Distribution by Scientific Domains

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  • Selected Abstracts

    The role of the ,-adrenergic receptor in the leg vasoconstrictor response to orthostatic stress

    ACTA PHYSIOLOGICA, Issue 3 2009
    M. Kooijman
    Abstract Aim:, The prompt increase in peripheral vascular resistance, mediated by sympathetic ,-adrenergic stimulation, is believed to be the key event in blood pressure control during postural stress. However, despite the absence of central sympathetic control of the leg vasculature, postural leg vasoconstriction is preserved in spinal cord-injured individuals (SCI). This study aimed at assessing the contribution of both central and local sympathetically induced ,-adrenergic leg vasoconstriction to head-up tilt (HUT) by including healthy individuals and SCI, who lack central sympathetic baroreflex control over the leg vascular bed. Methods:, In 10 controls and nine SCI the femoral artery was cannulated for drug infusion. Upper leg blood flow (LBF) was measured bilaterally using venous occlusion strain gauge plethysmography before and during 30° HUT throughout intra-arterial infusion of saline or the non-selective ,-adrenergic receptor antagonist phentolamine respectively. Additionally, in six controls the leg vascular response to the cold pressor test was assessed during continued infusion of phentolamine, in order to confirm complete ,-adrenergic blockade by phentolamine. Results:, During infusion of phentolamine HUT still caused vasoconstriction in both groups: leg vascular resistance (mean arterial pressure/LBF) increased by 10 ± 2 AU (compared with 12 ± 2 AU during saline infusion), and 13 ± 3 AU (compared with 7 ± 3 AU during saline infusion) in controls and SCI respectively. Conclusion:, Effective ,-adrenergic blockade did not reduce HUT-induced vasoconstriction, regardless of intact baroreflex control of the leg vasculature. Apparently, redundant mechanisms compensate for the absence of sympathetic ,-adrenoceptor leg vasoconstriction in response to postural stress. [source]

    Has the education of professional caregivers and lay people in dental trauma care failed?

    Ulf Glendor
    This situation could seriously affect the outcome of TDIs, especially a complicated TDI. The overall aim of this study was to present a review of dental trauma care with focus on treatment and dentists and lay persons' lack of knowledge on how to manage a TDI. A further aim is to introduce the actors involved and the outcome of their education. Material and method:, The databases Medline, Cochrane, SSCI, SCI and CINAHL from the year 1995 to the present were used. Focus was on treatment need, inadequate care, lack of knowledge and poor organization of emergency care. Result:, Studies from different countries demonstrated that treatment needs were not properly met despite the fact that not all untreated teeth needed treatment. Treatment in emergency dental care was often inadequate or inappropriate. With the exception of lay people, teachers, medical personnel and even dentists performed inadequate care. Furthermore, information to the public was insufficient. Despite a low level of knowledge, lay people expressed a strong interest in helping someone with a TDI. Conclusion:, The conclusion from this review is that consideration must be given the problematic results from different studies on education or information about dental trauma care. Despite that the studies reviewed were from different countries and groups of people, the results seem to be consistent, i.e. that a large part of the educational process of professional caregivers and lay people has failed. Too much hope seems to be put on lay people to handle difficult cases such as tooth avulsion. Education of caregivers and lay people is a field where much remains to be explored. [source]

    Mixed primary culture and clonal analysis provide evidence that NG2 proteoglycan-expressing cells after spinal cord injury are glial progenitors

    Soonmoon Yoo
    Abstract NG2+ cells in the adult rat spinal cord proliferate after spinal cord injury (SCI) and are postulated to differentiate into mature glia to replace some of those lost to injury. To further study these putative endogenous precursors, tissue at 3 days after SCI or from uninjured adults was dissociated, myelin partially removed and replicate cultures grown in serum-containing or serum-free medium with or without growth factors for up to 7 days in vitro (DIV). Cell yield after SCI was 5,6 times higher than from the normal adult. Most cells were OX42+ microglia/macrophages but there were also more than twice the normal number of NG2+ cells. Most of these coexpressed A2B5 or nestin, as would be expected for glial progenitors. Few cells initially expressed mature astrocyte (GFAP) or oligodendrocyte (CC1) markers, but more did at 7 DIV, suggesting differentiation of glial precursors in vitro. To test the hypothesis that NG2+ cells after SCI express progenitor-like properties, we prepared free-floating sphere and single cell cultures from purified suspension of NG2+ cells from injured spinal cord. We found that sphere cultures could be passaged in free-floating subcultures, and upon attachment the spheres clonally derived from an acutely purified single cell differentiated into oligodendrocytes and rarely astrocytes. Taken together, these data support the hypothesis that SCI stimulates proliferation of NG2+ cells that are glial progenitor cells. Better understanding the intrinsic properties of the NG2+ cells stimulated by SCI may permit future therapeutic manipulations to improve recovery after SCI. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source]

    Induction of endogenous neural precursors in mouse models of spinal cord injury and disease

    M. F. Azari
    Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin-positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord. [source]

    Involvement of mitochondrial signaling pathways in the mechanism of Fas-mediated apoptosis after spinal cord injury

