Clozapine, haloperidol, and the D4 antagonist PNU-101387G: in vivo effects on mesocortical, mesolimbic, and nigrostriatal dopamine and serotonin release

With in vivo microvoltammetry, the dopamine (DA) receptor antagonists, clozapine (D4/D2), haloperidol (D2) and the selective D4 antagonist, PNU-101387G, were evaluated for their effects on DA and serotonin (5-HT) release within A10 neuronal terminal fields [mesocortical, prefrontal cortex (PFC), mesolimbic, nucleus accumbens, (NAcc)] and within A9 neuronal terminal fields [nigrostriatal, caudate putamen (CPU)], in chloral hydrate anesthetized rats. Clozapine, which also has 5-HT2 receptor antagonist properties, significantly (p < 0.001) increased DA release within A10 terminal fields, PFC and NAcc; DA release was not increased by clozapine within A9 terminals, CPU. Serotonin release was significantly (p < 0.001) increased by clozapine within A10 and A9 terminal fields. Haloperidol significantly (p < 0.001) increased DA release within PFC, dramatically and significantly (p < 0.001) increased DA release within CPU, but not within NAcc; haloperidol had a small but statistically significant (p < 0.05) increase on 5-HT release within PFC [only at the highest dose studied (2.5 mg/kg)] and within CPU [only at the lowest dose studied 1.0 mg/kg) (p < 0.05)]. The selective D4 antagonist, PNU-101387G dramatically and significantly (p < 0.001) increased DA release within PFC, modestly, but significantly (p < 0.001) increased DA release within CPU, did not alter DA release within NAcc at the lowest dose studied (1.0 mg/kg) and significantly (p < 0.05) decreased DA release within NAcc at the highest dose studied (1.0 mg/kg). The selective D4 antagonist did not affect 5-HT release within either A10 or A9 terminal fields. The present data are discussed in terms of the neurochemistry, antipsychotic activity, and side effect profiles of clozapine and haloperidol, in order to provide comparative profiles for a selective D4 antagonist, PNU-101387G.     

Grief as pathology: The evolution of grief theory in psychology from Freud to the present.

The emergence of grief as a topic worthy of psychological study is an early 20th century invention. Freud published his influential essay on mourning and melancholia in 1917. Since he proposed the concept of “grief work,” contemporary psychologists have examined his theory empirically and have claimed that grief is a pathology that should be included within the psychological domain. How, and why, has grief theory evolved within the discipline of psychology in this way? In what ways do these changes in the understanding of grief coincide with other historical developments within the discipline? In this article, I trace the development of grief, originally conceived by Freud within a psychoanalytic and nonpathological framework, to the current conceptualization of grief within the disease model. I show how grief theory has evolved within the discipline of psychology to become (a) an object worthy of scientific study within the discipline, and subsequently, (b) a pathology to be privatized, specialized, and treated by mental health professionals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunolocalisation of the glutathione S-transferases, GST-26 and GST-28, within adult Schistosoma japonicum

This paper describes the first ultrastructural immunolocalisation study of the 26-kDa and 28-kDa glutathione S-transferases within adult Schistosoma japonicum (GST-26 and GST-28). Polyclonal antibodies raised against GST-28 (in mice) and against GST-26 (in rabbits) were used to examine the distribution of the proteins within adult parasites. Both proteins were localised within the parenchymal region of the male parasite. Additionally, both proteins were present within parenchymal cells located between the vitelline glands of female parasites. There were no detectable levels of GST-26 or GST-28 on the surface or within the tegument matrix of either the male or female worms. Possible functions for GST-26 and GST-28 within S. japonicum and their significance as vaccine target molecules are addressed.     

Characterization of grlA, grlB, gyrA, and gyrB mutations in 116 unrelated isolates of Staphylococcus aureus and effects of mutations on ciprofloxacin MIC

One hundred sixteen unrelated clinical isolates of Staphylococcus aureus (70 ciprofloxacin resistant and 46 ciprofloxacin susceptible) from eight countries were studied for the presence of mutations in the grlA, grlB, gyrA, and gyrB gene loci. Two mutations within grlA (located at codons 80 and 84) and two mutations within gyrA (located at codons 84 and 88) were clearly associated with ciprofloxacin resistance, although other mutations detected within the four genes studied may also contribute to decreased susceptibility.     

