ABSTRACT
This study investigated the therapeutic effects of low-level laser irradiation (LLLI) on the recovery of motor function and its underlying mechanisms in rats with spinal cord injury (SCI). The spinal cord was contused at the T11 level using a New York University impactor. Thirty-eight rats were randomly divided into four groups: LLLI with 0.08 J, 0.4 J, 0.8 J, and sham. We transcutaneously applied at the lesion site of the spinal contusive rats 5 min after injury and then daily for 21 days. The Basso, Beattie and Bresnahan (BBB) locomotor scale and combined behavioral score (CBS) were used to evaluate motor function. The spinal segments of rostral and caudal from the lesion site, the epicenter, and L4–5 were collected from normal and the all groups at 7 days after SCI. The expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) was compared across groups in all regions. In the present study, LLLI with 0.4 J and 0.8 J led to a significant improvement in motor function compared to sham LLLI, which significantly decreased TNF-α expression at the lesion epicenter and reduced iNOS expression in the caudal segment for all LLLI groups and in the L4–5 segments for the 0.4 J and 0.8 J groups when compared to sham LLLI group. Our results demonstrate that transcutaneous LLLI modulate inflammatory mediators to enhance motor function recovery after SCI. Thus, LLLI in acute phase after SCI might have therapeutic potential for neuroprotection and restoration of motor function following SCI.
Subject(s)
Animals , Rats , Necrosis , Neuroprotection , Nitric Oxide Synthase Type II , Recovery of Function , Spinal Cord Injuries , Spinal Cord , Therapeutic UsesABSTRACT
Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain.
Subject(s)
Animals , Rats , Analgesia , Cholecystokinin , Morphine , Neuralgia , Nociception , Spinal Cord InjuriesABSTRACT
Heat shock proteins (HSPs) are specifically induced by various forms of stress. Hsp70.1, a member of the hsp70 family is known to play an important role in cytoprotection from stressful insults. However, the functional role of Hsp70 in motor function after spinal cord injury (SCI) is still unclear. To study the role of hsp70.1 in motor recovery following SCI, we assessed locomotor function in hsp70.1 knockout (KO) mice and their wild-type (WT) mice via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, before and after spinal hemisection at T13 level. We also examined lesion size in the spinal cord using Luxol fast blue/cresyl violet staining. One day after injury, KO and WT mice showed no significant difference in the motor function due to complete paralysis following spinal hemisection. However, when it compared to WT mice, KO mice had significantly delayed and decreased functional outcomes from 4 days up to 21 days after SCI. KO mice also showed significantly greater lesion size in the spinal cord than WT mice showed at 21 days after spinal hemisection. These results suggest that Hsp70 has a protective effect against traumatic SCI and the manipulation of the hsp70.1 gene may help improve the recovery of motor function, thereby enhancing neuroprotection after SCI.
Subject(s)
Animals , Humans , Mice , Cytoprotection , Heat-Shock Proteins , HSP70 Heat-Shock Proteins , Paralysis , Spinal Cord , Spinal Cord Injuries , ViolaABSTRACT
PURPOSE: We screened more than 350 compounds with an endoperoxide ring structure in search of an anti-leukemic drug and found that compound 127 (c-127) could induce significant cytotoxicity in HL-60 cells. In this study, we investigated the molecular mechanisms of compound 127-induced antitumor activity on HL-60 cells. METHODS: HL-60 cells were cultured in Rosewell Park Memorial Institute 1640 and cell viability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], a tetrazole assay. Apoptosis was assessed by a DNA fragmentation test. Apoptotic machineries were determined by Western blot analysis. RESULTS: C-127 could induce a cytotoxic effect at 24 h and apoptosis at 6 h, which was demonstrated with MTT assay and DNA fragmentation test, respectively. The apoptotic effect of this drug was caused by the activation of the intracellular caspase-8,3 activation, the cleavage of pro-apoptotic Bid, and the increase of c-Jun expression accompanied with JNK (Jun N-terminal kinases) phosphorylation. On the contrary, it increased the expression of anti-apoptotic Bcl-2 levels, leading to the induction of the induction of anti-apoptotic effect. Taken together, the present study demonstrated that c-127 was a potent inducer of cytotoxicity on HL-60 cells through apoptotic mechanisms, which included the activation of caspase family, the regulation of Bcl-2 family, and the activation of JNK signaling pathway. CONCLUSION: Our results suggest that c-127 has a strong antitumor activity through the regulation of various apoptotic machineries on HL-60 cells. The compound may be utilized as an effective and potentially therapeutic drug in leukemia.
