Identification of potent P2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate

1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3. Monophosphate analogues that were the most potent activators of the C6 cell P2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate were potent P2Y-purinoceptor agonists no effect of these analogues on the human P2U-purinoceptor were observed. 5. These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P2Y-purinoceptors, and provide insight for strategies for development of novel P2Y-purinoceptor agonists of high potency and selectivity.     

A PET study of the neural systems of stuttering

The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking.     

Integrative Cognitive Therapy for Depression: A Preliminary Investigation.

This study is a preliminary investigation of an integrative treatment aimed at improving the efficacy of cognitive therapy (CT) for depression. The development of the treatment protocol was based on process findings, which suggested that strategies used in CT to resolve alliance ruptures may actually exacerbate problems in the therapeutic relationship. The protocol integrates, within the traditional CT treatment manual, procedures to repair alliance ruptures that are derived from or consistent with humanistic and interpersonal therapies. Although conducted by inexperienced therapists, the integrative treatment led to greater improvement than a waiting-list condition. The results also compare favorably to previous findings for CT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Orbital volume measurement in the management of pure blowout fractures of the orbital floor

With the recent advent of accurate orbital volume assessment by computed tomography, a retrospective analysis was made of 31 patients with 'pure' blowout fracture of the orbital floor, managed either surgically or conservatively, to determine whether orbital volume measurement could provide an additional parameter of use in the management of such fractures. There was a significant difference in orbital volume discrepancy between patients managed surgically or conservatively suggesting that this investigation may be of use in decision making on surgical intervention in patients with orbital blowout fractures.     

Understanding source effects in ADHD rating scales: Reply to DuPaul (2003).

G. J. DuPaul (see record 2003-02033-012) offered two suggestions for additional research to understand the strong source effects reported by R. Gomez, G. L Burns, J. A. Walsh, and M. A. de Moura (see record 2003-02033-001) in attention-deficit/ hyperactivity disorder (ADHD) rating scales. The first suggestion was to determine whether the source effects represent mostly bias or accuracy. The second suggestion was to minimize source effects through the development of better ADHD rating scales. Because source effects can represent bias or accuracy, it is important to minimize the bias aspect through content validation procedures prior to attempts to determine whether source effects better reflect bias or accuracy. This comment offers various suggestions to reduce the bias in ADHD rating scales. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Professionally-led support groups for cancer patients: an intervention in search of a model

OBJECTIVE: The objective of this review was to evaluate the clinical and research literature on professionally-led support groups for cancer patients and to propose an approach that would address patients' needs from diagnosis through survivorship. METHOD: Computerized and manual searches, including Medline and Psychlit searches, were completed for reviews of the literature. Twelve research studies were identified that met our criteria for in-depth review. A clinical model emerged from discussions of an oncology study group based on theoretical formulations and clinical experience with oncology patients. RESULTS: We found that recent research suggests that professionally-led support groups are increasing in number and that participation in such groups seems to enhance patients' quality, and possibly even quantity, of survival. Despite this, little effort has been made to determine what type of group may be appropriate for which patients and when in their course of care. CONCLUSIONS: If psychosocial intervention, in the form of professionally-led support groups for cancer patients, is to be more effective, it should be guided by a model which takes into consideration the changing needs and concerns of patients over the course of illness and, in many cases, recovery. The authors present an outline delineating what such a model might entail.