Speech language characteristics and intervention approaches in lockedin syndrome post snake envenomation

The present case study illustrates hypoxic-ischemic encephalopathy as a result of neuroparalytic snake envenomation in an 11 year old male patient. Detailed speech assessment was done which revealed diverged oral structures and language loss. The study aims to document speech and language characteristics as well as rehabilitation in terms of speech therapy. The study enlightens the role of speech language pathologist in assessment and intervention of locked in syndrome. Study shows the swapped roles of traditional therapy approaches and the importance of augmentative and alternative communication as compassion and a beneficial technique in an intricate incident like hypoxic-ischemic encephalopathy as a result of neuroparalytic snake envenomation.

Zika virus syndrome, lack of environmental policies and risks of worsening by cyanobacteria proliferation in a climate change scenario / Síndrome do zika vírus, carência de políticas ambientais e riscos de agravamento por proliferação de cianobactérias em um cenário de mudanças climáticas

ABSTRACT Almost half of the Brazilian population has no access to sewage collection and treatment. Untreated effluents discharged in waters of reservoirs for human supply favor the flowering of cyanobacteria - and these microorganisms produce toxins, such as saxitoxin, which is a very potent neurotoxin present in reservoirs in the Northeast region. A recent study confirmed that chronic ingestion of neurotoxin-infected water associated with Zika virus infection could lead to a microcephaly-like outcome in pregnant mice. Cyanobacteria benefit from hot weather and organic matter in water, a condition that has been intensified by climate change, according to our previous studies. Considering the new findings, we emphasize that zika arbovirus is widespread and worsened when associated with climate change, especially in middle- or low-income countries with low levels of sanitation coverage.

RESUMO No Brasil, quase metade da população não tem acesso a coleta e tratamento de esgotos. Os efluentes não tratados, devido a contaminação das águas de reservatórios para abastecimento humano, geram florações de cianobactérias - e esses microrganismos produzem toxinas, como a saxitoxina, uma neurotoxina bastante potente e presente nos reservatórios da região Nordeste. Estudo recente confirmou que a ingestão crônica de água contaminada com neurotoxinas associada a infeção pelo zika vírus em camundongos prenhes poderia levar a desfecho semelhante a microcefalia. Cianobactérias são beneficiadas por tempo quente e matéria orgânica na água, e essas condições estão sendo intensificadas pelas mudanças climáticas, segundo nossos estudos anteriores. Aqui, ressaltamos que, à luz dos novos achados, a arbovirose do zika, associada às mudanças do clima, se amplifica e se agrava, sobretudo em países de média ou baixa renda, com baixos níveis de cobertura de saneamento.

Transtorno do espectro autista: uma revisão sistemática sobre aspectos nutricionais e eixo intestino-cérebro / Autism spectrum disorder: a systematic review about nutritional aspects and gut-brain axis

O número de indivíduos diagnosticados com o transtorno do espectro autista (TEA) registrou aumento evidente na última década. Os principais sintomas, apresentados pelo portador, são neurológicos e digestórios, estando às intervenções nutricionais dentre as terapêuticas mais promissoras para amenizar a sintomatologia clínica. Assim, objetivou-se revisar sistematicamente os estudos sobre distúrbios alimentares e do trato gastrointestinal apresentado pelo indivíduo portador do TEA, a fim de compreender como o comportamento alimentar influência na etiopatogênese e manifestações clínicas da doença, com foco no eixo intestinocérebro. Para isso realizou-se uma revisão sistemática, seguindo as diretrizes PRISMA. A partir de uma busca estruturada e abrangente em bases de dados eletrônicas, 23 estudos foram recuperados e incluídos na revisão. Os critérios de inclusão definiam ser artigos originais relacionando o TEA com alterações nutricionais e/ou com o eixo intestino-cérebro. Após análise da composição da microbiota intestinal, os estudos mostraram um quadro de desequilíbrio. Foram encontradas, também, alterações na barreira de muco e permeabilidade intestinal e alterações em proteínas envolvidas na digestão e absorção de alimentos. Dietas restritivas e a modulação da microbiota, com uso de probióticos e de antibióticos específicos, são apresentadas como estratégias terapêuticas adjuvantes promissoras. Conclui-se que o eixo intestino-cérebro está envolvido tanto na etiologia, quanto nas manifestações clínicas do TEA. Porém, não sendo certo se alterações intestinais são causa ou consequência das alterações neurológicas. Até o presente momento, a comunidade científica não tem conclusões suficientes para indicar o uso de dietas restritivas, e uso de probióticos e de antibióticos como terapêutica para o TEA.

