Hussain Al Dera

Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral challenges. Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children using atomic absorption spectrometry. Receiver Operating Characteristics (ROC) analysis of the obtained data was performed to measure the predictive value of their absolute and relative concentrations. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity.

Prominent contribution of L-type Ca2+ channels to cutaneous neurovascular transmission that is revealed after spinal cord injury augments vasoconstriction

In patients with spinal cord injury (SCI), somatosympathetic reflexes produce exaggerated decreases in skin blood flow below the lesion. This hypoperfusion appears to result from an increased responsiveness of cutaneous arterial vessels to neural activation. Here we investigated the mechanisms that underlie SCI-induced enhancement of neurovascular transmission in a cutaneous vessel, the rat tail artery. Isometric contractions of arterial segments from T11 spinal cord transected and sham-operated rats were compared 6 wk postoperatively. SCI more than doubled the amplitudes of contractions of arteries in response to moderate frequencies of nerve stimulation (0.1 to 1 Hz). In arteries from SCI rats, but not those from sham-operated rats, the L-type Ca(2+) channel blocker nifedipine (1 μM) reduced the amplitudes of nerve-evoked contractions. Furthermore, while the sensitivity to the agonists phenylephrine (α(1)-adrenoceptor selective) and clonidine (α(2)-adrenoceptor selective) did not differ significantly between arteries from SCI and sham-operated rats, nifedipine had a greater inhibitory effect on contractions to both agents in arteries from SCI rats. Although sensitivity to clonidine was unchanged, SCI selectively reduced the contribution of postjunctional α(2)-adenceptors to nerve-evoked contractions. In arteries from unoperated rats, the L-type channel agonist BAY K 8644 (0.1 μM) produced a similar enhancement of nerve-evoked contraction to that produced by SCI and also selectively reduced the contribution of α(2)-adrenceptors to these responses. Together the findings demonstrate that the SCI-induced enhancement of neurovascular transmission in the rat tail artery can largely be accounted for by an increased contribution of L-type Ca(2+) channels to activation of the vascular smooth muscle.

Spinal cord injury increases the reactivity of rat tail artery to angiotensin II.

Studies in individuals with spinal cord injury (SCI) suggest the vasculature is hyperreactive to angiotensin II (Ang II). In the present study, the effects of SCI on the reactivity of the rat tail and mesenteric arteries to Ang II have been investigated. In addition, the effects of SCI on the facilitatory action of Ang II on nerve-evoked contractions of these vessels were determined. Isometric contractions of artery segments from T11 (tail artery) or T4 (mesenteric arteries) spinal cord-transected rats and sham-operated rats were compared 6–7 weeks postoperatively. In both tail and mesenteric arteries, SCI increased nerve-evoked contractions. In tail arteries, SCI also greatly increased Ang II-evoked contractions and the facilitatory effect of Ang II on nerve-evoked contractions. By contrast, SCI did not detectably change the responses of mesenteric arteries to Ang II. These findings provide the first direct evidence that SCI increases the reactivity of arterial vessels to Ang II. In addition, in tail artery, the findings indicate that Ang II may contribute to modifying their responses following SCI.

Descriptive characteristics of children with autism at Autism Treatment Center, KSA.

Autism characteristics in sixty children (aged from 2 to 8) were assed. Their behavioral symptoms were evaluated using the Autism Treatment Evaluation Checklist (ATEC). ATEC has four main domains of autistic disorders (Speech/Language/Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) in children with clinical diagnosis by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and Childhood Autism Rating Scale (CARS) of autism spectrum disorder (ASD). Utilizing ATEC checklist, our study describes significant behavioral observations between autistic children which could effectively contribute to better understanding and treatment during their early intervention stage.Autism characteristics in sixty children (aged from 2 to 8) were assed. Their behavioral symptoms were evaluated using the Autism Treatment Evaluation Checklist (ATEC). ATEC has four main domains of autistic disorders (Speech/Language/Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) in children with clinical diagnosis by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and Childhood Autism Rating Scale (CARS) of autism spectrum disorder (ASD). Utilizing ATEC checklist, our study describes significant behavioral observations between autistic children which could effectively contribute to better understanding and treatment during their early intervention stage.

Effect of Diet on Gut Microbiota as an Etiological Factor in Autism Spectrum Disorder

Abstract The gut microbiota is a complex ecosystem that makes a great contribution toward the health of its host. One of the recent findings is the importance of the gut–brain axis as a bidirectional pathway through which the microbiota in the gut has potential influence on behavior and mental states. Gastrointestinal disorders are commonly reported in autistic patients, which may be due to altered composition of the gut microbiota, promoting the overgrowth of pathogenic bacteria. This can support the role of dysbiosis in the development of persistent autistic features. It is well known that diet plays an important role in the etiology of autism. Understanding the mechanism of diet–microbiota interaction may help to avoid the increasing prevalence of this disorder. Strategies to decrease the overgrowth of pathogenic bacteria and thus improve the composition of gut microbiota of autistic patients through dietary intervention may help to ameliorate gastrointestinal disorders commonly seen in autistic patients.

