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Favourable Effects (favourable + effects)
Selected AbstractsEffects of insulin resistance on endothelial function: possible mechanisms and clinical implicationsDIABETES OBESITY & METABOLISM, Issue 10 2008D Tousoulis Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin,angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials. [source] Diabetes mellitus and alcoholDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2004Albert van de Wiel Abstract Alcohol influences glucose metabolism in several ways in diabetic patients as well as in non-diabetic patients. Since alcohol inhibits both gluconeogenesis and glycogenolysis, its acute intake without food may provoke hypoglycaemia, especially in cases of depleted glycogen stores and in combination with sulphonylurea. Consumed with a meal including carbohydrates, it is the preferred fuel, which may initially lead to somewhat higher blood glucose levels and hence an insulin response in type 2 diabetic patients. Depending on the nature of the carbohydrates in the meal, this may be followed by reactive hypoglycaemia. Moderate consumption of alcohol is associated with a reduced risk of atherosclerotic disorders. Diabetic patients benefit from this favourable effect as much as non-diabetic patients. Apart from effects on lipid metabolism, haemostatic balance and blood pressure, alcohol improves insulin sensitivity. This improvement of insulin sensitivity may also be responsible for the lower incidence of type 2 diabetes mellitus reported to be associated with light-to-moderate drinking. In case of moderate and sensible use, risks of disturbances in glycaemic control, weight and blood pressure are limited. Excessive intake of alcohol, however, may not only cause loss of metabolic control, but also annihilate the favourable effects on the cardiovascular system. Copyright © 2004 John Wiley & Sons, Ltd. [source] Could Bt transgenic crops have nutritionally favourable effects on resistant insects?ECOLOGY LETTERS, Issue 3 2003Ali H. Sayyed Abstract We present an idea that larvae of some Bacillus thuringiensis (Bt,) resistant populations of the diamondback moth, Plutella xylostella (L.), may be able to use Cry1Ac toxin derived from Bt as a supplementary food protein. Bt transgenic crops could therefore have unanticipated nutritionally favourable effects, increasing the fitness of resistant populations. This idea is discussed in the context of the evolution of resistance to Bt transgenic crops. [source] Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial stateEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2004A. Jellema Abstract Background, In obese subjects, chronic low-grade inflammation contributes to an increased risk of metabolic abnormalities, which are reversed by weight loss. Sustained weight loss, however, is difficult to achieve and more insight into dietary approaches on anti-inflammatory responses in obese subjects is needed. In this respect, fish oil deserves attention. Material and methods, Eleven obese men (BMI: 30,35 kg m,2) received daily fish oil (1·35 g n-3 fatty acids) or placebo capsules in random order for 6 weeks. Eight subjects continued with a weight reduction study that lasted 8 weeks. Mean weight loss was 9·4 kg. At the end of each experimental period a postprandial study was performed. Results, Relative to fasting concentrations, interleukin-6 (IL-6) levels increased by 75% 2 h and by 118% 4 h after the meal (P < 0·001), when subjects consumed the control capsules. In contrast, C-reactive protein (C-RP) concentrations decreased slightly by 0·7% and 6·6% (P = 0·046), and those of plasminogen activator inhibitor-1 (PAI-1) antigen by, respectively, 26% and 53% (P < 0·001). Tumour necrosis factor-, (TNF-,; P = 0·330) and soluble TNF-receptor concentrations (sTNF-R55 and sTNF-R75; P = 0·451 and P = 0·108, respectively) did not change. Changes relative to fasting concentrations were not significantly affected by either fish oil or weight reduction. Absolute IL-6, C-RP, sTNF-R55, sTNF-R75, and PAI-1 antigen concentrations, however, were consistently lower after weight reduction, but not after fish oil consumption. Conclusion, For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low-grade inflammatory state as weight reduction. [source] Effects of ,-aminoisobutyric acid on leptin production and lipid homeostasis: mechanisms and possible relevance for the prevention of obesityFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2010Karima Begriche Abstract ,-Aminoisobutyric acid (BAIBA) is a catabolite of thymine and antiretroviral thymine analogues AZT and d4T. We recently discovered that this ,-amino acid is able to enhance fatty acid oxidation and reduce body weight in mice through an increased