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1.
Acta Cir Bras ; 34(11): e201901105, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31859818

RESUMEN

PURPOSE: To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP). METHODS: The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity. RESULTS: Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively). CONCLUSION: The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Dexmedetomidina/farmacología , Neuropatías Diabéticas/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/análisis , Receptores Purinérgicos P2X4/análisis , Columna Vertebral/efectos de los fármacos , Animales , Western Blotting , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Neuropatías Diabéticas/patología , Modelos Animales de Enfermedad , Interleucina-1beta/análisis , Interleucina-1beta/efectos de los fármacos , Masculino , Microscopía Electrónica de Transmisión , Proteína con Dominio Pirina 3 de la Familia NLR/efectos de los fármacos , Conducción Nerviosa/efectos de los fármacos , Umbral del Dolor , Distribución Aleatoria , Ratas Sprague-Dawley , Receptores Purinérgicos P2X4/efectos de los fármacos , Reproducibilidad de los Resultados , Transducción de Señal/efectos de los fármacos , Columna Vertebral/patología , Estreptozocina , Nervio Sural/efectos de los fármacos , Nervio Sural/patología , Factores de Tiempo
2.
Artículo en Inglés | MEDLINE | ID: mdl-31487774

RESUMEN

Pesticide exposure is an important rural public health concern that is linked to a spectrum of health outcomes in farmers. However, little is known about these effects on residents living in close proximity to agricultural fields and who are not involved in regular farming. This paper compared the effects of residential proximity to farming lands on a number of neurological and mental health outcomes in adults. A cross-sectional study was performed on 57 adults involved in farming only occasionally in rural Matlab in Bangladesh. A health and demographic surveillance system (HDSS) and geocoding were used to define proximity to the agricultural field. Neurological health was measured using the trail making test, vibrotactile threshold measurement, and dominant ulnar nerve conduction velocity (NCV) amplitude. An adapted Center for Epidemiological Studies Depression scale (CES-D) questionnaire was used to evaluate mental health. Results indicated that respondents living near agricultural fields had significantly higher vibrotactile threshold in big toes (p < 0.004) and needed a longer time to complete the trail making test (p < 0.004) than those living far from fields after accounting for the covariates. Results of this pilot study suggest further investigations to establish the impact of pesticide exposure among occasional and non-farmers on neurological health outcomes.


Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Salud Mental/estadística & datos numéricos , Conducción Nerviosa/fisiología , Plaguicidas/efectos adversos , Población Rural/estadística & datos numéricos , Prueba de Secuencia Alfanumérica/estadística & datos numéricos , Adulto , Bangladesh , Estudios Transversales , Granjas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Proyectos Piloto , Características de la Residencia
3.
Ideggyogy Sz ; 72(5-6): 159-164, 2019 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-31241259

RESUMEN

Background and purpose: The purpose of this prospective study was to investigate whether mid-term treatment with oral isotretinoin may impact peripheral nerve function. Methods: In this study, we included 28 patients with no apparent neurological or neurophysiological findings. The patients received treatment with oral isotretinoin for papulopustular or nodulocystic acne. The patients with normal findings in the first examination were given 1 mg/kg/day oral isotretinoin. Neurological examinations and electroneurographic studies were performed before and 6 months after the onset of isotretinoin treatment. Results: Clinical examinations and electroneurographic evaluations prior to treatment revealed no abnormalities in any of the patients. However, 20 patients (72%) displayed one or more abnormal values in the tested parameters after treatment. Although the mean amplitudes of compound muscle action potential of the ulnar and median nerves did not vary, significant decreases were observed in the mean sensory conduction velocities of median, ulnar, sural, medial plantar, medial dorsal cutaneous, and dorsal sural nerves 6 months after the onset of treatment. Conclusion: Systemic use of isotretinoin may cause electroneurographic changes. Probable electroneurographic alterations may be detected at a much earlier period via dorsal sural nerve tracing when electrophysiological methods used in routine clinical practice cannot detect these changes.


Asunto(s)
Acné Vulgar/tratamiento farmacológico , Fármacos Dermatológicos/administración & dosificación , Isotretinoína/administración & dosificación , Conducción Nerviosa/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Nervio Sural/efectos de los fármacos , Administración Oral , Fármacos Dermatológicos/efectos adversos , Esquema de Medicación , Humanos , Isotretinoína/efectos adversos , Nervios Periféricos/fisiopatología , Estudios Prospectivos , Enfermedades de la Piel/tratamiento farmacológico , Nervio Sural/fisiopatología
4.
J Neuroinflammation ; 16(1): 73, 2019 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-30953561

