Enhancement of the hypothermic response of mice to delta-9-tetrahydrocannabinol by subhypothermic doses of chlorpromazine and phentolamine

Pretreatment with subhypothermic doses of chlorpromazine, given directly into the IIIrd cerebral ventricle via a chronically implanted cannula (50 micrograms) or subcutaneously (0.75 mg/kg), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC: 5 20 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22 degrees C. Subcutaneous pretreatment with a subhypothermic dose of phentolamine (30 mg/kg) had a similar effect, whereas pretreatment with desipramine (10 mg/kg s.c.), mepyramine (2.3 and 11.5 mg/kg s.c.), methysergide (2 mg/kg s.c.), pimozide (1 and 5 mg/kg s.c.) or lignocaine (50 mg/kg s.c.), had no effect. Intracerebroventricular pretreatment with phentolamine was also without effect and it is concluded that this drug interacts with THC at some site located outside the brain. Since, in mg/kg terms, chlorpromazine was more potent in enhancing THC-induced hypothermia when given subcutaneously than when injected into the IIIrd ventricle, it too may interact with THC at a peripheral site. Indeed, chlorpromazine and phentolamine may both increase the hypothermic response to THC by antagonizing alpha-adrenoceptors on cutaneous blood vessels, thereby decreasing the capacity of animals to minimise peripheral blood flow by vasoconstriction. Alternatively, since the distribution of chlorpromazine within the brain may well have been less efficient after intraventricular than after subcutaneous injection, the possibility remains that chlorpromazine interacted centrally with THC.     

Improved tool for testing screen-film contact in mammography

Good screen-film contact is essential to obtain high definition in radiographic images. We compared the conventional test tool for measuring screen-film contact, which uses #8 mesh (eight wires per inch [about three wires per centimeter]), with a prototype tool of #40 copper mesh. The conventional tool did not adequately test screen-film contact for mammography, in which significantly higher resolution is obtained. We believe #40 copper mesh should be used to test screen-film contact of mammographic cassettes. We also found that entrapped air may reduce screen-film contact and, therefore, recommend that cassettes be loaded at least 15 minutes before they are exposed.     

No alterations in the performance of two interval timing operant tasks after alpha-difluoromethylornithine (DFMO)-induced cerebellar stunting.

The cerebellum is critically involved in temporal processes in the millisecond range and may be involved in longer time estimations (i.e. in the seconds range). Estimates in the millisecond range are impaired after developmentally induced cerebellar alterations, however, little is known about the effects of similar alterations on longer timing performance. Appropriately timed DFMO treatment reliably causes cerebellar stunting in rats, however, its effects on temporal estimation performance are unknown. Here, male and female Sprague-Dawley rats were treated with subcutaneous injections of 500 mg/kg DFMO on postnatal days 5-12, causing a 10% cerebellar weight reduction at adulthood. As adults, subjects were tested under one of two paradigms - a differential reinforcement of low response rate (DRL) task requiring that subjects withhold a lever press response for 10-14 s or a temporal response differentiation (TRD) task requiring that subjects maintain a lever press response for 10-14 s. Training and steady-state performance of the DRL and TRD tasks were not significantly altered by DFMO treatment. Performance after acute challenges with two dopaminergic agonists (2.00-7.50 mg/kg methylphenidate and 0.10-1.00 mg/kg d-amphetamine) was measured after which all subjects underwent behavioral extinction. Generally, performance after methylphenidate and d-amphetamine was similar in control and DFMO-treated rats and DFMO treatment had no differential effects on performance during extinction. These results support findings from an earlier study [Ferguson SA, Paule MG, Holson RR. Neonatal dexamethasoneon day 7 in rats causes behavioral alterations reflective of hippocampal, but not cerebellar, deficits. Neurotoxicol Teratol, 2001; 23:57-69] indicating that developmental cerebellar stunting has few effects on time estimation within the range of seconds.     

Smooth muscle tumors of the rectum and anus: a collective review of the world literature.

In this collective review, we have compiled all the reported cases of smooth muscle tumors of the rectum/anus in the world literature from 1959 to 1989. Our goal was to increase the data pool of smooth muscle tumors by adding these new data to that previously collected from 1881 to 1959. We increased the pool for leiomyomas from 89 to 148 and that for leiomyosarcomas from 54 to 215. By doing this, we hoped to make more accurate conclusions about smooth muscle tumors based on this increased data pool. Some interesting findings included three cases in small children that were found in our recent review: a 2-year-old with a leiomyoma and two small infants, aged 12 days and 36 days, with leiomyosarcomas. Again, the findings were probably consistent with an increased data pool. We were also able to find several more cases involving the anal region. We found the highest incidence of leiomyomas to have increased by a decade from the 40-49 year age group to the 50-59 year age group, while among leiomyosarcomas, there was about equal incidence among the 50-59 and 60-69 age groups. We doubt that these represent actual changes in the demographics, but rather that these latter findings are more accurate based on the greater quantity of cases available to us. As a further example, we found no appreciable sex difference; however, we did find more cases reported in females. From our increased data pool, we were able to find 16 more cases that were described as dumbbell-shaped, compared to one that was reported before 1959. Palpable mass, hemorrhage, and pain/discomfort continued as the most common symptoms reported at presentation. With regard to size, the majority of leiomyomas were found to be less than 5 cm in diameter, closely followed by those 5-9 cm. The majority of leiomyosarcomas were 5-9 centimeters at discovery. Most cases of leiomyoma were treated by excision, while most cases of leiomyosarcoma were treated by abdominoperineal resection, a finding consistent with old data. We hope that this paper thoroughly reviews pertinent information about leiomyomas and leiomyosarcomas of the rectum/anus and, in doing so, serves to refresh a few memories, stimulate others, and teach a few.     

