ADHD is a common neurodevelopmental disorder with onset of symptoms typically in early childhood. First signs of the disorder, including language delay, motor delay and temperament characteristics, ...may be evident as early as infancy. The present review describes published evidence about early motor signs of either children with later symptoms of ADHD or a later diagnosis of the disorder. Nine published cohort studies were included after a systematic search of related terms in PubMed and PsycInfo databases. Study eligibility criteria included: (1) report on early motor function or any motor-related signs; (2) the presence of a participants’ assessment by/at 12 months of age; (3) report of a later presence of ADHD symptoms. The limited number of reports included suggests an association between mild early neurological markers and later developmental coordination disorder and motor overflow movements. Unfortunately, due to their small sample sizes and focus on group reports rather than individuals, they have limited power to find strong associations. Early motor indicators of ADHD, if present, appear to be non-specific, and therefore not yet useful in clinical screening. Spontaneous motility seems to be a promising measure for early ADHD detection, although further studies with large cohorts are recommended to determine its clinical role in children at risk for ADHD.
Abstract Parkinsonian patients are treated with dopamine replacement therapy (typically, intermittent administration of the dopamine precursor l -DOPA); however, this is associated with the onset of ...abnormal involuntary movements, which seriously impair the quality of life. The molecular mechanisms underlying abnormal involuntary movements represent an intense field of investigation in the area of neurobiology of disease, although their aetiology remains unclear. Apart from the fine cellular mechanisms, the pathways responsible for the generation of abnormal involuntary movements may involve changes in neurotransmitter systems. A potential candidate is noradrenaline, since a severe loss of this neurotransmitter characterizes Parkinson's disease, and noradrenergic drugs produce a symptomatic relief of l -DOPA-induced dyskinesia. In previous studies we found that pulsatile dopamine release, in the absence of the physiological noradrenaline innervation, produces motor alterations and ultrastructural changes within striatal neurons. In the present study we demonstrate that a unilateral damage to the noradrenaline system anticipates the onset and worsens the severity of l -DOPA-induced contralateral abnormal involuntary movements in hemi-parkinsonian rats. Similarly, ubiquitin-positive striatal ultrastructural changes occur in unilaterally dopamine-depleted, noradrenaline-deficient rats following chronic l -DOPA administration. This study confirms a significant impact of the noradrenergic system in the natural history of Parkinson's disease and extends its role to the behavioural and morphological effects taking place during pulsatile dopamine replacement therapy.
The effects of training are dependent on complex, adaptive changes which are induced by acute physical exercise at different levels. In particular, evidence shows that the ...hypothalamus-pituitary-adrenocortical axis, as well as the sympatho-adrenomedullary system, is mainly involved in mediating the physiological effects of physical exercise. The aim of the present study was to investigate, through a morphological and biochemical approach, the effects of training on the adrenal gland of mice, following two different protocols consisting of either low- or high-intensity training. Mice were run daily on a motorised treadmill for 8 weeks, at a velocity corresponding to 60% (low-intensity exercise) or 90% (high-intensity exercise) of the maximal running velocity previously determined by an incremental exercise test. We found that physical exercise produced an increase in the adrenal gland size compared with the control (sedentary) mice. The increase was 31.04% for mice that underwent high-intensity exercise and 10.08% for mice that underwent low intensity exercise, and this appeared to be the result of an increase in the area of both the adrenal cortex and adrenal medulla. Morphological analysis of the adrenal cortex showed that both types of exercise produced an increase in cytoplasmic vacuoles in steroidogenic cells, appearing more abundant after high-intensity exercise. No change was found in the reticulate zone. In the adrenal medulla, despite the absence of morphological changes, immunohistochemistry for tyrosine hydroxylase, dopamine β-hydroxylase and phenyl-ethanolamine-N-methyltransferase demonstrated an increased immunopositivity for these cathecolamine-synthesizing enzymes after intense exercise. These results were confirmed by immunoblot accompanied by densitometric analysis.