Locating eating pathology within an empirical diagnostic taxonomy: Evidence from a community-based sample.

Existing structural models of psychopathology need to be expanded to include additional diagnostic constructs beyond mood, anxiety, substance use, and antisocial behavior disorders. The goal of this study was to locate eating disorders within a hierarchical structural model of psychopathology that is anchored by broad Internalizing and Externalizing factors. Participants were female adolescent twins (N = 1,434) from the Minnesota Twin Family Study. The authors compared the fit of 4 models in which eating disorders (a) defined their own diagnostic class, (b) represented a subclass within Internalizing, (c) formed a subclass within Externalizing, and (d) were allowed to cross-load on both Internalizing and Externalizing. In the best fitting model, eating disorders formed a subfactor within Internalizing. These findings underscore the value of developing more comprehensive empirically based models of psychopathology to increase researchers' understanding of diverse mental disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electroconvulsive shock does not induce c-fos and junB, but TIS1 and TIS8/zif-268, in neonatal rat hippocampus

Insular neurons responsive to baroreceptor challenge have been identified in the rat, but not previously in primates. Characterization of baroreceptor-related neurons was performed in 15 anesthetized monkeys (Macaca fascicularis) using extracellular single-unit recording techniques. 131 units were investigated within the insula and surrounding regions. Based on their responses to phenylephrine hydrochloride (PE) and sodium nitroprusside (SNP), three types of units were distinguished: 35/131 (27%) sympathoexcitatory (SE), 12/131 (9%) sympathoinhibitory (SI) and 84 (64%) null units. More baroreceptive units were found within the insula (38/73, 52%) than in surrounding areas (9/58, 16%) (p < 0.001). Lateralization was indicated with more baroreceptive units being encountered within the right insula (28/44, 64%) than the left (10/29, 34%) (p = 0.02). The majority of the responsive units were located within the dysgranular and granular insula in layers II, III and V/VI. These data suggest that cardiovascular representation may occur in the primate insula as has been shown in other species.     

Effects of some phenylethylamines in rhesus monkeys trained to discriminate (+)-amphetamine from saline

The distribution of intraepithelial nerve fibres and neuroendocrine cells within the surface and glandular epithelium of human nasal mucosa and larynx was examined using immunohistochemical techniques. Neuronal structures were immunostained for the general neuroendocrine marker protein gene-product (PGP) 9.5, and the two neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) using immunofluorescence and streptavidin-biotin-peroxidase complex (S-ABC) methods. Intraepithelial nerve fibres with free nerve endings contained PGP 9.5 and were found within the respiratory surface epithelium of the nasal mucosa and the squamous epithelium of the larynx. A subpopulation of these nerve fibres showed positive immunoreactivties with antibodies against SP and CGRP. Nerve fibres within the ductal epithelium of subepithelial excretory ducts passing the basal membrane and reaching the luminal part were detected. These nerve fibres showed CGRP-like immunoreactivity but not for SP. A dense network of nerve fibres within the squamous surface epithelium was detected in the subglottic and epiglottic region containing CGRP and SP in a small subpopulation of nerve fibres. Single intraepithelial taste buds in the epiglottic region and neuroendocrine cells within the subglottic epithelium expressed PGP 9.5.     

What is satisfying about satisfying events? Testing 10 candidate psychological needs.

Three studies compared 10 candidate psychological needs in an attempt to determine which are truly most fundamental for humans. Participants described "most satisfying events" within their lives and then rated the salience of each of the 10 candidate needs within these events. Supporting self-determination theory postulates (Ryan & Deci, 2000)—autonomy, competence, and relatedness, were consistently among the top 4 needs, in terms of both their salience and their association with event-related affect. Self-esteem was also important, whereas self-actualization or meaning, physical thriving, popularity or influence, and money–luxury were less important. This basic pattern emerged within three different time frames and within both U.S. and South Korean samples and also within a final study that asked, "What's unsatisfying about unsatisfying events?" Implications for hierarchical theories of needs are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Controlled delivery of therapeutics from microporous membranes. II. In vitro degradation and release of heparin-loaded poly(D,L-lactide-co-glycolide)