The number of individuals diagnosed with autism spectrum disorder (ASD) had an evident increase in the last decade. The primary symptoms exhibited amongst these patients were mostly digestive and neurological disorders; with nutritional interventions being one of the most promising therapies to assuage this clinical symptomology. As such, following the PRISMA guidelines, we systematically reviewed the research studies apropos of the ASD patients manifesting said digestive disorders, to comprehend how dietary behavior can influence the etiopathogenesis and clinical manifestations of the disease, with primary focus on the gut-brain axis. From a comprehensive and structured search through electronic databases, 23 studies were retrieved and admitted in this review. The inclusion criteria defined that there be original articles consociating ASD with nutritional disorders and/or with the gut-brain axis. These studies analyzed the composition of the intestinal flora of diagnosed patients, subsequently discerning cases of varying imbalances. Alterations in the gene expression of the proteins involved in the digestion and absorption of food, the mucous barrier and the intestinal permeability were described. Accordingly, restrictive diets and the modulation of the microbiota by administering specific anti- & probiotics were initially identified as promissory therapies. In conclusion, the gut-brain axis was observed to be a determinant factor in both the etiology and clinical symptomology of ASD - though it is still debatable the correlation of intestinal alterations with neurological changes. At present, there is no concrete scientific proof accrediting to restrictive diets and the use of specific anti- & probiotics, as successful treatments for ASD.

Application of botulinum toxin type A in gummy smile: case report / Aplicação da toxina botulínica tipo A em sorriso gengival: relato de caso

ABSTRACT Gummy smile is one of the major complaints of patients, due to its influence on the self-esteem. It is known that it has a multifactorial cause and can be present in the excessive vertical growth of the maxilla, excessive labial contraction, short upper lip and extrusion of the anterior teeth. The use of the botulinum toxin can be associated with additional treatments or be applied individually, according to the need of each patient. The goal of this research study was to present a clinical case using botulinum toxin type A as an alternative therapy to correct the gummy smile. A 22-year-old patient, presenting vertical maxillary growth, reporting aesthetic discomfort while smiling, chose for an alternative treatment therapy with the application of botulinum toxin to correct the accentuated gingival display. The results show that the toxin is a satisfactory treatment option and its indication is considered a fast, effective, easy and safe treatment method, being a more conservative approach compared to surgical procedures.

RESUMO O sorriso gengival, é uma das grandes queixas dos pacientes, devido a sua influência na auto estima do mesmo. Sua causa é multifatorial, podendo estar presente no excesso de crescimento vertical da maxila, contração labial excessiva, lábio superior curto e extrusão dos dentes anteriores. A aplicação da toxina botulínica pode ser associada a outros tratamentos ou isoladamente, de acordo com a necessidade de cada paciente. O objetivo desse trabalho foi apresentar um caso clinico utilizando a toxina botulínica tipo A como uma alternativa terapêutica para a correção do sorriso gengival. Paciente, 22 anos, apresentando crescimento vertical da maxila, relatando desconforto estético ao sorrir, optou pela alternativa terapêutica, com a aplicação da toxina botulínica para correção da exposição gengival acentuada. Os resultados encontrados mostram que a toxina é um tratamento satisfatório e sua indicação é considerada um tratamento rápido, eficaz, fácil e seguro. Um método mais conservador quando comparado aos procedimentos cirúrgicos.

