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Biomedical subjects

R Fukushima

Publications and source records attributed to R Fukushima.

53 records · Page 3Linked to original sources
PubMed1993

Prostaglandin E1 analogues misoprostol and enisoprost decrease microbial translocation and modulate the immune response.

The aim of this study was to investigate the ability of two prostaglandin E1 (PGE1) analogues, misoprostol and enisoprost, to alter bacterial translocation following burn injury. Balb/c mice were treated with misoprostol (n = 36) or enisoprost (n = 36) for 3 days with different doses (20 or 200 micrograms/kg/day) prior to receiving a 20% full-thickness burn and simultaneous gavage with 1 x 10(10) 14C-Escherichia coli. Animals were sacrificed 4 and 24 hr postburn, and blood, peritoneal fluid, mesenteric lymph nodes, spleen, liver, and lungs were harvested aseptically. Radionuclide counts, number of viable bacteria, and percentage of translocating bacteria remaining alive in each tissue suggested that the high doses of misoprostol or enisoprost decreased the magnitude of 14C-E. coli translocation, while the low dose of both drugs enhanced bacterial clearance. Therefore, both misoprostol and enisoprost reduce bacterial translocation, and modulate bacterial clearance in a dose-dependent manner.

Alprostadil↗
PubMed1993

Translocation of Candida albicans is related to the blood flow of individual intestinal villi.

Splanchnic ischemia is associated with increased bacterial translocation, but previous observations showed that translocation of Candida albicans did not occur uniformly among individual intestinal villi. This study was performed to investigate the relationship between the degree of Candida translocation and the microcirculation of individual villi. Thiry-Vella intestinal loops were created in eight guinea pigs. One week later, the distal aorta and right carotid artery were cannulated, and systemic blood pressure was recorded throughout the entire experiment. C. albicans (1 x 10(10)) was introduced into the Thiry-Vella loop, and the animals underwent a 40% full-thickness burn. Systolic hypotension was observed in the first 75 minutes postburn; then the systemic blood pressure returned to a normal range. Four hours after burn, 8 x 10(7) microspheres (10 microns) were injected into the aorta. The animals were sacrificed, and the Thiry-Vella loops were harvested and processed for light microscopy. At the microscopic level, within each villus, both the number of beads trapped in the arterioles and the number of Candida translocated into the enterocytes were counted. An inverse linear correlation between number of beads and number of translocated yeast per individual villus was found (r = -0.78; P < 0.005). These data provide further evidence that blood flow is an important determinant of the magnitude of microbial translocation, even within individual villi.

Animals↗
PubMed1993

[Antiinflammatory effects of the betamethasone sodium phosphate enema on carrageenan induced colitis in the rabbit].

The effect of the betamethasone sodium phosphate (BSP) enema on the colonic mucosal lesions in the carrageenan induced colitis (rabbit) was examined laboratory and histologically. The effect of drugs were evaluated by the changes of body weight, fecal occult blood, blood analysis, and histological examinations. Fecal occult blood were highly positive in the physiological saline treated but less positive in the BSP groups. In the blood analysis, anemia was not detected in both groups. Histological findings such as the defect of superficial epithelium, crypt abscess, inflammatory cell infiltration, atrophic changes, defect of muscularis mucosae, goblet cell depletion, goblet cell depletion, ulcer formation, and edematous change were scored to evaluate the colonic mucosal lesions. These scores (Mean +/- S.D.) were 4.4 +/- 1.96, 7.7 +/- 3.67 for BSP, physiological saline groups respectively. From these results, BSP enema showed an antiulcerative effect on the entire colonic lesions in the carrageenan induced colitis in the rabbit.

Animals↗
PubMed1992

Marked and prolonged depression of factor XIII after esophageal resection.

Anastomotic leakage is one of the most common complications of esophagectomy and, since Factor XIII is required for normal wound healing, we investigated the temporal changes in plasma Factor XIII following esophagectomy and hepatectomy. A control group of patients undergoing other abdominal operations was also studied. Factor XIII activity was determined before surgery and on postoperative days (POD) 1, 3, 7 and 14. The plasma levels of acute phase protein were also measured. The plasma Factor XIII activity decreased significantly in both the hepatectomy and control groups until POD 7, reaching the lowest level on POD 3. In contrast, the esophagectomy group showed significant decreases in Factor XIII levels throughout the postoperative study period, with a nadir with an average activity of 56 per cent on POD 7. Preoperative transferrin levels had a positive correlation with Factor XIII levels measured on POD 3 and there was also a positive significant correlation between Factor XIII activity and alpha 2-macroglobulin levels on POD 3. These results suggest that there is a marked and prolonged depression of plasma Factor XIII activity following esophagectomy which may be attributed to accelerated tissue demands, inadequate synthesis or increased degradation. Moreover, the severe and sustained decrease in Factor XIII activity may be related to poor wound healing after esophagectomy.

