Combined effect of different lactic acid bacteria strains on the mode of cytokines pattern expression in human peripheral blood mononuclear cells.

The balance between immunogenic and tolerogenic activities in human immune system strongly depends on microflora-induced pro-and anti-inflammatory activities. Lactic acid bacteria (LAB) are important components of microflora. The interactions of the different strains of LAB and the cells of immune system are largely unknown. To assess if LAB strains composition would have an effect on the cellular responses profile (proliferation, cytokines synthesis) peripheral blood mononuclear cells (PBMC) model system was used. PBMC were induced by three different strains of LAB: Lactobacillus acidophilus, Lactobacillus delbrueckii spp. bulgaricus, Bifidobacterium bifidum. Tested strains were mixed together, in combinations with each other (pairs) or alone. Both, the LAB mixture as well as the pairs and the single LAB strains induced low lymphocyte proliferation (about 10% of ConA-induced response). However, the single LAB strains and their combinations were quite different cytokines inducers. First, L. acidophilus was much stronger IFN-gamma inducer than the LAB mixture, being a few times higher IL-12 stimulator than L. bulgaricus and B. bifidum. Second, L. bulgaricus and B. bifidum suppressed L.acidophilus-induced IFN-gamma synthesis to the level equal to that induced by the LAB mixture, limiting IL-12 production by about 30% and 70%, respectively. Third, the LAB strains were good IL-10 and TNF-alpha inducers, irrespectively of their combinations used. We conclude that LAB strains' pro or anti-inflammatory potentials are at least in part dependent on their composition. Low LAB mixture-induced IL-12 and IFN-gamma production and relatively high IL-10 and TNF-alpha expression may represent cellular activities normally induced in vivo by a combined action of bacterial antigens. Their presence is important to limit pro-inflammatory reactions (via IL-10) and to provide protection against infections (via TNF-alpha).

Inhibitory effect of Greenland shark liver oil combined with squalen and arctic birch ashes on angiogenesis and L-1 sarcoma growth in Balb/c mice.

Sharks have been claimed to be resistant to cancer and oil from their livers have been used in Scandinavian folk medicine as anti-tumor drug. Shark liver oil contains 40% or more of squalene. Fish liver oil is also rich in squalene and polyunsaturated n-3 fatty acids. The aim of this work was to determine the anti-angiogenic and anti-tumor effects of these substances, together with another Scandinavian traditional remedy--arctic birch ashes--in Balb/c mice after transplantation of syngeneic L-1 sarcoma. All substances tested, alone or in combinations, significantly diminished cutaneous angiogenesis induced by tumor cells, and tumor growth.

Value of VLCD supplementation with medium chain triglycerides.

BACKGROUND: Medium chain triglycerides (MCT) are energetically less dense, highly ketogenic, and more easily oxidised than long chain triglycerides (LCT). MCT also differ from LCT in their digestive and metabolic pathways. OBJECTIVE: To test the effects of MCT supplementation during a very low calorie diet (VLCD). SUBJECTS AND METHODS: Three groups of tightly matched obese women with body mass index (BMI)>30 kg/m(2) received an isoenergetic (578.5 kcal) VLCD (Adinax, Novo Vital, Sweden) enriched with MCT or LCT (8.0 and 9.9 g/100 g Adinax respectively) or a low-fat (3 g/100 g) and high-carbohydrate regimen. The diets were administered over 4 weeks. Body composition was measured with DEXA and appetite/satiety-according to Blundell. Beta hydroxybutyric acid concentration in plasma and nitrogen excretion in urine was measured during consecutive days of VLCD. The study was performed in a randomised double-blind manner. RESULTS: The MCT group showed a significantly greater decrease in body weight during the first 2 weeks. The contribution of body fat to the total weight loss was higher while the contribution of fat-free mass (FFM) was lower. The MCT group had a higher concentration of ketone bodies in plasma and a lower nitrogen excretion in urine. Hunger feelings were less intense while satiety was higher. These differences were observed during the first 2 weeks of treatment and gradually declined during the third and fourth weeks. CONCLUSIONS: Replacement of LCT by MCT in the VLCD increased the rate of decrease of body fat and body weight and has a sparing effect on FFM. The intensity of hunger feelings was lower and paralleled the higher increase of ketone bodies. These effects gradually declined, indicating subsequent metabolic adaptation. Further studies are required to confirm the protein-sparing and appetite-suppressing effects of MCT supplementation during the first 2 weeks of VLCD treatment.