Research advances in small molecule inhibitors of botulinum neurotoxins / 中国药理学与毒理学杂志

Botulinum neurotoxins (BoNTs) are the most deadly biological substances, including seven BoNT serotypes (A-G), and characterized by persistent flaccid paralysis of peripheral never terminals with high specificity called botulism. Due to their easy production and well-defined biological mechanism, BoNTs are wildly used in cosmetics and as very particular biopharmaceuticals in clinical therapy, so there is the risk of poisoning caused by accidental overdose. Also, because of their high toxicity, they are potential bioterrorism weapons. Thus, there is an urgent need for the development of BoNT inhibitors. In this review, based on the structure of BoNTs and the mechanism of botulism, we summarize recent advances in small molecule inhibitors targeting the Zn2+ active site of BoNT/A, such as 8-hydroxyquinoline and hydroxamic acid, or exosite of BoNT/A, small molecule inhibitors of BoNT/A through covalent binding that are irreversible, as well as small molecule inhibitors of targeting BoNT/B/ E light chain (LC).

Development of immunodetection system for botulinum neurotoxin serotype E

Background & objectives: Botulism, a potentially fatal paralytic illness, is caused by the botulinum neurotoxins (BoNTs) secreted by Clostridium botulinum. It is an obligate anaerobic, Gram-positive, spore-forming bacterium. BoNTs are classified into seven serotypes based on the serological properties. Among these seven serotypes, A, B, E and, rarely, F are responsible for human botulism. The present study was undertaken to develop an enzyme-linked immunosorbent assay (ELISA)-based detection system for the detection of BoNT/E. Methods: The synthetic gene coding the light chain of BoNT serotype E (BoNT/E LC) was constructed using the polymerase chain reaction primer overlapping method, cloned into pQE30UA vector and then transformed into Escherichia coli M15 host cells. Recombinant protein expression was optimized using different concentrations of isopropyl-?-D-1-thiogalactopyranoside (IPTG), different temperature and the rBoNT/E LC protein was purified in native conditions using affinity column chromatography. The purified recombinant protein was checked by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and further confirmed by western blot and matrix-assisted laser desorption ionization-tandem time-of-flight (MALDI-TOF). Polyclonal antibodies were generated against rBoNT/E LC using Freund's adjuvant in BALB/c mice and rabbit. Sandwich ELISA was optimized for the detection of rBoNT/E LC and native crude BoNT/E, and food matrix interference was tested. The developed antibodies were further evaluated for their specificity/cross-reactivity with BoNT serotypes and other bacterial toxins. Results: BoNT/E LC was successfully cloned, and the maximum expression was achieved in 16 h of post-induction using 0.5 mM IPTG concentration at 25癈. Polyclonal antibodies were generated in BALB/c mice and rabbit and the antibody titre was raised up to 128,000 after the 2nd booster dose. The developed polyclonal antibodies were highly specific and sensitive with a detection limit about 50 ng/ml for rBoNT/E LC and 2.5�[3] MLD50 of native crude BoNT/E at a dilution of 1:3000 of mouse (capturing) and rabbit (revealing) antibodies. Further, different liquid, semisolid and solid food matrices were tested, and rBoNT/E LC was detected in almost all food samples, but different levels of interference were detected in different food matrices. Interpretation & conclusions: There is no immune detection system available commercially in India to detect botulism. The developed system might be useful for the detection of botulinum toxin in food and clinical samples. Further work is in progress.

Clostridium botulinum spores in Polish honey samples

The aim of this study was an examination of 240 multifloral honey samples collected from Polish apiaries to determine Clostridium botulinum occurrence. Honey was collected from apiaries directly after the extraction process. Samples were inoculated by using the dilution and centrifugation method. Suspected isolates were examined by using mouse bioassay, polymerase chain reaction (PCR), and real-time PCR methods. C. botulinum type A and B strains were detected in 5 of 240 examined honey samples (2.1%). Bacterial strains were also detected that were phenotypically similar to C. botulinum but that did not exhibit the ability to produce botulinum toxins and did not show the presence of the botulinum cluster (ntnh and bont genes) or expression of the ntnh gene. The methods used in the examination, especially the expression analysis of ntnh gene, enabled specific analysis of suspected strains and could be used routinely in environmental isolate analyses of C. botulinum occurrence.

