Yoghurt containing galacto-oligosaccharides, prunes and linseed reduces the severity of mild constipation in elderly subjects.

OBJECTIVE: Constipation is a common problem in the elderly. Dietary fibre is recommended for its treatment. The aim was to examine whether yoghurt containing galacto-oligosaccharides (GOS), prunes and linseed relieve constipation in elderly subjects. DESIGN: A randomized, double-blinded, cross-over study. SETTING: Free-living subjects. SUBJECTS: A group of 43 elderly subjects with self-reported constipation (mean age 76 years, range 61-92 years, 32 females, 11 males). INTERVENTIONS: The study consisted of a 2-week baseline period and 2, 3-week dietary interventions, with a 2-week wash-out period between the interventions. During the interventions, the subjects ingested, in random order, 260 g/day of either control yoghurt or test yoghurt containing GOS (12 g/day), prunes (12 g/day) and linseed (6 g/day). The use of laxatives was controlled and only allowed after 2 days without defecation. RESULTS: Defecation frequency was 5.7 times/week during the baseline period. During the test yoghurt period, defecation frequency was higher (8.0 vs 7.1 times/week, P=0.011), defecation was easier (on the scale 0-3, 1.3 vs 1.5, P=0.010), and there was a tendency towards softer stools (on the scale 0-3, 2.1 vs 2.2, P=0.059) compared with the control yoghurt period. The subjects felt that the test yoghurt relieved constipation more effectively than the control yoghurt (P=0.005). The sum of gastrointestinal symptoms did not differ between the interventions. The use of laxatives remained constant throughout the study. CONCLUSIONS: Daily intake of yoghurt containing GOS, prunes and linseed reduced the severity of constipation in elderly subjects with mild constipation. SPONSORSHIP: Valio Ltd, R&D.

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.

Dietary fatty acid composition influences the degree of human LDL oxidation, but has only minor effects on vascular tone in a bioassay system.

BACKGROUND AND AIM: Oxidized LDL has been detected in atherosclerotic vessels and presumed to be one of the major risk factors in atherosclerosis and cardiovascular diseases. The aims of the present study were to clarify whether the oxidation degree of LDL influences arterial tone and whether different long-lasting dietary habits have effects on biological variables. METHODS AND RESULTS: The lag phase of LDL oxidation was shorter (117 +/- 6 min) in the fish diet group than in the vegetarian (153 +/- 5 min) or the control diet group (152 +/- 10 min). The rat mesenteric arterial rings, which were preincubated with LDL oxidized to 1-30%, from the vegetarian and the fish diet groups showed (p < 0.05) decreased NA-induced maximal contraction forces when compared to the control diet. The LDL oxidation degrees of 31-60% and 61-90% had no effect on NA- and KCl-induced maximal contraction forces when compared to native LDL, nor were there differences between the diet groups. Endothelium-dependent and independent relaxation responses behaved similarly in all groups and were independent of the degree of oxidation. CONCLUSIONS: Dietary habits change the fatty acid composition of LDL, but have only minor effects on the vasoactive properties of oxidized LDL.

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.

Development of chronic allograft rejection and arterial hypertension in Brown Norway rats after renal transplantation.

The cardiovascular and renal pathophysiology associated with chronic renal allograft rejection under triple drug immunosuppressive treatment was studied using a recently developed model (Brown Norway (BN) rats) in a 6-week experiment. Renal transplantation was performed to 10-week-old rats in a rat strain combination of Dark Agouti (DA) --> BN. The right kidney was removed from another group of BN rats (uninephrectomized). A triple drug treatment comprising cyclosporine (10 mg/kg subcutaneously, s.c.), azathioprine (2 mg/kg s.c.) and methylprednisolone (1.6 mg/kg s.c.) was given to each rat daily for 6 weeks. A control group underwent no operations nor drug treatment. After the transplantation, the systolic blood pressure in this group was increased from 116 +/- 2 to 166 +/- 2 mmHg, while in the uninephrectomized group the rise was from 115 +/- 4 to 146 +/- 4 mmHg, and no change was observed in the blood pressures of the control group. The vascular relaxation responses of mesenteric arterial rings in vitro to acetylcholine were inhibited in both the transplantation group and the uninephrectomized group as compared with the control group, but few significant differences were found in the contraction responses to noradrenaline and potassium chloride. Graft histology was examined after 6 weeks, quantified by using the chronic allograft damage index (CADI). Changes specific to a chronic rejection reaction were observed in the allografts (CADI mean 6.0) but no injuries were seen in the rats' own kidneys (CADI mean 1.2). Our findings show that allograft rejection in BN rats after renal transplantation is associated with the development of arterial hypertension. The combination of cyclosporine, methylprednisolone and azathioprine also rises blood pressure in uninephrectomized BN rats. The hypertensive effects of the drug treatment and graft rejection are associated with endothelial dysfunction.