In vitro degradation and release of five types of heparin/surfactant-loaded poly(D,L-lactide-co-glycolide 50:50) (PLG) microspheres alone and also incorporated within microporous polyurethane tubes were studied over a 3-month period. Degradation was studied with scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). Heparin release was characterized using a modified Azure A assay. SEM suggests that microspheres may be entrapped within polyurethane fibrils of the polyurethane tubes, thereby reducing contact with their hydrated environment. FTIR transmittance spectra confirm microsphere incorporation within the polyurethane tubes and PLG ester hydrolysis occurring over the 3-month period. A correlation was observed between decreasing molecular weights and glass transition temperatures (Tg). The microspheres alone exhibited a change in Tg but not when incorporated within the microporous tubes. Release profiles revealed a burst effect occurring during the first 4h and total release of the heparin from the microspheres by 12 weeks.     

The variation of integrated backscatter in human hearts in differing ultrasonic transthoracic views

It has been shown previously that in normal subjects the interventricular septum imaged in the long-axis view (LAX) and the left ventricular posterior wall imaged in both the LAX and the short-axis view (SAX) exhibit cyclic variation of integrated backscatter (IB) throughout the cardiac cycle, with maximum values occurring at end diastole (ED) and minimum at end systole (ES). The ability to demonstrate this cyclic variation within these myocardial regions in only two ultrasonic views has limited the potential clinical utility of an IB imaging system. To determine whether clinically useful information on the variation of IB is available from different myocardial regions in different ultrasonic views, we measured ED to ES variation of IB from the parasternal and apical views in normal subjects with a radiofrequency acquisition technique. Two independent clinical observers analyzed ED to ES variation of IB from 14 normal volunteers (mean age 32 +/- 6 years; range 21 to 45 years) in reconstructed two-dimensional ultrasonic images obtained from the parasternal LAX and SAX and apical two-chamber (2C) and four-chamber (4C) views. ED to ES variation of IB was measured from manually traced regions of interest (ROI) within the myocardium. These ROIs were chosen interactively and were located within the midposterior wall and the midanteroseptum in LAX views; within the midposterior wall, midanteroseptum, midseptum, and midlateral wall in SAX views; within the midseptum and the midlateral wall in 4C views; and within the midinferior wall and the midanterior wall 2C views. In all analyzed ROIs within the parasternal and apical views, ED to ES variation of IB was found. We have shown that the maximum magnitude of IB was at ES within the midseptum and in 10 out of 14 volunteers in the midanteroseptum measured from SAX views, the midanterior wall from 2C views, and the midlateral wall from 4C views. The rest of the ROIs analyzed exhibited the maximum value of IB cyclic variation at ED. We have confirmed that the ED to ES variation of IB is present not only when measured from the two standard parasternal views but also from the two apical views in all analyzed myocardial walls, and the minimum of this cyclic variation was not always coincident with ES nor the maximum with ED.     

Serotonin regulation of aggressive behavior in male golden hamsters (Mesocricetus auratus).

These studies examined the neurochemistry and neuroanatomy of the serotonin (5-HT) system innervating the anterior hypothalamus (AH) and the interaction of 5-HT receptor agonists with arginine vasopressin (AVP) in the regulation of offensive aggression in golden hamsters. Because specific 5-HT1A, 5-HT1B, and AVP V1A binding sites were observed within the AH by in vitro autoradiography, the hamsters were tested for offensive aggression after microinjections of AVP in combination with either the 5-HT1A agonist 8-hydroxy-2-(di-n-propylarnino) tetraline (DPAT) or the 5-HT1B agonist CGS-12066A (CGS) directly within the AH. Though treatment with DPAT resulted in a dose-dependent inhibition of AVP-facilitated offensive aggression, CGS was ineffective. In addition, a retrograde tracer was injected within the AH to localize the distribution of 5-HT neurons projecting to the area. Retrogradely labeled 5-HT neurons were found within the dorsal, median, and caudal linear raphe nuclei and are suspected to inhibit AVP-facilitated offensive aggression by an activation of 5-HT1A receptors in the AH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aerosols: a re-emerging treatment

