Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain

Abstract 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.

Topography of the medullary cone of the feline night monkey: Clinical implications in epidural anesthesia / Topografia do cone medular do macaco-da-noite: auxiliando a abordagem peridural

Feline night monkey (Aotus azarae infulatus) is an arboreal primate that sleeps during the day hidden among branches of trees, leaving its hideout after nightfall. Little is known about the morphology of these animals, which leads to some difficulty in clinical and surgical approaches, as there has been substantial growth in the veterinarian’s role in maintaining the health and well-being of wildlife. Thus, we sought to investigate the topography and morphometry of the medullary cone, a small portion of the nervous system of the feline night monkey, which is of paramount importance in approaches for epidural anesthesia. Specimens from five young females were used, each with eight lumbar vertebrae, three sacral vertebrae, and a medullary cone with an average length of 7.5 cm, located between L5 and S3. Based on this finding, we suggest that a probable site for the application of epidural anesthesia is the space between S3 and Cc1.

O macaco-da-noite (Aotus azarae infulatus) é um animal arborícola que dorme durante o dia escondido entre os ramos, saindo do esconderijo após o anoitecer. Pouco se sabe sobre a morfologia destes animais, o que gera certa dificuldade nas abordagens clínico-cirúrgicas, uma vez que cresce substancialmente o papel do médico veterinário nas questões de saúde e bem-estar de animais selvagens. Visando contribuir com esses profissionais, buscou-se investigar a topografia e morfometria de uma pequena porção do sistema nervoso do macaco-da-noite, o cone medular, que é de suma importância nas abordagens quanto à anestesia peridural. Foram utilizados cinco espécimes fêmeas, jovens, de macaco-da-noite, que apresentavam oito vértebras lombares e três vértebras sacrais, e cone medular possuindo em média de 7,5 cm de comprimento, localizando-se entre L5 e S3. Este achado nos leva a sugerir como sítio provável para a aplicação de anestesia epidural, o espaço entre S3 e Cc1.

Efectos del ranelato de estroncio sobre la densidad mineral ósea en hombres / Effect of strontium ranelate on bone mineral density in men

La osteoporosis afecta al 6-7% de la poblaciónmasculina. Es alta la proporción de pacientes confractura osteoporótica sin diagnóstico previo de estaenfermedad. La mortalidad luego de una fracturaes mayor en hombres que en población femenina;a pesar de esto, la mayoría de los pacientes no reciben tratamiento. Los fármacos aprobados, en nuestro medio, para tratar la osteoporosis masculina son:bifosfonatos, teriparatida y ranelato de estroncio. Elobjetivo de este estudio fue evaluar el efecto del ranelato de estroncio sobre la densidad mineral ósea enhombres después de 1 año de tratamiento. Se incluyeron los registros de 20 hombres de 67.8±3.0 años,tratados con ranelato de estroncio (2 g/día) durante 1año. Todos los pacientes presentaban un T-score inferior a -2.5 en cadera o columna vertebral o un T-scoreinferior a -2.0 y factores de riesgo de fractura. Nohubo modificación de parámetros de laboratorio luego del tratamiento (calcemia, calciuria, fósforo sérico,parathormona, 25(OH)vitamina D, fosfatasa alcalinay desoxipiridinolina). Luego de 1 año de tratamiento con ranelato de estroncio se observó incrementode la densidad mineral ósea en columna lumbar:0.953±0.029 versus 0.997±0.030 g/cm2 (p=0.0068),cuello femoral: 0.734±0.013 versus 0.764±0.016 g/cm2 (p=0.0084) y cadera total: 0.821±0.02 versus0.834±0.02 g/cm2 (p=0.0419). Conclusión: luego de1 año de tratamiento el ranelato de estroncio produjoun incremento significativo de la densidad mineralósea en columna lumbar y fémur proximal en hombres con osteoporosis (AU)

Osteoporosis affects 6-7% of the male population. The proportion of patients with fragility fractures but without diagnosis of the disease is high. Mortality after hip fracture is higherin men than in women; in spite of this, mostpatients are left without treatment for osteoporosis. Drugs approved, for the treatment ofosteoporosis in our country are bisphosphonates, teriparatide, and strontium ranelate (SrR).The objective of this study was to evaluate theeffect of SrR on axial BMD in men after one yearof treatment. We obtained pertinent data frommedical registries of 20 men aged 67,8±3,0 years,treated with oral SrR (2 g/day) for 12 months. All patients had a T-score below -2,5 at the hipor the lumbar spine, or a T-score below -2,0and one or more risk factors for fracture. Thelevels of serum calcium, phosphate, alkalinephosphatase, 25-hydroxyvitamin D, or PTH,or urinary calcium and desoxipyridinoline remained unchanged following SrR administration. After treatment with SrR there weresignificant increases in BMD at the lumbarspine: 0,953±0,029 versus 0,997±0,030 g/cm2(p=0,0068), femoral neck: 0,734±0,013 versus 0,764±0,016 g/cm2 (p=0.0084), and total hip: 0,821±0,02 versus 0,834±0,02 g/cm2(p=0,0419). Conclusion: in osteoporotic men,treatment with SrR significantly increases BMDin the lumbar spine and the proximal femur (AU)

Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement / Hipoparatiroidismo: aspectos clínicos, microestrutura esquelética e reposição do paratormônio

OBJECTIVE: Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. SUBJECTS AND METHODS: Standard histomorphometric and µCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. RESULTS: Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. CONCLUSION: Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D.

