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Biomedical subjects

Y Fukuchi

Publications and source records attributed to Y Fukuchi.

At least 199 records · Page 11Linked to original sources

[The effect of ageing on airway responsiveness].

In order to evaluate the significance of airway responsiveness in the elderly: 1. Airway responsiveness in the healthy elderly was evaluated and compared with that of the healthy young adults. Methacholine dose response curve was constructed by measuring total respiratory resistance using the modified partial airway occlusion method which provides a simple, convenient, and non-invasive assessment of the resistance of the total respiratory system. Although the responders were fewer and the average threshold values were higher in the elderly, there was no significant differences in the methacholine dose response curve. 2. In vivo and in vitro methacholine dose response relationship was measured in the old guinea pigs (20 to 25 months old) and was compared with that of the young adult guinea pigs. Although no significant differences in the threshold values was observed, the in vivo airway response to the methacholine dose of 1 mg/ml was significantly lower in the old guinea pigs than in the young. The old guinea pig showed small but significant right side shift in the in vitro methacholine dose response relationship. 3. The intra-tracheal instillation of hydrochloric acid to the guinea pig was used as an animal model of aspiration pneumonia. The airway responsiveness was evaluated before and after the instillation. The acid instillation caused the acute and transient bronchoconstriction and the airway responsiveness was markedly increased one hour after the instillation. We conclude that the airway responsiveness may be unchanged or somewhat decreased in the elderly and that the increased airway responsiveness may play a role in the phathologic state such as an aspiration pneumonia.

Adult↗

A new murine model of aging lung: the senescence accelerated mouse (SAM)-P.

The senescence accelerated mouse (SAM) has recently been characterized as a unique model to investigate age-related disorders, including amyloidosis, cataract, osteoporosis and dementia. However, little is known as to the properties of the lung in these animals. Tobacco smoke is also associated with enhanced loss of elastic recoil and the development of emphysema. We have attempted to examine morphological as well as biochemical changes of the distal lung in SAM-P/2, as the senescence-prone series and SAM-R/1, as the senescence-resistant series. The animals were intermittently exposed to tobacco smoke or air by Hamburg II machines for 5 weeks. Then both groups of animals were killed for histologic and biochemical study. Compared with SAM-R/1, SAM-P/2, even with air exposure, showed a higher value of the mean linear intercept without alveolar wall destruction. It became even greater due to tobacco exposure with emphysematous change. Tobacco exposure accumulated inflammatory cells into alveoli in SAM-P/2, but not in SAM-R/1. Oxygen radical generation by those cells was also higher in SAM-P/2. Analysis of bronchoalveolar lavage fluid in SAM-P/2 after tobacco exposure disclosed increases in albumin content, total protein content and elastase-like activity. There were decreases in the ratio of elastase inhibitory capacity (EIC) to trypsin inhibitory capacity (TIC), contents of glutathione and total free thiol groups. Moreover, SAM-P/2 showed significantly lower EIC/TIC ratio in serum, even with air exposure, than that of SAM-R/1. These results indicate that SAM-P/2 can be a good model for the study of natural evolution of the aging lung as well as its susceptibility to tobacco smoke in the development of emphysema.

Aging↗

The effect of beta-adrenergic blockade in dilated cardiomyopathy--a questionnaire study in Japan.

The effect of beta-blockade in dilated cardiomyopathy was studied by a questionnaire survey. Thirty-three cases were monitored in whom metoprolol (22 patients, 35.9 +/- 20.4 mg, mean +/- SD), propranolol (four patients, 26.3 +/- 7.5 mg), or other beta-blockers (seven patients) were administered. Four patients died, but no direct relationship was found between administration of beta-blocker and death. The NYHA functional class improved significantly. The mean heart rate decreased from 96/min to 77/min (P less than 0.01). The mean cardiothoracic ratio decreased from 55.6% to 52.1% (P less than 0.01). The mean ejection fraction of the left ventricle measured by echocardiogram increased from 30.4% to 36.9% (P less than 0.01). Exercise tolerance in the treadmill test improved significantly. There was no change in blood pressure, nor were there arrhythmias seen on Holter electrocardiograms. In two patients, congestive heart failure deteriorated after administration of beta-blockers. It is concluded that beta-adrenergic blockade has a beneficial effect in most of the patients with dilated cardiomyopathy.

