Plasma tyrosine/neutral amino acid ratio correlated with clinical response to nortriptyline in endogenously depressed patients.

Ratios in plasma of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 26 endogenous depressives before and after treatment with nortriptyline in doses adequate to achieve a steady-state serum level between 70 and 130 ng/ml, i.e., within the recommended therapeutic range. Pretreatment plasma Trp ratio and Tyr ratio were normal and did not change significantly during treatment. The plasma Trp and Tyr concentrations and the plasma Trp ratio showed no significant association with the therapeutic response. However, the pretreatment plasma Tyr ratio correlated significantly and directly with the final Hamilton rating score, and inversely with the per cent reduction of Hamilton rating score. Moreover, depressives with plasma Tyr ratio below the normal mean showed significantly greater clinical improvement than patients with higher plasma Tyr ratio with comparable serum nortriptyline levels. Evidence has been presented that biochemical variables in depressed patients are important determinants of clinical improvement following pharmacotherapeutic treatment. Moreover, the results suggest that the plasma Tyr ratio may be a guideline for antidepressant response to nortriptyline.

Circadian variation of serum thyrotropin in endogenous depression.

The circadian variation of serum thyrotropin (thyroid-stimulating hormone; TSH) was studied in nine patients with endogenous depression before and after recovery. Depressed state did not appear to influence the pattern of TSH. When 2 mg of dexamethasone was administered, serum TSH was significantly reduced for 18 hours, whereafter the effect leveled off. The TSH response to thyrotropin-releasing hormone (TRH) was evaluated 25 hours after the administration of dexamethasone and the response was found to be unchanged.

Local regulation of blood flow in subcutaneous tissue in patients with acute myocardial infarction.

1. Local regulation of subcutaneous blood flow in the forearm was studied in the acute phase of myocardial infarction. Blood flow was measured by the local 133Xe-washout technique. 2. Plasma concentrations of noradrenaline and adrenaline were increased on day 1, suggesting an increase in sympathetic neuronal activity, but gradually returned to normal thereafter. 3. Subcutaneous blood flow on day 1 was far below normal (38%) and steadily increased to reach normal at day 7 after coronary occlusion. The sympathetic vasoconstrictor activity that caused the initial reduction in flow could be blocked by proximal nervous blockade, increasing the subcutaneous blood flow by 130, 63 and 14% on days 1, 3 and 7 respectively after coronary occlusion. A normal response to decrease in arterial perfusion pressure was observed, suggesting that intrinsic vascular reactions responsible for autoregulation of blood flow were not affected by the increase in sympathetic vasoconstrictor activity. The vasoconstrictor response to increase in venous transmural pressure could not be demonstrated on day 1 after coronary occlusion but gradually reappeared during the following days. 4. Abolition of the vasoconstrictor response is most likely to be due to a centrally elicited increase in sympathetic activity, as a normal vasoconstrictor response was obtained after proximal nervous blockade. Thus the local sympathetic reflex mechanism underlying the vasoconstrictor response appears to be suppressed by a centrally elicited increase in sympathetic discharge rate.

Influence of epidural analgesia on the catecholamine and cyclic AMP responses to surgery.

The effects of neurogenic block on plasma concentrations of adrenaline, noradrenaline and cyclic AMP were studied. Eighteen patients were subjected to surgery of moderate or minor extent under enflurance anesthesia with or without epidural analgesia. The results show that adrenaline secretion during surgical stress is a response to neurogenic stimuli, since the increase found in patients subjected to hysterectomy under general anesthesia is blocked by the addition of epidural analgesia. Furthermore, plasma adrenaline after neurogenic block is comparable with adrenaline levels during minor surgical stress. The plasma noradrenaline concentration does not correlate with the extent of trauma. In contrast to adrenaline levels, noradrenaline concentrations varied insignificantly during and after surgery. However, the addition of epidural block induced a postoperative increase in noradrenaline apparently unrelated to changes in heart rate or blood pressure. Simultaneous measurements of the catecholamines and cyclic AMP indicate that adrenaline is of minor importance for plasma cyclic AMP in resting patients, whereas the increase in cyclic AMP elicited by surgery reflects adrenaline-stimulated beta-adrenergic activity.