The synergistic effect of lactic acid bacteria and alkylglycerols on humoral immunity in mice.

Investigations on immune suppression and reconstitution of immune functions dependent on the presence of physiological microflora allow us to conclude that symbiotic microorganisms such as Lactobacillus sp. are essential for adequate activity of the defense system in humans. In addition to their beneficial influence on the intestinal microbial balance, these microorganisms exert a variety of immunomodulatory effects on the host immune system. On the other hand, immunostimulatory animal-derived substances rich in alkylglycerols have been shown to enhance lactic acid bacteria proliferation. Therefore, the aim of the present study was to evaluate the effects on murine humoral response of the combined administration of lyophilized combination of three lactic acid bacteria: L. acidophilus, L. bulgaricus and Bifidobacterium bifidum together with alkylglycerol-rich shark liver oil. The lactic acid bacteria mixture induced markedly stronger enhancement of the humoral response than alkylglycerols did. A significant synergistic stimulatory effect of lactic acid bacteria and alkylglycerols was observed in both treatment schedules: post- as well as in preimmunization with sheep red blood cells. However, their concomitant administration exerted stronger immunomodulatory effect than did the alternative route of treatment.

Thyroid hormones and treatment of obesity.

Thyroid hormones have important thermogenic function. Nevertheless, thyroid dysfunctions are often associated with minor changes in body weight and fat mass. On the other hand, both overfeeding and fasting have important effects on iodothyronine metabolism and regulation of deiodinase activity. Although under debate, there are clinical and theoretical reasons to administer low-dose thyroid hormones (T3) in selected obese patients. This short review deals with both pathophysiological and clinical aspects of thyroid hormone used in the therapy of obesity.

Loss of total body potassium during rapid weight loss does not depend on the decrease of potassium concentration in muscles. Different methods to evaluate body composition during a low energy diet.

OBJECTIVE: The aim of the study was to elucidate whether combustion of skeletal muscle glycogen during a very low calorie diet (VLCD) was associated with decreased muscle potassium content. A comparison between different methods was also performed to evaluate body composition during a VLCD and a low calorie diet (LCD). DESIGN: Dietary treatment of obese women by VLCD and LCD. Measurements after 1 and 2 weeks of VLCD and 6 months of LCD. SUBJECTS: Fifteen perimenopausal obese women aged 46.5+/-1.3 y and 15 of 48.0+/-0.7 y of age. MEASUREMENTS: Skeletal muscle biopsies under local anaesthesia. Body composition measurements by means of deal-energy X-ray absorptiometry (DEXA), and measurements of total body potassium (40K) and total body nitrogen (TBN). Measurements of electrolytes and glycogen concentration in muscle samples. RESULTS: In the first study (1 week of VLCD) skeletal muscle glycogen decreased (P<0.01), but muscle potassium increased (P<0.01). Muscle sodium decreased (P<0.01), while muscle magnesium was unaltered. Body weight decreased by 2.9+/-0.5 kg and 40K decreased. Fat-free mass (FFM) calculated from 40K and DEXA decreased by 2.7 vs 1.9 kg (P<0.001). Body fat measured with DEXA decreased by 1.1 kg (P<0.01), but not body fat calculated from 40K. TBN decreased by 0.03+/-0.01 kg (P<0.05) and FFM calculated from TBN by 2.9+/-0.5 kg (P<0.002). In the second study, 6 months on the LCD resulted in 17.0+/-2.0 kg weight reduction and this was mainly due to reduced body fat, 14. 0+/-2.0 kg measured with DEXA and from 40K (P<0.001). The decrease in FFM was slight. CONCLUSION: One week of VLCD resulted in muscle glycogen depletion but increased muscle potassium content in spite of decreased total body potassium. FFM contributed to the main part of body weight loss during short periods of severe energy restriction, but remained unchanged during long-term dietary treatment. Body fat became mostly responsible for the body weight loss during long-term LCD. Calculations of changes of FFM from 40K and TBN seem to overestimate the FFM decrease associated with short-term VLCD. International Journal of Obesity (2000)24, 101-107

Inhibitory effect of shark liver oil on cutaneous angiogenesis induced in Balb/c mice by syngeneic sarcoma L-1, human urinary bladder and human kidney tumour cells.

