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Overconsumption of high-fat diets (HFDs) can critically affect synaptic and cognitive functions within telencephalic structures such as the medial prefrontal cortex (mPFC). The underlying mechanisms, however, remain largely unknown. Here we show that adolescence is a sensitive period for the emergence of prefrontal cognitive deficits in response to HFD. We establish that the synaptic modulator reelin (RELN) is a critical mediator of this vulnerability because (1) periadolescent HFD (pHFD) selectively downregulates prefrontal RELN+cells and (2) augmenting mPFC RELN levels using transgenesis or prefrontal pharmacology prevents the pHFD-induced prefrontal cognitive deficits. We further identify N-methyl-d-aspartate-dependent long-term depression (NMDA-LTD) at prefrontal excitatory synapses as a synaptic signature of this association because pHFD abolishes NMDA-LTD, a function that is restored by RELN overexpression. We believe this study provides the first mechanistic insight into the vulnerability of the adolescent mPFC towards nutritional stress, such as HFDs. Our findings have primary relevance to obese individuals who are at an increased risk of developing neurological cognitive comorbidities, and may extend to multiple neuropsychiatric and neurological disorders in which RELN deficiency is a common feature.

Background/Objectives:: Malnutrition is an established risk factor for adverse clinical outcomes. Our aim was to assess nutritional status among geriatric trauma patients. Subjects/Methods:: We enrolled 169 consecutive patients (⩾70 years) admitted to the Geriatric Traumatology Centre (University Hospital Zurich, Switzerland). On admission to acute care, nutritional status was assessed with the mini nutritional assessment (score<17=malnourished (M), ⩽23.5=at risk of malnutrition (ARM), >23.5=normal). At the same examination, we assessed mental (Geriatric Depression Scale; GDS) and cognitive function (Mini-Mental State Examination; MMSE), frailty status (Fried Scale), and number of comorbidities and medications. Further, discharge destination was documented. All analyses were adjusted for age and gender. Results:: A total of 7.1% of patients were malnourished and 49.1% were ARM. Patients with reduced mental health (GDS⩾5: 30.5 vs 11.5%; P=0.004), impaired cognitive function (MMSE⩽26: 23.6±0.5 vs 26.0±0.6; P=0.004), prevalent frailty (32.5 vs 8%; P<0.001), more comorbidities (2.3±0.1 vs 1.3±0.2; P<0.0001) and medications (5.6±0.3 vs 3.4±0.4; P<0.0001) were more likely to have an impaired nutritional status (M+ARM). Further, M+ARM patients were twice as likely to be discharged to destinations different to home (odds ratio=2.08; confidence interval 1.07−4.05). Conclusions:: In this consecutive sample of geriatric trauma patients, 56.2% had an M+ARM upon admission to acute care, which was associated with indicators of worse physical, mental and cognitive health and predicted a more than twofold greater odds of being discharged to a destination other than home.

In response to luminal food stimuli during meals, enteroendocrine cells release gastrointestinal (GI) peptides that have long been known to control secretory and motor functions of the gut, pancreas and liver. Glucagon-like peptide-1 (GLP-1) has emerged as one of the most important GI peptides because of a combination of functions not previously ascribed to any other molecule. GLP-1 potentiates glucose-induced insulin secretion, suppresses glucagon release, slows gastric emptying and may serve as a satiation signal, although the physiological status of the latter function has not been fully established yet. Here we review the available evidence for intestinal GLP-1 to fulfill a number of established empirical criteria for assessing whether a hormone inhibits eating by eliciting physiological satiation in man and rodents.

