In vitro metabolism of 1-phenyl-2-(n-propylamino) propane (N-propylamphetamine) by rat liver homogenates.

In vitro incubation of (+/-)-N-(n-propyl)amphetamine (NPA) with the 12000 g supernatant fraction of rat liver hmogenate resulted in the formation of two N-oxygenated products identified as N-hydroxy-1-phenyl-2(n-propylamino)propane and N-[(1-methyl-2-phenyl) ethyl]-1-propanamine N-oxide by g.l.c., g.l.c.-m.s. and t.l.c. Amphetamine, phenylacetone,...     

The in vitro metabolism of mephentermine

The metabolism of mephentermine (Ie) to phentermine (Ia), N-hydroxyphentermine (Ib) and N-hydroxymephentermine (If) was investigated using hepatic microsomal preparations from various species. Liver microsomes from rabbit were the best homogenate fractions to metabolise Ie. The effect of incubation times, various substrate concentrations, addition of selective inhibitors and activators and species differences suggested that the dealkylation of Ie to Ia involved a separate metabolic route than the N-oxidation of Ie to Ib and If and that both hydroxylamino compounds Ib and If resulted from metabolic oxidation at the nitrogen atom of Ie. A mechanism explaining the separate formation of Ib and If through a common intermediate resulting from N-oxidation of Ie is proposed. The synthesis and the properties of N-methyl-(α,α-dimethyl-β-phenethyl)nitrone (Ig) are reported.     

Auditory stimulation alters the pattern of 2-deoxyglucose uptake in the inner ear

The 2-deoxy-d-glucose (2-DG) autoradiographic technique was adapted for application to the inner ear. The uptake of [¹⁴C]2-DG during silence was compared with that observed during exposure to wide band noise (WBN) or pure tones at an intensity level of 85 dB SPL. In silence, the highest levels of 2-DG uptake were observed in the spiral ligament, spiral prominence and stria vascularis, with approximately equal levels of uptake in each structure. The high levels of 2-DG uptake observed in the ligament and prominence are suprising, and suggest a more active role for these structures in cochlear function than has previously been suspected. Levels of uptake in the organ of Corti, spiral ganglion and VIIIth nerve were much lower, although well above background. During exposure to WBN, 2-DG uptake increased markedly in the VIIIth nerve, and spiral ganglion throughout the cochlea, and in the organ of Corti in the lower basal turn. 2-DG uptake did not change significantly in the spiral ligament or stria vascularis. During pure tone exposure, increased 2-DG uptake was noted in localized regions of the VIIIth nerve and spiral ganglion.     

Radiolocalization of human prostate tumor in a mouse subrenal capsule model by monoclonal antibody TURP-27

The subrenal capsule assay was used to determine if 125I-labeled anti-prostate monoclonal antibody TURP-27 could target human prostate tumor fragments implanted under the renal capsule of normal immunocompetent C57 BL/6 mice. Maximal binding and optimal tumor to non-tumor tissue ratios occurred within 24-48 hours postadministration of 125I-TURP-27. No significant localization was observed in mice bearing TURP-27 antigen-negative human colon tumor tissue implants or with an isotype-matched control monoclonal antibody. These preclinical data suggest that TURP-27 may have clinical application for imaging metastatic prostate tumors and further application in immunoconjugate and/or radiotherapy of prostate cancer.     

Management of the patient presenting as an emergency with hypergastrinemia

The emergency management of patients presenting with the Zollinger-Ellison syndrome (ZES) consists of medical measures to control acid-pepsin hypersecretion; emergency surgery should be confined to urgent complications of ulceration or tumor growth and spread. Operation for ulcer complications should be restricted to conventional surgical procedures with biopsy of suspicious lesions. Emergency total gastrectomy or resection of pancreas and duodenum is contraindicated. Once the emergency has been controlled, the diagnosis of ZES can be confirmed by basal serum gastrin measurements and the secretin provocation test. Other endocrine adenopathies should be excluded. An attempt is then made to localize the tumor(s) and any metastases. With techniques such as selective portal venous sampling, it may be possible to define the small group of patients with lesions amenable to surgical cure. For the remainder, continued control of gastric secretion can be achieved by H₂-receptor antagonists, but elective total gastrectomy or the combination of vagotomy with pharmacological blockade offer valid alternatives in long-term management. Effective medical or surgical control of the peptic ulcer diathesis means that tumor progression is now the major cause of death in ZES patients, and advances in the fields of chemotherapy and radiotherapy are urgently required to control this aspect of the disease.

