Biomedical subjects

K Hata

Publications and source records attributed to K Hata.

At least 55 records · Page 3Linked to original sources

PubMed2000

Gene expression for dihydropyrimidine dehydrogenase and thymidine phosphorylase influences outcome in epithelial ovarian cancer.

PURPOSE: Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine salvage enzyme responsible for degradation of thymine, which is produced from thymidine by thymidine phosphorylase (TP). Our purpose was to determine whether DPD affects prognosis in patients with epithelial ovarian cancer and how the two enzymes may interact in such effects. PATIENTS AND METHODS: DPD gene expression was analyzed by reverse transcription-polymerase chain reaction in 27 samples from normal ovaries and the 85 epithelial ovarian cancers previously studied with regard to TP gene expression. RESULTS: DPD gene expression was significantly lower in epithelial ovarian cancers than in normal ovaries (P: <.0001), whereas TP gene expression and the ratio of TP to DPD gene expression (TP:DPD) were significantly higher in epithelial ovarian cancer (P: <.0001 for both). In patients with epithelial ovarian cancer, DPD gene expression and the TP:DPD ratio did not significantly correlate with any clinicopathologic factors. Patients with a high TP:DPD ratio (higher than the median) had significantly poorer outcomes than those with lower ratios (P: =.0002). The difference in survival between groups with high and low TP:DPD ratios was greater than the difference between groups with high and low TP gene expression. Multivariate analysis showed the TP:DPD ratio to be the independent prognostic factor (P: =.0002). In tumors with high TP gene expression, low DPD gene expression significantly correlated with poor survival (P: =. 04). CONCLUSION: Downregulation of DPD gene expression may enhance the negative prognostic effect of high TP gene expression in patients with epithelial ovarian cancer. Certain newly available chemotherapeutic choices may take the TP:DPD ratio into consideration.

Adult↗

PubMed2000

Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The results of recent studies suggest that NO synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular (LV) contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure. METHODS AND RESULTS: We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (E(max), the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MVO(2)), and mechanical efficiency (measured as EW/MVO(2)) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4. 8+/-0.3 microg. kg(-1). min(-1) IV). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 200 micromol). DOB increased E(max), EW, and MVO(2) (by 77+/-17%, 39+/-5%, and 21+/-5%, respectively), leading to an increase in mechanical efficiency (25.4+/-3.1% to 29.6+/-4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased E(max), EW, and MVO(2) (by 140+/-21%, 64+/-9%, and 35+/-5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3+/-3.3% to 29.5+/-4.5%) because EW and MVO(2) increased in parallel. Conclusions-These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO(2) through attenuation of LV contractile response to beta-adrenergic stimulation while maintaining LV energy-converting efficiency.

Adrenergic beta-Agonists↗

PubMed2000

Secretory leukocyte protease inhibitor is a novel inhibitor of fibroblast-mediated collagen gel contraction.

Cultured epithelial cells, including those from the oral epithelium, have been successfully applied in the promotion of scarless wound healing. Factors released from the epithelial cells are thought to contribute significantly to the beneficial effects. In the conditioned medium of human oral epithelial cells, we found a factor that inhibited fibroblast-mediated collagen gel contraction, an in vitro model of wound healing and scar formation. Biochemical analysis identified the factor to be human secretory leukocyte protease inhibitor (SLPI). Fibroblasts transfected with SLPI cDNA showed reduced gel-contracting activity. SLPI purified from the conditioned medium inhibited gel contraction in a dose-dependent manner, and anti-SLPI antibody counteracted this activity. Upon SLPI treatment, human skin fibroblasts in collagen gel became shorter in length and were inhibited in pseudopodia extension. Furthermore, after SLPI treatment, alpha(1)-integrin immunoreactivity decreased, and cyclic AMP levels increased. Excessive gel contraction was observed when fibroblasts treated with TGF-beta1 and fibroblasts from hypertrophic and from keloid scar tissue were cultured in collagen gel. SLPI was also effective in inhibiting gel contraction in the above three models of scar formation. These results suggest that SLPI may be useful in promoting scarless wound healing.