RESUMEN

BACKGROUND: Autoantibodies against the paranodal protein contactin-1 have recently been described in patients with severe acute-onset autoimmune neuropathies and mainly belong to the IgG4 subclass that does not activate complement. IgG3 anti-contactin-1 autoantibodies are rare, but have been detected during the acute onset of disease in some cases. There is evidence that anti-contactin-1 prevents adhesive interaction, and chronic exposure to anti-contactin-1 IgG4 leads to structural changes at the nodes accompanied by neuropathic symptoms. However, the pathomechanism of acute onset of disease and the pathogenic role of IgG3 anti-contactin-1 is largely unknown. METHODS: In the present study, we aimed to model acute autoantibody exposure by intraneural injection of IgG of patients with anti-contacin-1 autoantibodies to Lewis rats. Patient IgG obtained during acute onset of disease (IgG3 predominant) and IgG from the chronic phase of disease (IgG4 predominant) were studied in comparison. RESULTS: Conduction blocks were measured in rats injected with the "acute" IgG more often than after injection of "chronic" IgG (83.3% versus 35%) and proved to be reversible within a week after injection. Impaired nerve conduction was accompanied by motor deficits in rats after injection of the "acute" IgG but only minor structural changes of the nodes. Paranodal complement deposition was detected after injection of the "acute IgG". We did not detect any inflammatory infiltrates, arguing against an inflammatory cascade as cause of damage to the nerve. We also did not observe dispersion of paranodal proteins or sodium channels to the juxtaparanodes as seen in patients after chronic exposure to anti-contactin-1. CONCLUSIONS: Our data suggest that anti-contactin-1 IgG3 induces an acute conduction block that is most probably mediated by autoantibody binding and subsequent complement deposition and may account for acute onset of disease in these patients. This supports the notion of anti-contactin-1-associated neuropathy as a paranodopathy with the nodes of Ranvier as the site of pathogenesis.


Asunto(s)
Contactina 1/inmunología , Síndrome de Guillain-Barré/complicaciones , Inmunización Pasiva/métodos , Inmunoglobulina G/farmacología , Trastornos Motores/fisiopatología , Trastornos Motores/cirugía , Animales , Moléculas de Adhesión Celular Neuronal/metabolismo , Complemento C1q/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Síndrome de Guillain-Barré/etiología , Humanos , Trastornos Motores/inducido químicamente , Conducción Nerviosa/efectos de los fármacos , Neuritis Óptica/sangre , Neuritis Óptica/inmunología , Nódulos de Ranvier/efectos de los fármacos , Nódulos de Ranvier/metabolismo , Ratas , Ratas Endogámicas Lew , Tiempo de Reacción/efectos de los fármacos , Recuperación de la Función/efectos de los fármacos , Prueba de Desempeño de Rotación con Aceleración Constante , Estadísticas no Paramétricas
5.
Biomed Res Int ; 2019: 9498656, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30915366

RESUMEN

Objectives: Carpal tunnel syndrome (CTS) is one of the most common nerve entrapment syndromes, which has a serious impact on patients' work and life. The most effective conservative treatment is steroid injection but its long-term efficacy is still not satisfactory. The aim of this study was to evaluate the effectiveness of steroid injection combined with miniscalpel-needle (MSN) release for treatment of CTS under ultrasound guidance versus steroid injection alone. We hypothesized that combined therapy could be more beneficial. Methods: Fifty-one patients with CTS were randomly allocated into two groups, namely, steroid injection combined with MSN release group and steroid injection group. The therapeutic effectiveness was evaluated using Boston Carpal Tunnel Questionnaire (BCTQ), cross-sectional area (CSA) of the median nerve, and four electrophysiological parameters, including distal motor latency (DML), compound muscle action potential (CMAP), sensory nerve action potential (SNAP), and sensory nerve conduction velocity (SNCV) at baseline, 4 and 12 weeks after treatment. Results: Compared with baseline, all the parameters in both groups showed statistically significant improvement at week 4 and week 12 follow-up, respectively (P<0.05). When compared with steroid injection group, the outcomes including BCTQ, DML, CMAP, SNCV, and CSA of the median nerve were significantly better in steroid injection combined with MSN release group at week 12 after treatment (P<0.05). Conclusions: The effectiveness of steroid injection combined with MSN release for CTS is superior to that of steroid injection alone, which may have important implications for future clinical practice. This Chinese clinical trial is registered with ChiCTR1800014530.