Adolescent↗

Intravenous bolus of prednisolone decreases 15-hydroxyeicosatetraenoic acid formation in the rat model of acid aspiration.

BACKGROUND AND METHODS: To test the hypothesis that the effect of steroids on hydrochloric acid aspiration may be involved in the metabolism of eicosanoids, we investigated the effects of an iv bolus of prednisolone on the metabolism of 15-hydroxyeicosatetraenoic acid and 11-dehydrothromboxane B2 (11-dehydro-TxB2) in the rat model of acid aspiration. Wistar rats were randomly selected for three groups and treated with either a) an iv bolus of saline after intratracheal injection of saline (control group), b) an iv bolus of saline after intratracheal injection of acid (acid-saline group), or c) an iv bolus of prednisolone after intratracheal injection of acid (acid-prednisolone group). The concentrations of 15-hydroxyeicosatetraenoic acid and 11-dehydro-TxB2 in bronchoalveolar lavage fluid were measured by radioimmunoassay. RESULTS: The concentration of 15-hydroxyeicosatetraenoic acid in bronchoalveolar lavage fluid of either acid-saline group (804 +/- 129 pg/mL) or acid-prednisolone group (748 +/- 112 pg/mL) was significantly greater than that of the control group (143 +/- 27 pg/mL, p less than .01) 1 hr after the administration. The iv bolus of prednisolone caused a significant decrease in 15-hydroxyeicosatetraenoic acid (acid-saline group 1027 +/- 43 pg/mL; acid-prednisolone group 514 +/- 62 pg/mL; p less than .01) and cell counts of bronchoalveolar lavage fluid 48 hrs after intratracheal injection of acid, while there was no significant change in 11-dehydro-TxB2. CONCLUSION: These findings suggest that corticosteroid administration may contribute to the inhibition of the inflammatory process of lungs after acid aspiration by decreasing the release of 15-hydroxyeicosatetraenoic acid in the distal lung unit.

Animals↗

Efficacy of oral administration of ofloxacin in lower respiratory tract infections in aged patients with chronic lung disease.

The efficacy of ofloxacin for the treatment of lower respiratory tract infection was evaluated in aged patients with chronic lung disease. Results are the following: improvement of leukocytosis and arterial oxygen tension was observed; peripheral blood cell analysis showed a decrease in natural killer cell counts and in helper/suppressor T cell ratio; superoxide production by peripheral blood white cells was decreased after treatment; interleukin-2 production was rather increased. We concluded that improvement in the immunological parameters indicated the efficacy of ofloxacin for lower respiratory tract infection in aged patients with chronic lung disease.

Administration, Oral↗

[A clinical evaluation of the inorganic mercurialism--its pathogenic relation to amyotrophic lateral sclerosis].

The pathogenic relation of chronic mercurialism and amyotrophic lateral sclerosis (ALS) was evaluated clinically on 83 ex-mercury workers who were poisoned or exposed to mercury vapor about 18 years ago at one of the biggest mercury mines in Hokkaido, as well as on the causes of 65 expired workers in the cohort. The 83 ex-mercury workers were subdivided into two groups according to severity of mercury poisoning: 31 ex-workers who had been hospitalized for treatment of mercury poisoning and the remaining 52 ex-workers severely exposed to mercury vapor but not hospitalized. Neurologic examinations and measurements of mercury contents in the blood, urine, and hair samples in the 83 cases, failed to disclose any pathogenicity of mercury to ALS. Among these 148 including the 65 deceased cases, no ALS cases were found. Further clinical and epidemiological studies should be required on mercury poisoning as one of the risk factors in the development of ALS, especially in relation to selenium.

Aged↗

Endothelin-1 stimulates arachidonate 15-lipoxygenase activity and oxygen radical formation in the rat distal lung.

