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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 415 records · Page 23Linked to original sources

[Effects of intravenous lansoprazole on acute gastric mucosal lesions and acid secretion].

The effects of lansoprazole given intravenously on gastric mucosal lesions, gastric bleeding and acid secretion were investigated in rats in comparison with those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited the formation of gastric mucosal lesions in rats induced by water-immersion stress or aspirin with ID50 values of 0.26 and 0.99 mg/kg, respectively, and also inhibited gastric bleeding induced by hemorrhagic shock or water-immersion stress with ID50 values of 0.46 and 1.22 mg/kg, respectively. Lansoprazole was more potent than omeprazole, famotidine and ranitidine in inhibiting gastric mucosal lesions and hemorrhagic shock- or stress-induced bleeding. Famotidine and ranitidine showed negligible inhibition of water-immersion stress-induced gastric bleeding. Lansoprazole strongly inhibited water-immersion stress-stimulated acid secretion in rats, whereas famotidine and ranitidine did not show a potent inhibitory effect. These results indicate that lansoprazole exerts prominent inhibitory actions against the formation of gastric mucosal lesions and gastric bleeding by inhibiting acid secretion, and they show that it is superior to histamine H2-receptor antagonists in inhibiting stress-induced gastric bleeding.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Role of capsaicin-sensitive sensory neurons and nitric oxide in the protective effect of lansoprazole, a proton pump inhibitor, on the gastric mucosa in rats.

The mucosal protective effect of lansoprazole, a proton pump inhibitor, was examined in ethanol- and acidified taurocholate-induced rat gastric lesion models. The formation of gastric lesions was markedly inhibited by prostaglandin E2 but hardly inhibited by cimetidine, ranitidine and famotidine. Lansoprazole (3-30 mg/kg, p.o.) inhibited the formation of gastric lesions in a dose-dependent manner, with ID50 values of 8.5 (ethanol) and 4.1 mg/kg, p.o. (acidified taurocholate). The protective effect of lansoprazole was significantly decreased by functional ablation of capsaicin-sensitive sensory neurons or prior administration of indomethacin or N(omega)-nitro-L-arginine methyl ester (L-NAME), a selective inhibitor of nitric oxide (NO) synthesis. The inhibitory effect of L-NAME was antagonized by prior administration of L-arginine, a substrate of endogenous NO, but not D-arginine. The antisecretory effect of lansoprazole on the basal acid secretion in pylorus-ligated rats was not affected by any of these treatments. Lansoprazole (5 and 15 mg/ml) administered directly into the gastric chamber obviously increased both the production of NO in the mucosa and mucosal blood flow, which was prevented by pretreatment with L-NAME. These results suggest that capsaicin-sensitive sensory neurons, NO and prostaglandins are involved in the mucosal protection afforded by lansoprazole possibly via an increase in mucosal blood flow, but are not involved in the antisecretory action of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Lessons for neurotoxicology from selected model compounds: SGOMSEC joint report.

The ability to identify potential neurotoxicants depends upon the characteristics of our test instruments. The neurotoxic properties of lead, methylmercury, polychlorinated biphenyls, and organic solvents would all have been detected at some dose level by tests in current use, provided that the doses were high enough and administered at an appropriate time such as during gestation. The adequacy of animal studies, particularly rodent studies, to predict intake levels at which human health can be protected is disappointing, however. It is unlikely that the use of advanced behavioral methodology would alleviate the apparent lack of sensitivity of the rodent model for many agents.

Animals↗

Evolution of our understanding of methylmercury as a health threat.

Methylmercury (MeHg) is recognized as one of the most hazardous environmental pollutants, primarily due to endemic disasters that have occurred repeatedly. A review of the earlier literature on the Minamata outbreak shows how large-scale poisoning occurred and why it could not be prevented. With the repeated occurrences of MeHg poisoning, it gradually became clear that the fetus is much more susceptible to the toxicity of this compound than the adult. Thus, recent epidemiologic studies in several fish-eating populations have focused on the effects of in utero exposure to MeHg. Also, there have been many studies on neurobehavioral effects of in utero exposure to methylmercury in rodents and nonhuman primates. The results of these studies revealed that the effects encompass a wide range of behavioral categories without clear identification of the functional categories distinctively susceptible to MeHg. The overall neurotoxicity of MeHg in humans, nonhuman primates, and rodents appears to have similarities. However, several gaps exist between the human and animal studies. By using the large body of neurotoxicologic data obtained in human populations and filling in such gaps, we can use MeHg as a model agent for developing a specific battery of tests of animal behavior to predict human risks resulting from in utero exposure to other chemicals with unknown neurotoxicity. Approaches developing such a battery are also discussed.

