Assessment of infarct size by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose: a new absolute threshold technique

Along with hibernating myocardium, infarct size is a critical term in the progression of left ventricular remodelling and congestive heart failure. Both infarcted and hibernating myocardium determine changes in remote non-ischaemic tissue. This study was designed to test the accuracy of a new technique to quantify infarct size using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG). Studies were carried out in (a) nine pigs with acute myocardial infarction (two sham-operated), produced by a 90-min occlusion of the circumflex coronary artery followed by a 4-h reperfusion, and (b) humans (six patients with ischaemic cardiomyopathy awaiting cardiac transplantation and five normal volunteers). In both animals and patients, myocardial FDG uptake was measured by PET during hyperinsulinaemic-euglycaemic clamp. Infarct size was quantified by an absolute threshold of tracer uptake obtained from the parametric (voxel-by-voxel) image of the metabolic rate of FDG. PET infarct size estimates were compared with independent ex vivo planimetric measurements of the explanted swine and patient hearts (at transplantation) after staining with triphenyltetrazolium chloride. There was good agreement between the planimetric and PET infarct size estimates both in pigs (n=9; r=0.96, v=0.94x+0.64, SEE=0.10, P<0.0001) and in humans (n=11; r=0.94, y=0.72x+2.93, SEE=0.09, P<0.0001). This study demonstrates the feasibility and accuracy of this PET method in estimating infarct size both in a model of reperfused acute myocardial infarction and in chronic ischaemic cardiomyopathy, although larger studies are needed to confirm these findings.     

GABAA and NMDA receptor density alterations and their behavioral correlates in the gestational methylazoxymethanol acetate model for schizophrenia

Hippocampal hyperactivity driven by GABAergic interneuron deficits and NMDA receptor hypofunction is associated with the hyperdopaminergic state often observed in schizophrenia. Furthermore, previous research in the methylazoxymethanol acetate (MAM) rat model has demonstrated that repeated peripubertal diazepam administration can prevent the emergence of adult hippocampal hyperactivity, dopamine-system hyperactivity, and associated psychosis-relevant behaviors. Here, we sought to characterize hippocampal GABA_A and NMDA receptors in MAM-treated rats and to elucidate the receptor mechanisms underlying the promising effects of peripubertal diazepam exposure. Quantitative receptor autoradiography was used to measure receptor density in the dorsal hippocampus CA1, ventral hippocampus CA1, and ventral subiculum. Specifically, [³H]-Ro15-4513 was used to quantify the density of α5GABA_A receptors (α5GABA_AR), [³H]-flumazenil to quantify α1-3;5GABA_AR, and [³H]-MK801 to quantify NMDA receptors. MAM rats exhibited anxiety and schizophrenia-relevant behaviors as measured by elevated plus maze and amphetamine-induced hyperlocomotion (AIH), although diazepam only partially rescued these behaviors. α5GABA_AR density was reduced in MAM-treated rats in all hippocampal sub-regions, and negatively correlated with AIH. Ventral hippocampus CA1 α5GABA_AR density was positively correlated with anxiety-like behavior. Dorsal hippocampus CA1 NMDA receptor density was increased in MAM-treated rats, and positively correlated with AIH. [³H]-flumazenil revealed no significant effects. Finally, we found no significant effect of diazepam treatment on receptor densities, potentially related to the only partial rescue of schizophrenia-relevant phenotypes. Overall, our findings provide first evidence of α5GABA_AR and NMDA receptor abnormalities in the MAM model, suggesting that more selective pharmacological agents may become a novel therapeutic mechanism in schizophrenia.Subject terms: Psychosis, Schizophrenia, Experimental models of disease, Schizophrenia, Psychosis     