The effect of shark liver oil on cutaneous angiogenesis induced in mice by intradermal grafting of tumour cells was evaluated. It was shown that this substance (Ecomer) suppressed neovascular response in mice grafted with sarcoma L-1 syngeneic cells, human kidney cancer and human urinary bladder cancer cells. In addition, strong stimulatory effect of this drug on mice blood granulocyte number and their metabolic activity was observed.

Upper motor neuron lesions: their effect on muscle performance and appearance in stroke patients with minor motor impairment.

OBJECTIVE: To evaluate muscular performance and appearance in patients with prior stroke who were ambulatory. DESIGN: Nonrandomized study. SETTING: University hospital laboratory. SUBJECTS: Sixteen persons (11 men, 5 women) with minor motor impairments, 6 to 24 months after stroke, were included. As reference, data were used from a population-based sample of 144 men and women. MAIN OUTCOME MEASUREMENTS: Muscle performance was evaluated using a Kin-Com dynamometer in both the affected and the nonaffected leg. Peak isometric strength was measured at a 60 degree angle in both extension and flexion. Maximal isokinetic strength was measured at 60 degrees/sec and at 180 degrees/sec. Endurance was evaluated during isometric and dynamic knee extensions. Muscle biopsies were taken on nine patients and muscle tissue areas were determined with computed tomography. RESULTS: The affected leg was weaker but not different in relative endurance compared with the nonaffected side. The performance of the nonaffected side was somewhat lower than that of a matched reference population. No major difference in fiber composition between the affected and nonaffected legs was noted, except for a lower degree of capillarization in the affected leg. CONCLUSION: In well-functioning stroke patients with good motor performance, further muscle training that includes resistance exercise might be indicated.

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome.

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity.

High blood pressure and muscle morphology/metabolism--causal relationship or only associated factors?

As muscle tissue constitutes a main target organ for glucose metabolism and is responsible for the development of insulin resistance, it seems plausible to elucidate the relationship between blood pressure and muscle morphology and metabolism. The association between blood pressure and capillarization/morphology of the vastus lateralis muscle and metabolic variables was evaluated in 24 perimenopausal obese women [body mass index (BMI) 34.9 +/- 1.1; waist-hip ratio (WHR) 0.90 +/- 0.02]. The muscle enzyme activity of lipoprotein lipase (LPL), citrate synthase and glycogen synthase was determined. There was a significant negative correlation between the percentage of type I fibres and relative fibre area of type I on the one hand and systolic and diastolic blood pressure on the other. There was a negative correlation between the capillary density (i.e. number of capillaries/muscle fibre) and a positive correlation between the diffusion distance (fibre area supplied by one capillary) and diastolic blood pressure. The activities of LPL and citrate synthase were positively correlated with the percentage of type I and negatively correlated with the percentage of type II muscle fibres. The activity of LPL was also negatively correlated with plasma glucose and the insulin/C-peptide ratio. The insulin/C-peptide ratio was positively correlated with the percentage of type II muscle fibres. In stepwise multiple regression analyses, 20-30% of the variation in systolic and diastolic blood pressure could be explained by the variables of muscle fibre distribution. Excluding muscle morphological variables from the regression model, the insulin/C-peptide ratio accounted for 13% of the variation in systolic and diastolic blood pressure. The results of the study show the close association between muscle morphology and blood pressure. It remains to be elucidated whether this association indicates a causal relationship.

Small doses of triiodothyronine can change some risk factors associated with abdominal obesity.

OBJECTIVE: To elucidate whether the administration of small doses of triidothyronine (T3) can increase concentrations of sex hormone binding globulin (SHBG) in obese women with different types of obesity and to evaluate the potential metabolic benefits of such treatment. DESIGN: Daily administration of 20 micrograms of T3 during six weeks while maintaining habitual food intake and physical activity. SUBJECTS: Seventy premenopausal obese women (age: 41.2 +/- 1.5 y mean +/- s.e.m., body mass index (BMI): 34.4 +/- 0.7). MEASUREMENTS: Plasma concentrations of SHBG, lipids, insulin, thyroid hormones, sex hormones, blood glucose and insulin sensitivity (by euglycemic insulin clamp in 12 patients) at base line after six weeks of treatment. RESULTS: Six weeks treatment with small doses of T3 resulted in a significant increase in plasma SHBG. The increase of SHBG was higher in abdominal obesity and not associated with a significant change in body weight, plasma insulin concentration, insulin/glucose ratio of plasma insulin sensitivity (glucose disposal during insulin clamp). In patients with initially high SHBG the significant increase of insulin removal (as judged from the increase of c-peptide/insulin ratio) was observed. Treatment resulted in a reciprocal increase of T3, decrease of thyroxine (T4), and a more than double increase of T3/T4 ratio. CONCLUSIONS: Administration of small doses of T3 can increase the concentration of SHBG without changing insulin concentrations or sensitivity. As there was a significant decrease (by 36%) of T4 and parallel increase of T3 with a clear increase of T3/T4 ratio it seems possible that rather than lack of thyroid hormones a lower peripheral deiodination of T4 might be a factor contributing to the low SHBG concentration in abdominal obesity. Treatment with small doses of T3 may be considered to ameliorate some of the risk factors associated with abdominal obesity, particularly in some subgroups of obese women with a relative resistance to thyroid hormones possibly dependent on decreased peripheral deiodination of thyroxine.

