Chemical and pharmacological studies of Phyllanthus caroliniensis in mice

We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.     

Current directions in research on understanding and preventing intoxicated aggression

The present paper describes promising research directions that emerged from a recent international conference on intoxication and aggression and from the scientific literature generally. In this overview, intoxicated aggression is seen as arising from an interactional process involving multiple contributing factors or causes. This model helps to define research directions that can further understanding and prevention. First, the societal/cultural framing of intoxication and aggression exerts a powerful influence on drinking behaviour and needs to be better understood. Another important area for research is the moderating role on alcohol-related aggression of personal factors such as predisposition to aggression and individual differences in expectations about alcohol and aggression. Research on the role of basic pharmacological effects of alcohol in increasing the likelihood of aggressive behaviour is also a critical aspect of understanding intoxicated aggression. Drinking contexts and environments play a considerable role in the relationship between intoxication and aggressive behaviour and need to be better understood. Another critical direction for future research is the study of intoxicated aggression as a process involving the interaction of the person, the situation and the effects of alcohol in natural and experimental settings. Finally, the paper highlights promising directions for research on interventions to prevent intoxicated aggression and violence.     

Phenylalanine and tyrosine metabolism in neonates receiving parenteral nutrition differing in pattern of amino acids

Tyrosine is considered to be an indispensable dietary amino acid in the neonate, yet achieving adequate parenteral tyrosine intake is difficult due to its poor solubility. Increasing the supply of phenylalanine is the most common means of compensating for low tyrosine levels. Unfortunately, plasma phenylalanine concentrations are sometimes elevated in infants receiving high phenylalanine intake. This led us to study the phenylalanine and tyrosine metabolism in 16 neonates randomized to receive total parenteral nutrition with either a high or a moderate phenylalanine-containing amino acid solution. A primed, 24-h continuous stable isotope infusion of L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine was given to enable the measurement of phenylalanine and tyrosine kinetics. Results demonstrated that 1) phenylalanine hydroxylation was significantly greater in infants receiving high phenylalanine, 2) phenylalanine oxidation and percent dose oxidized was also significantly greater in infants receiving high phenylalanine, 3) apparent phenylalanine retention was greater in neonates receiving high phenylalanine, and 4) alternate catabolites of phenylalanine and tyrosine metabolism were significantly greater in infants receiving high phenylalanine compared with moderate phenylalanine. We conclude that neonates respond to increased parenteral phenylalanine intake by increasing their hydroxylation and oxidation rates. The greater oxidation of phenylalanine in infants receiving high phenylalanine in conjunction with the urinary excretion of alternate catabolites of phenylalanine and tyrosine suggests that the high phenylalanine intake may be in excess of needs. However, the lower apparent phenylalanine retention observed in infants receiving moderate phenylalanine suggests that the total aromatic amino acid level of moderate phenylalanine may be deficient for neonatal needs.     

Racial differences in nitric oxide-mediated vasodilator response to mental stress in the forearm circulation

An abnormal hemodynamic response to stressful stimuli has been proposed as a mechanism involved in the higher prevalence of hypertension in blacks. Given the important role of nitric oxide (NO) in the regulation of cardiovascular homeostasis, we investigated the possibility of racial differences in vascular NO activity during mental stress. To test this hypothesis, we compared the forearm blood flow (FBF) response to mental stress in 14 white and 12 black healthy subjects during intra-arterial infusion of either saline or NO synthesis inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min). We also examined vascular responses of the two groups to intra-arterial infusion of sodium nitroprusside (0.8 to 3.2 microg/min), an exogenous NO donor. During saline infusion, the increase in FBF from baseline induced by mental stress was significantly higher in whites than in blacks (109+/-20% versus 58+/-8%; P=0.03). L-NMMA significantly reduced stress-induced increase in FBF in whites (from 109+/-20% to 54+/-11%; P=0.004) but not in blacks (from 58+/-8% to 42+/-10%; P=0.24); thus, the vasodilator effect of stress testing during L-NMMA was similar in whites and blacks (54+/-11% versus 42+/-10%; P=0.44). The vasodilator response to sodium nitroprusside was also lower in blacks than in whites (maximum flow, 6.9+/-2 versus 11.6+/-3.5 mL x min(-1) x dL(-1); P=0.001) and was not significantly modified by L-NMMA in either group. Our findings indicate that blacks have a reduced NO-dependent vasodilator activity during mental stress. This difference seems related to reduced sensitivity of smooth muscle to the vasodilator effect of NO and may play some role in the increased prevalence of hypertension and its complications in blacks.