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Biomedical subjects

K Ikegami

Publications and source records attributed to K Ikegami.

At least 37 records · Page 2Linked to original sources
PubMed1997

Apafant (a PAF receptor antagonist) suppresses the early and late airway responses in guinea pigs: a comparison with antiasthmatic drugs.

We studied the effects of apafant (WEB 2086 BS), a specific and potent platelet activating factor (PAF) receptor antagonist, on the early and late airway responses in conscious and actively sensitized guinea pigs. An increase in airway resistance (Rs) was seen 1 min after the inhaled antigen challenge (early airway response), followed by another increase in Rs which peaked between 4 and 8 h after the provocation (late airway response). Oral administration of apafant as well as theophylline inhibited both early and late airway responses. Ozagrel, an inhibitor of thromboxane A2 synthetase, salbutamol, a beta2-adrenoceptor agonist, and dexamethasone significantly inhibited either the early or the late airway response only. Disodium cromoglycate inhibited neither the early nor the late airway response. The results showed that apafant inhibited both the early and late airway responses in sensitized guinea pigs and its effect was comparable or superior to that of anti-asthmatic drugs used clinically.

Administration, Inhalation↗
PubMed1997

Novel renin inhibitors containing (2S,3S,5S)-2-amino-1-cyclohexyl-6-methyl-3,5-heptanediol fragment as a transition-state mimic at the P1-P1' cleavage site.

A series of renin inhibitors containing the (2S,3S,5S)-2-amino-1-cyclohexyl-6-methyl-3,5-heptanediol (2-amino-3,5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3,5-anti-diol fragment at the P1-P1' position showed high in vitro renin-inhibitory activity with IC50 values in the 10(-8)-10(-10) M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4-hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect.

Administration, Oral↗
PubMed1997

Deformity of the proximal end of the femur following open reduction for developmental dislocation of the hip.

We studied deformity of the proximal end of the femur following open reduction using the wide exposure method for developmental dislocation of the hip. We reviewed radiographs of 22 children with unilateral dislocation of the hip who had undergone open reduction between one and three years of age. Ages at final examination ranged from 14 to 21 years. None of the patients in this study had undergone any additional surgery. Avascular necrosis of the femoral head was not observed in any patients. Radiographic measurements were observed when the children were 3, 6, 9, and 12 years old, and at the final examination. Coxa magna and valga were the factors associated with poor results. Coxa valga had occurred at 6 to 12 years of age, but rapidly improved thereafter. Throughout the course of treatment the epiphysis-femoral neck angle was within the normal range. The fusion of the epiphyseal growth plates on both sides occurred simultaneously. The coxa valga was due to valgus of the femoral neck, and not to valgus head tilt. These results suggest that, provided the mechanics of the joint have been properly corrected as in our operation, the biomechanics of the hip will improve until growth ceases, but that it may take more than ten years to attain normality.

Adolescent↗
PubMed1996

Evaluation of an artificial dermis full-thickness skin defect model in the rat.

An artificial dermis product was applied to full-thickness skin defects in rats and cell infiltration into the collagen matrix was investigated. Host fibroblasts and capillaries infiltrated as far as the upper end of the collagen matrix by day 14 after application. Determination of glycosaminoglycan levels in the matrix showed that hyaluronic acid was generated in a similar amount to that seen in the intact skin by day 14. An autologous thin split-thickness skin graft was placed onto the artificial dermis simultaneously or several days after its application to the defect. The take rate was 100% when a split-thickness skin graft was performed on day 14 after application of the artificial dermis. At 6 weeks after the skin defect was created, the wound area was 80% of the original area and the dermis at the grafted site was as thick as that of normal skin. These results suggested that the artificial dermis provides a good matrix for thin split-thickness skin graft and is useful for the reconstruction of full-thickness skin defects. This method is considered to be an alternative to the conventional procedure using thick skin grafts or skin flaps.

Animals↗
PubMed1996

Histological evaluation of skin reconstruction using artificial dermis.

An artificial dermis, composed of a collagen matrix, was applied to a full-thickness skin defect prepared on the back of rats. Two weeks later, a thin split-thickness skin autograft was overlaid on the matrix at each recipient site. The dermal layer at the recipient sites was 1.02 mm thick with prior application of artificial dermis, as compared with the 0.46 mm thickness observed without such pretreatment. Histologically, the split-thickness skin graft normally lies with no gap on the artificial dermis, which looks like natural dermis. Six days after grafting, the epithelial basal cells in the grafts showed an active uptake of bromodeoxyuridine (a thymidine analogue), indicating high activity of cell proliferation. About 50 and 20% respectively of the artificial dermis remained at each recipient site at 12 and 20 weeks after its application (after the skin defect). This finding indicates that bovine collagen, which is a constituent of the artificial dermis, is gradually replaced by the host tissue.

