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R Korpela

Publications and source records attributed to R Korpela.

At least 37 records · Page 2Linked to original sources

Acute effects of the cys-leukotriene-1 receptor antagonist, montelukast, on experimental colitis in rats.

Cysteinyl leukotrienes play a part in inflammatory reactions such as inflammatory bowel diseases. The aim of the present study was to evaluate the acute effects of a cys-leukotriene-1 receptor antagonist, montelukast, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Montelukast (5, 10 or 20 mg kg(-1) day(-1)), a 5-lipoxygenase inhibitor, zileuton (50 or 100 mg kg(-1) day(-1), a positive control), or the vehicle was administered intracolonically to the rats twice daily throughout the study, starting 12 h before the induction of colitis with TNBS. The severity of colitis (macroscopic and histological assessment, as well as myeloperoxidase activity), the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2, and eicosanoid production in colonic tissue incubation were assessed 24 and 72 h after colitis induction. Montelukast increased prostaglandin E(2) production at 24 h and tended to reduce the cyclooxygenase-2 protein expression at 72 h, but did not influence the severity of colitis. Zileuton failed to decrease the inflammatory reaction in spite of reduced leukotriene B(4) production at 72 h. The results suggest that drugs that block cysteinyl leukotriene receptors have limited potential to ameliorate acute TNBS-induced colitis, but that they exert some beneficial effects which make them capable of modulating the course of colitis.

Acetates↗

Calcium-sensitive potassium channel inhibitors antagonize genistein- and daidzein-induced arterial relaxation in vitro.

Estradiol-17beta relaxes rabbit coronary artery rings via large conductance Ca2+-activated K+-channels (K(Ca)). Genistein and daidzein are plant-derived estrogen-like compounds. The aim of the present study was to investigate whether potassium channels participate in the genistein- and daidzein-induced arterial relaxation like they do in the case of estradiol-17beta. Endothelium-denuded superior mesenteric arterial rings from non-pregnant Wistar female rats were used. At a concentration of 10 microM, estradiol-17beta, genistein and daidzein relaxed noradrenaline precontracted arterial rings, (58 +/- 4%, 45 +/- 5% and 31 +/- 3%, respectively; (n=6-8)). Genistein- and daidzein-induced relaxations were inhibited both by iberiotoxin (1-10 nM) and charybdotoxin (30 nM), the antagonists of large conductance Ca2+-activated K+-channels (K(Ca)). Estradiol-17beta-induced relaxation was reduced by iberiotoxin (30 nM). Estradiol-17beta- and daidzein-induced relaxations were also decreased by apamin (0.1-0.3 microM), an antagonist of small conductance Ca2+-activated K+-channels. The antagonists of voltage-dependent K+-channels (K(V)) (4-aminopyridine), ATP-sensitive K+-channels (K(ATP)) (glibenclamide), or inward rectifier K+-channels (KIR) (barium) had no effect on the relaxation responses of any of the compounds studied. Estrogen receptor antagonist tamoxifen did not inhibit the relaxations. In conclusion, in the noradrenaline precontracted rat mesenteric arteries, the relaxations caused by estradiol-17beta, genistein and daidzein were antagonized by large and small conductance K(Ca)-channel inhibitors, suggesting the role of these channels as one of the relaxation mechanisms.

Animals↗

Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial.

OBJECTIVE: To examine whether long term consumption of a probiotic milk could reduce gastrointestinal and respiratory infections in children in day care centres. DESIGN: Randomised, double blind, placebo controlled study over seven months. SETTING: 18 day care centres in Helsinki, Finland. PARTICIPANTS: 571 healthy children aged 1-6 years: 282 (mean (SD) age 4.6 (1.5) years) in the intervention group and 289 (mean (SD) age 4.4 (1.5) years) in the control group. INTERVENTION: Milk with or without Lactobacillus GG. Average daily consumption of milk in both groups was 260 ml. MAIN OUTCOME MEASURES: Number of days with respiratory and gastrointestinal symptoms, absences from day care because of illness, respiratory tract infections diagnosed by a doctor, and course of antibiotics. RESULTS: Children in the Lactobacillus group had fewer days of absence from day care because of illness (4.9 (95% confidence interval 4.4 to 5.5) v 5.8 (5.3 to 6.4) days, 16% difference, P=0.03; age adjusted 5.1 (4.6 to 5.6) v 5.7 (5.2 to 6.3) days, 11% difference, P=0.09). There was also a relative reduction of 17% in the number of children suffering from respiratory infections with complications and lower respiratory tract infections (unadjusted absolute % reduction -8.6 (-17.2 to -0.1), P=0.05; age adjusted odds ratio 0.75 (0.52 to 1.09), P=0.13) and a 19% relative reduction in antibiotic treatments for respiratory infection (unadjusted absolute % reduction -9.6 (-18.2 to -1.0), P=0.03; adjusted odds ratio 0.72 (0.50 to 1.03), P=0.08) in the Lactobacillus group. CONCLUSIONS: Lactobacillus GG may reduce respiratory infections and their severity among children in day care. The effects of the probiotic Lactobacillus GG were modest but consistently in the same direction.

