Increased cardiac production of dihydroxyphenylalanine (DOPA) during sympathetic stimulation in anaesthetized dogs.

Entry of dihydroxyphenylalanine (DOPA) into plasma from specific organs may reflect regional activity of tyrosine hydroxylase, the enzyme responsible for the immediate synthesis of DOPA and rate-limiting for subsequent formation of catecholamines. Therefore, cardiac spillovers of DOPA, noradrenaline and the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), were examined during two periods of graded electrical stimulation of the sympathetic nerves to the heart in anesthetized dogs. Responses were examined before and after neuronal uptake blockade with desipramine. Cardiac spillover of DOPA increased by 1.8- and 4.4-fold during sympathetic stimulation before desipramine and by 1.6- and 3.3-fold after desipramine. Fold increases in cardiac spillover of DOPA were much lower than but positively related with fold increases in noradrenaline spillover (5.9- and 13.8-fold increases before and 9.0- and 15.8-fold increases after desipramine). Increases in cardiac spillover of DHPG (1.5- and 2.3-fold increases) were blocked by desipramine so that fold changes in spillover of DOPA were greater than and poorly related to changes in spillover of DHPG. Fold increases in cardiac spillover of DOPA showed a close one-to-one positive relationship with fold increases in the sum of cardiac spillovers of noradrenaline and dihydroxyphenylglycol before and after desipramine. For a given fold increase in noradrenaline release, transmitter turnover is increased fractionally and noradrenaline synthesis need also only increase fractionally to maintain transmitter stores constant. The close relationship between fold increases in cardiac spillover of DOPA and combined spillovers of noradrenaline and DHPG is consistent with regulation of tyrosine hydroxylase activity to match changes in noradrenaline synthesis with changes in noradrenaline turnover. Changes in cardiac spillover of DOPA appear to reflect local changes in tyrosine hydroxylase activity.     

Direct determination of homovanillic acid release from the human brain, an indicator of central dopaminergic activity

The plasma concentration of the dopamine (DA) metabolite, homovanillic acid (HVA), is used as an indicator of central nervous system dopaminergic activity. Using percutaneously inserted catheters we were able to obtain blood samples simultaneously from the right and left internal jugular veins. Veno-arterial HVA plasma concentration differences combined with adjusted organ plasma flows were used, according to the Fick Principle, to determine the HVA overflow from the brain. The HVA overflow from the liver was also measured. HVA overflow from the brain represented 12% of the total body HVA production. A similar amount was released from the liver, illustrating the limited validity of peripheral plasma HVA measurements as an indicator of central dopaminergic activity. HVA release from the human brain displayed a degree of asymmetry, the overflow into the left internal jugular vein being 36% greater than that into the right. Cerebral venous blood flow scans indicated that cortical cerebral regions drained preferentially into the right internal jugular; by inference the higher HVA overflow on the left originated from dopamine-rich subcortical brain areas. Since HVA in plasma may arise from the metabolism of DA existing either as a neurotransmitter or a norepinephrine (NE) precursor we measured the internal jugular vein plasma concentrations of NE, and its metabolite dihydroxyphenylglycol (DHPG), to determine whether they displayed a similar pattern of release to HVA. The overflow of both NE and DHPG into the right internal jugular vein was approximately double that on the left. Since the overflow of HVA did not parallel that of NE and DHPG it may be inferred that the origin of much of the subcortically produced HVA is from dopaminergic neurons and not from the metabolism of precursor DA in noradrenergic neurones or cerebrovascular sympathetic nerves.     

The comparison of selected life-history characteristics of Mesembryanthema species occurring on and off Mima-like mounds (heuweltjies) in semi arid southern Africa