    Wen Ru Yu
    Abstract Activation of the Fas receptor has been recently linked to apoptotic cell death after spinal cord injury (SCI). Although it is generally considered that Fas activation mediates apoptosis predominantly through the extrinsic pathway, we hypothesized that intrinsic mitochondrial signaling could be involved in the underlying mechanism of Fas-induced apoptosis after SCI. In the present study, we utilized the FejotaTM clip compression model of SCI at T5,6 in C57BL/6 Fas-deficient (lpr) and wild-type mice. Complementary studies were conducted using an in vitro model of trauma or a Fas-activating antibody to induce apoptosis in primary neuronal,glial mixed spinal cord cultures. After in vivo SCI, lpr mice, in comparison with wild-type mice, exhibited reduced numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells at the lesion, reduced expression of truncation of Bid (tBid), apoptosis-inducing factor, activated caspase-9 and activated caspase-3, and increased expression of the antiapoptotic proteins Bcl-2 and Bcl-xL. After in vitro neurotrauma or the induction of Fas signaling by the Jo2 activating antibody, lpr spinal cord cultures showed an increased proportion of cells retaining mitochondrial membrane integrity and a reduction of tBid expression, caspase-9 and caspase-3 activation, and TUNEL-positive cells as compared to wild-type spinal cord cultures. The neutralization of Fas ligand (FasL) protected against traumatically induced or Fas-mediated caspase-3 activation and the loss of mitochondrial membrane potential and tBid expression in wild-type spinal cord cultures. However, in lpr spinal cord cultures, FasL neutralization had no protective effects. In summary, these data provide direct evidence for the induction of intrinsic mitochondrial signaling pathways following Fas activation after SCI. [source]

    Glial cell loss, proliferation and replacement in the contused murine spinal cord

    Judith M. Lytle
    Abstract Studies in the rat have shown that contusive spinal cord injury (SCI) results in devastating pathology, including significant loss of mature oligodendrocytes and astrocytes even in spared white matter. Subsequently, there is increased proliferation of endogenous NG2+ cells, postulated to contribute to replacement of mature glia chronically, which is important for functional recovery. Studies of mechanisms that stimulate endogenous progenitor cells would be facilitated by using mouse models with naturally occurring and genetically engineered mutations. To determine whether the murine response is similar to that in the rat, we performed contusive SCI on adult female C57Bl/6 mice at the T8,9 level. Animals received bromodeoxyuridine injections in the first week following injury and were killed at 1, 3, 4, 7 or 28 days postinjury (DPI). The overall loss of macroglia and the temporal,spatial response of NG2+ cells after SCI in the (C57Bl/6) mouse was very similar to that in the (Sprague,Dawley) rat. By 24 h after SCI nearly half of the macroglia in spared ventral white matter had been lost. Cell proliferation was increased at 1,7 DPI, peaking at 3,4 DPI. Dividing cells included NG2+ cells and Cd11b+ macrophages and microglia. Furthermore, cells dividing in the first week expressed markers of mature glia at 28 DPI. The similarities in endogenous progenitor cell response to SCI in the mouse and rat suggest that this is a fundamental injury response, and that transgenic mouse models may be used to further probe how this cellular response to SCI might be enhanced to improve recovery after SCI. [source]

    Triptolide promotes spinal cord repair by inhibiting astrogliosis and inflammation

    GLIA, Issue 8 2010
    Zhida Su
    Abstract Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Traumatic SCI directly damages the cell bodies and/or processes of neurons and triggers a series of endogenous processes, including neuroinflammatory response and reactive astrogliosis. In this study, we found that triptolide, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis and inflammation and promoted spinal cord repair. Triptolide was shown to prevent astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced in injured spinal cord treated with triptolide. Triptolide treatment was also shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion site. Using neurofilament staining and anterograde tracing, a significantly greater number of regenerative axons were observed in the triptolide-treated rats. Importantly, behavioral tests revealed that injured rats receiving triptolide had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These results suggested that triptolide promoted axon regeneration and locomotor recovery by attenuating glial scaring and inflammation, and shed light on the potential therapeutic benefit for SCI. © 2010 Wiley-Liss, Inc. [source]

    Chemokine expression in the white matter spinal cord precursor niche after force-defined spinal cord contusion injuries in adult rats

    GLIA, Issue 8 2010
    Friederike Knerlich-Lukoschus
    Abstract Inflammatory cascades induced by spinal cord injuries (SCI) are localized in the white matter, a recognized neural stem- and progenitor-cell (NSPC) niche of the adult spinal cord. Chemokines, as integrators of these processes, might also be important determinants of this NSPC niche. CCL3/CCR1, CCL2/CCR2, and SDF-1,/CXCR4 were analyzed in the ventrolateral white matter after force defined thoracic SCI: Immunoreactivity (IR) density levels were measured 2 d, 7 d, 14 d, and 42 d on cervical (C 5), thoracic (T 5), and lumbar (L 5) levels. On day post operation (DPO) 42, chemokine inductions were further evaluated by real-time RT-PCR and Western blot analyses. Cellular phenotypes were confirmed by double labeling with markers for major cell types and NSPCs (nestin, Musashi-1, NG2, 3CB2, BLBP). Mitotic profiles were investigated in parallel by BrdU labeling. After lesion, chemokines were induced in the ventrolateral white matter on IR-, mRNA-, and protein-level. IR was generally more pronounced after severe lesions, with soaring increases of CCL2/CCR2 and continuous elevations of CCL3/CCR1. SDF-1, and CXCR4 IR induction was focused on thoracic levels. Chemokines/-receptors were co-expressed with astroglial, oligodendroglial markers, nestin, 3CB2 and BLBP by cells morphologically resembling radial glia on DPO 7 to DPO 42, and NG2 or Musashi-1 on DPO 2 and 7. In the white matter BrdU positive cells were significantly elevated after lesion compared with sham controls on all investigated time points peaking in the early time course on thoracic level: Here, chemokines were co-expressed by subsets of BrdU-labeled cells. These findings suggest an important role of chemokines/-receptors in the subpial white matter NSPC niche after SCI. © 2010 Wiley-Liss, Inc. [source]

    Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes

    GLIA, Issue 13 2008
    Wei-Lin Liu
    Abstract Reactive gliosis caused by post-traumatic injury often results in marked expression of chondroitin sulfate proteoglycan (CSPG), which inhibits neurite outgrowth and regeneration. Methylprednisolone (MP), a synthetic glucocorticoid, has been shown to have neuroprotective and anti-inflammatory effects for the treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG expression in reactive glial cells remains unclear. In our study, we induced astrocyte reactivation using ,-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and cyclothiazide to mimic the excitotoxic stimuli of SCI. The expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivation, and CSPG neurocan and phosphacan were significantly elevated by AMPA treatment. The conditioned media from AMPA-treated astrocytes strongly inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG expression in adult rats with SCI. Additionally, both the glucocorticoid receptor (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression. Taken together, these results suggest that MP may improve neuronal repair and promote neurite outgrowth after excitotoxic insult via GR-mediated downregulation of astrocyte reactivation and inhibition of CSPG expression. © 2008 Wiley-Liss, Inc. [source]

    Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction,

    Summary The purpose of this review is to present the current understanding of penile vibratory stimulation (PVS) and electroejaculation (EEJ) procedures and its clinical use in men with ejaculatory dysfunction. Unfortunately, the record of treating such individuals has been quite poor, but within recent years development and refinement of PVS and EEJ in men with spinal cord injury (SCI) has significantly enhanced the prospects for treatment of ejaculatory dysfunction. The majority of spinal cord injured men are not able to produce antegrade ejaculation by masturbation or sexual stimulation. However, approximately 80% of all spinal cord injured men with an intact ejaculatory reflex arc (above T10) can obtain antegrade ejaculation with PVS. Electroejaculation may be successful in obtaining ejaculate from men with all types of SCI, including men who do not have major components of the ejaculatory reflex arc. Because vibratory stimulation is very simple in use, non-invasive, it does not require anaesthesia and is preferred by the patients when compared with EEJ, PVS is recommended to be the first choice of treatment in spinal cord injured men. Furthermore, EEJ has been successfully used to induce ejaculation in men with multiple sclerosis and diabetic neuropathy. Any other conditions which affect the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully with EEJ. Finally, for sperm retrieval and sperm cryopreservation before intensive anticancer therapy in pubertal boys, PVS and EEJ have been successfully performed in patients who failed to obtain ejaculation by masturbation. Nearly all data concerning semen characteristics in men with ejaculatory dysfuntion originate from spinal cord injured men. Semen analyses demonstrate low sperm motility rates in the majority of spinal cord injured men. The data give evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few weeks) an acute SCI. Furthermore, it is suggested that some factors in the seminal plasma and/or disordered storage of spermatozoa in the seminal vesicles are mainly responsible for the impaired semen profiles in men with chronic SCI. Home insemination with semen obtained by penile vibratory and introduced intravaginally in order to achieve successful pregnancies may be an option for some spinal cord injured men and their partners. The majority of men will further enhance their fertility potential when using either penile vibratory or EEJ combined with assisted reproduction techniques such as intrauterine insemination or in-vitro fertilization with or without intracytoplasmic sperm injection. [source]

    Usefulness of a malleable penile prosthesis in patients with a spinal cord injury

    Young Dong Kim
    Objectives: The usefulness of a malleable penile prosthesis was evaluated in patients with spinal cord injury (SCI) by investigating the complications and the patients' satisfaction. Methods: A total of 48 patients with a SCI, who underwent malleable penile prosthesis (AMS 600) insertion from 1990 to 2004 were evaluated by reviewing the patients' medical records and interviewing them via questionnaires. The mean patients age was 58.9 years, and the mean follow-up period was 11.7 years. In 23 patients, penile prosthesis implantation was carried out to improve urinary management and to treat erectile dysfunction (ED). Results: Complications occurred in eight patients (16.7%). Wound infections in four (8.3%). Two patients were treated with conservative management, and two were managed through prostheses removal. Other complications were erosion in two patients (4.2%), uncontrolled penile pain owing to excessive prosthesis length in one patient (2.1%), and supersonic transporter (SST) deformity in one patient (2.1%). The overall patient satisfaction rate was 79.2%. The dissatisfaction was mainly due to the complications that resulted in the removal of the prosthesis, or partner's unnatural sensation. All of the prostheses that were implanted in the patients for the improvement of their urinary management gave them the benefit of convenient urinary management, except for two patients, whose prostheses were removed. Conclusions: The insertion of malleable penile prostheses in patients with SCI is associated with low complication rates and good patient satisfaction. It is therefore still an attractive option. [source]

    Histological evidences suggest recommending orchiopexy within the first year of life for children with unilateral inguinal cryptorchid testis

    Kwan Hyun Park
    Objective: To determine the optimal timing for orchiopexy, we evaluated the histological parameters of the cryptorchid testis. Methods: We prospectively performed testicular biopsy in a total of 65 consecutive children with palpable unilateral inguinal cryptorchid testes. For controls, we used testicular histological slides from 15 age-matched children with testicular tumor. To investigate the fertility potential, we analyzed the parameters including mean tubular diameter (MTD), mean tubular fertility index (MTFI), germ cell count/tubule (GCC), Sertoli cell index (SCI) and interstitial fibrosis index (IFI). Results: The MTFI and GCC in children ,1 years of age were significantly higher than those of other older age groups. The MTFI, GCC and IFI were significantly better in patients ,2 years of age when compared to those of > 2 years. Compared to the controls, the MTFI and GCC in the patients were significantly worse in those aged > 2 years at surgical repair. In the ,2-year age group, the MTFI and GCC of the cryptorchid testis showed a decreasing tendency with age, which were contrasting with the ascending curves in the control and the curves crossed at 1,2 years of age in each parameter. Conclusions: To protect fertility potential, we recommend, orchiopexy should be performed within the first year of life, and no later than 2 years of age in patients with palpable inguinal cryptorchid testes. [source]

    Intrathecal glutamate promotes glycinergic neuronal activity and inhibits the micturition reflex in urethane-anesthetized rats

    Objectives: In order to clarify the role of glutamate in the micturition reflex and in glutamatergic and glycinergic neuronal activity, we examined the effects of intrathecal (IT) injection of glutamate or MK-801 (an N- methyl-D-aspartate receptor antagonist) on bladder activity and on the glutamate and glycine levels in the lumbosacral cord of female rats with or without acute lower thoracic spinal cord injury (SCI). Methods: Under urethane anesthesia, isovolumetric cystometry was performed in rats with or without SCI before and after IT injection of glutamate or MK-801 at the lumbosacral cord level. The glutamate and glycine levels of the whole lumbosacral cord were measured after IT injection of glutamate or MK-801 in both groups. Results: In intact rats, IT glutamate (100 µg) prolonged the interval between bladder contractions and decreased the amplitude of contractions. IT MK-801 (3,100 µg) also prolonged the interval between bladder contractions and decreased the amplitude in intact rats. In SCI rats, cystometry demonstrated the disappearance of bladder contractions, and the glycine level in the lumbosacral cord was elevated. In intact rats, IT glutamate (0.3,100 µg) increased the glycine level in the lumbosacral cord. On the other hand, IT MK-801 (3,100 µg) decreased both glutamate and glycine levels in intact and SCI rats. Conclusions: These results suggest that glutamatergic neurons have stimulatory projections to both glutamatergic and glycinergic neurons in the lumbosacral cord, and that glutamatergic neurons inhibit the micturition reflex by stimulating glycinergic neurons. [source]

    Effect of surface conditions on the color of dental resin composites

    Yong-Keun Lee
    Abstract The objectives of this study were to evaluate the effect of surface conditions of dental resin composites on the measured color depending on the measuring geometry (SCE, SCI), and to determine the color difference (,E*) caused by varied surface conditions. Color and surface roughness (Ra) of five brands of resin composites of A2 shade were measured after polymerization and polishing with 600-, 1000-, or 1500-grit SiC paper. Color was measured according to the CIE L*a*b* color scale. ,E* between different surface conditions was calculated by the equation ,E* = [(,L*)2 + (,a*)2 + (,b*)2]1/2. Before polishing, CIE L* values with the SCE were significantly lower than those measured with the SCI. Before polishing, ,E* values depending on the measuring geometry were very high (3.78,5.93). However, those after polishing were lower than 1.61. CIE L* values increased after polishing (p < 0.05) with the SCE; however, they were not changed with the SCI. ,E* values between Mylar-covered and 600-grit polished specimens were 4.20,5.99 with the SCE and 0.27,1.46 with the SCI. Measurement with the SCE geometry may result in accurate color determination, which reflects the surface conditions of dental restorative materials. ,E* values measured with the SCE between the specimens of different surface conditions were significantly higher than those with the SCI (p < 0.05). © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 657,663, 2002 [source]

    Color characteristics of low-chroma and high-translucence dental resin composites by different measuring modes

    Yong-Keun Lee
    Abstract The objective of the described research was the evaluation of the effects of the differences in the color-measuring geometry (SCE, SCI) and the standard illuminant on the color and color change after polymerization and thermocycling of resin composites. White, translucent, and conventional shades of two brands of resin composites were measured before and after polymerization and after thermocycling according to the CIE L*a*b* color scale on a reflection spectrophotometer with SCE and SCI geometry under the standard illuminants A, D65, and C. Under both SCE and SCI modes, the color differences (,E*) of specimens between the values measured under illuminants A and D65 or A and C were larger than those between D65 and C in unpolymerized, polymerized, and thermocycled conditions. With SCE geometry, ,E* after polymerization of the white shade group was 8.7,9.8 under D65, and was higher than the conventional shade group (p < 0.05) in both materials. With SCE geometry, ,E* between polymerized and thermocycled white, translucent shade was 4.4,7.1 under D65. With SCI geometry, the results were in general agreement with those of SCE mode. After polymerization, ,E* measured under illuminant A was generally higher than that under D65 or C (p < 0.01). After thermocycling, the color change was different depending on the color-measuring geometry and standard illuminant. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 613,621, 2001 [source]

