Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats / 中国结合医学杂志

OBJECTIVE@#To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.@*METHODS@#Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.@*RESULTS@#EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01).@*CONCLUSION@#EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Peripheral neuropathy in COVID-19 is due to immune-mechanisms, pre-existing risk factors, anti-viral drugs, or bedding in the Intensive Care Unit / Neuropatia periférica na COVID-19 com mecanismos immunológicos, fatores de risco preexistentes, medicamentos antivirais e compressão dos nervos periféricos nos leitos da Unidade de Terapia Intensiva

ABSTRACT Background: This mini-review aims to summarize and discuss previous and recent advances in the clinical presentation, pathophysiology, diagnosis, treatment, and outcome of SARS-CoV-2-associated peripheral neuropathies. Methods: Literature review. Results: Altogether, 105 articles about SARS-CoV-2-associated neuropathy describing 261 patients were retrieved. Peripheral neuropathy in patients with COVID-19 is frequent and predominantly due to immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, due to the compression of peripheral nerves resulting from prolonged bedding in the Intensive Care Unit (ICU) and pre-existing risk factors such as diabetes. SARS-CoV-2 does not cause viral neuropathy. Neurotoxic drugs such as daptomycin, linezolid, lopinavir, ritonavir, hydro-chloroquine, cisatracurium, clindamycin, and glucocorticoids should be administered with caution and patients should be appropriately bedded in the ICU to prevent SARS-CoV-2-associated neuropathy. Patients with Guillain-Barré syndrome (GBS) benefit from immunoglobulins, plasma exchange, and steroids. Conclusions: Neuropathies of peripheral nerves in patients with COVID-19 are frequent and mostly result from immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, from the compression of peripheral nerves due to prolonged bedding on the ICU. SARS-CoV-2 does not cause infectious neuropathy.

RESUMO Introdução: A presente minirrevisão tem como objetivo resumir e discutir os avanços dos aspectos clínicos, fisiopatológicos, de diagnóstico, tratamento e evolução das neuropatias dos nervos periféricos associadas à COVID-19. Métodos: Revisão da literatura. Resultados: Foram avaliados 105 artigos sobre neuropatia associada à COVID-19. Nesses estudos, 261 pacientes apresentaram boa evolução. As neuropatias dos nervos periféricos em pacientes com COVID-19 são frequentes e se devem, principalmente, aos mecanismos immunológicos ou efeitos colaterais neurotóxicos dos medicamentos utilizados para o tratamento da COVID-19, a fatores de risco pré-existentes, como diabetes e, em menor parte, à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia viral. Os medicamentos neurotóxicos, como daptomicina, linezolida, lopinavir, ritonavir, hidro-cloroquina, cisatracúrio, clindamicina e glicocorticoides devem ser administrados com cautela, e os pacientes deve ser adequadamente admitidos nos leitos da UTI para prevenir o desenvolvimento de neuropatia associada à COVID-19. Pacientes com síndrome de Guillain-Barré (GBS) se beneficiam de imunoglobulinas, plasmaférese e esteroides. Conclusões: As neuropatias dos nervos periféricos em pacientes com COVID-19 são raras e predominantemente devidas aos efeitos colaterais neurotóxicos das mecanismos immunológicos ou drogas utilizadas para o tratamento de COVID-19 e, em menor parte, devido à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia infeciosa.

Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.

Interleukin-4 protects from chemotherapy-induced peripheral neuropathy in mice modal via the stimulation of IL-4/STAT6 signaling

Abstract Purpose: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Methods: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. Results: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. Conclusion: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.

Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61%) vs 23 (39%) males, and of whites, 49 (83.1%) vs 10 (16.9%) blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6). Regarding staging at diagnosis, 27 (45.7%) patients were in stage III-A, with 12 (20.3%) patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40) were: neutropenia (42.5%), diarrhea (47.5%), and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26) and sc (n=14) administration routes (P=0.343). In the group treated with thalidomide (n=19), 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038). Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%). Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

Chemotherapy-induced peripheral neuropathies: an integrative review of the literature / Neuropatía periférica inducida por la quimioterapia: revisión integradora de la literatura / Neuropatia periférica induzida pela quimioterapia: revisão integrativa da literatura

OBJECTIVE: To identify scientific studies and to deepen the knowledge of peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence for assistance to cancer patients. METHOD: Integrative review of the literature conducted in the databases Latin American and Caribbean Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), the Cochrane Library and the Spanish Bibliographic Index Health Sciences (IBECS). RESULTS: The sample consisted of 15 studies published between 2005-2014 that met the inclusion criteria. Studies showed aspects related to advanced age, main symptoms of neuropathy and chemotherapy agents as important adverse effect of neuropathy. CONCLUSION: We identified a small number of studies that addressed the topic, as well as low production of evidence related to interventions with positive results. It is considered important to develop new studies proposed for the prevention and/or treatment, enabling adjustment of the patient's cancer chemotherapy and consequently better service. .

OBJETIVO: Identificar las publicaciones científicas y profundizar el conocimiento acerca de las neuropatías periféricas inducidas por quimioterápicos antineoplásicos, buscando subsidios para la asistencia al paciente oncológico. MÉTODO: Revisión integradora de la literatura realizada en las bases de datos Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), en la biblioteca COCHRANE y el Índice Bibliográfico Español en Ciencias de la Salud (IBECS). RESULTADOS: La muestra estuvo constituida de 15 estudios publicados en el período de 2005 a 2014 que atendieron los criterios establecidos. Los estudios evidenciaron aspectos relacionados con la edad avanzada de los pacientes, principales síntomas de la neuropatía y los quimioterápicos que tienen la neuropatía como efecto adverso relevante. CONCLUSIÓN: Identificamos pequeño número de estudios que abordaban la temática, así como poca producción de evidencias relacionadas con las intervenciones con resultados positivos. Se considera importante el desarrollo de nuevos estudios con propuestas de prevención y/o tratamiento, facilitando la adecuación del paciente a la quimioterapia antineoplásica y consecuentemente una mejor asistencia. .

OBJETIVO Identificar publicações científicas e aprofundar o conhecimento sobre as neuropatias periféricas induzidas por quimioterápicos antineoplásicos, buscando subsídios para assistência ao paciente oncológico. MÉTODO Revisão integrativa da literatura realizada nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), na biblioteca COCHRANE e no Índice Bibliográfico Espanhol de Ciências da Saúde (IBECS). RESULTADOS A amostra foi constituída por 15 estudos publicados no período de 2005 a 2014 que atenderam os critérios estabelecidos. Os estudos evidenciaram aspectos relacionados à idade avançada dos pacientes, principais sintomas da neuropatia e os quimioterápicos que têm a neuropatia como efeito adverso relevante. CONCLUSÃO Identificamos pequeno número de estudos que abordavam a temática, assim como baixa produção de evidências relacionadas a intervenções com resultados positivos. Considera-se importante o desenvolvimento de novos estudos com propostas de prevenção e/ou tratamento, possibilitando ajustamento do paciente à quimioterapia antineoplásica e consequentemente melhor assistência. .

Neurotoxicidad secundaria a metronidazol: un efecto adverso reversible. Caso clínico / Reversible neurotoxicity secondary to metronidazole report of one case

Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

Relationship between Quality of Life and Nurse-led Bedside Symptom Evaluations in Patients with Chemotherapy-induced Peripheral Neuropathy

