Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in transfected CHO cells without the concomitant administration of a Ca2+-mobilizing agent

In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3-PPP], also induced AA release, but with somewhat lower efficacy (maximal effect: 165%; EC50=91 nM). The AA-releasing effect of dopamine was counteracted by pertussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calcium from the medium, by the phospholipase A2 (PLA2) inhibitor, quinacrine, and by long-term pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, it was antagonized by the D2 antagonists, raclopride and (-)-sulpiride--but not by (+)-sulpiride--and absent in sham-transfected CHO cells devoid of D2 receptors. The results obtained contrast to the previous notion that dopamine and other D2 receptor agonists require the concomitant administration of calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimycin), thrombin, and TRH, to influence AA release from various cell lines.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

Noninvasive measurement of distal radius instability

Except for subjective clinical criteria, there is no formal definition of distal radius fracture instability in the literature. The purposes of this ex vivo biomechanical study were (1) to provide an objective mechanical definition of fracture instability and (2) to demonstrate a noninvasive method that allows for direct measurement of instability. The following 3 questions are addressed: (1) Can the stability of distal radius fractures be measured using computed tomography (CT)? (2) Are the stability measurements reproducible? (3) How does external fixation change stability? A CT technique is described that was used to measure displacement of fracture fragments and measure the compliance of ex vivo distal radius fractures before and after external fixation. Validation studies of the CT technique revealed a mean coefficient of variation of 0.38. There was a linear relationship between measured and known displacements for all 3 orthogonal planes (coefficient of determination 0.99; p < .01). There was significant fracture displacement with loads as small as 20 N. The slope of the load-displacement curve (structural compliance) provided a quantitative measure of fracture instability. Fracture compliance decreased up to 69% after application of an external fixator.     

New nonsteroidal androgen receptor modulators based on 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g] quinolinone

Typhoid fever is often associated with abnormal liver biochemical tests, but severe hepatic involvement with a clinical feature of acute hepatitis is a rare complication. There have been more than 150 cases of salmonella hepatitis reported from both developed and developing countries. The documented incidence varies widely from less than 1% to 26% patients with enteric fever. The possible associated factors for development of salmonella hepatitis are virulence of the organisms, delayed treatment and poor general health of the patients. The pathogenesis of severe hepatic involvement in salmonella infection may be multifactorial and includes endotoxin, local inflammatory and/or host immune reactions. Clinical jaundice in salmonella hepatitis usually occurs within the first 2 weeks of the febrile illness. Hepatomegaly and moderate elevation of transaminase levels are common findings. Extreme hepatic dysfunction with hepatic encephalopathy is a rare coexisting complication in salmonella hepatitis. A positive culture for salmonella from blood or stool is essential to differentiate salmonella hepatitis from other causes of acute hepatitis. Hepatic pathology is characterized by the presence of typhoid nodules with marked hyperplasia of reticuloendothelial cells. The prognosis is usually good as salmonella hepatitis responds well to a specific antibiotic therapy and juandice resolves with clinical improvement. The clinical course can be severe with a mortality rate as high as 20%, particularly with delayed treatment or in patients with other complications of salmonella infection. As enteric fever is a common infection, the recognition of salmonella hepatitis is of clinical importance.     

Chemical synthesis and physiological activity of sulfonium analogues of platelet activating factor

Phosphatidylsulfocholine (PSC), the sulfonium analogue of phosphatidylcholine (PC), occurs naturally in some diatoms. The replacement of the −N⁺(CH₃)₃ group by a −S⁺(CH₃)₂ results in an increase in the polar head group size in PSC relative to that of PC, consistent with the observed increase in permeability of PSC bilayers towards urea. It was of interest to see whether replacement of the −N⁺(CH₃)₃ group in platelet activating factor (PAF) by an −S⁺(CH₃)₂ group leads to any change in platelet aggregation or other physiological activity. Synthesis of the sulfonium analogue of PAF was carried out by suitable modifications of known procedures. The PAF-sulfonium analogue was found to have almost the same platelet aggregating activity as PAF itself, in the concentration range 1–20 μM, but a much lower activity in the range 0.01–1 μM. The analogue had little or no effect on the platelet aggregation activity of PAF when added in the concentration range 0.01–1 μM and had about half the hypotensive activity of PAF towards hypertensive CDF male rats. The sulfonium analogue, however, was much more cytotoxic to HL-60 cells than PAF itself, in the concentration range 0–15 μM; replacement of the acetate group by a benzyl group increased the cytotoxicity to the level of that of the methoxy analogue of PAF. Thus, replacement of the −N⁺(CH₃)₃ group by a −S⁺(CH₃)₂ group in the polar head group region of PAF results in a relatively small change in its platelet aggregation activity and a decrease in its hypotensive activity, but greatly increases its antitumor activity. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 8–12, 1989.     