Lipid peroxides production after strenuous exercise and in relation to muscle morphology and capillarization.

The antioxidative capacity of slow twitch muscle fibers has been reported to be higher than that of fast twitch ones. The purpose of this study was to relate the production of lipid peroxides during exercise to the morphology and capillarization of human muscles. Twenty-seven healthy volunteers performed a strenuous 90-min exercise. The content of malonyldialdehyde (MDA) in the middle portion of vastus lateralis muscle was found positively correlated with percentage and the relative cross-sectional area of the type 1 of muscle fibers (r = 0.46, P < 0.05, r = 0.43, P < 0.05, respectively) but negatively with type II muscle fibers (r = -0.46, P < 0.05, r = -0.43, P < 0.05, respectively), especially type IIB. The content of MDA in the vastus lateralis muscle correlated positively with the number of capillaries around type II muscle fibers (r = 0.71, P < 0.001). It is suggested that the production of lipid peroxides parallels the exercise-induced increase of oxygen uptake in the muscle, being highest in more oxidative and better perfused, oxygen-consuming muscle fibers.

Phosphate supplementation prevents a decrease of triiodothyronine and increases resting metabolic rate during low energy diet.

Thirty overweight women participated in 8 week slimming program consisting of a self-controlled low-energy diet (4.2 MJ/day) supplemented with highly viscous fibres and mineral tablets containing calcium, potassium and sodium phosphates (Redusan Combi, Biokraft Pharma AB, Sweden). Half of the patients received in double blind manner mineral tablets during first 4 weeks and placebo (without phosphates) during next 4 weeks (group 1) while the remaining patients were treated (cross-over) with placebo first and mineral tablets in the final period (group 2). The rate of weight loss was similar in groups 1 and 2 (4.7 vs 5.2 kg during the first 4 weeks and 2.7 vs 3.0 kg in the further 4 weeks). During periods of phosphate supplementation, the resting metabolic rate (RMR) increased by approx. 12% (p < 0.05) in group 1 and 19% (p < 0.05) in group 2. Phosphate supplementation ameliorated also a decrease in plasma triiodothyronine level and a decrease in thyroxine to triiodothyronine ratio. There were no differences between groups in the plasma insulin, catecholamine, growth hormone, cortisol and testosterone levels. Phosphate supplementation did not affect plasma lipids or blood glucose concentration. It is concluded that phosphate supplementation in obese patients on a low-energy diet enhances RMR irrespectively of the rate of weight loss. This effect seems to be, at least partly, due to an influence of phosphates on peripheral metabolism of thyroid hormones.

The concentrations of monoamine metabolites and neuropeptides in the cerebrospinal fluid of obese women with different body fat distribution.

