Clinical and Histological Effects of the Intrathecal Administration of a Single Dose of Dexmedetomidine in Rabbits.

BACKGROUND: There is experimental evidence that dexmedetomidine has neuroprotective effects. So, it could be expected that its intrathecal or epidural administration presents no harm. However, whether dexmedetomidine is neurotoxic to the spinal cord remains to be fully elucidated. OBJECTIVE: To evaluate the effect of preservative-free dexmedetomidine administered as a subarachnoid single injection on the spinal cord and meninges of rabbits. STUDY DESIGN: Research article. SETTING: Experimental research laboratory. METHODS: Twenty young adult female rabbits, each weighing between 3200 and 4900 g, and having a spine length between 36 and 40 cm, were divided by lot into 2 groups (G): 0.9% saline in G1 and preservative-free dexmedetomidine in G2 (dose of 10 µg). After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random 5 µl.cm-1 of spinal length (0.2 mL) of solution (saline or dexmedetomidine) was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. RESULTS: None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group showed signs of injuries to meninges. In the dexmedetomidine group, however, 9 animals presented with signs of meningeal injury. The main histological changes observed were areas with meningeal thickening and lymphoplasmocitary infiltration in the pia-mater and arachnoid. Further histological examination also revealed adherence areas among the pia and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. LIMITATIONS: Evaluation of the possible analgesic effects of the intrathecal dexmedetomidine was not performed. CONCLUSION: On the basis of the present results, dexmedetomidine administered in the subarachnoid space in a single dose of 10 µg is capable of producing histological changes over the meninges of rabbits.

O programa de assistência pré-natal nos Cuidados de Saúde Primários em Portugal: uma reflexão / The prenatal care program in Primary Care in Portugal: a reflection / El programa de vigilancia prenatal en la Atención Primaria en Portugal: una reflexión

A melhoria da qualidade dos cuidados prestados à grávida e ao recém-nascido é uma das áreas de intervenção prioritária do Plano Nacional de Saúde. Embora se reconheça que as medidas introduzidas nos últimos anos têm contribuído para diminuir os valores da mortalidade materna e perinatal, é necessário referir, também, que continuam a ocorrer gravidezes não planeadas que, não raras vezes, resultam do início tardio, ou mesmo da ausência, da assistência pré-natal. Neste artigo, procuramos refletir sobre a assistência pré-natal no contexto de saúde reprodutiva, de forma a constituir um contributo para os enfermeiros que prestam uma assistência integral e humanizada às grávidas e às suas famílias. Concluímos que a assistência pré-natal engloba um conjunto de cuidados específicos dirigidos a um grupo vulnerável, constituindo uma área muito importante na avaliação dos cuidados de saúde primários.

The quality improvement of care provided to the pregnant women and newborn is one of the priority areas for intervention of the National Health Plan. While acknowledging that the measures introduced in recent years have contributed to lower the values of maternal and perinatal mortality, it should also be mentioned that unplanned pregnancies continue to occur, and that they often result in a delayed or absent prenatal surveillance. In this paper, we seek to reflect on the prenatal surveillance program under Primary Health Care relating to quality of health care provided in the context of reproductive health. We concluded that prenatal surveillance includes a set of specific care services targeted at a vulnerable group, constituting an important and susceptible area of evaluation in primary care.

Mejorar la calidad de la atención a embarazada y recién nacido es una de las áreas prioritarias de intervención del plan nacional de salud. Aunque se reconoce que las medidas adoptadas en los últimos años han contribuido a reducir los valores de la mortalidad materna y perinatal, es necesario mencionar, también, que embarazos no planificados siguen produciéndose a menudo resultado de la aparición, o incluso ausencia, de vigilancia prenatal. En este artículo, reflexionamos sobre el programa de vigilancia prenatal en el marco de la atención primaria de salud, vinculándola con la calidad de la atención de la salud en el contexto de la salud reproductiva. Concluimos que la vigilancia prenatal comprende un conjunto de cuidados específicos dirigidos a un grupo vulnerable, lo que constituye un área sensible y evaluación importante en atención primaria.

Effects caused by the spinal administration of ketamine S (+) 5% with no preservatives, using a single puncture, and located on the spinal cord and meninges in rabbits.