Absenteeism↗

Induction of nitric oxide synthesis by probiotic Lactobacillus rhamnosus GG in J774 macrophages and human T84 intestinal epithelial cells.

BACKGROUNDS AND AIMS: Probiotic Lactobacillus rhamnosus GG (LGG) has proved to be beneficial in the treatment of viral- and antibiotic-associated diarrhea but the mechanisms of action remain unknown. Nitric oxide (NO) is involved in the protective mechanisms in the gastrointestinal tract and may contribute to some of the beneficial effects of probiotics. The aim of the present study was to investigate if induction of NO synthesis is involved in the cellular actions of LGG. METHODS: NO synthesis and its regulation were measured in cultures of J774 murine macrophages and human T84 colon epithelial cells. NO production was measured as its metabolite nitrite accumulated into the culture medium. Inducible nitric oxide synthase (iNOS) protein and iNOS mRNA were detected by Western blot and RT-PCR, respectively. RESULTS: In J774 macrophages, LGG induced a low level production of NO in the presence of gamma interferon (IFNgamma) and it was inhibited by NOS inhibitors, cycloheximide and by a NF-kappa B inhibitor pyrrolidinedithiocarbamate. Accordingly, LGG and IFNgamma-stimulation increased iNOS mRNA and protein levels. T84 cells produced NO in response to LGG when first primed with a combination of IL-1beta, TNFalpha and IFNgamma. Lipoteichoic acid (LA), an antigenic structure in gram-positive bacteria, also induced NO formation in J774 cells in the presence of IFNgamma suggesting that LA may be the active component in LGG. CONCLUSIONS: LGG induces NO production in J774 macrophages and in human T84 colon epithelial cells through induction of iNOS by a mechanism involving activation of transcription factor NF-kappaB. Induction of iNOS and low-level synthesis of NO may be involved in the protective actions of LGG in the gastrointestinal tract.

Cell Line↗

Effects of a COX-2 preferential agent nimesulide on TNBS-induced acute inflammation in the gut.

In inflammatory bowel disease, increased production of prostaglandins by cyclooxygenase-2 (COX-2) contributes to bowel dysfunction, inflammatory edema, and hyperemia suggesting that inhibitors of COX-2 may have beneficial effect in gut inflammation. We compared the effects of nimesulide, a preferential COX-2 inhibitor, with those of indomethacin, acetylsalicylic acid (ASA), and dexamethasone in a 24-h model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat. TNBS-induced colitis was associated with enhanced COX-2 expression in the gut and increased circulating concentrations of PGE2 metabolite (PGEM). Treatment with nimesulide (10 mg/kg), indomethacin (10 mg/kg), or dexamethasone (1 mg/kg) reduced plasma PGEM concentrations and edema in the inflamed bowel. In addition, nimesulide and dexamethasone treatments decreased neutrophil infiltration into the inflamed colon mucosa. ASA (10 mg/kg) did not have a significant effect on any of these measures of inflammation. None of the studied drugs reduced the size of inflammatory mucosal lesions in the colon. In TNBS-induced acute inflammation of the colon, nimesulide reduced the formation of inflammatory edema, probably by a mechanism related to inhibition of PGE2 production by COX-2 pathway. In addition, nimesulide inhibited neutrophil infiltration into inflamed mucosa mimicking the action of dexamethasone.

Acute Disease↗

Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolaemia.

The objective of the present study was to assess the effect of consumption of a yoghurt-based drink enriched with 1-2 g plant sterols/d on serum lipids, transaminases, vitamins and hormone status in patients with primary moderate hypercholesterolaemia. Thirty patients were randomly assigned to one of two treatment groups: a low-fat low-lactose yoghurt-based drink enriched with 1 g plant sterol extracted from soyabean/d v. a low-fat low-lactose yoghurt, for a period of 4 weeks. After a 2-week wash-out period, patients were crossed over for an additional 4-week period. Second, after a 4-week wash-out period, eleven patients were treated with 2 g plant sterols/d in a second open part of the study for a period of 8 weeks. The yoghurt enriched with plant sterols significantly reduced, in a dose-dependent manner, serum total cholesterol and LDL-cholesterol levels and LDL-cholesterol:HDL-cholesterol (P<0.001), whereas no changes were observed in HDL-cholesterol and triacylglycerol levels, either in the first or the second part of the study. There were only slight, not statistically significant, differences in serum transaminase, vitamin and hormone levels. To conclude, a low-fat yoghurt-based drink moderately enriched with plant sterols may lower total cholesterol and LDL-cholesterol effectively in patients with primary moderate hypercholesterolaemia.