PURPOSE: This cross-sectional study aimed at determining the relationship between patient-reported quality of life (QOL) and nurse-led bedside evaluations of chemotherapy-induced peripheral neuropathy symptoms. METHODS: One hundred ninety-five patients treated at the oncology clinic at our institution were assessed using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity and nurse-led bedside examinations. The relationship between self-reported QOL and bedside examinations was evaluated using Spearman rank correlations. RESULTS: Scores of upper and lower extremity muscle strength based on the bedside examinations showed a weak negative correlation with the emotional well-being subscale of Functional Assessment of Cancer Therapy-General. Further, weak negative relationships were present between QOL and the following nurse-reported parameters: vibration perception in the hand, upper extremity muscle strength, touch and vibration perception in the feet, and tendon reflexes. CONCLUSION: Collectively, our results indicate that nurse-led bedside evaluation is a noninvasive and useful method for detecting neurotoxicity and evaluating the patient's QOL both during and after treatment.

Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial / Vitamina E na prevenção de neuropatia periférica induzida pela oxaliplatina: estudo clínico piloto randomizado

Oxaliplatin is one of the chemotherapy regimens most used for treating colorectal cancer. One of the main limitations to its use is induction of peripheral neuropathy. Previous studies have shown that vitamin E can reduce the incidence of peripheral neuropathy by 50%. This study aimed to assess the effectiveness of vitamin E for prevention of oxaliplatin-induced peripheral neuropathy.

Prospective, phase II, randomized pilot study developed at a university hospital in the Greater ABC region.

Patients were randomized five days before starting oxaliplatin treatment, to receive either vitamin E or placebo until the end of the chemotherapy regimen. The outcome was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3, and specific gradation scales for oxaliplatin-induced peripheral neuropathy. Patients with colorectal and gastric cancer who had been scheduled to receive oxaliplatin-based chemotherapy were included. Both groups received calcium and magnesium supplementation before and after oxaliplatin infusions.

Eighteen patients were randomized to the vitamin E group and 16 to the placebo group. Cumulative incidence of 83% with peripheral neuropathy grades 1/2 was observed in the vitamin E group, versus 68% in the placebo group (P = 0.45). A trend towards more diarrhea was observed among patients who received vitamin E (55.6% vs. 18.8%; P = 0.06). There were no other significant differences in toxicity between the groups.

No significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy was demonstrated through vitamin E use.

A oxaliplatina é um dos quimioterápicos mais utilizados no tratamento do câncer colorretal, sendo a indução da neuropatia periférica (NP) uma das principais limitações para o seu uso. Trabalhos anteriores demonstraram que a vitamina E poderia reduzir a incidência dessa neuropatia em 50%. Este estudo teve como objetivo avaliar a efetividade da vitamina E na prevenção da NP induzida pela oxaliplatina.

Estudo piloto prospectivo e randomizado de fase II desenvolvido em hospital universitário do Grande ABC.

Os pacientes foram randomizados para receber vitamina E ou placebo por cinco dias antes do início do tratamento com oxaliplatina e até o término do regime quimioterápico. O desfecho foi avaliado através dos Critérios Comuns de Toxicidade do Câncer versão 3 (CTCAE) e escalas específicas de gradação da NP induzida por oxaliplatina. Foram incluídos pacientes com câncer colorretal e gástrico programado para receber quimioterapia baseada em oxaliplatina. Ambos os grupos receberam suplementação de cálcio e magnésio antes e depois das infusões de oxaliplatina.

Dezoito pacientes foram randomizados para grupo da vitamina E e 16 para o grupo placebo. Observou-se incidência cumulativa de 83% das classes I/II de neuropatia periférica no grupo da vitamina E, contra 68% no grupo placebo (P = 0,45). Observou-se maior tendência à diarreia em pacientes que receberam vitamina E (55,6% versus 18,8%, P = 0,06). Não houve outras diferenças significativas quanto às toxicidades entre os grupos. ...

