The role of the neuromodulator adenosine in alcohols actions.

The interaction between the neuromodulator adenosine and adenosine receptors on the surface of neurons modifies the neurons responses to neurotransmitters. The activated adenosine receptors alter the levels of small signaling molecules (i.e., second messengers) in the cells. Depending on the receptors and cells involved, these changes can make it easier or more difficult for neurotransmitters to excite the cell. Adenosines activity is regulated by proteins called nucleoside transporters, which carry adenosine into and out of the cell. Alcohol interferes with the function of the adenosine system. For example, both acute and chronic alcohol exposure affect the function of the adenosine-carrying nucleoside transporters, thereby indirectly altering the second-messenger levels in the cells. Through this mechanism, adenosine may mediate some of alcohols effects, such as intoxication, motor incoordination, and sedation

Differential Muc2 and Muc5ac secretion by stimulated guinea pig tracheal epithelial cells in vitro

BACKGROUND: Mucus overproduction is a characteristic of inflammatory pulmonary diseases including asthma, chronic bronchitis, and cystic fibrosis. Expression of two mucin genes, MUC2 and MUC5AC, and their protein products (mucins), is modulated in certain disease states. Understanding the signaling mechanisms that regulate the production and secretion of these major mucus components may contribute significantly to development of effective therapies to modify their expression in inflamed airways. METHODS: To study the differential expression of Muc2 and Muc5ac, a novel monoclonal antibody recognizing guinea pig Muc2 and a commercially-available antibody against human MUC5AC were optimized for recognition of specific guinea pig mucins by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry (IHC). These antibodies were then used to analyze expression of Muc2 and another mucin subtype (likely Muc5ac) in guinea pig tracheal epithelial (GPTE) cells stimulated with a mixture of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interferon- γ (IFN-γ)]. RESULTS: The anti-Muc2 (C4) and anti-MUC5AC (45M1) monoclonal antibodies specifically recognized proteins located in Muc2-dominant small intestinal and Muc5ac-dominant stomach mucosae, respectively, in both Western and ELISA experimental protocols. IHC protocols confirmed that C4 recognizes murine small intestine mucosal proteins while 45M1 does not react. C4 and 45M1 also stained specific epithelial cells in guinea pig lung sections. In the resting state, Muc2 was recognized as a highly expressed intracellular mucin in GPTE cells in vitro. Following cytokine exposure, secretion of Muc2, but not the mucin recognized by the 45M1 antibody (likely Muc5ac), was increased from the GPTE cells, with a concomitant increase in intracellular expression of both mucins. CONCLUSION: Given the tissue specificity in IHC and the differential hybridization to high molecular weight proteins by Western blot, we conclude that the antibodies used in this study can recognize specific mucin subtypes in guinea pig airway epithelium and in proteins from GPTE cells. In addition, Muc2 is highly expressed constitutively, modulated by inflammation, and secreted differentially (as compared to Muc5ac) in GPTE cells. This finding contrasts with expression patterns in the airway epithelium of a variety of mammalian species in which only Muc5ac predominates

Antimicrobial proteins and polypeptides in pulmonary innate defence

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future

Primary cerebellar glioblastoma multiforme

Glioblastoma multiforme in adults arising in the cerebellum is a rare tumor, well documented in only 13 cases in the literature. We report a fourteenth case, an 80-year-old female, and reassess the clinical and CT aspects of this tumor based on a review of the world's literature. The median age of patients is 53 years with a median survival of three months, which is less than adult cerebral hemisphere malignant gliomas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45390/1/11060_2004_Article_BF00151226.pd

The role of the neuromodulator adenosine in alcohols actions.

The interaction between the neuromodulator adenosine and adenosine receptors on the surface of neurons modifies the neurons responses to neurotransmitters. The activated adenosine receptors alter the levels of small signaling molecules (i.e., second messengers) in the cells. Depending on the receptors and cells involved, these changes can make it easier or more difficult for neurotransmitters to excite the cell. Adenosines activity is regulated by proteins called nucleoside transporters, which carry adenosine into and out of the cell. Alcohol interferes with the function of the adenosine system. For example, both acute and chronic alcohol exposure affect the function of the adenosine-carrying nucleoside transporters, thereby indirectly altering the second-messenger levels in the cells. Through this mechanism, adenosine may mediate some of alcohols effects, such as intoxication, motor incoordination, and sedation

