Pharmacological studies of the involvement of hypothalamic prostaglandins in the regulation of thyrotropin secretion.

A case is made for the involvement of pituitary prostaglandins (PGs) in the regulation of thyrotropin (TSH) secretion by citing recent evidence that TSH release in vivo and in vitro is enhanced by treatment with exogenous PGs and is inhibited by drugs (e.g., indomethacin) that block PG synthesis. Pharmacological studies were then performed to test the hypothesis that hypothalamic PGs also affect TSH secretion indirectly via the appropriate hypothalamic hormones that regulate pituitary secretion. The inhibition of thyroidectomy-induced TSH secretion was used as an endpoint in choosing the best of several drugs purported to inhibit PG synthesis. The established effectiveness of indomethacin and aspirin were used for reference in testing the following drugs: naproxen, mefenamic acid, tranylcypromine, and phenelzine. Only naproxen was found to be effective, but since it was no more potent than indomethacin, the latter drug was used for subsequent work. Indomethacin was stereotaxically implanted into several hypothalamic regions known to regulate TSH secretion, and sequential plasma samples were analyzed for TSH by radioimmunoassay. Bilateral implants of indomethacin in the anterior hypothalamic area increased TSH secretion throughout the 72 hr period of study. Sham inplants at this site and indomethacin implants in other nearby sites were ineffective. These findings suggest that endogenous PGs play an inhibitory role in the hypothalamic regulation of pituitary secretion

Factors modulating the secretion of thyrotropin and other hormones of the thyroid axis.

The first portion of this paper is devoted to an overview of the normal function of the hypothalamo-pituitary-thyroid axis. This section emphasizes areas of current research interest and it identifies several sites and mechanisms that are potentially important interfaces with toxins or toxic mechanisms. We then describe an in vitro technique for the continuous superfusion of enzymatically dispersed pituitary cells; this approach is particularly valuable in studying the dynamics of the TSH responses to the factors known (or suspected) to regulate TSH secretion in vivo. Using this technique, we have found that 10(-5)M prostaglandin (PG)I2 stimulates TSH secretion without altering the response to TRH (10(-8)M), and that this stimulation is not due to its rapid conversion to 6-keto PGF1 alpha. In contrast PGs of the E series (PGE1 and PGE2, 10(-5)M) increase responsiveness to TRH but have no effect alone. We found no effects of any of the other prostanoids tested (PGs A2, B2, F1 alpha, F2 alpha, thromboxanes A2 and B2, and the endoperoxide analog, U-44069. Somatostain (10(-9)M inhibits TRH-induced TSH secretion, but does not alter the responsiveness to PGI2. These findings suggest that somatostatin blocks TSH secretion at a point that is functionally prior to the involvement of the PGs, and perhaps does so by blocking synthesis or limiting availability of selected PGs

Inability to improve performance with control shows limited access to inner states

Any repeatedly performed action is characterized by endogenous variability, affecting both speed and accuracy—for a large part presumably caused by fluctuations in underlying brain and body states. The current research questions concerned (a) whether such states are accessible to us and (b) whether we can act upon this information to reduce variability. For example, when playing a game of darts, there is an implicit assumption that people can wait to throw until they are in the right perceptual-attentional state. If this is true, taking away the ability to self-pace the game should worsen performance. We first tested precisely this assumption asking participants to play darts in a self-paced and a fixed-paced condition. There was no benefit of self-pacing, showing that participants were unable to use such control to improve their performance and reduce their variability. Next, we replicated these findings in 2 computer-based tasks, in which participants performed a rapid action-selection and a visual detection task in 1 self-paced and 3 forced-paced conditions. Over 4 different empirical tests, we show that the self-paced condition did not lead to improved performance or reduced variability, nor to reduced temporal dependencies in the reaction time (RT) series. Overall, it seems that, if people have any access to their fluctuating performance-relevant inner states, this access is limited and not relevant for upcoming performance

Low and variable correlation between reaction time costs and accuracy costs explained by accumulation models: Meta-analysis and simulations.

The underpinning assumption of much research on cognitive individual differences (or group differences) is that task performance indexes cognitive ability in that domain. In many tasks performance is measured by differences (costs) between conditions, which are widely assumed to index a psychological process of interest rather than extraneous factors such as speed–accuracy trade-offs (e.g., Stroop, implicit association task, lexical decision, antisaccade, Simon, Navon, flanker, and task switching). Relatedly, reaction time (RT) costs or error costs are interpreted similarly and used interchangeably in the literature. All of this assumes a strong correlation between RT-costs and error-costs from the same psychological effect. We conducted a meta-analysis to test this, with 114 effects across a range of well-known tasks. Counterintuitively, we found a general pattern of weak, and often no, association between RT and error costs (mean r = .17, range −.45 to .78). This general problem is accounted for by the theoretical framework of evidence accumulation models, which capture individual differences in (at least) 2 distinct ways. Differences affecting accumulation rate produce positive correlation. But this is cancelled out if individuals also differ in response threshold, which produces negative correlations. In the models, subtractions between conditions do not isolate processing costs from caution. To demonstrate the explanatory power of synthesizing the traditional subtraction method within a broader decision model framework, we confirm 2 predictions with new data. Thus, using error costs or RT costs is more than a pragmatic choice; the decision carries theoretical consequence that can be understood through the accumulation model framework

Slow and steady? Strategic adjustments in response caution are moderately reliable and correlate across tasks.

