Studies of the mechanism of chloroquine binding to synthetic DOPA-melanin

In order to elucidate the mechanism of drugs binding to melanin, effects of pH, ionic strength and organic solvent on the interaction of chloroquine with synthetic dopa-melanin were studied. The results indicate that electrostatic, hydrophobic and van der Waals' forces participate in the formation of the chloroquine-melanin complex. Binding analysis by the Scatchard method showed that two classes of binding sites take part in the complex formation: strong binding sites with the association constant k1 approximately to 10(5) and weak binding sites with K2 approximately 10(4). Experiments with chemically modified melanin yielded some information about binding sites of this biopolymer. The obtained results suggest that strong binding involves both hydrophobic interaction and electrostatic attraction between the protonated ring system of chloroquine and the ortho-semiquinone groups of melanin. However, the weakly reacting sites can be identified as ionic bonds between protonated aliphatic nitrogen of chloroquine molecule and carboxyl groups of melanin. Van der Waals' forces occurring at the conjunctions of the aromatic rings of the drug and the aromatic indole-nuclei of the melanin probably take part in the weak binding too.     

Subacute myocardial hypoxia in the rat. An electron microscopic study of the left ventricular myocardium

Electron microscopic analysis of left ventricular myocardium from rats made hypoxic for 2h, 10 and 30 days showed focal intracellular oedema as the only alteration in acute severe hypoxia (6% oxygen). No mitochondrial lesions were seen. In chronically hypoxic hearts (9% oxygen) the mitochondrial structure also remained normal.Morphometric analysis has showed a significant increase in capillary density and in the number of mitochondria. The mean diameter of the latter seems to be smaller in hypoxic than in control hearts.     

C-band pattern in lymphocytes of patients with soft tissue sarcomas

The pattern of heteromorphisms in the C-band-positive constitutive heterochromatin of human chromosomes No. 1, 9, and 16 was studied in peripheral lymphocytes of 45 patients with soft tissue sarcomas and 78 control individuals. The parameters of the heterochromatic regions analyzed were relative size, symmetry-asymmetry within homologous pairs, and incidence of inversions. No consistent differences were found in these parameters between controls and sarcoma patients.     

In vivo atrial excitability and anti-arrhythmic drugs

The threshold of excitability of the atrial muscle was studied in the in vivo beating canine heart. Unipolar cathodal and anodal strength-interval curves were constructed and found to be dissimilar in shape. It was found that at any interval within the relative refractory period of the atrium, as in the ventricle, there is a wide range of current levels delineated by an upper (Tu) and lower (Tl) limit of threshold which can stimulate the atrial myocardium. Within these limits the threshold varies spontaneously and can be reduced to Tl level by a run of extrasystoles.Such Tu and Tl curves were repeatedly determined following administration of therapeutic doses of quinidine, procaine amide or lidocaine. It was observed that all three drugs prolonged the refractory period. The Tu values increased following each of the drugs, and mostly after quinidine, while the Tl curve was less affected by quinidine. It is suggested that the exit block thus produced is the principal mechanism whereby quinidine depresses atrial disrhythmias.     

Clinical and therapeutic aspects of sinusitis in children with bronchial asthma

Eighty children between 4 and 14 years of age suffering from bronchial asthma were investigated. Fifty-five of them showed clinical and radiological findings of sinusitis. Of these, 13 patients with purulent postnasal drip were treated with ampicillin, phenylephrine and triprolidine (therapy A) and for the other 42 ampicillin was replaced by beclomethasone (therapy B). Thirtyfour of 55 children showed improvement in sinus X-rays; 20 children had a considerable decrease in the severity of asthma and many symptoms cleared up after the therapy for sinusitis (P < 0.001). In conclusion, owing to the high prevalence of sinusitis in children with bronchial asthma, all asthmatic children should be investigated to check for a sinus disease.     

Depression of blast transformation of peripheral leukocytes by plasma from pregnant women.

The blast transformation of peripheral leukocytes from pregnant and nonpregnant women has been studied at different time intervals with graded concentrations of phytohemagglutinin. The transformation is markedly depressed during pregnancy. Leukocytes from nonpregnant women and men show diminished transformation when cultured in a medium containing plasma from pregnant women.     

Middle-sized ninhydrin-positive molecules in uraemic patients treated by repeated haemodialysis. I. Preliminary characteristics

In 11 patients suffering from chronic terminal renal insufficiency and therefore treated with repeated haemodialysis, ninhydrin-positive compounds of molecular weight 1500–5000 were investigated in plasma before and after haemodialysis.The fractions of middle-sized molecules were isolated by filtration on Sephadex G-25 fine followed by dialysis.In some patients analogous fractions were examined in the dialysate. A pre-dialysis raised level of this group of middle-sized molecules in the plasma and a subsequent fall in this level by about 50% after dialysis were confirmed.By means of thin-layer electrophoresis on Sephadex G-25 fine gel the presence of 7–8 bands was shown: out of these some appeared in patients in a much more intensive form, these being found in much higher concentration in the dialysate.Some differences were found also between the behaviour of these compounds originating from patients and healthy persons during separation of these substances by the finger-printing method.