production of leptin by the white adipose tissue (WAT). Furthermore, BAIBA could have favourable effects on nonalcoholic steatohepatitis in a leptin-independent manner. In the present review, we shall recall the circumstances that led us to discover the effects of BAIBA on body fat mass and lipid homeostasis. In addition, we put forward several hypothetical mechanisms whereby BAIBA could enhance leptin secretion by WAT and present some anti-inflammatory effects in the liver. We also discuss in this review (i) the deleterious impacts caused by the absence of, or low leptin expression on lipid homeostasis and body weight in humans and animals and (ii) recent data from other investigators suggesting that increasing leptin levels and/or responsiveness may be indeed an attractive pharmacological strategy in order to prevent (and/or treat) obesity, at least in some individuals. [source] Irbesartan has no short-term effect on insulin resistance in hypertensive patients with additional cardiometabolic risk factors (i-RESPOND)INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010K. G. Parhofer Summary Aims:, Intervention studies have shown that angiotensin receptor blockers (ARB) may reduce the incidence of type 2 diabetes mellitus. It is currently unclear whether short-term therapy with ARBs affects metabolic parameters. Methods:, i-RESPOND, a randomised, controlled, multicentre, double-blind study evaluated the effect of 16 weeks of irbesartan vs. hydrochlorothiazide (HCTZ) on insulin resistance as well as on lipid and inflammatory parameters in hypertensive subjects with metabolic syndrome. Patients received irbesartan (150 mg/d; n = 211) or HCTZ (12.5 mg/d; n = 215), titrated to 300 mg/day and 25 mg/day respectively. In a second part of the study (weeks 16,28), patients initially randomised to irbesartan received additional HCTZ and vice versa. Results:, At week 16 both irbesartan and HCTZ had no effect on insulin resistance measured by the Matzuda index and beta-cell function. Similarly, in the second part of the study (week 16,28) no differences between irbesartan and HCTZ with respect to glucose metabolism were observed. However, irbesartan induced beneficial changes in high-sensitivity-C-reactive protein (hs-CRP) (irbesartan: ,5.5 ± 5.2%; HCTZ + 19.9 ± 6.5%, p = 0.0024) and in urinary albumin/creatinine ratio (ACR) (irbesartan: ,13%; HCTZ + 9%; p = 0.0041) compared with HCTZ despite a similar decrease in blood pressure in both treatment groups. Irbesartan and HCTZ were well tolerated and adverse events were comparable. Conclusion:, Irbesartan did not show significant favourable effects on insulin resistance compared with HCTZ in this study; however, may have beneficial effects on inflammation and microalbuminuria in hypertensive patients with metabolic syndrome. [source] The use of coal fly ash in sodic soil reclamationLAND DEGRADATION AND DEVELOPMENT, Issue 3 2003D. Kumar Abstract An experiment was conducted for two years in northwest India to explore the feasibility of using coal fly ash for reclamation of waterlogged sodic soils and its resultant effects on plant growth in padi,wheat rotation. The initial pH, electrical conductivity, exchangeable sodium percentage and sodium adsorption ratio of the experimental soil were 9.07, 3.87,dS,m,1, 26.0 and 4.77 (me l),1/2, respectively. The fly ash obtained from electrostatic precipitators of thermal power plant had a pH of 5.89 and electrical conductivity of 0.88,dS,m,1. The treatments comprised of fly ash levels of 0.0, 1.5, 3.0, 4.5, 6.0 and 7.5 per cent, used alone as well as in combination with 100, 80, 60, 40, 20 and 10 per cent gypsum requirement of the soil, respectively. There was a slight reduction in soil pH while electrical conductivity of the soil decreased significantly with fly ash as measured after padi and wheat crops. The sodium adsorption ratio of the soil decreased with increasing fly ash levels, while gypsum treatments considerably added to its favourable effects. Fly ash application increased the available elemental status of N, K, Ca, Mg, S, Fe, Mn, B, Mo, Al, Pb, Ni, Co, but decreased Na, P and Zn in the soil. An application of fly ash to the soil also increased the concentrations of above elements except Na, P and Zn in the seeds and straw of padi and wheat crops. The available as well as elemental concentrations in the plants was maximum in the 0 per cent fly ash,+,100 per cent gypsum requirement treatment except Na and heavy elements like Ni, Co, Cr. The treatment effects were greater in the fly ash,+,gypsum requirement combinations as compared to fly ash alone. Saturated hydraulic conductivity and soil water retention generally improved with the addition of fly ash while bulk density decreased. Application of fly ash up to 4.5 per cent level increased