Serotonin receptors are involved in the spinal mediation of descending facilitation of surgical incision-induced increase of Fos-like immunoreactivity in rats

Background: Descending pronociceptive pathways may be implicated in states of persistent pain. Paw skin incision is a well-established postoperative pain model that causes behavioral nociceptive responses and enhanced excitability of spinal dorsal horn neurons. The number of spinal c-Fos positive neurons of rats treated intrathecally with serotonin, noradrenaline or acetylcholine antagonists where evaluated to study the descending pathways activated by a surgical paw incision. Results: The number of c-Fos positive neurons in laminae I/II ipsilateral, lamina V bilateral to the incised paw, and in lamina X significantly increased after the incision. These changes: remained unchanged in phenoxybenzamine-treated rats; were increased in the contralateral lamina V of atropine-treated rats; were inhibited in the ipsilateral lamina I/II by 5-HT(1/2B/2C) (methysergide), 5-HT(2A) (ketanserin) or 5-HT(1/2A/2C/5/6/7) (methiothepin) receptors antagonists, in the ipsilateral lamina V by methysergide or methiothepin, in the contralateral lamina V by all the serotonergic antagonists and in the lamina X by LY 278,584, ketanserin or methiothepin. Conclusions: We conclude: (1) muscarinic cholinergic mechanisms reduce incision-induced response of spinal neurons inputs from the contralateral paw; (2) 5-HT(1/2A/2C/3) receptors-mediate mechanisms increase the activity of descending pathways that facilitates the response of spinal neurons to noxious inputs from the contralateral paw; (3) 5-HT(1/2A/2C) and 5-HT(1/2C) receptors increases the descending facilitation mechanisms induced by incision in the ipsilateral paw; (4) 5-HT(2A/3) receptors contribute to descending pronociceptive pathways conveyed by lamina X spinal neurons; (5) alpha-adrenergic receptors are unlikely to participate in the incision-induced facilitation of the spinal neurons.

Human Dental Pulp Cells: A New Source of Cell Therapy in a Mouse Model of Compressive Spinal Cord Injury

Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists and neuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in terms of functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mouse model of compressive spinal cord injury (SCI). These cells present some advantages, such as the ease of the extraction process, and expression of trophic factors and embryonic markers from both ecto-mesenchymal and mesenchymal components. Young adult female C57/BL6 mice were subjected to laminectomy at T9 and compression of the spinal cord with a vascular clip for 1 min. The cells were transplanted 7 days or 28 days after the lesion, in order to compare the recovery when treatment is applied in a subacute or chronic phase. We performed quantitative analyses of white-matter preservation, trophic-factor expression and quantification, and ultrastructural and functional analysis. Our results for the HDPC-transplanted animals showed better white-matter preservation than the DMEM groups, higher levels of trophic-factor expression in the tissue, better tissue organization, and the presence of many axons being myelinated by either Schwann cells or oligodendrocytes, in addition to the presence of some healthy-appearing intact neurons with synapse contacts on their cell bodies. We also demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functional analysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCs may be feasible candidates for therapeutic intervention after SCI and central nervous system disorders in humans.

Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

Background: Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods: B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results: Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19Arf and nutlin-3. Conclusions: To the best of our knowledge, this is the first study to apply both p19Arf and nutlin-3 for the stimulation of p53 activity. These results support the notion that a p53 responsive vector may prove to be an interesting gene transfer tool, especially when combined with p53- activating agents, for the treatment of tumors that retain wild-type p53.

