Kai Setälä

Pilocarpine in Salivary Gland and Thyroid Photoscanning

Experimental studies in mice have revealed that high quantities of incorporated radioisotopes (131I, 85Sr, 89Sr, 90Sr) can be removed through the salivary and the intestinal glands by activating the extrarenal mineral/fluid-balance-regulatory system through administration of a parasympathicomimeticum, Pilocarpine nitrate (Setala 1962, 1965; Setala and Kuikka, 1963; Setala, Kuikka and Nyyssonen 1963; Setala, Lindroos and Kuikka, 1964). The same technique is directly applicable to human subjects, and it can be used with a number of radioisotopes in diagnosis and therapy of various diseases of the salivary glands and the thyroid. So far 30 photoscannings have been performed. The purpose of the present report is to outline the technique and show its suitability by demonstrating a case with the Gougerot-Houwer- Sjogren syndrome.

The essentially different pharmacodynamic response to colchicine of benign and of malignant epidermal hyperplasia in skin-tumor-resistant RA mice

*) Wilson Laboratories, Chicago 9, Illinois. 1) RUHENSTROTH-BAuER, G., G. BRITTINGER, ]~. GRANZER U. G. NASS: Dtsch. meal. Wsehr. 85, 803 (1960). 2) GRANZER, E.: Hoppe-Seylers Z. physiol. Chem. 332, 88 (1963). 8) MAKITA, A., u. T. YAMAKAWA: J. Biochem. (Tokyo) 51, 124 (t962). 4) SVSNNERHOLM, E., U. L. SVENNERHOLM: Nature 19s, 688 (1963); Biochim. et biophys. Acta 70, 432 (1963).

Zur Bestimmung der Fettsäurekomponente einiger nichtionisierbaren oberflächenaktiven Tumorauslösersubstanzen

A study was made of the fatty acid components of a number of commercial non-ionic surface active tumour promoting agents (sorbitan fatty acid esters, and polyoxyethylene fatty acid esters). According to the animal experiments carried out in this laboratory, there is season to believe that — in addition to given physico-chemical properties required of an effective surface active tumour promoter of the above mentioned type — the fatty acid coponent would be of significance. For identification of the fatty acids a technique was developed which was based on the capacity of lipase to free fatty acids by splitting the ester bonds; as a result of this the lipophilic-hydrophilic materials became decomposed. The liberated fatty acids were analyzed paperchromatographically, and the spots examined under ultraviolet light. The results were compared with values obtained with corresponding pure fatty acids. It was demonstrated that the non-ionic surface active agents investigated contained only the one fatty acid which it has been declared to do. The results are discussed, with special emphasis on the fact that — although the lipase action in the present work was employed for analytic purpose only — this phenomenon has an important aspect: through decomposing by the lipase, non-ionic lipophilic-hydrophilic tumour promoters („co-carcinogenic lipids”) lose their capacity, i. e., it is possible to influence by biological means the effectiveness of a tumour promoter.

A new suggestion for the design of rational anticancer therapy: Experimental studies in mice

In attempts to develop a rational anticancer strategy the same homologous tissue in 3 conditions were used side by side as targets: normal epidermis of the mouse back. Tween 60R-provoked benign epidermal hyperplasia, and carcinogen-provoked malignant condition. In contrast to the highest tolerated doses of the cytostatics conventionally used, the dose was stepwise decreased towards the subthreshold level. Then the smallest dose that caused the slightest detectable injury to the malignant cells was employed. The results show that the dose of the cytostatics (colchicine, and vinblastine sulfate) can be reduced to 1/12 if the drug is linked to dimethyl-sulfoxide (DMSO), a compound with unique hydrating and oxido-reducing properties. The cytostatic-DMSO complex acts selectively, sparing the viability of the normal and hyperplastic cells, but at the same time increasing the vulnerability of the malignant cells. The specific target for cytostatic-DMSO complex is the 3-dimensional cytoskeleton (the differentiation organelle) which is deranged in malignant cells. The measure causes a morbid swelling (20-fold, or more) of the cytoplasm which leads to collapse of the cytoskeleton, so that the marginal quantities of the cytostatics can exert their effects in the highly re-hydrated water matrix of the malignant cells. It is, moreover, probable that the doses of the cytostatic in DMSO could be further reduced to 1/100, or even to 1/1,000. The polarization microscopic technique reveals events down to the (sub)-molecular level. The cytological material comprises 930,000 karyokinetic assemblies and 14,522,600 corresponding nucleated non-dividing cells in various cutaneous conditions of 1,860 mice. The conclusions were drawn only when the differences between corresponding parameter pairs were statistically highly significant (P less than 0.001).

Intravenous meningorachidian phlebography

A u c h ande re MSgl ichkei ten s ind zu priifen. Die G l yc inwi rkung k a n n viel le icbt du rch B i ldung von Guanid iness igs / iure bzw. v o n K r e a t i n p h o s p h a t z u s t a n d e k o m m e n oder a u c h d u t c h eille Wiede rhe r s t e l l ung der P o r p h y r i n k e r n e , wobei Olycin, wie be im P u r i n k e r n m i t der ganzen 3/folekel u n d m i t einer In tegra t io l l s geschwind igke i t y o n unge f~hr 2 4 4 8 Std e in t r i t t [7~. Oerade diese Zeit spiel t bei der S c h u t z w i r k u n g des Glycins eille besondere Rolle (s. Tabelle) .

Über das Verhalten der nichtionisierbaren oberflächenaktiven tumorauslösenden Substanzen zu der Cytochromoxydase

A study was made of the behaviour of a number of non-ionic surface active tumour promoting agents (sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters) towards cytochrome oxydase, employing the Warburg respirometer. Derivatives of the same compounds, as well as one anionic and one cationic detergent, and croton oil were investigated too. Indications were given why the present study was carried out. It was demonstrated that potent non-ionic surface active tumour promoters do not inhibit cytochrome oxydase in vitro. On the other hand, however, certain derivatives of the agents investigated, when used anone, were capable of more or less inactivating the enzyme. The following points are discussed: the investigation technique, the significance of the observations on the behaviour of the compounds examined, and the possible nature of the intercation between synthetic detergents and proteins. It is concluded, that merely the formation of micellar aggregates (=solubilization), which is characteristic of surface active agents in general, does not per se cause inhibition of the enzyme and, further, that in cases in which inhibition occurs (ionic detergents) it is due to other properties of the surface active agents.A study was made of the behaviour of a number of non-ionic surface active tumour promoting agents (sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters) towards cytochrome oxydase, employing the Warburg respirometer. Derivatives of the same compounds, as well as one anionic and one cationic detergent, and croton oil were investigated too.

Angiographic Recognition of Diseases Involving the Spine

Early and accurate diagnosis of disease—both of malignant and of non-malignant character—involving the bones and blood vessels of the skull, spine and pelvis is of the utmost importance. However, the angiographic visualisation of various pathological conditions within the spine is particularly difficult and on occasion impossible. This is primarily due to the peculiar anatomical and physiological nature of the meningo-rachnoidian venous system (MRVS) (Batson, 1940; Borak, 1942; Bachman and Sproul, 1955; Abrams, 1961). We have developed a new technique for the introduction of a radio-opaque medium intravenously directly into the MRVS through the intercostal veins (Setala, Tarkiainen and Nyyssonen, 1966; Tarkiainen, 1966). The purpose of this paper is to demonstrate the accuracy of the technique in the light of one case randomly selected from our files of about 250 examinations. All surgical and radiographic measures were performed by the authors.