Animals↗
PubMed1996

Fluid resuscitation with deferoxamine hetastarch complex attenuates the lung and systemic response to smoke inhalation.

BACKGROUND: We determined the effect of infusing the iron chelator deferoxamine complexed to hetastarch on the degree of lung dysfunction and systemic abnormalities produced by a severe smoke exposure. METHODS: Adult sheep were given a smoke exposure under anesthesia that produced a peak carboxyhemoglobin between 40% and 45%. Twenty-eight sheep were studied; eight were given smoke alone and resuscitated with sufficient lactated Ringer's solution to maintain baseline hemodynamics. Seven sheep were given a bolus plus 1 ml/kg/hr of a 10% deferoxamine-hetastarch solution for resuscitation; five were given hetastarch alone. The response was compared with eight controls during a period of 24 hours. RESULTS: Smoke alone and smoke with hetastarch resulted in a shunt fraction of greater than 25% and a 50% decrease in compliance, severe airway inflammation, mucosal slough, atelectasis, and some alveolar edema. Increased lipid peroxides measured as malondialdehyde were present in airway fluid. In addition, oxygen consumption increased by 100% early after injury, net 24-hour positive fluid balance was almost 3 L, and a significant increase occurred in liver lipid peroxidation. The group given deferoxamine had a significantly attenuated lung response, with only modest airway damage lung dysfunction, and minimal systemic changes including a net positive fluid balance of just over 1L and no liver lipid peroxidation. CONCLUSIONS: An iron chelator deferoxamine complexed to hetastarch, given after a severe smoke exposure, significantly attenuates the airway and the systemic inflammatory (oxidant) injury, indicating free iron release and subsequent increased oxidant activity to be a major etiologic factor.

Animals↗
PubMed1996

Immunohistochemical examination of phosphorylated tau in granulovacuolar degeneration granules.

Granulovacuolar degeneration (GVD) and neurofibrillary tangles (NFT) are neuropathological features in Alzheimer's disease (AD). The molecular mechanism of GVD formation remains unknown. Recent immunohistochemical investigations suggested a potential link of NFT to GVD formation. Enzyme histochemical studies and electronmicroscopic findings suggested that GVD is formed through lysosomal autophagy of intraneuronal substances. We recently demonstrated that in non-demented cases NFT was phosphorylated at serines 199, 202 and 422 in paired helical filament (PHF)-tau more than in serine 396, while NFT in AD cases was similarly phosphorylated at these four sites in tau. In this study, we demonstrated immunohistochemically a similar phosphorylation state of tau in GVD granules to that in NFT in both non-demented cases and AD patients by using a mouse monoclonal anti-tau antibody and three phosphorylation site-specific antibodies for PHF-tau, indicating that GVD granules and NFT are composed of similar phosphorylated-tau. However, we could not detect PHF structures within any GVD using electronmicroscopy, indicating that PHF itself is not phagocytized by lysosomes during GVD formation. Therefore, the source of GVD granules might be phosphorylated pre-PHF-tau.

Aged↗
PubMed1996

A bibliometric study of the trend in articles related to epidemiology published in occupational health journals.

OBJECTIVES: To study the role assumed by epidemiology in occupational health literature and characterise its change over the years. METHODS: A bibliometric study was conducted with a MEDLINE search to evaluate 9024 articles published in eight representative occupational health journals for the period 1980-93. Articles related to epidemiology were found by descriptors indexed in the articles and their numbers and proportions among all published articles was tabulated for the study period. RESULTS: The proportion of source items indexed by epidemiology as a descriptor increased over threefold from 7.9% (42/534) in 1980 to over 25% after 1990. Epidemiology was indexed most frequently as a subheading associated with other descriptors-for example, occupational diseases-epidemiology. Cohort studies had the largest increase in the descriptors that indicated epidemiological type of studies during the period studied. CONCLUSION: Epidemiology is assuming increasing importance in occupational health literature. This was shown quantitatively and qualitatively by the use of descriptors in the MEDLINE database.

Abstracting and Indexing↗
PubMed1996

[Free radicals and surgical stress].

Free radicals have at least one unpaired electron. Some of them have very high reactivity and harmful to cells and tissues. O2-. and HO. are generated during re-perfusion phase of shock. Both induce lipid peroxidation and this attack initiates auto-continuing injury of membrane lipid by lipid peroxide. This may result in damage of membrane function and permeability alteration. NO is an another type of free radical and huge amount of NO is generated by inducible NO synthase with variety of stimulation. NO decreases vascular tonus and may be related with hyperdynamic circulatory status in sepsis. NOx and ONOO- which are NO derivatives, deteriorate mitochondrial function. Free radicals are one of major agents which damages patients under surgical stress, however, they also have important rules in our defense system. In this sense, control rather than suppression may be important to ameliorate injury caused by surgical stress.