Intersucking, i.e., cattle sucking the udder of heifers or cows, is a frequent problem in dairy herds and may lead to udder damage, mastitis, milk loss, and culling of breeding animals. Using epidemiological methods, we conducted an observational cross-sectional study to investigate risk factors for intersucking in Swiss dairy cows. We asked 114 randomly selected dairy farmers about a broad spectrum of environmental factors possibly associated with intersucking, such as housing conditions, management, and feeding of calves, heifers, and cows. Thirty of the 114 farms were confronted with intersucking in cows. The mean proportion of intersucking cows per farm was 1.6%. From a total of 3077 cows (Swiss Brown Cattle, Simmental, and Holstein Friesian) we recorded 49 cows that had performed or were currently intersucking. In 69% of these cows, intersucking had been observed as heifers. Using path analysis and multivariable stepwise backward logistic and linear regression analyses, we revealed that the most important risk factor for intersucking cows was the presence of intersucking heifers on a farm (odds ratio = 7.8). The results suggest that intersucking in cows is the continuation of a habit that was already established in a cow's subadult life. This emphasizes the importance of looking not only at the animal's current environmental situation but also considering its entire life history for the prevention of behavioral problems.

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 viafish 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.

Cytokines, such as interleukins and tumor necrosis factor-α (TNFα ), are produced in response to immune stimulation and have systemic effects, mediated by the central nervous system (CNS). Interleukins, in particular interleukin [IL]-1β, and TNFα 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-1β and TNFα 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-1β and TNFα 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, α-melanocyte stimulating hormone, and neuropeptide Y. The well-documented cytokine production in the gut in relation to feeding and the expression of TNFα by adipocytes suggest that IL-1β and TNFα 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. Copyright 1999 Harcourt Publishers Ltd

The contribution of α- and β-adrenergic receptor mechanisms to epinephrine-induced hyperglycemia, to prandial hepatic glycogenolysis, and to epinephrine-induced inhibition of feeding were investigated in rats, because epinephrine's hyperglycemic and anorectic effect might be related to each other. Intraperitoneal injection of the selective α-adrenergic receptor antagonist phentolamine (0.5 mg/kg body weight) but not of the selective β-adrenergic receptor antagonist propranolol (0.5 mg/kg body weight) reduced the hyperglycemic effect of a subsequent epinephrine injection (0.05 mg/kg body weight). In addition, injection of phentolamine (0.5 mg/kg b.w.) or injection of phentolamine plus propranolol (0.5 mg/kg b.w. each) similarly inhibited epinephrine-induced hepatic glycogenolysis. In contrast, phentolamine injection did not affect prandial hepatic glycogenolysis. Neither phentolamine nor propranolol i injection was sufficient to affect the inhibition of feeding induced by subsequent epinephrine injection, but the combination of both receptor blockers completely abolished epinephrine's effect on food intake. These findings are not consistent with the idea that epinephrine-induced hypophagia is related to epinephrine's effect on hepatic carbohydrate metabolism. In addition, the data suggest that catecholamines are not the main contributors to prandial hepatic glycogenolysis in rats.

For further investigation of the mechanism involved in D,L-3 hydroxybutyrate (DL3HB)-induced inhibition of feeding [5], we measured cumulative food intake following subcutaneous injections of DL3HB or D-(−)-3-hydroxybutyrate (D3HB), and plasma ketone levels following subcutaneous injections of D3HB or acetoacetate (ACAC) in rats. Subcutaneously injected DL3HB (10 mmoles/kg body weight) and D3HB (5 mmoles/kg body weight) reduced food intake a similar amount. After injection of D3HB or ACAC (5 mmoles/kg body weight) plasma concentrations of the injected ketone bodies reached a similar high level at 20 min and then decreased with time (40 and 60 min). Even though ACAC failed to reduce food intake, injected ACAC disappeared faster from the circulation than injected D3HB. The data are consistent with the idea that oxidation of injected D3HB to ACAC reduces food intake in rats.

