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I Klimes

Publications and source records attributed to I Klimes.

At least 19 recordsLinked to original sources
PubMed2006

Insulin sensitivity indices: a proposal of cut-off points for simple identification of insulin-resistant subjects.

Demanding measurement of insulin sensitivity using clamp methods does not simplify the identification of insulin resistant subjects in the general population. Other approaches such as fasting- or oral glucose tolerance test-derived insulin sensitivity indices were proposed and validated with the euglycemic clamp. Nevertheless, a lack of reference values for these indices prevents their wider use in epidemiological studies and clinical practice. The aim of our study was therefore to define the cut-off points of insulin resistance indices as well as the ranges of the most frequently obtained values for selected indices. A standard 75 g oral glucose tolerance test was carried out in 1156 subjects from a Caucasian rural population with no previous evidence of diabetes or other dysglycemias. Insulin resistance/sensitivity indices (HOMA-IR, HOMA-IR2, ISI Cederholm, and ISI Matsuda) were calculated. The 75th percentile value as the cut-off point to define IR corresponded with a HOMA-IR of 2.29, a HOMA-IR2 of 1.21, a 25th percentile for ISI Cederholm, and ISI Matsuda of 57 and 5.0, respectively. For the first time, the cut-off points for selected indices and their most frequently obtained values were established for groups of subjects as defined by glucose homeostasis and BMI. Thus, insulin-resistant subjects can be identified using this simple approach.

Adolescent↗
PubMed2006

Multiple organochlorine pollution and the thyroid.

OBJECTIVE: Although the biological effects of major persistent organochlorinated pollutants (POPs) appear to be essentially similar, some effects which would be specific for certain substance cannot be excluded. We attempted to study the thyroid volume and thyrotropin level in the population living in the area with multiple pollution by polychlorinated biphenyls (PCBs) and pesticides (DDE and hexachlorobenzene - HCB). METHODS: A total of 454 adults was examined within the pilot field survey in 1998. Among them were 237 males (age range 19-78 years, median 47) and 227 females (age range 19-78 years, median 48). Fifteen environmentally prevalent congeners of polychlorinated biphenyls and also p,p-DDE (2,2-bis(4-chlorophenyl)-1,1-dichloroethylene), p,p-DDT (2,2-bis(4-chlorophenyl)- 1,1,1-trichloro-ethane), hexachlorobenzene (HCB) as well as alpha-, beta- and gamma-hexachlorocyclohexane (HCH) were determined in serum by high resolution gas chromatography using microelectron capture detector and microcapillary column. Thyroid volume (ThV) was measured by real time sonography using the ellipsoid method with the aid of sonographic instrument Sonoline SI-400 (Siemens, Germany). The level of TSH was estimated by supersensitive immunoradiometric method using commercial kits by Immunotech (Marseille, France). Pearsons correlation coefficients after logarithmic transformation of values and Spearmans correlation coefficients were used for statistical evaluation. RESULTS: Significant positive association (p<0.01) was found between DDE and PCB, DDE and HCB, while that between PCB and HCB was not significant. Similar positive association (p<0.01) was also found between each individual organochlorine and their sum. Significant negative association (p<0.01) was found between ThV and TSH. When using categorical PCB values either >2000 (N=208) or >3000 (N=127) ng/g lipid, significant positive association (p<0.05 and p<0.01, respectively) was found between the sum of all organochlorines (PCB+DDE+HCB) and ThV, while that between PCB and ThV (p<0.01) was found only at the PCB levels >3000 ng/g lipid. When using Spearmans correlation coefficients, significant negative association appeared between PCB and TSH (p<0.05), sum of organochlorines and TSH (p<0.05) and ThV and TSH (p<0.01). CONCLUSIONS: Although several significant positive and negative associations were found, this study, like several others, could not exactly define the participation level of individual POPs in their common toxic effects, but possibly contributed to the recognition and elucidation of some problems related to this task.

Adult↗
PubMed2005

Human thyroid in the population exposed to high environmental pollution by organochlorinated pollutants for several decades.