We investigated the effects of intravenous bolus of endothelin-1 on the metabolism of eicosanoids and oxygen radicals in the distal lung unit of the rat. Intravenous bolus of endothelin-1 caused a significant increase in 15-hydroxyeicosatetraenoic acid of bronchoalveolar lavage fluid and oxygen radicals produced by the bronchoalveolar cells. Endothelin-1 exhibited a stimulatory effect on the 15-lipoxygenase activity in the lung homogenate. Thus, endothelin-1 may contribute to the inflammatory and hyperreactive process of lungs, by enhancing the release of 15-hydroxyeicosatetraenoic acid and oxygen radicals in the distal lung unit.

Animals↗

Circadian rhythms in the number of gastrin cells, DNA synthesizing cells and labelling index of gastrin cells in the antral mucosa of the rat.

Circadian variations of the gastrin cell (G-cell) number, the DNA synthesizing cell (S phase cell) number and labelling index of G-cell in antral mucosa were studied using the simultaneous double immunoenzymatic labelling method of gastrin and bromodeoxyuridine (BrdU) both in fed and 24 h fasted rats. No significant change was observed in the G-cell number. The S phase cell number and labelling index of G-cell showed significant circadian rhythms. Labelling index of G-cell markedly decreased in 24 h fasted rats in comparison to that in fed rats. These results suggest that DNA synthesis in G-cells has a circadian rhythm and that the activity is influenced by food ingestion.

Animals↗

Reduction of 15-hydroxyeicosatetraenoic acid (15-HETE) in tracheal fluid by high frequency oscillatory ventilation.

The effects of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) on tracheal secretion were compared in 6 anesthetized dogs. Using a double-balloon endotracheal catheter, 5 ml of saline was instilled into an isolated tracheal segment during HFOV and CMV for 10 min respectively. Two eicosanoids, 15-hydroxyeicosatetraenoic acid (15-HETE) and 11-dehydrothromboxane B2 (11-dehydro-TXB2) were measured by radioimmunoassay in each sample. HFOV (stroke volume: 6 ml/kg, f: 10 Hz, bias flow: 5 l/min) and CMV (stroke volume: 12 ml/kg, f: 15/min) were performed in random sequence and achieved comparable gas exchange. The concentration of 15-HETE in tracheal fluid during HFOV (87 +/- 67 pg/ml) was decreased to less than half of that during CMV (286 +/- 184 pg/ml, P less than 0.05), while there was no significant change of 11-dehydro-TXB2 either in tracheal fluid or in plasma. This reduction of 15-HETE was tended to be enhanced by vagotomy (HFOV: 42 +/- 14, CMV: 120 +/- 103 pg/ml) with the concentration ratio of CMV/HFOV remaining unchanged. HFOV may provide hitherto unrecognized advantage over CMV by reducing airway secretion of 15-HETE, a potent inflammatory mediator.

Animals↗

Effect of endothelin-1 on pulmonary resistance in rats.

We examined the effect of endothelin-1 (ET-1), a novel 21-residue vasoconstrictor peptide, on pulmonary resistance (RL) in Wistar rats. The lung volume, tracheal flow, and transpulmonary pressure of tracheotomized and paralyzed rats were measured with a fluid-filled esophageal catheter and a pressure-sensitive body plethysmograph. RL was calculated by the method of von Neergaard. The femoral artery was cannulated to measure the mean arterial blood pressure. Intravenous bolus administration of synthetic ET-1 provoked a dose-dependent increase in RL in rats. The bronchoconstricting effect reached maximum at 500 pmol/kg. This bronchoconstriction was observed in less than 5 min, increased up to 15 min, and was sustained for 60 min. ET-1 increased the mean arterial blood pressure in a dose-dependent manner. We conclude that ET-1 is a hitherto unknown potent bronchoconstrictor that has a sustained effect in vivo. The potential physiological and pathophysiological role of this new peptide in the development of respiratory disease warrants further investigation.

Airway Resistance↗

Chronic arterial occlusion with PGE1-resistant skin lesions treated by glycosaminoglycan compound--case reports.