    ERK 1/2 signaling pathway is involved in nicotine-mediated neuroprotection in spinal cord neurons

    Michal Toborek
    Abstract Evidence indicates that agonists of neuronal nicotinic receptors (nAChRs), including nicotine, can induce neuroprotective and anti-apoptotic effects in the CNS. To study these mechanisms, the present study focused on nicotine-mediated modulation of the extracellular regulated kinase 1 and 2 (ERK1/2) pathway in cultured spinal cord neurons. Exposure to nicotine (0.1,10 µM) for as short as 1 min markedly upregulated levels of phosphorylated ERK1/2 (pERK1/2) and increased total ERK1/2 activity. Inhibition studies with mecamylamine and ,-bungarotoxin revealed that these effects were mediated by the ,7 nicotinic receptor. In addition, pre-exposure to U0126, a specific inhibitor of the ERK1/2 signaling, prevented nicotine-mediated anti-apoptotic effects. To indicate if treatment with nicotine also can activate ERK1/2 in vivo, a moderate spinal cord injury (SCI) was induced in rats using a weight-drop device and nicotine was injected 2 h post-trauma. Consistent with in vitro data, nicotine increased levels of pERK1/2 in this animal model of spinal cord trauma. Results of the present study indicate that the ERK1/2 pathway is involved in anti-apoptotic effects of nicotine in spinal cord neurons and may be involved in therapeutic effects of nicotine in spinal cord trauma. J. Cell. Biochem. 100: 279,292, 2007. © 2006 Wiley-Liss, Inc. [source]

    Effects of dexmedetomidine or methylprednisolone on inflammatory responses in spinal cord injury

    M. CAN
    Background: The aim of this study was to compare the anti-inflammatory response of methylprednisolone and the ,2-agonist dexmedetomidine in spinal cord injury (SCI). Methods: Twenty-four male adult Wistar albino rats, weight 200,250 g, were included in the study. The rats were divided into four groups as follows: the control group (n: 6) received only laminectomy; the SCI group (n: 6) with trauma alone; the SCI+methylprednisolone group (n: 6) with trauma and 30 mg/kg methylprednisolone, followed by a maintenance dose of 5.4 mg/kg/h; and the SCI+dexmedetomidine group (n: 6) with trauma and 10 ,g/kg dexmedetomidine treatment intraperitoneally. Twenty-four hours after the trauma, spinal cord samples were taken for histopathological examination and serum samples were collected for interleukin-6 (IL-6) and tumor necrosis factor (TNF)-, measurement. Results: TNF-, (P=0.009) and IL-6 (P=0.009) levels were significantly increased in the SCI group. TNF-, and IL-6 levels were significantly decreased with methylprednisolone (P=0.002, 0.002) and dexmedetomidine (P=0.002, 0.009) treatment, respectively. Methylprednisolone and dexmedetomidine treatment reduced neutrophils' infiltration in SCI. Conclusions: The current study does not clarify the definitive mechanism by which dexmedetomidine decreases inflammatory cytokines but it is the first study to report the anti-inflammatory effect of dexmedetomidine in SCI. Further studies are required to elucidate the effects of dexmedetomidine on the inflammatory response. [source]

    A review of pervaporation for product recovery from biomass fermentation processes,

    Leland M Vane
    Abstract Although several separation technologies are technically capable of removing volatile products from fermentation broths, distillation remains the dominant technology. This is especially true for the recovery of biofuels such as ethanol. In this paper, the status of an emerging membrane-based technology, called pervaporation, for this application is reviewed. Several issues and research priorities which will impact the ability of pervaporation to be competitive for biofuel recovery from fermentation systems are identified and discussed. They include: increased energy efficiency; reduction of capital cost for pervaporation systems; longer term trials with actual fermentation broths; optimized integration of pervaporation with fermentor; synergy of performing both alcohol recovery and solvent dehydration by pervaporation with dephlegmation fractional condensation technology; and updated economic analyses of pervaporation at various biofuel production scales. Pervaporation is currently viable for biofuel recovery in a number of situations, but more widespread application will be possible when progress has been made on these issues. Published in 2005 for SCI by John Wiley & Sons, Ltd. [source]

    The past, present, and future of chemometrics worldwide: some etymological, linguistic, and bibliometric investigations,

    R. Kiralj
    Abstract Internet surfing for the word chemometrics in national languages and, in the Science Citation Index (SCI), searching for articles containing chemometr * were performed. The bibliometric, webometric, and country development descriptors from literature were then treated by Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). In total, 82 written and 127 pronunciation forms of chemometrics were found in 48 languages worldwide. The forms ending in ,- y' (chemometry) and ,- ics' (chemometrics) can be grouped into at least three groups (I, J, K). Scientific collaboration, country development, geography, history, and language were shown to be important determinants in creation of form(s) of chemometrics in a particular country or language. PCA and HCA show that tradition in chemometrics, level of country development, and its scientific production are important for the existence of chemometric societies and laboratories worldwide. Today, the world tends toward becoming more homogeneous with respect to chemometric activity, and will reach a corresponding normal distribution in about 70 years from now. Copyright © 2007 John Wiley & Sons, Ltd. [source]

