RESUMO
Resumo Objetivo: Verificar a presença das células-tronco mesenquimais (MSC) na área próxima ao nervo óptico de coelhos previamente lesado com álcool absoluto. Métodos: Os 12 coelhos da raça Nova Zelândia foram distribuídos em 2 lotes. Após sedação, cada olho do animal recebeu uma injeção retrobulbar de 1 ml de álcool absoluto em um dos olhos e de 1 ml de solução fisiológica 0,9% (SF) no olho contralateral. Após 15 dias deste procedimento inicial todos os olhos dos animais pertencentes ao lote A, receberam via retrobulbar, uma solução contendo MSC de tecido adiposo humano e previamente marcadas com Qdots,. Todos os olhos dos animais do lote B receberam solução PBS. Resultados: Após 15 dias desta última aplicação os animais foram sacrificados e as lâminas foram analisadas. A presença das MSC foi observada em 100% dos olhos dos animais do lote A. Conclusão: Os resultados sugerem que a marcação prévia das MSC com Qdots permitiu o acompanhamento das mesmas na região aplicada e em áreas mais internas do nervo óptico. A permanência de MSC após 15 dias de aplicação ao redor do nervo óptico sugere a viabilidade e possível participação das mesmas no processo de regeneração do tecido lesado. Nas condições deste estudo, a via de aplicação retrobulbar permitiu a mobilização das células tronco do local de aplicação até áreas centrais dos nervos ópticos nos animais do lote A, sugerindo que esta poderá ser uma via de acesso eficaz para as MSC no processo de regeneração de neuropatias ópticas.
Abstract Obtective: To verify the presence of mesenchymal stem cells (MSC) in the area close to the optic nerve of previously injured with absolute alcohol. Methods: Twelve New Zealand breed rabbits were divided into two groups, and after sedation, each eye of the animal received a retrobulbar injection of 1 ml of absolute ethanol in one eye, and 1 ml of physiological solution 0.9 % (PS) in the contralateral eye. After 15 days all eyes of animals belonging to group A, received via retrobulbar a solution containing MSCs from human adipose tissue (AT) and previously marked with Qdots, while all eyes of animals from group B received solution containing PBS. Results: The presence of MSC was observed in 100% of the eyes of the animals of group A and the more central areas near and into the optic nerve. Conclusion: The results suggest that the appointment of MSC with Qdots allowed their follow-up applied in the region and in the inner areas of the optic nerve. The MSC permanence after 15 days of application around the optic nerve suggests the feasibility and possible involvement of the same during the damaged tissue regeneration process. Under the conditions of this study, the route of retrobulbar application and the presence of the stem cells to the central areas of the optic nerves in animals of group A, suggests that this might be an effective approach for MSCs in regeneration process of optic neuropathies.
Assuntos
Animais , Feminino , Coelhos , Doenças do Nervo Óptico/terapia , Tecido Adiposo/citologia , Adipócitos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Regeneração Nervosa , Nervo Óptico/citologia , Semicondutores , Diferenciação Celular , Células Cultivadas , Doenças do Nervo Óptico/induzido quimicamente , Método Duplo-Cego , Pontos Quânticos , Injeções IntraocularesRESUMO
BACKGROUND: Toxic optic neuropathies are alterations of the optic nerve and can be caused by environmental, pharmacological, or nutritional agents. CASE: It is about a 7-year-old male patient, a native of the State of Mexico, Mexico who was diagnosed with cervical mycobacterial lymphadenitis that required management with linezolid. OBSERVATIONS: After 7 months of treatment, visual acuity of the left eye decreased and was accompanied by headache. Neuroinfection and other central nervous system affections were discarded. An adverse effect related to treatment with linezolid was suspected, and linezolid was suspended. The symptoms subsided after discontinuation; however, the patient continued to show decreased visual acuity of the left eye, assessed by his ability to count 2 fingers. The right eye remained unaffected. CONCLUSIONS: Neurotoxicity can be decreased by reducing the total dose of linezolid or by administrating it in an intermittent form. To avoid progression and loss of vision, we suggest frequent periodic ophthalmological evaluation in patients treated with linezolid.
Assuntos
Antibacterianos/efeitos adversos , Linezolida/efeitos adversos , Linfadenite/tratamento farmacológico , Linfadenite/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Doenças do Nervo Óptico/induzido quimicamente , Criança , Humanos , Masculino , Micobactérias não Tuberculosas , Acuidade VisualRESUMO
OBJECTIVE: Peripheral neuropathy (PN) and optic neuropathy (ON) associated with linezolid use are described in the adult literature; however limited information is available in pediatrics. The purpose of this communication is to summarize pediatric cases of linezolid-associated neuropathy and to increase awareness of these neurologic side effects so that clinicians can most appropriately balance the benefits and risks of linezolid in the pediatric population. METHODS: A search of the FDA Adverse Events Reporting System was performed for all pediatric cases of neuropathy from April 2000-2009. AERS includes both inpatient and outpatient data. Inpatient utilization patterns for linezolid were also assessed from January 2000 to December 2008. RESULTS: Eight pediatric cases of linezolid-associated neuropathy were identified. Treatment duration ranged from 4 weeks to 1 year. Five patients had PN alone, one had only ON and two had both. Symptoms of PN included pain, numbness, weakness, and paresthesias. Symptoms of ON included decreased visual acuity and color vision. Three children had other adverse events associated with linezolid including acidosis, anemia, and leukopenia. Outcomes were reported in 5 cases. Resolution of symptoms occurred between 2 weeks and 6 months after discontinuation of linezolid. Utilization data showed that during the study period, overall inpatient utilization of linezolid had increased. CONCLUSIONS: While linezolid may be used to treat serious infections often needing extended courses of therapy, potential safety concerns should be kept in mind. In the circumstance of prolonged use of linezolid in children, it is likely that more cases of neuropathy may occur.
Assuntos
Acetamidas/efeitos adversos , Doenças do Nervo Óptico/induzido quimicamente , Oxazolidinonas/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Adolescente , Anti-Infecciosos/efeitos adversos , Argentina/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Infecções/tratamento farmacológico , Linezolida , Masculino , Doenças do Nervo Óptico/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Perfluorocarbon liquid (PFC) has been used for almost 2 decades in many intraocular procedures. In this report we comment on 3 patients with retained PFC in vitreous cavity (VC) following complicated phacoemulsification surgery. METHODS: Retrospective chart review. RESULTS: All patients had pars plana vitrectomy performed after the initial complicated cataract surgery in which PFC was inappropriately used to recover a dropped nuclei. The time between the first and the second surgery was 1 week for the first patient, 2 weeks for the second patient, and 3 months for the third patient. A better outcome was seen in the patient with the shorter interval between the surgeries. Reduced visual acuity, retinal and optic nerve pallor were found in the patient that had the PFC in the VC for a longer period. INTERPRETATION: Complete consideration of the potential risks should be performed before attempting to recover fallen nuclei by injecting PFC. If complications cannot be resolved in the same surgical procedure, it is advisable to reschedule the patient for a posterior segment surgery.
Assuntos
Fluorocarbonos/efeitos adversos , Complicações Intraoperatórias , Subluxação do Cristalino/cirurgia , Doenças do Nervo Óptico/induzido quimicamente , Facoemulsificação , Doenças Retinianas/induzido quimicamente , Idoso , Feminino , Humanos , Subluxação do Cristalino/etiologia , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Óptico/diagnóstico , Doenças Retinianas/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , Acuidade Visual/efeitos dos fármacos , Vitrectomia , Corpo Vítreo/efeitos dos fármacosRESUMO
Adverse effects of acute exposure to hydrogen sulfide (H2S) are well documented, but long-term effects of occupational exposure to low levels of the gas are not. To evaluate effects of such exposure we performed physical, neurologic, psychiatric, and chemosensory (smell and taste) examinations of four workers who were present but did not lose consciousness when the gas was accidentally released at a construction site. None of the four workers tested positive for functional problems, but all met diagnostic criteria for at least three, and up to eight, H2S-induced neuropsychiatric clinical disorders and from zero to two subclinical disorders. All four had abnormal P300 evoked responses (electrical neurophysiologic tests of brain waves). Our data indicate that exposures to even relatively low concentrations of H2S are hazardous. A rigorous epidemiologic investigation of persons who work with H2S is warranted.
