Antinociceptive effect of N-(9,13b-dihydro-1H-dibenzo[c, f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide on different pain models in mice

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.

Muscle pain induced by static contraction is modulated by transient receptor potential vanilloid 1 and ankyrin 1 receptors

Abstract Molecular mechanisms involved in the development of muscle pain induced by static contraction are not completely elucidated. This study aimed to evaluate the involvement of the transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1) receptors expressed in peripheral and central terminals of primary afferents projected to gastrocnemius muscle and spinal cord in muscle pain induced by static contraction. An electrical stimulator provided the contraction of rat gastrocnemius muscle and mechanical muscle hyperalgesia was quantified through the pressure analgesimeter Randall-Selitto. AMG9810 and HC030031 were used. When administered in ipsilateral, but not contralateral gastrocnemius muscle, drugs prevented mechanical muscle hyperalgesia induced by static contraction. Similar results were obtained by intrathecal administrations. We propose that, in an inflammatory muscle pain, peripheral and central TRPV1 and TRPA1 work together to sensitize nociceptive afferent fibers, and that TRPV1 and TRPA1 receptors are potential target to control inflammatory muscle pain.

Cirugía precoz en la prevención de la sepsis del recién nacido con mielomeningocele / Precocious surgery in preventing the sepsis of newborn with meningomyelocele

El mielomeningocele es una malformación congénita por defecto del cierre del tubo neural, se produce en las primeras semanas de crecimiento intrauterino. Consiste en una masa quística que incluye tejido nervioso y meninges, acompañadas de una fusión incompleta de los arcos vertebrales. Produce severos daños neurales y puede asociarse a otras malformaciones. Su reparación, en las primeras horas de vida, es necesaria para evitar complicaciones que pueden comprometer la vida del niño o causar mayor discapacidad. Se reportó un caso de un recién nacido con diagnóstico de mielomeningocele fisurado, a nivel lumbar. Se intervino quirúrgicamente en las primeras 6 h de vida; se disecó el saco dural y se separaron las raíces, logrando el cierre completo de la duramadre. Se reparó la piel con afrontamiento de los bordes y adecuada cicatrización de la herida. Fue aplicada antibioticoterapia profiláctica con cefalosporina de tercera generación. El infante egresó a los 10 días de operado sin complicaciones neuroquirúgicas asociadas (AU).

Meningomyelocele is a congenital malformation by defect of neural tube closing, produced in the first weeks of intrauterine grow. It is a cystic mass that includes nervous tissues and meninges, together with an incomplete fusion of the vertebral arches. It produces severe neural damages and could be associated to other malformations. It is necessary to repair it during the first hours after birth to avoid complications that could compromise the child’s life or cause more disability. The case of a new-born child diagnosed with fissured meningomyelocele at the lumbar level is presented. He was operated in the first six hours after birth; the dural sac was dissected and the roots separated, reaching the complete dura mater closure. The skin was repaired with edges affronting and adequate wound healing. Prophylactic antibiotic therapy with third generation cephalosporin was applied. The child was discharged 10 days alter the surgery without associated neurosurgical complications (AU).

The Use of Magnetic Resonance Imaging in Predicting the Clinical Outcome of Spinal Arteriovenous Fistula

PURPOSE: Magnetic resonance imaging (MRI) has been used to screen and follow-up spinal dural arteriovenous fistulae (SDAVF). The purpose of this study was to evaluate the association between MRI findings and neurologic function in SDAVF. This study also investigated clinical features and treatment results of SDAVF. MATERIALS AND METHODS: A total of 15 consecutive patients who underwent embolization or surgery for SDAVF were included. We treated seven (60%) patients with embolization and six (40%) with surgery. We analysed clinical features, MRI findings, treatment results, and neurologic function. Neurologic function was measured by the Aminoff-Logue disability scale (ALS). RESULTS: Patients with longer levels of intramedullary high signal intensity in preoperative T2-weighted images (T2WI) exhibited worse pre- and postoperative ALS scores (r=0.557, p=0.031; r=0.530, p=0.042, Pearson correlation). Preoperative ALS score was significantly correlated with postoperative ALS score (r=0.908, p=0.000, Pearson correlation). The number of levels showing intramedullary high signal intensity in T2WI decreased significantly postoperatively (5.2+/-3.1 vs. 1.0+/-1.4, p=0.001, Wilcoxon ranked test). CONCLUSION: The number of involved levels of high signal intensity in preoperative T2WI is useful for predicting pre- and postoperative neurologic function in SDAVF.

