The REACH registration process: A case study of metallic aluminium, aluminium oxide and aluminium hydroxide.

The European Union's REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances: metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports.

Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has caused a global pandemic in only 3 months. In addition to major respiratory distress, characteristic neurological manifestations are also described, indicating that SARS-CoV-2 may be an underestimated opportunistic pathogen of the brain. Based on previous studies of neuroinvasive human respiratory coronaviruses, it is proposed that after physical contact with the nasal mucosa, laryngopharynx, trachea, lower respiratory tract, alveoli epithelium, or gastrointestinal mucosa, SARS-CoV-2 can induce intrinsic and innate immune responses in the host involving increased cytokine release, tissue damage, and high neurosusceptibility to COVID-19, especially in the hypoxic conditions caused by lung injury. In some immune-compromised individuals, the virus may invade the brain through multiple routes, such as the vasculature and peripheral nerves. Therefore, in addition to drug treatments, such as pharmaceuticals and traditional Chinese medicine, non-pharmaceutical precautions, including facemasks and hand hygiene, are critically important.

Vitamin D and the nervous system.

Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.

The effect of Hordeum vulgare on the monoaminergic system modulating neural-thyroid dysfunction in hypothyroid female rats.

Thyroid hormones regulate the development and maturation of the brain by maintaining levels of neurotransmitters and their related metabolites. The present work emphasizes the neural dysfunction in the brain caused by hypothyroidism and the potential role of Hordeum vulgare (water soluble barley, (B)) in ameliorating these effects. The study was conducted on euothyroid and hypothyroid adult female rats. The induction of hypothyroidism was conducted by oral-administration of neo-mercazole (5.0 mg.kg-1) daily for thirty days prior the study and terminated at the end of the study. The groups were assigned as; euthyroid (EU) and hypothyroid (H) groups and other two groups were treated with 100 mg.kg-1 water soluble barley; daily for one month and assigned as (EU+B) and (H+B) groups. Compared with EU and EU+B groups, a reduction in fT4, and ERK1/2 levels and elevation in TSH in brain tissue, Moreover, a  significant elevation in 8-OH deoxyguanosine and caspase-3 levels, confirmed with increase percentage DNA-damage in the brain and thyroid tissues in hypothyroid control rats. Furthermore, a significant decrease in all monoamines levels in different brain areas and downregulation of dopamine and 5-hydroxytreptamin receptors transcription, with a significant increase in excitatory amino acids and no significant change in the levels inhibitory amino acids were recorded in control hypothyroid group. Treatment of hypothyroid group with Hordeum vulgare improved the above-mentioned adverse impact by ameliorating the thyroid hormone levels with depleting the DNA-degradation and elaborating the levels of neurotransmitters with related receptors and amino acids in brain areas.  Water soluble Hordeum vulgare as a phytonutrient, is safe and efficient agent in ameliorating the neural dysfunction resulting from hypothyroidism status in adult female rats.

Mechanism of electroacupuncture on inflammatory pain: neural-immune-endocrine interactions.

Nociceptive signals are transmitted by peripheral afferents to the central nervous system under pain condition, a process that involves various neurotransmitters and pathways. Electroacupuncture (EA) has been widely used as a pain management technique in clinical practice. Emerging studies have shown that EA can inhibit the induction and transmission of pain signals and, consequently, mediate anti-nociceptive and anti-inflammatory effects by rebalancing the neural-immune-endocrine interactions. This review summarizes the neural-immune-endocrine circuit including peripheral afferent and central efferent, contributing to EA-induced neuroimmune and neuroendocrine modulation in inflammatory pain models. The peripheral afferent circuit includes crosstalk among immune cells, inflammatory cytokines, peripheral nociceptors. In central efferent primarily involves the neuroinflammatory interactions between spinal nociceptive neurons and glial cells. Furthermore, the hypothalamic-pituitary-adrenal axis, sympathetic and vagal nervous may serve as an essential pathway involved in the mechanism of acupuncture-mediated analgesia within the interactions of the central, immune and endocrine systems. Overall, this review focuses on the interactions of neural-immune-endocrine in inflammatory pain, which may be underlying the mechanism of EA-induced anti-inflammatory and antinociceptive effect.