OBJECTIVE: To study possible effects of long-time exposure of chemical factory employees and population of surrounding polluted area to polychlorinated biphenyls and pesticides on the thyroid volume and function as compared to the population from the area of background pollution. METHODS: A total of 461 adults consisting of 239 men and 222 women was examined and divided into four groups according to their permanent domicile as related to the level of environmental pollution, e.g. SR (area of background pollution, n = 207), SI (slightly polluted area, n = 59), MI (polluted city of Michalovce, n = 94) and CH (employees of chemical factory subjected to high PCB exposure, n = 101), combined first three groups being also called LPA (less polluted areas, n = 360). Thyroid volume (ThV) and echogenicity were measured by real time sonography. The level of polychlorinated biphenyls (PCB) and pesticides (hexachlorbenzene--HCB, DDE (2,2'-2-bis(4-chlorobiphenyl)- 1,1-dichloroethylene), p,p'-DDT (2,2'-bis(4-chlorophenyl)- 1,1,1-trichloroethane) and alpha-, beta- and gamma-hexachlorcyclohexane--HCH) was estimated by congener specific analysis using HP 5890 gas chromatograph with a 63Ni electron capture detector. Serum levels of thyrotropin (TSH) and thyroid peroxidase antibodies (anti-TPO) were measured by specific sensitive immunoassays. RESULTS: The association of very high PCB level (e.g. 7300 +/- 871 ng/g lipid; mean +/- S.E.) with increased ThV (e.g. 16.3 +/- 0.73 ml) in CH has been found, the values being significantly higher than these of 360 subjects in LPA (e.g. 2045 +/- 147 ng/g, p < 0.001 for PCB and 14.0 +/- 0.32 ml, p < 0.001 for ThV). In 23 subjects from CH with PCB level > 10000 ng/g the ThV was 18.7 +/- 2.32 ml, while that in 251 subjects from LPA with PCB level of < 2000 ng/g was 13.8 +/- 0.35 ml (p < 0.05). In addition, ThV as well as PCB levels were strikingly increasing with age. In parallel with PCB levels, also the levels of other organochlorines estimated (namely these of DDE) were increasing. Although the participation of these substances in the development of adverse effects cannot yet be defined, it cannot be excluded. The association of increased levels of episodic congener PCB 101 with increased ThV appeared to be more pronounced than that of stable congeners PCB 153 and 180. Finally, significant increase in the frequency of thyroid hypoechogenicity by ultrasound, ThV > 20.0 ml and thyroperoxidase antibodies in CH area was observed as compared to LPA. CONCLUSIONS: Several associations of high PCB and pesticides level with characteristics of thyroid disorders (e.g. increased thyroid volume, frequency of hypoechogenicity and frequency of positive thyroperoxidase antibodies level in blood) were observed in the area with heavy industrial pollution by PCB.

Adult↗
PubMed2004

Mapping of genetic determinants of the sympathoneural response to stress.

Activation of the sympathoadrenal system (SAS, comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defense mechanism as well as a contributor to several cardiovascular diseases. There is variability in the SAS response to stress, although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hypertriglyceridemic (hHTg) rat, are hyperresponsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats (n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma norepinephrine (NE) and epinephrine (Epi) levels, indices of activation of the sympathoneural and adrenal medulla components, respectively, measured in the resting state and in response to an immobilization stress. Responses were assessed early (20 min) and late (120 min) after the application of the stress. A genome scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak LOD scores of 4.17 and 3.52, respectively) influencing both the early and late plasma NE response to stress were found on chromosome 10. Together, the QTLs accounted for approximately 20% of the total variation in both the early and late NE responses in the F(2) rats. Interestingly, the QTLs had no effect on plasma Epi response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the SAS response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases.

Animals↗
PubMed2004

Impact of a general practice based group parenting programme: quantitative and qualitative results from a controlled trial at 12 months.