Combined Monte Carlo and quantum mechanics study of the solvatochromism of phenol in water. The origin of the blue shift of the lowest pi-pi* transition

A combined and sequential use of Monte Carlo simulations and quantum mechanical calculations is made to analyze the spectral shift of the lowest pi-pi* transition of phenol in water. The solute polarization is included using electrostatic embedded calculations at the MP2/aug-cc-pVDZ level giving a dipole moment of 2.25 D, corresponding to an increase of 76% compared to the calculated gas-phase value. Using statistically uncorrelated configurations sampled from the MC simulation,first-principle size-extensive calculations are performed to obtain the solvatochromic shift. Analysis is then made of the origin of the blue shift. Results both at the optimized geometry and in room-temperature liquid water show that hydrogen bonds of water with phenol promote a red shift when phenol is the proton-donor and a blue shift when phenol is the proton-acceptor. In the case of the optimized clusters the calculated shifts are in very good agreement with results obtained from mass-selected free jet expansion experiments. In the liquid case the contribution of the solute-solvent hydrogen bonds partially cancels and the total shift obtained is dominated by the contribution of the outer solvent water molecules. Our best result, including both inner and outer water molecules, is 570 +/- 35 cm(-1), in very good agreement with the small experimental shift of 460 cm(-1) for the absorption maximum.

Contuse lesion of the rat spinal cord of moderate intensity leads to a higher time-dependent secondary neurodegeneration than severe one - An open-window for experimental neuroprotective interventions

Secondary neurodegeneration takes place in the surrounding tissue of spinal cord trauma and modifies substantially the prognosis, considering the small diameter of its transversal axis. We analyzed neuronal and glial responses in rat spinal cord after different degree of contusion promoted by the NYU Impactor. Rats were submitted to vertebrae laminectomy and received moderate or severe contusions. Control animals were sham operated. After 7 and 30 days post surgery, stereological analysis of Nissl staining cellular profiles showed a time progression of the lesion volume after moderate injury, but not after severe injury. The number of neurons was not altered cranial to injury. However, same degree of diminution was seen in the caudal cord 30 days after both severe and moderate injuries. Microdensitometric image analysis demonstrated a microglial reaction in the white matter 30 days after a moderate contusion and showed a widespread astroglial reaction in the white and gray matters 7 days after both severities. Astroglial activation lasted close to lesion and in areas related to Wallerian degeneration. Data showed a more protracted secondary degeneration in rat spinal cord after mild contusion, which offered an opportunity for neuroprotective approaches. Temporal and regional glial responses corroborated to diverse glial cell function in lesioned spinal cord. (C) 2007 Elsevier Ltd. All rights reserved.

Combined photocatalytic and fungal processes for the treatment of nitrocellulose industry wastewater

The objective of this work was to characterize the delignification effluent originating from the delignification industry and evaluate the combination of the fungus and photocatalytic process (TiO(2)/UV system) for the treatment of this effluent. The delignification effluent has proven harmful to the environment because it presents high color (3516 CU), total phenol (876 mg/L and TOC (1599 mg/L) and is also highly toxic even in a low concentration. The results of photocatalysis were 11%, 25% and 13% higher for reductions in color, total phenol and TOC, respectively. The combined treatments presented benefits when compared to the non-combined treatments. Fungus and photocatalysis in combination proved to be the best treatment, reducing the color, total phenol, toxicity (inhibition of Escherichia coli growth) and TOC by 94.2%, 92.6%, 4.9% and 62%, respectively. (C) 2008 Elsevier B.V. All rights reserved.

Optimisation of environmental gas cleaning routes for solid wastes cogeneration systems. Part II - Analysis of waste incineration combined gas/steam cycle

In the first paper of this paper (Part I), conditions were presented for the gas cleaning technological route for environomic optimisation of a cogeneration system based in a thermal cycle with municipal solid waste incineration. In this second part, an environomic analysis is presented of a cogeneration system comprising a combined cycle composed of a gas cycle burning natural gas with a heat recovery steam generator with no supplementary burning and a steam cycle burning municipal solid wastes (MSW) to which will be added a pure back pressure steam turbine (another one) of pure condensation. This analysis aims to select, concerning some scenarios, the best atmospheric pollutant emission control routes (rc) according to the investment cost minimisation, operation and social damage criteria. In this study, a comparison is also performed with the results obtained in the Case Study presented in Part I. (c) 2007 Elsevier Ltd. All rights reserved.