Dolor lumbar somático tratado con terapia neural y ozono paravertebral / Somatic low back pain treated with neural therapy and paravertebral ozone

La presente investigación tuvo como objetivo general evaluar el efecto de la terapia neural e infiltración paravertebral segmentaria con ozono en el dolor lumbar somático de los pacientes que asistieron a la consulta de terapia del dolor en el Hospital Dr. Pedro García Clara, Ciudad Ojeda Estado Zulia-Venezuela, en el periodo comprendido del 01 de abril al 31 de mayo del 2016. Fue un estudio prospectivo, explicativo-comparativo y el diseño fue cuasi-experimental. Se seleccionaron 60 pacientes de ambos sexos entre edades comprendidas de 18 a 60 años, se dividieron en dos grupos de 30 pacientes, al primer grupo denominado A, se le realizó terapia neural segmentaria lumbar utilizando procaína al 1% y consecutivamente se le aplicó infiltración paravertebral con ozono a una concentración de 15ug; y al grupo B, se le realizó terapia neural con lidocaína al 1% y posteriormente se le aplicó la infiltración paravertebral con ozono a una concentración de 15ug, ambos grupos con un volumen de 10mL. Para el análisis de los datos se utilizó estadística descriptiva e inferencial, específicamente la prueba t de Student para las muestras relacionadas. Resultados: indicaron que en ambas terapias, al evaluar el dolor con la escala visual análoga, se encontraron diferencias estadísticamente significativas (p<0,05), en ambos grupos. Conclusiones: no hubo diferencias estadísticamente significativas con respecto a los cambios hemodinámicos y la disminución del dolor fue significativa en ambos grupos, pero más notable en el grupo A(AU)

The present study was aimed at evaluating the overall effect of neural therapy and segmental paravertebral ozone infiltration in lumbar somatic pain patients attending the consultation of pain therapy Dr. Pedro Garcia Clara Hospital of Ciudad Ojeda Estado Zulia-Venezuela, in the period from 01 April to 31 May 2016. It was a comparative-explanatory, prospective study design was quasi-experimental, 60 patients of either sex between aged from 18 to 60 years were selected, they were divided into two groups of 30 patients, the first group called A, underwent neural therapy lumbar segmental using procaine 1% and consecutively was applied paravertebral infiltration with ozone at a concentration of 15ug; and group B, underwent neural therapy with lidocaine 1% and was subsequently applied the paravertebral infiltration with ozone at a concentration of 15ug, both groups with a volume of 10mL. For data analysis the mean, standard deviation, and inferential statistics, specifically the Student t test for related samples was used. Results: indicated that both therapies, to assess pain with visual analogue scale, statistically significant differences (p<0.05) in both groups. Conclusions: There were no statistically significant differences with respect to hemodynamic changes and pain reduction was significant in both groups, but more remarkable in group A(AU)

A Review on the Possible Neuroprotective Effects of Moringa Oleifera Leaf Extract.

Moringa oleifera is an edible plant that has been reputed to be a miracle plant by numerous authors, with effects on practically every body system. Phytochemical analyses have demonstrated that the leaves are rich in various minerals, vitamins and antioxidants. Its use in some continents dates back to Antiquity. Neurodegeneration are chronic diseases of the nervous system. There is currently an increase in the use of natural products to combat these debilitating diseases. So far, no suitable cure has been found, and conditions are managed and the symptoms treated. This article reviews the literature on the effects of Moringa oleifera leaves on the nervous system in vivo and in vitro.

Sesamol ameliorates high-fat and high-fructose induced cognitive defects via improving insulin signaling disruption in the central nervous system.