Animals↗

Ambulatory blood pressure monitoring in evaluating the prevalence of hypertension in adults in Ohasama, a rural Japanese community.

We estimated the prevalence of hypertension and evaluated the degree of blood pressure control on the basis of ambulatory blood pressure monitoring in patients receiving antihypertensive medication. A total of 969 adults (mean age +/- SD, 59.3 +/- 12.1 years old range: 20-79 yr) among 1,575 eligible persons (65.1%) recruited from a total adult population of 2,789 people living in a rural region of northern Japan underwent measurement of initial screening blood pressure; ambulatory blood pressure was measured subsequently. A total of 285 subjects (66.5 +/- 9.2 years old) were taking antihypertensive medication (treated group), while 684 (56.3 +/- 12.0 years old) were not (untreated group). The WHO criteria were used to categorize screening blood pressure. Ambulatory blood pressure levels were classified as follows: hypertension, systolic blood pressure > or = 144 mmHg and/or diastolic blood pressure > or = 85 mmHg; and normotension, systolic blood pressure < or = 133 and diastolic blood pressure < or = 78 mmHg. Of the 285 treated subjects, 49 (17.2%) were classified as hypertensive by screening measurements, while 36 (12.6%) were classified as such by ambulatory blood pressure monitoring. Only 12 (24.5%) of the former 49 subjects were also classified as hypertensive, while 20 (40.8%) were classified as normotensive by ambulatory blood pressure monitoring. Of the 684 untreated subjects, 34 (5.0%) were hypertensive by screening measurements and 43 (6.3%) were hypertensive by ambulatory blood pressure monitoring. Only 14 (41.2%) of the former 34 subjects were classified as hypertensive by ambulatory blood pressure monitoring. Of the 34 untreated subjects classified as hypertensive by screening measurements, ambulatory blood pressure monitoring showed 12 (35.3%) to be normotensive, suggesting that they were cases of "white coat" hypertension. The study first confirmed, based on community-derived data, that there are large discrepancies between screening (casual) blood pressure measurements and ambulatory blood pressure monitoring with respect to the recognition of hypertension and normotension. The determination of blood pressure levels by ambulatory blood pressure monitoring may result in a different prognosis of hypertension from that made on the basis of screening blood pressure measurements. The prognostic value of ambulatory blood pressure has to be further investigated.

Adult↗

The brain histamine (HA) and pituitary luteinizing hormone (LH) levels in female rats anesthetized with ether on proestrus.

Levels of brain histamine (HA) and pituitary luteinizing hormone (LH) were determined in female rats anesthetized with ether in the afternoon of proestrus. The rats after 6-hr ether anesthesia had an average HA concentration higher than that of non-anesthetized rats in the hypothalamus, but not in the cortex or diencephalon. Ether-anesthetized rats also showed a higher LH level in the pituitary than that of non-anesthetized rats. These findings agree well with our previous observation of an inhibited ovulation associated with a decrease in serum LH in female rats anesthetized with ether in the afternoon of proestrus. Furthermore, it is suggested that the release of pituitary LH into the circulating blood is regulated by the level of HA in the hypothalamus.

Anesthesia↗

Analysis of trace elements in the central nerve tissues with inductively coupled plasma-mass spectrometry.

To investigate the roles of various elements in neurological disorders, multi-element analysis of limited quantities of samples in the central nervous system is required. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis suits this requirement, but spectral and non-spectral interferences are inevitable. We studied correction methods for the non-spectral interferences by analyzing signals of 21 elements in various concentrations of HNO3 as well as 5 major elements (Na, K, P, Ca, and Cl). Using internal standards, the interferences caused by the major elements were corrected, but the interferences caused by HNO3 were impossible to correct for the elements with high ionization potentials. Thus, we decided to use a standard addition method to correct these interferences. The spectral interferences on Mn and Fe rising from HNO3 or major elements were compared with the signals of samples. Although the interferences on Mn were negligible, those on Fe were considerable and careful blank subtraction were needed. We measured concentrations of elements in the spinal cord of 4 controls and a patient with amyotrophic lateral sclerosis (ALS) using the standard addition method. The concentrations of Mn, Se, Fe, and Zn in the controls were nearly the same as previously reported values, whereas Mn concentrations in the ALS patient were higher.

