Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

BACKGROUND: Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. METHODS: Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 µg/kg bolus plus infusion 0.5 µg/kg/min (n = 7), levosimendan 24 µg/kg plus infusion 0.2 µg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. RESULTS: During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. CONCLUSIONS: These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium.

Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort.

BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36,037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

Supplementation of omega-3 fatty acids in patients with ankylosing spondylitis.

OBJECTIVE: To study the effect of supplementation with omega-3 fatty acids on disease variables and drug consumption in patients with ankylosing spondylitis (AS). METHODS: Twenty-four patients were randomized to either a low-dose (1.95 g omega-3/day) or a high-dose (4.55 g omega-3/day) supplement. Disease activity, functional impairment, erythrocyte sedimentation rate (ESR), and drug consumption were assessed during visits at baseline and at weeks 7, 14, and 21. RESULTS: Eighteen patients completed the study, nine patients from each group. The patients in the high-dose group exhibited a significant decrease in disease activity according to the Bath Ankylosing Disease Activity Index (BASDAI; p = 0.038), which was not seen in the low-dose group. Significant differences were not found on drug consumption or in functional capacity in either of the groups. No significant differences were found when comparing the results between the high- and low-dose groups. CONCLUSION: Omega-3 fatty acids in adequate doses may have the capacity to decrease the disease activity of AS. However, larger and better controlled studies are needed before any further conclusions can be made on the extent of this capacity.

Food habits of young Swedish and Norwegian vegetarians and omnivores.

OBJECTIVE: To determine the prevalence of vegetarianism and compare food habits among vegetarian and omnivorous adolescents in Sweden and Norway. DESIGN: Cross-sectional study by questionnaire in Sweden and Norway to gather information about food habits. SETTING: The municipalities of Umeå and Stockholm in Sweden, and Bergen in Norway. SUBJECTS: In total 2041 ninth-grade students (578 from Umeå, 504 from Stockholm and 959 from Bergen), mean age 15.5 years, were included. The response rate was 95% in Umeå, 91% in Stockholm and 83% in Bergen. RESULTS: There was a significantly higher prevalence of vegetarianism in Umeå (15.6%) than in Stockholm (4.8%) and Bergen (3.8%). Vegetarians generally wanted more information about a healthy diet and vegetarian females ate dietary supplements to prevent deficiencies more often than omnivorous females (P < 0.01). The young male vegetarians more or less excluded animal products from their diet without changing their food frequency intake or modifying their dietary habits in other respects, while the young female vegetarians more often consumed vegetables and dietary supplements (P < 0.05). However, there was no difference between the intake of fruits/berries, alcoholic beverages, ice cream, sweets/chocolates and fast foods by vegetarians compared with omnivores. CONCLUSIONS: There were three to four times more vegetarians in Umeå than in Stockholm and Bergen. The food habits of the young vegetarians differed from those of omnivorous adolescents and also in some respects from previously published comparative studies of vegetarians' and omnivores' food habits. It is uncertain whether the health benefits shown in previous studies on vegetarianism will be experienced by this young generation of vegetarians.

Effects of mouthrinses with linseed extract Salinum without/with chlorhexidine on oral conditions in patients with Sjögren's syndrome. A double-blind crossover investigation.

OBJECTIVES: To study the effect of mouthrinses with salivary replacement substances on oral conditions in patients with primary Sjögren's syndrome. DESIGN: Cross-over, double-blind study. SETTING: Facilities at the Centre for Oral Health Sciences, Malmö University and at Malmö University Hospital, Malmö, Sweden. SUBJECTS: Twenty-two patients with Sjogren's syndrome. INTERVENTION: Linseed extract Salinum alone (Sal) or with addition of chlorhexidine (Sal/Chx) was used for mouthrinsing during 3-week periods of rinsings separated by a 3-week "wash-out" period. MEASUREMENTS: Recordings of percentages of sites with dental plaque and bleeding on probing, mirror friction test and microbiological analyses. Questionnaire on oral symptoms due to reduced salivation. RESULTS: Dental plaque and bleeding on probing were reduced after Sal and after Sal/Chx. Friction was reduced after both treatments. No significant differences for counts of studied microbial groups were seen after Sal but the total anaerobically cultured microorganisms and of mutans streptococci fell after Sal/Chx (p<0.05 and p<0.001). Symptoms of oral dryness improved following Sal and Sal/Chx (p<0.05 and p<0.001 respectively). Speaking problems and burning mouth symptoms improved after use of Sal (p<0.05). CONCLUSIONS: Positive effects on symptoms in patients with Sjögren's syndrome were seen after use of Salinum without or with chlorhexidine.