Adult↗

Effects of Lactobacillus rhamnosus GG and Lactobacillus reuteri R2LC on acetic acid-induced colitis in rats.

BACKGROUND: Certain lactobacilli reduce the severity of experimental colitis. The aim of this study was to compare the effects of a human strain Lactobacillus rhamnosus GG and a rat strain Lactobacillus reuteri R2LC on acetic acid-induced colitis in rats. METHODS: Lactobacillus rhamnosus GG, Lactobacillus reuteri R2LC or sulphasalazine were given orally to the rats. Colitis was assessed 72 h after induction with acetic acid. RESULTS: Lactobacillus reuteri R2LC significantly antagonized body weight loss caused by inflammation compared with Lactobacillus rhamnosus GG and sulphasalazine, and oedema formation in the colon compared with sulphasalazine. Lactobacillus reuteri R2LC reduced the median value of macroscopic ulceration and the protein content of inducible nitric oxide synthase by 50% and the median of the protein content of inducible cyclooxygenase by 30% compared with that of the colitis control group, and Lactobacillus rhamnosus GG reduced the median of inducible nitric oxide protein content by 40% and increased the median of inducible cyclooxygenase protein content by 30% compared with the median value of the colitis control group, but these differences were not statistically significant. CONCLUSIONS: The rat strain Lactobacillus reuteri R2LC, but not the human strain Lactobacillus rhamnosus GG, is of benefit in reducing the severity of acetic acid-induced colitis in rats. These results suggest that it is not the total amount of Lactobacillus but the particular species or strain of Lactobacillus that is important in attenuating experimental colitis.

Acetic Acid↗

Suppression of acute experimental colitis by a highly selective inducible nitric-oxide synthase inhibitor, N-[3-(aminomethyl)benzyl]acetamidine.

High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) are associated with ulcerative inflammation and disease activity in colitis. Therefore, inhibition of iNOS serves as a novel experimental approach to treat gut inflammation. The aim of the present study was to investigate the effects of a novel highly selective iNOS inhibitor, N-[3-(aminomethyl)benzyl]acetamidine (1400W), as compared with a nonselective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME), in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in the rat. Increased expression of iNOS protein and mRNA was found in acute TNBS-induced colitis along with neutrophil infiltration, inflammatory edema, and tissue damage. In a 24-h model of acute colitis, subcutaneous injections of 1400W (5 or 10 mg/kg t.i.d.) produced a 56 and 95% reduction in inflammatory edema formation, a 68 and 63% reduction in neutrophil infiltration (measured as myeloperoxidase activity), and a 19 and 26% decrease in the size of mucosal lesions as compared with vehicle treatment. Administration of L-NAME (35 mg/kg) failed to produce any significant beneficial effects as compared with vehicle treatment in this experimental model of acute colitis. Treatment with 1400W, a highly selective inhibitor of iNOS, reduced formation of edema, neutrophil infiltration, and macroscopic inflammatory damage in experimentally induced acute colitis in the rat. In contrast, nonselective nitric-oxide synthase inhibition with L-NAME provided no benefit. These results support the idea that selective iNOS inhibitors have a promise in the treatment of colitis.

Amidines↗

Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats.

Effect of long-term intake of isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), or a sour milk product containing these peptides on development of hypertension was investigated in spontaneously hypertensive rats (SHR). Six-week-old SHR were given: 1) water (control group), 2) IPP and VPP dissolved in water (peptide group) or 3) sour milk containing IPP and VPP (sour milk group) for 12 weeks. Systolic blood pressure (SBP) was measured by tail-cuff method. Development of hypertension was attenuated in the groups receiving tripeptides or sour milk as compared to the control group. At the end of treatment period, SBP was 176 +/- 1 mmHg in sour milk group, 181 +/- 2 mmHg in peptide group, and 193 +/- 1 mmHg in control group (P < 0.001). After treatment withdrawal, SBP rose gradually reaching the level of control group within four weeks' follow-up. In functional bioassay of ACE inhibitory activity, effect of the tripeptides on angiotensin I or angiotensin II-induced contraction in rat mesenteric arteries was evaluated. IPP inhibited the angiotensin I-induced contraction, whereas the angiotensin II-induced contraction remained unaltered. In conclusion, long-term intake of IPP and VPP, or a sour milk containing these tripeptides attenuated the development of hypertension in SHR. One possible mechanism underlying this effect is ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗

Alpha-lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats.