Asunto(s)
Síndrome del Túnel Carpiano/tratamiento farmacológico , Terapia Combinada , Esteroides/administración & dosificación , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/fisiopatología , Síndrome del Túnel Carpiano/cirugía , Terapia Combinada/métodos , Femenino , Humanos , Ligamentos/diagnóstico por imagen , Ligamentos/efectos de los fármacos , Masculino , Nervio Mediano/diagnóstico por imagen , Nervio Mediano/efectos de los fármacos , Nervio Mediano/patología , Persona de Mediana Edad , Agujas , Conducción Nerviosa/efectos de los fármacos , Resultado del Tratamiento
6.
Neurol Res ; 41(6): 569-576, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30887907

RESUMEN

BACKGROUND: Vitamin B12 (B12) has a fundamental role in both central and peripheral nervous system function at all ages. Neurologic manifestations may be the earliest and often the only manifestation of B12 deficiency. Mostly because of the poor sensitivity of methods of determination for B12 levels, peripheral neuropathy remains a classical but underdiagnosed complication of B12 deficiency. So the clinical and electrophysiological characteristics of B12-responsive neuropathy are not well known. METHODS: A retrospective study of patients with B12-responsive neuropathy was conducted at our hospital on a 3-year period. The criteria for inclusion were: (a) neuropathy confirmed by the electrophysiological study (nerve conduction study); and (b) improvement of at least 1 point of the total Overall Neuropathy Limitations Scale score after vitamin B12 treatment. RESULTS: Nine patients were identified. Serum B12 level was low in only four. Four patients had sensorimotor (predominantly sensory) axonal polyneuropathy while five had only sensory neuronopathy. Six improved in less than 1 month after B12 supplementation. CONCLUSION: B12-responsive neuropathy is a more heterogeneous group of neuropathy than previously described. B12 deficiency is a cause of peripheral neuropathy and should systematically be ruled out in the clinical setting of idiopathic neuropathy or sensory neuronopathy because of potential reversibility. ABBREVIATIONS: B12: vitamin B12; CMAP: compound muscle action potentials; DRG: dorsal root ganglia; ENMG: electroneuromyography; MCCT: motor central conduction time; MEP: motor evoked potentials; MMA: methylmalonic acid; MMCoAM: L-methylmalonyl-CoenzymeA mutase; ONLS: overall neuropathy limitations scale; SCV: sensory conduction velocities; SNAP: sensory nerve action potentials; SNN: sensory neuronopathy; SSS: SNAP sum score.


Asunto(s)
Electromiografía , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Deficiencia de Vitamina B 12/tratamiento farmacológico , Vitamina B 12/uso terapéutico , Adulto , Anciano , Electromiografía/métodos , Potenciales Evocados/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Examen Neurológico , Estudios Retrospectivos , Deficiencia de Vitamina B 12/complicaciones
7.
J Neuroinflammation ; 16(1): 58, 2019 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-30851725

RESUMEN

BACKGROUND: Corticosteroids dominate in the treatment of chronic autoimmune neuropathies although long-term use is characterized by devastating side effects. METHODS: We introduce the intrathecal application of the synthetic steroid triamcinolone (TRIAM) as a novel therapeutic option in experimental autoimmune neuritis in Lewis rats RESULTS: After immunization with neuritogenic P2 peptide, we show a dose-dependent therapeutic effect of one intrathecal injection of 0.3 or 0.6 mg/kg TRIAM on clinical and electrophysiological parameters of neuritis with a lower degree of inflammatory infiltrates (T cells and macrophages) and demyelination in the sciatic nerve. In vitro studies in Schwann cell cultures showed an increased expression of IL-1 receptor antagonist and reduced expression of Toll-like receptor 4 after incubation with TRIAM as well as a protective effect of TRIAM against oxidative stress after H2O2 exposure. CONCLUSION: Intrathecal TRIAM application could be a novel immunomodulatory and potentially neuroprotective option for autoimmune neuropathies with a direct effect on Schwann cells.


Asunto(s)
Antiinflamatorios/administración & dosificación , Neuritis Autoinmune Experimental/tratamiento farmacológico , Neuritis Autoinmune Experimental/patología , Estrés Oxidativo/efectos de los fármacos , Células de Schwann/efectos de los fármacos , Triamcinolona Acetonida/administración & dosificación , Animales , Antígenos CD/metabolismo , Técnicas de Cultivo de Célula , Modelos Animales de Enfermedad , Adyuvante de Freund/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Inyecciones Espinales/métodos , Ganglios Linfáticos/citología , Masculino , Conducción Nerviosa/efectos de los fármacos , Neuritis Autoinmune Experimental/inducido químicamente , Ratas , Ratas Endogámicas Lew , Factores de Transcripción SOXE/metabolismo , Antígenos Thy-1/metabolismo
8.
Neurotoxicology ; 72: 107-113, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30790592

RESUMEN

While neonicotinoid insecticides impair visually guided behaviours, the effects of their metabolites are unknown and measurements of environmental concentrations of neonicotinoids, typically lower than those required to elicit toxic effects, tend to exclude metabolites. Here we examined the contributions of imidacloprid and two of its metabolites, imidacloprid-olefin and 5-hydroxy-imidacloprid, on neural conduction velocity, visual motion detection and flight in the locust (Locusta migratoria) using a combination of electrophysiological and behavioural assays. We show reduced visual motion detection and impaired flight behaviour following treatment of metabolite concentrations equal to sublethal doses of the parent compound. Additionally, we show for the first time that imidacloprid and its metabolites result in a decrease in conduction velocity along an unmyelinated axon. We suggest that secondary effects of the insecticide on the biophysical properties of the axon may result in decreased neural conduction. As these metabolites display neurotoxicity similar to the parent compound they should be considered when quantifying environmental concentrations.


