Tissue-type plasminogen activator (tPA) is a major protease of the central nervous system. Most studies to date have used in situ-or gel-based zymographic assays to monitor in vivo changes in neural tPA activity. In this study, we demonstrate that the amidolytic assay can be adapted to accurately detect changes in net tPA activity in mouse brain tissues. Using the amidolytic assay, we examined differences in net tPA activity in the cerebral cortex, sub-cortical structures and cerebellum in wildtype (WT) and tPA À/À mice, and in transgenic mice selectively overexpressing tPA in neurons. In addition, we assessed changes in endogenous net tPA activity in WT mice following morphine administration, epileptic seizures, traumatic brain injury and ischaemic stroke-neurological settings in which tPA has a known functional role. Under these conditions, acute and compartment-specific regulation of tPA activity was observed. tPA also participates in various forms of chronic neurodegeneration. Accordingly, we assessed tPA activity levels in mouse models of Alzheimer's disease (AD) and spinocerebellar ataxia type-1 (SCA1). Decreased tPA activity was detected in the cortex and subcortex of AD mice, whereas increased tPA activity was found in the cerebellum of SCA1 mice. These findings extend the existing hypotheses that low tPA activity promotes AD, whereas increased tPA activity contributes to cerebellar degeneration. Collectively, our results exemplify the utility of the amidolytic assay and emphasise tPA as a complex mediator of brain function and dysfunction. On the basis of this evidence, we propose that alterations in tPA activity levels could be used as a biomarker for perturbations in brain homeostasis.

These data suggest that striatal CREB1 regulates sensitivity to psychostimulants and that CREM acting via CBP is able to partially compensate in the absence of CREB1 signalling.

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an 123 I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than nonfamilial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient. 2006; 43: 156-160 Case report Ann Clin BiochemA 61-year-old gentleman with a long-standing history of hypertension presented with syncopal episodes to the casualty department in December 1999. The initial diagnosis was thought to be recurrent transient ischaemic attacks in association with bilateral carotid bruits. Following a neck ultrasound scan, carotid angiography revealed bilateral large carotid body tumours encircling each common carotid artery with splaying of the internal and external carotid arteries; a characteristic benign tumour blush was seen (Figure1). The masses in the neck (Figure 2) were ¢rst commented on by an Ear, Nose and Throat (ENT) surgeon when the patient underwent a tonsillectomy 20 years ago to alleviate sleep apnoea. Due to recurrence of this problem, a trachaeostomy was carried out, and due to episodes of collapse ascribed to asystole as a result of carotid sinus baroreceptor hypersensitivity secondary to his carotid body tumours, a permanent pacemaker was inserted. 1 Although these interventions brought about signi¢-cant improvement in the clinical condition of the patient, his blood pressure and heart rate showed large variations on 24 h monitoring (70/41--219/102 mmHg, 14--98 bpm). The patient is not currently receiving any medical management for his labile hypertension.Baseline laboratory investigations were normal (urea. As his blood pressure remained labile, urinary catecholamines were requested. Dopamine excretion was signi¢cantly elevated at 20,679 nmol/24 h (upper limit of reference range 4440 nmol/24 h); excretion of the dopamine metabolite homovanillic acid (HVA) was also increased at 13.1mmol/mol creatinine (upper limit of reference range 5 mmol/mol creatinine). Excretion of noradrenaline, adrenaline, normetadrenalin...