the straw and grain yield of padi and wheat crops significantly in both years. The results indicated that for reclaiming sodic soils of the southwest Punjab, gypsum could possibly be substituted up to 40 per cent of the gypsum requirement with 3.0 per cent acidic fly ash. Copyright © 2003 John Wiley & Sons, Ltd. [source] Barrett's oesophagus, dysplasia and pharmacologic acid suppressionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2001R. C. Fitzgerald Barrett's oesophagus, a significant complication of gastro-oesophageal reflux disease (GERD), is the single most important risk factor for oesophageal adenocarcinoma. The strong association between Barrett's oesophagus and chronic GERD suggests that abnormal oesophageal acid exposure plays an important role in this condition. The progression of Barrett's oesophagus from specialized intestinal metaplasia to dysplasia and finally invasive carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In ex vivo organ culture experiments, cell proliferation is increased after exposure to short pulses of acid, whilst proliferation is reduced in Barrett's oesophagus specimens taken from patients with oesophageal acid exposure normalized by antisecretory therapy. In long-term clinical studies, consistent and profound intra-oesophageal acid suppression with proton pump inhibitors decreases cell proliferation and increases differentiation in Barrett's oesophagus, but the clinical importance of such favourable effects on these surrogate markers is not clear. In clinical practice, proton pump inhibitors relieve symptoms and induce partial regression to squamous epithelium, but abnormal oesophageal acid exposure and the risk for dysplasia or adenocarcinoma persist in many patients. The ability of proton pump inhibitors to suppress acid profoundly and consistently may be critical in the long-term management of Barrett's oesophagus. [source] Glycaemic control and metabolic risk: getting the extra mile from diabetes controlPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 6 2008M Devers MBChB, MRCP Specialist Registrar Abstract Cardiometabolic risk is an emerging term which has been used to denote the cluster of risk factors defined by the metabolic syndrome and, in addition, to include the newer risk factors which are now recognised to occur in association with dysglycaemia and abdominal obesity. Interventions for diabetes can have effects on cardiometabolic risk factors beyond lowering of hyperglycaemia, and may be an explanation for the reductions in cardiovascular events that are seen with some but not all antidiabetic drugs. Newer antidiabetic agents and the weight-reducing drug, rimonabant, have demonstrated favourable effects on cardiometabolic risk factors and on glycaemia, and should be further studied in long-term cardiovascular outcomes trials. Copyright © 2008 John Wiley & Sons. [source] Hepatic Effects of Rosiglitazone in Rats with the Metabolic SyndromeBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Zvi Ackerman In this study, we characterized the hepatic effects of rosiglitazone in fructose-enriched diet rats. Rats were randomly divided into three groups. One group was maintained on standard rat chow diet for 6 weeks, whereas the other two groups were given fructose-enriched diet for 6 weeks. Four weeks after the initiation of fructose-enriched diet, one of the fructose-enriched diet groups was also given rosiglitazone (10 mg/kg/day) for an additional 2 weeks. Rosiglitazone administration to the fructose-enriched diet rats was associated with decreases in the following parameters: blood pressure (,17%), plasma triglycerides (,62%), hepatic total lipids (,19%), hepatic triglycerides (,61%), hepatic malondialdehyde (,88%), glutathione reductase activity (,84%). An increase in adiponectin plasma levels (+329%), hepatic phospholipids (+46%), hepatic ,-tocopherol concentrations (+24%) and hepatic paraoxonase activity (+68%) was observed. Rosiglitazone caused a decrease in hepatic macrovesicular steatosis score but no change in hepatic fibrosis. Administration of rosiglitazone, to rats with the metabolic syndrome has limited hepatic favourable effects: it improves hepatic lipid metabolism, decreases macrovesicular steatosis and improves some of the hepatic oxidative,anti-oxidative milieu but has no effect on hepatic fibrosis. [source] Quantification of heparin-induced TFPI release: a maximum release at low heparin doseBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2002Michiel J. B. Kemme Aims Heparin releases tissue factor pathway inhibitor (TFPI) from the endothelium and this release may decrease after repeated high dose heparin administration. The primary aim was to investigate and quantify this phenomenon during a short low dose heparin infusion. Also, the