On the Mechanism of Palladium(0)-Catalyzed Reactions of Allylic Substrates with Nucleophiles. Origin of the Loss of Stereospecificity

The mechanism of the loss of stereospecificity in palladium-catalyzed nucleophilic substitution of allylic substrates has been investigated. Eight substrates (cis and trans isomers of 1a-d) and two nucleophiles (Et₂NH and NaCH(SO₂Ph)₂) were studied. In the animation reactions two pathways are responsible for the formation of anomalous inversion product, viz., isomerization of the starting material (path B, Scheme 2) and isomerization of the π-allyl intermediate via displacement of palladium by Pd(0) (path C, Scheme 2), the latter of which predominates. In the alkylation the results indicate that loss of stereospecificity is caused only by path C. The use of a more reactive substrate increased the stereospecificity of the reaction and suppressed the isomerization pathway. An analysis of the kinetics is consistent with the hypothesis that path C is the major pathway for the stereochemical loss.     

Dietary fish oils and long-term malaria protection in mice

Previous studies indicate a suppressive influence of fish oils on rodent malaria. The present work was carried out to study (i) the dose-effect relation between dietary fish oils and lethality of primary malaria infection in mice; (iii) the modifying influence of vitamin E; and (iii) the effect of previous fish oil feeding on parasitemia and lethality of a rechallenge infection. For two or four weeks, groups of weanling male mice were fed a standard laboratory diet or one of eight purified diets containing various amounts of fish oil (providing 6–21% of energy). The diets were prepared with and without vitamin E. After the two-or four-week feeding period, the mice were injected intraperitoneally withPlasmodium yoelii yoelii-infected erythrocytes. Six months after the primary infection (four months after discontinuing fish oil feeding), the surviving mice were again injected intraperitoneally with parasitized red blood cells (or even better—erythrocytes, erythrocytes are used elsewhere). Primary malaria infection was lethal in mice fed standard diet alone or with fish oil and vitamin E added. In contrast, feeding a fish oil-based diet without vitamin E improved survival to at least 70% if the mice had been fed these diets for four weeks. Protection against malaria did not seem to be related to the fish oil dose used. Regardless of the previous fish oil dose, all the mice surviving the primary infection survived the rechallenge infection with low parasitaemias. The results suggest that the prooxidant nature of highly unsaturated fatty acids in fish oils may beneficially influence malaria infection, and may also increase the resistance against reinfection for some time after discontinuing fish oil intake.     

Spatiotemporal patterns of drivers of episodic acidification in Swedish streams and their relationships to hydrometeorological factors

This study examined the spatiotemporal patterns of episodic acidification in 87 weakly buffered streams in Sweden at a monthly sampling frequency during a ten-year study period (1998-2007). Time series of pre-industrial pH (pH₀) were reconstructed from the acidification model Meta_MAGIC, and the acidification impact was defined by the difference between the pH₀ and the contemporary pH (i.e., ΔpH = pH₀ − pH_t). Acidification episodes were defined as observations for which the pH_t was at least 0.4 units lower than average, in combination with a ?pH at least 0.2 units higher than average. Thus, only occasions in which the stream water was both more acidic and more acidified than average were characterized as acidification episodes. For each observed episode, the primary cause was identified from one of the following five possible drivers: dilution, increase in sulfate, nitrate or organic acids, or sea salt deposition. In total, 258 episodes were observed during the study period. The study showed that streams that were acidified during baseflow (ΔpH > 0.4), but not chronically acidic (pH > 5.2), were subjected to regular episodic acidification. Dilution was the single most important cause and the main driver for 58% of the identified episodes. Increases in sulfate concentrations were also relatively common (26% of episodes), whereas increases in nitrate and organic acids as well as sea salt deposition were of minor importance. The total number of dilution-related acidification episodes within a year had a significant (p = 0.005) positive correlation (r = + 0.83) with the average annual precipitation. Occurrences of sulfate episodes were related to droughts during the preceding summers. While the number of streams that are susceptible to episodic acidification will decrease as a consequence of recovery from acidification, the hydrological and meteorological consequences of future climate change may make episodic acidification more common.     

Parathyroid hormone-related protein in patients with primary breast cancer and eucalcemia

Parathyroid hormone-related protein (PTHrP) is a causative factor of humoral hypercalcemia in breast cancer and other malignancies. We studied circulating PTHrP levels with three different immunoassays directed against different parts of the PTHrP molecule in 48 patients with breast cancer and eucalcemia. The methods used were: (a) a RIA with antibodies directed toward the midregion (63-78); (b) an immunofluorometric assay with two antibodies against 1-34 and 38-67; and (c) an immunoradiometric assay with antibodies against 1-40 and 1-72. Although most patients had PTHrP levels indistinguishable from normal when measured by all three methods, four patients had increased serum levels in the IFMA. PTHrP was detected by immunohistochemistry in tumors from nearly all patients. One patient with elevated PTHrP in plasma measured by IFMA showed intense staining of tumor by immunohistochemistry; the tumor was histologically graded as III (severe) and was the largest of all tumors in this patient group. The IFMA can identify increased serum PTHrP in some patients with breast cancer who are not hypercalcemic. This assay may be especially useful in screening patients for this tumor during a relative early phase of the disease.     

