Search PubMed⌕ Search

Biomedical subjects

W Langhans

Publications and source records attributed to W Langhans.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anorexia of infection: current prospects.

The anorexia of infection is part of the host's acute phase response (APR). Despite being beneficial in the beginning, long lasting anorexia delays recovery and is ultimately deleterious. Microbial products such as bacterial cell wall compounds (e.g., lipopolysaccharides and peptidoglycans), microbial nucleic acids (e. g., bacterial DNA and viral double-stranded RNA), and viral glycoproteins trigger the APR and presumably also the anorexia during infections. Microbial products stimulate the production of proinflammatory cytokines (e.g., interleukins [ILs], tumor necrosis factor-alpha, interferons), which serve as endogenous mediators. Several microbial products and cytokines reduce food intake after parenteral administration, suggesting a role of these substances in the anorexia during infection. Microbial products are mainly released and cytokines are produced in the periphery during most infections; they might inhibit feeding through neural and humoral pathways activated by their peripheral actions. Activation of peripheral afferents by locally produced cytokines is involved in several cytokine effects, but is not crucial for the anorectic effect of microbial products and IL-1beta. Cytokines increase leptin expression in the adipose tissue, and leptin may contribute to, but is also not essential for, the anorectic effects of microbial products and cytokines. In addition, a direct action of cytokines and microbial products on the central nervous system (CNS) is presumably involved in the anorexia during infection. Cytokines can reach CNS receptors through circumventricular organs and through active or passive transport mechanisms or they can act through receptors on endothelial cells of the brain vasculature and stimulate the release of subsequent mediators such as eicosanoids. De novo CNS cytokine synthesis occurs in response to peripheral infections, but its role in the accompanying anorexia is still open to discussion. Central mediators of the anorexia during infection appear to be neurochemicals involved in the normal control of feeding, such as serotonin, dopamine, histamine, corticotropin releasing factor, neuropeptide Y, and alpha-melanocyte-stimulating hormone. Reciprocal, synergistic, and antagonistic interactions between various pleiotropic cytokines, and between cytokines and neurochemicals, form a complex network that mediates the anorexia during infection. Current knowledge on the mechanisms involved suggests some therapeutic options for treatment. Substances that block common key steps in cytokine synthesis or cytokine action, or inhibitors of eicosanoid synthesis, may hold more promise than attempts to antagonize specific cytokines. To target the neurochemical mediation of the anorexia during infection may be even more efficient. Future research should address these neurochemical mechanisms and the cytokine actions at the blood-brain barrier. Further unanswered questions concern the modulation of the anorexia during infection by gender and nutritional state.

Acute-Phase Reaction↗
PubMed2000

Lactational and metabolic effects in cows of lysine and methionine added to a ration deficient according to the I.N.R.A. method.

The effects of adding lysine and/or methionine to a ration of calculated deficiency in these amino acids of 10% and 20%, respectively, were studied in 24 Brown Swiss cows. The mixed rations (27% grass silage, 19% maize silage, 5% hay and 49% concentrate on DM basis) contained 14.5% CP on average. Lysine supply was selectively elevated by adding fish meal in exchange for other concentrate ingredients. Methionine was supplied in a rumen-protected form. Milk protein content was elevated whereas fat amount decreased by adding both amino acids. Lactose content increased without additional lysine from fish meal. Live weight, milk yield, milk fat content and protein amount remained unaffected by any variation of amino acids supply. Also nutrient digestibility and nitrogen balance were not changed by the treatments. Blood plasma concentrations confirmed the assumed variation in metabolic lysine and, less clear, methionine supply. Effects on plasma concentrations of other amino acids were relatively small. Most plasma hormones and enzymes, and metabolites in plasma, urine and milk did not respond to the variation in amino acid supply. Lysine addition via fish meal increased aspartate amino transferase and decreased urinary allantoin concentration. Additional methionine elevated plasma ornithine. Overall lysine and methionine appear to have been only marginally deficient in the unsupplemented ration fed for 3 weeks despite the deficiency of 10% to 20% as calculated by the I.N.R.A. method.

Amino Acids↗
PubMed2000

Prandial lactate infusion inhibits spontaneous feeding in rats.