Effect of botulinum neurotoxin type A heavy chain on the growth-related proteins after spinal cord injury in rats / 中国比较医学杂志

Objective To investigate the effect of recombinant botulinum neurotoxin serotype A heavy chain (BoNT/A heavy chain)on local proteins which are related to nerve growth after spinal cord injury in rats,and to get some experimental evidence to explain the mechanism of BoNT/A heavy chain in stimulating neuritogenesis. Methods Recombinant botulinum neurotoxin serotype A heavy chain was applied locally or intrathecally to rats with ipsilateral semi-dissociated lumbar spinal injury. Local spinal tissue was extracted for general protein expression by two dimension electrophoresis plus nitrate silver staining after different time period of injury. Based on the results of 2-D gel electrophoresis,growth-associated protein 43(GAP-43)and of superior cervical ganglion 10(SCG 10)were selected to examine the changes of their expression and distribution features under BoNT/A heavy chain administration using SDS-PAGE,western blot and immunofluorescence. Results (1)The model of spinal cord injury(SCI)in this study was an ipsilateral semi-dissociated lumbar SCI in rat. The rats showed obvious motor and sensory dysfunction in the ipsilateral hind limb.(2)The results from 2-D gel electrophoresis plus nitrate silver staining showed that the administration of BoNT/A heavy chain based on SCI altered the local protein expression pattern. The decrease or increase in the expression of some protein dots /dots group was clearly seen after single SCI. However, these changes were transformed by BoNT/A heavy chain treatment,which appeared as a reversed pattern turning toward that in control group or further increased expression upon SCI,such as the dots located respectively at 35-45 kDa and 18-25 kDa level,pI between 5-7. In addition,the expression of the two dots located at the level as above increased after SCI only, and showed further increase in their expression with BoNT/A heavy chain intervention.(3)The changes of selective GAP-43 and SCG 10 expression and distribution by western blot and immunofluorescence indicated that the administration of BONT/A heavy chain based on SCI amplified the expression of GAP-43 and SCG 10(P < 0.05). Meanwhile,the positive immuonfluorescent staining for both GAP-43 and SCG 10 mainly distributed nearby the proximal area of injury, both cytoplasm and neuronal processes were positively stained. Conclusions Intrathecal delivery of BoNT/A heavy chain increases the expression of growth-associated proteins GAP 43 and SCG 10 after SCI in rats.

Estudio bioquímico del veneno de la anémona de mar Phymactis papillosa (Actiniidae)

En este trabajo se ha estudiado bioquímicamente el veneno de Phymactis papillosa, colectadas en la bahía de Ancón. El veneno fue obtenido mediante shock hipotónico y luego se liofilizó. El análisis electroforético del veneno soluble mostró la presencia de 5 bandas proteicas con pesos moleculares entre 5 y 25.1 kDa. El veneno soluble fue fraccionado por cromatografía de filtración en una columna de Sephadex G-50, obteniéndose cuatro picos de proteína (I, II, III y IV). Tanto en el veneno soluble como en las fracciones colectadas se midió actividad de proteasa, fosfolipasa, hialuronidasa, fosfatasa ácida y fosfatasa alcalina; así como, actividad hemolítica y neurotóxica. Se encontró actividad proteolítica sobre caseína, en el veneno soluble y en los picos I y III. No se detectó actividad de fosfolipasa, hialuronidasa, fosfatasa ácida y fosfatasa alcalina. La actividad hemolítica, ensayada sobre eritrocitos humanos, se encontró en el veneno soluble y en el pico II. Finalmente, tanto el veneno soluble como el pico III mostraron ser neurotóxicos al ser inyectados en ratones albinos vía intraperitoneal. Se concluye que el veneno soluble de P. papillosa tiene actividad proteolítica, hemolítica y neurotóxica

