Global database of paleocurrent trends through the Phanerozoic and Precambrian.

Paleocurrents are sedimentological features contained in all sedimentary deposits, enabling the direction of movement of the sediment and the containing fluid at the time of deposition to be determined. This database contains paleocurrent directions and other relevant associated data from published sources and theses and dissertations for the entire Phanerozoic and Precambrian for all continents. Such information may be of general interest to sedimentologists and will be of specific interest in sedimentary basin analysis, and to petroleum geologists and mineralogists seeking source areas. Paleocurrents may also be useful in plate reconstructions and in testing the timing of global tectonic events.

Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.

A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers.

Benzo- and cyclohexanomazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.

A series of mazindol (1), homomazindol (2), and bishomomazindol (3) derivatives with a benzo or cyclohexano ring fused at various sites were prepared as part of an SAR study to determine the effect of increased aliphatic and aromatic lipophilicity on selected in vitro assays used to identify potential cocaine-like and cocaine antagonism activity. Very good (IC(50) = 2-3 nM) inhibition of [(3)H] WIN 35,428 and [(125)I] RTI-55 binding on rat or guinea pig striatal membranes and HEK cells expressing cDNA for the human dopamine transporter (HEK-hDAT) was shown by the 8,9-benzomazindol 25 and 9,10-benzohomomazindol 28. All new compounds were weaker inhibitors of [(3)H] DA uptake in HEK-hDAT cells than 1 and 2. No improvement in the binding selectivity ratio (SERT/DAT and NET/DAT) was found when compared to 2. Compounds 25and 28 showed a considerable increase versus 1 in uptake/binding discrimination ratios at the DAT (311.0 and 182.1 vs 0.9), SERT (33.6 and 127.3 vs 1.9), and NET (7.3 and 10.0 vs 0.3).

Predicting treatment response in depressed and non-depressed chronic pain patients.

Although it has often been observed that chronic pain and depression are associated, there have been few systematic comparisons of chronic pain patients with and without depression. In the study reported in this article, depressed and non-depressed chronic pain patients were found to be quite similar with respect to demographic, pain-related, and treatment response variables. The primary aim of the study, however, was to examine the hypothesis that treatment response in these two groups of patients would be predicted by different patterns of variables. In non-depressed patients, beneficial response to treatment was related to a greater number of treatment visits, not receiving workmen's compensation, fewer previous types of treatment, and low back pain. As predicted, a different pattern of predictors of treatment response was found for the depressed patients, who were more likely to benefit when they were employed at the beginning of treatment and when their pain was of shorter duration. These results suggest that activity and active involvement in treatment are particularly important with chronic pain patients who are depressed. In addition, they suggest that the best prediction of treatment response in future research on chronic pain patients may be achieved by dividing patients into groups based on psychological characteristics.

Unraveling the effects of compensation, litigation, and employment on treatment response in chronic pain.

Although it has often been suggested that chronic pain patients who are receiving workmen's compensation or who have litigation pending are less likely to benefit from treatment, the results of outcome studies of this question conducted by various pain clinics have been inconsistent. We hypothesized that poorer outcome in such patients may be related to the fact that they are less likely to be working and that the inconsistent results in the literature may therefore be explained by variability among studies in the percentages of patients who are receiving compensation (or who have litigation pending) who are also working. We examined the relationships among compensation, litigation, employment, and short- and long-term treatment response in a series of 454 chronic pain patients. Compensation benefits and employment status both predicted poorer short-term outcome in univariate analyses; however, when employment and compensation were jointly used to predict outcome in multiple regression analyses, only employment was significant. In additional analyses, only employment significantly predicted long-term outcome, whereas compensation and litigation did not. Our results suggest that it would be valuable to redirect attention away from the deleterious effects of the 'compensation neurosis' and toward the roles of activity and employment in the treatment and rehabilitation of chronic pain patients.