MAOA and MAOB are key iso-enzymes that degrade biogenic and dietary amines. MAOA preferentially oxidizes serotonin (5-hydroxytryptamine, or 5-HT) and norepinephrine (NE), whereas MAOB preferentially oxidizes beta-phenylethylamine (PEA). Both forms can oxidize dopamine (DA). A mutation in MAOA results in a clinical phenotype characterized by borderline mental retardation and impaired impulse control. X-chromosomal deletions which include MAOB were found in patients suffering from atypical Norrie's disease, which is characterized by blindness and impaired hearing. Reduced MAOB activity has been found in type-II alcoholism and in cigarette smokers. Because most alcoholics smoke, the effects of alcohol on MAOB activity remain to be determined. Here we show that targetted inactivation of MAOB in mice increases levels of PEA but not those of 5-HT, NE and DA, demonstrating a primary role for MAOB in the metabolism of PEA. PEA has been implicated in modulating mood and affect. Indeed, MAOB-deficient mice showed an increased reactivity to stress. In addition, mutant mice were resistant to the neurodegenerative effects of MPTP, a toxin that induces a condition reminiscent of Parkinson's disease.

Two cases are reported of congenital intrahepatic portacaval shunts in middle-aged women who had encephalopathy or hypoglycemia. Real-time ultrasound (US) investigations revealed vascular communication between the left portal and hepatic veins in one patient and communication between the right portal and hepatic veins in the other. These findings were confirmed using angiography with pressure measurement. One patient underwent surgery; the other received dietetic treatment. The findings in these two cases are compared with those of three previously reported cases.

A single preoperative dose of diclofenac reduces the intensity of acute postcraniotomy headache and decreases analgesic requirements over five postoperative days in adults: a single center, randomized, blinded trial This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. KTIA_13_NAP-A-II/5. None of the authors has a personal financial interest in this research. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2 AbstractObjective: Postcraniotomy headache causes considerable pain and can be difficult to treat. We therefore tested the hypothesis that a single 100-mg preoperative dose of diclofenac reduces the intensity of postcraniotomy headache, and reduces analgesic requirements.Methods: 200 patients having elective craniotomies were randomly assigned to diclofenac (n=100) or control (n=100). Pain severity was assessed by an independent observer using a 10-cm-long visual analogue scale the evening of surgery, and on the 1st and 5th postoperative days. Analgesics given during the first five postoperative days were converted to intramuscular morphine equivalents.Results were compared using Mann-Whitney-tests; P<0.05 was considered statistically significant.Results: Baseline and surgical characteristics were comparable in the diclofenac and control groups. Visual analogue pain scores were slightly, but significantly lower with diclofenac at all times (means and 95% confidence intervals): the evening of surgery, 2.47 (1.8-3.1) vs. 4. 37(5.0-3.7), (P<0.001); first postoperative day, 3.98 (3.4-4.6) vs.5.6 (4.9-6.2) cm (P<0.001) and 5th postoperative day: 2.8 (2.2-3.4) vs. 4.0 ± (3.3-4.7) cm (P = 0.013). Diclofenac reduced systemic analgesic requirements over the initial five postoperative days (mean and 95% CI): 3.3 (2.6 -3.9) vs. 4.3 (3.5-5.1) mg morphine equivalents (p<0.05). Conclusions: Preoperative diclofenac administration reduces postcraniotomyheadache and postoperative analgesic requirements -a benefit that persisted throughout five postoperative days.

The generation of nitric oxide (NO) aggravates neuronal injury. (6R)-5,6,7,8-Tetrahydro-L-biopterin (BH4) is an essential cofactor in the synthesis of NO by nitric oxide synthase (NOS). We attempted to attenuate neuron degeneration by blocking the synthesis of the cofactor BH4 using N-acetyl-3-O-methyldopamine (NAMDA). In vitro data demonstrate that NAMDA inhibited GTP cyclohydrolase I, the rate-limiting enzyme for BH4 biosynthesis, and reduced nitrite accumulation, an oxidative metabolite of NO, without directly inhibiting NOS activity. Animals exposed to transient forebrain ischemia and treated with NAMDA demonstrated marked reductions in ischemia-induced BH4 levels, NADPH-diaphorase activity, and caspase-3 gene expression in the CA1 hippocampus. Moreover, delayed neuronal injury in the CA1 hippocampal region was significantly attenuated by NAMDA. For the first time, these data demonstrate that a cofactor, BH4, plays a significant role in the generation of ischemic neuronal death, and that blockade of BH4 biosynthesis may provide novel strategies for neuroprotection.