IN THE PRESENT STUDY WE INVESTIGATED THE EFFECT OF TWO DIFFERENT EXERCISE PROTOCOLS ON FIBRE COMPOSITION AND METABOLISM OF TWO SPECIFIC MUSCLES OF MICE: the quadriceps and the gastrocnemius. Mice ...were run daily on a motorized treadmill, at a velocity corresponding to 60% or 90% of the maximal running velocity. Blood lactate and body weight were measured during exercise training. We found that at the end of training the body weight significantly increased in high-intensity exercise mice compared to the control group (P=0.0268), whereas it decreased in low-intensity exercise mice compared to controls (P=0.30). In contrast, the food intake was greater in both trained mice compared to controls (P < 0.0001 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively). These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls (P=0.03 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively); in particular, blood lactate levels after high-intensity exercise were significantly lower than those measured in low-intensity exercise mice (P=0.0044). Immunoblotting analysis demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial enzymes contained within gastrocnemius and quadriceps muscles. These changes were associated with an increase in the amount of slow fibres in both these muscles of high-intensity exercise mice, as revealed by the counts of slow fibres stained with specific antibodies (P < 0.0001 for the gastrocnemius; P=0.0002 for the quadriceps). Our results demonstrate that high-intensity exercise, in addition to metabolic changes consisting of a decrease in blood lactate and body weight, induces an increase in the mitochondrial enzymes and slow fibres in different skeletal muscles of mice, which indicates an exercise-induced increase in the aerobic metabolism.
Trimethyltin-induced intoxication has a great impact on human health due to the widespread occurrence of methyltin compounds. Acute TMT intoxication in humans leads to a variety of neurological ...symptoms which involve primarily the limbic system. In the present review we summarized the neuromorphological correlates of this neurological syndrome extending the analysis to various extra-limbic regions and detailing the fine ultrastructure of TMT-induced neuronal alterations. In order to comprehend the pathophysiology of TMT-induced neuronal damage we analysed the various experimental models of TMT-induced neurotoxicity. When comparing various animal species, it seems that the variety of neuropathological correlates are not related to species difference in the sensitivity to TMT toxicity but to a different susceptibility to secondary effects produced by TMT. In fact, apart from a primary neurotoxic damage induced by TMT at neuronal level, this compound promotes the onset of limbic and generalized seizures, which in turn add a secondary damage to that induced immediately by TMT. Thus, the different neuropathology observed in different animal species is produced mainly by a different sensitivity to epilepsy-induced brain damage.
Research providing an evidence-base for autistic adult services is sparse. The Autism Spectrum Disorders in the European Union (ASDEU) network implemented an on-line survey to determine gaps in ...autistic adult diagnostic evaluation and post-diagnostic support services. More than 55% in all groups experienced most of the recommended features for diagnostic evaluation for autistic adults. In contrast, < 2% of adults or carers, and < 21% of professionals experienced each of the recommended features for post-diagnostic support. In contrast to 61% of professionals, only about 30% of autistic adults and carers had knowledge of good local services models for autism diagnosis in adulthood. There are major differences between good practice guidelines for diagnostic and post-diagnostic care for autistic adults, and what is actually experienced by services users and professionals.