effects of heparin on tissue plasminogen activator (t-PA) were studied. Methods Nine healthy, nonsmoking, male volunteers (range 19,23 years) received a continuous heparin infusion (2000 IU) over 40 min. The endothelial TFPI release rate was estimated from the total TFPI concentration profile using a pharmacokinetic model. Results , Mean ,±,s.d. ,total ,and ,free ,TFPI ,increased ,from ,62.9 ± 9.4/8.3 ± 2.1 ng ml,1 at baseline to 237.2 ± 40.9/111.0 ± 19.9 ng ml,1 after 40 min infusion. The relationship between heparin concentration (anti-IIa activity) and TFPI concentration followed a maximum effect model and a clockwise loop (proteresis) was observed. The TFPI release rate rapidly increased to maximum of 200 ± 45 µg min,1 after 17.5 min heparin infusion but did not increase further although heparin concentrations further doubled. In contrast to TFPI, t-PA antigen decreased from 5.6 ± 1.0 at baseline to 4.5 ± 1.0 ng ml,1 at the end of infusion (t = 40 min) (difference of 1.1 ng ml,1 (95% confidence interval; 0.9, 1.3). Conclusions Our application of concentration-effect models and pharmacokinetic principles to these haemostatic variables showed that endothelial TFPI release has a maximum that is already reached at low heparin dose, corresponding with an anti-IIa activity of 0.08 IU ml,1. The relationship between anti-IIa activity and TFPI release rate showed signs of acute tolerance (clockwise loop) indicating exhaustion of endothelial TFPI pools. These findings may be of importance for the heparin dose used in conditions such as unstable angina, in which the favourable effects of heparin have been ascribed to its ability to release TFPI. [source] Pharmacokinetics of tibolone in early and late postmenopausal womenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2002C. J. Timmer Aims, Tibolone is a tissue-specific compound with favourable effects on bone, vagina, climacteric symptoms, mood and sexual well being in postmenopausal women, without stimulating the endometrium or breast. Since tibolone is used for the treatment of both young and elderly postmenopausal women, its pharmacokinetics were studied to investigate potential differences with age. In addition, the bioequivalence of the 1.25 and 2.5 mg tablets was evaluated. Methods, Single doses of 1.25 or 2.5 mg of tibolone were given in a double-blind, randomized, two-way cross-over study to women aged between 45 and 55 years or between 65 and 75 years of age. Results, Age did not have a significant effect on Cmax, tmax, and t½ of tibolone and its metabolites and on the body weight standardized oral clearance (CL/F kg,1) of the 3,- and 3,-hydroxy tibolones. In early postmenopausal women, significantly lower values were found for the AUC(0,16 h), and AUC(0,,) of 3,-hydroxy tibolone 24.6±6.6 vs 29.2±4.9 and 27.1±6.9 vs 32.3±6.5 ng ml,1 h for the 1.25 mg tablet, respectively, and 45.4±13.9 vs 55.7±14.1 and 49.6±14.6 vs 62.6±17.3 ng ml,1 h for the 2.5 mg tablet, respectively. When these values were adjusted for the significantly higher body weight of the early postmenopausal women, the differences disappeared. No significant differences between early and late postmenopausal women were found for the AUC(0,8 h), and AUC(0,,) of 3,-hydroxy tibolone. The rate of absorption of tibolone and the rates of absorption or formation of the 3,- and 3,-hydroxy tibolones were significantly higher after the 1.25 mg dose than after the 2.5 mg tablet, resulting in increases of 32%, 27% and 17% for the dose normalized- Cmax of tibolone and the 3,- and 3,-hydroxy tibolones, respectively. tmax for tibolone and its metabolites was 12,27% less after 1.25 mg compared to 2.5 mg, which was statistically significant. The two formulations were bioequivalent with respect to the dose-normalized AUC(0,,) and the AUC(0,tfix) values for the 3,-hydroxy tibolone (ratio point estimate [90%, confidence limits]: 1.08 [1.04, 1.14] and 1.08 [1.03, 1.13], respectively) and for the 3,-hydroxy tibolone (1.07 [1.01, 1.14] and 1.04 [0.96, 1.12], respectively). Both formulations were also bioequivalent with respect to CL/F kg,1 and t½. Conclusions, The pharmacokinetics of tibolone are similar in early (age 45,55 years) and late (65,75 years) postmenopausal women. The 2.5 and 1.25 mg tablets are bioequivalent with respect to the extent of absorption. The rate of absorption or formation of the metabolites of tibolone were not bioequivalent, but these differences are considered to have no clinical relevance in view of the chronic administration of tibolone. [source] Activating and inhibitory killer immunoglobulin-like receptors (KIR) in haploidentical haemopoietic stem cell transplantation to cure high-risk leukaemiasCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009A. Moretta Summary A number of experimental