The Use of Magnetic Resonance Imaging in Predicting the Clinical Outcome of Spinal Arteriovenous Fistula

PURPOSE: Magnetic resonance imaging (MRI) has been used to screen and follow-up spinal dural arteriovenous fistulae (SDAVF). The purpose of this study was to evaluate the association between MRI findings and neurologic function in SDAVF. This study also investigated clinical features and treatment results of SDAVF. MATERIALS AND METHODS: A total of 15 consecutive patients who underwent embolization or surgery for SDAVF were included. We treated seven (60%) patients with embolization and six (40%) with surgery. We analysed clinical features, MRI findings, treatment results, and neurologic function. Neurologic function was measured by the Aminoff-Logue disability scale (ALS). RESULTS: Patients with longer levels of intramedullary high signal intensity in preoperative T2-weighted images (T2WI) exhibited worse pre- and postoperative ALS scores (r=0.557, p=0.031; r=0.530, p=0.042, Pearson correlation). Preoperative ALS score was significantly correlated with postoperative ALS score (r=0.908, p=0.000, Pearson correlation). The number of levels showing intramedullary high signal intensity in T2WI decreased significantly postoperatively (5.2+/-3.1 vs. 1.0+/-1.4, p=0.001, Wilcoxon ranked test). CONCLUSION: The number of involved levels of high signal intensity in preoperative T2WI is useful for predicting pre- and postoperative neurologic function in SDAVF.

Retalho de rotação com cicatriz resultante em tridente para fechamento de meningomielocele / Closure of myelomeningocele defects using a rotation flap that resulted in a trident scar

Myelomeningocele is a defect of the spinal cord, spinal column, and skin covering these areas that results in the defective closure of the posterior portion of the neural tube during the fourth week of gestation. Its etiology is multifactorial and has yet to be clarified. The objective of this study was to demonstrate an addítional skin fiap alternative for the treatment of this defect. Closure with a flap that creates a trident-shaped scar has been shown to bea viable alternative that is easy to implement, reduces surgical time, minimizes blood loss, and requires no cutaneous grafts to cover the flap donor area.

A meningomielocele é um defeito da medula espinhal, da coluna vertebral e da pele sobre essa área, resultando em defeito no fechamento da porção posterior do tubo neural durantea quarta semana de gestação. Sua etiologia é multifatorial e ainda não está esclarecida. O objetivo deste trabalho é demonstrar mais uma opção de retalho de pele para tratamento desse defeito. O fechamento com retalho resultando em cicatriz em formato de tridente apresentou-se como alternativa viável, de fácil execução, com tempo cirúrgico reduzido e mínima perda sanguínea, não requerendo enxertos cutâneos para cobertura da área doadorados retalhos.

Spinal cord demyelination in biotinidase deficiency: a case report

Biotinidase deficiency is a treatable cause of severe neurological disorders and skin disorders. Most symptomatic patients will have neurological, cutaneous manifestations and typical organic aciduria. Spinal cord involvement is a rare manifestation of this disease and is commonly unrecognized. We report a previously healthy boy who presented at the age of 28 months with recurrent ataxia and mild alopecia, and MRI evidence of spinal cord demyelination. Biotinidase deficiency was confirmed later. Supplementation with biotin resulted in disappearance of the symptoms and normalization of the MRI spinal cord changes. Biotinidase deficiency, as a treatable condition, should be considered in the differential diagnosis in any child who presents with neurological symptoms and spinal cord demyelination with or without alopecia

Micosis intramedular: informe de caso / Intramedullary micosis: case report

Introducción. Las micosis intramedulares son infrecuentes. Asimismo, la manifestación neurológica de la histoplasmosis es una entidad poco común y más infrecuente aún es la manifestación de la histoplasmosis a través de un granuloma intramedular. Caso Clínico. Se presenta el caso de una niña con síndrome medular a quien se realizó resección quirúrgica de una lesión patológicamente compatible con histoplasmosis, quien desarrolló hidrocefalia, lesiones isquémicas en fosa posterior y falleció a pesar del l tratamiento establecido. Conclusión. Aunque las micosis de médula espinal son infrecuentes, es conveniente considerar a la hora de realizar los diagnósticos diferenciales de lesiones granulomatosas en esta localización anatómica...