The present study compared the effects of vasopressin on plasma concentrations of corticotropin, cortisol and glucose in cattle and sheep. After intravenous injection of 1, 0.1 and 0.01 µg vasopressin per kg body weight, the plasma vasopressin concentration increased proportionally to the injected dose, and this increase was similar in cattle and sheep. Doses of 1 and 0.1 µg per kg body weight of vasopressin triggered significant responses of corticotropin, cortisol and glucose in cattle and sheep. The corticotropin response to both doses was significantly greater in sheep, whereas the glucose response was greater in cattle. The cortisol response did not differ between species. The lowest dose of vasopressin (0.01 µg per kg body weight) still induced a significant cortisol response without a substantial effect on plasma corticotropin, suggesting that a direct action of vasopressin on the adrenals may contribute to the observed cortisol response. The results demonstrate that vasopressin increases plasma levels of corticotropin, cortisol and glucose in cattle, as it does in sheep, but the intensities of the corticotropin and glucose responses to vasopressin differ between cattle and sheep. The reasons for these differences remain to be clarified.

In der vorliegenden Studie wurde der Einfluß der Kohlenhydrataufnahme während eines Langstreckenlaufes über 46,6 km auf Leistungsfähigkeit, Energieumsatz und Stoffwechsel untersucht. Gut trainierte Läufer erhielten während des Laufes entweder ein kohlenhydrathaltiges (KH[+]) oder ein kohlenhydratfreies (KH[−]) Getränk. Der respiratorische Quotient (RQ), die Plasmakonzentrationen von Metaboliten des Kohlenhydrat- bzw. Fettstoffwechsels und von Hormonen (Insulin, Glucagon) wurden gemessen. Die mittlere Geschwindigkeit über die gesamte Distanz betrug 13,6 (KH[+]) bzw. 13,4 (KH[−]) km/h. Dabei war der gegen Ende des Laufes allgemein feststellbare Leistungsabfall bei Aufnahme des KH[+]-Getränkes etwas schwächer ausgeprägt als bei Aufnahme des KH[−]-Getränkes. Der RQ nahm unabhängig von der Kohlenhydrataufnahme während des gesamten Laufes annähernd linear ab. Die während des Laufes feststellbaren Veränderungen der Plasmakonzentrationen von Lactat, Freien Fettsäuren (FFS), Glycerin, D-3-Hydroxybutyrat (DHB), Glucagon und Insulin wurden durch die Kohlenhydrataufnahme nicht signifikant beeinflußt. Die Aufnahme des KH[+]-Getränkes verhinderte jedoch den unter Kontrollbedingungen gegen Ende des Laufes feststellbaren Abfall der Plasmaglucosekonzentration sowie den steilen Anstieg des Plasmaspiegels von DHB nach dem Lauf. Ferner führte die Kohlenhydrataufnahme zu einem raschen Abfall der Plasmakonzentrationen von FFS und Glucagon nach dem Lauf und erhöhte die Plasmakonzentration von Insulin geringfügig. Die Ergebnisse zeigen, daß die exogene Zufuhr von Kohlenhydraten den Stoffwechsel erst in der Endphase eines Langstreckenlaufes sowie in der anschließenden Erholungsphase beeinflußt. Ein positiver Effekt der Kohlenhydrataufnahme auf die Leistungsfähigkeit tritt ebenfalls erst in der Endphase eines so langen Laufes auf. The present study addressed the effects of carbohydrate consumption during endurance exercise on performance, energy turnover, and metabolism. Well-trained endurance runners consumed a beverage with (cho[+]) or without (cho[−]) carbohydrates during a long-distance run (46.6 km). The respiratory quotient (RQ), plasma levels of carbohydrate and fat metabolites, and of hormones (insulin, glucagon) were measured before, several times during, and after the run. The mean running speed for the entire distance was 13.6 and 13.4 km/h with the cho[+] and cho[−] beverage, respectively. The decrease in speed that was observed towards the end of the run was somewhat more pronounced with consumption of the cho[−] beverage. The RQ decreased during the run almost linearily. This decrease was independent of the consumed beverage. The changes in plasma levels of lactate, free fatty acids (FFA), glycerol, D-3-hydroxybutyrate (DHB), glucagon and insulin that occurred during the run were not affected by intake of the cho[+] beverage. However, intake of the cho [+] beverage prevented the decrease in plasma glucose observed towards the end of the run under control conditions, and eliminated the steep postexercise increase in plasma DHB. The intake of the cho[+] beverage also caused a rapid decrease in plasma levels of FFA and glucagon after the run, and slightly increased plasma insulin. The results demonstrate that ingestion of a carbohydrate-containing beverage during a long-distance run affects metabolism only during the final phase of the run and during the subsequent recovery period. Moreover, carbohydrate consumption improves performance only during the final phase of a long-distance run.