Assuntos
Acidentes de Trabalho , Poluentes Atmosféricos/efeitos adversos , Sulfeto de Hidrogênio/efeitos adversos , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Encefalopatias/induzido quimicamente , Transtornos Cognitivos/induzido quimicamente , Doenças dos Nervos Cranianos/induzido quimicamente , Potenciais Evocados P300/efeitos dos fármacos , Cefaleia/induzido quimicamente , Humanos , Doenças do Nervo Óptico/induzido quimicamente , Polineuropatias/induzido quimicamente , Transtornos de Estresse Pós-Traumáticos/etiologia , Ilhas Virgens Americanas , Nervo Vestibulococlear/efeitos dos fármacosRESUMO
We studied 62 patients aged 48 years as an average and diagnosed with bilateral optical neuropathy during an epidemics in Pinar del Río province. Of these patients, 42 showed the optical form whereas 20 had the mixed form of optical neuropathy. We researched into the levels of formate and folate in serum and cerebrospinal fluid samples and we found a marked deficiency of folates in more than 50% of samples and high formate concentration levels in almost 25% of samples. We concluded that nutritional shortages that lead to a reduction of folates, and the intake of small amounts of methanol in alcoholic drinks could lead to lacking energetic states which would facilitate that the optical nerve be affected and the epidemic optical neuropathy appear.
Assuntos
Surtos de Doenças , Deficiência de Ácido Fólico/complicações , Ácido Fólico/sangue , Ácido Fólico/líquido cefalorraquidiano , Formiatos/sangue , Formiatos/líquido cefalorraquidiano , Doenças do Nervo Óptico/epidemiologia , Consumo de Bebidas Alcoólicas , Feminino , Humanos , Masculino , Metanol/efeitos adversos , Pessoa de Meia-Idade , Doenças do Nervo Óptico/sangue , Doenças do Nervo Óptico/líquido cefalorraquidiano , Doenças do Nervo Óptico/induzido quimicamente , Fatores de Risco , Solventes/efeitos adversosRESUMO
We studied 62 patients aged 48 years as an average and diagnosed with bilateral optical neuropathy during an epidemics in Pinar del RÝo province. Of these patients, 42 showed the optical form whereas 20 had the mixed form of optical neuropathy. We researched into the levels of formate and folate in serum and cerebrospinal fluid samples and we found a marked deficiency of folates in more than 50 of samples and high formate concentration levels in almost 25 of samples. We concluded that nutritional shortages that lead to a reduction of folates, and the intake of small amounts of methanol in alcoholic drinks could lead to lacking energetic states which would facilitate that the optical nerve be affected and the epidemic optical neuropathy appear.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Ácido Fólico/sangue , Ácido Fólico/líquido cefalorraquidiano , Deficiência de Ácido Fólico/complicações , Surtos de Doenças , Doenças do Nervo Óptico/epidemiologia , Formiatos , Consumo de Bebidas Alcoólicas , Doenças do Nervo Óptico/sangue , Doenças do Nervo Óptico/induzido quimicamente , Doenças do Nervo Óptico/líquido cefalorraquidiano , Metanol , Fatores de Risco , SolventesRESUMO
This report describes clinical and pathological findings in 2 flocks in Brazil where blindness and deaths in sheep occurred after closantel overdosage. Depression, weakness, and blindness affected 37 animals and 17 died in 2 flocks of 190 animals. Two animals submitted for ophthalmic examination showed no inflammation in the anterior segment of both eyes; posterior segment evaluation by indirect ophthalmoscopy suggested retinal degeneration. One postmortem evaluation local spongy vacuolization was in several regions of the brain and the optical nerves had severe axonal degeneration.