Lumbar Epidural Anesthesia in the Treatment of Discal Lombosciatalgia: A Comparative Clinical Study between Methylprednisolone and Methylprednisolone with Levobupivacaine

Sousa FAEF, Colhado OCG - Lumbar Epidural Anesthesia in the Treatment of Discal Lombosciatalgia: A Comparative Clinical Study between Methylprednisolone and Methylprednisolone with Levobupivacaine. Background and objectives: Lumbar epidural technique has been used in the treatment of lombosciatalgia since 1953. In most cases, methylprednisolone is used along with a local anesthetic, and it is not known whether the isolated use of methylprednisolone is equally effective in relieving symptoms. The objective of this study was to compare the efficacy of two different solutions - methylprednisolone with saline and methylprednisolone with levobupivacaine injected in the epidural space to heal lombosciatalgia secondary to lumbar herniated disk. Methods: Sixty individuals ASA I and II, of both genders, ages 18 to 65 years participated in this randomized, double-blind study over a period of one year. They underwent interlaminar lumbar epidural analgesia without radioscopic control to heal a lombosciatalgia and they were divided into two groups: G-M (methylprednisolone + saline) and G-M + L (methylprednisolone + levobupivacaine + saline) both at a volume of 10 mL. Diagnosis was based on history, physical exam, and imaging exam (MRI). The Visual Analogue Scale (VAS) was applied in a total of two blockades, 15 days apart. Results: A reduction in pain severity was observed in the methylprednisolone-levobupivacaine group, but without statistical significance. Conclusions: The analgesic efficacy of the G-M + L solution was superior to that of the G-M solution in the treatment of discal lombosciatalgia regarding the shorter time to onset of analgesia, but this was not significant at the time of discharge, and both solutions were effective in the treatment of discal lombosciatalgia.

Utility of Quantitative Ultrasound of the Calcaneus in Diagnosing Osteoporosis in Spinal Cord Injury Patients

Bittar CK, Cliquet A Jr, dos Santos Floter M: Utility of quantitative ultrasound of the calcaneus in diagnosing osteoporosis in spinal cord injury patients. Am J Phys Med Rehabil 2011;90:477-481. Objective: The aim of this study was to assess the utility of quantitative ultrasound of the calcaneus in diagnosing osteoporosis in spinal cord injury patients in a Brazilian Teaching Hospital. Design: This is a diagnostic test criterion standard comparison study. Between January 2008 and October 2009, the bone density of 15 spinal cord injury patients was assessed for analysis before beginning rehabilitation using muscle stimulation. The bone density was assessed using bone densitometry examination (DEXA) and ultrasound examination of the calcaneus (QUS). The measurements acquired using QUS and DEXA were compared between patients with spinal cord injury and a control group of ten healthy individuals. Results: The T-score values for femoral neck using DEXA (P < 0.0022) and those using QUS of the calcaneus (P < 0.0005) differed significantly between the groups, and the means in the normal subjects were higher than those in spinal cord injury patients who would receive electrical stimulation. In spinal cord injury patients, the significant differences were found between the QUS T-score for calcaneus and the DEXA scores for the lumbar spine and femoral neck. Conclusions: Because of the low level of mechanical stress on the calcaneus, the results of the QUS could not be correlated with the DEXA results for diagnosing osteoporosis. Therefore, QUS seems to be not a good choice for diagnosis and follow-up.

Combined heuristic with fuzzy system to transmission system expansion planning

A heuristic algorithm that employs fuzzy logic is proposed to the power system transmission expansion planning problem. The algorithm is based on the divide to conquer strategy, which is controlled by the fuzzy system. The algorithm provides high quality solutions with the use of fuzzy decision making, which is based on nondeterministic criteria to guide the search. The fuzzy system provides a self-adjusting mechanism that eliminates the manual adjustment of parameters to each system being solved. (C) 2010 Elsevier B.V. All rights reserved.

Altered left ventricular diastolic function in subjects with spinal cord injury

Study design: This is cross-sectional study. Objectives: The aim of this study is to investigate the cardiac structure and function of subjects with spinal cord injury (SCI) and the impact of metabolic, hemodynamic and inflammatory factors on these parameters. Setting: Sao Paulo, Brazil. Methods: Sixty-five nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI and 31 healthy subjects) were evaluated by medical history, anthropometry, laboratory tests, analysis of hemodynamic and inflammatory parameters and echocardiography. Results: Subjects with SCI had lower systolic blood pressure and higher levels of C-reactive protein and tumor necrosis factor receptors than the healthy ones. Echocardiography data showed that the SCI group presented similar left ventricular (LV) structural and systolic parameters, but lower initial diastolic velocity (Em) (9.2 +/- 0.5 vs 12.3 +/- 0.5 cm s(-1); P<0.001) and higher peak early inflow velocity (E)/Em ratio (7.7 +/- 0.5 vs 6.1 +/- 0.3; P = 0.009) compared with the able-bodied group, even after adjustment for systolic blood pressure and C-reactive protein levels. Furthermore, injured subjects with E/Em >8 had lower peak spectral longitudinal contraction (Sm) (9.0 +/- 0.7 vs 11.6 +/- 0.4cm s(-1); P<0.001) and cardiac output (4.2 +/- 0.2 vs 5.0 +/- 0.21 min(-1); P = 0.029), as well as higher relative wall thickness (0.38 +/- 0.01 vs 0.35 +/- 0.01; P = 0.005), than individuals with SCI with E/Em<8, but similar age, body mass index, blood pressure, injury level, metabolic parameters and inflammatory marker levels. Conclusion: Subjects with SCI presented impaired LV diastolic function in comparison with able-bodied ones. Moreover, worse LV diastolic function was associated with a pattern of LV concentric remodeling and subclinical decreases in systolic function among injured subjects. Overall, these findings might contribute to explain the increased cardiovascular risk reported for individuals with SCI. Spinal Cord (2011) 49, 65-69; doi: 10.1038/sc.2010.88; published online 27 July 2010

Effects of quadriceps and anterior tibial muscles electrical stimulation on the feet and ankles of patients with spinal cord injuries

Study design: Controlled clinical test. Objectives: The purpose of this study was to assess the effects of quadriceps and anterior tibial muscles electrical stimulation on the feet and ankles of patients with spinal cord injuries and to compare them with able-bodied individuals and a group of patients who did not undergo neuromuscular electrical stimulation (NMES). Setting: This study was conducted at the Hospital das Clinicas of Unicamp, Campinas, Sao Paulo, Brazil. Methods: Between January and April 2008, 30 patients at the spinal cord injury ambulatory clinic who underwent NMES (group A) were submitted to a clinical and radiographic assessment of their feet and ankles and compared with a spinal cord injury group (group B) who did not undergo NMES and a group of able-bodied individuals (group C). The Kruskal-Wallis test was used to compare all the three groups, and between-group differences (P < 0.05) were investigated with the Mann-Whitney test. Results: The mean mobility of the midfoot and ankle subtalar joint was significantly higher in group C than in groups A and B. Differences in the mean measurements of the profiles of the talocalcaneal and the talus-first metatarsal angles were statistically significant for group A vs the other groups (P = 0.0020, 0.0024, respectively). Foot deformities were found in groups including claw toes and flat feet (group A) and grade I ulcers on the lateral malleolus and calcaneus (group B). Conclusion: Partial-load NMES maintains the feet and ankles in a planted and adequate walking position in patients with spinal cord injuries, a favorable result of new technologies that allows these patients to reacquire independent walking capacity. Spinal Cord (2010) 48, 881-885; doi:10.1038/sc.2010.50; published online 18 May 2010

Sagittal spinal alignment in paraplegics: a new paradigm for the rehabilitation under neuromuscular electrical stimulation