Influence of age on the endocrine-metabolic response to surgery.

The pathogenesis of the increased operative risk in elderly patients is unknown. From a theoretical point of view, a change in endocrine-metabolic response might be involved. In the present study, a battery of hormonal and metabolic variables were measured in eight young and eight elderly healthy males undergoing elective inguinal hernial repair under general anesthesia. Blood was drawn before induction of anesthesia, at skin incision, and one, two, and six hours after skin incision. The findings were: 1) Plasma cortisol increase was significantly higher in elderly than in young controls. 2) Plasma renin level was lower in old age, but renin-aldosterone and electrolyte response patterns were alike in the two groups. 3) Thyroid parameters, in terms of serum T4, serum T3, serum rT3, and T3-resin uptake, responded normally to surgery and showed no age-related differences. 4) The hyperglycemic response was not significantly influenced by age indicating unchanged glycoregulatory mechanisms also verified by determinations of plasma catecholamines, cAMP, and insulin. 5) Blood lymphocyte count was constantly lower in elderly than in young and decreased with time, but the age-related difference was not significant. 6) Blood polymorphonuclear leukocytes showed an increase of the same magnitude in both age groups, although at a significantly slower rate in the elderly. It is concluded that age affects some aspects of the initial endocrine-metabolic response to surgery.

Cyclic AMP, adrenaline and noradrenaline in plasma during surgery.

Plasma concentrations of cyclic AMP, adrenaline and noradrenaline were measured in 6 patients undergoing hysterectomy from before induction of anaesthesia to 6 h after skin incision. Noradrenaline did not vary significantly during the observation period, whereas cyclic AMP and adrenaline increased after skin incision. A significant correlation was found between plasma concentrations of cyclic AMP and adrenaline (r = 0.84, P less than 0.01), suggesting that the latter is responsible for the increase in plasma cyclic AMP which is observed in relation to surgical procedures. Peak concentrations of cyclic AMP and adrenaline were seen in the early postoperative phase. This indicates that the most pronounced acute endocrine stress response to surgery of moderate severity occurs after termination of anaesthesia.

[The action of reserpine on the concentration of 5-hydroxytryptamine, epinephrine and norepinephrine in the venous blood of migraine patients]. / L'azione della reserpina sulla concentrazione della 5-idrossitriptamina, dell'epinefrina e della norepinefrina nel sangue venoso di pazienti emicranici

Vasoactive amines, particularly 5-hydroxy-tryptamine (5-HT) have been implicated as the cause of migraine. Our study was a biochemical one on the effect of reserpine on the content of 5-HT, NE and E in migraneurs. The effect of one single infection of reserpine. 23 migrainous patients and 7 controls were given one i.m. injection of reserpine (1,5 mg/1.7 m2 surface). The content of 5-HT in blood platelets of 8 migraneurs and 7 controls 6 hours after the injection of reserpine decreased to comparable levels in both groups. The serotonin releasing effect of reserpine, however, is different from that of tyramine. The effect of prolonged reserpine medication. The effect of i.v. injection of reserpine over a period of 6 weeks on 5-HT, NE and E, was investigated. The doses of reserpine corresponded exactly to the doses already used by Nattero et al. (0.2 mg reserpine 3 times a week for 6 weeks). In correspondance with this work a double blind clinical examination was carried out by Nattero et al. (1975). Blood amine levels were measured weekly. The NE decreased to a minimum of 62% of basal mean value after 3-7 weeks of treatment. The decrease is significant from the third to the sixth week. Basal value was not reached until 6 weeks after withdrawal of reserpine. The concentration of 5-HT in blood platelets decreased to 5% of basal mean value and remained low during the reserpine treatment. The decrease is highly significant. A clinical improvement began 1-2 weeks after the introduction of reserpine treatment, continued during treatment and for 2-6 weeks after. In the open trial performed by us, we can confirm the results of Nattero et al. We demonstrated a marked decrease in concentration of blood amines corresponding to clinical improvement.