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Résumé Le traitement des malades atteints de Syndrome de Zollinger-Ellison consiste dans l'emploi d'agents thérapeutiques susceptibles de contrôler l'hypersecrétion acido-peptique gastrique. Le traitement chirurgical est à réserver aux complications de l'ulcère et aux tumeurs à développement et à extension rapide. Les complications ulcéreuses doivent être traitées par les méthodes conventionnelles cependant que la biopsie des lésions doit être systématique lors de l'intervention.La gastrectomie totale d'urgence ou la duodénopancréatectomie sont contre-indiquées.Le diagnostic de Zollinger Ellison doit de toute façon être confirmé par le dosage de la gastrinémie et par le test à la secrétine. Les tumeurs endocriniennes éventuellement associées doivent être recherchées systématiquement. Il convient également de localiser la tumeur et ses éventuelles métastases à l'aide du prélèvement étage du sang portai de façon à définir les lésions susceptibles d'être guéries chirurgicalement. Le contrôle définitif de l'hypersécrétion acido-peptique peut être obtenu par l'administration permanente des antagonistes H2-recepteurs encore qua le gastrectomie totale élective ou que l'association de la vagotomie hypersélective et des antagonistes puisse être envisagée.Le contrôle efficace de la diathèse ulcéreuse peptique par les moyens médicaux ou les interventions chirurgicales décrites permet d'affirmer que la cause principale de la mort des malades atteints du syndrome de Zollinger Ellison reléve de la progression inexorable du processus tumoral. Les progrés de la chimiothérapie et de la radiothérapie devraient apporter une solution á ce probléme dans un proche avenir.

     

Pharmacological manipulation of ultrasound induced defence behaviour in the rat

Rats exposed to aversive stimuli display species specific defence behaviour as part of their natural survival strategy. One component of this behaviour is the production of ultrasonic calls in the 20 to 27-kHz range, which are thought to serve a communicative role. The present study has examined the behavioural effects of exposing, rats to artificially generated ultrasound and the ability of three distinct pharmacological agents to modify this response. Single tone 20 kHz ultrasound exposure for 1 min produced intensity-related locomotor behaviour, characteristic of defence behaviour, which could be measured using a computer tracking system. This was significantly reduced by peripheral pretreatment with the benzodiazepine, diazepam (0.3 and 3.0 mg/kg IP). Pretreatment with the 5-HT agonist 1-(3-chlorophenyl) piperazine (mCPP) (0.5–2.0 mg/kg IP) produced a dose-related reduction in the ultrasound-induced response. Theα ₂ adrenoceptor antagonist, yohimbine (0.5–5.0 mg/kg IP), caused an increase in the response at the lower doses (2.0 and 5.0 mg/kg). The present findings suggest that defence behaviour in the rat can be artificially produced by 20 kHz ultrasound; this is sensitive to pharmacological manipulation and may offer a novel animal model of aversive behaviours that are associated with human panic.     

Routine detection and identification in urine of stimulants and other drugs, some of which may be used to modify performance in sport

A general procedure for the analysis in urine of basic drugs (and their metabolites), some of which may be misused as stimulants in sport, has been developed. The techniques used include gas-liquid and thin-layer chromatography and linked gas-liquid chromatography—mass spectroscopy. It is recommended that international control of drug-taking in sport be based primarily upon urine analysis by gas-liquid chromatography systems and also derivative formation followed by gas-liquid chromatography. The principles outlined in the procedure can be applied in a much wider forensic context.