The use of liposomes in the topical application of steroids.

The effect of topical application of the androgen 5 alpha-dihydrotestosterone (DHT), both encapsulated in liposomes and solved in acetone, has been evaluated using the female hamster flank organ as a model system. Systemic absorption of DHT was significant from the acetone solution, but negligible from the liposome system. The topical biological effect is, however, proportionally diminished when the liposome system is used. Under the experimental conditions used, the lited using the female hamster flank organ as a model system. Systemic absorption of DHT was significant from the acetone solution, but negligible from the liposome system. The topical biological effect is, however, proportionally diminished when the liposome system is used. Under the experimental conditions used, the liposome system had no advantages over application in acetone in this model.

[Local anesthesia after percutaneous application. II]. / Lokalansthesie nach percutaner Aufnahme. II. Mitteilung

Cyclohexane and hexadecane have been found to accelerate the penetration of local anesthetics (lidocaine, fomocaine, procaine) through the intact skin of guinea-pigs. Dissolved in cyclohexane, the potency of lidocaine is twice that of fomocaine, the latter being more active than procaine. When dissolved in hexadecane, the activity of the local anesthetics in markedly reduced. In combination with 2-butanone, (30% w/w), a solvent without any apparent effect on the permeability of skin, enhanced anesthetic effects are noted. The anesthetic bases, dissolved in dimethyl sulfoxide, produce a much deeper and longer local anesthetic effect than the solutions of their salts.

[Local anesthesia after percutaneous administration. I]. / Lokalanästhesie nach percutaner Aufnahme. I. Mitteilung

Local anesthesia of the intact skin is difficult because of the skin barrier to epicutaneous penetration. Using solutions of local anesthetics in organic agents, which have the ability of penetrating the skin without causing irreversible damage and enhancing the percutaneous absorption of all materials dissolved therein, topical anesthesia seems to be attainable. A satisfactory method for determining pain threshold in uninjured skin of animals has been set up. Measurments of the pricking pain threshold have been made by exposing the skin of guinea-pigs to defined mechanical and electrical stimuli. A nociceptive muscle reflex (twitch) has been taken as the index of pain sensation. The suppression of this twitch has been used as an indicator of anesthetic potency. Two methods have been applied with varying parameters: stimulation at a fixed intensity until the pain threshold was reached (duration of anesthetic effect) and stimulation with increasing stimulus strenght until the cutaneous reflex was elicited (intensity or "depth" of anesthesia). The local anesthetic effects of lidocaine, fomocaine and procaine bases were studied, after dissolving them in dimethyl sulfoxide (DMSO), a wellknown carrier for transmembranal application. The duration of local anesthesia measured by electrical stimuli was longer than that obtained with mechanical ones. Differences are discussed. All results indicate that fomocaine (5%) has a greater local anesthetic potency than procaine (5%) but both are less active than lidocaine (5%). No effect could be seen after application of DMSO alone.

[Action of fomocaine on heart and circulation (author's transl)]. / Herz-Kreislaufwirkungen des Fomocains

Fomocaine shows antiarrhythmic properties. It prolongs the periods of the ECG (anaesthetized cats) and the functional refractory period (left atria of guinea-pigs, electrically driven). Effects on these parameters are qualitatively the same as with quinidine. Quantitatively fomocaine prolongs the functional refractory period in the same, the PQ-interval to a greater extent than does quinidine. In contrast quinidine has a greater effect on QRS- and QT-interval. Up to higher doses fomocaine's efficacy on contractility (dp/dtmax) and blood pressure is opposite to quinidine because they are increased by fomocaine and decreased by quinidine. The lack of toxic ECG-signs prior to lethal dosis makes fomocaine dangerous in overdosage.

Absence of the sequence G-T-psi-C-G(A)- in several eukaryotic cytoplasmic initiator transfer RNAs.

The nucleotide sequence G-T-Psi-C-G(A)- has previously been found in every tRNA of known sequence that is active in protein biosynthesis. An exception to this generalization is the recently sequenced initiator tRNA from yeast cytoplasm. It is now reported that cytoplasmic initiator tRNAs from wheat germ, rabbit liver, and sheep mammary gland also lack the G-T-Psi-C-G(A)- sequence. Thus: (i) nucleoside composition analyses show the absence of T in all these tRNAs; (ii) analyses of oligonucleotide fragments produced by T1 ribonuclease show the absence not only of the T-Psi-C-G(A)- sequence, but also of U-Psi-C-G(A)- or U-U-C-G(A)- sequences in such digests. The absence of G-T-Psi-C-G(A)- in the eukaryotic cytoplasmic initator tRNAs is, therefore, not simply due to lack of enzymatic modification of U to T.