OBJETIVO: O hipoparatiroidismo é uma doença em que há diminuição dos níveis circulantes do paratormônio, em geral, causada por destruição autoimune ou exerese cirúrgica. O objetivo deste estudo foi descrever as anormalidades microestrutrurais esqueléticas, como também o potencial terapêutico do uso do PTH(1-84). SUJEITOS E MÉTODOS: Histomorfometria padrão e análise de micro-CT foram realizadas em biópsias de crista ilíaca de indivíduos com hipoparatiroidismo. Os participantes foram tratados com PTH(1-84) por dois anos. RESULTADOS: A densidade óssea aumentou e os achados esqueléticos refletiram o estado de baixa remodelação óssea com maior BV/TV, Tb Wi e CT Wi, como também supressão de MS e BFR/BS quando comparado com o grupo controle. Com o uso de PTH(1-84), a remodelação óssea aumentou e a densidade óssea aumentou na coluna lombar. As necessidades de cálcio e vitamina D diminuíram e a calciúria não mudou. CONCLUSÃO: A microestrutura esquelética anormal no hipoparatiroidismo reflete a ausência do PTH. A terapia de reposição com PTH tem o potencial de reverter essas anormalidades, como também reduzir as necessidades de cálcio e vitamina D.

Comparison of Effects of Alendronate and Raloxifene on Lumbar Bone Mineral Density, Bone Turnover, and Lipid Metabolism in Elderly Women with Osteoporosis

PURPOSE: To compare the effects of alendronate and raloxifene on lumbar bone mineral density (BMD), bone turnover, and lipid metabolism in elderly women with osteoporosis. Subjects and Methods: One hundred twenty-two postmenopausal women with osteoporosis (mean age: 69.4 years) were randomly divided into 2 groups of 61 patients: the alendronate group and the raloxifene group. BMD of the lumbar spine, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP), total cholesterol (TC), high and low density lipoprotein cholesterols (LDL-C and HDL-C, respectively), and triglycerides (TG) were measured during the 12-month-treatment period. RESULTS: The trial in 50 patients in the alendronate group and 52 patients in the raloxifene group could be completed. Both alendronate and raloxifene increased lumbar BMD (+8.0% and +2.4% at 12 months, respectively), followed by reductions of urinary NTX level and serum ALP level; however, the effects of alendronate were more pronounced than those of raloxifene. Only raloxifene reduced the serum levels of TC and LDL-C (-3.9% and -7.7% at 12 months, respectively), without any significant effect on the serum HDL-C and TG levels. CONCLUSION: The present study confirmed the efficacy of alendronate greater than raloxifene in increasing lumbar BMD through its effect on marked reduction of the bone turnover more than by raloxifene, and some beneficial effects of raloxifene on lipid metabolism in elderly women with osteoporosis.

[ teratogenic effect of lamotrigine on vertebral column, sternum and ribs of mice fetus]

One of the most important complications of anti-epileptic drugs [AEDs], used during pregnancy, is the increasing of congenital malformation in neonates. One of these drugs, lamotrigine [LTG], in addition to treatment of epilepsy, is used in many of the chronic neural diseases. There are a few controversial reports about teratogenic effect of this drug. Based on these reports, oral usage of this drug is not teratogenic. Therefore, the aim of this study was to investigate about the teratogenic effect of this drug on a number of mice fetuses following the interaperitoneal injections. In this study, 150 mice were divided in four groups: 1] control 1, no material administration, 2] control 2, ip ethanol solution was administrated, 3] case 1, LTG was administrated ip [25 mg/kg, tid] 4] fourth group [case 2], LTG was administrated ip 3 time/day [75 mg/kg] from the 9th to 18th day of gestation. Fetuses were collected on the GD 18 and then some of embryos were used for alizarin red and alcian blue staining. By this method of staining soft tissue would become clear, cartilages become blue, and bones turn to red. Then malformations in vertebral column, sternum and ribs were considered in four groups and were compared. In the group treated with LTG, different types of skeletal malformations were increased [p<0.001] and the incretion was drug dose-dependent. The results of this study showed that LTG is likely a risk factor in occurrence of skeletal malformation in mice fetus

Effect of combined treatment with calcitonin on bone densitometry of patients with treated hypothyroidism

