5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

The binding and processing of monoclonal human IgG1 by cells of a human macrophage-like cell line (U937)

The goal of these experiments was to assess the relationship between the binding and processing of IgG by Fc-receptor-bearing cells. Cells of the U937 human macrophage-like cell line were incubated with 125I- labeled monomers, dimers, oligomers (composed of 2-4 IgG1 subunits), and HP (heavy polymers composed of 5 or more subunits per polymer) of monoclonal human IgG1 in vitro. Binding was assessed by spinning cells through a layer of phthalate oils. Internalization of IgG1 was assessed by quantitating residual binding to cells after surface-bound IgG was removed by a brief treatment with a solution containing 0.25 M acetic acid and 0.5 M sodium chloride. Catabolism was assessed by measuring the release of radioactive fragments of IgG1, which were not precipitated by 10% trichloroacetic acid. Unstimulated U937 bound about 10,000 molecules per cell of IgG1 monomer, with an equilibrium binding constant (Ka) of 5 X 10(8) M-1. After stimulation with a conditioned medium in vitro, binding per cell was increased 3-7--fold, and the Ka was decreased 2-4--fold. Both unstimulated and stimulated cells internalized and catabolized labeled IgG1 HP, but stimulated cells internalized and digested much more IgG1 HP per cell than unstimulated cells. Both monomers and dimers of IgG1 were internalized and degraded very slowly by stimulated cells, even though both preparations readily bound to cells. In contrast, oligomers and (to an even greater extent) IgG1 HP were internalized and degraded much more rapidly. Internalization of IgG1 HP was markedly inhibited by incubation at 4 degrees C, but not by incubation with a variety of metabolic inhibitors. Catabolism was inhibited by chloroquine and monensin (inhibitors of lysosomal acidification) and by cytochalasin (an inhibitor of microfilament polymerization). Binding to the surface of cells was not markedly inhibited by any agent tested. The capacity of cells to bind labeled IgG1 was markedly reduced by prior incubation in the presence of unlabeled IgG1. This reduction was in part due to the steric blockade of receptors caused by the avid, but reversible, binding of IgG1. In addition, IgG1 oligomers or HP (but not IgG1 monomers or dimers) also caused an irreversible reduction in the number of Fc receptors by a process analogous to receptor down-regulation, as observed in other receptor--ligand systems.     

Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial

Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.     

A study of the effect of oral glucose loading on plasma oxidant:antioxidant balance in normal subjects

Summary Background Antioxidant defence has been reported to decrease, and oxidative stress to increase, after oral glucose loading in both normal and diabetic subjects. If confirmed in normal subjects, glucose–induced antioxidant depletion has important implications for health in relation to the modern, sugar–rich diet. Aim of the study To investigate changes in plasma biomarkers of oxidant:antioxidant balance in non–diabetic subjects following oral glucose loading. Baseline inter–relationships between biomarkers of glycaemic control, oxidant:antioxidant balance and inflammation were also explored. Methods A singleblinded, placebo–controlled, crossover intervention trial involving 10 healthy, consenting subjects. Venous blood was collected after ingestion of 75 g glucose in 300 mL water, or of water alone. Blood was collected at 0 time (fasting) and 30, 60, 90, 120 min post–ingestion. Within 2 weeks the procedure was repeated with volunteers crossedover onto the other treatment. Plasma total antioxidant capacity (as the FRAP value), ascorbic acid, –tocopherol, uric acid, malondialdehyde (MDA), allantoin and high sensitivity C–reactive protein (hsCRP), glucose and insulin, were measured in all samples. Paired results post–glucose and post–water at each time interval were compared using the Wilcoxon matched–pairs signed–ranks test. Results Normal glucose tolerance was observed in all subjects, although, as expected, plasma glucose and insulin increased significantly (p < 0.05, n = 10) after glucose loading. Post–glucose responses in plasma FRAP and the individual antioxidants tested were not significantly different to the responses seen post–water, although both FRAP and –tocopherol decreased slightly. Neither were postglucose changes in plasma MDA and allantoin, putative biomarkers of oxidative stress, significantly different to those after intake of water alone. Plasma FRAP and -tocopherol also decreased slightly, but not significantly, after intake of water. A significant direct correlation (r = 0.867, p < 0.001, n = 10) was found between fasting allantoin and (log transformed) hsCRP concentrations. Conclusions These new data from a controlled intervention trial indicate that acute, transient increases in plasma glucose following oral intake of a large glucose load do not, as previously reported, cause a significant decrease in plasma antioxidants or increase oxidative stress in non–diabetic subjects. This is reassuring given the large quantities of sugar ingested by children and adolescents. However, a small decrease in plasma antioxidant capacity was seen after ingestion of water and of glucose, and it is possible that intake of glucose without concomitant intake of antioxidants in susceptible individuals may cause oxidative stress. Further work is needed in relation to diabetic subjects and a possible glucose threshold for this. The finding of a direct relationship between allantoin, a biomarker of oxidative stress, and hsCRP, a marker of inflammation and CHD predictor, in healthy subjects is interesting and indicates a link between sub–clinical inflammation and oxidative stress.     

Diet and health: nursing perspective for the health of our aging population

For most age-related disorders there is no cure, and treatment is expensive and often ineffective. Thus, disease prevention is an issue of increasing concern and importance. Nurses form the largest professional healthcare group in the world, and the professional code of the modern day nurse advocates health promotion as a primary role. Nurses, by virtue of their close, direct interaction with their community and clients, are in a strong position to disseminate and reinforce the message of health promotion with the aim of achieving functional longevity in our aging population. This requires that nurses themselves increase their awareness, knowledge and understanding of relevant interdisciplinary research findings. In the current review, the influence of diet on the risk of four of the most prevalent age-related diseases (cancer, cardiovascular disease, dementia and diabetes) is presented, and the underlying mechanisms of influence are discussed, with particular focus on antioxidant-rich foods.