Patients with SAH given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit. Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone; these data could be used to select therapies for patients with SAH. EudraCT no: 2009-013897-42; Current Controlled Trials no: ISRCTN88782125.

The effect of host genetic variation on the outcome of hepatitis C virus (HCV) infection and its treatment is poorly understood. The chemokine receptors CCR5, CCR2, and CCR3 and their ligands, RANTES, MCP-1, MCP-2, and MIP-1␣, are involved in the immune responses and the selective recruitment of lymphocytes to the liver in HCV infection. We studied 20 polymorphisms within these genes and investigated their association with persistent carriage of HCV, severity of liver disease, hepatic inflammation, and response to treatment in a large European cohort. Significant associations were found between CCR5-⌬32 and reduced portal inflammation (P ‫؍‬ H epatitis C virus (HCV) is a major global health problem with 1% to 2% of the world's population chronically infected. The prevalence of infection in the United Kingdom is approximately 0.5%, 1 but it is likely that this figure will continue to rise as more cases come to light. Persistent HCV infection has a very variable outcome, with 25% of those infected developing cirrhosis within 20 years, of whom 3% to 5% per year will proceed to hepatocellular carcinoma. A further 5% per year will develop liver failure, and 2% per year will die of a liver-related death. There is also a very variable response to treatment because only 40% of those treated with interferon alfa and ribavirin successfully clear the virus. 2,3 There are a number of epidemiologic and viral factors that influence susceptibility to persistent HCV infection, progression of HCV-related liver disease, and response to treatment, but host genetic factors are also influential. This study has examined 20 polymorphisms in the genes for the CC chemokine receptors (CCR) CCR5, CCR2, and CCR3 and their ligands, RANTES (regulated and normal T-cell expressed and secreted), MCP-1 (monocyte chemotactic protein), MCP-2, and MIP-1␣ (macrophage inflammatory protein), to try and elucidate their role in the immunopathologic outcome of HCV infection..Chemokines constitute a large family of small (8-10 kD) cytokines that are up-regulated in inflammation and whose effects are mediated by members of a family of 7 transmembrane domain, G protein-coupled receptors. 4 Their major role is in leukocyte migration and dependent processes such as immune surveillance and innate and adaptive immune responses. Chemokines have been

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Short-term treatment with lithium chloride stimulates the uptake of tryptophan and its conversion to serotonin by striate synaptosomes. Preincubation of striate synaptosomes with L-tryptophan and in vivo administration of L-tryptophan appear to act in a similar manner. Midbrain tryptophan hydroxylase activity is reduced in temporal continuity with the lithium-induced activation of tryptophan uptake and conversion. By 10 days, conversion of tryptophan to serotonin in nerve endings becomes a joint function of the maintained increased uptake of tryptophan and a decreased level of tryptophan hydroxylase activity in nerve endings. The occurrence of this delayed alteration corresponds in time to the previously described axoplasmic flow rate for tryptophan hydroxylase.

The effects of short- and long-term administration of morphine on the activity of two measurable forms of rat brain tryptophan hydroxylase were studied. Morphine administration produced an immediate decrease and a long-term increase in the nerve ending (particulate) enzyme activity but did not change the cell body (soluble) enzyme activity. Cocaine administration demonstrated a short-term decrease in measurable nerve ending enzyme activity that was due to the inhibition of the high affinity uptake (the Michaelis constant, K m is 10 -5 molar) of trytophan, the serotonin precursor. Cocaine did not affect the low affinity uptake (K m = 10 -3 molar) of tryptophan. Both the uptake of the precursor and the enzyme activity appeared to be drug-sensitive regulatory processes in the biosynthesis of serotonin.

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