In this work, the poison of Phymactis papillosa collected in Ancón bay has been studied biochemically. The venom was obtained by hypotonic shock and then lyophilized. Electrophoretic analysis of the soluble poison showed the presence of 5 protein bands with molecular weights between 5 and 25.1 kDa. The soluble venom was fractionated by filtration chromatography on a Sephadex G-50 column, yielding four protein peaks (I, II, III and IV). In the soluble venom and collected fractions was measured protease activity, phospholipase, hyaluronidase, acid phosphatase and alkaline phosphatase; as well as hemolytic and neurotoxic activity. Proteolytic activity on casein was found in the soluble venom and peaks I and III. Was not detected phospholipase activity, hyaluronidase, acid phosphatase and alkaline phosphatase. Hemolytic activity on human red cells tested, was found in the soluble venom and peak II. Finally, the soluble venom as the peak III showed be neurotoxic when injected into white mice intraperitoneally. It is concluded that the soluble venom of P. papillosa has proteolytic, hemolytic and neurotoxic activity

Biological and molecular properties of yellow venom of the Amazonian coral snake Micrurus surinamensis

Abstract INTRODUCTION: The coral snake Micrurus surinamensis, which is widely distributed throughout Amazonia, has a neurotoxic venom. It is important to characterize the biological and molecular properties of this venom in order to develop effective antitoxins. METHODS: Toxins from the venom of M. surinamensis were analyzed by two-dimensional polyacrylamide gel electrophoresis and their neurotoxic effects in vivo were evaluated. RESULTS AND CONCLUSIONS: Most proteins in the venom had masses < 14kDa, low phospholipase A2 activity, and no proteolytic activity. The toxins inhibited the coagulation cascade. The venom had neurotoxic effects in mice, with a median lethal dose upon intravenous administration of 700 µg/kg. Immunogenic studies revealed abundant cross-reactivity of antielapidic serum with 14kDa toxins and limited cross-reactivity with toxins < 10kDa. These results indicate that antielapidic serum against M. surinamensis venom has weak potency (0.35mg/ml) in mice.

Gut microbiota and Alzheimer’s disease / 国际药学研究杂志

Gut microbiota GM consists of a complex community of microorganism species that live in the digestive tracts of animals including humans. Dysbiosis is believed to involve in the development of some diseases. Recently dysbiosis in the patients with Alzheimer’s disease AD and AD rat models was reported. GM may influence the pathogenesis and development of AD in several ways. Some neurotoxic substances produced by GM can invade into the brain via circulation and impair the neural functions. These substances include ammonia， cyanobacteria-produced β-N-methylamino-L-alanine， saxitoxin，anatoxin-α and amyloid. The decrease in brain-derived neurotrophic factor BDNF in hippocampus and cerebral cortex induced by dysbiosis contributes to the cognitive dysfunction. Dysbiosis related endotoxin can induce inflammation， which is one important risk factor for obesity， insulin resistance IR and type 2 diabetes mellitus TIDM . AD and diabetes have good correlation and similarity. Probiotics， prebiotics and Chinese herbal medicines can rebuild GM and have been reported to ameliorate the memory loss of AD patients or model rats. However， whether and how their preventative and therapeutic effects on AD mediated by GM are worthy of further investigation.

Gut microbiota and Alzheimer′s disease / 国际药学研究杂志

Gut microbiota(GM)consists of a complex community of microorganism species that live in the digestive tracts of animals including humans. Dysbiosis is believed to involve in the development of some diseases. Recently dysbiosis in the patients with Alzheimer′s disease(AD)and AD rat models was reported. GM may influence the pathogenesis and development of AD in several ways. Some neurotoxic substances produced by GM can invade into the brain via circulation and impair the neural functions. These sub?stances include ammonia,cyanobacteria-producedβ-N-methylamino-L-alanine,saxitoxin,anatoxin-αand amyloid. The decrease in brain-derived neurotrophic factor(BDNF)in hippocampus and cerebral cortex induced by dysbiosis contributes to the cognitive dys?function. Dysbiosis related endotoxin can induce inflammation,which is one important risk factor for obesity,insulin resistance(IR) and type 2 diabetes mellitus(TIDM). AD and diabetes have good correlation and similarity. Probiotics,prebiotics and Chinese herbal medicines can rebuild GM and have been reported to ameliorate the memory loss of AD patients or model rats. However ,whether and how their preventative and therapeutic effects on AD mediated by GM are worthy of further investigation.