studies have shown that natural killer (NK) cells can eliminate cancer cells and the mechanisms involved in this effect have been uncovered during the last two decades. Clinical data from haploidentical haematopoietic stem cell transplantation (haplo-HSCT) revealed that NK cells were responsible for remarkably favourable effects in both adult and paediatric high-risk leukaemias. NK receptors specific for major histocompatibility complex (MHC) class I molecules, including killer immunoglobulin (Ig)-like receptors (KIR) and CD94/NKG2A, play a major role in the anti-leukaemia effect (mediating either inhibitory or activating signals). Haplo- HSCT requires a heavy conditioning regimen for the patient and the use of large numbers of T cell-depleted HSC to be grafted. After transplantation, natural killer cells develop from HSC shortly after engraftment and may include ,alloreactive' NK cells that kill leukaemic cells and prevent graft- versus -host disease (GvHD). Alloreactive NK cells are characterized by the expression of KIR that are not engaged by any of the human leucocyte antigen (HLA) class I alleles expressed by the patient. Their generation is dependent upon the existence of a KIR/HLA class I mismatch between donor and recipient. Novel important information on the function and specificity of different KIR has been obtained recently by the analysis of donor-derived alloreactive NK cells in a cohort of paediatric patients given haplo-HSCT to cure acute, high-risk leukaemias. [source] Growth hormone, acromegaly, and heart failure: an intricate triangulationCLINICAL ENDOCRINOLOGY, Issue 6 2003Luigi Saccà Summary Short-term GH or IGF-I excess provides a model of physiological cardiac growth associated with functional advantage. The physiological nature of cardiac growth is accounted for by the following: (i) the increment in cardiomyocyte size occurs prevalently at expense of the short axis. This is the basis for the concentric pattern of left ventricular (LV) hypertrophy, with consequent fall in LV wall stress and functional improvement; (ii) cardiomyocyte growth is associated with improved contractility and relaxation, and a favourable energetic setting; (iii) the capillary density of the myocardial tissue is not affected; (iv) there is a balanced growth of cardiomyocytes and nonmyocyte elements, which accounts for the lack of interstitial fibrosis; (v) myocardial energetics and mechanics are not perturbed; and (vi) the growth response is not associated with the gene re-programming that characterizes pathologic cardiac hypertrophy and heart failure. Overall, the mechanisms activated by GH or IGF-I appear to be entirely different from those of chronic heart failure. Not to be neglected is also the fact that GH, through its nitric oxide (NO)-releasing action, contributes to the maintenance of normal vascular reactivity and peripheral vascular resistance. This particular kind of interaction of GH with the cardiovascular system accounts for: (i) the lack of cardiac impairment in short-term acromegaly; (ii) the beneficial effects of GH and IGF-I in various models of heart failure; (iii) the protective effect of GH and IGF-I against post-infarction ventricular remodelling; (iv) the reversal of endothelial dysfunction in patients with heart failure treated with GH; and (v) the cardiac abnormalities associated with GH deficiency and their correction after GH therapy. If it is clear that GH and IGF-I exert favourable effects on the heart in the short term, it is equally undeniable that GH excess with time causes pathologic cardiac hypertrophy and, if it is not corrected, eventually leads to cardiac failure. Why then, at one point in time in the natural history of acromegaly, does physiological cardiac growth become maladaptive and translate into heart failure? Before this transition takes places, the acromegalic heart shares very few features with other models of chronic heart failure. None of the mechanisms involved in the progression of heart failure is clearly operative in acromegaly, save for the presence of insulin-resistance and mild alterations of lipoproteins and clot factors. Is this enough to account for the development of heart failure? Probably not. On the other hand, it must be stressed that GH and IGF-I activate several mechanisms that play a protective role against the development of heart failure. These include ventricular unloading, deactivation of neurohormonal components, antiapoptotic effect and enhanced vascular reactivity. Ultimately, all data available concur to hypothesize that acromegalic cardiomyopathy represents a progressive model of cardiac hypertrophy in which the cardiotoxic and pro-remodelling effect is intrinsic to the excessive and unrestrained myocardial growth. [source] | |||||||||||||||||||||||||