Cardiovascular effects of subcutaneous administration of synthetic alpha-lactorphin, a tetrapeptide (Tyr-Gly-Leu-Phe) originally derived from milk alpha-lactalbumin, were studied in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY) with continuous radiotelemetric monitoring. Alpha-lactorphin dose-dependently lowered blood pressure (BP) without affecting heart rate in SHR and WKY. The lowest dose which reduced BP was 10 microg/kg, and the maximal reductions in systolic and diastolic BP (by 23+/-4 and 17+/-4 mm Hg, respectively) were observed at 100 microg/kg dose in SHR. No further reductions were obtained at a higher dose of 1 mg/kg. There were no significant differences in the BP responses to alpha-lactorphin between SHR and WKY. Naloxone (1 and 3 mg/kg s.c.), a specific opioid receptor antagonist, abolished the alpha-lactorphin-induced reduction in BP and reversed it into a pressor response, which provides evidence for an involvement of opioid receptors in the depressor action of the tetrapeptide.

Angiotensin-Converting Enzyme Inhibitors↗

Soy based diet attenuates the development of hypertension when compared to casein based diet in spontaneously hypertensive rat.

The purpose of this study was to compare the effects of soy and casein based diets on blood pressure and cardiovascular functions in male and female spontaneously hypertensive rats (SHR). The systolic blood pressure was measured at the beginning and at the end of study. After a five week supplementation period with three different diets, the rats were decapitated and arterial responses and the weight-to-body weight-ratios of the organs were studied. The development of hypertension was attenuated in both female and male rats on soy protein diet when compared to the casein diet. Soy based diet lowered serum total cholesterol level when compared to the control diet. Both casein and soy protein supplementation in diet induced a significant renal hypertrophy in both female and male SHR rats when compared to SHR rats on the control diet. Soy protein supplementation reduced significantly serum estradiol-17beta concentration when compared to the control diet. There were no differences in the serum testosterone concentrations between the diet groups. When compared to the casein based diet the soy based diet attenuated the development of hypertension and decreased serum total cholesterol level in SHRs. These effects were independent of gender. The mechanisms and clinical importance of these findings remain to be clarified.

Animals↗

Oxidized LDL from subjects with different dietary habits modifies atherogenic processes in endothelial and smooth muscle cells.

Low-density lipoprotein (LDL) activates a number of processes involved in atherogenesis and vasoconstriction. Evidence suggests that oxidation increases the atherogenicity of LDL. We investigated the effects of oxidized LDL (ox-LDL) on cytotoxicity, prostacyclin (PGI2), and cyclic guanosine-3',5'-monophosphate (cGMP) production in rat vascular smooth muscle cell (VSMC) and rat heart endothelial cell (EC) culture, as well as EC- and VSMC-mediated LDL oxidation. Native LDL (n-LDL) was isolated from subjects on three long-term diets with differing fatty acid content (control diet rich in saturated fat and vegetarian and fish diets). The Cu2+-catalyzed oxidation of n-LDL was monitored using conjugated diene formation and stopped at various time points to achieve 20%, 45%, 70%, and 100% levels of ox-LDL. The lag phase of oxidation by Cu2+ was shortest and thiobarbituric acid-reactive substance (TBARS) formation by VSMC-mediated oxidation was highest with n-LDL obtained from the fish diet group. There were no differences between the ox-LDLs obtained from the different diet groups in their cytotoxicity in EC culture. The degree of oxidation did not influence LDL cytotoxicity. In VSMC culture PGI2 production was increased by ox-LDLs from all diet groups. In EC culture only the extensively oxidized LDLs obtained from the vegetarian diet group were able to induce PGI2 production. The LDLs did not affect basal cGMP production in either EC or VSMC culture.

Adult↗

Utstein style reporting of in-hospital paediatric cardiopulmonary resuscitation.