Por que a ingestão de carambola é proibida para pacientes com doença renal crônica? / Why eating star fruit is prohibited for patients with chronic kidney disease?

Resumo Novos estudos têm mostrado o mecanismo pelo qual a carambola (Averrhoa carambola) torna-se tóxica para indivíduos com doença renal crônica (DRC). O objetivo deste trabalho foi revisar a literatura atual sobre o tema. Trata-se de artigo de revisão, com publicações de 2000 a 2014 disponíveis em bases de dados científicas. Há relatos de que a neurotoxicidade ocorre devido à presença de oxalato na carambola; porém, achados recentes mostram que o efeito neurotóxico se dá pela toxina caramboxina, que parece inibir o sistema GABAérgico, que é o principal sistema inibitório do sistema nervoso central (SNC), envolvendo alterações como soluços e confusão mental, até quadros mais sérios como convulsões e morte. É importante a ação multiprofissional para alertar os pacientes com DRC quanto à proibição do consumo da carambola.

Abstract New studies have shown the mechanism by which the star fruit (Averrhoa carambola) becomes toxic to individuals with chronic kidney disease (CKD). The aim of this study was to review the current literature on the topic. This is a review article, with publications from 2000 to 2014 available in scientific database. There are reports that neurotoxicity is due to the presence of oxalate in star fruit, but recent findings show that the neurotoxic effect of the toxin is by caramboxin, which appears to inhibit the GABAergic system which is the major inhibitory system in the central nervous system (CNS), involving changes as sobs and confusion, to more serious conditions such as seizures and death. It is important to multidisciplinary action to alert patients with CKD as the prohibition of the star fruit consumption.

Study on the mechanism of human large cell lung cancer NCI-H661 cells apoptosis induced by crotoxin / 国际肿瘤学杂志

Objective To observe the apoptosis of human large cell lung cancer NCI-H661 cells induced by crotoxin,and to explore its mechanism. Methods The growth suppression of crotoxin on the NCI-H661 cells was detected by CCK-8 colorimetry,and the formation of NCI-H661 cells was observed by the plat colony experiment. This experiment included 4 groups:negative control group,crotoxin group(60 μg/ ml cro-toxin acted for 24 h),crotoxin + SB203580 group(pretreated cells using 5 μmol/ L SB203580 for 1 h,then 60 μg/ ml crotoxin acted for 24 h),SB203580 group(pretreated cells using 5 μmol/ L SB203580 for 1 h,then cultivated cells using complete culture solution). They were detected that the cell cycle and apoptosis rate of NCI-H661 cells treated with crotoxin by the flow cytometry. Additionally,they were tested that the change of the cell cycle and apoptosis rate after the NCI-H661 cells were treated with crotoxin and the activity of p38MAPK was inhibited by SB203580. Results When the concentration of crotoxin was greater than or equal to 30 μg/ ml,the inhibitory effect of crotoxin on the activity of NCI-H661 cells and colony formation,and inhibi-tion rate rose with increasing function of time and drug concentration. Flow cytometry showed that the apoptosis rate of crotoxin group and crotoxin + SB203580 group were(16. 70 ± 1. 38)% and(2. 15 ± 0. 54)% ,com-pared to the control group(1. 47 ± 0. 29)% ,and the former difference was statistically significant and the latter was not statistically significant(t = - 18. 763,P = 0. 000;t = - 1. 935,P = 0. 125). The G1 period cells of crotoxin group and crotoxin + SB203580 group were(57. 25 ± 1. 09)% and(48. 04 ± 1. 03)% ,compared to the control group(47. 46 ± 0. 69)% ,and the former difference was statistically significant and the latter was not statistically significant(t = - 13. 124,P = 0. 000;t = - 0. 809,P = 0. 464). Conclusion Crotoxin can promote the apoptosis of human large cell lung cancer NCI-H661 cells,and this effect may be related to the excitation of p38MAPK signal pathway.

