Thirst and artificial heat acclimatization in man

The purpose of this study was to investigate the relationship between serum osmotic changes, water intake and water balance in four, fit young men during and after exercise in the heat, before and after artificial heat acclimatization. During exercise, before steady-state conditions were reached, voluntary water intakes generally paralleled but were not proportional to the serum osmotic pressure. In steady-state conditions, drinking was approximately proportional to the effective osmotic pressure of the serum. During the post-exercise recovery period, when serum osmolarity returned to normal levels, water intake also subsided even though there was a total body water (wt) deficit of about 3%. Body weight did not return to control levels until 62 to 86 hr following the exercise. This slow recovery could not be accounted for by a loss of water associated with glycogen utilization during exercise or by sweat electrolyte depletion. In general, the results supported Dill's hypothesis but plasma volume changes, in addition to osmotic factors,are very likely operative in the initiation and satiation of drinking under these conditions. Perhaps slower acting volume control mechanisms mediate the slow recovery of total body water.

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Zusammenfassung Untersucht wurde die Beziehung zwischen osmotischen Veränderungen im Serum, Wasseraufnahme und Wassergleichgewicht bei 4 gesunden,jungen Männern während und nach körperlicher Arbeit in der Hitze vor und nach künstlicher Hitzeakklimatisation. Die freiwillige Wasseraufnahme während der Arbeit, ehe ein steady state erreicht wurde, war im allgemeinen gleichlaufend, aber nicht proportional dem osmotischen Serumdruck. Im steady state war die Trinkmenge ungefähr proportional dem effektiven osmotischen Serumdruck. Wenn die Serumosmolarität während der Erholungsphase zur normalen Werten zurückkehrte, liess die Wasseraufnahme ebenfalls nach,obwohl das Gesamtkörperwasserdefizit ungefähr 3% betrug.Die Körpergewichte erreichten die Ausgangswerte 62–86 Std nach der Arbeit. Diese langsame Erholung war nicht bedingt durch einen Wasserverlust dur Glykogenverwertung während der Arbeit oder durch Elektrolytverluste beim Schwitzen. Die Ergebnisse stützen Dill's Hypothese, doch unter diesen Bedingungen wirken Plasmavolumen-Veränderungen zusätzlich zu osmotischen Faktoren sehr wahrscheinlich mit bei der Auslösung des Trinkens und der Sättiging mit Wasser. Vielleicht vermitteln langsamer wirkende Volumenkontrollmechanismen die langsame Wiederherstellung der Gesamtkörper-Wasservorräte.

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Resume On a examiné les relations existant chez 4 jeunes hommes sains entre les variations de la pression osmotiques du sérum d'une part,l'ingestion d'eau et l'équilibre acqueux du corps d'autre part et cela pendant et après un travail corporel à la chaleur tant avant qu'après une acclimatisation artificielle au chaud.L'ingestion volontaire d'eau évolue similairement à la pression osmotique du sérum, mais ne lui est pas proportionnel. Ce phénomène s'observe jusqu'à ce qu'un état dit stationnaire soit atteint. Dès ce moment, les quantités bues sont à peu près proportionnelles à la pression osmotique effective. Pendant la phase de récupération, la pression osmotique redevient normale et l'eau ingérée diminue bien que le déficit en eau pour le corps entier soit encore de 3% environ.Le poids du corps ne retrouve sa valeur initiale que 62 à 86 heures après la période de travail. Ce lent rétablissement n'est pas dû à des pertes d'eau par suite de l'utilisation de glycogènes pendant l'exercice ou par suite de la perte d'électrolytes par la sueur. Ces résultats viennent confirmer les hypothèses de Dill. Pourtant, dans ces conditions, les variations de volume du plasma agissent très vraisemblablement en plus des facteurs osmotiques dans le besoin de boire ou l'état de satiété. Il est possible que des mécanismes de contrôle du volume agissant plus lentement président aux phénomènes de rétablissement des réserves en eau dans son ensemble.

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Results were presented in part at the "Symposium on Nutrition and Physical Activity", The Swedish Nutrition Foundation, Tylösand, Sweden, 15–17 August,1966.     

Actin Involvement in Exocytosis from PC12 Cells: Studies on the Influence of Botulinum C2 Toxin on Stimulated Noradrenaline Release

Botulinum C2 toxin is known to ADP-ribosylate actin. The toxin effect was studied on [3H]noradrenaline secretion of PC12 cells. [3H]Noradrenaline release was stimulated five- to 15-fold by carbachol (100 microM) or K+ (50 mM) and 10-30-fold by the ionophore A23187 (5 microM). Pretreatment of PC12 cells with botulinum C2 toxin for 4-8 h at 20 degrees C, increased carbachol-, K+-, and A23187-induced, but not basal, [3H]noradrenaline release maximally 1.5-to three-fold, whereas approximately 75% of the cellular actin pool was ADP-ribosylated. Treatment of PC12 cells with botulinum C2 toxin for up to 1 h at 37 degrees C also increased stimulated [3H]noradrenaline secretion, whereas toxin treatment for greater than 1 h decreased the enhanced [3H]noradrenaline release stimulated by carbachol and K+ but not by A23187. Concomitantly with toxin-induced stimulation of secretion, 20-50% of the cellular actin was ADP-ribosylated, whereas greater than 60% of actin was modified when exocytosis was attenuated. The data indicate that ADP-ribosylation of actin by botulinum C2 toxin largely modulates stimulation of [3H]noradrenaline release. Moreover, the biphasic toxin effects suggest that distinct mechanisms are involved in the role of actin in secretion.     