Subject(s)
Humans , Apoptosis , Artemisinins , Blotting, Western , Cell Survival , DNA Fragmentation , HL-60 Cells , Leukemia , MAP Kinase Signaling System , Phosphorylation , TetrazolesABSTRACT
The present study was performed to observe the time course of behavioral signs of painful sensations in sciatic neurectomy animal model and to test the effects of sympathectomy and saphenous nerve section on these behavioral signs. Sciatic nerve was ligated and cut at the mid-thigh level under gaseous anesthesia. The application of von Frey filaments to the medial plantar surface of foot revealed weak and long-lasting mechanical allodynia (until end of test period, 20 weeks PO). Acetone application to the plantar surface of foot was used ti measure the sensitivity to cold stimulation. Cold allodynia which is interpreted as increased response to acetone application developed fairly well and lasted the end of test period (20 weeks PO). The cumulative duration of foot lifts off neutral or cold plate was used to test spontaneous, ongoing pain and was increased until 16 weeks PO and 20 weeks PO respectively. These results suggest that sciatic neurectomy which has been widely used as chronic pain model shows behavioral signs suggsting painful sensations except autotomy, which has been used as index of pain in experimental animal. Surgical sympathectomy performed 1 week after sciatic neurectomy partially reduced the behavioral signs of mechanical allodynia and cold allodynia, suggesting behavioral changes developed following section of sciatic nerve was partially sympathetic dependent. Saphenous nerve section 1 week after sciatic neurectomy almost completely reduced mechanical allodynia and cold allodynia, but did not change spontaneous, ongoing pain. These results suggest that evoked responses such as mechanical and cold allodynia are mediated by saphenous nerve activity and activating and/or maintaining mechanisms of spontanous, ongoing pain and evoked pain may be different.
Subject(s)
Animals , Rats , Acetone , Anesthesia , Chronic Pain , Cold Temperature , Foot , Hyperalgesia , Models, Animal , Neuralgia , Sciatic Nerve , Sensation , SympathectomyABSTRACT
Sometimes, spinal cord injury (SCI) results in various chronic neuropathic pain syndromes that occur diffusely below the level of the injury. It has been reported that behavioral signs of neuropathic pain are expressed in the animal models of contusive SCI. However, the observation period is relatively short considering the natural course of pain in human SCI patients. Therefore, this study was undertaken to examine the time course of mechanical and cold allodynia in the hindpaw after a spinal cord contusion in rats for a long period of time (30 weeks). The hindpaw withdrawal threshold to mechanical stimulation was applied to the plantar surface of the hindpaw, and the withdrawal frequency to the application of acetone was measured before and after a spinal contusion. The spinal cord contusion was produced by dropping a 10 g weight from a 6.25 and 12.5 mm height using a NYU impactor. After the injury, rats showed a decreased withdrawal threshold to von Frey stimulation, indicating the development of mechanical allodynia which persisted for 30 weeks. The withdrawal threshold between the two experimental groups was similar. The response frequencies to acetone increased after the SCI, but they were developed slowly. Cold allodynia persisted for 30 weeks in 12.5 mm group. The sham animals did not show any significant behavioral changes. These results provide behavioral evidence to indicate that the below-level pain was well developed and maintained in the contusion model for a long time, suggesting a model suitable for pain research, especially in the late stage of SCI or for long term effects of analgesic intervention.
Subject(s)
Animals , Humans , Rats , Acetone , Benzeneacetamides , Cold Temperature , Contusions , Follow-Up Studies , Hyperalgesia , Hypersensitivity , Models, Animal , Neuralgia , Piperidones , Salicylamides , Spinal Cord , Spinal Cord InjuriesABSTRACT
Diamino-diphenyl-sulfone (Dapsone) is widely used in the treatment of leprosy and a variety of blistering skin diseases. It sometimes has adverse side effects with common usual doses, such as skin, nervous system, gastrointestinal tract, liver, kidney and hematologic toxicity. One of these side effects is a rare but serious hypersensitivity reaction called dapsone syndrome, which occurs several weeks after the initial administration of the drug and results in unpredictable, sometimes fatal outcomes. This report deals with a 13-year-old girl's case with typical features of dapsone syndrome that included fever, exfoliative dermatitis, jaundice, hemolytic anemia and pleural effusion after being treated with dapsone for four weeks.