OBJECTIVE: To describe the variation in the use of radiotherapy (RT) in women in Ontario within 1 year of diagnosis of breast cancer, from 1982 to 1991, and to identify factors associated with these variations. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario. POPULATION: All women registered by the Ontario Cancer Registry (OCR) with a diagnosis of invasive breast cancer between Jan. 1, 1982, and Dec. 31, 1991. INTERVENTIONS: RT to any anatomic site within 1 year of the diagnosis of breast cancer. OUTCOME MEASURES: Odds of receiving RT within 1 year of diagnosis (from RT files from all radiotherapy departments in Ontario) associated with year and with geographic, age-related and socioeconomic factors. RESULTS: Use of RT within 1 year of diagnosis increased from 21.1% (95% confidence interval [CI] 19.8-22.4) in 1982 to 44.7% (95% CI 43.4-46.0) in 1991 (p < 0.0001). Among the regions of Ontario, the use of RT varied from 24.5% (95% CI 23.5-25.6) to 44.4% (95% CI 43.0-45.9) (p < 0.0001). Increasing age was associated with decreasing likelihood of receiving RT (test for trend p < 0.0001), as was decreasing income (test for trend p < 0.0001). CONCLUSIONS: The use of RT within 1 year of the diagnosis of breast cancer in women in Ontario varies by region, age and income. Despite universal and comprehensive health insurance coverage, women with breast cancer in some populous regions of Ontario were less likely to receive RT within 1 year of their diagnosis than women in other populous regions.     

Safety Hazard Identification on Construction Projects

Hazard identification is fundamental to construction safety management; unidentified hazards present the most unmanageable risks. This paper presents an investigation indicating the current levels of hazard identification on three U.K. construction projects. A maximum of only 6.7% of the method statements analyzed on these projects managed to identify all of the hazards that should have been identified, based upon current knowledge. Maximum hazard identification levels were found to be 0.899 (89.9%) for a construction project within the nuclear industry, 0.728 (72.8%) for a project within the railway industry, and 0.665 (66.5%) for a project within both the railway and general construction industry sector. The results indicate that hazard identification levels are far from ideal. A discussion on the reasons for low hazard identification levels indicates key barriers. This leads to the presentation of an Information Technology (IT) tool for construction project safety management (Total-Safety) and, in particular, a module within Total-Safety designed to help construction personnel develop method statements with improved levels of hazard identification.     

Adiabatic shear bands on the titanium side in the titanium/mild steel explosive cladding interface: Experiments, numerical simulation, and microstructure evolution

The microstructure and microtexture in adiabatic shear bands (ASBs) on the titanium side in the titanium/mild steel explosive cladding interface are investigated by means of optical microscopy, scanning electron microscopy/electron backscattered diffraction (SEM/EBSD), and transmission electron microscopy (TEM). Highly elongated subgrains and fine equiaxed grains with low dislocation density are observed in the ASBs. Microtextures (25 deg, 75 deg, 0 deg), (70 deg, 45 deg, 0 deg), and (0 deg, 15 deg, 30 deg) formed within the ASBs suggest the occurrence of the recrystallization. The grain boundaries within ASBs are geometrically necessary boundaries (GNBs) with high angles. Finite element computations are performed to obtain the effective strain and temperature distributions within the ASBs under the measured boundary conditions. The rotation dynamic recrystallization (RDR) mechanism is employed to describe the kinetics of the nanograins’ formation and the recrystallized process within ASBs. During the deformation time (about 5 to 10 μs), the following processes take place: dislocations accumulate to form elongated cell structures, cell structures break up to form subgrains, and subgrains rotate and finally form recrystallized grains. The small grains within ASBs are formed during the deformation and do not undergo significant growth by grain boundary migration after deformation.     

Reconsidering Jung's psychology.

Reconsiders Jung's (1939 [1959]) psychology within an interactionist and interpersonal framework, emphasizing the use of his 2 major concepts (complex and archetype) for understanding nonrational communications between persons. The concepts of complex and archetype provide an exemplary model of the unification of affect and cognition in symbolic imagery and gestural communications. Archetype is compared to J. Bowlby's (1969) concept of human instinct as patterned action and thought in social communications between persons. Contributions of Jung's psychology are highlighted within a historical, conceptual framework: (1) reconstruction of the client's current attitude within the therapeutic domain; (2) individuation as a developmental model for practicing therapy with couples and individuals; and (3) interpretation of the archaic, symbolic aspects of communication, differentiating these from the rational, narrative aspects. The case of a married couple in therapy illustrates this framework. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Widespread sites of brain stem ventilatory chemoreceptors