Oral mucous membrane flora in patients using saliva substitutes.

UNLABELLED: Salivary substitutes are sometimes valuable for elderly people and radiotherapy patients, and may be used indefinitely. It is possible that this change in the ecology may effect the oral flora. OBJECTIVE: To analyse the presence of micro-organisms on oral mucous membranes during use of saliva substitutes. DESIGN: Cross-over single-blind study. SETTING: Clinic for Maxillofacial Surgery, Malmö University Hospital and Department of Oral Microbiology, Malmö University. SUBJECTS: 19 patients with low salivary secretion who had been radiated for cancer in the head and neck region. INTERVENTION: Two saliva substitutes: linseed extract and a carboxymethyl cellulose preparation (Salinum and MAS-84) were used for 3 week periods. MEASUREMENTS: Microbial samples taken, processed and analysed. RESULTS: No differences were observed when comparing baseline values with the results after the saliva substitutes and no significant differences between the use of different agents. CONCLUSION: The study suggests that use of linseed extract and carboxymethyl cellulose preparation during periods of weeks does not influence flora commonly related to caries, periodontitis or infections in the oral mucous membranes.

Aspects of teeth from archaelogic sites in Sweden and Denmark.

The purpose of this study was to examine ground sections of primary second molars and permanent first molars from the same jaws. Teeth from 11 individuals were collected from archaeologic sites in Sweden and Denmark. Longitudinal buccolingual sections were examined in a polarization light microscope and in a Philips scanning electron microscope (SEM). The seven teeth from Sweden appeared to have been subjected to environmental influences at their burial site, which had affected both the dentin and the enamel. The teeth from the Danish sites had a normal color, and no disintegration of the dentin was seen. The general morphologic appearance was normal in all primary and permanent teeth. The position of the neonatal line indicated a normal full-term gestational age. The observed accentuated incremental lines in both the primary and permanent enamel suggested periods of dietary changes, possibly related to periods of illness. SEM images of the surface area of the Swedish teeth showed an extremely porous enamel surface with severe changes in the prism structure as an effect of acid penetration. The Danish teeth did not show any marked changes in the enamel.

Cloning and characterization of a cDNA encoding a cellobiose dehydrogenase from the white rot fungus Phanerochaete chrysosporium.

The cDNA of cellobiose dehydrogenase (CDH) from Phanerochaete chrysosporium has been cloned and sequenced. The 5' end was obtained by PCR amplification. The cDNA contains 2310 translated bases excluding the poly(A) tail. The deduced mature protein contains 770 amino acid residues and is preceded by a 18 residue long signal peptide. The regions of the amino acid sequence corresponding to the heme and FAD domains of CDH were identified as well as the nucleotide-binding motif, the disulfide pairing and a methionine residue chelating the heme iron. No homologous sequences were found for the heme domain, however, the FAD domain appears to be distantly related to the GMC oxidoreductase family.

Comparison of the effect of the linseed extract Salinum and a methyl cellulose preparation on the symptoms of dry mouth.

