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Biomedical subjects

S Oikawa

Publications and source records attributed to S Oikawa.

At least 19 recordsLinked to original sources
PubMed2006

Prednisolone inhibits hyperosmolarity-induced expression of MCP-1 via NF-kappaB in peritoneal mesothelial cells.

The mechanism of peritoneal fibrosis in patients on continuous ambulatory peritoneal dialysis (CAPD) is poorly elucidated. We investigated the cellular mechanism of high-glucose-induced expression of monocyte chemoattractant protein-1 (MCP-1), which is important in recruiting monocytes into the peritoneum and progression of peritoneal fibrosis, and examined the inhibitory mechanism of glucocorticoids. Rat peritoneal mesothelial cells were cultured in high-glucose-containing medium and then analyzed for phosphorylation levels of p42/44 and p38 mitogen-activated protein (MAP) kinases (MAPK), MAPK or extracellular signal-regulated kinase kinase (MEK)1/2, c-Jun N-terminal kinase (JNK)1/2, and protein kinase C (PKC) by Western blotting. Expression of MCP-1 was examined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. DNA-binding activity of nuclear factor (NF)-kappaB was measured by electrophoretic mobility shift assay. High glucose increased MCP-1 mRNA and MCP-1 protein expression. Although glucose increased phosphorylation of MEK1/2, p42/44 MAPK, p38 MAPK, JNK1/2, and PKC, and DNA-binding activity of NF-kappaB, its effect on MCP-1 expression was suppressed only by PKC and NF-kappaB inhibitors. Mannitol caused a similar increase in PKC and NF-kappaB activation and MCP-1 synthesis. Prednisolone increased I-kappaB-alpha expression and inhibited glucose/mannitol-induced NF-kappaB DNA binding and MCP-1 expression without affecting PKC phosphorylation. The inhibitory effects of prednisolone on MCP-1 expression were reversed by mifepristone, a glucocorticoid receptor antagonist. Our results indicate that glucose induces MCP-1 mainly through hyperosmolarity by activating PKC and its downstream NF-kappaB, and that such effect was inhibited by prednisolone, suggesting the efficacy of prednisolone in preventing peritoneal fibrosis in patients on CAPD.

Animals↗
PubMed2006

Decreased insulin response in dairy cows following a four-day fast to induce hepatic lipidosis.

Negative energy balance has been implicated in the development of fatty liver, insulin resistance, and impaired health in dairy cows. A 4-d fasting model previously was reported to increase liver triglycerides more than 2.5-fold. The purpose of the present study was to evaluate insulin response in this fasting model. Nonlactating, nonpregnant Holstein cows were fasted for 4 d (6 cows) or fed continuously as control cows (4 cows). Samples were collected 5 d before fasting, during fasting, and immediately after the 4-d fast, 8 d after the fast, and 16 d after the fast. Fasted cows had greater liver triglyceride content (49.4 vs. 16.2 mg/g, wet-weight basis) at the end of the fasting period compared with control cows. Fasted cows also had increased plasma nonesterified fatty acid (NEFA) concentrations (1.24 vs. 0.21 mmol/L) and increased plasma beta-hydroxybutyrate (BHBA) concentrations at the end of the fasting period. Liver triglyceride, plasma NEFA, and plasma BHBA in fasted cows returned to prefasting concentrations by the end of the experiment. Plasma glucose concentrations were not affected by fasting. Plasma insulin concentrations were decreased (6.3 vs. 14.1 microU/mL) and insulin-stimulated blood glucose reduction was decreased (24.9 vs. 48.6%) in the fasted cows compared with control cows at the end of the fast, indicating reduced insulin response. Insulin response was negatively correlated with plasma NEFA and liver triglycerides. Decreased insulin response may be an important complication of negative energy balance and hepatic lipidosis.

3-Hydroxybutyric Acid↗
PubMed2005

Prevention of diet-induced obesity by dietary isomerized hop extract containing isohumulones, in rodents.