Sesamol, a nutritional component from sesame, possesses antioxidant, lipid lowering and antidepressant activities. Nonetheless, few studies report its effects on high-energy-dense diet-induced cognitive loss. The present research aimed to elucidate the action of sesamol on high-fat and high-fructose (HFFD) "western"-diet-induced central nervous system insulin resistance and learning and memory impairment, and further determined the possible underlying mechanism. 3 month-old C57BL/6J mice were divided into 3 groups with/without sesamol in the drinking water (0.05%, w/v) and standard diet, HFFD, and HFFD with sesamol supplementation. Morris water maze tests demonstrated that sesamol improved HFFD-elicited learning and memory loss. Sesamol was also found to attenuate neuron damage in HFFD-fed mice. Importantly, sesamol treatment up-regulated brain insulin signaling by stimulating IRS-1/AKT as well as ERK/CREB/BDNF pathways; meanwhile it down-regulated neuronal death signaling GSK3ß and JNK. Moreover, sesamol also normalized mRNA expressions of neurotrophins including BDNF and NT-3, as well as expressions of mitochondrial metabolic and biogenesis related genes Sirt1 and PGC1α. Consistently, sesamol also reversed high-glucose-induced oxidized cellular status, mitochondrial membrane potential loss, insulin signaling inhibition and cell death in SH-SY5Y neuronal cells. Taken together, the current study proved that sesamol reduced western-diet-induced cognitive defects in a mouse model by inhibiting insulin resistance, normalizing mitochondrial function and cell redox status, and improving IRS/AKT cell surviving and energy metabolism regulating signaling. This compelling evidence indicated that sesamol is a potential nutritional supplement to prevent unhealthy-diet-induced learning and memory loss.

Protective effect of green tea against neuro-functional alterations in rats treated with MnO2 nanoparticles.

BACKGROUND: Inhalation of manganese-containing metal fumes at workplaces can cause central nervous damage including a Parkinson-like syndrome. Oxidative stress is likely to be involved in the pathomechanism, due to the presence of nano-sized metal oxide particles with high biological and chemical activity. Oxidative damage of the nervous system could be prevented or ameliorated by properly applied antioxidants, preferably natural ones such as green tea, a popular drink. The aim of this work was to see if orally applied green tea brew could diminish the functional neurotoxicity of manganese dioxide nanoparticles introduced into the airways of rats. RESULTS: Young adult male Wistar rats were treated intratracheally for 6 weeks with a suspension of synthetic MnO2 nanoparticles (4 mg/kg body weight), and received green tea brew (1 g leaves 200 mL-1 water) as drinking fluid. Reduced body weight gain, indicating general toxicity of the nanoparticles, was not influenced by green tea. However, in rats receiving green tea the nervous system effects - changes in the spontaneous and evoked cortical activity and peripheral nerve action potential - were diminished. CONCLUSION: The use of green tea as a neuroprotective functional drink seems to be a viable approach. © 2016 Society of Chemical Industry.

Early life programming of pain: focus on neuroimmune to endocrine communication.

Chronic pain constitutes a challenge for the scientific community and a significant economic and social cost for modern societies. Given the failure of current drugs to effectively treat chronic pain, which are based on suppressing aberrant neuronal excitability, we propose in this review an integrated approach that views pain not solely originating from neuronal activation but also the result of a complex interaction between the nervous, immune, and endocrine systems. Pain assessment must also extend beyond measures of behavioural responses to noxious stimuli to a more developmentally informed assessment given the significant plasticity of the nociceptive system during the neonatal period. Finally integrating the concept of perinatal programming into the pain management field is a necessary step to develop and target interventions to reduce the suffering associated with chronic pain. We present clinical and animal findings from our laboratory (and others) demonstrating the importance of the microbial and relational environment in programming pain responsiveness later in life via action on hypothalamo-pituitary adrenal (HPA) axis activity, peripheral and central immune system, spinal and supraspinal mechanisms, and the autonomic nervous system.

