Caffeic acid improves the bioavailability of l‐dopa in rabbit plasma

The impacts of caffeic acid (3,4‐dihydroxycinnamic acid, CA) on the pharmacokinetics of levodopa (L‐dopa) were studied in rabbits. A single dose of 5/1.25 mg·kg^?1 l ‐dopa/carbidopa was administered alone or was co‐administered with three different doses of caffeic acid (2.5, 5, and 10 mg·kg^?1), or a single dose of 5 mg·kg^?1 caffeic acid was administered alone via an intramuscular route to six rabbits each in a crossover treatment protocol. Plasma levels of l ‐dopa, 3‐O‐methyldopa (3‐OMD), caffeic acid, and ferulic acid were determined and subsequently used to calculate their pharmacokinetic parameters. The results indicated that caffeic acid administered at a dose of 10 mg·kg^?1 decreased about 22% of the peripheral formation of 3‐OMD and about 31% of the C_max of 3‐OMD. In addition, the metabolic ratios (MR, AUC of 3‐OMD/AUC of L‐dopa) decreased by about 22%. Results also indicated that caffeic acid significantly decreased the proportion of 3‐OMD (p < 0.05). In contrast, the parameters of neither caffeic acid nor ferulic acid were significantly affected by l ‐dopa/carbidopa. In conclusion, caffeic acid at a dose of 10 mg·kg^?1 can significantly affect the COMT metabolic pathway of L‐dopa. Copyright © 2009 John Wiley & Sons, Ltd.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Changes in the Amphibian Antibody Repertoire are Correlated With Metamorphosis and not With Age or Size

Tadpole and adult Xenopus, manipulated to be of comparable size, exhibited stagespecific antibody expression. The production of adult-type higher-affinity anti-DNP antibodies proved to be independent of the age and size of the individual and is concomitant with the completion of metamorphosis. The appearance of new antibody specificities at such a time suggests that their expression occurs with the cell turnover and renewal during a period of morphological changes.     

Small isolated paraspinal arteriovenous fistula.

We report a case of a small, isolated paraspinal arteriovenous fistula (AVF) that arose in an adult without obvious trauma. The fistula, despite its extraspinal location and small size, caused hypertension of the intrathecal venous system and produced symptoms that were similar to those of spinal dural AVF. Detecting such a small lesion is difficult, but contrast-enhanced MR imaging can prove helpful in this regard.     

NMR Microscopy of Single Neurons Using Spin Echo and Line Narrowed 2DFT Imaging

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T₂ relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T₂ difference between the nucleus and cytoplasm in these cells represents primarily a true T₂ relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.     

Factors influencing calcitriol metabolism in renal failure

Metabolic clearance rate (MCR) and production rate (PR) of calcitriol is decreased in experimental renal failure. In this experiment, we studied uremia and secondary hyperparathyroidism as possible causes of the abnormal calcitriol metabolism. Normal rats were made uremic by infusing phosphorus-free urine for 24 hours. Both the MCR (0.22 +/- 0.01 ml/min/kg, N = 6 P less than 0.001) and the PR (16.6 +/- 1.97 ng/kg/day, P less than 0.01) of calcitriol were significantly suppressed in normal rats following urine infusion when compared to saline infused rats (MCR, 0.30 +/- 0.01; PR, 32.9 +/- 4.1, N = 6). Different levels of protein intake by rats with renal failure produced by subtotal nephrectomy also alter the PR but not the MCR of calcitriol. Thus, the synthesis of calcitriol was significantly lower in rats with renal failure fed a high protein (50% protein) diet (17.6 +/- 0.7 ng/kg/day, N = 8, P less than 0.001) than in rats with renal failure fed a normal protein (20% protein) diet (22.2 +/- 1.4, N = 7). Thyroparathyroidectomy (TPTX) did not alter the MCR of calcitriol in renal failure, even though parathyroid hormone, which may suppress the degradation enzyme, could be elevated in this model of renal failure. The MCR of TPTXed rats with renal failure (0.15 +/- 0.01 ml/min/kg, N = 7) remained lower than that of the TPTXed control rats (0.19 +/- 0.01, N = 7, P less than 0.001), and chronic infusion of PTH to TPTXed rats with renal failure did not change the MCR of calcitriol (0.15 +/- 0.01, vs. control, 0.24 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)