Adult↗

Distribution of selenium in human plasma detected by high performance liquid chromatography-plasma ion source mass spectrometry.

The distribution of selenium in human plasma has been investigated by high performance liquid chromatography (HPLC) connected directly to inductively coupled plasma mass spectrometry (ICP-MS). Human plasma was loaded on to a size exclusion column and eluted with 0.01 M sodium phosphate buffer (pH 7.0) at a flow rate of 0.6 ml/min. Four peaks of selenium were detected in the chromatogram. The first selenium peak was obtained in the void volume. The retention time of the third peak was in accord with that of bovine serum albumin as a standard. The forth peak was thought to be a ghost. The method was applied to identify the chemical form of selenium in blood plasma immediately after intestinal absorption. The chromatographic pattern of selenium in postprandial human plasma was compared with that in fasting plasma. The first and third peaks in the postprandial plasma sample were slightly higher than those in the fasting plasma sample. This finding suggests that absorbed selenium is associated with the high molecular weight fraction and mercaptalbumin in blood plasma.

Adult↗

Microwave digestion using dual PTFE containers for analysis of trace elements in small amounts of biological samples.

The analysis of trace elements in biological samples is essential to extend our knowledge on human health and disease. Inductively coupled plasma mass spectrometry (ICP-MS) makes it possible to simultaneously determine these elements in trace amounts. Before analysis, however, biological samples such as organs and tissues must be liquefied and extra organic materials must be decomposed by acid digestion. We established a method of microwave digestion using dual PTFE containers to minimize the amount of samples. Samples (35-45 mg) of standard reference materials, bovine liver (1577a, NIST) and fish flesh (MA-A-2, IAEA), were weighed in PTFE-PFA vials and a small amount of nitric acid (0.5 ml) was added. The vials were sealed and two PTFE-PFA vials were placed in a PTFE-TFM vessel containing 6 ml of pure water. Then the vessels were placed in a rotor and the samples were digested for 38 min in a microwave oven according to a pre-set program. After the program was completed, the samples were analyzed by ICP-MS. The determined values of elements of the microwave-digested samples matched the certified values of the standard reference materials. Therefore, the digestion using dual containers was successfully applied to small samples.

Animals↗

Parathyroid carcinoma with metastatic calcification identified by technetium-99m methylene diphosphonate scintigraphy.

We describe herein a case of parathyroid carcinoma accompanied with metastatic calcification identified by technetium-99m methylene diphosphonate (Tc-99m MDP) scintigraphy in the lungs, kidneys and stomach. Parathyroid carcinoma remains a rare disorder despite the increased prevalence of primary hyperparathyroidism. Metastatic calcification is noted infrequently even in primary hyperparathyroidism and it may cause respiratory failure. Tc-99m MDP scintigraphy three months after surgery showed a complete disappearance of Tc-99m uptake in the stomach and an obvious reduction in the kidneys but no significant change in the lungs, indicating metastatic calcification can be reversibly reabsorbed. This case indicates that the adequate excision of parathyroid carcinoma as well as the early detection of metastatic calcification by Tc-99m MDP are obligatory.

Calcinosis↗

Unilateral acute exacerbation of pulmonary fibrosis in association with Sjögren's syndrome.

A 70-year-old female had an abnormal chest roentgenogram. Infiltrative shadows were recognized in the right lung, and an open lung biopsy (OLB) specimen revealed usual interstitial pneumonia (UIP). Xerostomia, keratoconjunctivitis sicca, and lymphocyte infiltration in salivary glands were consistent with Sjögren's syndrome; she was diagnosed as having pulmonary fibrosis in association with Sjögren's syndrome (SjS-IP). Acute exacerbation occurred and she was successfully treated with corticosteroids. Unilateral exacerbation and UIP in SjS-IP are rare. OLB is useful for diagnosis and to select a pertinent therapy if lung involvement is unilateral in Sjögren's syndrome.

Acute Disease↗

Prevalence of hypertension and rate of blood pressure control as assessed by home blood pressure measurements in a rural Japanese community, Ohasama.

