18F]fluoroalkyl analogues of the potent 5-HT1A antagonist WAY 100635: radiosyntheses and in vivo evaluation

Two analogues of the potent 5-HT1A antagonist WAY 100635 have been synthesized and radiolabelled with 18F, namely N-[2-[4-(2-2'-[18F] fluoroethoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xan e carboxamide ([18F]FEC) and N-[2-[4-(2-3'-[18F] fluoropropoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cycloh exa ne carboxamide ([18F]FPC). Biodistribution studies in rats showed selective uptake of both radiotracers in regions known to be rich in 5-HT1A receptors following i.v. injection. The ratio of radioactivity in hippocampus to that in the cerebellum was 5.5 (for [18F]FEC) and 7.5 (for [18F]FPC) at 60 min postinjection. Regional brain heterogeneity of radioactivity could be abolished by pretreatment with WAY 100635 and FPC but was unaffected by pretreatment with a variety of drugs including ketanserin, sulpiride, and SCH 23390. These results are compared vis-a-vis with those obtained using [11C]WAY 100635 to evaluate [18F]FEC and [18F]FPC as potential radiotracers for imaging 5-HT1A receptors by positron emission tomography.     

Annealing and aging of interstitial C in α-Fe,As measured by internal friction

The diffusion of interstitial C in α-Fe has been studied by the dynamic mechanical relaxation method, and the isothermal aging kinetics of the removal of interstitial C by precipitation from its saturated state has been measured at several temperatures. The height of the Snoek peak is found to decrease according to the relation Q_max ^-1(T,t) = Q_max ^-1(T,t → ∞) + δQ_max ^-1(T) exp {- t/[k₀ exp (E/RT)}], where t is the aging time, k₀ a time constant, and E the activation energy for the precipitation of C atoms. The anelastic relaxation time is independent of the amount of C in α-Fe and varies according to Τ = 3.45 × 10^-15 exp [80.0 (kJ/mol)/RT]. The diffusion coefficient varies according to D = 6.61 × 10^-3 exp [-(80.0/RT) cm² s^-1 over the temperature range 303 to 357 K. The effect of chemical composition on k₀ has been determined and a procedure for determining the constant of proportionality between Q_max ^-1 and the amount of dissolved carbon in steel is described. A concept of accumulated equivalent aging time is introduced and theoretically justified on the bases of time-temperature superposition of aging effects. Calculations and experiments show that a substantial decrease occurs in the C content of steel when it is heated to high temperatures and that this effect alters the shape of the Snoek peak.     

Resurgence of derived stimulus relations

Resurgence has been shown in human and nonhuman operant behavior, but not in derived relational responses. The present study examined this issue. Twenty-three undergraduates were trained to make conditional discriminations in a three-choice matching-to-sample paradigm. The training resulted in three equivalence classes, each consisting of four arbitrarily configured visual stimuli. The same 12 stimuli were then reorganized, and the conditional discrimination training was repeated such that three new classes were possible. In a subsequent test of derived relations, most subjects showed response patterns that were consistent with the altered conditional discriminations. Subjects were then exposed to conditional discrimination trials under extinction. Most subjects continued to respond consistently with the most recently reinforced conditional discrimination trials. During the next phase, subjects were exposed to symmetry and equivalence trials. Responses consistent with the most recent training produced feedback saying that the responses were incorrect, whereas other responses produced no feedback. Most subjects showed a resurgence of responding that was consistent with their earlier training. Finally, subjects were exposed to conditional discrimination trials carried out in extinction. Most subjects continued to show a resurgence of responding that was consistent with their early training.     

Replication of O6-methylguanine-containing DNA by repair and replicative DNA polymerases

The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol beta could not replicate m6G-containing DNA, but we find that pol beta can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol beta activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol beta as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion.     

Social evolution and the emergence of leadership.