Hypocretins, Neural Systems, Physiology, and Psychiatric Disorders.

The hypocretins (Hcrts), also known as orexins, have been among the most intensely studied neuropeptide systems since their discovery about two decades ago. Anatomical evidence shows that the hypothalamic neurons that produce hypocretins/orexins project widely throughout the entire brain, innervating the noradrenergic locus coeruleus, the cholinergic basal forebrain, the dopaminergic ventral tegmental area, the serotonergic raphe nuclei, the histaminergic tuberomammillary nucleus, and many other brain regions. By interacting with other neural systems, the Hcrt system profoundly modulates versatile physiological processes including arousal, food intake, emotion, attention, and reward. Importantly, interruption of the interactions between these systems has the potential to cause neurological and psychiatric diseases. Here, we review the modulation of diverse neural systems by Hcrts and summarize potential therapeutic strategies based on our understanding of the Hcrt system's role in physiology and pathophysiological processes.

Multi-electrode neurostimulation system for treatment of cognitive impairments.

Peculiarities of neurostimulation organization by a multi-electrode system are considered. The system forms the spatially distributed field of current pulses that impact the nerve centers of the neck. An example is given for technical implementation of such a system in device SYMPATHOCOR and the method of its application: the dynamic correction of activity of the sympathetic nervous system. Results of its clinic application to treating the children with the attention deficit syndrome are given. It is shown that taking into account pathophysiological peculiarities of such a syndrome, it could be considered as a general model of cognitive impairments.

Adverse events associated with yoga: a systematic review of published case reports and case series.

While yoga is gaining increased popularity in North America and Europe, its safety has been questioned in the lay press. The aim of this systematic review was to assess published case reports and case series on adverse events associated with yoga. Medline/Pubmed, Scopus, CAMBase, IndMed and the Cases Database were screened through February 2013; and 35 case reports and 2 case series reporting a total of 76 cases were included. Ten cases had medical preconditions, mainly glaucoma and osteopenia. Pranayama, hatha yoga, and Bikram yoga were the most common yoga practices; headstand, shoulder stand, lotus position, and forceful breathing were the most common yoga postures and breathing techniques cited. Twenty-seven adverse events (35.5%) affected the musculoskeletal system; 14 (18.4%) the nervous system; and 9 (11.8%) the eyes. Fifteen cases (19.7%) reached full recovery; 9 cases (11.3%) partial recovery; 1 case (1.3%) no recovery; and 1 case (1.3%) died. As any other physical or mental practice, yoga should be practiced carefully under the guidance of a qualified instructor. Beginners should avoid extreme practices such as headstand, lotus position and forceful breathing. Individuals with medical preconditions should work with their physician and yoga teacher to appropriately adapt postures; patients with glaucoma should avoid inversions and patients with compromised bone should avoid forceful yoga practices.

Tempo de cérebro / Brain time

No encontro entre matemática, física, química, biologia, psicologias, filosofia e artes, as neurociências fascinam o público pela possibilidade de compreensão dos mecanismos das emoções, pensamentos e ações, doenças e loucuras, aprendizado e esquecimento, sonhos e imaginação, fenômenos que nos definem e constituem. Como interpretar as novas descobertas das neurociências? O presente artigo aborda alguns tópicos de amplo interesse social: o envelhecimento, a educação, as drogas, o retorno científico à psicanálise e o problema da consciência.

A pilot study on the relationship between tongue manifestation and the degree of neurological impairment in patients with acute cerebral infarction.

