Dual mechanisms of regulation of type I iodothyronine 5''-deiodinase in the rat kidney, liver, and thyroid gland. Implications for the treatment of hyperthyroidism with radiographic contrast agents.

Alterations in thyroid hormone status and the administration of radiographic contrast agents can markedly influence iodothyronine metabolism and, in particular, the activity of type I 5'-deiodinase (5'DI). In the present studies, the mechanisms responsible for these effects have been reassessed. As previously reported, the addition of iopanoic acid (IOP) to broken cell preparations resulted in a competitive pattern of 5'DI inhibition. However, the in vivo administration to rats of IOP or 3,3',5'-triiodothyronine (rT3) resulted in a noncompetitive pattern of inhibition of 5'DI in the liver, kidney, and thyroid gland, whereby marked decreases in maximal enzyme velocity (V max) were noted, with no change in the value of the Michaelis-Menten constant. In rats rendered hyperthyroid by the injection of 3,5,3'-triiodothyronine (T3), 5'DI activity was significantly increased in the liver and the kidney. The administration of IOP to these thyrotoxic animals resulted in a rapid loss of enzyme activity characterized by an approximate 80% decrease in 5'DI V max values in both tissues. Furthermore, this inhibitory effect persisted for longer than 60 h after a single IOP injection. IOP administration also decreased 5'DI V max levels in the thyroid gland by 52%. In other experiments, treatment of intact Reuber FAO hepatoma cells with IOP or rT3 induced a rapid decrease in 5'DI V max levels. In cells treated with cycloheximide, these agents enhanced the rate of disappearance of enzyme activity by greater than 12-fold, indicating a predominant effect on accelerating the rate of enzyme inactivation and/or degradation. These studies demonstrate that iodothyronines and other iodinated compounds have complex regulatory effects on 5'DI that entail alterations in the rates of both enzyme activation and inactivation. The previously accepted concept that rT3 and IOP impair thyroxine (T4) to T3 conversion in vivo by acting as competitive inhibitors is an oversimplification. Rather, the clinically beneficial effects of administering these agents to patients with hyperthyroidism may result primarily from the rapid and prolonged inactivation of 5'DI which occurs in the thyroid gland and peripheral tissues.     

Das Zytokinnetzwerk

Cytokines are extracellular mediators which co-ordinate the immune system and which are essential for several differentiation processes e.g.hematopoiesis.Cytokines bind to specific receptors on the surface of target cells thereby initiating an intracellular signalling cascade leading to cytokine- and cell-specific reactions.The cytokine network is characterised by diverse regulation mechanisms and by the close interaction of different cytokine systems.Interaction and regulation takes place at the level of cytokines, its receptors and at the level of intracellular signal transduction molecules.The resulting network allows the co-ordinated response of different cell types and tissues to environmental changes.A detailed knowledge of this “language of the immunsystem” may reveal many new therapeutical strategies for the treatment of inflammation, autoimmune disease or neoplasia.     

Decreased blood perfusion in canine tibial diaphysis after filling with acrylic bone cement compared with inert bone wax

Sixteen dogs had one tibia filled with acrylic PMMA bone cement and the opposite, control tibia filled with inert bone wax. After 1, 4, and 12 weeks, the blood perfusion in diaphyses was measured with Sc-46 labeled microspheres. The blood flow rates increased from 1 to 4 weeks and dropped to about the 1-week level after 12 weeks on both sides, with the acrylic side lower than the control side. On both sides, Disulphine Blue staining of the bones showed severe endosteal avascularity after 1 and 4 weeks and massive periosteal apposition after 4 and 12 weeks. The initial increase in blood flow is considered due to periosteal apposition, and the differences in blood flow rates are attributed to avascularity caused by the polymerization heat and toxicity of the acrylic cement.     

Buchbesprechungen

Ohne Zusammenfassung     

Continuous recording of urethral activity in healthy female volunteers

The pressure variations at the maximal urethral closure pressure (MUCP) were continuously recorded in healthy female volunteers by means of a two-point microtip transducer catheter for one hour. Before the investigation a normal voiding was assured objectively and bladder instability was excluded. All women showed pressure variations both at the MUCP and more distally. The pressure variations, from 3 to 66 cm H₂O, showed rhythmicity and three frequency ranges could be identified. Slow pressure waves with a frequency of one in eight to 19 minutes were observed. Relatively fast-pressure waves were observed (one every one to four minutes) and relatively fast-frequency pressure waves were observed (rate: one to eight per minute). The pressure variations of the urethra seem to be an aspect of normal urethral physiology possibly contributing to continence and urinary tract infection prevention.     

Exhaled gas analysis. Technical and clinical aspects of capnography and oxygen consumption

Infrared absorption and mass spectrometry represent two common techniques used for measurement of end-tidal carbon dioxide concentration in expired air. Continuous capnographic monitoring may be useful in assessing changes in ventilation, pulmonary blood flow, and metabolism. Accuracy may be affected by the type of gas sampling technique used, as well as altered ventilation and perfusion matching in the lung. Oxygen uptake at the mouth may be measured by either an open- or closed-circuit technique. Calculated values of oxygen consumption obtained from pulmonary artery catheter data and blood gases correlate well with direct gas measurement. Accurate bedside determination requires a thorough knowledge of equipment and proper gas collection, especially at high inspired oxygen levels. This information may be useful in nutritional assessments, during mechanical ventilation, and in evaluation of therapeutic interventions aimed at optimizing peripheral oxygen delivery.     

Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?

OBJECTIVE: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). METHODS: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. RESULTS: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (+/-SD) numbers of removed lymph nodes were 7+/-6.1 per patient following LS vs.18.6+/-9.3 following LA (P=0.001). An average mean of 1+/-0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7+/-0.8 following LA (P<10(-6)). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00-2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. CONCLUSIONS: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy.