The thyrotropin response to thyrotropin-releasing hormone in endogenous depression

In 1958 a new therapy for depressions was introduced: medication with antidepressants. Almost simultaneously, but independendy, two types of compounds with an antidepressant effect were discovered: the tricyclic antidepressants (prototype: imipramine) and the monoamine oxidase inhibitors (MAOIs*) prototype: iproniazide). Previously, only amphetamine derivatives and opiates had been available for antidepressant medication. The effect of amphetamines on affective life was variable and brief, and often followed by a hangover; opiates actually acted mainly on anxiety and agitation. The antidepressants, with an effect on mood regulation which in suitable cases was primary and lasting, represented a new pharmacothera-peutic principle.

Amine Hypotheses of Affective Disorders

The brain is known to contain many peptides of diverse molecular weight and complexity. The larger ones contribute to the structure and to the enzymatic machinery essential for the metabolism of this complex organ. Smaller ones are hormones and some may be involved in the formation of long-term memory. Still others may arise as a consequence of generalized experiences such as sleep. Because the number of possible amino acid combinations is immense, it is likely that many more peptides will be discovered and that these will be found to have functions unique to the brain.

Peptides and the Central Nervous System

Radiopharmaceutical-related pitfalls and artifacts

— The experience of using thyroid hormones in affective disorders is summarized. This includes: 1) Using thyroid hormones alone in depression; 2) their combined use with tricyclic antidepressants; 3) addition of thyroid hormones to non-tricyclic antidepressants; 4) the use of thyroid stimulating hormone; and 5) thy-rotropin releasing hormone in depression. Suggested mechanisms of action are discussed. A special attention is paid to the place of thyroid hormones in the treatment of rapid cycling affective disorder.

Thyroid hormones in the treatment of affective disorders.

In a double reversal design the potency of thyrotropin releasing hormone (TRH) (500 mug intravenously) as a quick-acting antidepressive agent was evaluated. A first injection did seem to give rise to a very slight short-lasting effect, though this could not be ascertained clearly. There were no visible effects after a second injection. The thyroid stimulating hormone (TSH) response curve after TRH administration in the depressive patients group was blunted in comparison with that in a matched control group of normals.

Thyrotropin releasing hormone (trh) as a possible quick-acting but short-lasting antidepressant

Publisher Summary This chapter focuses on the action of releasing factors on unit activity in the forebrain. Single unit activity was recorded from the cerebral cortex and rostral hypothalamus in urethane anesthetized rats. Recordings were made from the central barrel of multibarreled micropipettes. The outer barrels were filled with 1.0 M sodium glutamate, 0.01 Moxytocin, 0.01 M LHRH, 0.03 A4 TRH and 2 M sodium chloride. A drug was considered to influence the activity of a cell if changes in firing rate, in excess of 20 % of the resting rate, were induced by application of ejecting currents (5-30 nA) to the drug containing barrels. The results demonstrate that releasing factors directly influence the electrical activity of the hypothalamus.

TRH as a possible quick-acting but short-lasting antidepressant.

For many years iodide-131 Hippuran has been used as a tracer to measure effective renal plasma flow (ERPF). Because of the low renal clearance of free131-Iiodide and the inability to count it separately from131I-Hippuran, free131I-iodide will lower the calculated131I-Hippuran clearance, resulting in a lower estimated ERPF. This study was performed to establish the maximum allowable radiochemical impurity of free131I-iodide in131I-Hippuran preparations for ERPF measurements in continuous clearance studies. A known amount of123I-iodide was added to the (131I-iodide-free)131I-Hippuran solution used for continuous infusion clearance studies in nine patients.123I-iodide activity was used because it can be counted separately from131I-Hippuran in the infusion solutions and plasma samples while it behaves exactly like131I-iodide, so that the results obtained with123I-iodide can be extrapolated to131I-iodide. After performing the clearance studies, the ERPF was calculated firstly with131I-Hippuran activity only (=true ERPF) and secondly including the free radioactive iodide activity (=false ERPF) in the clearance formula. As expected, if free131I-iodide is present in the infusion solution, its concentration in plasma will be highest at the end of the clearance study. The131I-iodide concentration in plasma relative to the131I-Hippuran concentration will be higher in patients with high ERPF values.131I-iodide in the infusion solution causes a fall in the ERPF as measured by the continuous infusion technique: 0.5%, 1% and 2% of free131I-iodide in the infusion solution result in a reduction in ERPF of about 1.5%, 3.5% and 7% respectively after 1.5 h and of 3.5%, 6.5% and 13% respectively after 5.5 h if ERPF is high. It is concluded that a maximum of 0.5% of free131I-iodide in131I-Hippuran preparations is permissible if ERPF is to be measured with an error of less than 5%.

Iodine-131 Hippuran for the estimation of renal plasma flow: requirements for radiochemical purity

Objective: The aim of the study is to use the activity-based costing approach to give a better insight in the actual cost structure of a positron emission tomography procedure (FDG-PET) by defining the constituting components and by simulating the impact of possible resource or practice changes. Methods: The cost datawere obtained from the hospital administration, personnel and vendor interviews as well as from structured questionnaires. A process map separates the process in 16 patientand non-patient-related activities, to which the detailed cost data are related. One-way sensitivity analyses shows to which degree of uncertainty the different parameters affect the individual cost and evaluate the impact of possible resource or practice changes like the acquisition of a hybrid PET/CT device, the patient throughput or the sales price of a 370MBq 18F-FDG patient dose. Results: The PET centre spends 73% of time in clinical activities and the resting time after injection of the tracer (42%) is the single largest departmental cost element. The tracer cost and the operational time have themost influence on cost per procedure. The analysis shows a total cost per FDG-PET ranging from 859 Euro for a BGO PET camera to 1142 Euro for a 16 slices PET-CT system,with a distribution of the resource costs in decreasing order:materials (44%), equipment (24%), wage (16%), space (6%) and hospital overhead (10%). Conclusions: The cost of FDG-PET is mainly influenced by the cost of the radiopharmaceutical. Therefore, the latter rather than the operational time should be reduced in order to fective improve its cost-ef

A.K. Van Zanten

Papers

Thyrotropin releasing hormone (trh) as a possible quick-acting but short-lasting antidepressant

TRH as a possible quick-acting but short-lasting antidepressant.

Iodine-131 Hippuran for the estimation of renal plasma flow: requirements for radiochemical purity

Activity-based costing evaluation of [F-18]Fludeoxyglucose Positron Emission Tomography study