[Subclinical neuropathy in workers occupationally exposed to n-hexane]

N-Hexane is widely used in the production of glues, lacquers, paints, plastics, and rubber products. Consequently, a significant potential for exposure to this toxic solvent exists in industrial settings. This study was undertaken to assess the neurophysiological abnormalities in shoe-makers occupationally exposed to n-hexane and determine whether these abnormalities have any correlation with important occupational parameters. Neurophysiological examinations of upper and lower extremities were made in 27 male-workers, and the results were compared with a sex- and age-matched reference group. In addition, the extent of exposure of individual workers and their urinary concentration of free 2,5-hexanedione were determined. Data were analyzed using the Statistical Package for Social Sciences [version 16.0. for windows]. The time-weighted average exposure to n-hexane and the mean urinary concentration of free 2,5-hexanedione were both lower than the respective TLV-TWA and Biological Exposure Index [BEI] values proposed by ACGIH. Although neurological examinations and nerve conduction velocities were normal, significant negative correlations were observed between the urinary concentration of free 2,5-hexanedione and the sensory nerve action potential [SAP] amplitudes for median [r=-0.67, p<0.001] and sural [r=-0.52, p<0.008] nerves. Reduced SAP amplitude for median and sural nerves appears to be the primary neurotoxic effect of 2,5-hexanedione and can be used as an appropriate indicator for screening subclinical peripheral neuropathy in n-hexane-exposed workers

Neuropatia periférica induzida por quimioterapia: uma revisão de literatura / Chemotherapy-induced peripheral neuropathy: a literature review

Peripheral neuropathy is a common side effect in patients undergoing cancer treatment with chemotherapy. This condition can affect patients in several different ways, interfering in their activities of daily living and autonomy. The present study aimed to review the literature on chemotherapy-induced peripheral neuropathy and its treatment or other possible interventions. The findings reveal that chemotherapy-induced peripheral neuropathy is a common condition that affects patients undergoing treatment with some specific drugs. Besides, several different substances have been used to treat or control this condition, although no significant evidence could be found in these studies.

A neuropatia periférica é um efeito colateral comum em pacientes sob tratamento quimioterápico. Essa condição pode se manifestar de diversas maneiras, interferindo na qualidade de vida e na autonomia nas atividades de vida diária dos pacientes em questão. O presente trabalho teve como objetivo revisar a literatura referente à neuropatia periférica induzida por quimioterapia, bem como propostas de tratamento e intervenção para o efeito colateral em questão. Foi possível observar que a neuropatia periférica induzida por quimioterapia é uma condição comum a pacientes sob tratamento com alguns quimioterápicos específicos. Além disso, foi possível identificar, embora sem evidência significativa, que diversas substâncias vêm sendo utilizadas como possível tratamento ou paliativo para o efeito colateral em questão.

Avaliação dos monofilamentos de Semmes-Weinstein e de um questionário de neurotoxicidade como instrumentos de detecção de neuropatia periférica induzida por quimioterapia / Evaluation of the Semmes-Weinstein Monofilaments and of a neurotoxicity questionnaire as tools to detect chemotherapy induced peripheral neuropathy