Free Radicals↗
PubMed1995

Alpha-tocopherol attenuates lung edema and lipid peroxidation caused by acute zymosan-induced peritonitis.

BACKGROUND: Inflammation-induced disease as seen with trauma and infection can lead to increased lung oxidant activity resulting in cell membrane lipid peroxidation. Acute zymosan-induced peritonitis in rats produces lung inflammation, edema, and lipid peroxidation. We determined whether administered alpha-tocopherol (vitamin E), the key antioxidant protection against cell membrane lipid peroxidation, would improve this process. METHODS: Male Wistar rats were given 0.75 mg/kg of intraperitoneal zymosan, volume resuscitated, monitored, and killed at 4 or 24 hours. Lung histologic changes and levels of conjugated dienes, a marker of lipid peroxidation, were used to monitor injury. The levels of vitamin E, vitamin C, and catalase were used to monitor antioxidant defenses. The effect of administering alpha-tocopherol (50 mg/kg) by gavage immediately after zymosan on the degree of the lung injury was then determined. RESULTS: Twenty-four hours after zymosan was administered, the vitamin E levels in plasma were significantly decreased, but lung tissue vitamin E levels were maintained, whereas tissue catalase and vitamin E levels decreased. Lung tissue-conjugated diene levels, alveolar edema, and neutrophil count were significantly increased. alpha-Tocopherol treatment increased the postzymosan plasma vitamin E levels by 50%. Lung tissue vitamin E levels did not increase; however, the degree of lung injury and lipid peroxidation was significantly attenuated. Tissue catalase levels were also maintained. CONCLUSIONS: We conclude that alpha-tocopherol given at the onset of a progressing inflammatory injury can protect the lung from oxidant damage and attenuate the degree of lung injury.

Acute Disease↗
PubMed1995

[Polymorphism of 3,9-bis-(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2- c]quinoline-6-one(KCA-098), a new benzofuroquinoline derivative].

Physicochemical properties of polymorphism of 3,9-bis-(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinol ine-6-one (KCA-098) have been investigated. The existence of four crystalline forms (designated as hydrate, I, II and III) was confirmed by X-ray powder diffraction, IR spectroscopy and thermal analysis (DSC and TG). The hydrate was found to be a monohydrate by elemental analysis and water content measurement. DSC measurement found that the hydrate was transformed fo form III at about 93 degrees C, and then to form II at about 152 degrees C, and finally to form I at about 260 degrees C. On the other hand, when suspended in water the forms I, II and III were transformed into hydrate. The transition rate from form III to hydrate was higher than those from form II to hydrate and from form I to hydrate. Form III as a metastable form showed higher solubility than any of form I, II and hydrate.

Chemical Phenomena↗
PubMed1994

Administration of large doses of vitamin C does not decrease oxidant-induced lung lipid peroxidation caused by bacterial-independent acute peritonitis.

Acute zymosan-induced peritonitis in rats produces lung inflammation and lipid peroxidation. The effect of this process on plasma and lung tissue ascorbic acid was determined, as was the effect of infusing 150 mg/kg of ascorbic acid immediately after zymosan on the degree of lung insult. Ascorbic acid levels were significantly decreased in plasma and lung tissue at 24 h after zymosan, and lung tissue conjugated diene and neutrophil content was also significantly increased. Vitamin C infusion increased postzymosan plasma levels by 50% over normal control levels. However, lung tissue ascorbic acid was still decreased, and no decrease in the lung injury process was noted. Added ascorbic acid also did not prevent a decrease in plasma vitamin E with the peritonitis. We conclude that the amount of ascorbic acid given in this study did not diminish the lung oxidant inflammatory changes. An insufficient dose or inadequate time for plasma ascorbic acid to equilibrate with the lung cytosol are possible explanations for the lack of attenuation of lung oxidant stress.

Acute Disease↗
PubMed1994

Comparison of plasma reduced glutathione and oxidized glutathione with lung and liver tissue oxidant and antioxidant activity during acute inflammation.

We determined whether plasma levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) accurately reflect the tissue GSH and GSSG levels in lung and liver during a progressive acute inflammation-induced increased oxidant activity. We also determined whether plasma GSH also reflected other antioxidant defenses. Male Wistar rats (n = 38) were given intraperitoneal zymosan (.75 mg/g body weight) producing an acute progressive peritonitis and generalized inflammation. Animals were resuscitated then killed at 4 or 24 h. Plasma and tissue levels of GSH, GSSG, vitamin C, alpha-tocopherol, and catalase were measured. Conjugated dienes and malondialdehyde were used as tissue markers of lipid peroxidation. We found lung and liver tissue GSH to be decreased significantly at 4 h while GSSG was increased. Lipid peroxidation was also present in the lung. At 24 h, GSH remained decreased in liver and GSSG remained increased in lung along with the lipid peroxides conjugated dienes and malondialdehyde. In addition, overall antioxidant defenses were decreased in both lung and liver. Plasma GSH remained decreased at 24 h corresponding with the decrease in liver GSH as well as the decrease in other plasma and tissue antioxidants. However, plasma GSSG levels were not significantly increased, at any time point, indicating plasma GSSG does not accurately reflect tissue oxidant activity.