AIMS: To test the effectiveness at one year of the Webster Stratton Parents and Children Series group parenting programme in a population sample of parents. METHODS: In a multicentre block randomised controlled trial, parents of children aged 2-8 years in 116 families who scored in the upper 50% on a validated behaviour inventory, took part in Webster-Stratton's 10 week parenting programme led by trained and supervised health visitors. The following outcome measures were used: Eyberg Child Behaviour Inventory, Goodman Strengths and Difficulties Questionnaire, General Health Questionnaire, Parenting Stress Index, Rosenberg Self Esteem Scale. RESULTS: The intervention significantly reduced child behaviour problems and improved mental health at immediate and 6 month follow ups. One year differences between control and intervention groups were not significant. Qualitative results suggest that these findings might be attributable in part to either Hawthorne effects or contamination of control group. At interview parents described ways in which the programme had improved their mental health. They reported gains in confidence and feeling less stressed. Some also reported beneficial changes in their own and their children's behaviour and improved relationships with their children. Some spoke of a need for further sessions to support the behaviour changes they had managed to make, and some the desire for attendance by both parents. CONCLUSIONS: Parenting programmes have the potential to promote mental health and reduce social inequalities, but further work is needed to improve long term effectiveness.

Child↗
PubMed2003

Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome.

AIMS/HYPOTHESIS: Hypertriglyceridaemia is an important risk factor for coronary heart disease, especially in the context of the insulin resistance syndrome where it often occurs with hypertension. The two phenotypes are also associated in the hereditary hypertriglyceridaemic (hHTg) rat. The aim of this study was to map quantitative trait loci that affect plasma triglyceride concentration in the hHTg rat and determine whether they co-localize with loci for blood pressure. METHODS: Second filial generation progeny (n=189) from a cross of the hHTg rat with the Brown Norway rat were phenotyped for fasting plasma triglyceride, glucose and insulin concentrations, and direct unrestrained resting blood pressure. A partial genome-scan was conducted using 153 microsatellite markers that were polymorphic between the two strains. RESULTS: A major locus (lod score 6.5) influencing plasma triglyceride concentration in a co-dominant fashion was mapped to chromosome 4 between D1Mit 5 and D1Mit17. Chromosome 8 contained multiple peaks with a lod score greater than 4.0 influencing triglyceride concentration. Importantly, none of the triglyceride loci had an effect on blood pressure. The triglyceride locus on chromosome 4 co-localized with a locus for fasting plasma insulin (lod score 4.1), although the effect on insulin concentration was in the opposite direction to that on triglyceride. CONCLUSION/INTERPRETATION: We have mapped the major loci that affect plasma triglyceride concentration in the hHTg rat. These loci do not influence blood pressure suggesting that these commonly associated phenotypes of the insulin resistance syndrome are not be due to pleiotropic effects of the same gene(s).

Animals↗
PubMed2003

The hypotriglyceridemic effect of dietary n-3 FA is associated with increased beta-oxidation and reduced leptin expression.

To study the mechanisms responsible for the hypotriglyceridemic effect of marine oils, we monitored the effects of high dietary intake of n-3 PUFA on hepatic and muscular beta-oxidation, plasma leptin concentration, leptin receptor gene expression, and in vivo insulin action. Two groups of male Wistar rats were fed either a high-fat diet [28% (w/w) of saturated fat] or a high-fat diet containing 10% n-3 PUFA and 18% saturated fat for 3 wk. The hypotriglyceridemic effect of n-3 PUFA was accompanied by increased hepatic oxidation of palmitoyl-CoA (125%, P < 0.005) and palmitoyl-L-carnitine (480%, P < 0.005). These findings were corroborated by raised carnitine palmitoyltransferase-2 activity (154%, P < 0.001) and mRNA levels (91%, P < 0.01) as well as by simultaneous elevation of hepatic peroxisomal acyl-CoA oxidase activity (144%, P < 0.01) and mRNA content (82%, P < 0.05). In contrast, hepatic carnitine palmitoyltransferase-1 activity remained unchanged despite a twofold increased mRNA level after n-3 PUFA feeding. Skeletal muscle FA oxidation was less affected by dietary n-3 PUFA, and the stimulatory effect was found only in peroxisomes. Dietary intake of n-3 PUFA was followed by increased acyl-CoA oxidase activity (48%, P < 0.05) and mRNA level (83%, P < 0.05) in skeletal muscle. The increased FA oxidation after n-3 PUFA supplementation of the high-fat diet was accompanied by lower plasma leptin concentration (-38%, P < 0.05) and leptin mRNA expression (-66%, P < 0.05) in retroperitoneal adipose tissue, and elevated hepatic mRNA level for the leptin receptor Ob-Ra (140%, P < 0.05). Supplementation of the high-fat diet with n-3 PUFA enhanced in vivo insulin sensitivity, as shown by normalization of the glucose infusion rate during euglycemic hyperinsulinemic clamp. Our results indicate that the hypotriglyceridemic effect of dietary n-3 PUFA is associated with stimulation of FA oxidation in the liver and to a smaller extent in skeletal muscle. This may ameliorate dyslipidemia, tissue lipid accumulation, and insulin action, in spite of decreased plasma leptin level and leptin mRNA in adipose tissue.