Subject(s)
Adolescent , Humans , Anemia , Anemia, Hemolytic , Blister , Dapsone , Dermatitis, Exfoliative , Fatal Outcome , Fever , Gastrointestinal Tract , Hypersensitivity , Jaundice , Kidney , Leprosy , Liver , Nervous System , Pleural Effusion , Skin , Skin DiseasesABSTRACT
PURPOSE: alpha-Galactosylceramide (alpha-GalCer)-stimulated human Valpha24 natural killer T (NKT) cells exert antitumor activity against some leukemia in a CD1d dependent and TCR-mediated manner, but could not kill CD1d-negative neuroblastoma (NB) cells. There are few reports about the direct antitumor effect of highly secreted cytokines by these cells on activation. In this study, using a cell-free supernatant (SPN) collected from plate bound hCD1d/alphaGalCer tetramers-stimulated NKT cells, we examined whether they could be helpful in the immunotherapeutic treatment of NB. METHODS: Cells were cultured in IMDM. The cytokines produced by NKT cells were measured with Cytometric Bead Array (CBA) analysis. Cell viability was evaluated by calcein-AM fluorescence with digital image microscopy scanning (DIMSCAN). The percentage of specific apoptosis was calculated by flow cytometric detection of apoptosis using annexin V and 7-AAD. RESULTS: The activated NKT cells secreted high levels of IL-2, INF-gamma, TNF-alpha. The SPN was significantly cytotoxic against four out of eight tested NB cell lines, through mainly apoptosis as evidenced by annexin-V staining and inhibition with the pretreatment of pancaspase blocker. This apoptosis was significantly inhibited when anti-TNF-alpha and anti-IFN-gamma neutralizing mAbs were used separately and it was completely abolished when the two mAbs were combined. CONCLUSION: IFN-gamma and TNF-alpha produced by NKT cells could exert synergistically direct anti-tumor activity through apoptosis on some NB cell lines.
Subject(s)
Humans , Annexin A5 , Apoptosis , Cell Line , Cell Survival , Cytokines , Fluorescence , Interleukin-2 , Leukemia , Microscopy , Natural Killer T-Cells , Neuroblastoma , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Recent findings suggest that a coupling between the somatic and sympathetic nervous system is critical not only for the development but also for the maintenance of pain behavioral changes. However, studies on the effect of sympathetic efferent system on sensory receptors in the visceral organ that is more dependent on the autonomic nervous system are lacking. This study examined whether norepinephrine (NE) had an influence on the mechanoreceptors in the feline urinary bladder. METHODS: Ten adult male cats were used and anesthetized with alpha-chloralose and artificially ventilated. A cannula with the pressure transducer was inserted through the urethra to apply mechanical stimuli and monitor the pressure of bladder. A tiny cannula inserted into the bilateral side branches of vesical arteries were used as a route for a NE (10A.M 9:40 01-10-08 bilaterally) injection. Nerve fiber recordings were obtained from the distal stump of the pelvic nerve. RESULTS: After the NE injection, the response of mechanoreceptors (n = 13) to the isotonic pressure stimulus (50 - 60 mmHg) decreased significantly (p < 0.05) in terms of sensitivity (i.e., ratio of nerve activity change to urinary bladder pressure change). The responses to pressure stimuli after an injection of an alpha1 adrenoceptor blocker (terazosin) reversed the effect of NE. The responses of mechanoreceptors to isotonic pressure stimulus were not affected significantly by NE with preinjection of an alpha2 adrenoceptor blocker (yohimbine). CONCLUSIONS: These results suggest that NE may have influence on the sensitivity of mechanoreceptors in the normal feline urinary bladder via an alpha1 adrenoceptor.
Subject(s)
Adult , Animals , Cats , Humans , Male , Adrenergic alpha-1 Receptor Antagonists , Arteries , Autonomic Nervous System , Catheters , Chloralose , Mechanoreceptors , Nerve Fibers , Norepinephrine , Sensory Receptor Cells , Sympathetic Nervous System , Transducers, Pressure , Urethra , Urinary BladderABSTRACT
It is well known that the inflammation of somatic tissues, bladder and colon can alter the sensitivity of primary afferents innervating these tissues. To see if uterine afferents also show altered sensitivity, we examined their responses to the algesic agent bradykinin before and after induction of uterine inflammation. Inflammation was induced by injecting the mustard oil into the uterine lumen of adult female rats. After induction of inflammation, the response latency to bradykinin did not change, but the duration and peak of the response and integrated impulse discharges during the response period increased significantly. Furthermore, after inflammation, the level of resting discharges of the afferents was much higher. These results are consistent with the idea that the inflammation can sensitize the uterine afferents.