Adolescent↗

PubMed2000

Expression of thymidine phosphorylase in epithelial ovarian cancer: correlation with angiogenesis, apoptosis, and ultrasound-derived peak systolic velocity.

OBJECTIVE: The objective of this study was to determine whether the expression of thymidine phosphorylase (TP) by epithelial ovarian cancer cells correlates with the density of microvessels within the tumor, apoptotic index (AI) within the tumor cells, and ultrasound-derived blood flow. METHODS: Color Doppler imaging and pulsed Doppler spectral analysis ultrasonography were used to scan 44 patients with an overt ovarian mass immediately before laparotomy. Sections of malignant tumors were analyzed for the cellular expression of TP and the intratumoral density of microvessels by immunohistochemistry using antibodies to TP and factor-VIII-related antigen, respectively. Moreover, AI was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling methods. RESULTS: Forty-four epithelial ovarian cancers were studied (6 low malignant potential, 15 serous cystadenocarcinoma, 9 mucinous cystadenocarcinoma, 8 endometrioid adenocarcinoma, 4 clear cell carcinoma, and 2 malignant Brenner tumors); 19 were Stage I, 6 Stage II, 15 Stage III, and 4 Stage IV. Fourteen tumors (32%) were classified as being TP positive. The proportion of Stage I tumors that was TP positive (16%) was significantly lower (P = 0.022) that the corresponding value for Stages II-IV (44%), although the values for microvessel count, AI, and peak systolic velocity (PSV) were similar. AI was significantly lower in TP-positive tumors than in TP-negative tumors (P = 0.015). The PSV was significantly higher in TP-positive tumors (P = 0.02). There was a significant correlation between the microvessel count and the PSV (r = 0.34, P = 0.024). Moreover, AI was significantly inversely related to the PSV (r = 0. 35, P = 0.023). The PSV in a subgroup with a high microvessel count and low AI was significantly higher than that in a subgroup with a low microvessel count and high AI (P = 0.0006). These findings significantly associated with TP expression (P = 0.024). CONCLUSIONS: The intratumoral PSV, as determined by color Doppler imaging and spectral analysis, might reflect the coordination of angiogenesis and apoptosis associated with TP expression in epithelial ovarian cancer.

Adult↗

PubMed2000

Effects of basic fibroblast growth factor on cultured rat and human submandibular salivary gland cells.

Basic fibroblast growth factor (bFGF) is a strong mitogen for most mesoderm- and ectoderm-derived cells. Although bFGF exists in rat and human salivary glands, its physiological role in those glands is unknown. In this study, the effects of bFGF were investigated in monolayer culture of normal rat and human submandibular gland cells. Epithelial cells from rat and human submandibular glands were cultivated with the aid of 3T3 cells as a feeder layer. The effects of different concentrations of bFGF on the second passage of these cultured cells were examined. In both the rat and human cells, the percentage of bromodeoxyuridine (BrdU)-positive cells gradually increased up to 50 ng/ml, and then increased sharply at 100 ng/ml. However, at concentrations higher than 100 ng/ml, the percentages of BrdU-positive cells reached a plateau. In both rat and human cells, total cell numbers at 100 ng/ml bFGF were significantly higher than those of the control group from culture day 4. On the other hand, the morphology of the cultured cells showed no difference either with or without bFGF. These results indicate that a major effect of bFGF on salivary gland epithelial cells is to act as a mitogenic stimulus.

3T3 Cells↗

PubMed2000

Prostaglandin A1 enhances c-fos expression and activating protein-1 activity.

Prostaglandin A1 (PGA1) increases heat shock element (HSE)-mediated transcription, thereby enhancing expression of HSE-bearing genes, including heat shock proteins. Because we recently found functional HSEs in the human and rodent c-fos promoters, we hypothesized that PGA1 might increase c-fos expression through the HSE. In this study, we revealed that PGA1 induces c-fos expression at least partly by increasing the binding between heat shock factor-1 and the HSE, and that PGA1 enhances activity of activating protein-1 (AP-1). Interestingly, so far as PGA, is present in the medium, AP-1-mediated transcription enhanced by PGA1 cannot be detected by the standard luciferase reporter gene assay. Instead, it can be detected by either checking luciferase mRNA levels in the presence of PGA1 or measuring luciferase activities just after removal of PGA1. These results showed that protein products of some stress-responsive genes can increase, not during the stressful condition, but immediately after recovery from stress.

Animals↗

PubMed2000

Brain imaging in childhood- and adolescence-onset schizophrenia associated with obsessive-compulsive symptoms.

OBJECTIVE: Childhood- and adolescence-onset schizophrenic patients with obsessive-compulsive symptoms (OCS) constitute a specific subgroup of schizophrenia. We performed magnetic resonance imaging in this group seeking evidence of neurodevelopmental insults. METHOD: Thirty-two schizophrenic patients were compared with 19 controls. Schizophrenic subjects were divided into 15 patients with OCS (SOCS+ group; onset at 15.5 +/- 1.6 years) and 17 without OCS (SOCS- group; onset at 15.3 +/- 1.3 years). Areas of the hippocampus, frontal lobe, corpus callosum and putamen were analysed morphometrically. RESULTS: The left hippocampus was significantly smaller in the SOCS+ group than in the SOCS- and control groups. CONCLUSION: Reduced size of the left hippocampus in the SOCS+ group supports a neurodevelopmental etiology in this subgroup.

Adolescent↗

PubMed2000

Cytokine regulation of chemokine (IL-8, MCP-1, and RANTES) gene expression in human pancreatic periacinar myofibroblasts.

BACKGROUND & AIMS: We have previously isolated and characterized human pancreatic periacinar myofibroblasts. In this study, to define the role of these cells in the pathogenesis of acute pancreatitis, we investigated chemokine expression in them. METHODS: Secretion of chemokines (interleukin [IL]-8, monocyte chemoattractant protein [MCP]-1, RANTES, and MIP [macrophage inflammatory protein]-1alpha) was evaluated by ELISA, Northern blotting, and nuclear run-on assays. The activation of NF-kappaB and NF-IL6 was assessed by an electrophoretic gel mobility shift assay. RESULTS: IL-8 and MCP-1 secretion was rapidly induced by both IL-1beta and tumor necrosis factor (TNF)-alpha. RANTES secretion was induced more slowly and was induced mainly by TNF-alpha. However, MIP-1alpha secretion was not induced by any stimuli. These responses were also observed at the messenger RNA level, and they were accompanied by an increase in transcriptional rate. The increase in transcriptional activation of chemokine genes correlated with the NF-kappaB and NF-IL6 activation. Furthermore, a blockade of NF-kappaB activation by PDTC and TPCK markedly reduced the IL-1beta- or TNF-alpha-induced chemokine gene expression. CONCLUSIONS: Chemokine secretion is differentially regulated in pancreatic periacinar myofibroblasts, suggesting a role for these cells in mediating the infiltration and accumulation of inflammatory cells in the pancreas.

Cells, Cultured↗

PubMed2000

Expression of the adrenomedullin gene in epithelial ovarian cancer.

Adrenomedullin (AM) gene expression was analysed in 60 cases of epithelial ovarian cancer, (29 serous, 14 mucinous, 13 endometrioid, three clear cell, and one undifferentiated) using reverse transcription-polymerase chain reaction (RT-PCR); 10 of the cases were of low malignant potential; 25 were stage I; three were stage II; 27 were stage III; and five were stage IV. The level of AM gene expression was described in terms of the relative yield of the AM gene to the beta2-microglobulin gene. AM gene expression ranged from 0.04 to 1.57 (median 0.36). The association between histological grade and AM gene expression was significant (P: = 0.027), however, the association with other clinico-pathological features, i.e. patients' age at diagnosis, stage of disease, residual tumour mass after initial surgery, and histological subtype were not significant. Survival data were available for all patients and univariate Cox regression analysis showed that the AM gene expression was significantly associated with a poor prognosis (P: = 0.019). Immunohistochemical studies showed that AM was localized in the outer cell membrane or the cytoplasm of the carcinoma cells and in the endothelial cells of the tumour stroma. The AM gene expression level may play a key role in the biology of epithelial ovarian cancer and may define a more aggressive tumour phenotype.

Adrenomedullin↗

PubMed2000

Expression of TP and TIE2 genes in normal ovary with corpus luteum and in ovarian cancer: correlation with ultrasound-derived peak systolic velocity.

Transvaginal colour and pulsed Doppler ultrasonography analyses of blood flow velocity have indicated that intra-tumoral peak systolic velocity (PSV) is a good indicator of ovarian malignancy. Therefore, we examined whether there was an association between the expression of angiogenic genes, e.g. thymidine phosphorylase (TP) and TIE2 and the PSV of blood flow in normal and cancerous ovaries. Initially, 40 patients were examined by transvaginal ultrasonography and 23 ovaries were surgically removed; 14 were normal with corpora lutea (CL) and nine showed ovarian cancer. The ovarian tissue was dissected according to areas of high blood velocity and gene expression was examined using the reverse transcriptase-polymerase chain reaction (RT-PCR). No significant differences were found between PSV in the normal ovary with CL and ovarian cancer (P = 0.95). TP gene expression was significantly higher in ovarian cancer than in normal ovary with CL (P = 0.02), while TIE2 gene expression was not significantly different (P = 0.186). There was a significant correlation between TIE2 gene expression and PSV in the normal ovary with CL (r = 0.633, P = 0.015), while TP expression was significantly correlated with the PSV in ovarian cancer (r = 0.757, P = 0.018). These results indicate that there is a biological difference between physiological and pathological angiogenesis, TIE2 having a physiological role and TP being involved in pathological angiogenesis.

Adult↗

PubMed2000

Midkine enhances early stages of collagen gel contraction.

Midkine (MK) is a heparin-binding growth/differentiation factor implicated in the control of development and repair of various tissues. To investigate the roles of MK in embryogenesis and in regulation of wound healing, we utilized a system of collagen gel contraction by dermal fibroblasts, which provides an in vitro model for studying fibroblast-collagen interactions important in various physiological and pathological phenomena. MK enhanced gel contraction 8-24 h after plating, and its effect was inhibited by anti-MK antibody. The effect was reduced after 48 h, while TGF-beta continued to be active in the later stage. Morphologically, MK-treated fibroblasts tended to be elongated more frequently than control fibroblasts. The effect of MK in the early stage of gel contraction suggests a role of MK as a modulator of cell-matrix interactions.

Carrier Proteins↗

PubMed2000

In vitro analysis of distraction osteogenesis.

Distraction osteogenesis has been widely used for lengthening craniomaxillofacial bone. The healing process of distracted bone has been studied mainly by histological observation in vivo. To analyze the cellular response to the mechanical stress of distraction, we have established and evaluated an in vitro model of distraction osteogenesis using an organ culture technique. Five-week-old male Wistar rats were used for the experiments. The tibial bone was fractured by hand and fixed for 1 week by acrylic resin. After the initial healing period, the tibial bone was harvested and used for this study. A distraction instrument was devised to control the strain on the cultured bone using a micrometer. After distraction, the samples were histologically evaluated for ossification by hematoxylin and eosin stain and Alcian blue stain. As a result, the histological finding for the bone region at a slow rate of distraction (0.5 mm/day) was different from that at a rapid rate of distraction (1.0 mm/day). The proliferation of cartilage was inhibited at the rapid distraction rate. Thus, we hypothesized that mechanical stress regulated cartilaginous growth in tissue cultivation. Judging from this experiment, the model was useful for investigation of the mechanism of bone formation in distraction osteogenesis, because it was simple and served to isolate many factors.

Acrylic Resins↗

PubMed2000

Monophosphoryl lipid A: a novel nitric oxide-mediated therapy to attenuate platelet thrombosis?

Nitric oxide (NO) is a potent inhibitor of platelet aggregation. However, the benefits of NO-based therapies can be confounded by concomitant hypotension. Monophosphoryl lipid A (MLA) is a nontoxic derivative of endotoxin that purportedly increases nitric oxide synthase (NOS) activity and, presumably, NO production, yet has a hemodynamically benign profile. Thus our aims were to determine whether (a) MLA attenuates in vivo platelet aggregation in damaged and stenotic canine coronary arteries by a NO-mediated mechanism but without reductions in arterial pressure; and (b) the platelet inhibitory effects are manifest in vitro. To address the first aim, anesthetized dogs underwent coronary injury + stenosis, resulting in cyclic variations in coronary blood flow (CFVs) caused by the formation/dislodgement of platelet-rich thrombi. In protocol I, dogs received MLA (100 microg/kg + 40 microg/kg/h) or vehicle beginning 15 min before stenosis. Protocol II was identical, except the NOS inhibitor aminoguanidine was coadministered with MLA/vehicle. Coronary patency was assessed throughout the initial 3 h after injury + stenosis. Infusion of MLA did not result in hypotension. However, in protocol I, the median nadir of the CFVs was higher (2.1 vs. 0.8 ml/min; p < 0.05), median duration of total thrombotic occlusion tended to be reduced (0 vs. 10.4 min; p = 0.1), and mean flow-time area, expressed as a percentage of baseline flow, was increased (53 +/- 9% vs. 33 +/- 3%; p < 0.05) in MLA-treated versus vehicle-treated dogs. In contrast, in protocol II, vessel patency was comparable in both groups. Finally, whole blood impedance aggregometry (protocol HI) revealed a significant reduction in the in vitro platelet aggregation in blood samples receiving exogenous MLA, which was blocked by coadministration of exogenous aminoguanidine. Thus MLA attenuates platelet-mediated thrombosis in both damaged and stenotic canine coronary arteries and in vitro, possibly by an NO-mediated mechanism, but without concomitant hypotension.

Adjuvants, Immunologic↗

PubMed2000

Transforming growth factor-beta1 acts as a potent inhibitor of complement C3 biosynthesis in human pancreatic cancer cell lines.

In this study, we attempted to determine how transforming growth factor (TGF)-beta1 affects complement C3 secretion in the pancreatic cancer cell lines PANC-1 and BxPC-3. We also compared the responses in C3 secretion with those in interleukin (IL)-8 secretion. The C3 and IL-8 expression was evaluated at the protein and messenger RNA (mRNA) levels. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-1beta and tumor necrosis factor (TNF)-alpha both induced a marked increase in C3 and IL-8 secretion. However, TGF-beta1 potently decreased the IL-1beta- and TNF-alpha-induced C3 secretion, whereas the IL-8 secretion was weakly but significantly enhanced. These responses were also observed at the mRNA level. In PANC-1 cells, IL-1beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-kappaB, and TGF-beta1 enhanced this activation slightly. The induction of Fos protein has been reported to be required for the inhibitory action of TGF-beta1, and the translocation of Fos protein into the nucleus was associated with TGF-beta1 stimulation in PANC-1 cells. Our results suggest that TGF-beta1 may act as a potent inhibitor of C3 secretion in pancreatic cancer cell lines under inflammatory conditions. This action of TGF-beta1 did not correlate with NF-kappaB activation, but associated with the translocation of Fos protein into the nucleus.

Antibodies↗

PubMed2000

The expression of chemokine genes correlates with nuclear factor-kappaB activation in human pancreatic cancer cell lines.