Toxicity study on bupivicaine to SH-SY5Y cells cultured by high-glucose / 重庆医学

Objective To discuss the effect of bupivacaine on SH‐SY5Y cells in high sugar environment and observe the ROS and apoptosis .Methods 1 mmol/L bupivicaine was added to medium with different concentrations of glucose for SH‐SY5Y cells , and the quantity of ROS in the cells and the situation of apoptosis were detected by flow cytometry ,and Western blot was uesd to detect the change of the related protein ,GRP78 .Results The contents of intarcellular ROS in different groups ,which had different concentration(7 .80 ,11 .10 ,13 .30 mmol/L) of sugar medium ,were high than those in groups with concentrations 5 .56 ,6 .10 ,7 .00 mmol/L of sugar medium ,and it showed statistical significance (P<0 .05) .Cell apoptosis rates among different groups had statisti‐cal significance(P<0 .05) .Expression of GRP78 in group of 5 .56 ,6 .10 and 7 .80 mmol/L were (1 .02 ± 0 .12) ,(0 .97 ± 0 .06) and (0 .49 ± 0 .04) ,respectively ,and they all were higher than that in group of 7 .00 mmol/L (0 .46 ± 0 .06) .The groups of 11 .10 mmol/L (0 .22 ± 0 .03) and 13 .30 mmol/L (0 .15 ± 0 .07) were lower than the other groups in the expression of GRP78 ,and all the difference shows statistical significance (P<0 .05) .Conclusion Increasing and apoptosis of intracellular ROS are associated with strengthened endoplasmic reticulum stress by bupivacaine .With the function degrading of GRP78 ,endoplasmic reticulum stress (ERS) may strengthen further .

Efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo animal / Neurotoxic effect of aqueous extract of boldo (Peumus boldus) in an animal model

Objetivos : Evaluar el efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo experimental. Materiales y métodos. Se diseñó un experimento, que incluyó 20 ratas macho Holtzman de 250 ± 15 gr, distribuidas aleatoriamente en cuatro grupos: el control negativo recibió solución salina (SS) por vía oral (VO), el control positivo que recibió 6-hidroxidopamina por vía intracraneal (VIC) y SS por VO, el grupo experimental 1 recibió extracto acuoso de boldo (EAB) por VO y el grupo experimental 2 recibió 6-hidroxidopamina por VIC y EAB por VO, en todos los casos durante 21 días. Se realizó una evaluación neurológica, la cual tuvo tres componentes: a) clínico, evaluado con el test de rotarod, b) bioquímico, mediante la determinación de niveles séricos de ácido úrico, y c) histopatológico, por inmunohistoquímica para neuronas dopaminérgicas de sustancia negra. Se empleó la prueba de Kruskal Wallis y el test de Dunn para evaluar las diferencias entre los grupos. Resultados. Se encontró disminución significativa en el tiempo de latencia del test de rotarod entre los grupos control negativo y control positivo (p<0,01), control negativo y experimental 1 (p=0,09), control negativo y experimental 2 (p<0,01), control positivo y experimental 1 (p=0,04), y experimental 1 y 2 (p=0,09). En la determinación de ácido úrico no hubo diferencia significativa intergrupal. En el conteo neuronal hubo depleción de neuronas dopaminérgicas totales, pero sin diferencia intergrupal. Conclusiones. Se evidencio un efecto neurotóxico del extracto acuoso de boldo en ratas macho de la cepa Holtzman a nivel clínico.