Animals↗
PubMed2003

Iodine deficiency in vegetarians and vegans.

Iodine content in food of plant origin is lower in comparison with that of animal origin due to a low iodine concentration in soil. Urinary iodine excretion was assessed in 15 vegans, 31 lacto- and lacto-ovovegetarians and 35 adults on a mixed diet. Iodine excretion was significantly lower in alternative nutrition groups - 172 microg/l in vegetarians and 78 microg/l in vegans compared to 216 microg/l in subjects on a mixed diet. One fourth of the vegetarians and 80% of the vegans suffer from iodine deficiency (iodine excretion value below 100 microg/l) compared to 9% in the persons on a mixed nutrition. The results show that under conditions of alternative nutrition, there is a higher prevalence of iodine deficiency, which might be a consequence of exclusive or prevailing consumption of food of plant origin, no intake of fish and other sea products, as well as reduced iodine intake in the form of sea salt.

Adult↗
PubMed2003

From naturally occurring goitrogens to the effects of anthropogenic endocrine disruptors on the thyroid in Slovakia.

The objective is to describe the effect of mandatory and well monitored prophylaxis of endemic goitre in Slovakia with the use of iodised salt for past 50 years and previous experimental attempts to assess a possible participation of naturally occurring goitrogens in the etiology of goitre. Previous observations by others showed a striking decrease of goitre prevalence in schoolchildren as early as few years after starting the prophylaxis in Slovakia and this success has been confirmed by a European study conducted by others in mid nineties. In the meantime, however, massive industrialisation of Slovakia and environmental negligence of the administration resulted in heavy airborne and mainly waterborne pollution of the food chain in certain areas around large chemical factories by industrial waste including polychlorinated biphenyls (PCB). Since Slovakia has been recently evaluated as an iodine replete country as based on the findings of the low thyroid volume by ultrasound and high urinary iodine, it became possible to evaluate the participation of factors different from iodine deficiency in the thyroid growth. Recent field surveys including an extensive international study PCBRISK repeatedly showed highly increased blood PCB level in subjects living in the polluted area and, at the same time, increased thyroid volume by ultrasound, increased frequency of positive thyroid antibodies and impaired glucose tolerance. (Ref. 59)

Child↗
PubMed2003

Thyroid function and cholesterol level: paradoxical findings in large groups of population with high cholesterol food intake.

OBJECTIVE: To compare the levels of serum cholesterol with thyroid function as estimated by the level of thyrotropin and free thyroxine with possible participation of thyroperoxidase antibodies in large number of adults examined within large field surveys focused on the evaluation of thyroid status of Slovak rural population. SUBJECTS AND METHODS: Serum level of cholesterol and thyrotropin (TSH) was estimated in a total of 2786 adults. In addition, in 2038 of them also the level of free thyroxine (FT4), total triiodothyronine (TT3), cholesterol, triglycerides and phospholipids was measured. The levels of TSH, anti-TPO and FT4 were estimated by supersensitive electrochemiluminiscent immunoassay using the automatic system Elecsys (Roche, Switzerland). RESULTS: A total of 2786 adults was stratified into 7 groups according to the range of TSH level as related to generally recognized level of thyroid function, e.g. 1. TSH <0.10 mU/L (overt hyperthyroidism, N=41), 2. TSH 0.11-0.30 mU/L (overt or subclinical hyperthyroidism, N=149), 3. TSH 0.31-2.50 mU/L (normal level, N=1750), 4. TSH 2.51-4.50 ("high normal" level, N=607), 5 TSH 4.51-6.50 (mild or incipient subclinical hypothyroidism, N=137), 6. TSH 6.51-10.00 mU/L (mild hypothyroidism, N=50), 7. TSH 10.01-99.00 mU/L (severe hypothyroidism, N=53). The average levels of cholesterol in all groups were very similar ranging from 5.53 to 6.17 mmol/L and no interrelations with TSH level were found. In addition, no considerable differences between these groups were found when considering the levels of medians, upper quartiles and 90th percentiles of individual groups. When male and female subjects were divided into age groups according to the decades, an age dependent increase of cholesterol level was found in both sexes. The fraction of 2038 subjects was divided into the same TSH related groups as defined above. Similarly as above, no considerable differences in cholesterol, triglycerides and phospholipids level were observed. However, the levels of FT4 and TT3 were significantly decreasing with the increase of TSH level which confirmed the continuing decrease of thyroid function. The frequency of positive anti-TPO in subjects with TSH >6.5 mU/l (71/86 = 82.5%) was significantly higher than that in subjects with TSH <6.5 mU/l (468/1952 = 23.9%). CONCLUSIONS: No difference in the level of cholesterol and triglycerides was found in large groups of rural adults from Slovakia with various thyroid function as estimated by the level of TSH, FT4, TT3 and anti-TPO. It is assumed that this interrelation resulted from very high cholesterol intake due to inappropriate general nutritional status of rural population resulting from the consumption of unhealthy foods.