Controlled experiments of habitat fragmentation: a simple computer simulation and a test using small mammals

Habitat fragmentation involves a reduction in the effective area available to a population and the imposition of hard patch edges. Studies seeking to measure effects of habitat fragmentation have compared populations in fragments of different size to estimate and area effect but few have examined the effect of converting open populations to closed ones (an effect of edges). To do so requires a shift in spatial scope-from comparison of individual fragments to that of fragmented versus unfragmented landscapes. Here we note that large-scale, controlled studies of habitat fragmentation have rarely been performed and are needed. In making our case we develop a simple computer simulation model based on how individual animals with home ranges are affected by the imposition of habitat edges, and use it to predict population-level responses to habitat fragmentation. We then compare predictions of the model with results from a field experiment on Peromyscus and Microtus. Our model treats the case where home ranges/territories fall entirely within or partially overlap with that of sample areas in continuous landscapes, but are restricted to areas within habitat fragments in impacted landscapes. Results of the simulations demonstrate that the imposition of hard edges can produce different population abundances for similar-sized areas in continuous and fragmented landscapes. This edge effect is disproportionately greater in small than large fragments and for species with larger than smaller home ranges. These predictions were generally supported by our field experiment. We argue that large-scale studies of habitat fragmentation are sorely needed, and that control-experiment contrasts of fragmented and unfragmented microlandscapes provide a logical starting point.     

Actions of an antispermatogenic, but non-mutagenic, indenopyridine derivative in mice and Salmonella typhimurium.

This paper describes a new antispermatogenic agent. Following single oral administration to mice, the indenopyridine derivative (4aRS,5SR,9bRS)-2-ethyl-1,3,4,4a,5,9b-hexahydro-7-methyl-5-p-tolyl-2H-indeno(1,2-c)pyridine hydrochloride, code No. 20-438, produced long-lasting inhibition of the spermatogenic process at dose levels of 10 mg/kg (1/40 of the lowest lethal dose) and higher. Testes weights were significantly reduced from days 2--217 after treatment, and no clear-cut evidence of a recovery was found during this time. The fertility of treated males was normal during the initial 2 weeks after treatment, followed by partial or total sterility in weeks 3--6, and incomplete recovery in weeks 7--29 after treatment. The antifertility effects were caused by maturation depletion of the germ cells, leading to oligospermia. The following rank of decreasing "susceptibility" of the germ cells was observed: Spermatocytes greater than early spermatids, intermediate spermatogonia greater than stem cells. Sperm and late spermatids were not affected. Despite the characteristic specific germ-cell pattern of antifertility effects, 20-438 showed neither indications of pre- and post-implantational dominant lethality, nor mutagenic potentiality as measured by cytogenetic analysis of spermatocytes or spermatogonia, the sperm abnormality assay, the micronucleus test, and the Salmonella assay. These data suggest that the action of 20-438, leading to oligospermia, does not involve genetic toxic effects.     

The isolated ER-Golgi intermediate compartment exhibits properties that are different from ER and cis-Golgi

A procedure has been established in Vero cells for the isolation of an intermediate compartment involved in protein transport from the ER to the Golgi apparatus. The two-step subcellular fractionation procedure consists of Percoll followed by Metrizamide gradient centrifugation. Using the previously characterized p53 as a marker protein, the average enrichment factor of the intermediate compartment was 41. The purified fraction displayed a unique polypeptide pattern. It was largely separated from the rough ER proteins ribophorin I, ribophorin II, BIP, and protein disulfide isomerase, as well as from the putative cis-Golgi marker N-acetylglucosamine-1-phosphodiester-alpha-N-acetylglucosaminidase, the second of the two enzymes generating the lysosomal targeting signal mannose-6-phosphate. The first enzyme, N-acetylglucosaminylphosphotransferase, for which previous biochemical evidence had suggested both a pre- and a cis-Golgi localization in other cell types, cofractionated with the cis-Golgi rather than the intermediate compartment in Vero cells. The results suggest that the intermediate compartment defined by p53 has unique properties and does not exhibit typical features of rough ER and cis-Golgi.     

Fc receptor endocytosis is controlled by a cytoplasmic domain determinant that actively prevents coated pit localization

Macrophages and B-lymphocytes express two major isoforms of Fc receptor (FcRII-B2 and FcRII-B1) that exhibit distinct capacities for endocytosis. This difference in function reflects the presence of an in-frame insertion of 47 amino acids in the cytoplasmic domain of the lymphocyte isoform (FcRII-B1) due to alternative mRNA splicing. By expressing wild type and mutant FcRII cDNAs in fibroblasts, we have now examined the mechanism by which the insertion acts to prevent coated pit localization and endocytosis. We first identified the region of the FcRII-B2 cytoplasmic domain that is required for rapid internalization. Using a biochemical assay for endocytosis and an immuno-EM assay to determine coated pit localization directly, we found that the distal half of the cytoplasmic domain, particularly a region including residues 18-31, as needed for coated pit-mediated endocytosis. Elimination of the tyrosine residues at position 26 and 43, separately or together, had little effect on coated pit localization and a partial effect on endocytosis of ligand. Since the FcRII-B1 insertion occurs in the membrane-proximal region of the cytoplasmic domain (residue 6) not required for internalization, it is unlikely to act by physically disrupting the coated pit localization determinant. In fact, the insertion was found to prevent endocytosis irrespective of its position in the cytoplasmic tail and appeared to selectively exclude the receptor from coated regions. Moreover, receptors bearing the insertion exhibited a temperature- and ligand-dependent association with a detergent-insoluble fraction and with actin filaments, perhaps in part explaining the inability of FcRII-B1 to enter coated pits.