Study design: Radiographic analysis of sagittal spinal alignment of paraplegics in a standing position under surface neuromuscular electrical stimulation (NMES). Objectives: Describing the radiographic parameters of the sagittal spinal alignment of paraplegics going through a rehabilitation program with NMES. Setting: The University Hospital`s Ambulatory (UNICAMP), Campinas, Sao Paulo, Brazil. Methods: Panoramic X-ray images in profile were taken for 10 paraplegics. All patients participated in the rehabilitation program and were able to perform gait through NMES of the femoral quadriceps muscles. The radiographic parameters used for the analysis were the same as those described in the literature for healthy people. The results were didactically organized into three groups: anatomical shape of the spine, morphology and kinetics of the pelvis and spinopelvic alignment. Results: The physiological curvature of the spine in paraplegics showed average values similar to those described in the literature for healthy patients. The inversion of the pelvic tilt and the increase in the sacral slope were defined by the anterior backward rotation of the pelvis. The existing theoretical mathematical formulas that define lumbar lordosis, pelvic incidence and pelvic tilt showed normal values, despite the anterior intense sagittal imbalance. Conclusions: The adaptive posture of the spine in paraplegics standing through the stimulation of the femoral quadriceps does not allow for a neutral sagittal alignment. This novel radiographic detailed description of the various segments of the spine can be of assistance toward the understanding of the global postural control for such subjects. Spinal Cord (2010) 48, 251-256; doi: 10.1038/sc.2009.123; published online 29 September 2009

Combined solution for fault location in three-terminal lines based on wavelet transforms

This work presents the study and development of a combined fault location scheme for three-terminal transmission lines using wavelet transforms (WTs). The methodology is based on the low- and high-frequency components of the transient signals originated from fault situations registered in the terminals of a system. By processing these signals and using the WT, it is possible to determine the time of travelling waves of voltages and/or currents from the fault point to the terminals, as well as estimate the fundamental frequency components. A new approach presents a reliable and accurate fault location scheme combining some different solutions. The main idea is to have a decision routine in order to select which method should be used in each situation presented to the algorithm. The combined algorithm was tested for different fault conditions by simulations using the ATP (Alternative Transients Program) software. The results obtained are promising and demonstrate a highly satisfactory degree of accuracy and reliability of the proposed method.

Relationship between median nerve somatosensory evoked potentials and spinal cord injury levels in patients with quadriplegia

Study design: Cross-sectional study. Objectives: To observe if there is a relationship between the level of injury by the American Spinal Cord Injury Association (ASIA) and cortical somatosensory evoked potential (SSEP) recordings of the median nerve in patients with quadriplegia. Setting: Rehabilitation Outpatient Clinic at the university hospital in Brazil. Methods: Fourteen individuals with quadriplegia and 8 healthy individuals were evaluated. Electrophysiological assessment of the median nerve was performed by evoked potential equipment. The injury level was obtained by ASIA. N(9), N(13) and N(20) were analyzed based on the presence or absence of responses. The parameters used for analyzing these responses were the latency and the amplitude. Data were analyzed using mixed-effect models. Results: N(9) responses were found in all patients with quadriplegia with a similar latency and amplitude observed in healthy individuals; N(13) responses were not found in any patients with quadriplegia. N(20) responses were not found in C5 patients with quadriplegia but it was present in C6 and C7 patients. Their latencies were similar to healthy individuals (P > 0.05) but the amplitudes were decreased (P < 0.05). Conclusion: This study suggests that the SSEP responses depend on the injury level, considering that the individuals with C6 and C7 injury levels, both complete and incomplete, presented SSEP recordings in the cortical area. It also showed a relationship between the level of spinal cord injury assessed by ASIA and the median nerve SSEP responses, through the latency and amplitude recordings. Spinal Cord (2009) 47, 372-378; doi:10.1038/sc.2008.147; published online 20 January 2009