Tumorigenesis of mammary gland by 7,12-dimethylbenz(a)anthracene during pregnancy: relationship with DNA synthesis

The relationship between mammary cell proliferation during pregnancy and susceptibility to 7,12-dimethylbenz(a)anthracene (DMBA) was examined. DMBA was administered intravenously to Sprague-Dawley rats on the 5th, 10th or 15th day of pregnancy. [3H]thymidine labelling index (LI) of the mammary cells at the time of treatment with the carcinogen was determined and found to be higher in the pregnant rats than in age-matched virgin controls. In spite of the high proliferative index of the mammary cells, significant inhibition of tumorigenesis occurred in the pregnancy rats allowed to complete pregnancy and parturition following treatment with DMBA. However, when pregnancy was terminated by cesarian section shortly after treatment with DMBA, there was a significantly higher tumor incidence as compared to the "full-term" rats. It was observed that the earlier the pregnancy was terminated, the greater was the incidence of mammary tumors. This would indicate that the inhibitory effect of pregnancy is related to changes occurring during the later half of gestation. The differentiation of mammary cells for milk synthesis as pregnancy progresses is postulated to be a major reason for the observed refractoriness of the mammary cells to DMBA at that time.     

Scintigraphic findings in peroneal tendonitis: a case report

A case report of radionuclide bone scan findings in a patient with peroneus brevis tendonitis is presented. Peroneal tendonopathy is a common cause of lateral ankle pain. Although magnetic resonance imaging (MRI) findings have been described in the literature, we know of no other detailed report of three-phase bone scan findings, which we believe can provide an alternate means to diagnose this condition. The positive findings consist of a curvilinear band of increased activity that corresponded to the anatomic position of the peroneus brevis tendon and was detected only on the first two phases of the study.     

In vitro metabolism of etoposide (VP-16-213) by liver microsomes and irreversible binding of reactive intermediates to microsomal proteins

We have studied the metabolism of VP-16-213 (etoposide, VP-16), an antitumor agent, by mouse liver microsomes to reactive intermediates and the subsequent covalent binding to microsomal proteins. This metabolism was shown to involve the O-demethylation of VP-16 and resulted in the formation of a 3',4'-dihydroxy derivative (DHVP-16) which was identified by both HPLC and mass spectrometry. The formation of DHVP-16 was cytochrome P-450-mediated as indicated by its dependence on NADPH, its increased production following treatment of mice with phenobarbital, and its marked inhibition by SKF-525A and piperonyl butoxide. Furthermore, DHVP-16 formation required oxygen. Microsomal incubation of VP-16 resulted in an irreversible binding of the drug to the proteins, which was also shown to be cytochrome P-450 dependent. The covalent binding of the VP-16 metabolite(s) was inhibited by DHVP-16 in a dose-dependent fashion, suggesting that the reactive intermediates that bound to proteins were derived from DHVP-16. Electron spin resonance studies indicated that the same semiquinone radical was formed during enzymatic (oxidation or reduction) metabolism of DHVP-16 and the o-quinone derivative of VP-16 (VP-16-Q). VP-16-Q and its semiquinone radical are suggested to be the bioalkylating species.     

Applications of Botulinum toxin in urogynaecology

Botulinum toxin (BTX) is a neurotoxin produced by bacterium clostridium. It is the most poisonous naturally occurring substance known to mankind. The neurotoxin binds to the peripheral cholinergic terminals and inhibits acetylcholine release at that junction leading to flaccid paralysis. This process appears to offer an attractive therapeutic option, filling the void between anticholinergics and surgery in cases of neurogenic and idiopathic detrusor overactivity, detrusor sphincter dyssynergia (DSD), interstitial cystitis and pelvic pain. This article reviews the application of Botulinum toxin A in these conditions.