    Sonographic evaluation of gallbladder contractility in patients with spinal cord injury

    Mauro Nakayama MD
    Abstract Purpose. To determine gallbladder volume with sonography during fasting and in response to a fatty meal in patients with spinal cord injuries (SCIs) and compare the results with those obtained in healthy controls. Method. Forty-three patients with SCI and 40 healthy volunteers without clinical evidence of gallbladder disease underwent sonography before and 30 and 60 minutes after the ingestion of a standard fatty meal. The gallbladder fasting volume, resting volume, and gallbladder contractility were calculated, and the results were compared. Correlation between gallbladder contractility and level of lesion, time since injury, use of oxybutynin, and body mass index (BMI) was also assessed. Results. The mean ejection fraction was significantly lower in the patients with SCIs (40%) compared with healthy controls (63%) (p < 0.001). Gallbladder mean residual volume 60 minutes after ingestion of the fatty meal was lower in the control group (p < 0.001). Conclusion. Gallbladder contractility is impaired in patients with SCI, which may predispose these patients to gallstone formation. There was no correlation between gallbladder contractility and level of the lesion, time since injury, use of oxybutynin, or BMI. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008 [source]

    Revisiting the Sense of Community Index: A confirmatory factor analysis

    Patricia L. Obst
    The Sense of Community Index (SCI) is one of the most commonly used measures of Psychological Sense of Community (PSOC). There is much discussion in the literature as to the validity of the scale as a measure not only of overall PSOC, but also of the dimensions (Membership, Influence, Needs Fulfillment, and Emotional Connection) theorized by McMillan and Chavis (1986) to underlie the construct. The current paper examines the factor structure of SCI in a study ( N = 219) that examines multiple community memberships, including neighborhood, student, and interest group communities. Data was analyzed by confirmatory factor analysis (CFA). The results showed that the SCI, in its original factor structure, did not adequately fit the data. The scale was revised, therefore, using CFA indicators, to produce a new four-factor structure based on the same items. This revised model was tested and found to display adequate fit indices to the data in all three communities. The results of the study provide empirical support for retaining measures that encapsulate the four dimensions of PSOC. © 2004 Wiley Periodicals, Inc. J Comm Psychol 32: 691,705, 2004. [source]

    Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats

    Dai-Shi Tian
    Abstract Tamoxifen has been found to be neuroprotective in both transient and permanent experimental ischemic stroke. However, it remains unknown whether this agent shows a similar beneficial effect after spinal cord injury (SCI), and what are its underlying mechanisms. In this study, we investigated the efficacy of tamoxifen treatment in attenuating SCI-induced pathology. Blood,spinal cord barrier (BSCB) permeability, tissue edema formation, microglial activation, neuronal cell death and myelin loss were determined in rats subjected to spinal cord contusion. The results showed that tamoxifen, administered at 30 min post-injury, significantly decreased interleukin-1, (IL-1,) production induced by microglial activation, alleviated the amount of Evans blue leakage and edema formation. In addition, tamoxifen treatment clearly reduced the number of apoptotic neurons post-SCI. The myelin loss and the increase in production of myelin-associated axonal growth inhibitors were also found to be significantly attenuated at day 3 post-injury. Furthermore, rats treated with tamoxifen scored much higher on the locomotor rating scale after SCI than did vehicle-treated rats, suggesting improved functional outcome after SCI. Together, these results demonstrate that tamoxifen provides neuroprotective effects for treatment of SCI-related pathology and disability, and is therefore a potential neuroprotectant for human spinal cord injury therapy. [source]

    Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury

    Barry W. Festoff
    Abstract Minocycline, a clinically used tetracycline for over 40 years, crosses the blood,brain barrier and prevents caspase up-regulation. It reduces apoptosis in mouse models of Huntington's disease and familial amyotrophic lateral sclerosis (ALS) and is in clinical trial for sporadic ALS. Because apoptosis also occurs after brain and spinal cord (SCI) injury, its prevention may be useful in improving recovery. We analyzed minocycline's neuroprotective effects over 28 days following contusion SCI and found significant functional recovery compared to tetracycline. Histology, immunocytochemistry, and image analysis indicated statistically significant tissue sparing, reduced apoptosis and microgliosis, and less activated caspase-3 and substrate cleavage. Since our original report in abstract form, others have published both positive and negative effects of minocycline in various rodent models of SCI and with various routes of administration. We have since found decreased tumor necrosis factor-,, as well as caspase-3 mRNA expression, as possible mechanisms of action for minocycline's ameliorative action. These results support reports that modulating apoptosis, caspases, and microglia provide promising therapeutic targets for prevention and/or limiting the degree of functional loss after CNS trauma. Minocycline, and more potent chemically synthesized tetracyclines, may find a place in the therapeutic arsenal to promote recovery early after SCI in humans. [source]