OBJECTIVE: Isomerized hop extract (IHE), which consists mainly of isohumulones and is required in the beer brewing process, was investigated for its effects on diet-induced obesity in two strains of mice. DESIGN: C57BL/6N and KK-A(y) mice were fed a standard or high-fat diet containing IHE and their body and tissue weights were measured at various time points. Oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were carried out in high-fat diet-fed C57BL/6N mice. The effects of IHE on intestinal lipid absorption were examined in Wistar rats using a plasma triacylglycerol assay after oral administration of a lipid emulsion. Fecal lipid levels were also measured in these animals after they were fed a high-fat diet containing IHE for 15 days. The effects of IHE on pancreatic lipase activity and the expression of genes involved in hepatic lipid metabolism were also examined using an in vitro assay and quantitative RT-PCR, respectively. RESULTS: Supplementation of high-fat-containing chow with IHE reduced body weight gain and improved glucose tolerance in our experimental mice. A reduction in body weight gain was also observed in C57BL/6N mice fed a standard diet containing IHE. Wistar rats fed a high-fat diet containing IHE showed reduced plasma triacylglycerol levels and an increase in their fecal lipid excretion. Similarly, their pancreatic lipase activity was inhibited and their elevation in plasma triacylglycerol levels seen after the oral administration of lipid emulsion was significantly suppressed. IHE-fed mice showed an increased expression in their lipid oxidation genes and a decreased expression in genes involved in triacylglycerol biosynthesis. CONCLUSION: The inhibition of intestinal dietary fat absorption may be the mechanism by which IHE induces its weight-lowering effects in high-fat diet-fed mice. The modulatory effect of IHE on lipid metabolism may also, at least partly, be responsible for its beneficial effects on body weight gain. These results suggest that IHE may be helpful in humans in preventing diet-induced obesity and perhaps even metabolic syndrome, the latter of which is known to be associated with obesity.

Animals↗
PubMed2004

Metabolic profiles and bile acid extraction rate in the liver of cows with fasting-induced hepatic lipidosis.

This study was designed to monitor lipid profile in the portal and hepatic blood of cows with fasting-induced hepatic lipidosis, and to compare the results with those in the jugular blood. The work was also carried out to investigate bile acid (BA) in these vessels, and further to investigate BA extraction rate in the liver. Five cows were equipped with catheters in the portal, hepatic and jugular veins (day 0), fasted for 4 days (day 1-day 4) and then refed (day 5-day 11). Before morning feeding, blood was sampled before, during and after fasting from the catheterized vessels. In the portal blood, the concentration of non-esterified fatty acids (NEFA) showed a progressive increase and at day 5 there was an approximate twofold rise. Increased NEFA concentrations were also found similarly in the other two veins. At day 5, beta-hydroxybutyrate (BHBA) in the portal, hepatic and jugular blood rose to 197, 190 and 186% of the pre-fasting value, respectively. However, the concentrations of NEFA and BHBA in the three veins gradually returned to pre-fasting concentration during the refeeding period. Compared with the pre-fasting value at day 0, the content of liver triglyceride (TG) increased significantly at day 5 (P < 0.01). In the liver, the hepatic extraction rate of BA dropped from 3.1 times pre-fasting to 2.2 times during fasting. There were no significant differences in the concentrations of glucose, TG, total cholesterol, cholesterol esters, free cholesterol and phospholipids. The results of the current study show that metabolic alterations occur in the portal, hepatic and jugular veins during induction of hepatic lipidosis in cows, and mostly metabolites, with exception of BA concentration, run parallel. The decreased BA extraction rate in the liver of fasted cows was considered to reflect hepatic cell impairment caused by TG accumulation. Hopefully, the findings, at least in part, contribute to the explanation of the pathophysiology of hepatic lipidosis in dairy cows.

Animals↗
PubMed2004

Morphological changes in the rat carotid body 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia.

Morphological changes in the rat carotid bodies 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia (10% O2 for 8 weeks) were examined by means of morphometry and immunohistochemistry. The rat carotid bodies after 8 weeks of hypoxic exposure were enlarged several fold with vascular expansion. The carotid bodies 1 and 2 weeks after the termination of 8 weeks of hypoxic exposure were diminished in size, although their diameter remained larger than the normoxic controls. The expanded vasculature in chronically hypoxic carotid bodies returned to the normoxic control state. In the carotid bodies 1 week after the termination of chronic hypoxia, the density of NPY fibers was remarkably increased and that of VIP fibers was dramatically decreased in comparison with the density in chronically hypoxic carotid bodies. In the carotid bodies 2 and 4 weeks after the termination of hypoxia, the density of SP and CGRP fibers was gradually increased. In the carotid bodies 8 weeks after the termination of hypoxia, the appearance of the carotid body returned to a nearly normoxic state, and the density of SP, CGRP, VIP, and NPY fibers also recovered to that of normoxic controls. These results suggest that the morphological changes in the recovering carotid bodies start at a relatively early period after the termination of chronic hypoxia, and a part of these processes may be under the control of peptidergic innervation.