To investigate the acute effects of lactate on spontaneous feeding, we infused lactate in the hepatic portal vein (0.5, 1.0, and 1.5 mmol lactate/meal) or in the vena cava (1.0 and 1.5 mmol lactate/meal) of ad libitum-fed rats during their first spontaneous nocturnal meal. Infusions (5 min, 0.1 ml/min) were remotely controlled, and a computerized feeding system recorded meal patterns. In separate crossover tests, meal size decreased independent of the infusion route after 1.0 and 1.5 mmol but not after 0.5 mmol lactate. The subsequent intermeal interval (IMI) tended to decrease only after vena cava infusion of 1.0 mmol lactate. The size of the second nocturnal meal increased after the 1.0 mmol lactate infusion. Hepatic portal infusion of 1.5 mmol lactate increased the satiety ratio [subsequent IMI (min)/meal size (g)] by 175%, which was higher than the insignificant 43% increase after vena cava infusion. Hepatic portal infusion of 1.5 mmol lactate also increased systemic plasma lactate but not glucose concentration at 1 min after the end of infusion. The results are consistent with the idea that meal-induced increases in circulating lactate play a role in the control of meal size (satiation). Moreover, the results suggest that lactate also contributes to postprandial satiety and that the liver is involved in this effect. The exact mechanisms of lactate's inhibitory effects on feeding and the site(s) where lactate acts to terminate meals remain to be identified.

Animals↗
PubMed2000

Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline.

Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1999

New approaches in the pharmacological treatment of obesity.

Many new substances are currently being investigated for their usefulness in the pharmaco-therapy of obesity. Most drugs interfere with monoamine neuro-transmitter (serotonin, noradrenalin, dopamine and histamine) effects and act as an appetite suppressant. Other approaches are to primarily increase thermogenesis (e.g. beta 3-adrenoceptor agonists), or to decrease fat absorption by inhibiting the pancreatic lipase (orlistat). New promising agents are substances that increase the effect of corticotropin releasing factor (CRF) or urocortin in the brain (CRF-binding protein ligand inhibitor) and a neuropeptide Y (NPY) Y5 receptor antagonist. The clinical relevance of leptin in the therapy of obesity is probably limited, but can not be fully evaluated at the moment. As obesity has a multifactorial basis, all these substances have in common the fact that they can not cure obesity. They should only be used as an adjunct to classical strategies like diet and exercise in severe obesity. For developing new, perhaps even more specific pharmacological agents, further research is needed to understand the individually different genetic and physiological basis of obesity.

Animals↗
PubMed1999

Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run.

BACKGROUND: Athletes consume arginine and/or aspartate as potential nutritional ergogenics. Their metabolic effects are controversial and there is some evidence that ingestion of large doses of single amino acids can adversely affect the nitrogen balance or induce an amino acid imbalance. Nevertheless, the general metabolic influence of an arginine aspartate supplementation during a prolonged exercise bout has not yet been investigated. AIM OF THE STUDY: The aim of this study was, therefore, to investigate the general metabolic impact of a chronic supplementation with arginine aspartate in endurance-trained athletes at rest and during a marathon run. METHODS: Fourteen endurance-trained runners participated in this field study which was carried out according to a double-blind crossover design. 15 g of arginine aspartate or a carbohydrate-based placebo were supplemented daily for 14 days before a marathon run. Blood samples for analysis of metabolites and hormones were collected shortly before the run, after 31 km, at the end of the run, and after a recovery period of two hours. Additionally, the respiratory exchange ratio was determined during the run. RESULTS: The plasma level of carbohydrate (glucose, lactate, pyruvate) and fat metabolites (fatty acids, glycerol, beta-hydroxybutyrate), cortisol, insulin, ammonia, lactate dehydrogenase, and creatine kinase as well as the respiratory exchange ratio were unaffected by the supplementation. In contrast, the plasma level of somatotropic hormone, glucagon, urea, and arginine were significantly increased, and the level of most of the remaining plasma amino acids as well as their sum was significantly reduced. CONCLUSIONS: There was no obvious metabolic benefit derived from the chronic supplementation with arginine aspartate. And since furthermore the consequences of a reduction of the total plasma amino acid level are not known, the practice of using single amino acid supplements as potential ergogenics should be critically reevaluated.

3-Hydroxybutyric Acid↗
PubMed1999

Interleukins and tumor necrosis factor as inhibitors of food intake.