Die Regulation der Nahrungsaufnahme läßt sich als Regelkreis mit negativem Feedback darstellen. Hunger und/oder Appetit veranlassen Mensch oder Tier, Nahrung aufzunehmen. Durch die aufgenommene Nahrung werden präoder postabsorptive Mechanismen aktiviert, die zu Sättigung führen. Präabsorptiv ist dabei vor allem die Stimulierung oraler und gastrointestinaler Chemo- und Mechanorezeptoren von Bedeutung. Auch dem Gastrointestinalhormon Cholecystokinin scheint eine physiologische Sättigungsfunktion zuzukommen. Präabsorptive Sättigungsmechanismen werden ferner durch die Geschwindigkeit der gastrointestinalen Passage der Digesta beeinflußt. Das pankreatische Inselzellhormon Glucagon, welches im Verlauf der Nahrungsaufnahme vermehrt sezerniert wird, sowie unterschiedliche Metaboliten tragen zur postabsorptiven Regulation der Nahrungsaufnahme bei, indem sie hepatische Chemorezeptoren aktivieren, die vorwiegend über vagale Afferenzen mit dem Gehirn verbunden sind. An der Regulation der Nahrungsaufnahme sind ferner Glucoserezeptoren im Gehirn beteiligt, die Veränderungen der Blutglucosekonzentration bzw. der Glucose-Utilisation registrieren. Die Glucoserezeptoren im Nucleus tractus solitarii der Medulla oblongata sind diesbezüglich offenbar von besonderer Bedeutung. Vom Nucleus tractus solitarii, in dem die Afferenzen von Gastrointestinaltrakt und Leber sowie auch Geschmacksafferenzen umgeschaltet werden, projizieren Nervenfasern zum Hypothalamus und zu anderen Vorderhirnarealen. In diesem neuronalen Netzwerk werden die aus der Peripherie eintreffenden Informationen durch unterschiedliche Neurotransmitter und -peptide integriert. Das Zusammenwirken und die genaue Funktion der daran beteiligten Substanzen sind allerdings noch nicht vollständig geklärt. Das Körpergewicht bzw. die Fettdepots des Organismus beeinflussen die Nahrungsaufnahme vermutlich über die Modulation eines postabsorptiven Mechanismus. Regulation of food intake is commonly treated as a negative feedbackloop. Hunger and/or appetite lead man and animals to ingest food. The subsequent meal-contingent activation of pre- and postabsorptive mechanisms then leads to satiety. The activation of oral and gastrointestinal chemo- and mechanoreceptors is important on the preabsorptive site. The gastrointestinal hormone cholecystokinin may also have a physiological satiety effect. Preabsorptive satiety mechanisms are influenced by the rate of gastrointestinal transit. The pancreatic hormone glucagon, which is released during meal taking, and various metabolites contribute to the postabsorptive regulation of food intake through activation of hepatic chemoreceptors, which are connected to the brain via predominantly vagal afferents. In addition, glucoreceptors in the brain, in particular in the nucleus of the solitary tract, contribute to food intake regulation by monitoring blood glucose concentration or, more specifically, glucose utilization. The nucleus of the solitary tract, which relays vagal afferents from gut and liver and also gustatory afferents, projects to the hypothalamus and to other forebrain structures. In this neural network the informations from the periphery are integrated by various neurotransmitters and neuropeptides, but the exact role of the substances involved is not fully understood yet. Body weight and, hence, body fat presumably affects feeding through modulation of a postabsorptive mechanism.