Adult↗
PubMed2002

An increase in peroxisomal fatty acid oxidation is not sufficient to prevent tissue lipid accumulation in hHTg rats.

We observed earlier that increased skeletal muscle lipid content in the hereditary hypertriglyceridemic (hHTg) rat is accompanied by a decline in plasma leptin. Leptin has recently been shown to enhance peripheral insulin sensitivity by decreasing the tissue triglyceride accumulation, possibly through regulation of fatty acid oxidation and lipogenesis. Thus, to test the hypothesis that insulin resistance and increased skeletal muscle lipid accumulation in hHTg rats are due to a defect in lipid catabolism, we measured mitochondrial and peroxisomal fatty acid oxidation and malonyl-CoA and acetyl-CoA carboxylase-2 content in skeletal muscles of these animals. In addition, we investigated possible molecular mechanisms responsible for the lower leptin levels in hHTg rats by measuring leptin and leptin-receptor (Ob-Ra) mRNA levels. We found the following: (1) in spite of a higher skeletal muscle malonyl-CoA content and an increased sensitivity of carnitine palmitoyltransferase-1 to malonyl-CoA, carnitine palmitoyltransferase-1 activity in muscle of hHTg rats was normal; (2) increased peroxisomal fatty acid oxidation did not seem to be sufficient to prevent the tissue lipid accumulation in these animals; (3) both lower leptin production by white adipose tissue and increased leptin uptake seem to be responsible for lower circulating leptin levels and therefore lower fatty acid catabolism.

Animals↗
PubMed2002

Insulin resistance in the hereditary hypertriglyceridemic rat is associated with an impairment of delta-6 desaturase expression in liver.

Our previous studies have shown that insulin resistance (IR) in the hereditary hypertriglyceridemic (hHTg) rat is accompanied by a specific fatty acid (FA) profile in insulin target tissues, possibly due to a defect in the desaturation pathway. Increased dietary intake of n-3 polyunsaturated fatty acids (PUFAs) was shown to shape FA composition and to improve insulin sensitivity in this animal strain. Thus, the aim of this study is twofold: (1) to evaluate a defect in the FA desaturation by direct measurement of enzyme activity and gene expression for Delta-6 desaturase (Delta-6 D) in liver of hHTg rats and (2) to investigate the effect of dietary n-3 PUFAs on hepatic Delta-6 D in relation to tissue FA composition. Male Wistar or hHTg rats were fed ad libitum for 21 days either the basal or fish oil (FO)-supplemented diets. Triglyceride (Tg) levels in serum and tissue lipid extracts were measured with the aid of a commercially available enzymatic set. Hepatic activity of the Delta-6 D was determined radiometrically in a microsomal fraction using 1-(14)C-linoleic acid as a substrate. The Delta-6 D mRNA levels were measured using the Northern blot technique. Tissue FA composition was determined by gas chromatography in the total phospholipid fraction after TLC separation. Increased levels of Tg in hHTg rat circulation were accompanied by raised accumulation of Tg in skeletal muscles. FO feeding lowered the concentration of Tg in serum and prevented their accumulation in skeletal muscles of hHTg rats. A pronounced decrease in the hepatic Delta-6 D activity in hHTg rats (by about 80%) was not further diminished by FO feeding. On the other hand, the activity of Delta-6 D in liver of control rats was reduced by about 40% after FO supplementation. These changes were paralleled by a decrease in the Delta-6 D index as calculated from the liver phospholipid FA profile. In particular, an increase in the amount of 18:2 n-6 and a decrease in arachidonic acid and PUFA n-6 metabolites were found. The results indicate that a decrease of insulin action in hHTg rats is accompanied by an impairment of the hepatic Delta-6 D activity already at the gene level, which is not further affected by n-3 PUFA supplementation.

Animals↗
PubMed2002

Impaired endothelial function of thoracic aorta in hereditary hypertriglyceridemic rats.

OBJECTIVE: Hereditary hypertriglyceridemia (hHTG) in rats was found to be associated with metabolic abnormalities and elevation of blood pressure. There is controversy regarding the relation between hHTG and vascular function. The aim of this study was to determine the reactivity and accompanying structural changes in thoracic aorta from hereditary hypertriglyceridemic rats and hHTG rats that were given, for a long time, N(G)-nitro-l-arginine methyl ester (L-NAME) with and without simultaneous captopril treatment. METHODS: Isolated rings of thoracic aorta were mounted in organ chambers for isometric tension recording or for measurement of endothelium-dependent relaxation. Morphological changes of thoracic aorta (wall thickness, diameter) were measured using light microscopy. RESULTS: Endothelium-dependent relaxation (EDR) to acetylcholine (ACh, 10(-5) M) was significantly attenuated in the hHTG group compared to control Wistar rats (59.3 +/- 8.5% vs. 95.8 +/- 6.5%, p < 0.001), but normalized after pretreatment with captopril. EDR to ACh was further inhibited in hHTG rats treated with L-NAME (36.0 +/- 2.3%, p < 0.001). Maximum residual relaxation was only partly restored with captopril treatment (72.4 +/- 5.8%, p < 0.001). Hypertriglyceridemia did not significantly alter the sensitivity of the thoracic aorta to exogenous noradrenaline. The diameter/wall thickness (D/W) ratio in aortas of control Wistar rats averaged 16.25 +/- 0.57. This ratio was significantly lower in hHTG rats (12.52 +/- 0.38, p < 0.01) and was not altered after treatment with captopril. In the hHTG rats treated with L-NAME, the D/W ratio was further significantly decreased (8.25 +/- 0.30, p < 0.001). Simultaneous captopril treatment attenuated the decrement of this ratio (9.80 +/- 0.75, p < 0.05). CONCLUSIONS: Results showed that hHTG is accompanied by functional and morphological alterations in the rat thoracic aorta. These changes in hHTG and in hHTG rats treated with L-NAME could be, at least in part, protected by captopril treatment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Improving mental health through parenting programmes: block randomised controlled trial.

AIMS: To assess the effectiveness of a parenting programme, delivered by health visitors in primary care, in improving the mental health of children and their parents among a representative general practice population. METHODS: Parents of children aged 2-8 years who scored in the upper 50% on a behaviour inventory were randomised to the Webster-Stratton 10 week parenting programme delivered by trained health visitors, or no intervention. Main outcome measures were the Eyberg Child Behaviour Inventory and the Goodman Strengths and Difficulties Questionnaire to measure child behaviour, and the General Health Questionnaire, Abidin's Parenting Stress Index, and Rosenberg's Self Esteem Scale to measure parents' mental health. These outcomes were measured before and immediately after the intervention, and at six months follow up. RESULTS: The intervention was more effective at improving some aspects of the children's mental health, notably conduct problems, than the no intervention control condition. The Goodman conduct problem score was reduced at immediate and six month follow up, and the Eyberg Child Behaviour Inventory was reduced at six months. The intervention also had a short term impact on social dysfunction among parents. These benefits were seen among families with children scoring in the clinical range for behaviour problems and also among children scoring in the non-clinical (normal) range. CONCLUSION: This intervention could make a useful contribution to the prevention of child behaviour problems and to mental health promotion in primary care.

Child↗
PubMed2002

Comparison of the extrapancreatic action of gamma-linolenic acid and n-3 PUFAs in the high fat diet-induced insulin resistance [corrected].