Cytokines, such as interleukins and tumor necrosis factor-alpha (TNFalpha), are produced in response to immune stimulation and have systemic effects, mediated by the central nervous system (CNS). Interleukins, in particular interleukin [IL]-1beta, and TNFalpha reduce food intake after peripheral and central administration, suggesting that they contribute to the anorexia during various infectious, neoplastic and autoimmune diseases. Because cytokines are mainly produced in the periphery during most of these diseases, IL-1beta and TNFalpha may inhibit feeding indirectly through neural and humoral pathways activated by their peripheral actions. Activation of afferent nerve fibers by locally produced cytokines in the periphery is involved in several cytokine effects, but is not crucial for the anorectic effect of systemic immune stimulation. Cytokines increase OB protein (leptin) expression in the adipose tissue, and leptin may contribute to, but is also not essential for, the anorectic effects of cytokines. Finally, circulating IL-1beta and TNFalpha may act directly on the brain or cytokine synthesis in the brain may contribute to the anorectic effect of systemic immune stimulation. Central mediators of the anorectic effects of cytokines appear to be neurochemicals involved in the normal control of feeding, such as serotonin, corticotropin releasing factor, histamine, alpha-melanocyte stimulating hormone, and neuropeptide Y. The well-documented cytokine production in the gut in relation to feeding and the expression of TNFalpha by adipocytes suggest that IL-1beta and TNFalpha may also play a role in the control of normal feeding and energy balance. All in all, reciprocal, synergistic and antagonistic interactions between various pleiotropic cytokines and between cytokines and neurochemicals form a complex network that mediates the effects of cytokines on feeding and energy balance.

Animals↗
PubMed1999

Metabolic effects of a protein-supplemented carbohydrate drink in marathon runners.

A field study was performed to investigate the acute influence of a milk protein hydrolysate supplemented drink (CHO+PRO) on metabolism during and after a marathon run compared to the same drink without protein (CHO). Carbohydrate metabolites and hormones were not influenced by CHO+PRO. Levels of plasma free fatty acids were significantly lower and levels of urea and most amino acids were significantly higher with CHO+PRO. Sweat urea and ammonia nitrogen excretion during the run as well as urinary 3-methylhistidine excretion during the entire exercise day was similar in both treatments. Urinary total nitrogen was significantly increased and urinary pH decreased with CHO+PRO. It was concluded that the supplemented protein was absorbed and probably at least partially oxidized during the run and that no obvious negative metabolic effects occurred. CHO+PRO did not acutely affect myofibrillar protein breakdown as assessed by the 3-methylhistidine method; however, total body protein breakdown was not measured.

Adult↗
PubMed1999

Effect of a prolonged low-dose lipopolysaccharide infusion on feed intake and metabolism in heifers.

Prolonged infusions of bacterial lipopolysaccharides (LPS) are known to model gram-negative bacterial infections, but the basic mechanisms of the LPS effects on feed intake and metabolism and their potential interdependence are largely unknown. The aim of the present study was to distinguish and to better characterize the feeding suppressive and metabolic effects of LPS. Six heifers were infused intravenously for 100 min with either 1) LPS (2 microg/kg BW) with free access to feed, 2) saline with free access to feed, or 3) saline with feeding restricted to the amount of feed consumed after LPS infusion. Feed intake, body temperature, plasma concentrations of various metabolites and hormones, and the respiratory quotient and heat production were measured. The LPS reduced feed intake and induced pronounced changes in metabolic energy turnover and fat and carbohydrate metabolism that were largely independent of the concomitant feed intake reduction. Some of the metabolic changes were biphasic; the first phase resembled a stress response with increases in plasma glucose and cortisol, and the second phase reflected a beginning energy deficit with low plasma glucose and enhanced lipolysis. The coincidence of a short-term surge of plasma insulin with marked transient decreases in plasma FFA, glycerol, and beta-hydroxybutyrate as well as with the transition from hyper- to hypoglycemia indicates that insulin plays a role in some of the metabolic responses to LPS. The failure of LPS to clearly increase energy expenditure despite the increase in body temperature suggests that anaerobic mechanisms of heat production and, perhaps, a reduced peripheral blood flow contributed to the fever. Many of the initial metabolic responses occurred before and, therefore, independent of, an increase in circulating tumor necrosis factor-alpha.