The effect of a linseed extract Salinum and a sodium carboxymethyl cellulose preparation called MAS-84 was compared with regard to its effect on the symptoms of dry mouth. Twenty patients with xerostomia, who had been treated for cancer in the head and neck by radiation were recruited from the clinic for maxillofacial surgery, Malmo University Hospital. Following radiation treatment the salivation was severely reduced. The symptoms of a general feeling of a dry mouth, difficulties in chewing and swallowing, taste disturbances, problems with speech and mouth burning were registered on a subjective verbal rating scale. In addition plaque index and gingival bleeding were determined. The study design was crossover and performed single blind. The experimental period was 7 weeks. The patients were randomly divided into 2 groups. One group used Salinum and the other MAS-84 for 3 weeks. The fourth week was a wash out period and for the next three weeks the patients shifted preparation. Each of the preparations was used ad libitum. Registrations of the various parameters were undertaken on days 0, 7 and 21 of the respective period. At the initial examination all patients reported considerable disturbances from mouth-dryness. These symptoms were reduced in 15 patients during the Salinum period and in 9 during the MAS-84 period. The relief was significantly more pronounced during the use of Salinum compared to that during the use of the methyl cellulose preparation. On day 21 plaque and gingival bleeding were significantly reduced during the Salinum period but not during the MAS-84 period. The results of the present study confirm those of a previous pilot study and indicate that the linseed mucilage significantly reduced the symptoms of dry mouth. This effect increased with increasing time of saliva substitute use. The linseed mucilage Salinum appeared to be a suitable saliva replacement in mouth dry patients.

The effect of Salinum on the symptoms of dry mouth: a pilot study.

The effect of a new saliva substitute, Salinum, was tested in 37 patients with severe symptoms of reduced salivation. The majority of the patients had suffered from hyposalivation and dry mouth for more than 8 years. The saliva substitute consisted of a water soluble extract of linseed. The physical properties of this extract are similar to those of the glycoproteins of the salivary secretions. The patients used the saliva substitute for a seven days period. Prior to the use of the extract the patients reported that the most severe symptoms of decreased salivation were a feeling of dryness in the mouth and burning sensations in the tongue, pharynx and oesophagus, The majority of the patients reported that the use of Salinum reduced the symptoms of hyposalivation. Great variation in effect occurred from patient to patient. Generally the patients with the most severe symptoms experienced the greatest relief of the symptoms when they used Salinum. Although of short duration the results of this pilot study indicate that an extract of linseeds may compensate for some aspects of the consequences of reduced salivation. Further studies are needed to elucidate the feasibility of the extract as saliva replacement.

Functional deterioration and selenium-vitamin E treatment in myotonic dystrophy. A placebo-controlled study.

OBJECTIVES: The aim of the investigations was to study the effect of a combined selenium and vitamin E treatment in patients with myotonic dystrophy. DESIGN: A double-blind placebo-controlled trial. SUBJECTS: Twenty-seven patients with myotonic dystrophy divided into an experimental (n = 13) and a control (n = 14) group. INTERVENTIONS: The experimental group was given increasing doses for 4 months up to a maximum of 1.6 mg selenium and 800 mg vitamin E daily and the control group a corresponding number of placebo tablets. The total treatment period was 2 years. MAIN OUTCOME MEASURES: Muscle strength (knee extension, knee flexion, hand-grip), maximal walking speed for 30 m, function in daily activities (disability), well-being and cognitive functioning. RESULTS: Before treatment, muscle strength showed moderately or markedly reduced values as did maximal walking speed. Disability was most markedly demonstrated in instrumental ADL-activities. Spatial ability was reduced in the majority of patients. During the 2-year follow-up period, the hand-grip strength and maximal walking speed decreased in both groups (P < 0.01). The reduction was not significantly different according to an 'intention-to-treat-analysis'. However, there was a significantly larger decline (P < 0.01) in the left-hand grip strength in the control group when all the patients with complete treatment compliance were included. CONCLUSIONS: A useful set of measurements has been developed for following functional deterioration in myotonic dystrophy. No conclusive evidence of beneficial effects of selenium and vitamin E treatment has been produced.

Trace element status in healthy subjects switching from a mixed to a lactovegetarian diet for 12 mo.

The consequences of a change from a mixed to a lactovegetarian diet for 12 mo on trace element concentrations in plasma, hair, urine, and feces were studied in 16 women and 4 men. After the diet shift, intakes of zinc and magnesium did not change but that of selenium decreased by 40%. Three months after the diet shift, plasma and hair concentrations of zinc, copper, and selenium had decreased but those of magnesium had increased and the concentrations of mercury, lead, and cadmium in hair were lower. Also, the excretion of zinc, copper, and magnesium in urine, and that of selenium in urine and feces had decreased. Only small changes occurred during the remaining lactovegetarian-diet period. Three years later trace element concentrations had reverted towards baseline concentrations; copper values were similar to baseline concentrations but data for magnesium were slightly higher, and more complex patterns were observed for zinc and selenium. It is concluded that a shift to a lactovegetarian diet changes trace element status.