Asunto(s)
Vuelo Animal/efectos de los fármacos , Insecticidas/toxicidad , Locusta migratoria/efectos de los fármacos , Percepción de Movimiento/efectos de los fármacos , Neonicotinoides/toxicidad , Conducción Nerviosa/efectos de los fármacos , Nitrocompuestos/toxicidad , Animales , Insecticidas/metabolismo , Locusta migratoria/fisiología , Masculino , Neonicotinoides/metabolismo , Nitrocompuestos/metabolismo
9.
J Clin Neuromuscul Dis ; 20(3): 111-119, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30801481

RESUMEN

OBJECTIVE: To assess tolerability and efficacy of amifampridine phosphate versus placebo for symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS). METHODS: This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in 26 adults with LEMS compared efficacy of amifampridine phosphate versus placebo over a 4-day period. The primary endpoints were quantitative myasthenia gravis score (QMG) and subject global impression, and the secondary endpoint was Clinical Global Impression-Improvement. The exploratory endpoints were 3TUG (timed up and go) test and QMG limb domain score. All participants had been receiving amifampridine phosphate (30-80 mg/d divided into 3 or 4 doses daily) in an expanded access protocol and had been titrated to the optimal dose and frequency for at least 1 week before randomization into the current study. After completion of assessments after 4 days of double-blind treatment, patients had the option to return to open-label amifampridine phosphate. The efficacy endpoints were mean changes from baseline in the various evaluation parameters. RESULTS: Amifampridine phosphate (n = 13) demonstrated significant benefit in QMG and subject global impression compared with placebo (n = 13) at 4 days. Other measures of efficacy, including Clinical Global Impression-Improvement, 3TUG, and QMG limb domain score also improved. The most common "adverse events" in the placebo group were muscle weakness (n = 5) and fatigue (n = 4), as expected from withdrawal of amifampridine phosphate, whereas only back pain (n = 1), pain in extremity (n = 1), and headache (n = 1) were reported in amifampridine phosphate group. CONCLUSIONS: This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in adults with LEMS provided class I evidence of efficacy of amifampridine phosphate as symptomatic treatment in LEMS.


Asunto(s)
Amifampridina/uso terapéutico , Síndrome Miasténico de Lambert-Eaton/tratamiento farmacológico , Fármacos Neuromusculares/uso terapéutico , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Estados Unidos
10.
Neurochem Res ; 44(5): 1056-1064, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30689163

RESUMEN

Peripheral neuropathy is the most prevalent chronic complication of diabetes mellitus. Good glycemic control can delay the appearance of neuropathic symptoms in diabetic patients but it is not sufficient to prevent or cure the disease. Therefore therapeutic approaches should focus on attenuation of pathogenetic mechanisms responsible for the nerve injury. Considering the role of polyol pathway in the etiology of diabetic neuropathy, we evaluated the effect of a novel efficient and selective aldose reductase inhibitor, 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (cemtirestat), on symptoms of diabetic peripheral neuropathy in Zucker Diabetic Fatty (ZDF) rats. Since the age of 5 months, male ZDF rats were orally administered cemtirestat, 2.5 and 7.5 mg/kg/day, for two following months. Thermal hypoalgesia was evaluated by tail flick and hot plate tests. Tactile allodynia was determined by a von Frey flexible filament test. Two-month treatment of ZDF rats with cemtirestat (i) did not affect physical and glycemic status of the animals; (ii) partially inhibited sorbitol accumulation in red blood cells and the sciatic nerve; (iii) markedly decreased plasma levels of thiobarbituric acid reactive substances; (iv) normalized symptoms of peripheral neuropathy with high significance. The presented findings indicate that inhibition of aldose reductase by cemtirestat is not solely responsible for the recorded improvement of the behavioral responses. In future studies, potential effects of cemtirestat on consequences of diabetes that are not exclusively dependent on glucose metabolism via polyol pathway should be taken into consideration.


