Effect of foreign innervation on the androgen-sensitive levator ani muscle of the rat

Summary Cross-union of the tibial with the pudendal nerve innervating the androgen-sensitive levator ani (LA) muscle of male rats, results in reversal of the histochemical muscle fibre pattern concerning myofibrillar ATPase, succinate dehydrogenase and phosphorylase enzyme activities. The homogeneous muscle fibre pattern of the LA muscle is changed to a mosaic pattern of muscles normally innervated by the tibial nerve. The success of the hetero-reinnervation is shown by practically full recovery of muscle weight and of isometric twitch-contraction properties of the LA muscle. Castration of 2-months duration, i. e. lack of the male sex hormone, leads to marked atrophy but no change in histochemical muscle fibre pattern. Hetero-reinnervation of the LA muscle results in change of histochemical enzyme pattern even if the cross-union of nerves is performed after long periods of castration leading to very marked decrease of muscle fibre size. However, testosterone application alone after castration increases markedly muscle fibre size but does not lead to reversal of muscle fibre pattern. The myotropic hormonal influence on the target (LA) muscle is therefore primarily of myogenic origin and specificity of hormonal action is maintained even with a foreign nerve innervating the muscle. The experiments, thus, provide evidence for the differentiation of specific neural influences affecting muscle fibre pattern and hormonal influences in respect to the myotropic action of the sex hormone on the androgen-sensitive LA muscle.     

Exploratory studies of some drug charge transfer interactions

Conductivity and capacitance titrations yield minima for the chlorpromazine hydrochloride-heparin interaction, confirming clinical suspicions of its occurrence. The effective dosage of heparin thus is reduced if administered in conjunction with chlorpromazine. The interaction is interpreted as charge transfer complex formation, occurring as an (electrode) surface reaction. It is suggested that the charge transfer complexing capability of heparin preparations, as evidenced by conductance and/or capacitance changes, evaluated against a well defined donor such as chlorpromazine hydrochloride, may be adapted as a more precise method of measuring heparin activity than coagulation time determinations. Phenytoin and chlorpromazine likewise yield conductance and capacitance minima; voltammetry indicates new peaks at +250mV and −300mV vers.SCE supporting the suggestions that an uncharged 1∶1 complex is being formed, again in a type of surface reaction. Phenytoin and lignocain form a precipitate at 0.002 equimolar; in conductance and capacitance titrations phenytoin behaves as a weak electron donor against iodine though as a weak acceptor against lignocain. Lignocain and chlorpromazine conductance and capacitance titrations using gold electrodes fail to show any evidence for their previously reported interaction on Pt/Pt electrodes. Voltammetry on Pt/Pt electrodes indicates 2 new peaks at zero and at −750mV vers.SCE. It is thought that these two compounds interact only on catalytically highly active surfaces, where they form a weak surface charge transfer complex. Adrenalin, in conductance and capacitance titrations, behaves amphoteric, i.e. as an electron acceptor against the strong donor chlorpromazine and as a donor against the strong acceptor tetramethyl-p-phenylenediamine. Voltammograms of the above listed interactions are interpreted as of the ECE type exhibiting mainly irreversible behaviour.     

Accumulation of organelles at the ends of interrupted axons

Summary Proximal and distal stumps of the sciatic nerve of rats were examined with the light and electron microscope in the course of 48 hours following nerve crush. On both sides of the lesion organelles accumulate in axons beyond regions disorganized by injury. A stretch of clear axoplasm filled with fine granules usually separates the cone of accumulating particles from the damaged part of the fibre. From two hours onwards closely packed vesicles, tubules, mitochondria and other organelles form dense pellets which fill up the whole lumen of the fibre. Further away from the fibre tip organelles are stranded at the circumference only, whereas the central core is occupied by neurofilaments. In a number of fibres no pellets are observed and only a moderately increased network of axoplasmic reticulum is seen at the fibre ends.Measurements on isolated fibres have shown that the length of the pellet increases with time on both sides of the lesion up to 18 hours after crush; thereafter the elongation is arrested in the distal stump, while in the proximal stump it continues further at a slower rate.The authors wish to acknowledge gratefully the technical assistance of Mrs. M. Sobotková, Mr. M. Doubek, Mrs. J. Waryszewska and Mrs. B. Lwowska.     

Replacement of the essential penicillin-binding protein 5 by high-molecular mass PBPs may explain vancomycin-β-lactam synergy in low-level vancomycin-resistant Enterococcus faecium D366

The mechanism of synergy between vancomycin and penicillin, as well as other beta-lactam antibiotics, was examined in a penicillin-resistant E. faecium (D366) expressing an inducible low-level resistance to vancomycin. It was demonstrated that penicillin per se was not able to reduce the inducible expression of the 39.5-kDa protein (VANB) or the carboxypeptidase activity which are involved in the mechanism of vancomycin resistance of this strain. Assays of competition between 3H-benzylpenicillin and diverse beta-lactam antibiotics suggested as the most likely explanation of the synergy that, once vancomycin resistance has been induced, the high-molecular mass penicillin-binding proteins (PBPs), and possibly PBP1 in particular, which have a high affinity for beta-lactam antibiotics, take over the role of the low-affinity PBP5 which is, in the non-induced strain, responsible for beta-lactam resistance.     

Estrogen replacement therapy (ERT) in high-risk cancer patients.

Menopausal estrogens are now being prescribed not only for symptom relief, but also to prevent the long-term sequelae of estrogen deficiency, namely osteoporosis and atherosclerotic disease. The well-established association between endometrial cancer and estrogen replacement therapy (ERT) has become less of a clinical concern due to the recognition of the protective effect of progestogens in this setting. A small literature has emerged suggesting that extending ERT to the woman with a history of endometrial carcinoma imposes no increased risk of recurrence and may improve survival. Candidates for ERT should be women with a better prognostic profile with reference to their cancer. The relationship between ERT and breast cancer remains a topic of intense debate and investigation. Overall, the current literature finds no significant increase in risk among healthy women without a family history of breast cancer. There are no guidelines with reference to the woman with a history of breast cancer and the use of ERT. The most prudent approach with this population is to consider alternative treatments until more is known.