    A study of juvenile rat spinal cord injury

    J. M. Wingrave
    Greater than 5% of all spinal cord injuries (SCI) in the US occur in people younger than 16, although a minority, children will require extended attention during their lifetime. While facing increased mortality in the initial 24 h after trauma, children with incomplete injuries seem to have a greater capacity for recovery of function compared to adults suggesting that there is a difference in injury tolerance in the young over the adult. Knowledge of the factors involved in this difference would not only increase understanding of SCI, but also potentiate new avenues for SCI treatment. Yet there has not been a model for the study of youth SCI. For these reasons, we developed a model of SCI in juvenile rats equivalent to an adult injury of 25 g cm force (GCF). To do so, we recorded spinal cord masses of Sprague,Dawley rats at 21, 30, 45, and 60 days of age, compared them to adult cord masses, and assembled a conversion factor that provides youth injuries comparable to adult. To investigate the pathophysiology in juvenile SCI, two cord segments, 1 cm long, were removed from animals 24 h following injury. One segment was centered at the impact site, the other immediately caudal. After homogenization, the samples were assayed by Western blot analysis for calpain content and degradation of 68K Neuro-Filament Protein (68K NFP), a neuronal structural protein. mCalpain expression, a neutral protease previously implicated in secondary SCI, was reduced in juvenile animals relative to adult cohorts. The degradation of 68K NFP was also found to be reduced in juvenile animals. From these analyses, it seems plausible that calpain expression and pathogenic activity is abated in the setting of young rat SCI. Acknowledgements:, Supported by grants from NIH-NINDS. [source]

    Estrogen as a neuroprotective agent in rat spinal cord injury

    N. L. Banik
    Spinal cord injury (SCI) is a neurological problem affecting approximately 11 000 Americans each year. Several treatment agents have been proposed; however, only methylprednisolone has limited efficacy. Estrogen is a multiactive neuroprotectant with antioxidant and anti-inflammatory properties and attenuates calcium (Ca2+) influx following neuronal injury. To examine the neuroprotective effects of estrogen in SCI, we induced SCI (40 g/cm injury) in rats. Treatment groups were sham (laminectomy only), SCI plus vehicle, and SCI plus estrogen. Injured rats were treated with either 4 mg/kg 17 ,-estradiol (estrogen group) or dimethylsulfoxide (vehicle group) at 15 min and 24 h following injury. All rats were killed at 48 h to analyze SCI segments for calpain content and Bax/Bcl-2 ratio by Western blotting. Tissue was also examined using calcium green-2 to measure intracellular [Ca2+], JC-1 to measure mitochondrial membrane potential, and double immunofluorescence for macrophages and calpain. Calpain content in the lesion penumbra, adjacent to the injury, was higher in vehicle than sham and this increase was attenuated in estrogen treated rats. In the lesion penumbra, the Bax/Bcl-2 ratio was increased in vehicle rats as compared to sham. This increase was attenuated in estrogen treated rats. Estrogen treated rats had less Ca2+ influx, less inflammatory cell infiltration, and increased maintenance of mitochondrial membrane potential compared to vehicle treated rats. Our preliminary data suggest that estrogen may be effective in decreasing Ca2+ influx, inflammatory cell infiltration, and Bax/Bcl-2 ratio following SCI. Acknowledgements:, Supported in part by grants from NIH-NINDS and South Carolina Electric and Gas. [source]

    Mechanisms of inflammation in spinal cord injury

    D. S. Rafati
    The inflammatory response initiated after spinal cord injury (SCI) is characterized by an increase in cytokines, notably IL-1,. Among its effects are the transcriptional control of cyclooxygenase 2 (COX-2) and the inducible form of nitric oxide synthase (iNOS). While they may ameliorate inflammation, they may also cause cellular damage via production of reactive oxygen species (O2 , ., OH·, NO·). The transcription factor NF-,B is a key intermediary in the signalling pathways leading from IL-1, expression to COX-2 and iNOS stimulation. Binding of NF-,B can be abrogated by the use of oligonucleotide ,decoys' that compete for the cognate endogenous NF-,B proteins. Using injections of fluorescent ,decoy' oligonucleotides into two-month-old-male rats after SCI into the site of injury, we found prompt, robust and transient uptake of labelled ,decoys' into both cytoplasm and nuclei of resident cells. Injection of ,decoys' containing the NF-,B binding sequences present in the COX-2 promoter region, together with a ,nonsense' sequence, showed selective effects on iNOS expression at the site of injury. These results are consistent with the hypothesis that NF-,B transcriptional regulation of COX-2 and iNOS are linked and may be an element in the pathophysiology and recovery of mammalian spinal cord after contusion injury. Acknowledgements:, Supported in part by NINDS Grant NS-39161 and Shriners Hospital Grant 8710. [source]