Estudo de corte transversal, comparativo, que investigou o uso dos Monofilamentos de Semmes-Weinstein (MSW) e do Questionário de Neurotoxidade Induzida por Antineoplásicos(QNIA) na detecção de neuropatia periférica sensorial em pessoas tratadas com quimioterápicos potencialmente neurotóxicos. A amostra foi composta por 117 indivíduos, subdividos em 02 grupos: pacientes e controles. O grupo pacientes foi composto por 87 pessoas em tratamento com oxaliplatina ou taxanes (paclitaxel ou docetaxel) e que haviam realizado no mínimo um ciclo de quimioterapia. O grupo controle foi composto por 30 pessoas jamais submetidas a qualquer tratamento antineoplásico. O projeto foi aprovado em todas as instâncias necessárias e atendeu às recomendações da Resolução 196/96. Para a coleta de dados foram utililizados os seguintes instrumentos: Formulário para dados sociodemográficos; Formulário para dados clínicos e Escala de Performance de ECOG; QNIA e Kit Estesiômetro Sorri®. Os dados foram inseridos no programa SPSS, versão 15.0, onde foram tratados e analisados, utilizando-se estatística descritiva, correlacional e comparativa, considerando-se um nível de significância de 5%. A média de idade dos pacientes foi de 54 anos (DP=11,9anos) e 44 anos para o grupo controle (DP=12,7 anos). Ambos os grupos foram compostos por mulheres casadas, com baixos níveis de escolaridade e socioeconômicos. A capacidade funcional dos grupos evidenciou significativa diferença entre eles (p=0,000). No grupo pacientes, o câncer de mama foi o mais frequente seguido pelos tumores de colon/reto e ginecológicos. Houve predomínio de protocolos envolvendo paclitaxel (68,9%; n=60) e oxaliplatina (28,73%; n=25).Na validação do QNIA, evidenciou-se boa confiabilidade do instrumento, com um alfa de Cronbach igual a 0,863. O teste de amostras pareadas evidenciou boa consistência interna. Na comparação entre os grupos foram encontradas diferenças estatisticamente significativas entre elesAU)

This transversal and comparative study investigated the use of the Semmes-Weinstein Monofilaments (SWM) and the Antineoplastic Induced Neurotoxicity Questionnaire (AINQ) to detect sensory neuropathy in persons receiving neurotoxic chemotherapy. A sample of 117 persons were divided into 02 groups: patient and control. The patient group included 87 persons who had completed at least one chemotherapy cycle with oxaliplatin or taxanes (paclitaxel or docetaxel). The control group included 30 people who had never received any antineoplastic treatment. The project had IRB approval and met the Resolution 196/96 recommendations. The data were collected using the following tools: a Sociodemographic Form, a Clinical Data Form, the ECOG Performance Scale, the AINQ, and a SWM Kit. Data were entered into the SPSS version 15.0, cleared up and analyzed using descriptive, correlational and comparative statistics, with a significance level of 5%. The mean age of the patients was 54 years (SD=11.9 years) and of the control group was 44 years (SD=12.7 years). Both groups were composed mainly by married women, with low socioeconomic and educational level. Functional performance was significantly different between the two groups (p=0,000). Breast cancer was the most frequent type of cancer in the patients, followed by colorectal and gynecologic tumors. The majority were in paclitaxel (68.9%; n=60) and oxaliplatin (28.73%; n=25) protocols. The AINQ was validated and showed good reliability, with a Cronbach alpha of 0.863. The results of the paired samples T- test confirmed good internal consistence. There were statistically significant differences (p<0.001) for all symptoms between the groups. Chemotherapy Induced Peripheral Neuropathy (CIPN) symptoms were not related to the type of the chemotherapy drug (p=0.478). In the patients group, the hand esthesiometry showed higher sensory changes frequency in all points of the ulnar, median and radial nerves (p<0.05)...

Vincristine induced neurotoxicity in cancer patients.

Ten out of 20 children, treated with usual doses of vincristine for various types of childhood cancers, developed neurotoxicity during treatment. Peripheral neurotoxicity (mixed motor-sensory 4/10, pure motor 3/10, pure sensory 3/10) was seen in the form of weakness of lower limbs, areflexia, neuropathic pain, or sensory loss. Autonomic neuropathy presented as constipation and urinary retention in 2 children, while 2 children developed encephalopathy in form of seizures, confusion, aphasia, and transient blindness. In children with severe neuropathy, vincristine administration was withheld/dose reduced till clinical improvement started, which took about 2-3 weeks time. Nerve conduction velocity showed motor-sensory axonal polyneuropathy. Electrophysiological abnormalities were found to persist even six months after clinical recovery in children with neurotoxicity. We found a relatively higher incidence of vincristine induced neuropathy in Indian children, which was probably due to coexistence of severe malnutrition in them.