Increase of cytosolic phospholipase A2 as hydrolytic enzyme of phospholipids and autism cognitive, social and sensory dysfunction severity

BackgroundAutism is neurodevelopmental disorder that is characterized by developmental, behavioral, social and sensory abnormalities. Researchers have focused in last years in immunological alteration and inflammation as a hot subject in autism field. This work aims to study the alteration in phospholipids (PE, PS, and PC) together with the change in cPLA2 concentration as the main phospholipid hydrolytic enzyme in autistic patients compared to control. It was also extended to find a correlation between these biomarkers and severity of autism measured as childhood autism rating scale (CARS), Social responsiveness scale (SRS), and Short sensory profile (SSP).MethodsPhospholipids (PE, PS, PC) and cPLA2 as biochemical parameters were determined in the plasma of 48 Saudi autistic male patients, categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS), social responsiveness scale (SRS) and short sensory profile (SSP) and compared to 40 age- and gender-matched control samples.ResultsThe reported data demonstrate significantly lower levels of PE, PS, and PC together with a significant increase in cPLA2. While association between severity of autism and impaired phospholipid concentration was completely lacked, an association between cPLA2 and impaired sensory processing was observed.ConclusionsThe impaired phospholipid level and remarkable increased in cPLA2 concentration asserted their roles in the etiology of autism. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of clinical symptoms and provide significant guidance for future therapeutic strategy to re-establish physiological homeostasis.

Changes in sympathetic neurovascular function following spinal cord injury

The effects of spinal cord injury (SCI) on sympathetic neurovascular transmission have generally been ignored. This review describes changes in sympathetic nerve-mediated activation of arterial vessels to which ongoing sympathetic activity has been reduced or silenced following spinal cord transection in rats. In all vessels studied in rats, SCI markedly enhanced their contractile responses to nerve activity. However, the mechanisms that augment neurovascular transmission differ between the rat tail artery and mesenteric artery. In tail artery, the enhancement of neurovascular transmission cannot be attributed to changes in sensitivity of the vascular muscle to α1- or α2-adrenoceptor agonists. Instead the contribution of L-type Ca2+ channels to activation of the smooth muscle by nerve-released noradrenaline is greatly increased following SCI. By contrast, mesenteric arteries from SCI rats had increased sensitivity to phenylephrine but not to methoxamine. While both phenylephrine and methoxamine are α1-adrenoceptor agonists, only phenylephrine is a substrate for the neuronal noradrenaline transporter. Therefore the selective increase in sensitivity to phenylephrine suggests that the activity of the neuronal noradrenaline transporter is reduced. While present evidence suggests that sympathetic vasoconstrictor neurons do not contribute to the normal regulation of peripheral resistance below a complete SCI in humans, the available evidence does indicate that these experimental findings in animals are likely to apply after SCI in humans and contribute to autonomic dysreflexia.

Modified Cytoplasmic Ca2+ Sequestration Contributes to Spinal Cord Injury-Induced Augmentation of Nerve-Evoked Contractions in the Rat Tail Artery

In rat tail artery (RTA), spinal cord injury (SCI) increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist) mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR) limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control) and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker) in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study

Abstract This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

Biomarkers-Directed Strategies to Treat Autism

Autism is a neurodevelopmental disorder characterized by social, communication, and behavioral symptoms. Recent research has attempted to identify the potential mecha‐ nisms that may contribute to the pathogenesis of autism. Biomarkers as noninvasive quantitative biological measures with accurate indication of a specific mechanism can lead to a better understanding of the pathogenesis required to design the most effective treatments of autism. There is also great hope that the discovery of valid and predictive biomarkers for this disorder will help earlier and more targeted methods for diagnosis and intervention. In this chapter, we discuss some of the current theorized mechanisms contributing to autism, including inflammation, oxidative stress, impaired detoxifica‐ tion, glutamate excitotoxicity, gut-microbiota-brain axis, impaired fatty acid profiling, and serotonin (5-HT)/oxytocin (OT) abnormalities as target to treat autism. Moreover, based on our understanding of the role of these mechanisms, selected treatment strategies are suggested. These strategies include nutraceuticals, probiotics/prebiotics and ω-3 supplementation, targeting glutamate transporters or selective 5-HT reuptake inhibi‐ tors, and intranasal OT treatment. Of course, the joint efforts of scientists, caregivers, and other stakeholders must combine to identify valid, clinically useful autism biomarkers that may lead to efficient treatment strategy and/or combined strategies.