Chemokines may regulate the process of immune cell infiltration that is often found in pancreatic cancer. In this study, we investigated the secretion of the chemokines [interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and RANTES (regulated on activation, normal T cell expressed and secreted)] in human pancreatic cancer cell lines. The chemokine secretion in three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BxPC-3) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and the activation of nuclear factor-kappaB (NF-kappaB) and NF-IL6 was assessed by an electrophoretic gel mobility shift assay (EMSA). Without any stimulation, IL-8 secretion was detected in all cell lines, and MCP-1 secretion was detected in PANC-1 and MIA PaCa-2 cells. However, RANTES secretion was not detected in all cells. The addition of IL-1beta and tumor necrosis factor (TNF)-alpha strongly enhanced IL-8, MCP-1, and RANTES secretion; these responses were observed at the mRNA level as well as at the protein level. IL-1beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-kappaB in PANC-1 cells, and the increase in chemokine mRNA expression correlated with NF-kappaB activation. The activation of NF-IL6 was modest. A blockade of NF-kappaB activation by TPCK markedly reduced the IL-1beta- and TNF-alpha-induced chemokine gene expression. Our findings indicate that chemokines are produced by pancreatic cancer cells, and suggest that these factors may contribute to the accumulation of tumor-associated immune cells. In addition, the transcriptional activation of chemokine genes in pancreatic cancer cells may be closely associated with NF-kappaB activation.

Cell Nucleus↗

PubMed2000

Negative inotropism of hyperthermia increases oxygen cost of contractility in canine hearts.

Heart temperature affects left ventricular (LV) function and myocardial metabolism. However, how and whether increasing heart temperature affects LV mechanoenergetics remain unclear. We designed the present study to investigate effects of increased temperature by 5 degrees C from 36 degrees C on LV contractility and energetics. We analyzed the LV contractility index (E(max)) and the relation between the myocardial oxygen consumption (MVO(2)) and the pressure-volume area (PVA; a measure of LV total mechanical energy) in isovolumically contracting isolated canine hearts during normothermia (NT) and hyperthermia (HT). HT reduced E(max) by 38% (P < 0.01) and shortened time to E(max) by 20% (P < 0.05). HT, however, altered neither the slope nor the unloaded MVO(2) of the MVO(2)-PVA relation. HT increased the oxygen cost of contractility (the incremental ratio of unloaded MVO(2) to E(max)) by 49%. When Ca(2+) infusion restored the reduced LV contractility during HT to the NT baseline level, the unloaded MVO(2) in HT exceeded the NT value by 36%. We conclude that HT-induced negative inotropism accompanies an increase in the oxygen cost of contractility.

Animals↗

PubMed2000

Thymidylate synthase expression in epithelial ovarian cancer: relationship with thymidine phosphorylase expression and prognosis.

OBJECTIVE: Thymidylate synthase (TS) and thymidine phosphorylase (TP) are important enzymes involved in the de novo DNA synthesis and the salvage pathways for pyrimidine, respectively. Our purpose was to determine whether the gene expression of TS together with TP correlate with prognosis in epithelial ovarian cancer. METHODS: TS gene expression was analyzed by reverse transcription-polymerase chain reaction in 20 samples from normal ovaries and 56 epithelial ovarian cancers previously studied regarding TP gene expression. TS and TP protein localization was examined by immunohistochemistry. RESULTS: TS gene expression was significantly higher in epithelial ovarian cancer than in normal ovaries (p = 0.001). In patients with epithelial ovarian cancer, TS gene expression did not correlate with patient age, clinical stage, histologic type, or histologic grade. High TS gene expression (> median) significantly correlated with a poorer survival (p = 0.02). No significant correlation between TS and TP gene expression and different immunoreactivity patterns were found. Combined analysis of TS and TP gene expression demonstrated that the relative risk of death for tumors with high TS and high TP expression was greater than that for either only high TS or high TP gene expression (p = 0.002). CONCLUSION: TS and TP combined may indicate a poor prognosis for patients with epithelial ovarian cancer.

Adult↗

PubMed2000

Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma.

Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro, and high dietary levels are associated with a lower incidence of inflammatory diseases. However, only limited effects have been demonstrated in asthma. The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. In order to minimize the effects of environmental inhaled allergens and diet, this study was performed in a long-term treatment hospital. Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. The daily dosages of EPA and DHA were 17.0-26.8 and 7.3-11.5 mg x kg body weight(-1), respectively. Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group (p<0.0088). No significant side-effects were observed. The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet.

Acetylcholine↗