Occupational Neurological Disorders in Korea

The purpose of this article was to provide a literature review of occupational neurological disorders and related research in Korea, focusing on chemical hazards. We reviewed occupational neurological disorders investigated by the Occupational Safety and Health Research Institute of Korean Occupational Safety and Health Agency between 1992 and 2009, categorizing them as neurological disorders of the central nervous system (CNS), of the peripheral nervous system (PNS) or as neurodegenerative disorders. We also examined peer-reviewed journal articles related to neurotoxicology, published from 1984 to 2009. Outbreaks of occupational neurological disorder of the CNS due to inorganic mercury and carbon disulfide poisoning had helped prompt the development of the occupational safety and health system of Korea. Other major neurological disorders of the CNS included methyl bromide intoxication and chronic toxic encephalopathy. Most of the PNS disorders were n-hexane-induced peripheral neuritis, reported from the electronics industry. Reports of manganese-induced Parkinsonism resulted in the introduction of neuroimaging techniques to occupational medicine. Since the late 1990s, the direction of research has been moving toward degenerative disorder and early effect of neurotoxicity. To understand the early effects of neurotoxic chemicals in the preclinical stage, more follow-up studies of a longer duration are necessary.

Lead-induced peripheral neuropathy following ayurvedic medication.

Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning.

Efecto de Spirulina platensis en la neuropatía axonal inducida por acrilamida en ratones / Effect of Spirulina platensis on acrylamide-induced axonal neuropathy in mice

INTRODUCCIÓN: Spirulina platensis es una microalga verde-azul de alto valor nutricional, la cual ha sido empleada como suplemento dietético. Varios de sus constituyentes ayudan al mantenimiento de la estructura y función de los tejidos nerviosos. OBJETIVO: determinar el efecto de esta microalga en un modelo de neuropatía axonal inducida por acrilamida, en ratones. MÉTODOS: el modelo consistió en la administración diaria de 70 mg/kg de acrilamida, por vía subcutánea, durante 3 semanas consecutivas; con la estimación del efecto neurotóxico de este compuesto mediante el registro, en los músculos de la pierna, del potencial de acción muscular compuesto, durante la estimulación supramáxima del nervio ciático. Después de finalizar las inyecciones de acrilamida, S. platensis se administró por vía oral, en dosis de 400 mg/kg, durante 5 semanas. RESULTADOS: al concluir la administración de acrilamida los animales presentaron una disminución estadísticamente significativa de los potenciales, acompañada de signos motores de neuropatía. La administración de S. platensis acortó el período recuperativo, lo que se evidenció por un restablecimiento más rápido del valor de los potenciales, así como por una disminución progresiva de la proporción de animales afectados. CONCLUSIONES: los resultados demuestran un efecto beneficioso de S. platensis en la neuropatía axonal inducida por acrilamida.

INTRODUCTION: Spirulina platensis is a green-blue microalga of a high nutritional value, which has been used as dietary supplement. Some of its constituents help in maintenance of structure and function of nerve tissues. OBJECTIVE: to determine the effect of this microalga on a model of acrylamide-induced axonal neuropathy in mice. METHODS: model included daily administration of 70 mg/kg of acrylamide (subcutaneous route) during 3 consecutive weeks; with estimation of neurotoxic effect of this compound by means of registry, in leg muscles, of composed muscular action potential, during supramaximal stimulation of sciatic nerve. After injections of acrylamide, S. platensis was administered per os, in doses of 400 mg/kg during 5 weeks. RESULTS: at the end of acrylamide administration animals showed a significance decrease of potentials, accompanied by the motor signs of neuropathy. Administration of S. platensis shortens recovery period, evidenced by a quicker restoration of potential values, as well as by a progressive decrease of affected animals' ratio. CONCLUSIONS: findings showed a beneficial effect of S. platensis on acrylamide-induced axonal neuropathy.

Ganglioside GM1 (porcine) ameliorates paclitaxel-induced neuropathy in rats.

