Age-related changes of exercise-induced plasma catecholamines and neuropeptide Y responses in normal human subjects.

Age-related plasma noradrenaline and neuropeptide Y were evaluated in seven young (mean +/- SD, 28 +/- 3 years) and seven elderly (64 +/- 8 years) normal subjects during rest and different work loads on a cycle ergometer. In the supine and the sitting position plasma noradrenaline and neuropeptide Y were almost identical in the two groups. Plasma neuropeptide Y did not increase during exercise at 100 W for 15 min. At this load plasma noradrenaline levels were higher in the older subjects (mean +/- SEM, 0.97 +/- 0.12 vs. 0.60 +/- 0.09 ng ml-1). There was a significant correlation between plasma noradrenaline and the relative work load at 100 W (r = 0.794, P = 0.0007). At 75% of maximal work load plasma noradrenaline and neuropeptide Y were higher in the young group (1.84 +/- 0.16 vs. 1.26 +/- 0.13 ng ml-1 (noradrenaline) and 38 +/- 4 vs. 22 +/- 5 pmol l-1 (neuropeptide Y)). In the elderly group plasma neuropeptide Y did not increase during exercise and showed a tendency to fall below basal level 5 min post-exercise. It is concluded, that plasma noradrenaline does not increase more in older subjects during exercise when correcting for the generally lower physical fitness in this group compared to younger subjects, and that plasma neuropeptide Y does not increase during exercise in older subjects, suggesting an age-reduced capacity in this system.     

Antacids in the treatment of duodenal ulcer

Fifty patients with endoscopically proven pyloric-prepyloric ulcers (PU/PPU) and 50 with duodenal ulcers (DU) completed a six-week double-blind clinical trial initially comprising 124 patients. The antacid-treated patients received 10 ml of an antacid suspension seven times a day (buffering 367.5 mmol acid). Healing rate after three weeks of treatment was 74% in the antacid and 42% in the placebo group (p less than 0.01). After six weeks the corresponding figures were 96 and 68% (p less than 0.001). Regarding the PU/PPU and DU subgroups we found significant differences compared to placebo in the PU/PPU group only. Antacids caused a significantly faster and more perceptible pain relief than placebo. We found no significant correlation between ulcer healing and smoking habits. Regression analyses showed that, besides antacids, ulcer size and peak acid output influenced the healing rate significantly.     

Terminal arbors of axons projecting to the somatosensory cortex of the adult rat. II. The altered morphology of thalamocortical afferents following neonatal infraorbital nerve cut

The organization of the whisker representation within the neocortex of the rat is dependent on an intact periphery during development. To further investigate how alterations in this cortical map arise we examined the organization of thalamocortical afferents to the whisker representation in adult animals in which the infraorbital branch of the trigeminal nerve was cut on the day of birth. The disrupted pattern of thalamocortical projections to the vibrissae representation was apparent in the abnormal pattern of the anterograde transport of horseradish peroxidase from the thalamus, as well as in the abnormal pattern of succinate dehydrogenase activity. To determine the morphology of individual thalamocortical axons associated with this disrupted pattern, terminal arbors were "bulk-labeled" by injections of horseradish peroxidase into the white matter beneath the somatosensory cortex. Terminal arbors were identified by their laminar distribution of boutons corresponding to the specific thalamocortical afferent. The medial to lateral extent of these terminal arbors varied dramatically, from 350 to 1500 microns. In addition, terminal arbors innervating the same local area of cortex appeared to have varying degrees of overlap. Thus, the disruption of the neocortical vibrissae representation appears to involve the abnormal arborization of individual thalamocortical afferents. This finding supports the hypothesis that the fine-grain organization of the somatotopic map is dependent on the morphology and organization of individual thalamocortical arbors, which, in turn, are dependent on the periphery during development.     

