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.

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. ...

Pure neural leprosy: steroids prevent neuropathy progression

Multidrug therapy (MDT), with rifampicin, dapsone, and clofazimine, treats leprosy infection but is insufficient in arresting or preventing the nerve damage that causes impairments and disabilities. This case-series study evaluates the benefits of the combined use of steroids and MDT in preventing nerve damage in patients with pure neural leprosy (PNL). In addition to MDT, 24 patients (88 percent male aged 20-79 years, median=41) received a daily morning dose of 60 mg prednisone (PDN) that was gradually reduced by 10 mg during each of the following 5 months. PNL was clinically diagnosed and confirmed by nerve histopathology or PCR. A low prevalence (8.3 percent) of reaction was observed after release from treatment. However, most of the clinical parameters showed significant improvement; and a reduction of nerve conduction block was observed in 42 percent of the patients. The administration of full-dose PDN improved the clinical and electrophysiological condition of the PNL patients, contributing to the prevention of further neurological damage.

A poliquimioterapia (PQT), com rifampicina, dapsona, e clofazimina, trata a infecção na hanseníase, mas é insuficiente para interromper ou prevenir o comprometimento neurológico que causa as incapacidades e desabilidades, nesta enfermidade. Este estudo de série de casos avalia o benefício do uso combinado de prednisona e PQT na prevenção do dano neurológico em pacientes com a forma neural pura da hanseníase (FNP). Além do PQT, 24 pacientes (88 por cento homens, com idade variando entre 20-79, mediana=41) receberam uma dose diária de 60 mg prednisona que foi reduzida gradualmente na dose de 10 mg durante cada um dos 5 meses subseqüentes. FNP foi diagnosticada clinicamente e confirmada através do estudo histopatológico ou PCR. Baixa prevalência de reação (8,3 por cento) foi observada apenas após o final do tratamento. A maioria dos parâmetros clínicos mostrou melhora significativa e redução do bloqueio de condução foi observada em 42 por cento dos pacientes. A administração de doses altas de prednisona melhora a evolução clínica e eletrofisiológica de pacientes com a FNP de hanseníase, contribuindo na prevenção de novos comprometimentos neurológicos.

Algorithms as guides for the prevention of permanent nerve damage in leprosy patients.

The responsibility for treating leprosy patients is being passed on to the general medical and health care services, predominantly located in primary health care centres. It therefore becomes necessary for the staff of these services to have clear guidelines on what they should do to prevent permanent nerve damage and its consequences when they come across a leprosy patient with neuritis or nerve function deficit. Six algorithms to help achieve this purpose are presented in this article.

Avaliação sensitiva do nervo tibial através de monofilamentos em portadores de diabetes mellitus / Sensitive evaluation of the tibial nerve through monofilaments in diabetes mellitus patients

O diabetes mellitus, caracterizado pela deficiência absoluta ou relativa na secreção ou ação da insulina, levando ao comprometimento do metabolismo dos carboidratos, gorduras e proteínas, pode ocasionar várias anomalias fisiológicas, dentre as quais estão as neuropatias perféricas. A detecção precoce desta, pode prevenir o desencadeamento do déficit sensitivo, motor e autonômico, bem como a conseqüente alteração biomecânica, prevenindo, desta maneira, a formação de calosidades que podem favorecer as ulcerações e culminar em amputações. Diante de tal fato, realizamos o presente estudo objetivando a detecção do acometimento sensitivo do nervo tibial através de monofilamentos Semmes-Weinstein, em 27 indivíduos portadores de diabetes mellitus tipo II. A avaliação sensitiva foi realizada na região plantar de ambos os pés, no dermátomo sensitivo correspondente ao nervo tibial. Concomitantemente foi colhida a história clínica, sendo abordados itens como o tempo de duração do diabetes, a presença de formigamento, sensação de queimação, adormecimento e presença de quadro álgico nos pés; bem como realizada a avaliação clínica dos pés dos indivíduos diabéticos a fim de determinar a presença de ressecamento, calosidades, fissuras, ferimentos, ulcerações e amputações. Foi detectado o acometimento sensitivo do nervo tibial, sugestivo de neuropatia diabética em 15 dos 27 indivíduos avaliados, sendo que todos os indivíduos que apresentaram ferimentos, ulcerações e amputações estavam entre estes 15. Os monofilamentos se mostraram ser um método eficaz, de fácil aplicação e baixo custo para detecção de alteração sensitiva sugestiva de neuropatia diabética