Acute Disease↗
PubMed1994

Comparison between lung and liver lipid peroxidation and mortality after zymosan peritonitis in the rat.

We compared the mortality rate and the lung and liver histologic injury with the degree of tissue lipid peroxidation after zymosan-induced peritonitis. Male Wistar rats were given .75 or 1 mg/g of zymosan intraperitoneally and monitored for 24 h. Tissue lipid peroxides were measured as conjugated dienes and malondialdehyde (MDA) as were the antioxidants, ascorbic acid and catalase. Mortality rates for the .75 and 1 mg/g groups were 15 and 50%, respectively. In lung, the degree of increase in conjugated dienes and MDA was significantly greater in nonsurvivors than survivors. Ascorbic acid and catalase levels were also significantly decreased to a greater degree in the sicker animals with ascorbic acid decreased to a greater degree in the higher dose and sicker animals. The level of MDA corresponded with the degree of histologic change. Catalase decreased to a greater degree in liver than lung. We conclude that the degree of lung and liver lipid peroxidation correlates with the degree of inflammation induced tissue injury and mortality.

Analysis of Variance↗
PubMed1994

Aerosolized deferoxamine prevents lung and systemic injury caused by smoke inhalation.

We assessed the role of oxidant release at the airway mucosal surface on airway injury and systemic response to a severe smoke insult. Adult sheep (n = 20) were insufflated with well-characterized smoke from burning cotton toweling. A standardized dose of 12 breaths of smoke with a tidal volume of 20 ml/kg was given under anesthesia. Sheep were awakened, monitored for 24 h, and killed; data were compared with control sheep. Sheep were given 1) humidified oxygen, 2) continuous aerosol of 10% deferoxamine (DFO)-pentastarch solution beginning after smoke, 3) DFO-alone aerosol, or 4) pentastarch-alone aerosol. DFO has antioxidant properties directly and chelates iron. Severe respiratory failure occurred in all but DFO-pentastarch group. Shunt fraction increased from a control of 4%. Histological assessment revealed severe airway mucosal edema, ulceration, bronchorrhea, and severe atelectasis but only moderate alveolar edema. Increased lipid peroxides were also noted in free airway fluid and in bronchoalveolar lavage fluid. In addition, oxygen consumption increased by 75%, fluid requirements increased threefold, and protein-rich systemic soft tissue lymph flow doubled, all significant increases compared with control sheep. No significant physiological or histological changes were noted in DFO-pentastarch aerosol group. We conclude that 1) oxidants possibly initiated through free iron release are involved in severe smoke-induced airway injury and resulting systemic inflammatory response, probably through an amplified oxidant injury and 2) an aerosol of a DFO-pentastarch complex prevents the injury process, whereas DFO alone is not effective as an aerosol.

Acute Disease↗
PubMed1994

Physiologic support of the septic patient.

The patient's response to inflammation, referred to as sepsis, is a complex process involving the degree of the inflammatory insult and the host response. Ischemia, from blood flow abnormalities and direct cell injury from mediators, produces the physiologic response. The treatment is focused first on restoring and maintaining perfusion through maintenance of increased oxygen delivery. The second approach is first surgical then pharmacologic attenuation of the inflammation-induced injury.

Hemodynamics↗
PubMed1993

Pericardial clot after open heart surgery: its specific localization and haemodynamics.

Transoesophageal echocardiography disclosed a localized pericardial blood clot compressing the right atrium (RA) and/or right ventricle (RV) in 15 patients suffering from low cardiac output failure soon after open-heart surgery. The left ventricular end-diastolic diameter was small (38.4 +/- 10.1 mm) and its fractional shortening normal (34.9 +/- 10.2%). These findings suggested cardiac tamponade as a result of pericardial clot. However, the 'y' trough of the RA pressure tracing was prominent, which is not characteristic of typical cardiac tamponade, but rather of constrictive pericarditis. This implies therefore that the pathophysiology of cardiac tamponade by pericardial clot differs from that of tamponade by fluid. Emergency open-chest removal of the pericardial clot was performed in seven patients, with good results. Pericardial clot produces low cardiac output soon after open-heart surgery, but its location is specific and its haemodynamics are not characteristic of cardiac tamponade.

Adult↗