Electrochemical oxidation by square-wave potential pulses in the imitation of oxidative drug metabolism

Electrochemistry combined with mass spectrometry (EC-MS) is an emerging analytical technique in the imitation of oxidative drug metabolism at the early stages of new drug development. Here, we present the benefits of electrochemical oxidation by square-wave potential pulses for the oxidation of lidocaine, a test drug compound, on a platinum electrode. Lidocaine was oxidized at constant potential and by square-wave potential pulses with different cycle times, and the reaction products were analyzed by liquid chromatography-mass spectrometry [LC-MS(/MS)]. Application of constant potentials of up to +5.0 V resulted in relatively low yields of N-dealkylation and 4-hydroxylation products, while oxidation by square-wave potential pulses generated up to 50 times more of the 4-hydroxylation product at cycle times between 0.2 and 12 s (estimated yield of 10%). The highest yield of the N-dealkylation product was obtained at cycle times shorter than 0.2 s. Tuning of the cycle time is thus an important parameter to modulate the selectivity of electrochemical oxidation reactions. The N-oxidation product was only obtained by electrochemical oxidation under air atmosphere due to reaction with electrogenerated hydrogen peroxide. Square-wave potential pulses may also be applicable to modulate the selectivity of electrochemical reactions with other drug compounds in order to generate oxidation products with greater selectivity and higher yield based on the optimization of cycle times and potentials. This considerably widens the scope of direct electrochemistry-based oxidation reactions for the imitation of in vivo oxidative drug metabolism.     

Employee attitudes toward a hard-core hiring program.

Assessed attitudes of 214 employees at all organizational levels in a large utility company toward a program involving hiring the hard-core unemployed both before program initiation and after 3 mo. of experience with the program. Ss were administered the Consequences Model Questionnaire. The hypothesized ambivalence of management personnel was verified, as was the differential impact of the program on employees at various levels. In general, the initially positive responses toward the program gave way to a position of balanced neutrality, a state in which assets were counterbalanced by liabilities. Results are interpreted in terms of the impact of the initial position of top management on program operation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bereavement, grieving and psychological morbidity after first trimester spontaneous abortion: comparing expectant management with surgical evacuation

Early pregnancy loss is a profound adverse life event for many women, and increased psychiatric morbidity has been shown to occur after spontaneous abortion. Dilatation and curettage (D&C) has been the cornerstone in the treatment of first trimester spontaneous abortion over the last few decades. During recent years the possibility of conservative management has, however, been increasingly discussed. In a prospective randomized trial, we compared psychological reactions and morbidity, after either expectant management or D&C, for miscarriages of < 13 weeks gestation in which a transvaginal ultrasound examination showed intrauterine tissue and/or blood clots with an antero-posterior diameter of between 15 and 50 mm. Of the 86 patients included, 58 were randomized to expectant management and 28 to primary D&C. In patients randomized to expectant management, pregnancy products shown by transvaginal ultrasound disappeared within 3 days in 43 cases (74%), whereas 15 patients (26%) underwent D&C owing to retained products of conception after 3 days. At 2 weeks after inclusion, all patients answered self-administered questionnaires, including visual analogue scales, concerning their experience of the pregnancy loss, the present situation and concerns about the future. A brief anxiety status inventory was included. This study showed no increase in anxiety or depressive reactions 2 weeks after a first trimester spontaneous abortion when these patients were compared with non-pregnant healthy working females 19-39 years of age. Moreover, there were no significant differences in psychological reactions between patients managed either expectantly or by D&C.     

Urolithiasis. A study of its frequency

Considering the general impression of an increased number of patients with acute renal colic, the frequencies of roentgenologically verified ureteral and kidney calculi in a Swedish urban district have been studied for the periods 1953-55 and 1968-70. In a material of 986 outpatients (793 men and 193 women) we have proved an increase in incidence for upper urinary tract calculi in men from 2.2 to 3.3 0/00 (p less than 0.001) and in women from 0.5 to 0.8 0/00 (0.01 less than p less than 0.05). For the material as a whole, we have found a 50% increase (from 1.3 to 2.0 0/00; p less than 0.001) of acute urolithiasis between the periods studied. Some implications of the results in connection with primary hyperparathyroidism are discussed.