Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure

(+/?)3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an abused psychostimulant that produces strong monoaminergic stimulation and whole‐body hyperthermia. MDMA‐induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP‐3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA‐induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature‐sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethyl‐1,4,7,10‐tetraacetate (DOTMA^4?)). The MDMA‐induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA‐induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA‐induced warming across brain regions. MDMA‐induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Mental retardation and psychiatric illness.

Although traditional diagnostic criteria are accepted for use with mentally retarded persons, diagnosis of psychiatric disorders in this population is often complicated by clinicians' ignoring or underestimating such disorders and by patients' communication problems. The revision of DSM-III and changes in policies of third-party payers have sensitized clinicians to the presence of psychopathology among mentally retarded persons. The authors discuss the relationship between mental illness and mental retardation and review recent research on the diagnosis of specific psychiatric disorders in these patients. Some problems, such as behavioral disruptiveness, psychoses, and phobias, are more prevalent among mentally retarded persons than among other populations, whereas other problems, such as alcoholism and suicide, may be less common.     

Edematous syndromes caused by capillary hyperpermeability. Diffuse angioedema

Edema due to increased capillary permeability (ICP) may be diffuse or localized. Local edemas (Quincke edema, angioneurotic edema) are most often allergic or very rarely due to a defect in C1-inhibitor. Generalized edemas due to ICP share the following clinical features: Fluid retention (subcutaneous edema and diffused swelling) is predominant in lower limbs; it is worsened by orthostatism and warmth and alleviated by decubitus and cold, with important weight variations between morning and evening. It is associated with enhanced thirst, hypotension, oliguria, headaches and blood volume reduction; secondary hyperaldosteronism is the main mechanism. These troubles are due to ICP, associated with lymphatic drainage abnormalities; ICP is measured by the isotopic Landis Test. This abnormality is present in several diseases. Idiopathic orthostatic edema (IOE) is frequent and often unrecognized, occurring mainly in women, often associated with luteal insufficiency. Iatrogenic complications (diuretic and laxative abuses) are frequently superimposed. ICP may be corrected by vitamins P (rutin, anthocyanosides, diosmin, Ginkgo biloba extracts...) Cyclic shock due to ICP is rare. It is characterized by cyclic edema and shock with hypovolemia, hypoproteinemia; the mechanism of shock is a severe loss of fluid and protein from the vascular bed. It is often associated with monoclonal gammapathy and complement activation. In our personal case, the trouble in CP was present all along the disease with permanent edema and low blood pressure (especially in orthostatism). Vit "P" and Ginkgo biloba extracts were able to partially improve CP and the clinical troubles. However, in spite of this treatment a fatal shock occurred after ten years follow-up. Episodic angioedema associated with eosinophilia was first described by Gleich.(ABSTRACT TRUNCATED AT 250 WORDS)     

Obsessive-compulsive disorder in mentally retarded patients

Of 283 mildly to profoundly retarded patients, 10 (3.5%) presented with compulsive behavior that significantly interfered with their daily functioning. Compulsions occurred in the context of obvious cerebral dysfunction and in the absence of anxiety or "ego-dystonic" qualities. The interrater reliability of the differential diagnosis between compulsions, stereotypies, and other repetitive behaviors was good (kappa = .82). A severity rating scale for the compulsive behavior yielded total scores with good interrater reliability (intraclass correlation coefficient = .82). Single items that described observable behaviors had good reliability, while inner resistance and subjective distress were not reliably assessed and contributed little to the total score. The authors suggest that the DSM-III-R diagnosis of obsessive-compulsive disorder be considered in mentally retarded patients, despite the absence of recognizable ego dystonic characteristics. Emphasis should be on the behavioral, externally observable components of the disorder, rather than on inner conflicts and anxiety. Such a diagnostic approach may also benefit nonretarded compulsive patients.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.