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.

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.

Ibuprofen augments gastrointestinal symptoms in lactose maldigesters during a lactose tolerance test.

BACKGROUND: Clinical symptoms during lactose tolerance test mimic those seen after therapeutic administration of prostaglandins, and resemble inflammatory processes. AIM: To investigate the possibility that lactose-induced gastrointestinal symptoms are associated with prostaglandins and/or nitric oxide. METHODS: After an overnight fast, nine maldigesters ingested lactose or sucrose with or without an inhibitor of prostaglandin synthesis (ibuprofen), in a randomised double-blind crossover trial. Gastrointestinal symptoms, concentrations of PGE2-M in blood and urine, and urinary 6-keto PGF1alpha (as indicators of prostaglandin synthesis), and urinary nitrate and nitrite as well as cyclic GMP excretions (as indicators of nitric oxide formation), were measured. RESULTS: Ibuprofen increased the first 3-h symptom scores (flatulence + borborygmi + abdominal bloating + pain) caused by lactose (P=0.008) but not sucrose. The concentrations of PGE2-M in the plasma and in the urine were unaffected. Lactose increased the urinary excretion of 6-keto PGF1alpha by about 30% (P=0.17), which was inhibited by ibuprofen (P=0.02). The production of nitric oxide was unaffected by lactose or ibuprofen. CONCLUSION: The inhibition of prostaglandin synthesis intensified gastrointestinal symptoms in lactose maldigesters, suggesting a negligible role for prostanoids in lactose-induced symptoms.

Influence of the pharmacological modification of gastric emptying on lactose digestion and gastrointestinal symptoms.

BACKGROUND: In lactose maldigesters the ingestion of food which retards gastric emptying improves tolerance to lactose. AIM: To study the effects of the pharmacological modification of gastric emptying on the speed of development of lactose-induced symptoms. METHODS: After an overnight fast, 18 lactose maldigesters were given, in a randomized double-blind study design at 1-week intervals, either propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg) or placebo, in identical capsules, 60 min before ingesting 50 g lactose coloured with 1 g carmine dye (to measure gastrointestinal transit time). Gastrointestinal symptoms, urinary galactose excretion, and breath hydrogen and blood glucose concentrations were recorded. RESULTS: The propantheline-induced prolongation of gastric emptying improved tolerance to lactose, as measured by reduced area under the gastrointestinal symptom score curve 0-12 h, compared to placebo (by 26%) (P < 0.05) or metoclopramide (by 30%) (P < 0.05). The total hydrogen excretion AUC (180 min follow-up) increased by 15% after metoclopramide as compared with placebo (P = 0.18). Propantheline decreased this variable by 15% from placebo (P = 0.17). No significant differences in blood glucose, urinary galactose or gastrointestinal transit time were found. CONCLUSIONS: In an oral lactose tolerance test, delaying gastric emptying with propantheline improved tolerance in lactose maldigesters, as measured by diminished gastrointestinal symptoms and reduced breath hydrogen concentration.

Plant derived estrogens relax rat mesenteric artery in vitro.

The aim of this study was to investigate whether plant derived estrogens have the same relaxing effects in vitro as estradiol-17beta on arterial smooth muscle. The mesenteric arterial rings of female and male Wistar rats were studied. The relaxing effects of estradiol-17beta, genistein, daidzein and beta-sitosterol were determined, with particular focus on the role of endothelium. B-sitosterol had no relaxing effect on the arteries. Estradiol-17beta, genistein and daidzein relaxed noradrenaline, potassium chloride and calcium chloride precontracted arterial rings endothelium-independently. The relaxation responses were also independent of gender. Neither the removal of endothelium, nor the inhibition prostacyclin or nitric oxide synthesis, had any effect on the relaxation responses. The exact mechanism of these findings is still unclear.