Non-steroidal anti-inflammatory drugs (NSAIDs) can damage the small intestine, mainly through an involvement of enteric bacteria. This study examined the pathophysiology of NSAID-associated ...intestinal lesions in a rat model of diclofenac-enteropathy and evaluated the effect of rifaximin on small bowel damage. Enteropathy was induced in 40-week old male rats by intragastric diclofenac (4 mg/kg BID, 14 days). Rifaximin (delayed release formulation) was administered (50 mg/kg BID) 1 h before the NSAID. At the end of treatments, parameters dealing with ileal damage, inflammation, barrier integrity, microbiota composition, and TLR-NF-κB-inflammasome pathway were evaluated. In addition, the modulating effect of rifaximin on NLRP3 inflammasome was tested in an
cell system. Diclofenac induced intestinal damage and inflammation, triggering an increase in tissue concentrations of tumor necrosis factor and interleukin-1β, higher expression of TLR-2 and TLR-4, MyD88, NF-κB and activation of caspase-1. In addition, the NSAID decreased ileal occludin expression and provoked a shift of bacterial phyla toward an increase in
and
abundance. All these changes were counterbalanced by rifaximin co-administration. This drug was also capable of increasing the proportion of Lactobacilli, a genus depleted by the NSAID. In LPS-primed THP-1 cells stimulated by nigericin (a model to study the NLRP3 inflammasome), rifaximin reduced IL-1β production in a concentration-dependent fashion, this effect being associated with inhibition of the up-stream caspase-1 activation. In conclusion, diclofenac induced ileal mucosal lesions, driving inflammatory pathways and microbiota changes. In conclusion, rifaximin prevents diclofenac-induced enteropathy through both anti-bacterial and anti-inflammatory activities.
Age-related macular degeneration (AMD) is a common retinal disorder, which became more and more prevalent in the last decades. AMD is now the most prevalent cause of blindness in the western world. ...The disorder is classified into two phenotypes named dry and wet AMD. This is based on the recruitment of novel blood vessels and inflammatory exudates in wet AMD. In both phenotypes, the pathological hallmark is the presence of proteinaceous aggregates called drusen, which mostly accumulate between the choroid and the retinal pigment. Drusen in dry AMD represent the evident pathological finding although they are present, though less defined, in wet AMD. In AMD drusen are supposed to be a pathogenic trigger of the disorder. In fact, drusen may mechanically alter retinal function. A novel hypothesis exists, suggesting that a metabolic defect (systemic or focal within the retinal pigment epithelium) may be the real determinant of visual impairment, while causing the concomitant accumulation of proteinaceous debris and lipids forming the drusen. Here we face such an issue by analyzing the retinal anatomy to correlate visual impairment with the occurrence of drusen number, size and the extent of a drusenoid area in the foveal region. A comparison is made with wet AMD where new vessels and retinal exudates prevail. The study is carried out in 120 patients affected by dry or wet AMD and 21 patients where paradoxical findings are described. The main question consists in inferring whether the occurrence of visual impairment is due, in fact, to a drusen-dependent mechanical damage or drusen just occurs as an independent consequence of an upstream metabolic alteration, which concomitantly impairs the visual process. The present data indicate that, despite a significant difference in visual function between mild and severe AMD patients in the amount of drusen exists, a strong correlation between drusen and visual impairment does not occur. This suggests that drusen and visual deterioration develop as a consequence of similar upstream biochemical alterations but it is likely that drusen do not produce visual deterioration. This is strengthened here by extreme clinical conditions, where visual impairment is severe with a slight alteration in the planar pattern of the retina or, vice versa an extended drusenoid area occurs concomitantly with fair visual acuity, contrast sensitivity and lack of metamorphopsia. A biochemical analysis of key areas in the function of specific domains in the pigment epithelium as described in the accompanying manuscript should help to better disclose the real morpho-functional deficit, which takes place in AMD.
The Autism Spectrum Disorders in the European Union (ASDEU) survey investigated local services’ use experiences of autistic adults, carers and professionals with interventions for autistic adults. ...The majority of the 697 participants experienced recommended considerations prior to deciding on intervention and during the intervention plan and implementation. Psychosocial interventions were the most commonly experienced interventions, while pharmacological interventions NOT recommended for core autistic symptoms were reported by fairly large proportions of participants. Family interventions were experienced slightly more commonly by carers than adults or professionals. Less than the 26% of autistic adult responders who had experienced challenging behaviors reported receiving an intervention to change them. These results provide insights for improving gaps in service provision of interventions among autistic adults.
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