Internal and external information processing by lateral hypothalamic glucose-sensitive and insensitive neurons during bar press feeding in the monkey

Single neuron activities in the lateral hypothalamic area (LHA) were recorded during bar press feeding task in the monkey. First registered neurons were sorted into 2 groups, glucose-sensitive (GS) and glucose-insensitive (GIS) neurons, depending on their glucose sensitivity. Then firing variations to feeding, electrophoretically applied catecholamines and opiate, and to odor and taste stimuli were investigated. GS neurons responded to dopamine, noradrenaline and morphine more often than GIS neurons. In feeding task GS neurons responded during bar press (BP) and reward (RW) periods with long-lasting inhibition of firing and at cue tone (CT) with transient inhibition, while GIS neurons responded during BP and RW periods mainly with excitation and at cue light (CL) with excitation. A majority of GS neurons responded to both odor and taste stimuli more often than GIS neurons. Data suggest that these two kinds of neurons in the LHA may be involved in different functional aspects of feeding: GS neurons, mainly in internal information processing and reward mechanism, and GIS neurons, in external information processing and motor aspects.     

MANIPULATION OF CHILDREN'S EATING PREFERENCES

Giving foods as rewards can enhance consumption of those foods, while giving rewards to induce consumption of foods can decrease subsequent consumption of those foods.     

Oxyntomodulin and glicentin are potent inhibitors of the fed motility pattern in small intestine

Glicentin (GLIC) and oxyntomodulin (OXM or GLIC 33-69) are gut hormones which regulate digestion. They are known to reduce digestive secretions and to delay gastric emptying. Their biological activities on intestinal motility are still unknown. The effect of a systemic GLIC or OXM increase was investigated in rats on the food intake, the postprandial myoelectrical activity of small intestine and the orocaecal transit. An OXM or GLIC i.v. infusion was applied during the 5 min preceding food onset and during the first 15 min of food intake. This determined a three- to fourfold increase of the preprandial OXM-GLIC level. The OXM or GLIC plasma increase did not modify food intake. OXM infusion slowed down gastric emptying when the stomach contained 3/4 of the ingested food (before T 3 h). The quantity of food delivered in jejunum was subsequently smaller (P < 0.05). In the small intestine, the duration of postprandial myoelectrical activity (50-60 min g(-1) of ingested food) was reduced by 70% (P < 0.001) on duodenum or jejunum and by 54% (P < 0.01) on ileum in OXM-treated rats. An interdigestive motility profile was settled and an acceleration of both gastric emptying and transit rate was thereafter evidenced (after T 3 h). GLIC also reduced the duration of the postprandial myoelectrical activity on duodenum and jejunum (65 and 63% respectively, P < 0.05), but was not as efficient as OXM on ileum. In pathological states such as acute adult gastroenteritis, OXM and GLIC exhibit a two- to fivefold increase in their plasma concentrations. The present findings suggest that OXM and GLIC could, in that disease, contribute to exclude pathogens, due to their joined action on gut motility.     

Comparatice effects of loratadine and selected antihistamines on sleep-waking patterns in the cat

The central effects of the new antihistamine loratadine and three reference antihistamine agents were studied in the cat. As a sensitive measure of drug action on the central nervous system (CNS) we evaluated changes in sleep-waking patterns. For comparison, diphenhydramine was studied as an example of an antihistamine having potent central effects; astemizole and terfennadine were used as examples of new agents claimed to be free of CNS effects. Diphenhydramine, given at 3 mg/kg p.o., increased spindle sleep, i.e., the electrophysiological correlate of drowsiness, and suppressed rapid eye movement (REM) sleep. In addition, cats displayed unusual sleep postures during the various sleep stages. Loratadine had little or no effect on the various features of sleep-waking patterns over a broad dose range (3 and 30 mg/kg p.o.). Astemizole, at 30 mg/kg p.p., significantly increased wakefulness and reduced both slow-wave sleep and REM. No significant changes of the sleep patterns occurred after the low dose of 3 mg/kg. Terfenadine reduced REM duration at 30 mg/kg p.o. but had no effects on sleep patterns at 3 mg/kg. The cat appeared to be a sensitive animal model to the central action of antihistamines since the reference drug diphenhydramine affected sleep-waking patterns at a dose that closely approximates the dose requirements for adverse CNS effects in man. Under the same conditions, loratadine was free of central actions at a dose range far above that effective either therapeutically or in standard tests in other animal species. Astemizole and terfenadine seemed to be devoid of CNS effects at doses similar to those effective as antihistamines in man, but they produced some central actions at higher doses. Comparing the clinically effective doses of the antihistamines examined, loratadine appears to be the least liable to produce adverse effects on the CNS function.     

Effect of electric and chemical stimulation of the raphe obscurus on phrenic nerve activity in the cat

The effect of electrical and chemical (l-glutamate) stimulation of the raphe obscurus on phrenic nerve activity was examined in the cat. Phrenic nerve activity was recorded from a C5 nerve root in anesthetized, paralyzed and artificially ventilated cats. Neural discharge was quantitated by integrating the phrenic nerve activity. The respiratory frequency was determined from the integrated nerve signal. Focal electrical stimulation (18–144 μA; 5–40 Hz; 100 μs pulse duration) resulted in significant (P < 0.05) increases in both integrated phrenic nerve (IPN) amplitude and respiratory frequency. These changes were dependent upon current intensity and frequency of stimulation. The largest increases in IPN amplitude and respiratory frequency were47 ± 17%and146 ± 8%, respectively. To insure that the changes in integrated phrenic nerve activity (IPNA) were the result of stimulation of cell bodies and not axons of passage,l-glutamate (100, 200 nmol) was microinjected (100 nl) into the raphe obscurus. Significant (P < 0.05) dose-related changes occurred in integrated phrenic nerve amplitude with an increase of44 ± 13% at 100 nmol and80 ± 13% at 200 nmoll-glutamate. No significant increase in respiratory frequency was observed withl-glutamate microinjection. The results suggest that the raphe obscurus may be involved in respiratory control.     