The effects of four equienergetic breakfasts with varying fiber and macronutrient contents on hunger and satiety ratings, on subsequent lunch intake, and on postprandial carbohydrate and fat metabolism were investigated in normal weight male subjects in two experiments, in which lunch was offered at a predetermined time (Experiment 1) or in which the subjects were free to choose when to eat lunch (Experiment 2). Consumption of either a commercially available high fiber cereal (HFC, 10 % fiber), a medium fiber cereal (MFC, 7 % fiber), a low fiber cereal (LFC, 3 % fiber), or a standard continental breakfast (0 % fiber) on nonconsecutive days did not differentially affect hunger and satiety ratings, the size or microstructure of the subsequent lunch, and the breakfast to lunch intermeal interval (in Experiment 2). Plasma concentrations of glucose, lactate, and insulin increased more after the LFC breakfast than after the other breakfast varieties. A reactive postprandial hypoglycaemia occurred after the LFC breakfast, shortly before lunch. The plasma concentrations of fat metabolites (triglycerides, free fatty acids, β-hydroxybutyrate) and of glucagon were not differentially affected by the breakfast varieties. The results are consistent with the assumption that energy content of a meal is the major determinant of subsequent energy intake in man and that fiber content and macronutrient composition have only a modulating effect. Der Einfluss von 4 isoenergetischen Frühstücken mit unterschiedlichem Nahrungsfaser-und Makronährstoffgehalt auf Hunger und Sättigung, auf das nachfolgende Mittagessen sowie auf den postprandialen Kohlenhydrat-und Fettstoffwechsel wurde an normalgewichtigen, männlichen Probanden in 2 Experimenten untersucht, in denen das Mittagessen entweder zu einem vorbestimmten Zeitpunkt angeboten wurde (Experiment 1), oder in dem die Probanden selbst den Zeitpunkt des Mittagessens bestimmen konnten (Experiment 2). Der Verzehr eines handelsüblichen Müslis mit hohem (10 %), mittlerem (7 %) und niedrigem (3 %) Fasergehalt (HFC, MFC und LFC) oder ein Standard-Frühstück (0 % Fasern) hatten keinen unterschiedlichen Einfluß auf Hunger und Sättigung, Grösse und Mikrostruktur des folgenden Mittagessens und auf die Zeitspanne zwischen Frühstück und Mittagessen (in Experiment 2). Die Plasmakonzentrationen von Glucose, Lactat und Insulin stiegen nach dem LFC-Frühstück stärker an als nach den anderen Frühstücksvarianten. Eine reaktive postprandiale Hypoglykämie trat nach dem LFC-Frühstück kurz vor dem Mittagessen auf. Die Plasmakonzentrationen von Metaboliten des Fettstoffwechsels (Triglyceride, freie Fettsäuren, β-Hydroxybutyrate) und von Glucagon wurden durch die Frühstücksvarianten nicht unterschiedlich beeinflusst. Die Resultate stehen im Einklang mit der Annahme, daß der Energiegehalt einer Mahlzeit die wichtigste Determinante für die nachfolgende Energieaufnahme ist. Der Faser- und Makronährstoffgehalt scheinen diesbezüglich nur einen modulierenden Effekt zu besitzen.

The DELPHI detector will be upgraded by a new silicon detector in the very forward region to fulfil the physics demands of the LEP200 program. This detector will cover the angular region between 10° and 25° with respect to the beam pipe and will have a two dimensional readout. The severe space restrictions in this region lead us to develop a new arrangement of detectors and electronic hybrids. In beam tests the layout of the detectors was optimised. Special attention was given to the charge loss in intermediate strips for detectors with large strip pitch. Beam test results obtained with different detector layouts, e.g. various implant widths, and different angle of the incident particles will be shown.