PURPOSE: To evaluate the effect of ketamine S (+) 5% with no preservatives and administered as a subarachnoid single puncture on the spinal cord and meninges of rabbits. METHODS: Twenty young adult female rabbits, each weighing 3500-5000 g and having a spine length between 34 and 38 cm, were divided by lot into two groups (G): 0.9% saline in G1 and ketamine S (+) 5% in G2, by volume of 5 µg per cm column (0.18 mL). After intravenous anaesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random solution was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. RESULTS: No histological lesions were found in the nervous tissue (roots and cord) or meninges in either group. CONCLUSION: The ketamine S (+) 5% unpreserved triggered no neurological or histological lesions in the spinal cord or meninges of rabbits.

Effects caused by the spinal administration of ketamine S (+) 5% with no preservatives, using a single puncture, and located on the spinal cord and meninges in rabbits

PURPOSE: To evaluate the effect of ketamine S (+) 5% with no preservatives and administered as a subarachnoid single puncture on the spinal cord and meninges of rabbits. METHODS: Twenty young adult female rabbits, each weighing 3500-5000 g and having a spine length between 34 and 38 cm, were divided by lot into two groups (G): 0.9% saline in G1 and ketamine S (+) 5% in G2, by volume of 5 μg per cm column (0.18 mL). After intravenous anaesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random solution was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain. RESULTS: No histological lesions were found in the nervous tissue (roots and cord) or meninges in either group. CONCLUSION: The ketamine S (+) 5% unpreserved triggered no neurological or histological lesions in the spinal cord or meninges of rabbits. .

The effects of subarachnoid administration of preservative-free S(+)-ketamine on spinal cord and meninges in dogs.

BACKGROUND: The N-methyl-d-aspartate receptor antagonist ketamine and its active enantiomer, S(+)-ketamine, have been injected in the epidural and subarachnoid spaces to treat acute postoperative pain and relieve neuropathic pain syndrome. In this study we evaluated the effects of a single dose of preservative-free S(+)-ketamine, in doses usually used in clinical practice, in the spinal cord and meninges of dogs. METHODS: Under anesthesia (IV etomidate (2 mg/kg) and fentanyl (0.005 mg/kg), 16 dogs (6 to 15 kg) were randomized to receive a lumbar intrathecal injection (L5/6) of saline solution of 0.9% (control group) or S(+)-ketamine 1 mg/kg(-1) (ketamine group). All doses were administered in a volume of 1 mL over a 10-second interval. Accordingly, injection solution ranged from 0.6% to 1.5%. After 21 days of clinical observation, the animals were killed; spinal cord, cauda equina root, and meninges were removed for histological examination with light microscopy. Tissues were examined for demyelination (Masson trichrome), neuronal death (hematoxylin and eosin) and astrocyte activation (glial fibrillary acidic protein). RESULTS: No clinical or histological alterations of spinal tissue or meninges were found in animals from either control or ketamine groups. CONCLUSION: A single intrathecal injection of preservative-free S(+)-ketamine, at 1 mg/kg(-1) dosage, over a concentration range of 6 to 15 mg/mL injected in the subarachnoid space in a single puncture, did not produce histological alterations in this experimental model.

Effect of central serotonin depletion on 5-HT receptor-mediated vasomotor responses in the middle meningeal artery of anaesthetized rats.

1 It has been hypothesized that craniovascular 5-HT receptors mediating dilatation of cranial vessels undergo sensitization on decreased serotonergic transmission in migraine. This study analysed the effect of chemical lesion of the 5-HT system in the brain with 5,7-dihydroxytryptamine (5,7-DHT) on 5-HT receptor-mediated dilator responses to 5-carboxamidotryptamine (5-CT) in the middle meningeal artery of anaesthetized rats. 5-CT has recently been shown to elicit dilator responses in this cranial vessel via 5-HT(7) receptors and, to a much lesser extent, 5-HT(1B/1D) receptors. 2 Pretreatment with 5,7-DHT produced a drastic and selective decrease of 5-HT levels in the brain (78 +/- 6% and 94 +/- 2% in dorsal raphe and hypothalamic paraventricular nuclei, respectively) compared with controls (1% ascorbic acid). 3 Topical application of 5-CT (1-1000 microm) to exposed dura mater encephali produced concentration-dependent decreases in diastolic blood pressure and dilator responses in the middle meningeal artery that were similar in vehicle- and 5,7-DHT-pretreaed animals. 4 Hypotensive and meningeal dilator responses to 5-CT were unaltered by the 5-HT(1B/1D) receptor antagonist, GR-127935 (1 mg kg(-1), i.v.), but were strongly inhibited by the 5-HT(7) receptor antagonist, SB-269970 (1 mg kg(-1), i.v.), with similar efficacy, in both groups of animals. Treatment with GR-127935 + SB-269970 (1 mg kg(-1), i.v. each), produced a stronger inhibitory effect than individual treatments on hypotensive but not on meningeal responses to 5-CT. Meningeal 5-HT(7) receptor-mediated responses (i.e. in GR-127935-pretreated animals) were unchanged by 5,7-DHT pretreatment. 5 Results suggest that the sensitivity of craniovascular 5-HT(7) receptors mediating dilatation is unaffected by a decrease of 5-HT levels in the brain. A neuronal involvement of 5-HT in migraine seems more likely, therefore.

The chemokine CCL5 is essential for leukocyte recruitment in a model of severe Herpes simplex encephalitis.

The Herpes simplex virus-1 (HSV-1) is responsible for several clinical manifestations in humans, including encephalitis. To induce encephalitis, C57BL/6 mice were inoculated with 10(4) plaque-forming cells of HSV-1 by the intracranial route. Met-RANTES (regulated upon activation, normal T cell expressed and presumably secreted) (10 microg/mouse), a CC chemokine family receptor (CCR)1 and CCR5 antagonist, was given subcutaneously the day before, immediately after, and at days 1, 2, and 3 after infection. Treatment with Met-RANTES had no effect on the viral titers. In contrast, intravital microscopy revealed that treatment with Met-RANTES decreased the number of leukocytes adherent to the pial microvasculature at days 1 and 3 after infection. The levels of the chemokines CCL3, CCL5, CXCL1, and CXCL9 increased after infection and were enhanced further by the treatment with Met-RANTES. Treatment with a polyclonal anti-CCL5 antibody 2 h before the intravital microscopy decreased leukocyte adhesion in the microcirculation of infected mice. In conclusion, CCL5, a chemokine that binds to CCR1 and CCR5, is essential for leukocyte adhesion during HSV-1 encephalitis. However, blocking of CCR1 and CCR5 did not affect HSV-1 replication, suggesting that other immune mechanisms are involved in the process of infection control.

The effects of intrathecal administration of betamethasone over the dogs' spinal cord and meninges.

PURPOSE: To determinate the potential clinical and histological changes due the injection of betamethasone, when administered into the canine intrathecal space. METHODS: Twenty one animals were included in a random and blind manner in the study. After general anesthesia, intrathecal puncture was performed and 1 ml of the random solution was injected. The G1 dogs received 0.9% saline solution, the G2 dogs received 1.75 mg betamethasone and the G3 dogs received 3.5 mg of betamethasone. The animals were clinically evaluated for 21 days and then sacrificed. The lumbar and sacral portions of the spinal cord were removed for light microscopy histological analyses. RESULTS: No clinical changes were observed in any of the animals included in this study. No histological changes were observed in G1 animals. Inflammatory infiltration was observed in two dogs, one in G2, another in G3. Hemorrhage and necrosis were also seen in the G2 dog which inflammatory infiltration was detected. In other two dogs, one from G2 and another from G3, there was discreet fibrosis and thickness of the arachnoid layer which was focal in one and diffuse in the other. CONCLUSION: Intrathecal administration of betamethasone caused histological changes in the spinal cord and meninges in some of the dogs involved in this study.

The effects of intrathecal administration of betamethasone over the dogs' spinal cord and meninges

PURPOSE: To determinate the potential clinical and histological changes due the injection of betamethasone, when administered into the canine intrathecal space. METHODS: Twenty one animals were included in a random and blind manner in the study. After general anesthesia, intrathecal puncture was performed and 1 ml of the random solution was injected. The G1 dogs received 0.9 percent saline solution, the G2 dogs received 1.75 mg betamethasone and the G3 dogs received 3.5 mg of betamethasone. The animals were clinically evaluated for 21 days and then sacrificed. The lumbar and sacral portions of the spinal cord were removed for light microscopy histological analyses. RESULTS: No clinical changes were observed in any of the animals included in this study. No histological changes were observed in G1 animals. Inflammatory infiltration was observed in two dogs, one in G2, another in G3. Hemorrhage and necrosis were also seen in the G2 dog which inflammatory infiltration was detected. In other two dogs, one from G2 and another from G3, there was discreet fibrosis and thickness of the arachnoid layer which was focal in one and diffuse in the other. CONCLUSION: Intrathecal administration of betamethasone caused histological changes in the spinal cord and meninges in some of the dogs involved in this study.