Morphological changes in the brachial enlargement of the spinal cord in offspring of diabetic rat

This study was conducted to evaluate the effects of maternal diabetes on fetal spinal structure, especially in brachial enlargement. Sixteen adult female rats were divided into two groups. Diabetes was induced in one group by alloxan agent. Both groups became pregnant by natural matting. On days 7, 14, 21 and 28 after birth, the brachial enlargement of the spinal cord was collected from offspring of all rats and the weight of neonates was measured. Various histological parameters were determined using histological techniques. The results revealed a significant decrease in transverse spinal diameter and number of neurons of gray matter and an increase in vertical spinal diameter in spinal cord of offspring of diabetic mothers [ODM] as compared with the control group. The body weight of ODM was significantly more than that of the control group [P<0.05]. Maternal hyperglycemia exhibited deleterious effects on spinal cord, especially brachial enlargement during fetal life which remained persistent during postneonatal period

Síndrome de médula espinal anclada en un cachorro bulldog inglés. Reporte de un caso / Síndrome de medula amarrada em um cão da raça bulldog inglês. Reporte do caso / Tethered spinal cord syndrome in an english bulldog puppy. A case report

El síndrome de médula espinal anclada es una patología del desarrollo diagnosticada en seres humanos pero de poco reporte en medicina de pequeñas especies animales. En este artículo se presenta un caso de disrafismo espinal, vértebra lumbar supernumeraria, espina bífida con meningocele, médula espinal anclada y seno dermoide en un cachorro de raza bulldog inglés de cuatro meses de edad, que presentó un cuadro clínico de incontinencia fecal, atrofia muscular en miembros pelvianos y ataxia. Se describe el procedimiento diagnóstico, el tratamiento y la evolución clínica del paciente. Con este reporte se pretende que el médico veterinario considere dentro de sus diagnósticos diferenciales la posibilidad de una afección de tipo neurológico cuando el paciente presente signos clínicos tipo incontinencias fecal y urinaria, ataxia y debilidad de miembros pelvianos, en perros de razas con predisposición a sufrir este tipo de síndrome; además, llamar la atención sobre este tipo de patologías que en la mayoría de los casos podrían ser subdiagnosticadas.

Tethered spinal cord syndrome is a developmental disease diagnosed in human but of rare report in small animal practice. In this report a case of spinal disrafism, spina bifida with menyngocele, tethered cord syndrome and dermoid sinus is described in a four months old English bulldog male, that presented a clinical condition of faecal incontinence, muscular atrophy in pelvic limbs and ataxia. The diagnostic procedure, treatment and evolution of the patient are described. The purpose of this report is to provide the practitioner with diagnostic tools to include a neurological entity as a differential diagnosis when attending a patient presenting clinical signs such as fecal and urinary incontinency, ataxia and pelvic limbs debility, in dogs of breeds predisposed to suffering this syndrome; in addition, to highlight this neurological pathologies that could be under diagnosed in most of the cases.

E síndrome de medula amarrada é uma doença diagnosticada em desenvolvimento humano, mas de rara incidência em prática dos pequenos animais. Neste relatório o caso clinica de disrafismos do tubo neural, espinha bífida com meningocele, e síndrome de seios dermoides são descrito em um cão da raça bulldog inglês de quatro meses de idade, que apresentou uma condição clínica de incontinência fecal, atrofia muscular nos membros pélvicos e ataxia. O procedimento diagnóstico, tratamento e evolução do paciente são descritos. O objetivo do presente articule consiste em fornecer o praticante com ferramentas diagnósticas para incluir uma entidade neurológica como um diagnóstico diferencial quando freqüenta um doente apresentar sinais clínicos tais como incontinência fecal e urinária, ataxia e debilidade de membros pélvicos, em cães de raças predispostas a este síndrome; além disso, para destacar estas patologias neurológicas que poderiam estar sob diagnosticada na maioria dos casos.

Perosomus elumbis em um cordeiro no Brasil / Perosomus elumbis in a sheep in Brazil

Perosomus elumbis designa um conjunto raro de anomalias congênitas que primariamente incluem agenesia parcial da medula espinhal e vértebras lombossacrais. O presente relato descreve a ocorrência da enfermidade em um ovino neonato no Brasil.

Perosomus elumbis designates a set of rare abnormal congenital abnormalities that primarily includes partial agenesis of spinal cord and lumbosacral vertebrae. The present paper reports the occurrence of the disease in a neonate sheep in Brazil.

Evaluation of an experimental model for anorectal anomalies induced by ethylenethiourea

PURPOSE: To evaluate an experimental model for anorectal anomalies and their principal associated malformations induced by ethylene thiourea (ETU). METHODS: Rat fetuses were utilized, divided into two groups: experimental group - fetuses from rats that received ETU on the 11th day of gestation at the dose of 125 mg/kg, diluted in distilled water to 1 percent concentration (12.5 ml/kg); and control group - fetuses from rats that received distilled water alone, at a volume of 12.5 ml/kg. On the 21st day of gestation, the animals were sacrificed by hypoxia in a carbon dioxide chamber, followed by laparotomy to remove the fetuses. These were initially examined externally to determine the sex and whether anorectal anomalies and malformations of the vertebral column and tail were present. Then, with the aid of microscopy, the fetuses underwent exploratory laparotomy to characterize the type of anorectal anomaly and investigate urological malformations. RESULTS: None of the fetuses in the control group presented anorectal anomaly, vertebral column malformation or urological structural alterations. In the experimental group, 71 percent presented anorectal anomaly, 80 percent presented vertebral column alterations and 35 percent presented urological alterations. CONCLUSION: The model described was shown to be easy to implement and presented results that allow its use in studying anorectal anomalies and associated malformations.