Subject(s)
Adult , Animals , Female , Humans , Rats , Bradykinin , Colon , Inflammation , Mustard Plant , Nerve Fibers , Reaction Time , Urinary Bladder , UterusABSTRACT
Experimental renovascular hypertensive model was established by clipping left renal artery and the right side of renal artery was taken 1 week and 1 month after the operation. The renal artery ring preparations were made for contractility studies of vascular wall. The relaxing and contractile responses were recorded and compared with the data obtained from control group. The following results were obtained: 1)One week after the clipping of renal artery, the renovascular hypertensive group showed increased contractility against the various contractile agents (high K+, norepinephrine, caffeine) compared to control group. 2)One month after the clipping of renal artery, the contractile responses to various contractile agents were restored to the level of control group. 3)One week after the clipping of renal artery, the renovascular hypertensive group showed increased responsiveness to acetylcholine treatment, however did not show any remarkable changes to other relaxing agents(sodium nitroprusside, verapamil). 4)One month after the clipping of renal artery, the responses to various relaxing agents showed almost same degree of responsiveness in the renovascular hypertensive group as compared with that of control group. From the above, it is suggested that stenosis- induced renovascular hypertension might induce exaggerated vascular response at early stage in intact renal artery. And the effects may be concerned with endothelium-dependent mechanism.
Subject(s)
Acetylcholine , Hypertension, Renovascular , Nitroprusside , Norepinephrine , Relaxation , Renal ArteryABSTRACT
PURPOSE: The purpose of this study was to evaluate the effects of theophylline in preterm infants with apnea on glucose homeostasis and insulin values. METHOD: In this prospective study, level of glucose and insulin were measured from peripheral blood of 8 neonates(1,450+/-114gm, 31+/-2.1week), who were admitted from April 1, 1997 to July 30, 1997 in Neonatal Intensive Care Unit of Wonkwang University Hospital, for apnea of prematurity(> 20 sec with bradycardia and/or cyanosis) were given aminophylline intravenously. Blood samples were collected at pretreatment, posttreatment 2hours, 1-2days, 3-4days, 5-7days and posttreatment 48hours, and compare to those of the 8 control neonates(1,711+/-232gm, 32+/-1.7week). RESULTS: The results were as follows: 1) Plasma glucose values were significantly higher in the treatment group than those of the control group at 1-2days(104.67+/-20.39mg/dL vs 83.43+/-15.86mg/dL) and 3-4days(111.0+/-32.39mg/dL vs 79.25+/-14.03mg/dL)(p 125mg/dL). 3) The mean posttreatment glucose levels drawn at 48hours after discontinuation of theophylline was significantly decreased to the values of pretreatment values compared to those of the 1-2days and 3-4days(p 125mg/dL) was not noted. So, plasma glucose may not need to be monitored in preterm apneic infants receiving theophylline. But, further studies are need to elucidate the effect of theophylline considering the serum toxic level of theophylline.
Subject(s)
Humans , Infant , Infant, Newborn , Administration, Intravenous , Aminophylline , Apnea , Blood Glucose , Bradycardia , Glucose , Homeostasis , Hyperglycemia , Infant, Premature , Insulin , Intensive Care, Neonatal , Plasma , Prospective Studies , TheophyllineABSTRACT
The aim of the present study is to verify the functional and anatomical neural pathways which innervate the urinary bladder in the central nervous system of the rat. To identify the functional neural pathway, the urinary bladder was stimulated by infusing formalin for 2 h. Then, brain and spinal cord were dissected out and immunohistochemistry was done by using anti-c-fos antibody. Many c-fos immunoreactive (IR) neurons were identified in the telencephalic cortical areas and in several brainstem nuclei, which are known mostly to be related with urinary bladder. In the spinal cord, a number of c-fos IR neurons were found in the lamina I, IIo, dorsal gray commissure, sacral parasympathetic nucleus. To identify the anatomical neural pathway of the urinary bladder, Pseudorabies virus (PRV) was injected into the wall of urinary bladder and was identified with anti-PRV by using immunohistochemistry. Most PRV labeled neurons were found where c-fos IR neurons were identified and few of them were also in the areas where c-fos IR neurons were not found, e.g., prefrontal cortex, agranular insular cortex, and subfornical organ. In the spinal cord, PRV labeled cells were found all over the gray matter. The present study presents morphological evidence demonstrating the supraspinal areas are related with the neural control of the urinary bladder and most functional neural pathway of the urinary bladder is well consistent with the anatomical neural pathway except in some telencephalic cortical areas.
Subject(s)
Female , Rats , Animals , Urinary Bladder/innervation , Central Nervous System/anatomy & histology , Herpesvirus 1, Suid/isolation & purification , Immunohistochemistry , Neural Pathways/anatomy & histology , Proto-Oncogene Proteins c-fos/analysis , Rats, Sprague-DawleyABSTRACT
No abstract available.