Interaction of [3H]GBR 12935 and GBR 12909 with the dopamine uptake complex in nucleus accumbens

Although some behavioral effects of cocaine are hypothesized to be due to blockade of dopamine uptake in nucleus accumbens, it has been reported that in nucleus accumbens there are no specific cocaine binding sites and that cocaine is a weak inhibitor of dopamine uptake. [3H]GBR 12935 and an unlabelled analog, GBR 12909, are ligands that bind with great affinity and specificity to a site on dopamine uptake complex in striatum. We therefore investigated the interaction of these GBR compounds with the dopamine uptake complex in nucleus accumbens. We found specific high affinity [3H]GBR 12935 binding and a significant correlation between displacement of [3H]GBR 12935 binding by a series of compounds in striatum and nucleus accumbens. GBR 12909 inhibited dopamine uptake with equal potency in nucleus accumbens and striatum. Thus, there appear to be some aspects of the dopamine uptake complex in nucleus accumbens and striatum that are similar.     

Impact of a Pharmacist-Based Consult Service on Nutritional Rehabilitation of Nonambulatory Patients with Severe Developmental Disabilities

A pharmacist consult service was developed to evaluate the appropriateness of enteral feeding through a permanent ostomy in 24 nonambulatory patients with severe developmental disabilities. Several problems with enteral nutrition were identified. Policies to improve them were instituted, and several educational presentations were made. Pharmacists' actions were implemented, including assessment of energy needs by indirect calorimetry and rearrangement of enteral feeding schedules to achieve optimal nutrition support and pharmacotherapy administration. By the fourth month of the consult service, body weight in these patients increased from 101 ± 6% of baseline to 109 ± 7% (p<0.05). Weight continued to increase through the seventh month of the consult service to 116 ± 12% of baseline (p<0.0001). Measured resting energy expenditure for the group was 889 ± 170 kcal/day compared with the predicted 1055 ± 163 kcal/day.     

Total cortisol,free cortisol,and growth hormone associated with brief social separation experiences in young macaques

Many behavioral, immunological, and physiological consequences of brief maternal separation in bonnet (Macaca radiata) and pigtail monkeys (Macaca nemistrina) have been documented. However, the impact of social separation on plasma cortisol and growth hormone is unknown for these particular species. In the present study, the behavioral and endocrinological consequences of a 2-week maternal separation in socially housed infant bonnet and pigtail monkeys were followed. In seven pairs (separated and matched control) of bonnet and six pairs of pigtail infants, plasma was obtained under baseline, separated, and reunion conditions twice weekly for the duration of the study. Blood samples were obtained from both infants of the pair in approximately 10 min. Plasma total cortisol, free cortisol, and growth hormone were measured in these samples. Focal animal behavioral observations were made on all subjects twice daily throughout the study period. In both species, total cortisol and free cortisol rose immediately following maternal separation in comparison to the matched nonseparated controls and returned to basal levels (e.g., that of matched non-separted controls) following reunion with the mother. In contrast, plasma growth hormone rose only in the pigtail infants over a time course that peaked around the time of reunion. Multiple regression techniques indicated for the first week of separation, in the separated but not control subjects, that mean plasma free and total cortisol was positively related to distress behaviors (vocalization and postural slouch) observed during this week and negatively related to social behaviors (play and proximity to others) noted during the same period. In contrast, plasma growth hormone was related to both species and sex of the subjects but unrelated to behavioral variables. © 1995 John Wiley & Sons, Inc.     

The palmar radiocarpal ligaments: A study of adult and fetal human wrist joints

The palmar radiocarpal ligaments were studied with use of fifty-four dissected adult cadaver wrists and serial sections on twenty-three wrists from fetuses ranging in size from 23 to 230 millimeters crown-rump length. Three palmar radiocarpal ligaments were clearly identified: the radioscaphocapitate, long radiolunate, and short radiolunate ligaments. The radioscaphocapitate ligament originates from the radial styloid process and inserts into the radial aspect of the waist of the scaphoid, hemicircumferentially around the distal pole of the scaphoid and interdigitates with fibers from the palmar aspect of the triangular fibrocartilage complex just palmar to the head of the capitate, with only a minor insertion distally into the body of the capitate. The long radiolunate ligament originates just ulnar to the radioscaphocapitate ligament, being separated from it throughout its course by the interligamentous sulcus. The long radiolunate supports, but is separate from, the palmar aspect of the scapholunate interosseous ligament, and inserts into the radial half of the palmar surface of the lunate. The short radiolunate ligament, previously not described, originates just palmar to the lunate facet of the distal radius articular surface and inserts as a flat sheet of fibers into the proximal margin of the palmar surface of the lunate. Each ligament is intracapsular, enveloped within a continuous superficial fibrous stratum and deep synovial stratum.     

Reconstruction of the lateral tibial plateau using a vascular pedicled patellar transplant

A case of surgical reconstruction in posttraumatic necrosis of the lateral tibial plateau after impression fracture is presented. Joint reconstruction was performed by transposition of the distally pedicled lateral third of the patella combined with a cancellous bone graft. The surgical procedure is described and the indications for it are discussed.     

Precision of dual-photon absorptiometry

Summary Precision of dual-photon absorptiometry (DPA) measurements was determined in a lumbar spine phantom and in humans. Approximately half of the measurements were made before and half after a¹⁵³gadolinium source change. The phantom was measured with different amounts of acrylic, which simulates human soft tissue, in order to evaluate the influence of body thickness on bone mineral density (BMD). Results of scans analyzed with two software versions from Lunar Radiation Corp., the widely used 08B and a prototype 08C, are compared. DPA with a cold source significantly overestimated BMD in the phantom in the presence of large amounts (more than 25 cm) of soft tissue equivalent with version 08B but not with the newer version 08C. Similiarly, in nine subjects, there was a significant decrease in spine BMD after a source change when scans were analyzed with version 08B (mean difference 0.026 g/cm²,P=0.002) but not with 08C (0.01 g/cm²,P=0.234). No systematic effect of source change on femoral BMD measurements was observed. The SD of the mean difference of two measurements of the nine subjects was 0.019 g/cm² (1.6% of the mean value) for the spine with software version 08B and 0.024 g/cm² (2.0%) with version 08C, 0.03 g/cm² (3.3%) for the femur neck, 0.03 g/cm² (4.0%) for the greater trochanter, and 0.04 g/cm² (4.9%) for Ward's triangle region of the proximal femur. The spine phanton was scanned on two other commercial bone densitometers in order to assess inter-instrument variation. Phantom measurements of L2-4 BMD made on two Lunar Radiation Corp model DP3 scanners which differed by 2% were 10 and 12% higher than those with a Norland Corp. model 2600 scanner.     

Chronopharmacokinetic and bioequivalence studies of two formulations of trimipramine after oral administration in man

The bioavailability of two oral formulations of trimipramine, tablets and solution, was performed in twelve healthy volunteers, in a cross-over study. Each formulation was administered in the morning after a fasted period, and in the evening after a meal, in order to evaluate the role of both administration time and food consumption on the plasma kinetic parameters, under usual therapeutic conditions. A high interindividual variability of data was found. First, the extent of bioavailability was identical for the two formulations but the rate of bioavailability seemed to be different, with the p.o. solution, being more rapidly absorbed (tmax = 1.50 h). The effect of administration time was more obvious for the solution as shown by a lower quantitative absorption as well as a delay in time to reach the maximal concentration. Regardless of formulation and administration time, the t1/2 beta was about 10 hours and the mean MRT value was 11 hours.     

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.