Asunto(s)
Aldehído Reductasa/farmacología , Neuropatías Diabéticas/tratamiento farmacológico , Conducción Nerviosa/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Aldehído Reductasa/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Neuropatías Diabéticas/metabolismo , Inhibidores Enzimáticos/farmacología , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Ratas Zucker
11.
Neurology ; 92(4): e359-e370, 2019 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-30626650

RESUMEN

OBJECTIVE: To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1). METHODS: In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18-70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. The primary outcome measure was the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS). Secondary outcomes included plasma sphingolipid levels, epidermal nerve fiber density, electrophysiologic measurements, patient-reported measures, and adverse events. RESULTS: Between August 2013 and April 2014, we enrolled and randomized 18 participants, 16 of whom completed the study. After 1 year, the l-serine group experienced improvement in CMTNS relative to the placebo group (-1.5 units, 95% CI -2.8 to -0.1, p = 0.03), with evidence of continued improvement in the second year of treatment (-0.77, 95% CI -1.67 to 0.13, p = 0.09). Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; p < 0.001). There were no serious adverse effects related to l-serine. CONCLUSION: High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression. CLINICALTRIALSGOV IDENTIFIER: NCT01733407. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1.


Asunto(s)
Neuropatías Hereditarias Sensoriales y Autónomas/tratamiento farmacológico , Serina/uso terapéutico , Resultado del Tratamiento , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Estudios de Seguimiento , Neuropatías Hereditarias Sensoriales y Autónomas/etiología , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Dimensión del Dolor , Serina C-Palmitoiltransferasa/genética , Esfingolípidos/metabolismo , Encuestas y Cuestionarios , Ubiquitina Tiolesterasa/metabolismo , Adulto Joven
12.
Muscle Nerve ; 59(2): 174-180, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30339737

RESUMEN

INTRODUCTION: In this study we explored the efficacy of nerve hydrodissection for mild-to-moderate carpal tunnel syndrome (CTS). METHODS: Thirty-four participants were randomly assigned to an intervention group or a control group. One 5-ml dose of normal saline was injected into the intracarpal and subcutaneous regions in subjects of both groups, respectively. The primary outcome measure was the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score. Secondary outcomes were cross-sectional area of the median nerve and electrophysiological studies. Assessments were performed before the injection and at 1, 2, 3, and 6 months postintervention. RESULTS: Compared with the control group, the intervention group showed significantly greater improvement at the second and third posttreatment months according to BCTQ severity score and at all time-points for cross-sectional area of the median nerve (P < 0.01). DISCUSSION: Our study demonstrates the therapeutic effects of nerve hydrodissection for mild-to-moderate CTS. Muscle Nerve 59:174-180, 2019.


Asunto(s)
Síndrome del Túnel Carpiano/tratamiento farmacológico , Nervio Mediano/efectos de los fármacos , Nervio Mediano/fisiología , Solución Salina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Síndrome del Túnel Carpiano/diagnóstico por imagen , Estudios Transversales , Método Doble Ciego , Estimulación Eléctrica , Femenino , Humanos , Masculino , Nervio Mediano/diagnóstico por imagen , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Dimensión del Dolor , Estudios Prospectivos , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Intervencional , Adulto Joven
13.
J Int Adv Otol ; 15(1): 43-50, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30541731

RESUMEN

OBJECTIVES: To investigate the effects of topical and systemic administrations of melatonin and dexamethasone on facial nerve regeneration. MATERIALS AND METHODS: In total, 50 male albino Wistar rats underwent facial nerve axotomy and neurorrhaphy. The animals were divided into 5 groups: control, topical melatonin, systemic melatonin, topical dexamethasone, and systemic dexamethasone. Nerve conduction studies were performed preoperatively and at 3, 6, 9, and 12 weeks after drug administrations. Amplitude and latency of the compound muscle action potentials were recorded. Coapted facial nerves were investigated under light and electron microscopy. Nerve diameter, axon diameter, and myelin thickness were recorded quantitatively. RESULTS: Amplitudes decreased and latencies increased in both the melatonin and dexamethasone groups. At the final examination, the electrophysiological evidence of facial nerve degeneration was not significantly different between the groups. Histopathological examinations revealed the largest nerve diameter in the melatonin groups, followed by the dexamethasone and control groups (p<0.05). Axon diameter of the control group was smaller than those of the melatonin (topical and systemic) and topical dexamethasone groups (p<0.05). The melatonin groups had almost normal myelin ultrastructure. CONCLUSION: Electrophysiological evaluation did not reveal any potential benefit of dexamethasone and melatonin in contrast to histopathological examination, which revealed beneficial effects of melatonin in particular. These agents may increase the regeneration of facial nerves, but electrophysiological evidence of regeneration may appear later.