Selected life-history characteristics of Mesembryanthema species occurring on and off mima-like mounds (heuweltjies) were compared at Tierberg in the southern Succulent Karoo, South Africa. Seed production, the number of seeds retained in seed capsules and germination behaviour were measured in fourteen species of Mesembryanthema which were representatives of two sub-families: the Ruschioideae and the Mesembryanthemoideae. Species occurring onheuweltjies had low overall germination and high seed retention compared with those species occurring offheuweltjies. A strong negative correlation was found between the degree of seed retention and maximum germination. It was proposed that rapid germination and low seed dormancy in species occurring on the flats would be a viable strategy where competition for safe recruitment sites is strong. Species occurring on the flats are long-lived woody shrubs, thus the resulting high levels of seedling mortality probably do not have a major impact on population dynamics.Heuweltjies are sites of intense disturbance. Plant species that occur onheuweltjies can also occur offheuweltjies in disturbed vegetation. Opportunistic life-history characteristics allow these species to colonise disturbed areas.Heuweltjie species thus act as pioneers in a successional process which results ultimately in the re-colonisation of the long-lived flats species. Phylogenetic factors may also determine the species distributions. Members of the Mesembryanthemoideae did not occur offheuweltjies in undisturbed areas. Most Ruschioideae were found on the flats but the few species that occurred onheuweltjies shared similar characteristics with the Mesembryanthemoideae. The primitive life-history characteristics exhibited by the Mesembryanthemoideae enable them to exploit disturbed conditions.     

Inhibition of Cell Growth and Proliferation in Human Glioma Cells and Normal Human Astrocytes Induced by 8-Cl-cAMP and Tiazofurin

Abstract

8–Cl-cAMP and tiazofurin (TR) are anti-tumor agents that besides their antiproliferative effect, also induce differentiation of tumor cells. Although, these agents exert a profound effect on the same events of tumor cell life, it is thought that 8-Cl-cAMP and TR act by modulating the signal transduction pathway through distinct mechanisms. We have compared their effect on two human glioma cell lines (U87 MG and U251 MG) and examined if there is selectivity in their action toward normal human astrocytes.     

Potential seed dispersal distances of native and non-native fleshy fruiting shrubs in the South African Mediterranean climate region

Bird flight distances for the small Zosterops capensis, the medium-size Pycnonotus capensis and the large Colius striatus were extracted from these birds’ initial ring and subsequent recapture locations and expressed on equivalent per km bases. The products of the bird-ring recapture records in nine different flight distance categories and daily consumption rates by these birds of seeds of two native (Chrysanthemoides monilifera and Olea europaea spp. africana) and two alien (Lantana camara and Solanum mauritianum) shrubs were used to construct seed dispersal curves. The dispersal distances to which ingested seeds were theoretically restricted were computed from the product of the retention time of seed in the birds’ guts and their flight speeds using published functions. All three bird species displayed thin long-tailed seed dispersal curves characterized by peaks at distances below 1 km which declined progressively with increasing distances, the tails extending to distances of up to 400 km. Flight distances corresponding with predicted seed gut retention times were 9.4 km in the small Z. capensis, 17.8 km in the medium size P. capensis and 21.2 km in the large C. striatus. These potential seed dispersal distances were much greater that the frequently reported long distance seed dispersal threshold of 1 km by frugivorous birds in fragmented landscapes.     

A preliminary study of the responsiveness to seasonal atmospheric and rainfall patterns of wash woodland species in the arid Richtersveld

Seasonal carbon and water relations were compared among seven tree or shrub wash woodland species in the winter rainfall desert of the Richtersveld National Park, South Africa. Plants were generally aseasonal with respect to gas exchange, but responsive to rainfall events with respect to water relations and phenology. Relatively narrow annual ranges in potential evapotranspiration due to the maritime influence could explain why these plants respond more to fluctuations in water acquisition potential than to evaporative demand. Two species were summer-deciduous, but one of them (Ozoroa concolor) responded to aseasonal summer rainfall by leafing out and flowering. These two species had high shoot xylem water potentials when in leaf. All other species were sclerophyllous evergreens with low water potentials, particularly the shallow-rooted shrub Zygophyllum prismatocarpum, and Boscia albitrunca which may have a different rooting pattern to the other phreatophytes. The latter species was also unique due to its high leaf nitrogen contents, photosynthetic rates and stomatal conductances, despite very low leaf water potentials. Leaf stable carbon isotope composition C¹³C) varied between species (–22 to –27), but was lower than the mean for arid regions worldwide. The values indicated moderately high levels of water use efficiency, but a less conservative strategy in two species, including Boscia albitrunca. The affinities of these species to summer rainfall biomes, their apparent decline in the western arid regions in recent geological history following aridification, and their absence southwards in the winter rainfall regions, suggest that these wash species rely on sporadic summer rainfall events to some extent. They may be at risk if predicted increases in temperature and changes in rainfall patterns alter their effective moisture availability.     