Speed-accuracy trade-offs are often considered a confound in speeded choice tasks, but individual differences in strategy have been linked to personality and brain structure. We ask whether strategic adjustments in response caution are reliable, and whether they correlate across tasks and with impulsivity traits. In Study 1, participants performed Eriksen flanker and Stroop tasks in two sessions four weeks apart. We manipulated response caution by emphasising speed or accuracy. We fit the diffusion model for conflict tasks and correlated the change in boundary (accuracy – speed) across session and task. We observed moderate test-retest reliability, and medium to large correlations across tasks. We replicated this between-task correlation in Study 2 using flanker and perceptual decision tasks. We found no consistent correlations with impulsivity. Though moderate reliability poses a challenge for researchers interested in stable traits, consistent correlation between tasks indicates there are meaningful individual differences in the speed-accuracy trade-off

Evaluation of antigens for the serodiagnosis of kala-azar and oriental sores by means of the indirect immunofluorescence antibody test (IFAT)

Antigens and corresponding sera were collected from travellers with leishmaniasis returning to Germany from different endemic areas of the old world. The antigenicity of these Leishmania strains, which were maintained in Syrian hamsters, was compared by indirect immunofluorescence (IFAT). Antigenicity was demonstrated by antibody titres in 18 sera from 11 patients. The amastigotic stages of nine strains of Leishmania donovani and four strains of Leishmania tropica were compared with each other and with the culture forms of insect flagellates (Strigomonas oncopelti and Leptomonas ctenocephali). Eighteen sera from 11 patients were available for antibody determination with these antigens. The maximal antibody titres in a single serum varied considerably depending on which antigen was used for the test. High antibody levels could only be maintained when Leishmania donovani was employed as the antigen, but considerable differences also occurred between the different strains of this species. The other antigens were weaker. No differences in antigenicity between amastigotes and promastigotes of the same strain were observed. It is important to select suitable antigens. Low titres may be of doubtful specificity and are a poor baseline for the fall in titre which is an essential index of effective treatment.Wir sammelten Parasiten und Seren von Reisenden, die aus verschiedenen endemischen Gebieten der Alten Welt mit einer Leishmaniasis nach Deutschland zurückkehrten. Die Antigenaktivitäten der isolierten und fortlaufend in Goldhamstern gehaltenenLeishmania-Stämme wurden im indirekten Immunofluoreszenztest (IFAT) verglichen. Die Antigenität wurde an Hand von Antikörpertitern in 18 Serumproben von 11 Patienten bewiesen. Neun Stämme desLeishmania donovani-Komplexes und vierLeishmania tropica-Isolate wurden in ihrem amastigoten Stadium miteinander verglichen. Hinzu kamen zwei Insekten-Flagellaten als Kulturformen:Strigomonas oncopelti undLeptomonas ctenocephali. 18 Serumproben von 11 Patienten standen für die Antikörperbestimmung mit diesen Antigenen zur Verfügung. Die maximalen Titerhöhen variierten in ein- und derselben antiserumprobe zum Teil erheblich, je nachdem, welches Antigen für den Test benutzt wurde. Hohe Antikörpertiter konnten nur erhalten werden, wennLeishmania donovani als Antigen vorlag, es ergaben sich aber auch zwischen den einzelnen Stämmen dieser Leishmaniaart erhebliche Unterschiede in der Antigenaktivität. Antigene anderer Art erwiesen sich als wenig wirksam. Zwischen amastigoten und promastigoten Entwicklungsformen einesLeishmania donovani-Stammes konnten keine Unterschiede in der Antigenaktivität erkannt werden. Für den Nachweis möglichst hoher Antikörpertiter im IFAT ist die Auswahl geeigneter Antigene von ausschlaggebender Bedeutung. Niedrige Titer erschweren deren Beurteilung als spezifisch und sind eine schlechte Ausgangsposition für die Beobachtung des obligatorischen Titerabfalles nach erfolgreicher Therapie

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

Smell-related quality of life changes after total laryngectomy : a multi-centre study

Purpose: A total laryngectomy creates an alternate airway for gas exchange that bypasses the upper aerodigestive tract. The subsequent reduction in nasal airflow, and therefore, reduction in deposition of particles to the olfactory neuroepithelium leads to hyposmia or anosmia. The aim of this study was to assess the quality of life impairment conferred by anosmia following laryngectomy and identify any specific patient-related risk factors that are associated with poorer outcomes. Methods: Consecutive patients with a total laryngectomy presenting for review at three tertiary head and neck services (in Australia, the United Kingdom and India) over a 12-month period were recruited. Patient demographic and clinical data were collected, and each subject completed the validated assessment of self-reported olfactory functioning and olfaction-related quality of life questionnaire (ASOF). Dichotomous comparisons were performed using the student's unpaired t-test for continuous variables (SRP), a chi-squared test for categorical variables, and a Kendall's tau-b for ordinal variables (SOC) to assess for a correlation with poorer questionnaire scores. Results: A total of 66 laryngectomees (13.4% female; age 65.7 ± 8.6 years) were included in the study. The mean SRP score of the cohort was found to be 15.6 ± 7.4, while the mean ORQ score was noted to be 16.4 ± 8.1. No other specific risk factors associated with poorer quality of life were identified. Conclusion: A significant quality of life detriment from hyposmia is conferred following laryngectomy. Further research to assess treatment options and the patient population that would best benefit from these interventions is required