Asunto(s)
Dexametasona/farmacología , Nervio Facial/efectos de los fármacos , Nervio Facial/trasplante , Melatonina/farmacología , Administración Tópica , Animales , Axotomía/métodos , Depresores del Sistema Nervioso Central/administración & dosificación , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Fenómenos Electrofisiológicos/efectos de los fármacos , Nervio Facial/fisiopatología , Nervio Facial/ultraestructura , Glucocorticoides/administración & dosificación , Masculino , Melatonina/administración & dosificación , Vaina de Mielina/ultraestructura , Regeneración Nerviosa/efectos de los fármacos , Conducción Nerviosa/efectos de los fármacos , Procedimientos Neuroquirúrgicos/métodos , Ratas , Ratas Wistar , Procedimientos Quirúrgicos Reconstructivos/métodos , Recuperación de la Función
14.
J Diabetes Investig ; 10(2): 466-474, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29975462

RESUMEN

AIMS/INTRODUCTION: Diabetic polyneuropathy is one of the most frequent diabetic complications, and impairs patients' quality of life. We evaluated the efficacy and safety of ranirestat (40 mg/day) in patients with diabetic polyneuropathy. MATERIALS AND METHODS: This was a multicenter, placebo-controlled, randomized double-blind, parallel-group, phase III study in which 557 patients were randomly assigned to either the ranirestat or placebo group and assessed for 52 weeks. The co-primary end-points were the changes in tibial motor nerve conduction velocity and total modified Toronto Clinical Neuropathy Score as a measure of clinical symptoms. RESULTS: There was a significant increase in tibial motor nerve conduction velocity in the ranirestat group compared with the placebo group. The difference between groups in the change at last observation was 0.52 m/s (P = 0.021). Increases in nerve conduction velocity in the ranirestat group were found not only in the tibial motor nerves, but also in the median motor nerves, proximal median sensory nerves and distal median sensory nerves. No significant differences in modified Toronto Clinical Neuropathy Score or safety parameters were found between the two groups. CONCLUSIONS: Ranirestat (40 mg/day) was well tolerated and improved nerve conduction velocity. Regarding symptoms and signs, no detectable benefits over the placebo were observed in the ranirestat group during the 52 weeks of treatment.


Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Neuropatías Diabéticas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Conducción Nerviosa/efectos de los fármacos , Pirazinas/uso terapéutico , Calidad de Vida , Compuestos de Espiro/uso terapéutico , Adulto , Anciano , Neuropatías Diabéticas/epidemiología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Adulto Joven
15.
Br J Anaesth ; 122(1): 141-149, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30579393

RESUMEN

BACKGROUND: Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown. METHODS: A diabetic state was established in adult male Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 µg kg-1 (alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements. RESULTS: Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fibre damage in control non-diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1ß and tumour necrosis factor-α was also seen. CONCLUSIONS: Ropivacaine 0.5% causes significant sciatic nerve injury in diabetic rats that is greatly potentiated by high-dose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted.


Asunto(s)
Anestésicos Locales/toxicidad , Dexmedetomidina/toxicidad , Diabetes Mellitus Experimental/complicaciones , Traumatismos de los Nervios Periféricos/inducido químicamente , Ropivacaína/toxicidad , Nervio Ciático/efectos de los fármacos , Adyuvantes Anestésicos/toxicidad , Animales , Citocinas/biosíntesis , Diabetes Mellitus Experimental/fisiopatología , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/fisiopatología , Sinergismo Farmacológico , Mediadores de Inflamación/metabolismo , Masculino , Bloqueo Nervioso/efectos adversos , Bloqueo Nervioso/métodos , Conducción Nerviosa/efectos de los fármacos , Traumatismos de los Nervios Periféricos/etiología , Traumatismos de los Nervios Periféricos/fisiopatología , Ratas Sprague-Dawley , Nervio Ciático/lesiones
16.
Medicine (Baltimore) ; 97(44): e13020, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30383660

RESUMEN

BACKGROUND: Prostaglandin E1 (P) or methylcobalamin (M) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in many clinical trial reports. However, the combined effects of 2 drugs still remain dubious. OBJECTIVE: The aim of this report was to evaluate the efficacy of M plus P (M + P) for the treatment of DPN compared with that of P monotherapy, in order to provide a reference resource for rational drug use. METHODS: Randomized controlled trials (RCTs) of M + P for DPN published up to September 2017 were searched. Risk ratio (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I test. Subgroup and sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects. RESULTS: Sixteen RCTs with 1136 participants were included. Clinical efficacy of M + P combination therapy was significantly better than P monotherapy (fifteen trials; RR 1.25, 95% CI 1.18-1.32, P < .00001, I = 27%). Compared with P monotherapy, the pooled effects of M + P combination therapy on nerve conduction velocity were (MD 6.29, 95% CI 4.63-7.94, P < .00001, I = 90%) for median MNCV, (MD 5.68, 95% CI 3.53-7.83, P < .00001, I = 94%) for median SNCV, (MD 5.36, 95% CI 3.86-6.87, P < .00001, I = 92%) for peroneal MNCV, (MD 4.62, 95% CI 3.48-5.75, P < .00001, I = 86%) for peroneal SNCV. There were no serious adverse events associated with drug intervention. CONCLUSIONS: M + P combination therapy was superior to P monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients. Moreover, no serious adverse events occur in combination therapy.


Asunto(s)
Alprostadil/administración & dosificación , Neuropatías Diabéticas/tratamiento farmacológico , Vitamina B 12/análogos & derivados , Alprostadil/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Conducción Nerviosa/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Vitamina B 12/administración & dosificación , Vitamina B 12/efectos adversos
17.
Eur J Pharmacol ; 840: 89-103, 2018 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-30268665

RESUMEN

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is often dose-limiting and impacts life quality and survival of cancer patients. Ghrelin agonists have neuroprotectant effects and may have a role in treating or preventing CIPN. We evaluated the CNS-penetrant ghrelin agonist HM01 in three experimental models of CIPN at doses of 3-30 mg/kg p.o. daily monitoring orexigenic properties, nerve conduction, mechanical allodynia, and intra-epidermal nerve fiber density (IENFD). In a cisplatin-based study, rats were dosed daily for 3 days (0.5 mg/kg i.p.) + HM01. Cisplatin treatment induced mechanical hypersensitivity which was significantly reduced by HM01. In a second study, oxaliplatin was administered to mice (6 mg/kg i.p. 3 times/week for 4 weeks) resulting in significant digital nerve conduction velocity (NCV) deficits and reduction of IENFD. Concurrent HM01 dose dependently prevented the decline in NCV and attenuated the reduction in IENFD. Pharmacokinetic studies showed HM01 accumulation in the dorsal root ganglia and sciatic nerves which reached concentrations > 10 fold that of plasma. In a third model, HM01 was tested in preventive and therapeutic paradigms in a bortezomib-based rat model (0.2 mg/kg i.v., 3 times/week for 8 weeks). In the preventive setting, HM01 blocked bortezomib-induced hyperalgesia and IENFD reduction at all doses tested. In the therapeutic setting, significant effect was observed, but only at the highest dose. Altogether, the robust peripheral nervous system penetration of HM01 and its ability to improve multiple oxaliplatin-, cisplatin-, and bortezomib-induced neurotoxicities suggest that HM01 may be a useful neuroprotective adjuvant for CIPN.


Asunto(s)
Antineoplásicos/efectos adversos , Derivados del Benceno/farmacología , Ghrelina/agonistas , Sistema Nervioso/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Peso Corporal/efectos de los fármacos , Cisplatino/efectos adversos , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Ratones , Conducción Nerviosa/efectos de los fármacos , Piperidinas , Ratas
18.
Ann Neurol ; 84(4): 601-610, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30187524

RESUMEN

OBJECTIVE: Perineural injection with 5% dextrose (D5W) is a novel strategy in the treatment of carpal tunnel syndrome (CTS). In contrast, perineural injection with corticosteroid has been used for decades for treating CTS, but possible neurotoxicity has been a major concern. No studies investigating the comparative effects have been published so far. The authors performed a prospective, randomized, double-blinded, head-to-head comparative trial to compare these two approaches for patients having mild-to-moderate CTS. METHODS: Fifty-four participants with mild-to-moderate CTS were randomly divided into dextrose and steroid groups. The patients were administered 1 session of perineural injection with 5ml D5W (dextrose group) or 3ml triamcinolone acetonide mixed with 2ml normal saline (steroid group), under ultrasound guidance. A visual analog scale was assigned to assess the primary outcome. The secondary outcomes were assessed using the Boston Carpal Tunnel Syndrome Questionnaire, cross-sectional area of the median nerve, and electrophysiological studies. The assessment was performed prior to injection and 1, 3, 4, and 6 months postinjection. RESULTS: All patients (27 wrists per group) completed the study. Compared with the steroid group, the dextrose group exhibited a significant reduction in pain and disability through the 4th to the 6th month (p < 0.01). INTERPRETATION: Our study demonstrates that perineural injection of D5W is more beneficial than that of corticosteroid in patients with mild-to-moderate CTS at 4 to 6 months postinjection. Ann Neurol 2018;84:601-610.