    GeneChip® analysis after acute spinal cord injury in rat

    Guoqing Song
    Spinal cord injury (SCI) leads to induction and/or suppression of several genes, the interplay of which governs the neuronal death and subsequent loss of motor function. Using GeneChip®, the present study analyzed changes in the mRNA abundance at 3 and 24 h after SCI in adult rats. SCI was induced at T9 level by the New York University impactor by dropping a 10-g weight from a height of 25 mm. Several transcription factors, immediate early genes, heat-shock proteins, pro-inflammatory genes were up-regulated by 3 h, and persisted at 24 h, after SCI. On the other hand, some neurotransmitter receptors and transporters, ion channels, kinases and structural proteins were down-regulated by 3 h, and persisted at 24 h, after SCI. Several genes that play a role in growth/differentiation, survival and neuroprotection were up-regulated at 24 h after SCI. Using real-time quantitative PCR, the changes observed by GeneChip® were confirmed for seven up-regulated (interleukin-6, heat-shock protein-70, heme oxygenase-1, suppressor of cytokine signaling 2, suppressor of cytokine signaling 3, interferon regulatory factor-1, neuropeptide Y), two down-regulated (vesicular GABA transporter and cholecystokinin precursor) and two unchanged (Cu/Zn-superoxide dismutase and phosphatidyl inositol-3-kinase) genes. The present study shows that inflammation, neurotransmitter dysfunction, increased transcription, ionic imbalance and cytoskeletal damage starts as early as 3 h after SCI. In addition to these effects, 24 h after SCI the repair and regeneration process begins in an attempt to stabilize the injured spinal cord. [source]

    Mobilization of CD133+CD34, cells in healthy individuals following whole-body acupuncture for spinal cord injuries,

    Sonja Moldenhauer
    Abstract Acupuncture can alleviate symptoms of spinal cord injuries (SCI). The underlying mechanism, however, is unknown. We hypothesized that stem cells could be mobilized by acupuncture. Therefore, we enrolled 14 healthy study participants using acupuncture points for the treatment of SCI. The frequency of CD133 and CD34 cells in peripheral blood and the serum concentrations of matrix metalloproteinase (MMP)-9, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and interleukin-6 were determined before and after acupuncture (<1 hr, 24 hr, and 48 hr). CD133+34, cells were doubled 48 hr after acupuncture, with concomitant decreases in BDNF and MMP-9 levels. Interleukin-6 remained below detectable levels, eliminating a stress-induced cell release. Individuals acupunctured on control counterpoints showed no changes in CD133+ cells. Our results indicate that acupuncture for SCI can mobilize human CD133+34, cells. © 2009 Wiley-Liss, Inc. [source]

    Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats

    Eric A. Sribnick
    Abstract Spinal cord injury (SCI) causes loss of neurological function and, depending on serverity, may cause paralysis. The only recommended pharmacotherapy for the treatment of SCI is high-dose methylprednisolone, and its use is controversial. We have previously shown that estrogen treatment attenuated cell death, axonal and myelin damage, calpain and caspase activities, and inflammation in acute SCI. The aim of this study was to examine whether posttreatment of SCI with estrogen would improve locomotor function by protecting cells and axons and reducing inflammation during the chronic phase following injury. Moderately severe injury (40 g · cm force) was induced in male Sprague-Dawley rats following laminectomy at T10. Three groups of animals were used: sham (laminectomy only), vehicle (dimethyl sulfoxide; DMSO)-treated injury group, and estrogen-treated injury group. Animals were treated with 4 mg/kg estrogen at 15 min and 24 hr postnjury, followed by 2 mg/kg estrogen daily for the next 5 days. After treatment, animals were sacrificed at the end of 6 weeks following injury, and 1-cm segments of spinal cord (lesion, rostral to lesion, and caudal to lesion) were removed for biochemical analyses. Estrogen treatment reduced COX-2 activity, blocked nuclear factor-,B translocation, prevented glial reactivity, attenuated neuron death, inhibited activation and activity of calpain and caspase-3, decreased axonal damage, reduced myelin loss in the lesion and penumbra, and improved locomotor function compared with vehicle-treated animals. These findings suggest that estrogen may be useful as a promising therapeutic agent for prevention of damage and improvement of locomotor function in chronic SCI. © 2010 Wiley-Liss, Inc. [source]

    Transplantation of galectin-1-expressing human neural stem cells into the injured spinal cord of adult common marmosets

    Junichi Yamane
    Abstract Delayed transplantation of neural stem/progenitor cells (NS/PCs) into the injured spinal cord can promote functional recovery in adult rats and monkeys. To enhance the functional recovery after NS/PC transplantation, we focused on galectin-1, a carbohydrate-binding protein with pleiotropic roles in cell growth, differentiation, apoptosis, and neurite outgrowth. Here, to determine the combined therapeutic effect of NS/PC transplantation and galectin-1 on spinal cord injury (SCI), human NS/PCs were transfected by lentivirus with galectin-1 and green fluorescent protein (GFP), (Gal-NS/PCs) or GFP alone (GFP-NS/PCs), expanded in vitro, and then transplanted into the spinal cord of adult common marmosets, 9 days after contusive cervical SCI. The animals' motor function was evaluated by their spontaneous motor activity, bar grip power, and performance on a treadmill test. Histological analyses revealed that the grafted human NS/PCs survived and differentiated into neurons, astrocytes, and oligodendrocytes. There were significant differences in the myelinated area, corticospinal fibers, and serotonergic fibers among the Gal-NS/PC, GFP-NS/PC, vehicle-control, and sham-operated groups. The Gal-NS/PC-grafted animals showed a better performance on all the behavioral tests compared with the other groups. These findings suggest that Gal-NS/PCs have better therapeutic potential than NS/PCs for SCI in nonhuman primates and that human Gal-NS/PC transplantation might be a feasible treatment for human SCI. © 2010 Wiley-Liss, Inc. [source]