Assuntos
Anti-Helmínticos/intoxicação , Doenças do Nervo Óptico/veterinária , Salicilanilidas/intoxicação , Doenças dos Ovinos/induzido quimicamente , Animais , Cegueira/induzido quimicamente , Cegueira/veterinária , Brasil , Overdose de Drogas , Degeneração Neural/induzido quimicamente , Degeneração Neural/veterinária , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia , Doenças do Nervo Óptico/induzido quimicamente , Doenças do Nervo Óptico/patologia , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/veterinária , Ovinos , Doenças dos Ovinos/patologiaRESUMO
BACKGROUND: Blindness from an optic neuropathy recently occurred as an epidemic affecting 50,000 patients in Cuba (CEON) and had clinical features reminiscent of both tobacco-alcohol amblyopia (TAA) and Leber's hereditary optic neuropathy (Leber's; LHON). Selective damage to the papillomacular bundle was characteristic, and many patients also developed a peripheral neuropathy. Identified risk factors included vitamin deficiencies as well as exposure to methanol and cyanide. In all 3 syndromes, there is evidence that singular or combined insults to mitochondrial oxidative phosphorylation are associated with a clinically characteristic optic neuropathy. PURPOSE: First, to test the hypothesis that a common pathophysiologic mechanism involving impairment of mitochondria function and, consequently, axonal transport underlies both genetic optic nerve diseases such as Leber's and acquired toxic and nutritional deficiency optic neuropathies. According to this hypothesis, ATP depletion below a certain threshold leads to a blockage of orthograde axonal transport of mitochondria, which, in turn, leads to total ATP depletion and subsequent cell death. Second, to address several related questions, including (1) How does impaired energy production lead to optic neuropathy, particularly since it seems to relatively spare other metabolically active tissues, such as liver and heart? (2) Within the nervous system, why is the optic nerve, and most particularly the papillomacular bundle, so highly sensitive? Although there have been previous publications on the clinical features of the Cuban epidemic of blindness, the present hypothesis and the subsequent questions have not been previously addressed. METHODS: Patients in Cuba with epidemic optic neuropathy were personally evaluated through a comprehensive neuro-ophthalmologic examination. In addition, serum, lymphocytes for DNA analysis, cerebrospinal fluid (CSF), sural nerves, and eyes with attached optic nerves were obtained from Cuban patients, as well as from Leber's patients, for study. Finally, we developed an animal model to match the low serum folic acid and high serum formate levels found in the CEON patients, by administering to rats low doses of methanol after several months of a folic acid-deficient diet. Optic nerves and other tissues obtained from these rats were analyzed and compared with those from the Cuban patients. RESULTS: Patients from the Cuban epidemic of optic neuropathy with clinical evidence of a selective loss of the papillomacular bundle did much better once their nutritional status was corrected and exposure to toxins ceased. Patients with CEON often demonstrated low levels of folic acid and high levels of formate in their blood. Histopathologic studies demonstrated losses of the longest fibers (in the sural nerve) and those of smallest caliber (papillomacular bundle) in the optic nerve, with intra-axonal accumulations just anterior to the lamina cribrosa. Our animal model duplicated the serologic changes (low folic acid, high formate) as well as these histopathologic changes. Furthermore, ultrastructural examination of rat tissues demonstrated mitochondrial changes that further matched those seen on ultrastructural examination of tissues from patients with Leber's. CONCLUSION: Mitochondria can be impaired either genetically (as in Leber's) or through acquired insults (such as nutritional or toxic factors). Either may challenge energy production in all cells of the body. While this challenge may be met through certain compensatory mechanisms (such as in the size, shape, or number of the mitochondria), there exists in neurons a threshold which, once passed, leads to catastrophic changes. This threshold may be that point at which mitochondrial derangement leads to such ATP depletion that axonal transport is compromised, and decreased mitochondrial transport results in even further ATP depletion. Neurons are singularly dependent on the axonal transport of mitochondria. (
Assuntos
Mitocôndrias/metabolismo , Doenças do Nervo Óptico/etiologia , Adulto , Idoso , Animais , Cuba , Surtos de Doenças , Exposição Ambiental , Feminino , Ácido Fólico/sangue , Formiatos/sangue , Humanos , Masculino , Estado Nutricional , Atrofias Ópticas Hereditárias/sangue , Atrofias Ópticas Hereditárias/metabolismo , Atrofias Ópticas Hereditárias/patologia , Doenças do Nervo Óptico/induzido quimicamente , Doenças do Nervo Óptico/epidemiologia , Doenças do Nervo Óptico/metabolismo , Doenças do Nervo Óptico/patologia , Ratos , Ratos Long-Evans , Toxinas BiológicasRESUMO
Amiodarone has been used for the last 20 years, initially as antianginal and then as antiarrhythmic agent. To the collateral effects described, the optic neuropathy must be added as a complication, not so frequent, caused apparently by the prolonged ingestion of it. Two patients treated with MDD of 250 mg of amiodarone, for a mean of 17 months, are reported. They presented a decrease of the visual acuity. After proposing the possible differential diagnosis, the relation between the use of amiodarone and the optic alteration observed is briefly exposed, relating it with the demyelination neuropathy induced by this drug. This presumption is corroborated by the ultrastructural alterations registered in the optic nerve of animals in which amiodarone was used, similar to those of the peripheral nerves, as an expression of a disorder of the lipidic metabolism, which allow it to be integrated to the so called iatrogenic lipidoses.