Objectives. To assess the neurotoxic effect of the aqueous extract of boldo (Peumus boldus) in an experimental model. Materials and methods. 20 male Holtzman rats of 250 ± 15 g were randomized into four groups: the negative control received saline solution (SS) orally (PO), the positive control received 6-hydroxydopamine intracranially (IC) and SS by PO. Experimental group 1 received aqueous extract of boldo (AEB) by PO, and experimental group 2 received 6-hydroxydopamine intracranially and AEB by PO. The experiment lasted 21 days. A neurological assessment was performed which had three components: a) clinical, evaluated with the rotarod test, b) biochemical, by measuring serum levels of uric acid, and c) histopathology, by immunohistochemistry for substantia nigra dopaminergic neurons. The Kruskal Wallis test and the Dunn test were used to assess differences between groups. Results. A significant decrease was found in the latency time of the rotarod test between the negative and positive control group (p<0.01), negative control and experimental 1 (p=0.09), negative control and experimental 2 (p<0.01), positive control and experimental 1 (p=0.04), and experimental 1 and 2 (p=0.09). There was no significant intergroup difference in the identification of uric acid. There was a depletion of the total dopaminergic neurons in the neuronal count, without intergroup difference. Conclusions. A neurotoxic effect of aqueous extract of boldo was recognized at a clinical level in Holtzman male rats.

Use of antivenoms for the treatment of envenomation by Elapidae snakes in Guinea, Sub-Saharan Africa

In Guinea Elapids are responsible for 20% of envenomations. The associated case fatality rate (CFR) ranged 15-27%, irrespective of treatment. Results We studied 77 neurotoxic envenomations divided in 3 groups: a set of patients that received only traditional or symptomatic treatments, and two other groups that received either 2 or 4 initial vials of Antivipmyn® Africa renewed as necessary. CFR was 27.3%, 15.4% and 17.6%, respectively. Although antivenom treatment was likely to reduce CFR, it didn’t seem to have an obvious clinical benefit for the patients, suggesting a low treatment efficacy. Mean delay to treatment or clinical stages were not significantly different between the patients who recovered and the patients who died, or between groups. Interpretation of these results is complicated by the lack of systematic studies under comparable conditions. Of particular importance is the absence of assisted ventilation, available to patients in all the other clinical studies of neurotoxic envenomation. Conclusion The apparent lack of clinical benefit may have several causes. The hypothesis of a limited therapeutic window, i.e. an insufficient formation of antigen-antibody complexes once toxins are bound to their targets and/or distributed beyond the reach of antivenom, should be explored.

Use of antivenoms for the treatment of envenomation by Elapidae snakes in Guinea, Sub-Saharan Africa

Background In Guinea Elapids are responsible for 20% of envenomations. The associated case fatality rate (CFR) ranged 15-27%, irrespective of treatment. Results We studied 77 neurotoxic envenomations divided in 3 groups: a set of patients that received only traditional or symptomatic treatments, and two other groups that received either 2 or 4 initial vials of Antivipmyn® Africa renewed as necessary. CFR was 27.3%, 15.4% and 17.6%, respectively. Although antivenom treatment was likely to reduce CFR, it didn’t seem to have an obvious clinical benefit for the patients, suggesting a low treatment efficacy. Mean delay to treatment or clinical stages were not significantly different between the patients who recovered and the patients who died, or between groups. Interpretation of these results is complicated by the lack of systematic studies under comparable conditions. Of particular importance is the absence of assisted ventilation, available to patients in all the other clinical studies of neurotoxic envenomation. Conclusion The apparent lack of clinical benefit may have several causes. The hypothesis of a limited therapeutic window, i.e. an insufficient formation of antigen-antibody complexes once toxins are bound to their targets and/or distributed beyond the reach of antivenom, should be explored. .

Mechanisms of oxaliplatin neurotoxicity and its predictions / 国际肿瘤学杂志

As the main drug in colorectal cancer chemotherapy,oxaliplatin is gradually infiltrated into other malignancies therapy.But oxaliplatin-induced peripheral neuropathy limits its clinical application.The mechanisms of oxaliplatin neurotoxicity are not yet clear.Recent researches show that the acute neurotoxicity of oxaliplatin is mediated through changes in Na + transient conductances.And the function of the mitogen-activated protein kinases in chronic neuropathy has already been demonstrated in vitro.Furthermore,numerous indicators can be used to predict oxaliplatin-induced peripheral neuropathy,which bring the hope for improving the continuity of chemotherapy and realizing personalized medicine therapy.

Occupational Neurotoxic Diseases in Taiwan

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization.