received omentum plombage. Furthermore tracheotomy was performed for pneumonia. He recovered gradually, and was discharged about 3 months after surgery. Echocardiography showed no residual shunt.

Evaluation of the clinical application of cystatin C, a new marker of the glomerular filtration rate, for the initial dose-setting of arbekacin.

OBJECTIVE: Recent studies have shown that serum cystatin C is a better marker for measuring the glomerular filtration rate (GFR) than the conventional method, using serum creatinine concentration. The purpose of this study is to evaluate the clinical application of serum cystatin C as a marker of GFR to determine the initial dosage of arbekacin, an antibiotic primarily excreted via the kidneys. In this study, the predictability of serum arbekacin peak and trough concentrations were assessed using estimated population mean GFR values calculated from either serum creatinine (Cockcroft-Gault equation) or cystatin C (Sjöström equation) concentrations. METHOD: Ninety-five patients treated with arbekacin for methicillin-resistant Staphylococcus aureus infection were divided into three groups according to their GFR values estimated by the serum cystatin C concentration as follows: normal to mild (GFR > 70 mL/min, n = 40), moderate (30

Hoek's formula, a cystatin C-based prediction formula for determining the glomerular filtration rate, is the most effective method for original adjusting the dosage of vancomycin.

OBJECTIVE: Some formulas using the serum cystatin C level to estimate the GFR have recently been reported. However, there has been no report of a serum cystatin C-based formula for adjusting the dosage of the drugs cleared by the kidney. In this study, we compared the predictive performance of the serum vancomycin trough concentration predicted using serum cystatin C-based formulas. METHOD: The data were collected from 158 hospitalized patients. Five formulas have been published to predict the GFR using serum cystatin C. The cystatin C-based formulas were divided into two groups, formulas with or without anthropometric data. We predicted the serum vancomycin trough concentrations using VCM-TDM S_edition ver. 1.00 software. RESULTS: In formulas with anthropometric data, the mean absolute error (MAE) using Hoek's formula was 2.38, the MAE using Grubb's 1 formula was 4.13, the MAE using Sjöström's formula was 2.90, and the MAE using Cockcroft and Gault formula based on creatinine was 4.42. On the other hand, in formulas without an anthropometric data group, the MAE using Larsson's formula was 3.07, and the MAE using Grubb's 2 formula was 3.63. CONCLUSION: These results suggested that Hoek's formula is the most useful formula for determining the initial dosage settings for vancomycin.

Improvement in insulin resistance and the restoration of reduced phosphodiesterase 3B gene expression by pioglitazone in adipose tissue of obese diabetic KKAy mice.

Phosphodiesterase (PDE) 3B is a key enzyme in the mediation of the antilipolytic action of insulin in adipocytes, and activation of this molecule results in a reduced output of free fatty acids (FFAs). An elevation of serum FFAs is known to cause insulin resistance in skeletal muscle and liver, which could be the primary cause of type 2 diabetes. To elucidate whether PDE3B is involved in this disease, we examined the PDE3B gene expression in epididymal fat tissues of obese insulin-resistant diabetic KKAy mice. We also examined the effect of an insulin-sensitizing drug, pioglitazone, on this gene expression. In adipose tissue of KKAy mice, PDE3B mRNA and its corresponding protein were reduced to 48 and 43% of those in C57BL/6J control mice. Basal and insulin-stimulated membrane-bound PDE activities were also decreased to 50 and 36% of those in the controls, respectively. Pioglitazone increased both PDE3B mRNA and protein levels by 1.8-fold of those in untreated KKAy mice. Basal and insulin-induced membrane-bound PDE activities were also increased by 1.6- and 2.0-fold, respectively. Pioglitazone reduced the elevated levels of serum insulin, glucose, FFAs, and triglyceride in KKAy mice. Thus, the reduced PDE3B gene expression in adipose tissues could be the primary event in the development of insulin resistance in KKAy mice, which was improved by pioglitazone possibly because of the restoration of the reduced PDE3B gene expression.

Adipocyte-specific reduction of phosphodiesterase 3B gene expression and its restoration by JTT-501 in the obese, diabetic KKAy mouse.

OBJECTIVE: Phosphodiesterase (PDE) 3B is a key enzyme involved in the anti-lipolytic action of insulin in adipocytes. PDE3B activation results in a reduced output of free fatty acids (FFA), whereas elevated serum FFA is known to cause insulin resistance. We have recently reported that reduced PDE3B gene expression is restored by treatment with pioglitazone, in the adipose tissues of obese, insulin-resistant diabetic KKAy mice. To determine whether the altered PDE3B gene expression is specific for adipocytes, the expression of this gene in liver and epididymal fat tissues of KKAy mice was examined. The effect of JTT-501, another peroxisome proliferator-activated receptor (PPAR)gamma ligand, which is different from thiazolidinedione, was also examined. METHODS: PDE3B mRNA and protein were quantified by an RNase protection assay and Western blotting respectively. Membrane-bound PDE activities were also measured. RESULTS: In adipose tissues of KKAy mice, PDE3B mRNA, protein and membrane-bound PDE activity were reduced to 47%, 57% and 51% respectively relative to those in C57BL/6J control mice. JTT-501 increased PDE3B mRNA, protein and membrane-bound PDE activity by 2.2-, 1.6- and 1.7-fold respectively over those of untreated KKAy mice. In the liver, PDE3B gene expression remained unchanged in KKAy mice, and was not affected by JTT-501. JTT-501 reduced the elevated levels of serum insulin, glucose, FFA and triglyceride in KKAy mice. CONCLUSIONS: PDE3B gene expression was specifically reduced in the adipose tissues of KKAy mice. JTT-501 restored this reduced gene expression with an accompanying improvement in elevated serum FFA and insulin resistance.

Phosphodiesterase 3B gene expression is enhanced in the liver but reduced in the adipose tissue of obese insulin resistant db/db mouse.

Phosphodiesterase (PDE) 3B, when activated by insulin, causes a decrease in intracellular cAMP concentration. The activation of this enzyme results in the reduced output of free fatty acids (FFA) from adipocytes, and an increased lipogenesis in liver. We have recently shown that PDE3B gene expression is reduced in adipose tissues of KKAy mice. We intend to further elucidate the regulation of PDE3B in liver as well as adipose tissues in relation to the insulin resistant state. We examined PDE3B gene expression in liver and adipose tissues of obese, insulin-resistant diabetic db/db mice and also checked the effect of an insulin-sensitizing drug, troglitazone, on this gene expression. In the liver of db/db mice, PDE3B mRNA, its corresponding protein, and the associated catalytic activity were all increased by 2.1, 1.9 and 1.6-fold, respectively, over those in db/+ control mice. Histological examination revealed substantial triglyceride storage in the liver of db/db mice. Conversely, in the adipose tissue of db/db mice, PDE3B mRNA, protein, and its associated activity were all decreased by 0.38, 0.33 and 0.36-fold, respectively. Troglitazone, which has no effect on PDE3B in liver, increased the expression of this gene in adipocytes. This increase is associated with a reduction in the elevated levels of serum insulin, glucose, FFA and triglycerides. The reduced PDE3B gene expression in adipose tissues, which results in the elevation of serum FFA, could be the primary event in the development of insulin resistance in db/db mice. The enhanced PDE3B gene expression may correlate with changes in triglyceride storage in the liver of these mice.

The role of renal kallikrein-kinin system and prostaglandins in diuresis and natriuresis following saline infusion in normotensives and essential hypertensives.

In order to clarify the significance of the renal kallikrein(KAL)-kinin(KIN) system and prostaglandins (PG) in exaggerated natriuresis in essential hypertensives, the effect of acute sodium load on urinary KAL, KIN, PG, and renal water and sodium handling were investigated in normotensives (NT) and patients with essential hypertension (EHT). Nine NT and seven EHT were studied following acute physiological saline infusion (1000 ml/2 hrs). Urine volume (UV), urinary sodium excretion (UNaV), fractional excretion of sodium (FENa), and fractional excretion of inorganic phosphorus (FEP) were measured by the clearance method. Urinary KAL and KIN were determined by direct-RIA. Urinary kininase (total, I and II) activities were measured by the kinin destroying capacity. Urinary PGE was measured by RIA. Following saline infusion, UV, UNaV, FEP, KAL, KIN and PGE significantly increased in both NT and EHT. The increases of UV, UNaV, FENa, FEP and KAL were remarkably greater in EHT than each in NT, while no significant difference was found in the increment of PGE between NT and EHT. Significantly positive correlations were observed between PGE and KAL or KIN in NT (r = 0.889, p less than 0.005; r = 0.574, p less than 0.05, respectively), but not in EHT. From these results, it was concluded that the exaggerated natriuresis observed in EHT following infusion may be significantly related to the augmentation of renal KAL-KIN system, but was not directly related to PGE.

A comparative study of the measurement of urinary kallikrein by various methods in patients with essential hypertension and patients with proteinuria.

In order to investigate the validity of urinary kallikrein (KAL) measurement, comparative studies were performed among the values obtained by various methods of urinary KAL measurements. Daily urine samples were collected from 37 hospitalized normal subjects (NS, 21 essential hypertensives without complications (EHT) and 20 patients with renal diseases associated with proteinuria (PU). Urinary KAL excretions were determined by direct radioimmunoassay (RIA), kininogenase assay (K-genase), TAMe esterase assay (TAMe), and PPA-MCA (MCA) and PPA-NE amidase assay (NE). By the desalting procedure, urinary KAL levels showed significant changes in TAMe, MCA and NE, but not in d-RIA and K-genase in all three groups. In TAMe, MCA and NE, the recovery of added KAL in urine was significantly lower in non-desalted samples in both EHT and PU, but not in NS. Impaired recovery and correlations between d-RIA or K-genase and TAMe, MCA or NE in non-desalted samples were improved by desalting. Although good correlations were observed between d-RIA or K-genase and TAMe, MCA or NE in desalted samples, the slopes of curves were steeper in EHT and PU than in NS, suggesting that the synthetic substrate methods still have some problems in the KAL measurement in these pathological states, KAL inhibitor, aprotinin and gabezate mesilate did not suppress the esterclytic and amidolytic activities completely, but suppressed K-genase activity completely in PU urine samples, suggesting that certain kinds of non-KAL esterases might remain in PU urine samples. Thus, d-RIA and K-genase appear to be the most reliable methods in the measurement of urinary KAL quantity and activity, respectively.

A sensitive method for differential determination of kininase I, II and neutral endopeptidase (NEP) in human urine.

In order to clarify the significance of NEP in human renal kallikrein-kinin system, an assay system was developed for the simultaneous determination of kininase I, II and NEP activities in human. Each kininase activity was determined by measuring the hydrolysis of bradykinin in the presence of specific inhibitors of kininase I (2-mercaptomethyl-3-guanidinoethylthiopropanoic acid), kininase II (captopril) and NEP (phosphoramidon) in 8 normal subjects. The effects of the different assay buffers on kininase activities were also investigated by using a phosphate buffer. Total kininase, kininase I, II and NEP activities were 499 +/- 65 ng/min/ml (mean +/- S.E.), 55 +/- 8, 141 +/- 21 and 299 +/- 42, respectively in our method using a tris buffer, while a phosphate buffer brought about activities of 358 +/- 43, 45 +/- 5, 156 +/- 21 and 135 +/- 25 ng/min/ml. The relative contributions of kininase I, II and NEP to total kininase activity were 11, 29 and 59% in our assay system, while they were 13, 44 and 35% when a phosphate buffer was used. From these results it was suggested that 1) phosphate may inhibit urinary NEP activity, so that a tris buffer should be used as the incubation buffer, 2) NEP is the major component of human urinary kininases, and 3) NEP may play an important role in the renal kallikrein-kinin system.

[Lipid peroxide and antioxidants in the elderly].

Aging is associated with changes in physical characteristics and decline of many physiological functions. The aging process have been described by various theories, in particular the free radical theory of aging has received widespread attention. It has been accepted that the oxidative stress or damage induced by free radicals is related to aging. In this study, we determined the serum concentration of lipid peroxide and antioxidant as biomarker for aging. Healthy subjects were classified into 3 groups, elderly (65-), middle-aged (40-64) and young group (20-39). Findings in the elderly were as follows: 1. Lipid peroxides in the elderly group were significantly higher than those in the young group. 2. Preventive antioxidant concentrations of superoxide dismutase, glutathione peroxidase and albumin were lower than those in the young group, but ceruloplasmin values increased and catalase activity was unchanged. 3. The total antioxidant capacity of serum was slightly decreased. 4. Superoxide generation by neutrophils while resting was significantly higher in the young group.

Study on the renal kallikrein-kinin system in normal and low renin subgroups of essential hypertension.