BACKGROUND: Paclitaxel, an anti-neoplastic agent effective against several solid tumors, has several side effects including peripheral neuropathy. So far, there are no effective treatments for this complication. Monosialic acid ganglioside (GM1) has been shown to protect neurons against injuries and degeneration. However, its efficacy in the treatment of paclitaxel-induced neuropathy has not been verified. OBJECTIVE: To evaluate the effect of porcine GM1 on neurophysiological abnormalities in rats receiving paclitaxel. MATERIAL AND METHOD: Fifty-four Wistar rats were divided into control, vehicle for paclitaxel (Cremophor EL), paclitaxel, and paclitaxel + GM1 groups. Paclitaxel 16 mg/kg/week for five consecutive weeks was given intraperitoneally. Treatment with 30 mg/kg 5 days per week of GM1 was started 3 days prior to the first dose and continued until 3 days after the last dose of paclitaxel. Tail and hind paw thermal thresholds including tail motor nerve conduction velocity (MNCV) were measured prior to and after the start of treatments. Histopathology of the sciatic nerve was also examined. RESULTS: Paclitaxel alone induced thermal hypoalgesia and reduced tail MNCV Less severe abnormalities were also found with the vehicle. GM1 appeared to prevent the development of hypoalgesia and ameliorated the decreased MNCV without any evidence of Guillain-Barre Syndrome. Mild endoneurial edema and axonal degeneration in the sciatic nerve sections were seen in paclitaxel treated rats. Microtubule accumulation and activated Schwann cell were also presented in the paclitaxel treated groups. CONCLUSION: These data suggest that porcine GM1 may be useful in the prevention and treatment of paclitaxel-induced neuropathy. However the adverse effect of Cremophor EL should be of concern.

Adverse effects of antiretroviral treatment.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has led to significant reduction in acquired immune deficiency syndrome (AIDS)-related morbidity and mortality. Adverse drug reactions (ADRs) to antiretroviral treatment (ART) are however, major obstacles in its success. AIMS: We sought to study the adverse effects of ART in a resource-restricted setting in India. METHODS: Hundred patients on ART were studied prospectively over a period of two years. All patients were asked to visit the clinic if they developed any symptoms or on a monthly basis. They were screened clinically and investigated suitably for any ADRs. RESULT: Out of the 100 patients, ten patients did not come for follow-up; only 90 cases were available for evaluation. ADRs were observed in 64 cases (71.1%) - the maximal frequency of ADRs was seen with zidovudine (AZT) (50%) followed by stavudine (d4T) (47.9%), efavirenz (EFV) (45.4%) and finally, Nevirapine (NVP) (18.4%). Most common ADRs were cutaneous (44.4%) followed by hematological (32.2%), neurological (31.1%), metabolic (22.2%) and gastrointestinal (20%). Most common cutaneous ADRs observed were nail hyperpigmentation (14.4%) and rash (13.3%). Immune reconstitution inflammatory syndrome (IRIS) was observed as a paradoxical reaction to ART in 20 (22.2%) cases. CONCLUSION: To optimize adherence and thus, efficacy of ART, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious.

Arsenic in the environment: effects on human health and possible prevention.

Arsenic is a major environmental pollutant and exposure occurs through environmental, occupational and medicinal sources. The contaminated drinking water is the main source of exposure and affected countries are India (West Bengal), Bangladesh, China, Taiwan, Thailand, Chile, Argentina and Romania. Concentrations of arsenic in affected areas are several times higher than the maximum contamination level (MCL) (10 microg/l). Arsenic exposure to human results in degenerative, inflammatory and neoplastic changes of skin, respiratory system, blood, lymphatic system, nervous system and reproductive system. There is no particular remedial action for chronic arsenic poisoning. Low socioeconomic status and malnutrition may increase the risk of chronic toxicity. Early intervention and prevention can give the relief to the affected population.