Animals↗
PubMed2003

Functionally essential neuronal population of the facial motor nucleus.

Cranial nerve impairment is one of the more serious complications in neurosurgery. Nevertheless, the important question of how many neurons are required for cranial nerve functions remains unanswered. The VIIth cranial nerve (facial nerve) in mice was subjected to graded crush injuries. After assessment of the facial function, the number of uninjured, healthy facial motor neurons was quantified with a retrograde neuronal tracer. We report that normal facial function is preserved if intact neurons account for more than 56% of the control value, while complete facial paralysis occurs if intact neurons are reduced to less than 32% of the control value.

Animals↗
PubMed2003

Regenerative process of the facial nerve: rate of regeneration of fibers and their bifurcations.

After the main trunk of the mouse facial nerve was injured by crushing, a fiber tracing method was used to quantify the facial motor neurons that extended regenerating nerve fibers to the specific site of the facial nerve branch. The total number of motor neurons retrogradely labeled with a fluorescent tracer, Fluoro-Gold (FG), were 0 on postsurgical days (PSDs) 1 and 2, 75+/-25 on PSD3, 264+/-21 on PSD4, 378+/-19 on PSD6, 428+/-19 on PSD8, 491+/-13 on PSD12 and 532+/-15 on PSD16. Assuming that the FG-positive neurons (535+/-11) of the control mice represent 100%, the FG-labeled neurons accounted for 0, 14, 49, 71, 80, 92 and 99% on the corresponding days. Two different fluorescent tracers were applied to the different facial nerve branches 16 days after facial nerve injuries. Double-labeled neurons were consistently found in the nerve-crushed facial nucleus (3.2%), and their number increased in the nerve-transected facial nucleus (12.2%). The present study indicates that the regenerating facial nerve consists of heterogeneous nerve fibers with varying growth rates and that excessive axonal branching occurs more frequently in the nerve-transected than in the nerve-crushed injuries.

Animals↗
PubMed2003

Ultrasonographic imaging of experimentally induced pancreatitis in cattle.

This study was conducted to determine the ultrasonographic patterns of pancreatitis evoked in cattle, with reference to laboratory and pathological findings. Using ultrasonographic guidance, acute necrotizing pancreatitis was induced in six cows by injecting chloroform into the pancreatic tissue. Ultrasonographic examination was then performed once daily for nine days. Pancreatic lesions were visible 24h after induction of pancreatitis, as represented by a uniform increase in echogenicity and by intralobular and subcapsular fluid accumulation. As the experiment progressed, patchy hypoechogenic foci appeared within the gland parenchyma. Amylase and lipase activities showed rapid increases. Post mortem examination revealed gross and microscopic necrotic and haemorrhagic lesions in the body and right lobe of the pancreas, accompanied by oedema and fibrosis. Ultrasonography was found to be extremely useful for the detection and characterization of experimentally induced pancreatitis and to monitor its progression in the cow. These findings are of potential value as a reference for the diagnostic workup of bovine pancreatitis, and ultrasonography is seen as a promising non-invasive technique for the diagnosis of suspected pancreatitis in cattle.

Animals↗
PubMed2003

Transcutaneous ultrasound-guided pancreatic biopsy in cattle and its safety: a preliminary report.

This study describes a free-hand technique for percutaneous pancreatic biopsy in cattle with ultrasound-guidance using a 14G spinal biopsy needle. Its safety was evaluated based on 36 consecutive procedures. To assess the immediate effects of pancreatic biopsy, 31 cows were necropsied shortly after the procedure and examined. The remaining five cows were examined daily for eight days and then necropsied and examined. No life-threatening complications nor clinically detectable abnormalities were observed. Changes indicative of inflammation were not apparent in total and differential WBC counts or in total protein and fibrinogen concentrations. A small increase of amylase activity was detected in only one cow kept for the eight-day observation period. Serum lipase activity increased significantly on day four after biopsy. Urea nitrogen, creatinine, glucose and the activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase remained within reference ranges. Changes in the peritoneum and pancreas observed at necropsy were negligible. We conclude that percutaneous ultrasound-guided pancreatic biopsy did not appear to influence the cow's condition adversely and the procedure provided an excellent method of obtaining a pancreatic specimen for histological examination. The procedure was considered safe, fast, cost-effective, and practical when performed properly. We believe that the technique can be used in cows with suspected pancreatic disease for making an ante mortem diagnosis.

Animals↗
PubMed2002

Bile acid extraction rate in the liver of cows fed high-fat diet and lipid profiles in the portal and hepatic veins.

The purposes of this study are to assess the responses of increased supplemental dietary fat in the cow, without upsetting rumen fermentation, on the bile acid (BA) extraction rate in the liver and to determine whether this diet would affect the postprandial lipid profiles in the portal and hepatic venous blood. Six Holstein cows were equipped with catheters fitted in the portal and hepatic veins. Two cows each were assigned randomly to a sequence of three dietary treatments of 21-day period. The methodology of this study was based on the supplementation of the basal concentrate diet with 0 (control), 5, or 10% calcium salts of fatty acids (CSFA). The total bile acids were significantly increased in the portal and hepatic veins with the 5% CSFA diet, whereas no increase occurred with the 10% CSFA diet. Data obtained in this study showed that 10% CSFA diet failed to stimulate BA secretion to exceed the values obtained with 5% CSFA-diet. Moreover, there was no change in the hepatic extraction rate of BA in animals fed either the 0 or 5% CSFA diets which ranged from 2.4 to 6.5-fold and 3.1 to 7.3-fold, respectively. However, the extraction rate increased sharply with the 10% CSFA diet (27-fold). The median portal and hepatic concentrations of total lipids, triglycerides, total cholesterol, phospholipids and non-esterified fatty acids did not show any significant increase during feeding of the control diet. Moreover, feeding either the 5 or 10% CSFA diet did not significantly increase these values in either vein.

Animals↗
PubMed2002

The minimum number of neurons in the central olfactory pathway in relation to its function: a retrograde fiber tracing study.

The present study was aimed at determining the functionally essential size of the neuronal population in the central olfactory nervous system. Using conditioned rats who had learnt to avoid repellent (cycloheximide) solution by olfaction, varying degrees of injuries were made to the lateral olfactory tract, a major central olfactory pathway connecting the olfactory bulb to the olfactory cortex. After examining their olfactory ability to discriminate cycloheximide solution from water, intact bulbar projection neurons (mitral cells) with fiber connections to the olfactory cortex were quantified using a retrograde fiber tracing technique. The numbers of retrogradely labeled mitral cells from the rats with normal olfaction ranged between 20 and 92% of the control value, while those numbers from the anosmic rats ranged between 0 and 22%. We conclude that the functionally essential neuronal population is approximately one-fifth of the total in the central olfactory pathway, a presumed threshold value in terms of the ability to avoid cycloheximide solution by olfactory discrimination.

Animals↗
PubMed2001

Protective effect of phytic acid on oxidative DNA damage with reference to cancer chemoprevention.

Phytic acid (myo-inositol hexaphosphate) is one of the most promising cancer chemopreventive agents. We investigated the mechanism by which phytic acid expresses preventive action to cancer. Phytic acid inhibited the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cultured cells treated with an H2O2-generating system, although it did not scavenge H2O2. Site-specific DNA damage by H2O2 and Cu(II) at GG and GGG sequences was inhibited by phytic acid, but not by myo-inositol. Phytic acid alone did not cause DNA damage and thus, it should not act as a prooxidant. We conclude that phytic acid acts as an antioxidant to inhibit the generation of reactive oxygen species from H2O2 by chelating metals, resulting in chemoprevention of cancer.

Binding Sites↗
PubMed2001

Mechanism of metal-mediated DNA damage induced by metabolites of carcinogenic 2-nitropropane.