OBJECTIVE: To discuss the relationship between tongue manifestation and the degree of neurological impairment in the patients with acute cerebral infarction. METHODS: Two hundred patients with first unilateral cerebral infarction were recruited. The relationship between different tongue manifestation and National Institute of Health Stroke Scale (NIHSS) were analyzed. RESULTS: NIHSS scores in the patients from different tongue color groups were analyzed and further analysis demonstrated that the NIHSS score was higher in the patients with red or bluish-purple tongue than that of those with the pink (P <0.01). On tongue fur, the NIHSS score in the patients with thick fur was higher than that of those with the thin (P=0.003). NIHSS score in patients with slippery, moist or dry fur was significant different (P=0.003), Further analysis demonstrated that the NIHSS score was higher in the patients with dry fur than that of those with moist fur, and had statistical significance (P=0.01). The NIHSS score was higher in patients from greasy fur group than that of the non-greasy (P=0.002). There was significant difference of NHISS score in the patients with different fur color (P=0.000), and further analysis demonstrated that the NHISS score in white-yellow, yellow fur group were higher than that of the white (P=0.06 or 0.000). CONCLUSION: The changes of tongue manifestation might be associated with the degree of neurological impairment in the patients with acute cerebral infarction.

Ca/Mg infusions for the prevention of oxaliplatin-related neurotoxicity in patients with colorectal cancer: a meta-analysis.

BACKGROUND: Oxaliplatin-related neurotoxicity is the main limitation for its continuation in adjuvant and palliative chemotherapy for patients with colorectal cancer. The purpose of this meta-analysis was to determine the efficacy of calcium and magnesium (Ca/Mg) infusions in oxaliplatin-induced neurotoxicity. METHODS: Two independent authors conducted database searches of the literature to find clinical-controlled trials analyzing Ca/Mg infusions in oxaliplatin-induced neurotoxicity. The keywords used to search were oxaliplatin, neurotoxicity, calcium, magnesium, neuropathy, and peripheral. Clinical studies that included at least one primary or secondary event were eligible for the analysis, where primary events were incidences of acute and cumulative neurotoxicity, and secondary events were the total doses and cycles of oxaliplatin, response rate (RR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORs) and weighted mean differences (MD) were analyzed using models of fixed and random effects. RESULTS: This meta-analysis comprised four prospective randomized clinical trials and three retrospective clinical trials involving 1170 colorectal cancer patients, of which 802 received Ca/Mg infusions (Ca/Mg group) and 368 did not (control group). According to the National Cancer Institute-Common Terminology Criteria for Adverse Events, the incidence of grade 3 acute neurotoxicity in those who received Ca/Mg was significantly lower than that of the control group (OR=0.26; 95% confidence interval (CI), 0.11 to 0.62; P=0.0002). The total rate of cumulative neurotoxicity, and that of grade 3 in particular, was significantly lower in the Ca/Mg group than in the control group (OR=0.42; 95% CI 0.26-0.65; P=0.0001; OR=0.60; 95% CI 0.39-0.92; P=0.02, respectively). The differences in total doses and cycles of oxaliplatin were also significant between the Ca/Mg and control group (MD=246.73 mg/m2; 95% CI 3.01-490.45; P=0.05; MD=1.55; 95% CI 0.46-2.63; P=0.005, respectively). No significant differences were found in median PFS (MD=0.71 month; 95% CI -0.59-2.01; P=0.29), median OS (MD=0.10 month; 95% CI -0.41-0.61; P=0.70) or RRs (OR=0.82; 95% CI 0.61-1.10; P=0.18). CONCLUSION: Ca/Mg infusions tend to decrease the incidence of oxaliplatin-induced acute and cumulative neurotoxicity and thus enhance patients' tolerance to oxaliplatin, without significantly altering the efficacy of chemotherapy.

Select exercise modalities may reverse movement dysfunction because of peripheral neuropathy.

Peripheral neuropathy (PN) is a highly prevalent and potentially debilitating disease linked to mobility and postural control impairments and movement dysfunction in goal-directed movements. Although different exercises have produced functional improvements in PN, recent evidence indicates that exercises like Tai Chi can alter the damaged sensory system and facilitate recovery of mobility and balance, potentially reducing the reliance on other people.