Terminal arbors of axons projecting to the somatosensory cortex of the adult rat. I. The normal morphology of specific thalamocortical afferents

A characteristic feature of the rat somatosensory neocortex is a discrete topographic representation of the facial whiskers. Afferent fibers projecting to this vibrissae representation were "bulk-labeled" by injecting horseradish peroxidase into the white matter. Terminal arbors with the morphological characteristics of Lorente de No's (1949) "specific" thalamocortical afferents were then reconstructed through serial sections. These terminal arbors, characterized by the discrete organization of their dense plexus in layer IV, have a laminar distribution of boutons that parallels the laminar pattern of terminal degeneration resulting from lesions of the ventral posterior nucleus of the thalamus. The regional distribution of different-sized arbors corresponds to the distribution of vibrissae-related clusters of different sizes. Larger arbors were found in the posteromedial region corresponding to the mystacial vibrissae representation, while smaller arbors were found in the anterolateral region corresponding to the representation of the anterior sinus hairs. Terminal arbors were also reconstructed from sections stained simultaneously to demonstrate the pattern of vibrissae-related clusters. The greatest concentration of boutons on these axons occurred within a single vibrissae-related cluster. Furthermore, when 2 fibers terminated within a single cluster, their terminal arbors appeared to be largely coextensive. The morphology, size, and distribution of these terminal arbors support the hypothesis that the layer IV plexus of a single specific thalamocortical afferent tends to fill a vibrissae-related cluster. Thus, the organization of specific thalamocortical afferents may be responsible for clustered organization within the somatotopic map of the rodent neocortex.     

Aggressive resection of metastatic disease in selected patients with malignant gastrinoma.

Fifteen patients with Zollinger-Ellison syndrome followed at the National Institutes of Health with extensive metastatic disease had an actuarial 5-year survival of 20%. Therefore, in 1982 a prospective study to examine the effect and feasibility of removing all gross tumor in selected patients with extensive metastatic disease was instituted. Five patients with extensive metastatic gastrinoma confined to the abdomen in whom imaging studies suggested the possibility of complete surgical resection were entered into this study and underwent attempted complete surgical resection and chemotherapy with streptozotocin, doxorubicin, and 5-fluorouracil. Median follow-up was 24 months. Surgical resection of all gastrinoma was possible in 4/5 patients attempted. In one patient in whom all gross disease could not be resected, the residual tumor progressed and the patient died 19 months after operation. All four patients with all disease resected appeared to benefit since all of them had a significant reduction in antisecretory medications and are enjoying normal activity and work. Three patients have had no detectable tumor on follow-up, and two of these patients are clinically and biochemically "cured" with normal fasting gastrin levels and negative provocative gastrin tests at 14 and 32 months. Therefore, aggressive resection of metastatic disease in selected patients with malignant gastrinoma is recommended.     

ZK 91296, a partial agonist at benzodiazepine receptors

ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.     

The toxicological response of the algaAnabaena flos- aquae (cyanophyceae) to cadmium

The toxicological response of the cyanophycean algaAnabaena flos- aquae to cadmium was investigated by three integrated approaches: 1) the determination of the incipient lethal concentration of the metal, 2) study of metal incorporation and cellular compartmentalization using X-ray energy dispersive analysis, and 3) the quantification of intracellular structural changes, after metal exposure, using morphometric analysis. After 96 hr of exposure, the incipient lethal concentration was calculated to be 0.118 ± 0.04 M cadmium. At concentrations three orders of magnitude higher than the incipient lethal concentration, cadmium was incorporated into both the cellular cytoplasm and the cell's polyphosphate bodies. Cadmium also caused the polyphosphate bodies to lose Mg and Ca, resulting in ionic changes in the elemental composition of these cellular inclusions. The utilization of stereological techniques for electron microscopic morphometric analysis established that all concentrations of cadmium tested caused significant reductions in the surface area of the cell's thylakoids. Cadmium induced changes in the numbers and relative volume of the cell occupied by polyhedral bodies, polyphosphate bodies, lipid inclusions, cyanophycin granules, membrane limited crystalline, inclusions, and changes in the volume of the cell wall layers were also documented. The physiological significance of these findings are discussed in terms of the toxic action of cadmium and the cellular mechanisms for detoxification of cations once they enter the cell.