A cross-sectional community survey using home blood pressure measurements was performed in northern Japan to estimate the prevalence of definite hypertension, white coat hypertension and the success of blood pressure control in patients receiving antihypertensive drugs. A total of 1334 subjects (mean age +/- SD, 53.8 +/- 17.3 years; 8-91 years) participated in the screening and home blood pressure measurement program. They measured blood pressure at home at least 3 times (mean measurement frequency, 20.8 +/- 8.3 times). Of these 1334 subjects, 314 (65.1 +/- 8.9 years) were taking drugs (treated group) while 1020 (50.3 +/- 17.8 years) were not (untreated group). The WHO criteria were used to categorize screening blood pressure. Criteria for diagnosis of hypertension by home blood pressure measurements were as follows: definitely hypertensive (systolic blood pressure > or = 144 mmHg and/or diastolic blood pressure > or = 89 mmHg) and normotensive (104 < systolic blood pressure < or = 131 mmHg and 60 < diastolic blood pressure < or = 79 mmHg). Of the 1018 subjects identified as normotensive on screening measurements, home measurements indicated that 73 (7.2%) were hypertensive and 765 (74.7%) were normotensive or lower. Of the 112 subjects identified as hypertensive on screening measurements, home measurements showed that 42 (37.5%) were hypertensive and 30 (26.8%) were normotensive or lower. Of the 314 treated subjects, 45 (14.3%) were identified as hypertensive by screening measurements and 88 (28.0%) as hypertensive by home measurements. Only 20 (44.4%) of the former 45 subjects were also defined as definitely hypertensive by home measurements. Of the 1020 untreated subjects, 67 (6.6%) were hypertensive by screening measurements and 84 (8.2%) by home measurements. Only 22 (32.8%) of the former 67 subjects were classified as hypertensive by home measurements. Of the 67 untreated subjects identified as hypertensive by screening measurements, 20 (29.9%) were normotensive or lower by home measurements, suggesting that these subjects were "white coat" hypertensives. The study first confirmed based on the large community data that there are large discrepancies between screening (casual) blood pressure and home blood pressure measurements for recognition of hypertension and normotension. Determination of blood pressure levels by home blood pressure measurements may predict prognosis of hypertension differently from that by screening blood pressure measurements. Further prospectively study is needed to validate the prognostic value of home blood pressure measurements.

Adolescent↗

Analysis of circadian variation of blood pressure and heart rate in dexamethasone-induced hypertensive rats.

We studied the effect of the chronic oral administration of dexamethasone (dexa) on arterial blood pressure (BP) in conscious rats. Special attention was paid to the effects of dexa on circadian rhythm of BP. As determined by the tail cuff-method, BP in the dexa-treated group was significantly higher than in the control group 24 h after treatment, then increased gradually, reaching a plateau on the 7th day of treatment. At that time, the difference in BP between the two groups was approximately 30 mmHg. When monitored directly and continuously on day 10, mean arterial pressure (MAP) in the dexa-treated group exceeded that of the control group by approximately 15 mmHg throughout the monitoring period. Thus, the circadian rhythm of MAP was sustained in the dexa-treated group, which was in contrast to the previously reported elimination of circadian rhythm in humans. In addition, the increase in BP may have been overestimated by tail-cuff plethysmography, possibly owing to a hightended cardiovascular reactivity to environmental stimuli in dexa-treated animals.

Administration, Oral↗

Predictive power of screening blood pressure, ambulatory blood pressure and blood pressure measured at home for overall and cardiovascular mortality: a prospective observation in a cohort from Ohasama, northern Japan.

OBJECTIVE: To investigate the risks of high and low blood pressure levels determined by ambulatory blood pressure monitoring and home blood pressure measurements. METHODS: A long-term prospective study of all-cause mortality and cardiovascular mortality has been conducted in Ohasama, Japan since 1987. RESULTS: The Cox proportional hazards model after adjusting for age and sex demonstrated that, during a 5-year follow-up period involving 893 of the subjects aged 50 years or more in this cohort, those with the lowest quintile of ambulatory blood pressure levels exhibited a significantly higher hazard ratio for cardiovascular and for all-cause mortality. During the same follow-up period, of 1226 subjects aged 50 years and more, those with the lowest and highest quintiles of home blood pressure levels demonstrated a significantly higher hazard ratio with respect to cardiovascular and all-cause mortality (i.e., a J-shaped relationship). CONCLUSION: These results suggest that there is a significant risk associated with low blood pressure levels, which can be determined by ambulatory and home blood pressure measurements, but not by casual blood pressure measurements.

Journal Article↗

[Invasive thymoma associated with pure red cell aplasia and lung cancer].