Asunto(s)
Antiinflamatorios/administración & dosificación , Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/tratamiento farmacológico , Glucosa/administración & dosificación , Triamcinolona Acetonida/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Composición de Medicamentos , Femenino , Humanos , Masculino , Nervio Mediano/diagnóstico por imagen , Nervio Mediano/efectos de los fármacos , Persona de Mediana Edad , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/fisiología , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía Intervencional/métodos
19.
Mol Med Rep ; 18(5): 4577-4586, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30221656

RESUMEN

The present study investigated whether insulin­like growth factor­1 (IGF­1) exerts a protective effect against neuropathy in diabetic mice and its potential underlying mechanisms. Mice were divided into four groups: Db/m (control), db/db (diabetes), IGF­1­treated db/db and IGF­1­picropodophyllin (PPP)­treated db/db. Behavioral studies were conducted using the hot plate and von Frey methods at 6 weeks of age prior to treatment. The motor nerve conduction velocity (NCV) of the sciatic nerve was measured using a neurophysiological method at 8 weeks of age. The alterations in the expression levels of IGF­1 receptor (IGF­1R), c­Jun N­terminal kinase (JNK), extracellular signal­regulated kinase (ERK), p38 and effect of IGF­1 on the sciatic nerve morphology were observed by western blotting and electron microscopy. Compared with the control group, the diabetes group developed hypoalgesia after 12 weeks, and neurological lesions improved following an intraperitoneal injection of recombinant (r)IGF­1. The sciatic NCV in the diabetes group was significantly lower compared with the control group. The sciatic NCV improved following rIGF­1 intervention; however, was impaired following administration of the IGF­1 receptor antagonist, PPP. The myelin sheath in the sciatic nerve of the diabetes group was significantly more impaired compared with the control group. The myelin sheath in the sciatic nerves of the rIGF­1­treated group was significantly improved compared with the diabetes group; whereas, they were significantly impaired following administration of the IGF­1R inhibitor. In addition, the expression of IGF­1R, phosphorylated (p)­JNK and p­ERK of sciatic nerves in the db/db mice was significantly increased following treatment with IGF­1. The expression levels of these proteins were significantly lower in the IGF­1­PPP group compared with the IGF­1 group; however, no significant difference was observed in the expression levels of p­p38 following treatment with IGF­1. The results of the present study demonstrated that IGF­1 may improve neuropathy in diabetic mice. This IGF­1­induced neurotrophic effect may be associated with the increased phosphorylation levels of JNK and ERK, not p38; however, it was attenuated by administration of an IGF­1R antagonist.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Factor I del Crecimiento Similar a la Insulina/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Animales , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatología , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Factor I del Crecimiento Similar a la Insulina/genética , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Ratones , Ratones Endogámicos NOD/genética , Vaina de Mielina/efectos de los fármacos , Vaina de Mielina/genética , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/genética , Fosforilación , Podofilotoxina/administración & dosificación , Podofilotoxina/análogos & derivados , Proteínas Recombinantes/genética , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiopatología , Proteínas Quinasas p38 Activadas por Mitógenos/genética
20.
Sci Rep ; 8(1): 12153, 2018 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-30108241

RESUMEN

Eye irritation assessment is compulsory to anticipate health risks in military personnel exposed to riot control agents such as capsaicin, the principal constituent of oleoresin capsicum, or pepper sprays. The present work investigates certain fundamental yet unaddressed pharmacological manifestations on ocular exposure to capsaicin. Ocular pharmacology of capsaicin was studied using acute eye irritation (AEI), bovine corneal opacity and permeability (BCOP) assay, corneal fluorescein staining and indirect ophthalmoscopy studies, transcorneal permeation, Schirmer tear secretion test, nerve conduction velocity study and enzyme-linked immunosorbent assay (ELISA). Additionally, histopathology and scanning electron microscopy (SEM) of bovine corneas and rat optic nerves were done to further estimate capsaicin induced morphological variations. Our findings demonstrated that AEI, BCOP, corneal fluorescein staining and indirect ophthalmoscopy were useful in assessing capsaicin induced ocular irritation; AEI and BCOP also contributed towards indicating the eye irritation potential of capsaicin as per the United Nations Globally Harmonized System of Classification and Labelling of Chemicals categorization. Additional experimental observations include considerable transcorneal permeation of capsaicin, capsaicin induced reduction in tear secretions and nerve conduction velocity and increased expression of proinflammatory cytokines by ELISA. Histopathology and SEM were favourable techniques for the detection of capsaicin induced ocular physiological modifications.


Asunto(s)
Capsaicina/toxicidad , Córnea/efectos de los fármacos , Opacidad de la Córnea/inducido químicamente , Sustancias para Control de Disturbios Civiles/toxicidad , Animales , Bioensayo , Capsaicina/farmacocinética , Bovinos , Córnea/metabolismo , Córnea/ultraestructura , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Aparato Lagrimal/efectos de los fármacos , Masculino , Microscopía Electrónica de Rastreo , Personal Militar , Conducción Nerviosa/efectos de los fármacos , Nervio Óptico/efectos de los fármacos , Nervio Óptico/ultraestructura , Permeabilidad , Conejos , Ratas , Ratas Wistar , Sustancias para Control de Disturbios Civiles/farmacocinética , Pruebas de Toxicidad Aguda
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