OBJETIVO: Determinar possíveis alterações clínicas e histológicas determinadas pela administração da betametasona no espaço subaracnóideo de cães. MÉTODOS: Vinte e um cães foram incluídos no estudo de forma aleatória e encoberta. Depois de anestesiados, os cães foram submetidos a punção subaracóidea com injeção de 1 ml da solução sorteada. Os animais receberam solução salina 0,9 por cento em G1, betametasona na dose de 1,75 mg em G2 e betametasona na dose de 3,5 mg em G3. Todos os animais foram mantidos em observação clínica por 21 dias, sendo posteriormente sacrificados. Porções da medula espinhal e sacral foram removidas para análise histológica por microscopia óptica. RESULTADOS: Não foram detectadas alterações clínicas em quaisquer dos animais incluídos no estudo. Da mesma forma, nenhum animal do G1 apresentou alterações histológicas. Infiltração inflamatória foi observada em dois cães, um do G2 e outro e G3. No cão do G2 onde a infiltração inflamatória foi observada ocorreu, conjuntamente, hemorragia e necrose. Em dois cães, um de G2 e outro de G3, observou-se discreta fibrose e espessamento da aracnóide, sendo focal em um e difusa no outro. CONCLUSÃO: A administração subaracnóidea de betametasona determinou alterações histológicas em medula e meninges de alguns dos cães envolvidos no estudo.

5-HT7 receptor-mediated dilatation in the middle meningeal artery of anesthetized rats.

Topical administration of 5-carboxamidotryptamine (5-CT; 0.01-1000 microM) to the exposed dura mater encephali of anesthetized rats produced decreases in blood pressure and dilatation in the middle meningeal artery. Pretreatment with the 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide hydrochloride monohydrate (GR-127935; 1 mg/kg, i.v.), unmasked meningeal dilator responses to lower concentrations of 5-CT, and attenuated those to higher concentrations; GR-127935 also inhibited 5-CT-induced hypotension. The 5-HT7 receptor antagonist, (R)-1-{(3-hydroxyphenyl)sulfonyl}-2-{2-(2-(4-methyl-1-piperidinyl) ethyl} pyrrolidine (SB-269970; 1 mg/kg, i.v.), strongly inhibited dilator and hypotensive responses to 5-CT; the combination of GR-127935+SB-269970 (1 mg/kg, i.v., each) further inhibited meningeal and hypotensive responses. Thus, 5-CT may produce dilatation in the middle meningeal artery via 5-HT7 receptors; complex effects appear to involve 5-HT(1B/1D) receptors.

Efeitos de diferentes doses de tenoxicam sobre a medula espinhal e as meningites. Estudo experimental em cäes / Effects of different doses of tenoxicam on spinal cord and meninges. Experimental study in dogs

Justificativa e objetivo - as açöes analgésicas das drogas antiinflamatórias näo esteroidais (AINE) resultam em inibiçäo da síntese periférica de prostaglandinas. Apesar de se enfatizar sua açäo periférica, várias pesquisas têm demonstrado potencial açäo central dessas drogas. Em ratos, doses de AINE, insuficientes para bloquear a dor quando administradas sistemicamente, foram efetivas em injeçöes intratecais. Esses efeitos seriam medidos por interaçäo com vias serotoninérgicas descendentes, juntamente com modulaçäo da neurotransmissäo dos receptores de glicina ou N-metil-D-aspartato. Nosso objetivo foi estudar os efeitos de diferentes doses de tenoxicam na histologia da medula espinhal e das meninges em cäes. Método - trinta e dois cäes (7 - 17 kg) foram distribuídos aleatoriamente em quatro grupos: G1 - controle com água destilada (AD); G2 - 2mg de tenoxicam diluídos em AD; G3 - 4mg de tenoxicam diluídos em AD; G4 - 10mg de tenoxicam diluídos em AD, em volume constante de 1ml. A anestesia foi induzida com etomidato e fentanil e a punçäo subaracnóidea foi realizada em L6-7 com agulha 25G. Os animais foram mantidos em cativeiro por 72 horas sob observaçäo clínica, quando foram sacrificados por eletrocussäo, sendo retirada a medula lombo-sacra para exame histológico. Resultados - todos os animais permaneceram clinicamente normais durante o período de observaçäo e näo foram observadas quaisquer alteraçöes histológicas na medula e nas meninges. Conclusöes - Em nosso modelo experimental, o tenoxicam em doses de até 10mg administradas no espaço subaracnóideo näo desencadeou alteraçöes histológicas no tecido nervoso e nas meninges de cäes