The authors report on 2 patients with chronic arterial occlusion in whom the intravenous administration of the glycosaminoglycan compound FPFD 101 was markedly effective. One patient suffered from thromboembolic episodes of the left hand, and the other had peripheral circulatory impairment related to collagen disease. In these patients, the oral administration of anticoagulants and antiplatelet agents in combination with intravenous infusion of prostaglandin E1 was not adequately effective. However, the addition of intravenous injection of FPFD 101 resulted in a marked improvement in their symptoms. FPFD 101, which has an anticoagulant effect and also inhibits platelet aggregation, seems to be useful for the treatment and prevention of chronic arterial occlusion when combined with drugs such as anticoagulants, antiplatelet agents, and vasodilators.

Alprostadil↗

[An aged case of orthostatic hypotension possibly due to parasympathetic neurodysfunction].

94-year-old male patient, with orthostatic hypotension, possibly due to impairment of vasoconstriction and parasympathetic nervous system dysfunction was reported. This patient experienced faintness and lower muscle weakness on standing. The blood pressure was 180/90 mmHg in a supine position, while it significantly decreased to 100/58 mmHg in an upright position. There was no evidence indicating the presence of organic brain diseases, cardiovascular diseases, and endocrine diseases, plasma catecholamine, renin, aldosterone, and vasopressin levels at rest were within normal range. Thus, the cause of orthostatic hypotension of this patient was unknown. His systolic blood pressure decreased by 70 mmHg, and his diastolic blood pressure also decreased by 25 mmHg in response to a 70 degrees head-up tilting test (170/71-100/46 mmHg). Plasma vasopressin level significantly increased in response to this test (0.62-67.2 pg/ml). Plasma catecholamine levels also increased (Adr 0.01-0.10 ng/ml, Ndr 0.05-0.22 ng/ml). Other autonomic nervous system examinations revealed normal responses to mental arithmetic test, hyperventilation test, cold pressure test, and adrenalin test. However, the results of the carotid occlusion test, acetylcholine test, atropine test, phenylephrine test were considered to be abnormal. From these findings, we concluded that the functions of sympathetic nervous system were almost intact, while the parasympathetic functions were impared in this case. The orthostatic hypotension of the patient as effectively treated with fludrocortisone. This report suggests that impairment of vasoconstriction and parasympathetic neurodysfunction might be involved in the development of orthostatic hypotension in the elderly.

Acetylcholine↗

[Cisplatin and vinca alkaloid combination chemotherapy of advanced non-small-cell lung cancer in the aged].

Fifteen patients aged over 65 years of age with advanced non-small-cl lung cancer (mean age = 70.7, stage IIIb: IV = 4:11) were treated with combination chemotherapy consisting of Cisplatin (50 or 80 mg/m2) and a vinca-alkaloid (Vindesine 3 mg/m2 or Etoposide 80 mg/m2). The effectiveness and side effects of this cisplatin therapy in different combinations of vinca-alkaloid regimens (Vindesine vs Etoposide) were examined. The mean dose of Cisplatin in the Etoposide combination group (75.2 mg/m2) was significantly higher than that in the Vindesine combination group (54.3 mg/m2) (p less than 0.01). A notable reduction the tumor size was observed in 25% of the Etoposide group, only. The 6-month survival rate and one-year survival rate were respectively 85.7%, 57.1% in the Vindesine + Cisplatin group, and 87.5%, 50% in the Etoposide + Cisplatin group. The common side effects were nausea, vomiting, anorexia, and alopecia. These symptoms were either alleviated by antiemetic drugs or followed by spontaneous recovery. Leucopenia, anemia and thrombocytopenia were found in both groups, and there was no difference in the time course of myelosuppression between the two groups. The extent of nephrotoxicity was assessed by creatinine clearance rate. Its decrease in the Vindesine group (60.1----38.9 ml/min) was higher than that in the Etoposide group (64.9----48.9 ml/min), while there was no significant change in BUN, serum creatinine and urine NAG between the two groups. There were no cases in which chemotherapy schedules had to be interrupted due to myelosuppression and nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Analysis of ventilatory parameters of nocturnal disturbed breathing in the elderly].