OBJETIVO: Avaliar o modelo experimental de AAR, induzido pela Etilenotiouréia (ETU), quanto à ocorrência de anomalia anorretal e das principais malformações associadas. MÉTODOS: Foram utilizados fetos de ratos distribuídos em 2 grupos: Grupo experimental - Fetos provenientes de ratas que receberam ETU no décimo primeiro dia de gestação na dose de 125 mg/Kg, diluída em água destilada na concentração de 1 por cento (12,5 ml/Kg) e Grupo controle - Fetos de ratas que receberam somente água destilada num volume de 12,5 ml/Kg. No 21° dia de gestação, os animais foram submetidos à eutanásia por hipóxia em câmara de gás carbônico e laparotomia para retirada dos fetos. Os fetos foram, inicialmente, examinados externamente para determinação do sexo, presença de AAR, de malformações de coluna vertebral e da cauda. A seguir, com o auxílio de microscopia, os fetos foram submetidos a laparotomia exploradora para caracterização do tipo de AAR e investigação de malformações urológicas. RESULTADOS: Nenhum dos fetos do grupo controle apresentou AAR, malformações de coluna vertebral e alterações urológicas estruturais. No grupo experimental, 71 por cento apresentaram anomalia anorretal, 80 por cento apresentaram alterações de coluna vertebral e 35 por cento apresentaram alterações urológicas. CONCLUSÃO: O modelo descrito se mostrou de fácil execução e apresentou resultados que permite o seu emprego no estudo das anomalias anorretais e das malformações associadas.

Surgical treatment of occult spinal dysraphism with tethered spinal cord

Occult spinal dysraphism [OSD] consists of a subgroup of spinal dysraphism in which the congenital abnormality of the spinal cord is covered by intact skin and is associated with dermatologic, skeletal, urogenital and/or neurological abnormalities. This study was undertaken to evaluate the early prophylactic effect of surgery on OSD on subsequent expression of neurologic and musculoskeletal abnormalities. Thirty six patients with OSD with tethered cord who underwent surgery for treatment from October 2001 to October 2004 in Department of Neurosurgery of Shiraz University of Medical Sciences affiliated hospitals were evaluated 6 and 12 months postoperatively including a complete history and physical examination with special attention on spinal cord and lower limb function, bladder muscular force, and urodynamic studies. The most frequent dermatologic expression of OSD included hairy patches, subcutaneous lipoma, skin dimple and haemangioma. Scoliosis was observed in 13 cases, among them 7 cases had split cord syndrome, 2 cases had hypertrophic filum terminal [HFT] and 4 cases had both of the conditions. Among those with split cord syndrome, 78.6%, 14.3% and 7.6% were bony, fibrocartilagenous and fibrotic respectively. All patients improved significantly after the procedure. It appears that prophylactic surgical intervention in cases of OSD is a safe and recommended procedure prior to the onset of neurologic deterioration

Comparative study of complex spina bifida and split cord malformation.

OBJECTIVE: To see the difference in clinical profiles, radiological findings and surgical outcome of the group 1 split cord malformation and meningomyelocele (SCM with MMC) from group 2 (SCM without MMC). METHODS: 46 patients of SCM were selected from a total of 138 cases of spinal dysraphism. They were divided into two groups, based on presence or absence of MMC. Group I (SCM with MMC) n =19 patients and Group II (SCM without MMC) n=27 patients. A detail clinical evaluation and MR screening of whole spine of all cases was performed. All patients underwent surgical detethering of cord. After an average follow-up of 1.7 years, the operative results were clinically assessed and statistical significance was calculated. RESULTS: Male to female ratio was 1:09. Mean age of presentation was 3.6 years. Cutaneous markers like tuft of hair, cutaneous haemangioma, etc, had a higher incidence in group II in comparison to group I (50% vs 10.5%). The incidence of motor deficits was significant in group I in comparison to group II (63% vs 40%). The incidences of sensory loss, trophic ulcers, sphincteric dysfunction and muscle atrophy were relatively more common in group I patients, while neuro-orthopedic deformities such as congenital telepes equinovarus (CTEV), scoliosis and limb shortening were more frequent (67%) in group II children as compared to group I (53%). Type I SCM has higher incidence in group I children. Low lying conus were found in 47% patient of group I, while in group II it was noticed in 69%. The associated cranial anomalies like hydrocephalus, ACM and syrinx, were slightly higher in group I patients. At surgery, dysgenetic nerve roots, neural placode, arachnoid bands and atrophic cord were seen mainly in group I. Postoperative complications like, CSF leak, pseudomeningocele and meningitis were more commonly encountered in group I patients. The patients of group II showed better operative outcome compared to group I cases. CONCLUSION: Incidence of SCM with MMC amount to 41% of total SCM cases. Progressive neurological deficit was higher in this group (SCM with MMC) in comparison to the group harboring SCM without MMC. In view of a significant association of SCM in MMC cases, associated with other craniospinal anomalies, a thorough screening of neuraxis (by MRI) is recommended to treat all treatable anomalies simultaneously for desired outcome.