In order to investigate the role of the renal kallikrein-kinin (K-K) system in normal (NRH) and low renin (LRH) subgroups of essential hypertension (EHT), daily excretions of urinary kallikrein (KAL) quantity and activity, kinin (KIN), total and pre-KAL, and kininase I and II were measured in 21 normotensives (NT), 29 patients with NRH and 16 patients with LRH. The daily excretions of both KAL quantity and activity, total and pre-KAL, and KIN were significantly lower in NRH and LRH than in NT. That of kininase I was significantly higher in NRH and LRH than in NT, but that of kininase II was not. In comparing NRH and LRH, the urinary excretions of KAL activity and KIN were lower in LRH than in NRH, and that of kininase I was higher in LRH than in NRH. The KAL/total KAL ratio did not show any significant difference among NT, NRH and LRH. These findings suggest that the suppression of the renal K-K system in EHT seems to be due to both the decrease of KAL through the pre-KAL synthesis in the kidney and an increase of kininase I activity, but not to the inhibition of conversion from pre-KAL to active KAL and the more obvious suppression of this system in LRH than in NRH may be partly explained by KAL inhibitors and/or increased kininase I activity.

A case of normotensive primary aldosteronism--comparison with 13 previously experienced cases with hypertension.

A 47-year-old woman with normotensive primary aldosteronism is reported. In this case, hypopotassemia was found, but the patient's blood pressure was within the normal range. Her condition was diagnosed as primary aldosteronism without hypertension, which is very rare, based on an increased level of plasma aldosterone concentration, low plasma renin activity, and a typical finding of aldosterone-producing adenoma by adrenal scintigraphy. In the present case, similar values for urinary volume, renal function, plasma aldosterone concentration, plasma renin activity, plasma volume, total exchangeable sodium, urinary kallikrein excretion and a similar weight of the resected adenoma, but a shorter duration between the onset of symptom and hospital admission were observed as compared with those in 13 previously experienced cases of primary aldosteronism with hypertension. Thus, a shorter duration of primary aldosteronism appears to be an important factor in explaining the mechanism of normotension. However, we were unable to reach a definite conclusion and this is only a hypothesis. Further investigation will be required to clarify the mechanism of normotension in primary aldosteronism.

Localization of renal kallikrein-kinin system components in the kidney.

In a study using a stop-flow technique in dog kidney, the existence of kallikrein and kinin was recognized in distal tubules. The presence of kininase I was seen in both distal and proximal tubules, and also partly in the distal tubules. The presence of kininase II in the distal tubules was again confirmed by pretreatment with SQ14225. No evidence of kinin formation, however, was obtained in the proximal nephrons in stop-flow method. From these results, it was suggested that kininase I and II localized in proximal tubules may destroy the kinin filtered from glomeruli at the proximal level, while kallikrein and kininogen and also kininase I and II in the distal tubules may regulate the activity of the renal kallikrein-kinin system in the distal nephrons.

Prevalence of asymptomatic ST segment elevation in right precordial leads with right bundle branch block (Brugada-type ST shift) among the general Japanese population.

OBJECTIVE: To examine the modality and morbidity of asymptomatic ST segment elevation in leads V1 to V3 with right bundle branch block (Brugada-type ST shift). METHODS: 8612 Japanese subjects (5987 men and 2625 women, mean age 49.2 years) who underwent a health check up in 1997 were investigated. Those with Brugada-type ST shift underwent the following further examinations over a two year period after the initial check up: ECG, echocardiogram, 24 hour Holter monitoring, treadmill exercise testing, signal averaged ECG, and slow kinetic sodium channel blocker loading test (cibenzoline, 1.4 mg/kg). RESULTS: Asymptomatic Brugada-type ST shift was found in 12 of 8612 (0.14%) subjects. Eleven of these 12 subjects were followed up. Follow up ECG exhibited persistent Brugada-type ST shift in seven of 11 (63.6%) subjects. ST shift was transformed from a saddle back to a coved type in three subjects. None of the subjects had morphological abnormalities or abnormal tachyarrhythmias. Positive late potentials were found in seven of 11 (63.6%) subjects. Augmentation of ST shift was shown by both submaximal exercise and drug administration in one of the 11 subjects (9.1%). CONCLUSIONS: Asymptomatic subjects with Brugada-type ST shift were not unusual, at a rate of 0.14% in the general Japanese population. Almost all of the subjects had some abnormalities in non-invasive secondary examinations. Additional and prospective studies are needed to confirm the clinical significance and the prognosis of asymptomatic Brugada-type ST shift.

Chronic treatment with propranolol enhances the synthesis of prostaglandins E2 and I2 by the aorta of spontaneously hypertensive rats.