Abdomen↗
PubMed1992

The degree of bacterial translocation is a determinant factor for mortality after burn injury and is improved by prostaglandin analogs.

Bacterial translocation and related mortality rates were examined in previously transfused BALB/c mice that were gavaged with 14C radioisotope-labeled Escherichia coli before inflicting a 20% full-thickness flame burn. Radionuclide counts were measured in blood obtained by retro-orbital puncture 4 hours postburn, and survival was recorded for 10 days. Radionuclide counts in the blood correlated well with both radionuclide counts and numbers of viable bacterial in the tissues. Survivors had significantly less bacterial translocation as evidenced by blood radionuclide counts compared with nonsurvivors, and there was a significant inverse correlation between the degree of translocation and the length of survival. In the next experiment, the prostaglandin E (PGE) analogs misoprostol, enisoprost, or 16,16-dimethyl PGE2 were administered to transfused animals for 3 days before burn. Prostaglandin E analogs significantly reduced bacterial translocation as measured by blood radionuclide counts 4 hours postburn and improved survival. The data demonstrate that the intensity of bacterial translocation after burn injury is significantly associated with subsequent death. Improvement of survival by PGE analogs is associated with decreased bacterial translocation.

16,16-Dimethylprostaglandin E2↗
PubMed1992

Different roles of IL-1 and TNF on hemodynamics and interorgan amino acid metabolism in awake dogs.

The present study examines the effects of interleukin 1 (IL-1) and tumor necrosis factor (TNF) on various hemodynamic parameters and interorgan fluxes of amino acids, glucose, and lactate in chronically catheterized awake dogs. The dogs received 5 micrograms.kg-1.h-1 of either human recombinant IL-1 beta or TNF intravenously for 2 h. Hemodynamic parameters and substrate fluxes across the gut and liver were determined during and 2 h after discontinuation of the cytokine infusions. Substrate fluxes were calculated by blood flows and arteriovenous differences. Both IL-1 and TNF enhanced the uptake of alanine, uptake of lactate, and output of glucose by the liver. These changes were associated with elevated arterial levels of alanine and lactate while arterial levels of glucose decreased. Uptake of glutamine by the liver was reduced by either IL-1 or TNF infusions. The effects of IL-1 and TNF on the hemodynamic parameters and on gut amino acid metabolism varied with the cytokine infused. IL-1 produced hyperdynamic state, increased splanchnic blood flow, and enhanced glutamine uptake by the gut. TNF infusion did not cause a hyperdynamic state, nor did it alter the gut handling of amino acids. We conclude that IL-1 and TNF exert distinct different effects on the systemic and hemodynamic parameters and on interorgan balances of amino acids, glucose, and lactate across the gut and the liver.

Amino Acids↗
PubMed1991

Striatal N-methyl-D-aspartate receptors in haloperidol-induced catalepsy.

Bilateral ablation of the frontal cortex of rats markedly reduced the catalepsy induced by haloperidol (1 mg/kg i.p.). Similarly, the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, D(-)-2-amino-5-phosphonopentanoic acid (10 micrograms/side), injected bilaterally into the rostral part of the caudate-putamen (CP) reduced haloperidol-induced catalepsy whereas its injection into the intermediate part of the CP was ineffective. The quisqualate receptor antagonist, L-glutamic acid diethyl ester (100 micrograms/side), did not affect haloperidol-induced catalepsy when injected into the rostral part of the CP. On the other hand, NMDA (1 micrograms/side) injected bilaterally into the rostral part of the CP was able to restore haloperidol-induced catalepsy in frontally decorticated rats without any notable cataleptic effect of its own. These findings suggest that a certain degree of tonic stimulatory effect of corticostriatal glutamatergic pathways on NMDA receptors within the rostral part of the CP is a prerequisite for the expression of the cataleptogenic action of haloperidol.

Animals↗
PubMed1990

Predictive factors for the response of ulcerative colitis patients during the acute-phase treatment.

Twenty-six consecutive admissions of 24 patients with severe ulcerative colitis (UC) hospitalized in our Department at some time between January 1983 and December 1988 were studied to identify factors useful in the prediction of response to medical treatment in the acute inflammatory phase of this disease. Results of laboratory tests (white blood cells, red blood cells, platelet count, hemoglobin, erythrocyte sedimentation rate, total protein, albumin, alpha 2-microglobulin, cholinesterase, total cholesterol, and triglycerides) and of endoscopic findings (extent of disease, progress of the lesions, sparing of the rectum, and presence of geographic ulcers, longitudinal ulcers, and polypoid mucosal tags) were analyzed for any relationship with the effect of medical treatment during the acute phase. The effect of treatment was evaluated in terms of days it took for a severe condition to improve to an intermediate one defined by Truelove and Witts' categories for UC severity. C-Reactive protein, nutritive condition (total protein, albumin, and cholinesterase), extent of the lesions, and existence of polypoid mucosal tags provide predictive factors useful in the management of UC during the acute phase.

Acute Disease↗
PubMed1990

[Long-term effects of postnatal hypoxia on monoamine and amino acid levels in the rat brain].

Perinatal hypoxia is known as a risk factor for human epilepsies. Previous studies in our laboratory have shown that the rats with postnatal hypoxia show facilitation of the kindling formation and enhanced susceptibility to pentylenetetrazol (PTZ)-induced seizures even after the maturation. In the present study, the effects of postnatal hypoxia (100% N2, for approximately 5 min, at ten days of age) on monoamine and amino acid levels in the brain of adult rats (three months of age) were investigated to clarify the biochemical basis of the enhanced seizure susceptibility. In the hypoxia-treated rats, norepinephrine (NE) was significantly decreased in the pons-medulla (82% of control) and hypothalamus (85%) as compared with controls. Dopamine (DA) was decreased in the pons-medulla (83%). A decrease in DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was also noted in the substantia nigra (71%) and hippocampus (64%), respectively. On the other hand, gamma-aminobutyric acid (GABA) was significantly increased in the striatum (121%). These findings indicate that the enhanced seizure susceptibility in these rats may be attributed to 1) impaired development of noradrenergic and dopaminergic neurons, of which these transmissions are known as inhibitory modulators of seizure discharge in some animal models of epilepsies, and 2) changes of GABAergic and dopaminergic transmissions in the striato-nigral pathway, which is a wellknown regulation system for seizure propagation.

Amino Acids↗
PubMed1984

Experimental studies on the effects of Mt. Sakurajima volcanic ashes on the respiratory organs.

Since 1978, the authors have collected ashes from Sakurajima volcanic eruption in Kagoshima City, and the ashes were administered to rats and rabbits through different routes and forms injecting into the trachea in order to see the effect of ashes on the respiratory organs. The authors experimentally and histopathologically demonstrated bronchitis, pulmonary emphysema, atelectasis lung, degeneration of blood vessel, dust nodes and induction of pneumoconiosis due to dust fibrosis in the study of the effect of volcanic ashes on the respiratory organs.

Animals↗
PubMedDate not supplied

Alanyl-glutamine enriched total parenteral nutrition improves local, systemic, and remote organ responses to intraperitoneal bacterial challenge.

BACKGROUND: Standard total parenteral nutrition (STD-TPN) may diminish host defense against infection. Glutamine (Gln) is suggested to enhance host immunity. This study investigated the effects of antecedent alanyl-glutamine enriched TPN (Ala-Gln-TPN) on host responses to intraperitoneal bacterial challenge compared with STD-TPN. METHODS: Rats were divided into STD-TPN and Ala-Gln-TPN groups. They received isocaloric and isonitrogenous nutrition for 7 days and were challenged intraperitoneally with E. coli. Rats were killed before (0 hour) challenge and at 2 and 6 hours after challenge. Bacterial numbers in peritoneal lavage fluid (PLF), liver, spleen, and blood were determined. Tumor necrosis factor-alpha (TNF), interleukin (IL)-8, and interferon-gamma (IFN) in plasma and PLF were measured. Hepatic TNF, splenic TNF, and splenic IFN levels were determined. RESULTS: The numbers of E. coli in systemic blood at 2 hours after intraperitoneal bacterial challenge were significantly lower in the Ala-Gln-TPN than in STD-TPN group. E. coli numbers in blood significantly correlated with those in the liver. The Ala-Gln-TPN also resulted in significantly higher PLF and hepatic TNF levels, higher splenic IFN levels, and lower plasma IL-8 levels at 6 hours after challenge compared with the STD-TPN. CONCLUSIONS: Antecedent Ala-Gln enriched TPN enhance local, systemic, and remote organ immune responses to intraperitoneal bacterial challenge. Ala-Gln-TPN may enhance host defense and be more beneficial than standard TPN in sepsis.

Animals↗
PubMedDate not supplied

Effects of growth hormone and insulin-like growth factor 1 (IGF-1) treatments on the nitrogen metabolism and hepatic IGF-1-messenger RNA expression in postoperative parenterally fed rats.