Autoradiography of hypothalamic regions after acute hyperosmolarity in mice.

Many regions around the third ventricle of the brain are thought to participate in the regulation of water intake. In this study we have visualized in acutely hyperosmolar mice the hypothalamic regions by using autoradiography and [14C]deoxyglucose as marker. By applying a recently published, inexpensive, calibrated photographic method for the analysis of the autoradiographs, we can show that the medial parts of the hypothalamus near the third ventricle increased their uptake of deoxyglucose in comparison with the lateral parts. Densitometric measurements confirmed the results. The results also indicate that parts of the medial hypothalamus, even those that are more caudal than the paraventricular nuclei, react to hyperosmolarity.

Catecholamine-induced free radicals in myocardial cell necrosis on experimental stress in pigs.

Normal pigs, crossbreeds of Swedish Landrace and Yorkshire, about 6 months old, were subjected to experimental stress, induced by the myorelaxant succinylcholine, for 12 min. Besides one group of control pigs, one group of pigs were pretreated with alpha-tocopherol (vitamin E) combined with selenium (Tokosel Vet) injected i.m. every second day for 11 days, and another group was given zinc (ZnSO4.7H2O) in the fodder for 1 month plus one injection i.p. 2 days before the stress. The stress-induced heart lesions, morphologically graded according to evaluation scores, were significantly reduced in both the pretreated groups when compared with the control pigs. The blood levels of catecholamines (CA) were increased to about the same degree in the three groups during the stress. The protection observed is suggested to be due to the fact that vitamin E, selenium and zinc are involved in systems acting as scavengers of free radicals. The present results together with earlier ones are discussed to support the CA-hypothesis for stress-induced heart lesions: some types of stress can increase the sympathetic activity to such an extent that released CA, via beta-adrenoceptor mechanisms affects the cell metabolism to such a degree that cytotoxic free radicals are formed, producing myocardial cell necrosis.

Pain and stress: correlation of stress hormone release to pain modulation in man.

The contribution of stress-induced and opioid-dependent mechanisms to the modulation of experimental pain was studied in man under different conditions. The contribution of these mechanisms to the possible attenuation of acute cardiac pain in human patients was also studied. According to the present series of investigations, stress-induced mechanisms might be involved in the modulation of pain caused by physical exercise but not by concurrent subacute pain or transcutaneous nerve stimulation. The lack of any negative correlation between the pain intensity and the release of stress hormones indicates that stress mechanisms do not attenuate acute ischaemic pain of the cardiac origin. The use of an opioid-antagonist, naloxone, and the measurement of plasma levels of beta-endorphin did not reveal any contribution of endogenous opinoids to pain modulation in the current study.

Deoxyglucose-autoradiography of the hypothalamus after food deprivation in the mouse.

[14C] deoxyglucose-autoradiography of mouse brain after food deprivation showed no specific changes in the ratio of autoradiographic optical density of the lateral nucleus of the hypothalamus (LH) versus ventromedial nucleus of the hypothalamus (VMH). The results show that even if there were differences in functional activity between these hypothalamic nuclei during conditions of hunger and satiety, they are not reflected as autoradiographically detectable in relative deoxyglucose uptake.

Changes in plasma zinc and urinary excretion of zinc after operation with extracorporeal circulation.

Sixteen adults undergoing cardiac surgery were studied with respect to postoperative levels of zinc in plasma and urinary excretion of zinc. The preoperative plasma concentrations of zinc were normal. On the first postoperative day the mean for the series had fallen from 15 to 7.2 mumol/l. A gradual rise followed, and on the fifth day all patients had plasma zinc above the lower limit of normal range. The urinary excretion of zinc was significantly increased on the first, second and fifth days after surgery. The mean total of zinc in the urine during five days was 67 mumol. The short-term fall in plasma zinc level had no discernible effect on wound healing. It was therefore apparently harmless and did not indicate a need for zinc supplementation.