Behavioral and genetic evidence for a novel animal model of Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Subtype

Background  

According to DSM-IV there are three subtypes of Attention-Deficit/Hyperactivity Disorder, namely: ADHD predominantly inattentive type (ADHD-PI), ADHD predominantly Hyperactive-Impulsive Type (ADHD-HI), and ADHD combined type (ADHD-C). These subtypes may represent distinct neurobehavioral disorders of childhood onset with separate etiologies. The diagnosis of ADHD is behaviorally based; therefore, investigations into its possible etiologies should be based in behavior. Animal models of ADHD demonstrate construct validity when they accurately reproduce elements of the etiology, biochemistry, symptoms, and treatment of the disorder. Spontaneously hypertensive rats (SHR) fulfill many of the validation criteria and compare well with clinical cases of ADHD-C. The present study describes a novel rat model of the predominantly inattentive subtype (ADHD-PI).     

Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration

During cortical development, embryonic neurons migrate from germinal zones near the ventricle into the cortical plate, where they organize into layers. Mechanisms that direct neuronal migration may include molecules that act as chemoattractants. In rats, GABA, which localizes near the target destination for migrating cortical neurons, stimulates embryonic neuronal migration in vitro. In mice, glutamate is highly localized near the target destinations for migrating cortical neurons. Glutamate-induced migration of murine embryonic cortical cells was evaluated in cell dissociates and cortical slice cultures. In dissociates, the chemotropic effects of glutamate were 10-fold greater than the effects of GABA, demonstrating that for murine cortical cells, glutamate is a more potent chemoattractant than GABA. Thus, cortical chemoattractants appear to differ between species. Micromolar glutamate stimulated neuronal chemotaxis that was mimicked by microM NMDA but not by other ionotropic glutamate receptor agonists (AMPA, kainate, quisqualate). Responding cells were primarily derived from immature cortical regions [ventricular zone (vz)/subventricular zone (svz)]. Bromodeoxyuridine (BrdU) pulse labeling of cortical slices cultured in NMDA antagonists (microM MK801 or APV) revealed that antagonist exposure blocked the migration of BrdU-positive cells from the vz/svz into the cortical plate. PCR confirmed the presence of NMDA receptor expression in vz/svz cells, whereas electrophysiology and Ca2+ imaging demonstrated that vz/svz cells exhibited physiological responses to NMDA. These studies indicate that, in mice, glutamate may serve as a chemoattractant for neurons in the developing cortex, signaling cells to migrate into the cortical plate via NMDA receptor activation.     

来那度胺＋低剂量地塞米松治疗多发性骨髓瘤疗效佳毒性低

高剂量地塞米松为多发性骨髓瘤常用治疗方案。本研究比较了高、低剂量地塞米松分别联合来那度胺治疗多发性骨髓瘤的临床疗效及毒副作用。     

Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets

Platelets stimulated with thrombin release an inhibitor of plasminogen activator (PAI), which has been shown previously to be neutralized by activated protein C (APC). The requirements for optimal neutralization of PAI activity were investigated. The releasate of gel-filtered human platelets stimulated with thrombin served as a source of PAI. When 6 X 10(8) platelets/mL were incubated with thrombin (1 IU/mL), the releasate contained 18 to 26 ng/mL PAI as determined by incubation of the releasate with urokinase and measurement of residual urokinase activity on plasminogen (S2251). Preincubation of PAI with up to 4 micrograms/mL APC for two hours yielded less than 20% neutralization of PAI activity. In the presence of protein S, phospholipid, and Ca2+, neutralization of PAI activity was time-dependent with 50% neutralization occurring in two hours with 1 microgram/mL APC. The cofactor effects of protein S and phospholipid were concentration- dependent with half-maximal acceleration at approximately 3 micrograms/mL protein S and 10 micrograms/mL phospholipid when the experiments were performed at 1 microgram/mL APC. Diisopropylfluorophosphate-inactivated APC, gla-domainless APC, and thrombin-cleaved protein S had no effect on PAI activity, indicating requirement for preservation of the APC active site and of the Ca2+ binding ability of both APC and protein S. These results suggest coordinate binding of APC and protein S onto phospholipid membrane as a prerequisite for optimal expression of PAI neutralized by APC.     

Nutritional care and candidates for small bowel transplantation

Twenty two children were evaluated for small bowel transplantation between 1989 and 1994. Eight were unfit for transplantation and died within three months; a raised plasma bilirubin concentration (> 200 mumol/l) predicted death from liver failure within six months (p = 0.0001). The 11 children who were not managed by a multidisciplinary nutritional care team were less well nourished at referral, had more complications with intravenous feeding catheters, and greater early mortality while awaiting transplantation (p < 0.05). It is recommended that children with chronic intestinal failure be referred for assessment early, before liver dysfunction is established.     

New method for determining faecal fat excretion in infancy

Collecting complete, timed stool samples for the estimation of faecal fat from infants wearing nappies is difficult. A gravimetric method has been adapted by applying a chloroform/methanol homophasic solvent system to extract lipids from whole soiled nappies. In a study of 22 collections in six infants, no stools were lost and the recovery of lipids was 96%, with results similar to a reference titrimetric method. In addition to total fat, individual lipids were measured using gas-liquid chromatography. The method simplifies stool collection and analysis, is aesthetically more acceptable, and leads to reduced microbial hazards. It also allows the detailed study of excreted lipid species enabling the coefficient of absorption of dietary lipids of various chain lengths to be determined individually.