STUDY OBJECTIVE: To report paediatric in-hospital cardiac arrest data according to Utstein style and to determine the effectiveness of cardiopulmonary resuscitation (CPR) in hospitalized children. DESIGN: Retrospective 5-year case series. SETTING: Urban, tertiary-care children's hospital. PARTICIPANTS: All patients who sustained cardiopulmonary arrest. RESULTS: Altogether 227 patients experienced a cardiopulmonary arrest during the study period, 109 (48.0%) were declared dead without attempted resuscitation, and CPR was initiated in 118 (52.0%). The incidence of cardiac arrest was 0. 7% of all hospital admissions and 5.5% of PICU admissions; the incidence of CPR attempts was 0.4 and 2.5%, respectively. Most of the CPR attempts (64.4%) took place in the PICU and the most frequent aetiology was cardiovascular (71.2%). The 1-year survival rate was 17.8%. Short duration of external CPR was the best prognostic factor associated with survival. With few exceptions, the Paediatric Utstein Style was found to be applicable for reporting retrospective data from in-hospital cardiac arrests in children. CONCLUSIONS: In-hospital cardiopulmonary resuscitation was shown to be an uncommon event in children; the survival rate was similar to earlier studies.

Adolescent↗

Temperature of a test solution influences abdominal symptoms in lactose tolerance tests.

In lactose maldigesters, retarding gastric emptying (food/pharmaceuticals) improves tolerance to lactose. The role of temperature of test solution on the indicators of lactose intolerance was studied. After an overnight fast, 10 lactose maldigesters ingested, in three sessions, 50 g lactose in a randomized cross-over trial. The solutions were at temperatures of 20-21 degrees C (room temperature), 2-3 degrees C (cold) and 55-58 degrees C (hot). Gastrointestinal symptoms and indicators measuring lactose absorption were recorded. Abdominal pain was noticeably increased by the modification of temperature. The cold solution reduced flatulence and abdominal bloating, whereas the hot solution increased bloating and borborygmi. Breath hydrogen excretion tended to be augmented and retarded after cold solution. The temperature of the solution used in a lactose tolerance test affects the gastrointestinal symptoms, but has only minor effects on the other indicators of lactose maldigestion. The constant tendencies observed suggest that a room temperature solution is to be recommended for testing lactose digestion.

Abdomen↗

Wide variations in the testing of lactose tolerance: results of a questionnaire study in Finnish health care centres.

About 70% of the world's adult population is unable to digest lactose, the sugar found naturally only in milk. This disability leads to gastrointestinal symptoms called lactose intolerance. In Finland, many patients visit health care centres because they are suffering from gastrointestinal symptoms. A few of them are diagnosed as being lactose intolerant. However, a far larger number diagnose themselves as suffering from lactose intolerance. Therefore the diagnostic tests used should be carefully validated and standardized in clinical laboratories throughout the country. The aim of this questionnaire study was to clarify the situation centres with adult patients in Finnish health care and to try to standardize procedures for administering lactose tolerance tests.

Adult↗

Lactose intolerance.

Lactose maldigestion has been under intensive research since its discovery in the 1960's. We know the prevalence of lactose maldigestion in a great number of countries and ethnic groups. However, there is often no provision made for the secondary type of maldigestion, and the study populations have sometimes been selected rather than picked at random. New methods for the measurement of lactose digestion have been developed, and its genetic mechanisms have received a great deal of attention during the last few years. However, in many studies the measurement and/or reporting of symptoms has quite often been overlooked. In this review, various topics related to lactose intolerance are discussed with a special emphasis on its symptoms.

Animals↗

A long-term fish diet modifies the toxic properties of human partially oxidized LDL on vascular preparations in vitro.

Both LDL oxidation and LDL fatty acid composition affect vascular relaxation and contraction. The aim of this study was to investigate whether long-lasting dietary habits (vegetarian, fish and high saturated fat as a control group) can change those properties of partially oxidized LDL (ox-LDL) which are reflected in altered vascular responses measured with a bioassay. The effects of ox-LDL were investigated on rat mesenteric arteries. In endothelium intact arterial rings the contractile responses to noradrenaline (NA) tended to be diminished in the presence of ox-LDL derived from the fish diet group compared with the other groups. In the endothelium denuded arterial rings the contractile responses to NA and KCl were significantly enhanced by ox-LDL from the fish diet group compared with the control group. The ox-LDL from the fish diet group increased the diclofenac, L-NAME resistant relaxations to ACh compared to the control diet group suggesting the role of endothelium derived hyperpolarizing factor (EDHF). In conclusion, partially oxidized LDL from subjects living on a fish diet is biologically more vasoactive in bioassay systems than partially oxidized LDL from those living on vegetarian or saturated fatty acid containing diets. The impaired responses in vasoconstriction and improved vasodilation seem to be endothelium dependent.

Acetylcholine↗