Effect of moisture and particle size on the extractability of oils from seeds with supercritical CO2

Moisture level and particle size of soybeans, peanuts and cottonseed were correlated with the extraction rate and yield of oil when extracted with supercritical carbon dioxide (SC-CO₂) at a constant temperature (50 C) and pressure (8000 psig). The rate of extraction and ultimate oil yields were quite low with cracked soybeans. However, good extraction rates and nearly theoretical oil yields were obtained from ground or thinly flaked (<0.010″) seeds. Moisture levels between 3% and 12% had little effect on extracability. Oil composition was not influenced by either parameter. Scanning electron microscopy was used to study seed structure before and after extraction with SC-CO₂. Micrographs of SC-CO₂-extracted seeds were similar to hexane-extracted seeds. Presented at the AOCS Meeting, May 1983, Chicago.     

Estimating the electrical conductivity of cement paste pore solutions from OH, K and Na concentrations

A proposed method for estimating the electrical conductivity of cement paste pore solution at 25 °C is based on the concentrations of OH⁻, K⁺ and Na⁺. The approach uses an equation that is a function of the solution ionic strength, and requires a single coefficient for each ionic species. To test the method, the conductivity of solutions containing mixtures of potassium hydroxide and sodium hydroxide with molar ratios of 4:1, 2:1 and 1:1, and having ionic strengths varying from 0.15 to 2.00 mol/l were measured in the laboratory and compared to predicted values. The proposed equation predicts the conductivity of the solutions to within 8% over the concentration range investigated. By comparison, the dilute electrolyte assumption that conductivity is linearly proportional to concentration is in error by 36% at 1 mol/l and in error by 55% at 2 mol/l. The significance and utility of the proposed equation is discussed in the context of predicting ionic transport in cement-based systems.     

Solvent extraction of oil from soybean flour II— pilot plant and two-solvent extractions

The process of grinding soybeans to a fine flour and extracting the flour with hexane was studied on a pilot plant scale. The crude oil from the pilot plant study had 15 ppm phosphorus and was suitable for physical refining after a light acid pretreatment and bleaching. The refined oil showed a Lovibond color of 1.4 yellow and 0.3 red. The pilot plant study also showed that grinding of the soybeans and the separation of solid from miscella were the most difficult steps in solvent extraction with fine flour. A laboratory study on separation of miscella from meal by aqueous ethanol reduced the hold-up volume, but it did not remove all the miscella. A test with betacarotene showed that only the miscella outside the flour particles was displaced. Aqueous ethanol solutions used as a second solvent extracted additional nontriglyceride materials (primarily phospholipids) from the meal. Also, the free fatty acid content of the oil was increased with aqueous ethanol solution wash. The quality of the extracted crude oil was lowered by using a second solvent, but it had the advantage of needing only one centrifugation to separate miscella from meal.     

Serum lipids in spontaneously hypertensive rats and sprague-dawley rats fed menhaden oil

Dietary n-3 fatty acids, abundant in fish oil, exert a variety of effects that attenuate cardiovascular disease. In this study, we assessed the effect of fish oil (menhaden oil) on the serum lipid profile in hypertensive and normotensive rats. Spontaneously hypertensive rats (SHR) or Sprague-Dawley rats (SD) were fed either standard powdered diet (L-485), or L-485+5% menhaden oil (MO) or L-485+5% corn oil (CO) from weaning through eight months of age. Systolic blood pressure (BP) was periodically determined on SHR. Serum lipid profiles were performed at eight months on sample taken from the exposed hearts of anesthetized, fasted rats. SHR, compared with SD (diets combined) had significantly lower triaclyglycerols (TG), higher cholesterol (CHOL), higher high density lipoprotein cholesterol (HDL CHOL), higher low density lipoprotein cholesterol (LDL CHOL), and a higher LDL:HDL ratio. Comparison among diets (strains combined) revealed that rats fed MO had the lowest values for TG, CHOL, LDL and LDL:HDL; HDL did no vary with diet. SHR were less responsive to diet-induced changes than were SD; no decrease in TG, LDL or LDL:HDL was observed in SHR, nor was degree of hypertension altered in SHR by the MO or CO diet. In summary, MO is more effective than CO in shifting the lipid profile of rats toward one that is less atherogenic. However, the SD rat is more susceptible to diet-induced lipid modification than is the SHR.