Relationship of sperm superoxide dismutase-like activity with other sperm-specific enzymes and experimentally induced lipid peroxidation in infertile men

Summary. Superoxide dismutase-like activity (SOD-like), isoenzyme lactate dehydrogenase-C4 (LDH-C4) and NADH-diaphorase activities in spermatozoa have been investigated from 58 normozoospermic and 27 oligozoospermic men. Significantly higher SOD-like, LDH-C4 and diaphorase activities ( P <0.01, P <0.005 and P <0.0001, respectively) were detected in spermatozoa from oligozoospermic men, compared to the activities found in normozoospermic samples. SOD-like activity (mean±SE) in oligozoospermic samples amounted to 8.3±1.6 U 10⁻⁸ spermatozoa, while in spermatozoa in normozoospermic men with a sperm concentration above 20 million of spermatozoa per ml amounted to 4.2±0.5 U 10⁻⁸. There was a close correlation between the SOD-like activity and biochemical indicators of the presence of residual cytoplasm i.e. isoenzyme LDH-C4 and NADH-diaphorase (r = 0.53 and r = 0.66 in normozoospermic and r = 0.63 and r = 0.54 in oligozoospermic men, respectively). A positive relationship between SOD-like activity and experimentally-induced lipid peroxidation was detected in 54 infertile men (r = 0.30; P <0.05). These findings suggest that a higher level of superoxide dismutase-like activity may reflect a defect in the development or maturation of spermatozoa and, thereby, a decreased fertility potential. Hence, determination of SOD-like activity may give information on the state of maturity of human spermatozoa, while its role in the antioxidative protection remains to be determined.     

Injections of -amphetamine into the ventral pallidum increase locomotor activity and responding for conditioned reward: a comparison with injections into the nucleus accumbens

The nucleus accumbens and ventral pallidum receive dopamine (DA) projections from the mesencephalon. Although DA inputs to the nucleus accumbens are implicated in both locomotion and reward processes, little is known of the behavioural significance of DA in the ventral pallidum. These studies examined the effects of -amphetamine injected into the nucleus accumbens or ventral pallidum on locomotor activity and responding for a conditioned reward (CR). In the nucleus accumbens -amphetamine dose dependently (1, 3 and 10 μg) increased locomotion within 5–10 min of injection. Intra-ventral pallidum microinjections of -amphetamine also increased activity in this dose range, but the effect occurred with a longer latency (5–20 min). The magnitude of the response evoked by ventral pallidum injections was lower than that evoked by nucleus accumbens injections. The GABA_A antagonist picrotoxin (0.1 μg) stimulated activity when injected into the ventral pallidum but not the nucleus accumbens, providing a pharmacological dissociation between the two injection sites. In the CR studies, -amphetamine injected into both sites potentiated responding for a CR previously paired with food delivery, without altering responding on an inactive lever. Picrotoxin injected into the ventral pallidum reduced responding and abolished the selectivity of responding for CR. The results show that DA release in the ventral pallidum enhances locomotion and responding for a CR, providing evidence that DA in the ventral pallidum plays a significant role in the mediation of the effects of -amphetamine. The failure of picrotoxin to elevate responding for CR despite increasing locomotor activity indicates that pharmacologically-induced blockade of GABA_A receptors in the ventral pallidum disrupts goal-directed responding.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 1: 6-Methyl Derivatives

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.     

Changes of circadian blood pressure patterns and cardiovascular parameters indicate lateralization of sympathetic activation following hemispheric brain infarction

The effects of left- and right-sided hemispheric brain infarction on variability in circadian blood pressure and cardiovascular measures were investigated in 35 patients to test for asymmetry of the sympathetic consequences of stroke. No significant differences regarding age, size of infarction or extent and frequency of damage to the insular cortex could be detected between the two groups. Patients with right-sided infarction showed a significantly reduced circadian blood pressure variability [diastolic: -1% (95% CI -4 to 1) vs -6% (-9 to -2);P < 0.05] and a higher frequency of nocturnal blood pressure increase (47% vs 35%;P < 0.05) as compared with patients with left-sided infarction. Right-sided infarction was also associated with higher serum noradrenaline concentrations [546 pg/ml (95% CI 415–677) vs 405 pg/ml (266–544);P < 0.05], and ECG more frequently showed QT prolongation (53% vs 35%;P < 0.05) and cardiac arrhythmias (67% vs 20%;P < 0.005). However, irrespective of the hemisphere damaged, patients with insular infarction showed the most pronounced changes of these parameters. In addition, two patients with right-sided strokes (13%) involving the insula, but none with a left-sided infarction, developed myocardial infarction. These findings suggest lateralization of sympathetic activation with right-sided dominance for sympathetic effects following hemispheric stroke.Supported by the Friedrich-Schiedel-Stiftung