Adipose Tissue↗
PubMed1998

Analysis of the phenotype and phagocytic activity of monocytes/macrophages from cattle infected with the bovine leukaemia virus.

The bovine leukaemia virus (BLV) is a retrovirus that infects mainly B lymphocytes of cattle, but proviral DNA can also be isolated from monocytes/macrophages. This study investigated the effect of BLV infection on surface antigens on freshly isolated peripheral blood monocytes and cultured monocyte-derived macrophages, with and without lipopolysaccharide (LPS) stimulation. The effect of BLV infection on phagocytic activity of CD14+ monocytes was also assessed. The percentage of monocytes expressing the surface antigens CD11b, CD32 (FcgammaRII), MHC class II and the surface antigen recognised by mAb DH59B were increased in BLV-positive cattle. In contrast, expression intensity of all markers was low in samples from BLV-positive cattle. CD14+ monocytes from BLV-positive cattle showed less Fcgamma-receptor-mediated phagocytosis compared to monocytes from BLV-negative cattle. After 7 days in culture, there was evidence for shedding/downregulation of surface antigens on monocyte-derived macrophages, in particular on cells from BLV-positive cattle. LPS stimulation decreased the percentage of cells expressing the measured markers in monocyte-derived macrophages taken from BLV-negative cattle, but not in cultures derived from BLV-positive cattle. The results provide further evidence for an altered function of monocytes and macrophages in BLV-infected cattle.

Animals↗
PubMed1998

Lipopolysaccharide-induced anorexia following hepatic portal vein and vena cava administration.

To examine the role of the liver in lipopolysaccharide (LPS)-induced hypophagia, we investigated the effect of hepatic portal and vena cava infusions (1 mL/30 min) of LPS (100 microg/kg of body weight) on feeding in rats. LPS infusion significantly reduced food intake when administered via either the hepatic portal vein or the vena cava. Both the magnitude and time course of this hypophagia were similar regardless of the infusion route. As in previous experiments of ours in which LPS was administered by intraperitoneal (i.p.) injection, LPS reduced food intake by decreasing meal frequency, without affecting meal size or duration. The results suggest that peripherally administered LPS does not act primarily in the liver to reduce food intake.

Animals↗
PubMed1998

TNF-alpha tolerance blocks LPS-induced hypophagia but LPS tolerance fails to prevent TNF-alpha-induced hypophagia.

To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in bacterial lipopolysaccharide (LPS)-induced hypophagia, we tested whether a cross tolerance between LPS and TNF-alpha exists with respect to their anorectic effects. Only the first of three subsequent intraperitoneal injections of LPS (100 micrograms/kg body wt) given every second day at dark onset (12:12-h light-dark cycle) led to a significant reduction of food intake in male rats. Likewise, intraperitoneal injections of human recombinant TNF-alpha (150 micrograms > or = 3 x 10(6) U/kg body wt) also resulted in tolerance to its hypophagic effect. LPS tolerance did not alter the hypophagic response to subsequently injected TNF-alpha (n = 14). However, TNF-alpha pretreatment completely blocked the hypophagic response to LPS (n = 14). The results demonstrate that tolerance to the hypophagic effect of exogenous TNF-alpha is sufficient to eliminate LPS-induced hypophagia. This is consistent with the hypothesis that endogenous TNF-alpha plays a major role in LPS-induced hypophagia. The ineffectiveness of LPS tolerance to attenuate TNF-alpha-induced hypophagia is compatible with findings demonstrating that reduced TNF-alpha production is an important feature of LPS tolerance.

Animals↗
PubMed1998

Chronic administration of OB protein decreases food intake by selectively reducing meal size in male rats.

The potent hypophagic effect of OB protein (OB) is well established, but the mechanism of this effect is largely unknown. We investigated the effects of chronic administration of a novel modified recombinant human OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male Sprague-Dawley rats (body weight at study onset: 292 g). Single daily subcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive days significantly reduced ad libitum food intake compared with vehicle injections from injection day 3 through postinjection day 3. Mod-OB-injected rats ate between 4.5 and 7.1 g (or 13-20%) per day less than controls, with the reduction primarily occurring during the dark period. Body weight gain was significantly decreased in response to Mod-OB from injection day 8 until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21-34% decrease in nocturnal spontaneous meal size. There was no significant effect of Mod-OB on nocturnal meal frequency or duration. Mod-OB also did not reliably affect the size, duration, or frequency of diurnal meals. Mod-OB-injected rats displayed no compensatory hyperphagia after the injection period. These results indicate that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.