A 71-year-old man was admitted to our hospital with vertigo and general fatigue. Examination of his blood and bone marrow showed pure red cell aplasia. His chest X-ray film revealed an anterior mediastinal mass and a nodular shadow in the right lower lobe. Extended thymothymectomy and right lower lobectomy were done. The mediastinal mass appeared to be an invasive thymoma and the nodular shadow in the right lower lobe proved to be from an adenocarcinoma. The patient was treated with radiation and steroids. Thymoma, pure red cell aplasia, and lung cancer had not recurred and he was alive and well as of 2 years after surgery.

Adenocarcinoma, Papillary↗

Ca(++)-dependence of caffeine modulation of the rate-force relation in canine cardiac Purkinje fibers.

The effects of caffeine on rate-force relation and their Ca++ dependence were studied in canine cardiac Purkinje fibers. At constant rate, caffeine increased and then decreased force. During drives at different rates (15, 60 and 120/min), 1 mM caffeine caused the largest positive inotropic effect at the slowest rate, but in 8.1 mM [Ca++]o caffeine no longer increased force even at 15/min. Interruptions of drive were followed by a positive and then a negative staircase: caffeine (1-4 mM) blunted these effects. A sudden decrease in rate caused a positive staircase: caffeine decreased and caffeine plus 8.1 mM [Ca++]o abolished it. A sudden increase in rate caused a negative staircase and on recovery a positive staircase: caffeine reduced and caffeine plus 8.1 mM [Ca++]o could reverse them. In low [Ca++]o (0.54 mM), caffeine caused only a positive inotropic effect and did not modify the rate-force relation patterns. High [Ca++]o ( > 8.1 mM) reversed the staircase patterns induced by a rate increase; adding caffeine shifted the reversal to lower [Ca++]o. Low [Na]o altered the rate-force relation similarly to high [Ca++]o, and caffeine exaggerated its effects. Decreasing [Ca++]i by means of tetrodotoxin or high [K+]o antagonized the caffeine effects on the rate-force relation. We conclude that caffeine markedly modulates the rate-force relation through a Ca(++)-dependent mechanism. This mechanism appears to involve a supraoptimal increase in [Ca++]i rather than a decrease in Ca++ released during the action potential.

Animals↗

Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat, human, and cdna-expressed human cytochrome P450.

Midazolam (MDZ) is metabolized in human liver microsomes by the cytochrome P450 (CYP) 3A subfamily to 1'-hydroxy (1'-OH) and 4-hydroxy (4-OH) metabolites. MDZ is metabolized in the rat primarily to 4-OH MDZ, 1'-OH MDZ, and 1',4-dihydroxy (1',4-diOH) MDZ. The kinetics of 4-OH and 1'-OH metabolite formation were determined using hepatic microsomes from control, Ro 23-7637 and dexamethasone-treated male rats. KM values for the major metabolite, 4-OH MDZ, were 24.5, 43.1, and 32.8 microM, and the corresponding Vmax values were 5.9, 28.9, and 13 nmol/mg/min for the control, DEX, and Ro 23-7637-treated animals, respectively KM values for 1'-hydroxylation of MDZ (the major metabolite) after incubation with human liver microsomes from three individuals were 5.57, 2.50, and 3.56 microM, and the corresponding Vmax values were 4.38, 0.49, and 0.19 nmol/mg/min, respectively. In parallel studies using cDNA-expressed human CYP3A4 microsomes, the KM for 1'-OH formation was 1.56 microM, and the corresponding Vmax was 0.16 nmol/mg/min. MDZ was not metabolized by cDNA-expressed human CYP2D6, CYP2E1, or CYP1A2, thus confirming that these isoforms were not responsible for its biotransformation. The formation of 1',4-diOH metabolite in rat and 1'-OH formation in cDNA-expressed human CYP3A4 microsomes showed a decrease in velocity at high substrate concentrations. Inhibition studies showed that MDZ hydroxylation was strongly inhibited by ketoconazole and Ro 23-7637 in rat, human, and cDNA-expressed human CYP3A4 microsomes. alpha-Naphthoflavone stimulated 1'-OH metabolite formation in human and cDNA-expressed human CYP3A4 microsomes at low concentration (10 microM). Naringenin, a flavonoid present in grapefruit juice, also inhibited MDZ metabolism in human liver microsomes. Immunoinhibition studies revealed that polyclonal anti-rat CYP3A2 antibody inhibited MDZ metabolism 80-90% in rat, human, and cDNA-expressed human CYP3A4 microsomes, thus suggesting that members of the CYP3A4 subfamily were involved in the metabolism.

Anesthetics, Intravenous↗