DESIGN AND SUBJECTS: Several studies suggest neuroendocrine abnormalities in, particularly, abdominal, central obesity in humans, a condition with high morbidity and mortality. Therefore the concentrations of neuropeptides and catecholamines in cerebrospinal fluid (CSF) were analysed in 48 obese women, subdivided into groups with central, abdominal and gluteo-femoral distribution of body fat, utilising the waist-to-hip circumference ratio (WHR) for division. RESULTS: In comparisons with non-obese control women concentration of 5-hydroxyindol acetic acid (5-HIAA), methoxyhydroxyphenylglycol (MHPG), corticotropin releasing hormone (CRH), beta-endorphins (END) and neuropeptide Y (NPY) were lower, while homovanillic acid (HVA) was not different in obese women, HIAA, HVA and END correlated negatively with the WHR only in abdominally obese women, suggesting a threshold effect. HIAA vs HVA as well as CRF vs END correlated strongly in the total and both subgroups. An interrelationship between all these four substances was found in abdominal but not in gluteo-femoral obesity, suggesting a tighter functional coupling in the former group. Several correlations were found between CSF substance levels and appetite registrations, including END vs voracious eating, and for carbohydrate craving vs HIAA and vs HVA (negatively). This was also found only in abdominally obese women. CONCLUSION: Although the concentrations of monoamine metabolites and neuropeptides in the CSF sampled at the level of the lumber spine might not be representative for those at regulatory centers in the brain, the findings suggest that low 5-HIAA is characteristic of human obesity, and coupled to CRH as well as eating abnormalities, particularly in abdominal obesity. Since CRH is regulating the balance between the autonomic nervous systems, insulin secretion and thermogenesis in animals, corresponding anomalies in abdominal obesity in humans may have a central origin.

Effects on muscle of dieting with or without exercise in overweight postmenopausal women.

The main aim of this study was to investigate the effect of an energy-restrictive, high-protein diet with or without exercise on muscle morphology and biochemistry. Moderately overweight postmenopausal women (49-58 yr, body mass index: 25-42 kg/m2) were randomly assigned to three groups for 12 wk of intervention; namely, a control group, a group on a 4.2 MJ/day diet, and a group on 4.2 MJ/day diet combined with aerobic and anaerobic exercise. Muscle morphology and biochemistry analysis were performed in 69 and 58 women, respectively. In contrast to the diet-only group, the die-plus- exercise group significantly increased the muscle fiber areas by 20-25%, the number of capillaries per muscle fiber type I by approximately 20%, and the activities of citrate synthase by approximately 35% and hexokinase by approximately 20% (P < 0.05). There were no statistically significant changes in any other muscle variable (P < 0.05). The respiratory exchange ratio decreased in both intervention groups by 2-4% (P < 0.01). It is concluded that 12-wk period of an energy-restrictive high-protein diet was not associated with major changes in muscle morphology or biochemistry. The addition of exercise to the die led to an adaptive increase in muscle fiber areas and in the oxidative capacity of the muscles.

Role of muscle morphology in the development of insulin resistance and metabolic syndrome.

Type IIB muscle fibres are among the most insulin-insensitive muscle fibres and are not adapted to oxidation of fat during muscle work. The first characteristic of this type of muscle fibre most probably reflects or contributes to further development of insulin resistance contribute to further perpetuation of obesity and to the channeling of excess free fatty acids to the liver followed by secondary deterioration of its function. The impaired functioning of the liver is epitomized, among other changes, by impairment of insulin extraction. The increasing hyperinsulinaemia is followed by inhibition of synthesis of specific proteins such as carrier proteins for transporting testosterone (sex hormone binding globulin, SHBG). This results in an increased free testosterone concentration which induces androgenization in women and may further increase insulin insensitivity in abdominal obesity in women. The poor capillarization and changed muscle morphology in spite of great interindividual variety is observed in several pathological conditions characterised by insulin sensitivity (stroke, PCO, hypertension, diabetes, obesity). It is suggested that, in addition to the previous concept of the main role of intraabdominal adipose tissue, even muscles and liver are also important organs contributing to the pathogenesis and development of the metabolic syndrome.

Muscle fiber composition and capillary density in women and men with NIDDM.

OBJECTIVE: To determine whether muscle fiber composition and capillary density differed between diabetic and nondiabetic subjects. RESEARCH DESIGN AND METHODS: Muscle fiber composition and capillary density were determined in biopsies from women and men with non-insulin-dependent diabetes mellitus (NIDDM) and compared with those of control subjects matched for gender, age, obesity, and the waist-to-hip ratio, which are all factors known to influence muscle morphology. RESULTS: Patients with NIDDM, as well as control subjects with abdominal obesity and insulin resistance, showed the same abnormalities in muscle morphology, namely, a low percentage of type I fibers, elevated type II (particularly type IIB) fibers, and a low capillary density. These changes correlated closely with insulin concentrations in both diabetic and nondiabetic groups. CONCLUSIONS: Recent information suggests that insulin may regulate myosin synthesis in muscle in the direction of the changes observed. Therefore, it is possible that muscle fiber composition abnormalities in insulin-resistant conditions are secondary to hyperinsulinemia. However, the low capillary density, hypothetically, may contribute to insulin resistance.