BACKGROUND: Few studies have made direct comparisons of the metabolic effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). We have assessed the dose-dependent effects of GH and IGF-1 treatments on nitrogen metabolism, intestinal structure, and hepatic IGF-1-messenger RNA (mRNA) expression in postoperative parenterally fed rats. METHODS: Rats were maintained on total parenteral nutrition (TPN) for 3 days after gastrectomy. GH (0.4 or 0.8 IU/kg/d) or IGF-1 (1,2, or 4 mg/kg/d) was infused throughout the experimental period. Anabolic effects of GH and IGF-1 were assessed by body weight change, nitrogen excretion, and whole-body protein turnover. Organ weights, intestinal structure, plasma IGF-1 levels and hepatic IGF-1-mRNA contents were also determined. RESULTS: Both GH and IGF-1 attenuated body weight loss and nitrogen excretion and increased whole-body protein synthesis and spleen weight. These observations suggest that the anabolic effects of 1 mg/kg/d of IGF-1 were equivalent to those of 0.66 IU/kg/d of GH. IGF-1, but not GH, reduced atrophy of the intestinal mucosa. GH treatment increased hepatic IGF-1-mRNA and the plasma IGF-1 level, whereas IGF-1 treatment increased the plasma IGF-1 level with no change in the hepatic IGF-1-mRNA content. CONCLUSIONS: Administration of GH or IGF-1 attenuates catabolism after surgery. The anabolic effects of 1 mg/kg/d of IGF-1 are equivalent to those of 0.66 IU/kg/d of GH. IGF-1 reduces intestinal mucosal atrophy. GH increases hepatic IGF-1-mRNA and the plasma IGF-1 level.

Animals↗
PubMedDate not supplied

Alanyl-glutamine-supplemented total parenteral nutrition improves survival and protein metabolism in rat protracted bacterial peritonitis model.

BACKGROUND: The effects of glutamine-enriched total parenteral nutrition (TPN) solution on survival, and protein turnover in the whole body and in individual organs were investigated in a rat protracted peritonitis model. METHODS: Twenty-three rats underwent venous catheter insertion. Osmotic pumps were implanted in the peritoneal cavity to allow continuous delivery of Escherichia coli (4 x 10(8) CFU/d). The conventional TPN group received a conventional amino acid solution. The Ala-Gln TPN group received an alanyl-glutamine-enriched TPN solution. The two TPN solutions were isocaloric and isonitrogenous. RESULTS: Over the 5 days of TPN treatment, the survival rate of the Ala-Gln group was significantly higher than that of the conventional group. The Ala-Gln group tended to have increased whole-body protein turnover compared with the conventional group. Fractional protein synthetic rates (FSR) in the liver and gastrocnemius muscle of the Ala-Gln group were significantly higher than those of the conventional group. The serum glutamine concentration correlated positively with the FSR of both liver and muscle. The Ala-Gln group showed significantly greater mucosal height and mitoses per crypt, in the small intestine, than did the conventional group. CONCLUSIONS: Our results suggested that, in comparison with standard glutamine-free TPN, Ala-Gln-supplemented TPN increases protein synthesis in the liver and skeletal muscle, protects the morphology of the intestinal mucosa, and improves survival in protracted bacterial peritonitis. Ala-Gln supplementation may be useful in septic patients.

Alanine↗
PubMedDate not supplied

Insulin-like growth factor 1 has beneficial effects, whereas growth hormone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury.

BACKGROUND: Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) improve protein metabolism after surgical insult in subjects without liver disease. However, these effects in chronic liver injury, in which the GH-IGF-1 axis is impaired, have not been investigated. We examined the anabolic effects of GH and IGF-1 after gastrectomy in rats with chronic mild liver injury. METHODS: Rats with chronic mild liver injury induced by thioacetamide were used. After gastrectomy, the rats were randomized into vehicle control, GH, and IGF-1 groups. In the latter two groups, 0.8 IU/kg/d of GH or 4 mg/kg/d of IGF-1 was infused for 72 hours. Anabolic effects were assessed by body weight change, 3-methylhistidine (3-MH) excretion, nitrogen excretion, and whole-body protein turnover. Organ weights, plasma levels of glucose, insulin, and IGF-1, tissue IGF-1 levels, hepatic messenger RNA (mRNA) content, and intestinal structure were also determined. RESULTS: Both GH and IGF-1 decreased nitrogen excretion. IGF-1, but not GH, increased postoperative body weight, whole-body protein turnover, and splenic weight. IGF-1 reduced atrophy of the intestinal mucosa. GH treatment increased hepatic IGF-1-mRNA and the plasma IGF-1 level, whereas IGF-1 treatment increased the plasma IGF-1 level with no change in the hepatic IGF-1-mRNA content. There were no significant differences in plasma glucose or insulin levels among the three groups. Neither GH nor IGF-1 affected the gastrocnemius muscle IGF-1 level. CONCLUSIONS: IGF-1 has beneficial effects, whereas GH has only limited effects on post-operative protein metabolism, gut integrity, and splenic weight in chronic mild liver injury.

Animals↗