The Social Science Blues

At the dawn of the new century, Robert Plomin was gloomy. As he recounts in Blueprint: How DNA Makes Us Who We Are, attempts to find the DNA responsible for the heritability of behavior failed. Month after month, journals would report new findings of specific genes for behavioral phenotypes, but they never replicated. One amazing genomic methodology after another was developed in biological genetics and applied to medicine, where it succeeded, and then to human behavior, where it failed. This was the moment of Plomin's despair. He had, with great intellectual courage, staked his reputation on the existence of actionable scientific knowledge of the DNA‐based genesis of twin‐based heritability. But Blueprint is hardly the product of a gloomy author. Quite the opposite: it is a declaration of victory of nature over nurture, a celebration of the vindication of Plomin as a scientist and of behavior genetics as a field of study. What happened between 2000 and 2019 to brighten Plomin's outlook so radically? Were the genes for schizophrenia and intelligence finally discovered? Are we at last on our way to understanding why, at a biological level, all differences in human behavior are substantially heritable? Alas, no. What happened is that Robert Plomin gave up on the search for individual genes that explain heritability and decided to be satisfied with much less.     

一个新型的双二萜生物碱

普格乌头(Aconitum pukeense W.T.Wang)分布于云南东北部和四川西南部,生长在海拔3400～3500米山地谷中竹林边或沟边。因其根部毒性很强,可用作箭毒,在云南巧家药山又称之为弩箭药。民间常将其泡制后用于治疗跌打损伤等症。该植物的化学成     

New compartmental model approach to dialysis

Compartmental models are used for solving the problem of the control of dialysis therapy. The inadequacy of the existing monocompartmental model is faced, first with a careful analysis of the physiology of the system, then with a method focused on the construction of a new multicompartmental model. Moreover, impedance techniques allow us to solve the problem of measuring the total body water for each patient.     

The philosophical and sociological context of mental health care legislation

This paper explores mental health legislation from a philosophical and sociological perspective. It is argued that mental health law exists primarily as a coercive social control instrument and that the maintenance of a separate legislative framework for the mentally ill is based upon dubious legal and philosophical grounds. The need for changes in mental health law has been accelerated by the move in Britain toward care in the community. One of the most important issues at the centre of the debate revolves around the concept of 'dangerousness' and mental disorder. The research into the extent to which the risk of violence can be predicted appears problematic from a reform perspective. Prediction is considered to be the overriding problem that leads to a violation of patients' civil rights, especially in relation to black and ethnic minority groups. Equity in law is necessary for the protection of patient's rights and particularly for the protection of those people who enter mental health care systems concerned with issues of control at the expense of care.     

The origins of insane asylums in England during the 19th century: a brief sociological review

This paper explores the origins of insane asylums in 19th century England by comparing the official 'received' medically dominated perspective with an alternative sociological perspective The major structural changes in provision are addressed as the focus for analysing the differing histories A brief review is presented of the responses to insane people prior to the national asylum programme following the 1845 Lunacy Act, and of the reform logic that underpinned asylum care The alternative sociological perspective presents the origins of psychiatric asylums as part of the social and economic changes occuring generally at that time As such the origins of insane asylums are presented as part of a state-guided 'sanitary'movement which included poor, criminal and insane people within its remit The effect of state-guided correction was the segregation of insane people from both the general population and other deviants who were formerly classed together Insane people are thus presented as a group of deviants who departed most radically from the 'rational individualist' qualities of self-control, predictability and responsibility required in the industrialized world of capital social relations that emerged during the last century     

In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease presenting with voluntary gaze difficulties, early falls, and Parkinsonism. Neuronal loss, associated with intracellular neurofibrillary tangles and activated microglia, is found targeting the basal ganglia, brainstem nuclei, and frontal cortex. [11C](R)-PK11195 PET is a marker of peripheral benzodiazepine binding sites (PBBS) expressed by activated microglia. We have used [11C](R)-PK11195 PET to demonstrate in vivo the degree and distribution of the glial response to the degenerative process in four patients with PSP. Compared to normal age-matched controls, the PSP patient group showed significantly increased mean [11C](R)-PK11195 binding in the basal ganglia, midbrain, the frontal lobe, and the cerebellum. Two of the patients were rescanned after 6 to 10 months and during that time the level of microglial activation remained stable. [11C](R)-PK11195 PET reveals a pattern of increased microglial activation in PSP patients involving cortical and subcortical regions that corresponds well with the known distribution of neuropathological changes. [11C](R)-PK11195 PET, therefore, may help in characterizing in vivo the underlying disease activity in PSP.