Effect of divalent cations on structure-function relationships of the antitumor protein α-sarcin

α-Sarcin binds one Zn(II) cation per protein molecule, with a K_d value of 0.9 mM, determined by equilibrium dialysis experiments. Ca(II), Mg(II), and Mn(II) do not bind to α-sarcin. Cd(II) and Co(II) also behave as Zn(II). The binding produces local modifications on the protein conformation affecting the microenvironment of tryptophan residues. The three cations modify the fluorescence emission of the protein. The near-u. v. circular dichroism spectrum of the protein is also altered. The binding of Zn(II) and related cations does not modify the secondary structure of the protein. The ribonucleolytic activity of a-sarcin is inhibited upon Zn(II) binding, but no alteration of the ability of the protein to aggregate phospholipid vesicles has been observed.     

ON THE USE OF A NEW SOMATOSTATIN ANALOGUE IN THE TREATMENT OF HYPOGLYCAEMIA IN PATIENTS WITH INSULINOMA

A novel potent analogue of somatostatin, the octapepide SMS 201-995 was tested as a therapeutic manoeuvre to prevent hypoglycaemia in patients with insulinoma. We investigated the acute effects of a single 50 micrograms dose of the analogue administered s.c. in three patients, comparing the results in two of them with those obtained after administration of saline (control) and native somatostatin. In addition two patients were treated for up to 5 d with two or three daily s.c. injections (daily dose of analogue ranging from 100 to 300 micrograms). In two of the three patients SMS 201-995 suppressed circulating insulin levels by more than 50% and increased plasma glucose to hyperglycaemic levels for 6-8 h after a single injection. No undesirable effects of the administration of the analogue were observed. As opposed to insulin suppression obtained with native somatostatin, no rebound increase in insulin levels was observed after administration of the analogue. We conclude that SMS 201-995 prevented hypoglycaemia in two out of three patients with insulinoma. The advantage of s.c. administration, the long duration of action and the absence of a rebound phenomenon give this analogue a place in the pre-operative management of patients with insulinoma.     

A COMPARISON BETWEEN THE EFFECTS OF SMS 201–995, BROMOCRIPTINE AND A COMBINATION OF BOTH DRUGS ON HORMONE RELEASE BY THE CULTURED PITUITARY TUMOUR CELLS OF ACROMEGALIC PATIENTS

The in-vivo reaction of the plasma GH concentration to the administration of the somatostatin analogue SMS 201-995, bromocriptine and their combination were compared with the in-vitro effects of both compounds and their combination on GH release and the GH tumour cell content of 9 acromegalic patients. Exposure of cultured GH-secreting pituitary tumour cells for 4-96 h to SMS 201-995 showed a variable, but in all instances during longer incubations statistically significant inhibition of GH release, which paralleled the sensitivity of GH secretion to the drug in vivo. This inhibitory effect on GH release was in two of the eight tumours accompanied by a decrease in the GH tumour cell content after 24-72 h of culture. These changes either reflect an inhibition of GH synthesis and/or an increase in intracellular breakdown (crinophagy) of GH and might be the basis for the tumour shrinkage which has been observed in about half of the acromegalic patients during long-term SMS 201-995 therapy. The inhibitory effects of bromocriptine on GH secretion were antagonized by haloperidol, while the inhibitory effect of SMS 201-995 was not affected by the dopamine receptor antagonist. This suggests that the effects of SMS 201-995 and bromocriptine are mediated via separate mechanisms involving different receptors. Additive but no potentiating inhibitory effects of both drugs on GH release were observed in a group of six patients in vivo and in three of six tumours in vitro.     

CHRONIC DOPAMINE RECEPTOR STIMULATION USING BROMOCRIPTINE: FAILURE TO MODIFY THYROID FUNCTION

Administration of 2.5 mg bromocriptine (Parlodel), a dopamine agonist, on two occasions to six normal volunteers did not alter the plasma TSH response to an i.v. injection of 100 micrograms TRH, but significantly (P less than 0.01) blunted it after 200 micrograms. Chronic bromocriptine treatment (7.5--50 mg/day) of fifteen acromegalic subjects failed to influence basal plasma TSH or the response pattern to 200 micrograms TRH. The thyroxine Binding Index (TBI) and the levels of T3 and T4 were not modified by treatment. These results indicate that chronic dopaminergic therapy with bromocriptine does not alter thyroid function.     

Allergy to olive pollen: T-cell response from olive allergic patients is restricted by DR7-DQ2 antigens

Backgound We have recently described the association between the IgE antibody response to Ole e I (the major antigen from olive tree pollen) and the DR7-DQ2 haplotype in a Spanish population. Objeectivc and methods Due to the linkage disequilibrium between DR7 and DQ2, and thus the dillicult distinction between the role of these two antigens in the T-cell activation response, we decided to solve this question by two approaches: 1. The study of another ethnic group, individuals of Arabic origin, with a presumably distinct disequilibrium linkage between DR and DQ antigens. Genomic DNA typing was performed in 46 subjects (allergic and non-allergic) by Restriction Fragment Length Polytnotphism (RFLP) and results showed that patients with specific IgE antibodies α-Ole e I, were DR7 and or DQ2. These data show a similar restriction pattern to those previously described for Spanish patients. The phenolypic frequency of DR7 antigen is significantly greater than in the non-allergic population, with a corrected P(PJ value of O.O.3 2 The analysis of the genetic requirements of Ole e I response, using T-cell lines speific for this antigen. This was first carried out by blocking the proliferative response of these T-cell lines with specific anti-human HLA class II antibodies and then testing the genetic restriction of this response using a panel of histoeompatible and histoincompatible Antigen Presenting Cells (APCs). Both experiments corroborate the hypothesis that DR7 and DQ2 are implicated in the recognition o(Ole e I.     

Post‐operative hyponatraemic encephalopathy: a successful outcome despite hypoxia

Hyponatraemia is the most common electrolyte disorder encountered in clinical practice. Symptomatic hyponatraemia reflects brain damage because of cerebral swelling. Some coexisting factors such as extreme ages, hypoxia and female sex are associated with poor prognosis. In this report, we describe the case of a 75‐year‐old patient who suffered from hyponatraemic encephalopathy after elective vaginal hysterectomy under spinal anaesthesia. After being transferred to the ward, she developed nausea, vomiting, hypertensive crisis and intense anxiety. These symptoms were followed by grand mal seizure. Serum sodium level was 108 mmol/l. She also presented hypoxia, considered an aggravating factor, which was probably caused by the combination of benzodiazepine intake and cerebral oedema. However, fast raise of serum sodium level was achieved by immediate treatment with hypertonic saline, and she was discharged home without any sequelae.     

Reticular erythematous mucinosis syndrome. Report of with positive immunofluorescence

We report a case with the clinical and histological features of the reticular erythematous mucinosis syndrome (REM), in which there was moderate, continuous, fine, granular, IgM deposition along the basal layer. Similar direct immunofluorescence results have been reported in only two previous cases.