Receptors mediating CGRP-induced relaxation in the rat isolated thoracic aorta and porcine isolated coronary artery differentiated by h(alpha) CGRP(8-37).

1 Receptors mediating CGRP-induced vasorelaxation were investigated in rat thoracic aorta and porcine left anterior descending (LAD) coronary artery and anterior interventricular artery (AIA), using CGRP agonists, homologues and the antagonist h(alpha) CGRP(8-37). 2 In the endothelium-intact rat aorta, h(alpha) CGRP, h(beta) CGRP, rat beta CGRP and human adrenomedullin caused relaxation with similar potencies. Compared with h(alpha) CGRP, rat amylin was about 25 fold less potent, while [Cys(ACM2,7)] h(alpha) CGRP and salmon calcitonin were at least 1000 fold weaker. 3 H(alpha) CGRP(8-37) (up to 10(-5) M) did not antagonize responses to h(alpha) CGRP, h(beta) CGRP or rat beta CGRP (apparent pKB <5). Peptidase inhibitors did not increase either the effect of h(alpha) CGRP or [Cys(ACM,2,7)] h(alpha) CGRP, while h(alpha) CGRP(8-37) remained inactive. Endothelium-dependent relaxation produced by h(alpha) CGRP was accompanied by increases in cyclic AMP and cyclic GMP, that were not inhibited by h(alpha) CGRP(8-37) (10(-5) M). 4 In porcine LAD and AIA, h(alpha) CGRP produced relaxation in an endothelium-independent manner. H(alpha) CGRP(8-37) competitively antagonized h(alpha) CGRP responses (pA2 6.3 and 6.7 (Schild slope 0.9+/-0.1, each), in LAD and AIA, respectively). In LAD artery, h(alpha) CGRP-induced relaxation was accompanied by increases in cyclic AMP that were inhibited by h(alpha) CGRP(8-37) (10(-7)-10(5 )). 5 In conclusion, the antagonist affinity for h(alpha) CGRP(8-37) in porcine coronary artery is consistent with a CGRP1 receptor, while the lack of h(alpha) CGRP(8-37) antagonism in rat aorta could suggest either a CGRP receptor different from CGRP1 and CGRP2 type, or a non-CGRP receptor.     

Chemotherapy for advanced pancreatic cancer. A comparison of 5-fluorouracil, adriamycin, and mitomycin (FAM) with 5-fluorouracil, streptozotocin, and mitomycin (FSM)

One hundred ninety-six patients with advanced pancreatic cancer were randomized to receive one of two combination chemotherapy programs: FAM (5-fluorouracil, Adriamycin [doxorubicin], mitomycin) or FSM (5-fluorouracil, streptozotocin, mitomycin). Patient characteristics were comparable in both groups. Overall response rates for those with measurable disease (14% on FAM, 4% on FSM) were not significantly different (P = 0.07). There was no significant difference in overall survival between patients treated with FAM and FSM (median survivals of 26 and 18 weeks, respectively). Survival benefits of FAM were significant only for patients with measurable disease. Toxicity of both regimens was acceptable and comparable, aside from greater renal toxicity and more nausea and vomiting with FSM. The results failed to confirm the 35% to 40% response rates previously reported for FAM and FSM in advanced pancreatic cancer.     

Validation and application of dual-energy X-ray absorptiometry to measure bone mineral density in rabbit vertebrae.

The rabbit could be a superior animal model to use in bone physiology studies, for the rabbit does attain true skeletal maturity. However, there are neither normative bone mineral density (BMD) data on the rabbit nor are there any validation studies on the use of dual-energy X-ray absorptiometry (DXA) to measure spinal BMD in the rabbit. Therefore, our aim was twofold: first, to investigate whether DXA could be used precisely and accurately to determine the bone mineral content (BMC). bone area (BA). and BMD of the rabbit lumbar spine: Second. to evaluate the new generation fan-beam DXA (Hologic QDR-4500) with small animal software by comparing two DXA methodologies QDR-1000 and QDR-4500 with each other, as well as against volumetric bone density (VBMD) derived from Archimedes principle. As expected. there was a magnification error in the QDR-4500 (BMC, BA. and BMD increased by 52%. 38%. and 10%, respectively, when the vertebrae were positioned flat against the scanning table). With the magnification error kept constant (vertebrae positioned 10 cm above the scanning table to match the height in vivo). there were no differences among the mean BMC. BA. and BMD of the rabbit vertebrae (Ll-L7) in vivo and in vitro using the QDR-4500 (p > 0.05). BMC, BA, and BMD differed between QDR-1000 and QDR-4500 in vitro because of a magnification error when the vertebrae were flat on the table (p <0.0001). and, consequently. the machines did not correlate with one another (p > 0.05). However, the BMC, BA, and BMD of the two DXAs did significantly correlate with each other in vivo and in vitro when the magnification error was compensated for (r = 0.44 and 0.52. i2 = 0.45 and 0.63. and 12 = 0.41 and 0.60. respectively. p < 0.05-0.008). The BMC and BMD (in vivo and in vitro) of the rabbit vertebrae measured by QDR-4500 was significantly correlated with VMBD, ash weight, and mineral content (,2 = 0.67-0.90,j <0.01-0.0001). Therefore, the QDR-4500 can be used to yield precise and accurate measurements of the rabbit spine.