The effects of treatment with dl, d- or l-propranolol (subcutaneously for 1 week) on arterial blood pressure and on 6-keto prostaglandin (PG) F1 alpha (stable metabolite of PGI2) and PGE2 production by aorta, renal medulla and renal cortex were examined in spontaneously hypertensive rats. dl-Propranolol and l-propranolol significantly (P less than .05) lowered blood pressures from 148 +/- 9/113 +/- 5 (n = 6) and 133 +/- 4/100 +/- 2 (n = 12) mm Hg to 112 +/- 3/80 +/- 3 and 121 +/- 3/81 +/- 3 mm Hg, respectively. Comparable treatment of spontaneously hypertensive rats with inactive d-propranolol was without effect. Basal immunoreactive (i) i6-keto-PGF1 alpha and iPGE2 production by isolated aorta, renal medulla and cortex was not different in vehicle compared to the dl-propranolol-treated rats. In contrast, norepinephrine (1 microM)-stimulated synthesis of i6-keto PGF1 alpha and iPGE2 by the aorta in the dl-propranolol-treated group was significantly (P less than .05) enhanced compared with the vehicle-treated group. Aortic i6-keto-PGF1 alpha and iPGE2 synthesis stimulated by norepinephrine in l-propranolol-treated rats was also significantly (P less than .05) higher than that observed in vehicle and d-propranolol-treated rats. dl-Propranolol treatment did not alter norepinephrine-stimulated renal cortical or medullary i6-keto-PGF1 alpha or iPGE2 synthesis. Indomethacin (5 mg/kg i.p.) given on the last 2 days of dl-propranolol treatment, significantly inhibited aortic i6-keto-PGF1 alpha and iPGE2 production and blunted the antihypertensive effect of dl-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of undiagnosed pheochromocytoma caused by negative metoclopramide test].

Metoclopramide (MCP), a dopamine antagonist, was recently used as the pharmacological test for the diagnosis of pheochromocytoma. There have been no reports involving false negative cases in the MCP test. We experienced a rare case of pheochromocytoma which showed a negative MCP test, and it caused a failure of the diagnosis. A 51-year-old man visited our hospital with a sudden onset of headache and palpitation. Blood pressure was 218/98 mmHg at another hospital. When he came to our hospital, blood pressure returned to normal (120/80 mmHg), and both serum adrenaline (E) and noradrenaline (NE) were within normal limits. A computed tomography, magnetic resonance imaging, and angiography demonstrated a 1.8 x 1.8 cm right adrenal mass. No changes in blood pressure and plasma catecholamine were observed following the injection of 10 mg of MCP. The pathologically resected right adrenal gland contained a typical pheochromocytoma which was 1.0 x 1.0 cm in size and weighed 8 g. The detailed mechanism of the negative MCP test in this case was not known but might be related to the small size of the tumor.

Identification of novel C253Y missense and Y864X nonsense mutations in the insulin receptor gene in type A insulin-resistant patients.

Mutations in the insulin receptor gene have been reported in cases of type A insulin resistance. We report herein two cases of type A insulin resistance, which involve some novel mutations. Case 1 is a heterozygote of the C253Y missense mutation and case 2 is a heterozygote of the Y864X nonsense mutation. In the C253Y missense mutation in exon 3, a cysteine residue is replaced with tyrosine in the cysteine-rich domain of the alpha subunit. The Y864X in exon 13 results in a truncated receptor, which is devoid of most of the beta subunit. This mutant receptor could not be expressed on a cell membrane since the transmembrane domain is missing. Other significant mutations were not found for the entire coding regions and splice/donor sites.

Urinary excretions of kininase I and kininase II activities in essential hypertension. A sensitive and simple method for its kinin-destroying capacity.

To further clarify the role of the renal kallikrein-kinin system in essential hypertension, a sensitive and simple method for the determination of both human urinary kininase I and kininase II was established, and the system components were determined in patients. In the measurement of kininase activity, desalted urine samples were incubated with synthetic bradykinin, and the reaction was terminated with kininase inhibitors, ethylene diamine tetraacetic acid and phenanthroline. Thus, kininase activity was determined as the kinin-destroying capacity. Moreover, the specific inhibitor for kininase II, SQ14225, was applied for the separation of kininase I and kininase II activities. Daily urinary excretions of total kininase and kininase I activities were significantly higher in essential hypertensive patients than those in normotensive subjects, whereas no difference was observed in kininase II activity. As reported previously, daily excretions of urinary kallikrein and kinin simultaneously determined in these patients were significantly lower than excretions in normotensive subjects. From these results, it was suggested that not only decreased renal kallikrein, but also increased kininase activity, may play an important role in the suppression of the renal kallikrein-kinin system through the reduction of active kinin level in essential hypertension.