Melatonin inhibition of nicotine-stimulated dopamine release in PC12 cells

Melatonin, a pineal hormone, modifies numerous physiologic processes including circadian rhythms and sleep. In specific tissues, melatonin appears to have an inverse relationship with dopamine. To examine this relationship, a pheochromocytoma cell line (PC12) was used to determine the extent of melatonin’s ability to inhibit nicotine-stimulated dopamine release. Multiple experiments were conducted that examined: (1) the dose response of acute melatonin (5 min); (2) the effects of chronic melatonin (16 h pre-exposure); (3) the effects of prior nicotine or melatonin exposure (5 min) on melatonin’s ability to alter dopamine release from a second 5-min nicotine exposure; and (4) the role of melatonin receptors (by pertussis toxin inhibition) on nicotine-stimulated dopamine release. In the dose response studies, melatonin inhibited nicotine-stimulated dopamine release with an ED50 of 8.6 μM. Chronic exposure to melatonin had no effect on melatonin’s acute inhibition of nicotine-stimulated dopamine release. Prior nicotine or melatonin exposure had little effect on subsequent melatonin or nicotine exposure, except that the cells exposed to nicotine were not responsive to a second exposure to nicotine. Blockade of melatonin receptor function by pre-exposure to pertussis toxin (16 h) did not prevent melatonin’s inhibition of nicotine-stimulated dopamine release. However, the toxin-treated cells were less inhibited by melatonin when compared to control cells suggesting a partial role for melatonin receptors. These results indicate that melatonin can acutely inhibit nicotine-stimulated dopamine release in PC12 cells. This model system allows detailed examination of melatonin’s cellular actions as well as supporting a role for melatonin on neuronal dopamine release

CARDIOMETABOLIC RESPONSES TO SELF-REGULATED SHALLOW WATER EXERCISE

M. Fisher, L. D’Acquisto, D. D’Acquisto, K. Roemer, J. Tesfaye, M. Dohrman, L. Miller Central Washington University, Ellensburg, WA Systematically regulating intensity while exercising in water is problematic given the nature of the workout medium. One approach to controlling exercise intensity is self-regulation by instructing participants to exercise over a range of prescribed rating of perceived exertions (e.g. RPE, Borg 6-20 scale). PURPOSE: This study investigated the cardiorespiratory responses to a series of incremental, perceptually self-regulated shallow water exercise (SR-SWE) efforts. It was hypothesized that (1) a steady rate cardiorespiratory response (oxygen uptake (V̇O2)& heart rate (HR)) for sustained SR-SWE efforts prescribed at RPE 9, 11, 13, 15 and 17 would be achieved, and (2) V̇O2 would be linearly, positively and strongly related to prescribed perceived exertions ranging from RPE 9 to 17. METHODS: Male volunteers (n=6, 23±1 years) participated in a familiarization session and a second testing period in which they performed five, five min SR-SWE efforts prescribed at RPE 9, 11, 13, 15, and 17. In addition, participants performed an incremental, five min SR-SWE bout to a max of RPE 20 to determine peak V̇O2 and HR. V̇O2 (Parvo-Medics TrueMax 2400, indirect calorimetry), HR (Polar, telemetry) and blood lactate (BLa) concentration (Analox Instruments) were measured for all SR-SWE efforts. Participants were immersed to axillary level (~75% of stature; water temperature, ~28-290 Celsius) for all exercise efforts. RESULTS: Peak V̇O2, HR, respiratory exchange ratio, and BLa was 3.63±0.25 l·min-1, 187±6 b·min-1, 1.08±0.03, and 11.7±1.2 mM, respectively. For RPE efforts 9, 11, 13, 15 & 17, both V̇O2 and HR for mins two through five were the same (P\u3e0.05). Steady rate V̇O2 and HR, and BLa ranged from 0.69±0.10 l·min-1, 83±5.8 b·min-1, 1.53±0.6 mM (RPE 9, “very light”) to 3.10±0.471 l·min-1, 168±7 b·min-1, and 6.4±1.5 mM (RPE 17, “very hard”), respectively (P\u3c0.05). Percent V̇O2 and %HR peak increased in a step-wise fashion from RPE 9 (19.0±2.0 and 44.3±2.7%) to RPE 17 (85.1±7.4 and 90.4±2.5%, respectively) (P\u3c0.05). V̇O2 and HR were linearly and strongly correlated with RPE (R ranged from 0.94 to 0.99, p\u3c0.05). CONCLUSION: Self-regulation of intensity based on prescribed RPE is a viable way of regulating intensity while exercising in a shallow water medium. Supported by CWU-Ellensburg Master\u27s Research or Creative Activity Fellowship