INTRODUCTION: Thyroid hormones (TH) may affect bone metabolism and turnover, inducing a loss of bone mass among hyperthyroid and in hypothyroid patients under hormone replacement treatment. Thyroid dysfunction leads to changes in the dynamics of parathyroid hormone (PTH) and calcitonin (CT) secretion. OBJECTIVE: The objective of the study was to determine the usefulness of CT as adjuvant therapy in the prevention of bone loss during the treatment of hypothyroidism. MATERIAL AND METHODS: We studied 16 female patients with recently diagnosed primary hypothyroidism, divided into two groups: group G1 (n=8) submitted to treatment with thyroxine (L-T4), and Group 2 (n=8) that, in addition to being treated with L-T4, received a nasal CT spray. All patients were submitted to determination of TSH, free T4, bone mineral densitometry (BMD) and total bone calcium (TBC) at the time of diagnosis, after 6 to 9 months of treatment, and after 12 months of treatment. RESULTS: No statistical significant differences were detected in either group between the total BMD values obtained for the femur and lumbar spine before and after treatment. However, group G1 presented a statistical significant TBC loss after 12 months of treatment compared to initial values. In contrast, no TBC loss was observed in the group treated with LT-4 in combination with CT, a fact that may suggest that CT was responsible for the lower bone reabsorption during treatment of hypothyroidism.

Efectos del alendronato oral, la hormonoterapia de reeplazo y la conbinacion de ambos sobre la masa osea en mujeres posmenopausicas: informe preliminar de um estudio comparativo / Effects on bone mass of oral alendronate, hormone replacement therapy and combined regimesns in post-menopausal women: p

Se informa el análisis comparativo preliminar de los efectos sobre la densidad mineral ósea de la terapia con alendronato, la hormonoterapia de reemplazo (HTR) y la asociación de ambas el primer año de tratamiento continuo. Se incluyeron en un estudio prospectivo y abierto mujeres posmenopáusicas de hasta 70 años de edad, con osteopenia de columna lumbar y/o de cuello de fémur (DMO menor que -1 DE del adulto joven) determinada por absorciometría de rayos X dual (DEXA). Noventa y seis pacientes fueron incluidas al azar en uno de los 4 grupos terapéuticos: Grupo I (n:19): hormonoterapia de reemplazo (HTR) con 17 beta estradiol 50 Mug/día por vía transdermal y medroxiprogesterona 2,5 mg/día por vía oral; Grupo II (n:42): alendronato 10 mg/día por vía oral; Grupo III (n:15): HTR + alendronato 10 mg/día y Grupo IV (n:20): HTR + alendronato 5 mg/día. Los resultados ajustados a los 12 meses de tratamiento, evidenciaron un aumento promedio significativo de la densidad mineral ósea (DMO) vertebral de 3,6 por ciento; 4,1 por ciento; 6,5 por ciento y 3,1 por ciento en los grupo I a IV respectivamente con respecto a la basal (p < 0,01), sin diferencias significativas entre los grupos. El porcentaje de pacientes respondedoras en columna lumbar en cada grupo fue del 68,8 por ciento; 92 por ciento; 90 por ciento y 83 por ciento, respectivamente. Los incrementos promedio sobre la DMO del cuello de fémur (CF) respecto a la basal no superaron la variación del método de determinación. El porcentaje de respondedoras sobre el CF en cada grupo fue de 58,8 por ciento; 60 por ciento; 62,5 por ciento y 45,5 por ciento, respectivamente. La disminución en los marcadores bioquímicos de metabolismo óseo, especialmente de la piridinolina urinaria y la osteocalcina indicaron la tendencia a la inhibición del metabolismo óseo, que fue más constante en el grupo III. Se concluye que, si bien todos los grupos favorecieron el balance óseo positivo, los resultados más favorables fueron observados con el tratamiento combinado con alendronato 10 mg y HTR (grupo III) sugiriendo el beneficio potencial de esta asociación.

Efeito de antiinflamatórios enzimáticos (bromelina, escina e papaína) no desenvolvimento de coluna vertebral de ratas / Effect of enzimatic anti-inflammatory agents (bromelain, aescin and papain) in development of vertebral column of rats

O presente trabalho foi desenvolvido com a utilizaçäo de antiinflamatórios de origem vegetal: bromelina, escina e papaína, em doses terapêuticas. Os antiinflamatórios foram injetados intraperitonealmente em ratas prenhas, com a finalidade de verificarmos os possíveis efeitos sobre o desenvolvimento óssseo das colunas vertebrais. Os resultados obtidos segundo as condiçöes de nossa pesquisa, foram: 1. As três drogas antiinflamatórias de origem vegetal - bromelina, escina e papaína - causaram reduçäo do crescimento das colunas vertebrais de ratas. 2. O grupo onde só as mäes tomaram papaína durante a prenhez, foi o mais atingido no crescimento da coluna vertebral, e o grupo onde as mäes e os filhotes tomaram papaína, foi o menos atingido. 3. Quanto ao crescimento, o grupo composto por animais que tomaram escina durante a prenhez, apresentou um aumento de peso significativo em relaçäo ao grupo controle. 4. Quanto à malformaçäo da coluna vertebral, todos grupos apresentaram leves deformaçöes em relaçäo ao grupo controle, sendo que o grupo onde as mäes e os filhotes tomaram escina, foi o que apresentou maior deformaçäo na estrutura da coluna vertebral