OBJECTIVE: The effect of dietary borage oil (rich in the gamma-linolenic acid [GLA]) on insulin sensitivity and lipid metabolism was compared with that of fish oil (rich in n-3 polyunsaturated fatty acids [PUFAs]) in high fat (HF) diet-induced insulin resistance (IR) of rats. METHODS: Male Wistar rats were fed ad libitum for 3 weeks a standard laboratory chow (Controls) or high fat diet consisting of 70-cal % fat. In addition, a group of rats was fed high fat (HF) diet where a part of saturated fat was replaced with fish oil as a source of n-3 PUFAs (HF+FO), or borage oil as a source of GLA (HF+GLA). In vivo insulin action was assessed by the euglycemic hyperinsulinemic clamp. Glucose, insulin, free fatty acids (FFA), triglycerides (Tg) and glycerol levels in blood and tissue depots were also measured. RESULTS: Increased levels of Tg, FFA and glycerol in circulation after HF diet were accompanied by their raised accumulation in insulin sensitive tissues. FO feeding lowered the concentration of all lipids in serum and prevented their accumulation in both tissues. On the other hand GLA supplementation into the high fat diet did not suppress increased levels of Tg, FFA and glycerol in circulation and tissue depots as well. FO feeding significantly reduced HF diet-induced in vivo IR, while GLA supplementation did not improve the in vivo insulin sensitivity in HF diet induced insulin resistance. CONCLUSIONS: 1. Substitution of FO into the high fat diet led to an improvement of in vivo insulin action; 2. this insulin sensitizing effect of FO was accompanied by a decrease of circulating Tg, FFA and glycerol levels in the postprandial state and by a lower lipid content in liver and skeletal muscle. 3. on the opposite, GLA treatment failed to improve in vivo insulin action; and 4. was associated with an adverse effect on lipid levels both in circulation and tissue depots.

Animals↗
PubMed2002

Effect of losartan on the Na+/Ca2+ exchanger in left ventricle of the insulin resistant and hypertensive hHTg rat.

As the Na+/Ca2+ exchanger plays an important role in the regulation of myocyte contractility, it has been suggested that alterations in this system might be involved in the development of insulin resistance and/or diabetes-induced myocardial alterations. Moreover, gene expression and function of the Na+/Ca2+ exchanger in states of combined hypertension and insulin resistance is of a special interest. Thus, we used hereditary hypertriglyceridemic (hHTg) rat (a model of genetically induced insulin resistance and hypertension) to study the effect of losartan, the blocker of type 1 angiotensin receptors, on the Na+/Ca2+ exchanger in the rat heart. We found that gene expression, but not activity of the Na+/Ca2+ exchanger was decreased in the left ventricle of hHTg rats when compared to their normotensive mates. No changes were observed in the right ventricle. In addition, losartan decreased mRNA levels of the Na+/Ca2+ exchanger in the left, but not in the right ventricle of normotensive rats. In hHTg rats, losartan had no effect on the gene expression of this transporter. Our results point to different modulatory pathways of Na+/Ca2+ exchanger in normotensive and hHTg rats.

Animals↗
PubMed2001

Nutrient sensing, leptin and insulin action.

The glucose-fatty acid cycle as proposed four decades ago by Randle suggests that insulin resistance develops in consequence of alterations of the metabolic pressure of lipids. The more recently published 'hexosamine pathway theory' and the 'malonyl-CoA hypothesis' depict insulin resistance as a consequence of an imbalance between utilization of lipids and carbohydrates. The latter is finely tuned by entry of fatty acids into the mitochondria and/or by entry of glucose to the hexosamine pathway. A significant body of evidence has also been accumulated which points to the complex effects of leptin, an adipocyte-derived signal of lipid stores, on the storage and metabolism of fats and carbohydrates. These are mediated either directly, through actions on specific tissues, or indirectly, via CNS, endocrine and neural mechanisms. The available literature also provides good evidence that leptin orchestrates the metabolic changes in a number of organs and tissues, and alters nutrient fluxes to favor energy expenditure over energy storage. In this article, the proposed lipopenic effects of leptin as studied in various animal models of diet-induced insulin resistance, and possible regulations of leptin production and action by marine fish oil feeding are reviewed.

Animals↗