To elucidate the effects of aging on ventilation in nocturnal disturbed breathing (NDB), we investigated 16 subjects aged 65 years or over with system developed by the authors using a respiratory inductive plethysmography connected to a personal computer. The subjects underwent 10 hours of continuous monitoring of lung volume and SaO2. Significant desaturation (SDS, greater than 4% drop in SaO2 from baseline value) and desaturation index [DI, sigma SDS(%) X duration (hr)] were calculated using the same program. The subjects with SDS below 50 were assigned to group A (n = 9, mean age = 79.7, male:female = 8:1) and the remaining subjects with SDS over 50 (n = 7, mean age = 74.7, male:female = 3:4) to group B. There was no significant difference in ventilatory parameters between group A and B. We then compared the male group (n = 11, mean age = 77.8) with the female group (n = 5, mean age = 76.8). The number of SDS in the female group (101.4 +/- 34.7) was significantly greater than that of the male group (33.4 +/- 8.3*, p less than 0.02), while minute ventilation of the female group (5.25 +/- 0.31 l/min) was significantly smaller than that of the male group (8.86 +/- 1.36* l/min, p less than 0.05). DI was found to significantly correlate with the SaO2 nadir and the number of apnea and SDS. There was no significant relationship between SDS and ventilatory parameters in this study. NDB among elderly female may be of more importance than has been reported.

Aged↗

Influences of inhaled tobacco smoke on the senescence accelerated mouse (SAM).

We studied the influences of inhaled tobacco smoke on lung structure, biochemical changes in bronchoalveolar lavage (BAL) fluid, and glutathione (GSH) content of the lung in the senescence accelerated mouse (SAM), using 30 female SAM-P/8 as the "senescence-prone series", compared with SAM-R/1 as the "senescence-resistant series". At 18 wks of age, half of each series were housed in Hamburg II machines and exposed to an atmosphere of tobacco smoke for 5 wks, 10 min a day, 5 days a wk. At 24 wks of age, all of the animals were sacrificed. Blood, lung, liver, kidney and eyes were removed and the contents of GSH and thiol group (-SH) were measured (n = 5). We also performed BAL, to determine its total protein, albumin, and fibronectin contents, and elastase-like activity, elastase inhibitory capacity (EIC), and trypsin inhibitory capacity (TIC) (n = 5). Histological changes of the lungs from non-lavaged animals were also examined by light microscopy (n = 5). In SAM-P/8 not exposed to tobacco smoke, the mean linear intercept was longer than that in SAM-R/1. The exposure of SAM-P/8 to tobacco smoke caused increases in its lung weight and the ratio of albumin to total protein in BAL fluid, a decrease in the EIC/TIC ratio in BAL fluid, and a decrease in the GSH content and the GSH/-SH ratio of the lung, compared with those not exposed. We also observed focal infiltration of macrophages into alveoli with hyaline membrane and thickened alveolar wall in SAM-P/8 with tobacco exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

[Quantitative assessment of dyspnea by introducing new indices based on the Borg scale during exercise test and the correlation with parameters of pulmonary functions at rest].

Incremental exercise test with a bicycle ergometer was performed on thirty eight patients (11 patients with chronic obstructive pulmonary disease, 6 patients with interstitial lung disease, 21 patients with preoperative check up for respiratory disease). In 34 patients except four patients with interstitial lung disease, there was a close correlation between dyspnea expressed on the Borg scale (BS) and oxygen consumption (VO2) (r = 0.778-0.998). To evaluate dyspnea in more quantitative manner, we introduced three parameters by the BS-VO2 regression line. The Borg scale slope (BSS) represents the slope of the regression line, threshold load of dyspnea (TLD) represents the onset of dyspnea on the regression line, and the breakpoint load of dyspnea (BLD) represents the maximum oxygen consumption before the subject interrupted exercise. BSS had significant negative correlations with VC, %VC, FEV1.0, TLC, DLco, and %DLco. TLD and BLD had significant positive correlations with VC, FEV1.0, DLco, and %DLco. No correlation was found between dyspnea evaluated by the Hugh-Jones classification and the parameters of pulmonary functions (VC, FEV1.0, DLco) at rest. From these findings, we conclude that the degree of dyspnea sensation on exercise correlated with parameters of pulmonary function at rest, and that these newly introduced parameters using the Borg scale were useful for a quantitative assessment of dyspnea in health and disease.

Dyspnea↗