The effects of male gender and female sex hormone deficiency on the vascular responses of the rat in vitro.

Male gender and menopause increase the risk for cardiovascular incidents by mechanisms that have not yet been fully clarified. Recent evidence suggests that the cardioprotective property of female sex hormones may be partly related to direct vasodilation. Accordingly, we examined the possible differences in arterial reactivity in vitro between normal female, ovariectomized female and normal male rats. Endothelium intact mesenteric artery rings were used to determine concentration response curves for noradrenaline, potassium chloride, acetylcholine and sodium nitroprusside. When compared to normal female rats, the maximal contractions to noradrenaline and potassium chloride were increased both in the ovariectomized female and in male rats. The relaxation induced by sodium nitroprusside was enhanced both in normal and ovariectomized females when compared to the male rats. There were no differences in relaxation responses to acetylcholine between normal or ovariectomized female or male rats. In conclusion, male gender and ovarian hormone deficiency increase arterial reactivity to constricting factors and reduce the vasodilatory effects of endothelium-independent relaxing agents.

Indapamide treatment modifies the vascular reactivity of normotensive rat mesenteric arteries ex vivo.

Indapamide is an antihypertensive diuretic drug of which the precise antihypertensive mechanism has not been clarified. The aim of the present study was to investigate with mesenteric arteries of normotensive rats the possible change in vascular reactivity ex vivo and in vitro after indapamide application, taking into special consideration the role of endothelium. After seven days of drug treatment in vivo with low-dose 0.3 mg/kg/day or high-dose 3 mg/kg/day of indapamide the effect on the vascular responses ex vivo were compared to controls. The contractions induced by noradrenaline (NA) or potassium chloride (KCl) were increased in vascular rings without endothelium in the high-dose indapamide group. No alterations in endothelium-dependent relaxation responses to acetylcholine (ACh) or endothelium-independent responses to sodium nitroprusside (SNP) were found between any of the treatment groups in vascular rings with or without endothelium. When indapamide (1 microM or 10 microM) was added in vitro for 10 min preincubation it did not significantly change the vascular contractions induced by cumulatively increased concentrations of NA or KCl. The relaxation responses induced by ACh or SNP were also not affected by indapamide pretreatment. Our results suggest that the lack of change in contractile response in vitro after indapamide pretreatment might be related to the prodrug nature of indapamide, which is not metabolized during the short preincubation.

Effect of nitric oxide donors on rat bronchial muscle in vitro.

Relaxing effects of the nitric oxide donors GEA 3175 (3-aryl-substituted oxatriazole derivative), SIN-1 and sodium nitroprusside (SNP) were compared in the rat bronchial rings in vitro. In epithelium intact rings, after metacholine precontraction ED50 of GEA 3175 and SNP were similar (2 and 3.5 microM respectively) while the maximum effect of the former was bigger (92% and 54% respectively). SIN-1 was less potent (ED50 50 microMx, maximum 55%). In the absence of the epithelium the effect of GEA 3175 was attenuated, while that of SIN-1 or SNP were abolished. In the KCl precontracted rings the effects of all compounds were smaller than after metacholine precontraction. Removal of the epithelium did not alter the effects of GEA 3175 or SIN-1 but clearly increased that of SNP (change of EC50 from 10 to 0.7 microM).

Replacement of salt by a novel potassium- and magnesium-enriched salt alternative improves the cardiovascular effects of ramipril.

1. The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2. Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3. Ramipril treatment at a daily dose of 3 mg kg-1 normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in the salt group was prevented by ramipril. 4. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5. Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment. 6. Both salt supplementations, irrespective of ramipril treatment, induced a six to eight fold increase in the urinary excretion of calcium. There was an expected 90 to 140% rise in the urinary excretion of magnesium and 200% rise in the urinary excretion of potassium in the salt alternative group. Salt also produced an approximately 50% increase in magnesuria.7. Our findings suggest that replacement of salt by the potassium-, magnesium- and L-lysine-enriched salt alternative improves the cardiovascular effects of ramipril. In the present study the beneficial effect was related to the increased intakes of potassium and/or magnesium and L-lysine from the salt alternative because the amount of sodium chloride was the same.