NPY and NPY Y1 receptor effects on noradrenaline overflow from the rat brain in vitro

Neurotransmitters and neuropeptides play important roles in the regulation of various neuroendocrine functions particularly feeding. The aim of this study was to investigate whether a functional interaction occurs among neuropeptide Y (NPY) at NPY Y₁ receptors and noradrenaline overflow, as this may contribute to the regulation of appetite. The release of endogenous noradrenaline and its metabolite 3,4-dihydroxyphenylglycol (DHPG) were examined from hypothalamic and medullary prisms using the technique of in vitro superfusion and high performance liquid chromatography (HPLC) with coulometric detection. Noradrenaline and DHPG overflow was investigated at rest, in response to NPY (0.1 μM) and in response to the NPY Y₁ receptor agonist, [Leu³¹,Pro³⁴]NPY (0.1 μM). Perfusion with NPY and [Leu³¹,Pro³⁴]NPY significantly reduced noradrenaline overflow from the hypothalamus and medulla. Perfusion with NPY and [Leu³¹,Pro³⁴]NPY was without significant effect on hypothalamic DHPG overflow, while medullary DHPG overflow was significantly reduced by NPY and [Leu³¹,Pro³⁴]NPY. Results from this study provide evidence of NPY Y₁ receptor-mediated inhibition of noradrenaline release in the hypothalamus and medulla, further illustrating a complex interaction between neurotransmitters and neuropeptides within the rat brain.     

Extra-adipocyte leptin release in human obesity and its relation to sympathoadrenal function

The link between the human sympathoadrenalmedullary system and the adipocyte hormone leptin is controversial. We measured total and regional norepinephrine spillover, epinephrine secretion rate, and extra-adipocyte leptin release in 22 lean [body mass index (BMI) < 26] and 20 obese (BMI > 28) normotensive men who underwent arterial and central venous catheterization. Because plasma clearance of leptin is primarily by renal removal, for men at steady state we could estimate whole body leptin release to plasma from renal plasma leptin extraction. Whole body leptin release was 1,950 +/- 643 (means +/- SE) ng/min in obese men and 382 +/- 124 ng/min in lean men (P < 0.05). Total and renal norepinephrine spillover rates correlated directly with whole body leptin secretion rate. Leptin is released from multiple nonadipocyte sites, which we tested by use of simultaneous arteriovenous blood sampling. We found a surprisingly large contribution of brain leptin release to the plasma leptin pool, 529 +/- 175 ng/min (> 40% whole body leptin release), with greater leptin release in obese than in lean men, 935 +/- 321 vs. 160 +/- 59 ng/min (P = 0.045). In parallel with leptin measurements, we also quantified brain serotonin turnover and jugular overflow of neuropeptide Y (NPY). Brain serotonin turnover was higher in obese than in lean men, 227 +/- 112 vs. 21 +/- 14 ng/min (P = 0.019), as was overflow of NPY from the brain, 12.9 +/- 1.4 vs. 5.3 +/- 2.2 ng/min (P = 0.042). These results suggest that leptin is released within the brain and at an increased rate in obese humans, in whom activation of brain serotonergic and NPY mechanisms also exists.     

Synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins

Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-]pyrimidine (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound 1e showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly.     

Relative performance of clumped vs. experimentally isolated plants in a South African winter-rainfall desert community

We conducted a factorial removal experiment in the arid strandveld onthe west coast of South Africa to test the hypothesis that perennial specieswith a preference for occurring in multi-species clumps shouldderive benefits from their association into clumps. Contrary to our hypothesis,we obtained evidence of competition for water in the clumped non-succulentspecies studied in the form of depressed water potentials. We were not able todetect any effect on leaf water contents associated with isolation, suggestingthat clumped plants are able to compensate physiologically in response tocompetitive stress. We also found that isolating individuals had no effect(positive or negative) on branch growth. Finally, we showed that isolatingindividuals exposed them to a far greater risk of damage by wind or animals. Inlight of these results we conclude that the spatial arrangement of plants inthis community does suggest a situation where the benefits associated withoccurring in clumps exceed any competitive costs.