We produced local tissue acidosis in various brain stem regions with 1-nl injections of acetazolamide (AZ) to locate the sites of central chemoreception. To determine whether the local acidosis resulted in a stimulation of breathing, we performed the experiment in chloralose-urethan anesthetized vagotomized carotid-denervated (cats) paralyzed servo-ventilated cats and rats and measured phrenic nerve activity (PNA) as the response index. Measurements of extracellular brain tissue pH by glass microelectrodes showed that AZ injections induced a change in pH at the injection center equivalent to that produced by an increase in end-tidal PCO2 of approximately 36 Torr and that the change in brain pH was limited to a tissue volume with a radius of < 350 microns. We found AZ injections sites that caused a significant increase in PNA to be located 1) within 800 microns of the ventrolateral medullary surface at locations within traditional rostral and caudal chemosensitive areas and the intermediate area, 2) within the vicinity of the nucleus tractus solitarii, and 3) within the vicinity of the locus coeruleus. Single AZ injections produced increases in PNA that were < or = 69% of the maximum value observed with an increase in end-tidal PCO2. We conclude that central chemoreceptors are distributed at many locations within the brain stem, all within 1.5 mm of the surface, and that stimulation of a small fraction of all central chemoreceptors can result in a large ventilatory response.     

Homosexuality and psychopolitics: An historical overview.

Traces various sources of attitudes toward homosexuality (HMSX) throughout history and explores the scientific and political forces that contributed to the depathologization of HMSX in the psychological community via the American Psychological Association. Advances in the understanding of lesbian and gay issues within psychology since the early 1970s are considered, as well as an analysis of the current state of attitudes toward HMSX within professional psychology. Attitudes toward HMSX within psychology have changed from viewing HMSX as a form of mental illness to considering gay males and lesbians to be an oppressed group in need of special considerations. However, more attention needs to be paid to the diversity within the lesbian and gay male populations in terms of race and ethnicity, religious diversity, class issues, and physical, emotional, and cognitive disability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visual search asymmetries within color-coded and intensity-coded displays.

Color and intensity coding provide perceptual cues to segregate categories of objects within a visual display, allowing operators to search more efficiently for needed information. Even within a perceptually distinct subset of display elements, however, it may often be useful to prioritize items representing urgent or task-critical information. The design of symbology to produce search asymmetries (Treisman & Souther, 1985) offers a potential technique for doing this, but it is not obvious from existing models of search that an asymmetry observed in the absence of extraneous visual stimuli will persist within a complex color- or intensity-coded display. To address this issue, in the current study we measured the strength of a visual search asymmetry within displays containing color- or intensity-coded extraneous items. The asymmetry persisted strongly in the presence of extraneous items that were drawn in a different color (Experiment 1) or a lower contrast (Experiment 2) than the search-relevant items, with the targets favored by the search asymmetry producing highly efficient search. The asymmetry was attenuated but not eliminated when extraneous items were drawn in a higher contrast than search-relevant items (Experiment 3). Results imply that the coding of symbology to exploit visual search asymmetries can facilitate visual search for high-priority items even within color- or intensity-coded displays. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flank-marking behavior and the neural distribution of vasopressin innervation in golden hamsters with suprachiasmatic lesions

In golden hamsters, microinjections of arginine-vasopressin (AVP) within the anterior hypothalamus trigger a stereotyped scent-marking behavior, flank marking. Our experiment was carried out to test the contribution of AVP neurons within the suprachiasmatic nucleus (SCN) in the control of this behavior. Our results suggest that the SCN does not contribute to flank-marking behavior. Whereas SCN lesions disrupted circadian rhythms of wheel running, the same lesions did not disrupt flank-marking. The results also suggest that neurons located outside the SCN contribute significantly to the vasopressinergic innervation of the brain and the expression of AVP-dependent behaviors, such as flank-marking behavior. Although AVP-immunoreactive fibers were severely (ca. 95%) depleted from several forebrain areas in SCN-lesioned hamsters, the effect of the lesions was much more limited within the forebrain areas involved in flank-marking behavior as well as within the midbrain and hindbrain.