Used a cross-generational procedure to examine E. R. Service's (1975) redistribution theory of social evolution. 432 university students participated. The procedure involved 3 4-person groups that produced different products that could be retained or traded and that could be eventually exchanged for money. One group was advantaged in the diversity of its products, the time it took to make the products, and the value of its products. All trade was channeled through this central group. At the end of each time period, 1 member of each group was removed ("deceased") and a new member added. The monetary results indicate that the central group made the most money but that all groups made more money across generations, partially due to increased trade and partially due to increased production. Consistent with Service's prediction, the central group was perceived by the "deceased" group members as the overall leader. Ratings by observers, ratings by "deceased" members, and the division of money at the end of each generation all indicated that each of the 3 groups developed a seniority rule for within-group leadership. Ratings by "deceased" members indicated that this rule was stronger for the central than for the peripheral groups. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Filipino elder: implications for nursing practice. Knowledge of heritage essential

1. Ethnic identity is an important variable in health promotion and care. Knowledge of cultural heritage is necessary to assess the unique needs of the individual. 2. Culture affects how one perceives and defines the meaning of illness. In turn, the way in which one defines the meaning of an illness will influence the expectations of both caregivers and clients within the nurse-client relationship. 3. Broadening our understanding of a diverse ethnic population is central to the concept of transcultural nursing. The importance of understanding differences in cultural heritage cannot be ignored by the nurse who cares for a new elderly Filipino immigrant.     

Trends in glove use by dentists in England and Wales: 1989-1992

The routine wearing of gloves during the dental treatment of patients forms an integral part of the recommended guidelines of many authorities worldwide. Compliance has been variable but there is evidence to show that this is increasing, as are other cross-infection control measures. A survey of glove use by general dental practitioners in England and Wales was carried out in 1989. This paper reports a follow up study in 1991/2 which aimed to identify any differences that had occurred in the interim. The results indicated that there was increasing compliance with recommended cross-infection control measures, although only one fifth of respondents were found to change gloves between patients. Of those practitioners who did not change gloves between patients, half considered that blood contact was not a reason for changing gloves. Comparisons are made with compliance rates in other countries and recommendations made for further education within the dental profession on the subject of cross-infection control.     

Exploiting tumor hypoxia through bioreductive release of diffusible cytotoxins: the cobalt(III)-nitrogen mustard complex SN 24771

PURPOSE: To assess the oxygen dependence of a novel cobalt-nitrogen mustard complex, SN 24771, designed to release a diffusible cytotoxic metabolite in hypoxic tumor microenvironments. METHODS AND MATERIALS: Oxygen dependence of cell killing was assessing in well-stirred single cell suspensions obtained by enzymatic dissociation of EMT6 spheroids, using a sensitive oxygen electrode to measure oxygen concentrations in solution. Cell killing in intact EMT6 spheroids was also compared with that in single cell suspensions. RESULTS: Cytotoxicity of SN 24771 in single cell suspensions was inhibited by very low concentrations of oxygen. The C50 value (O2 required for 50% inhibition of log cell kill) was ca. 0.02% O2 at 1 h, and the K value (O2 required to give a cytotoxic potency equal to the average of that at zero and infinite O2) was of a similar order. However, intact spheroids were much more sensitive to SN 24771 than could be accounted for by the K curve for single cell suspensions, this estimate being based on published data for the oxygen concentration profile in these spheroids. CONCLUSION: The cytotoxicity of SN 24771 is inhibited appreciably at oxygen concentrations which are too low to provide radiosensitization. In this respect, SN 24771 resembles organic bioreductive drugs such as quinones and nitroaromatic compounds. However, the extensive killing observed in multicellular spheroids is consistent with release of a diffusible nitrogen mustard on reduction. Bioreductive drugs with a low K value for activation, but which release a diffusible cytotoxin, may have desirable properties as tumor radiosensitizers.     

Aberrant reinnervation following hypoglossal nerve damage

Hypoglossal nerve damage is a known complication of carotid endarterectomy, occurring in approximately 5% of endarterectomies. The vast majority of these patients recover without functional disability from this injury even if the tongue remains hemiplegic. We report 2 patients who suffered hypoglossal nerve section during neck surgery. Although they were initially mildly symptomatic, they developed increasingly severe dysarthria and dysphagia beginning 4 months after surgery. EMG revealed abnormal coactivation of the genioglossus and styloglossus muscles on the affected side, suggesting aberrant reinnervation. Aberrant reinnervation is a well-known complication of facial nerve injury, but has not been previously recognized in hypoglossal nerve injury. Like the face, the tongue is composed of many muscles that must perform complex movements. Normally, injury to one hypoglossal nerve causes little or no disability, but when aberrant reinnervation occurs, the tongue no longer moves in a coordinated manner, and significant dysarthria ensues.