Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2007
Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation.
UV radiation (UVR) is a complete carcinogen that elicits a constellation of pathological events, including direct DNA damage, generation of reactive oxidants that peroxidize lipids and damage other cellular components, initiation of inflammation, and suppression of the immune response. Recent dramatic increases in the incidence of nonmelanoma skin cancers are largely attributable to higher exposure of an aging population to UVR. Therefore, the development of cellular strategies for intrinsic protection of the skin against the deleterious effects of UVR is imperative. ⋯ Topical application of sulforaphane-rich extracts of 3-day-old broccoli sprouts up-regulated phase 2 enzymes in the mouse and human skin, protected against UVR-induced inflammation and edema in mice, and reduced susceptibility to erythema arising from narrow-band 311-nm UVR in humans. In six human subjects (three males and three females, 28-53 years of age), the mean reduction in erythema across six doses of UVR (300-800 mJ/cm(2) in 100 mJ/cm(2) increments) was 37.7% (range 8.37-78.1%; P = 0.025). This protection against a carcinogen in humans is catalytic and long lasting.
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2007
Gossip as an alternative for direct observation in games of indirect reciprocity.
Communication about social topics is abundant in human societies, and many functions have been attributed to such gossiping. One of these proposed functions is the management of reputations. Reputation by itself has been shown to have a strong influence on cooperation dynamics in games of indirect reciprocity, and this notion helps to explain the observed high level of cooperation in humans. ⋯ We show that gossip has a strong influence on the resulting behavior even when participants have access to the original information (i.e., direct observation) as well as gossip about the same information. Thus, it is evident that gossip has a strong manipulative potential. Furthermore, gossip about cooperative individuals is more positive than gossip about uncooperative individuals, gossip comments transmit social information successfully, and cooperation levels are higher when people encounter positive compared with negative gossip.
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2007
S-nitrosohemoglobin deficiency: a mechanism for loss of physiological activity in banked blood.
RBCs distribute oxygen to tissues, but, paradoxically, blood transfusion does not always improve oxygen delivery and is associated with ischemic events. We hypothesized that storage of blood would result in loss of NO bioactivity, impairing RBC vasodilation and thus compromising blood flow, and that repleting NO bioactivity would restore RBC function. ⋯ In addition, canine coronary blood flow was greater during infusion of renitrosylated RBCs than during infusion of S-nitrosothiol-depleted RBCs, and this difference in coronary flow was accentuated by hypoxemia (P < 0.001). Our findings indicate that NO bioactivity is depleted in banked blood, impairing the vasodilatory response to hypoxia, and they suggest that SNO-Hb repletion may improve transfusion efficacy.
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Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit and risk of RBC transfusion. We analyzed changes occurring during RBC storage focusing on RBC deformability, RBC-dependent vasoregulatory function, and S-nitrosohemoglobin (SNO-Hb), through which hemoglobin (Hb) O(2) desaturation is coupled to regional increases in blood flow in vivo (hypoxic vasodilation). ⋯ RBC deformability assayed at a physiological shear stress decreased gradually over the 42-day period (P < 0.001). Time courses vary for several storage-induced defects that might account for recent observations linking blood transfusion with adverse outcomes. Of clinical concern is that SNO levels, and their physiological correlate, RBC-dependent vasodilation, become depressed soon after collection, suggesting that even "fresh" blood may have developed adverse biological characteristics.
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2007
Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus.
Bilateral, high-frequency stimulation (HFS) of the subthalamic nucleus (STN) is the surgical therapy of choice for movement disability in advanced Parkinson's disease (PD), but this procedure evokes debilitating psychiatric effects, including depressed mood, of unknown neural origin. Here, we report the unexpected finding that HFS of the STN inhibits midbrain 5-hydroxytryptamine (5-HT) neurons to evoke depression-related behavioral changes. We found that bilateral HFS of the STN consistently inhibited (40-50%) the firing rate of 5-HT neurons in the dorsal raphe nucleus of the rat, but not neighboring non-5-HT neurons. ⋯ Importantly, the depressive-like behavior elicited by HFS of the STN was reversed by a selective 5-HT-enhancing antidepressant, thereby linking the behavioral change to decreased 5-HT neuronal activity. Overall, these findings link reduced 5-HT function to the psychiatric effects of HFS of the STN observed in PD patients and provide a rational basis for their clinical management. More generally, the powerful interaction between the STN and 5-HT system uncovered here offers insights into the high level of comorbidity of basal ganglia disease and mood disorder.