2-Nitropropane (2-NP), a widely used industrial solvent, is carcinogenic to rats. To clarify the mechanism of carcinogenesis by 2-NP, we investigated DNA damage by 2-NP metabolites, N-isopropylhydroxylamine (IPHA) and hydroxylamine-O-sulfonic acid (HAS), using 32P-5'-end-labelled DNA fragments obtained from genes that are relevant to human cancer. In the presence of Fe(III) EDTA, both IPHA and HAS caused DNA damage at every nucleotide position without marked site preference. The damage was inhibited by free hydroxyl radical (-*OH) scavengers, catalase and deferoxamine mesilate, an iron chelating agent. These results suggest that the DNA damage was caused by -*OH generated via H(2)O(2) by both IPHA and HAS. In contrast, in the presence of Cu(II), IPHA frequently caused DNA damage at thymine. The Cu(II)-mediated DNA damage caused by IPHA was inhibited by catalase, methional and bathocuproine, a Cu(I)-specific chelator, suggesting the involvement of H(2)O(2) and Cu(I). These results suggest that the DNA damage induced by IPHA in the presence of Cu(II) was caused by a reactive oxygen species like the Cu(I)-hydroperoxo complex. On the other hand, HAS most frequently induced DNA damage at 5'-TG-3', 5'-GG-3' and 5'-GGG-3' sequences. Catalase and methional only partly inhibited the Cu(II)-mediated DNA damage caused by HAS, suggesting that the reactive oxygen species and another reactive species participate in this process. Formation of 8-oxodG by IPHA or HAS increased in the presence of metal ions. This study suggests that metal-mediated DNA damage caused by 2-NP metabolites plays an important role in the mutagenicity and the carcinogenicity of 2-NP.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Oxidative DNA damage by an N-hydroxy metabolite of the mutagenic compound formed from norharman and aniline.

Norharman (9H-pyrido[3,4-b]indole), which is a heterocyclic amine included in cigarette smoke or cooked foodstuffs, is not mutagenic itself. However, norharman reacts with non-mutagenic aniline to form mutagenic aminophenylnorharman (APNH), of which DNA adducts formation and hepatocarcinogenic potential are pointed out. We investigated whether N-OH-APNH, an N-hydroxy metabolite of APNH, can cause oxidative DNA damage or not, using 32P-labeled DNA fragments. N-OH-APNH caused Cu(II)-mediated DNA damage. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH) was added, the DNA damage was greatly enhanced. Catalase and a Cu(I)-specific chelator inhibited DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). Typical -*OH scavenger did not inhibit DNA damage. These results suggest that the main reactive species are probably copper-hydroperoxo complexes with DNA. We also measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation by N-OH-APNH in the presence of Cu(II), using an electrochemical detector coupled to a high-pressure liquid chromatograph. Addition of NADH greatly enhanced 8-oxodG formation. UV-VIS spectra and mass spectra suggested that N-OH-APNH was autoxidized to nitrosophenylnorharman (NO-PNH). We speculated that NO-PNH was reduced by NADH. Cu(II) facilitated the redox cycle. In the presence of NADH and Cu(II), very low concentrations of N-OH-APNH could induce DNA damage via redox reactions. We conclude that oxidative DNA damage, in addition to DNA adduct formation, may play an important role in the expression of genotoxicity of APNH.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds.

DNA damage in cultured cells and in lungs of rats induced by nickel compounds was investigated to clarify the mechanism of nickel carcinogenesis. DNA strand breaks in cultured cells exposed to nickel compounds were measured by using a pulsed field gel electrophoresis technique. Among nickel compounds (Ni(3)S(2), NiO (black), NiO (green), and NiSO(4)), only Ni(3)S(2), which is highly carcinogenic, induced lesions of both double- and single-stranded DNA in cultured human cells (Raji and HeLa cells). Treatment of cultured HeLa cells with Ni(3)S(2) (10 microg/ml) induced a 1.5-fold increase in 8-hydroxy-2'-deoxyguanosine (8-OH-dG) compared with control, whereas NiO (black), NiO (green), and NiSO(4) did not enhance the generation of 8-OH-dG. Intratracheal instillation of Ni(3)S(2), NiO(black), and NiO(green) to Wistar rats increased 8-OH-dG in the lungs significantly. NiSO(4) induced a smaller but significant increase in 8-OH-dG. Histological studies showed that all the nickel compounds used induced inflammation in lungs of the rats. Nitric oxide (NO) generation in phagocytic cells induced by Ni(3)S(2), NiO(black), and NiO(green) was examined using macrophage cell line RAW 264.7 cells. NO generation in RAW 264.7 cells stimulated with lipopolysaccharide was enhanced by all nickel particles. Two mechanisms for nickel-induced oxidative DNA damage have been proposed as follows: all the nickel compounds used induced indirect damage through inflammation, and Ni(3)S(2) also showed direct oxidative DNA damage through H(2)O(2) formation. This double action may explain relatively high carcinogenic risk of Ni(3)S(2).

8-Hydroxy-2'-Deoxyguanosine↗