Animals↗
PubMed1998

Chronic administration of OB protein decreases food intake by selectively reducing meal size in female rats.

The mechanisms by which OB protein controls food intake and energy balance are unknown. Therefore, we investigated the effects of a novel modified human recombinant OB protein (Mod-OB) on spontaneous feeding patterns, body weight, running wheel activity, and ovarian cycling in female rats. Mod-OB or vehicle was injected (4 mg . kg-1 . day-1 sc) for 2 ovarian cycles (8 days) using a within-subjects design. Observations were continued for five ovarian cycles after injections; treatments were then reversed. Mod-OB reduced food intake approximately 20% from injection day 1 to postinjection day 2. Body weight was reduced from injection day 3 to postinjection day 15 (maximum decrease, 25 +/- 4 g, postinjection days 3 and 4). Food intake was reduced due to decreases in nocturnal meal size, which appeared to be superimposed on the normal pattern of spontaneous feeding (i.e., reductions in meal size at estrus). Mod-OB did not significantly affect diurnal food intake or meal patterns, failed to alter wheel running, and did not disrupt the rats' ovarian cycles. We conclude that chronically administered Mod-OB reduces food intake in female rats by selectively affecting the mechanisms controlling meal size.

Analysis of Variance↗
PubMed1998

Vagal and splanchnic afferents are not necessary for the anorexia produced by peripheral IL-1beta, LPS, and MDP.

We investigated the extrinsic gut neural mediation of the suppression of food intake in male Sprague-Dawley rats induced by peripheral intraperitoneal administration of 2 microg/kg interleukin-1beta (IL-1beta), 100 microg/kg bacterial lipopolysaccharide (LPS), and 2 mg/kg muramyl dipeptide (MDP). Food intake during the first 3 and 6 h of the dark cycle was measured in rats with subdiaphragmatic vagal deafferentation (n = 9), celiac superior mesenteric ganglionectomy (n = 9), combined vagotomy and ganglionectomy (n = 9), and sham deafferentation (n = 9). IL-1beta, LPS, and MDP suppressed food intake at 3 and 6 h in all surgical groups. The results demonstrate that neither vagal nor nonvagal afferent nerves from the upper gut are necessary for the feeding-suppressive effects of intraperitoneal IL-1beta, LPS, or MDP in the rat and suggest that peripheral administration of immunomodulators produces anorexia via a humoral pathway.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1998

Dietary fat level and short-term effects of a high-fat meal on food intake and metabolism.

After determining the dietary fat intake in 40 subjects based on a 7-day recording period, the effects of a high-fat breakfast (52% of metabolizable energy from fat) on postprandial fat and carbohydrate metabolism as well as on subsequent lunch intake were investigated in 28 lean, male subjects with habitual dietary fat intakes between 21 and 44% (of daily energy intake). Correlational analysis and comparisons between a low-fat group (LF; fat intake < or =35%, n = 10) and a high-fat group (HF; fat intake > or =40%, n = 11) with a similar body mass index (LF: 22.7, HF: 22.4) and a low body fat content (LF and HF: 10.7) demonstrated that the fat level of the habitual diet did not affect the baseline values and the postprandial changes in the respiratory quotient and in the plasma levels of glucose, insulin, lactate, free fatty acids, beta-hydroxybutyrate, and triglycerides induced by the high-fat breakfast. Only the area under the curve for insulin was higher, and the lactate/insulin ratio was lower in the HF group than in the LF group. Moreover, hunger and satiety ratings and lunch intake (amount, duration, microstructure of eating) after the high-fat breakfast were similar in all subjects. Thus, the habitual level of dietary fat did not alter the acute effects of a fat-rich breakfast on whole-body and hepatic fatty acid oxidation and eating behavior at lunch under the present test conditions. Yet, a long-term high fat intake appears to have subtle effects on postprandial metabolism which are consistent with early signs of a developing insulin resistance.

Adult↗