Evidence for improved neuropharmacological efficacy and decreased neurotoxicity in mice with traditional processing of Rhizoma Arisaematis.

Rhizoma Arisaematis (RA, the rhizome of Pinellia pedatisecta Schott) is a traditional Chinese medicine commonly used in the treatment of convulsions, inflammation, and cancer. Despite the fact that it has been used for more than 2000 years, the pharmacological and toxic effects of traditionally processed products of RA are still unclear. In this study, we attempted to investigate the effects exerted by untreated crude RA and different preparations of RA treated with alumen in combination with ginger juice (Zhinanxing) or bile juice (Dannanxing) in ICR mice. The results showed that both the Zhinanxing and Dannanxing water extracts exerted significantly increased sedative effects, as indicated by the inhibitory effects on ambulatory distances, jumps, vertical-plane entries, and prolonged pentobarbital-induced sleeping time. The extracts also exerted significantly increased analgesic effects (increase of tail flick latency in nociceptive testing) in mice than did the unprocessed crude RA after oral administration for one to three days, and effects persisted 18 days after the cessation of treatment. By contrast, the toxic effects, such as an increase in stereotype-1 episodes of locomotor activities and reduction of the retention time on a rotating rod (motor equilibrium dysfunction), were observed only in mice treated with the unprocessed crude RA for three consecutive days, and effects persisted for 18 days after the cessation of treatment. These neurotoxic effects were accompanied by an increase in plasma lipid peroxidation (LPO), decrease in whole blood nitric oxide (NO(x)) levels, and inhibition of Na(+)/K(+)-ATPase activities in membrane fractions of erythrocytes and in the cerebral cortex. In conclusion, these findings provide scientific evidence that the processed RA indeed possesses not only enhanced neuropharmacological efficacy but also reduced neurotoxic effects as compared to the unprocessed crude RA. The signaling of NO(x)/oxidative stress/Na(+)-K(+)- ATPase activities played a role, at least in part, in the underlying mechanisms of neurotoxic effects induced by the crude RA.

Inhaled nitric oxide improves outcomes after successful cardiopulmonary resuscitation in mice.

BACKGROUND: Sudden cardiac arrest (CA) is a leading cause of death worldwide. Breathing nitric oxide (NO) reduces ischemia/reperfusion injury in animal models and in patients. The objective of this study was to learn whether inhaled NO improves outcomes after CA and cardiopulmonary resuscitation (CPR). METHODS AND RESULTS: Adult male mice were subjected to potassium-induced CA for 7.5 minutes whereupon CPR was performed with chest compression and mechanical ventilation. One hour after CPR, mice were extubated and breathed air alone or air supplemented with 40 ppm NO for 23 hours. Mice that were subjected to CA/CPR and breathed air exhibited a poor 10-day survival rate (4 of 13), depressed neurological and left ventricular function, and increased caspase-3 activation and inflammatory cytokine induction in the brain. Magnetic resonance imaging revealed brain regions with marked water diffusion abnormality 24 hours after CA/CPR in mice that breathed air. Breathing air supplemented with NO for 23 hours starting 1 hour after CPR attenuated neurological and left ventricular dysfunction 4 days after CA/CPR and markedly improved 10-day survival rate (11 of 13; P=0.003 versus mice breathing air). The protective effects of inhaled NO on the outcome after CA/CPR were associated with reduced water diffusion abnormality, caspase-3 activation, and cytokine induction in the brain and increased serum nitrate/nitrite levels. Deficiency of the α1 subunit of soluble guanylate cyclase, a primary target of NO, abrogated the ability of inhaled NO to improve outcomes after CA/CPR. CONCLUSIONS: These results suggest that NO inhalation after CA and successful CPR improves outcome via soluble guanylate cyclase-dependent mechanisms.