Spinal arteriovenous malformations: surgical outcome

Spinal arteriovenous malformations are relatively rare, being one tenth as common as cerebral AVMs and one tenth as common as primary spinal neoplasms. The aim of this retrospective study was to see distribution of this disease in spinal cord and analyse outcome of surgical treatment in our set-up. 5 patients with neurologic deficit due to spinal AVMs were operated upon from March 2000 to Feb 2005. Age ranged from 25-45 years with mean of 35 years. There were 2 females and 3 males with sex ratio of 1:1.5 respectively. Spinal AVMs were categorized as one of 4 types based on pattern of arterial and venous supply. We found that 60% [3 cases] in our series were intradural AVMs while 40% [2 cases] were dural type. We conclude that glomus variety of intradural AVMs was the commonest. The commonest presentation was acute spinal dysfunction and paraparesis. Selective spinal angiography can be negative in spinal AVMs, [20%] in our series, in which CT angiography provided clue to the feeding vessels

Intramedullary neurenteric cyst in mid thoracic spine in an adult: a case report.

Neurenteric cysts are very rare, particularly in adults. These are congenital intraspinal cysts of endodermal origin. A 67 years old man, presenting with backache and paraesthesiae of one and half years' duration, followed by subacute flaccid paraplegia, developing in a week is described. MRI revealed intramedullary cyst at T7. He underwent emergency thoracic laminectomy and complete excision of the cyst. Histopathology confirmed a neurenteric cyst. In view of their rarity, peculiarity in terms of age, location and presentation, we report this case.

Split cord malformations--a clinical study of 48 cases.

OBJECTIVE: To determine the clinical profile of split cord malformations and to evaluate the results of surgery. DESIGN: Retrospective. SUBJECTS: Forty-eight patients of split cord malformation operated during a six years period were studied clinically and radiologically. RESULTS: The mean age of symptomatic patients was more than that of asymptomatic ones (6.85 years vs 2.03 years). The dorsolumbar and lumbar regions were most frequently involved and in three cases the cervical spine was affected. Weakness of lower limbs (n=37), muscle atrophy (n=23) and gait disturbance were the most common indicators of motor system involvement. The sensory complaints were mainly hypoesthesia (n=16), trophic ulcer (n=4) and autoamputation (n=3). Hypertrichiosis was the most common cutaneous marker present alone or in combination with other markers in 21 cases. MRI, done in all cases, correctly established the diagnosis. Additional lesions causing tethering were seen in 50% cases and were simultaneously treated. Associated Chiari malformation was seen in 12%. Of the 42 symptomatic patients, 21 improved, in 17 (40%) the neurological deficits stabilized and 4 showed deterioration. CSF leak occurred in 4 patients and 3 had wound infections. Among the asymptomatic patients none had neurological deterioration postoperatively. CONCLUSIONS: Split cord malformations are rare spinal cord disorders. Complete neural axis should be scanned at the first instance to determine associated lesions. Good results can be expected in about 90% patients with minimal complications.

C-T Metrizamid and surgical corelation in Spina Bifida Cystica

This work was conducted on 38 cases of spina bifida cystica with employment of C.T. mitrizamid as preliminary methods of investigation and treated by microsurgical technique. The work showed that the agreement of surgical verification with C.T. mitrizamid was in 32 cases with percentage of 84.21%. The disagreement was only in 15.79% of the cases [6 cases]. So, C.T. mitrizamid is trustful method of investigation as regard to study of both vertebral lipoma in wide anomalies. MRI can be use as confirmatory method if intraspinal lipoma in wide spinal canal suspected to give more delineation of the soft tissue contents