dinoprost and Spinal-Cord-Injuries

The effect of N-acetylcysteine administration intravenously before hemilaminectomy surgery on neurologic outcome and 15F 2t isoprostane excretion in dogs was examined in a blinded, placebo-controlled trial.. To determine the effect of N-acetylcysteine administration on urinary 15F 2t isoprostane excretion and neurologic outcome following hemilaminectomy for intervertebral disc disease.. Oxidative stress is a mediator of secondary injury to the spinal cord following trauma. Acute intervertebral disc disease is associated with increased oxidative damage in dogs. N-acetylcysteine has preserved neurologic function following experimental spinal cord injury.. Seventy dogs with naturally occurring acute intervertebral disc disease were administered either with saline placebo or N-acetylcysteine intravenously before hemilaminectomy surgery. Serial neurologic examinations were performed before and 1, 2, 7, 14, and 42 days following treatment. Urinary excretion of 15F 2t isoprostane excretion was determined before treatment and 1 hour after surgery.. Analysis of subjective data did not reveal any significant effect of N-acetylcysteine on neurologic outcome or rate of improvement of neurologic score in the 42 days following treatment. Urinary 15F 2t isoprostane excretion was not significantly different between treatment groups (P > 0.05).. N-acetylcysteine intravenously before hemilaminectomy has no effect on urinary 15F 2t isoprostane excretion or neurologic outcome. Treatment of dogs with the antioxidant N-acetylcysteine before hemilaminectomy, while not detrimental, does not affect neurologic outcome in the 42 days following surgery.

Topics: Acetylcysteine; Animals; Antioxidants; Biomarkers; Dinoprost; Disease Models, Animal; Dog Diseases; Dogs; Female; Infusions, Intravenous; Intervertebral Disc; Intervertebral Disc Displacement; Laminectomy; Male; Oxidative Stress; Random Allocation; Spinal Cord Injuries; Time Factors

Isoprostanes are prostaglandin-like end products of arachidonic acid peroxidation that are produced by a free radical-catalyzed mechanism. Considering its free radical-dependent formation and potent contractor effect, it is postulated that isoprostane 8-iso PGF2alpha may play an important role in oxidative stress-related smooth muscle dysfunction. These substances may also influence bladder activity directly by effects on the smooth muscle. The present study was designed to measure traditional biochemical parameters (MDA, TAS, vitamin E) in plasma and 8-iso PGF2alpha concentrations in urine of patients with spinal cord injury and to evaluate the relation of urinary isoprostane concentrations to the bladder function.. All spinal cord patients underwent urodynamic evaluations. The biochemical tests were performed in both hyperreflexic bladder group (n = 23) and areflexic bladder group (n = 10), and the findings were compared to those of the patients with normally functioning bladder (controls, n = 19).. Urine 8-iso PGF2alpha concentrations were significantly increased in hyperreflexic group (median value 0.89 pg/mg creatinine) compared to both control (0.52 pg/mg creatinine) and areflexic groups (p < 0.001). The lowest concentrations of urinary 8-iso PGF2alpha were observed in the areflexic group (0.22 pg/mg creatinine), and these were positively correlated to the plasma MDA concentrations in areflexic patients (p = 0.05; r = 0.684).. Isoprostanes may be involved in the pathogenesis of neurogenic bladder dysfunction. It may be of value to determine the urinary concentrations of 8-iso PGF2alpha in order to distinguish areflexic bladders from the hyperreflectics.

Topics: Adult; Antioxidants; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Malondialdehyde; Middle Aged; Spinal Cord Injuries; Uric Acid; Urinary Bladder, Neurogenic; Vitamin E

Neuropathic pain arising from peripheral nerve injury is a clinical disorder characterized by a combination of spontaneous pain, hyperalgesia and tactile pain (allodynia), and remains a significant clinical problem since it is often poorly relieved by conventional analgesics. To seek an analgesic compound(s) in Chinese herbs, we examined the effect of seven Chinese herbs that are routinely prescribed for pain management in two neuropathic pain models: allodynia induced by intrathecal administration of prostaglandin F2alpha (PGF2alpha) and by selective L5 spinal nerve transection. The extracts of Moutan cortex and Coicis semen dose-dependently alleviated the PGF2alpha-induced allodynia by oral administration 1 h before intrathecal injection of PGF2alpha. When orally administrated every day for 7 days, these extracts attenuated neuropathic pain in the ipsilateral side, but not in the contralateral side, day 7 after L5 spinal nerve transection. The increase in NADPH diaphorase activity in the spinal cord associated with neuropathic pain was also blocked by these extracts. These results suggest that Moutan cortex and Coicis semen contain substances effective in neuropathic pain.

Topics: Anesthesia; Animals; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Male; Mice; NADPH Dehydrogenase; Neuralgia; Paeonia; Pain Measurement; Spinal Cord; Spinal Cord Injuries; Time Factors

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprost; Enzyme Induction; Inflammation; Interleukin-1; Isoenzymes; Kinetics; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Rats; Spinal Cord Injuries; Tumor Necrosis Factor-alpha

The present study explores in vivo whether and how prostaglandin F(2alpha) (PGF(2alpha)), a membrane phospholipid hydrolysis product, causes neuronal death. The concentration of PGF(2alpha) measured by microdialysis sampling increased threefold immediately following impact injury to the rat spinal cord. Administration of PGF(2alpha) into the cord through a dialysis fiber caused significant cell loss, increased extracellular levels of hydroxyl radicals and malondialdehyde - an end product of membrane lipid peroxidation - to 3.3 and 2.3 times basal levels, respectively. This suggests that PGF(2alpha)-induced cell death is partly due to hydroxyl radical-triggered peroxidation. Generating hydroxyl radical by administering Fenton's reagents into the cord through the fibers significantly increased malondialdehyde production - the first direct in vivo evidence that hydroxyl radical triggers membrane lipid peroxidation. Methylprednisolone significantly reduced the release of PGF(2alpha) upon spinal cord injury and blocked PGF(2alpha)-induced hydroxyl radical and malondialdehyde production, but did not significantly reduce Fenton's reagent-induced malondialdehyde production, despite the production of more malondialdehyde by PGF(2alpha). This suggests that methylprednisolone may not directly scavenge hydroxyl radical, and that its 'antioxidant' effect is a consequence of blocking the pathways for producing toxic PGF(2alpha) and for PGF(2alpha)-induced hydroxyl radical formation, thereby reducing membrane lipid peroxidation.

Topics: Animals; Cell Death; Dinoprost; Hydroxyl Radical; Injections, Spinal; Male; Malondialdehyde; Methylprednisolone Hemisuccinate; Microdialysis; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Time Factors

This study investigates how strenuous arm exercise affects oxidized-low density lipoprotein (O(X)-LDL) mediated-platelet activation in patients with SCI. Ten patients with SCI and ten age- and sex-matched healthy subjects exercised strenuously using an arm crank ergometer. The following measurements were taken both when the subjects were at rest, and immediately after exercise: plasma lipid profile, O(X)-LDL mediated platelet aggregability and [Ca(2+)]i, urinary 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 8-iso-prostaglandin F(2alpha), (8-iso-PG F(2alpha)) contents, and plasma NO metabolite (nitrite plus nitrate) level. Based on these measurements, the major findings of this study can be summarized as follows: 1) the SCI group had higher urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB2 contents, but a lower plasma nitrite plus nitrate level than the control group; 2) at rest, the SCI group had a higher platelet aggregability and [Ca(2+)]i, and O(X)-LDL-potentiated platelet activation than the control group; 3) O(X)-LDL-potentiated platelet aggregation was enhanced by strenuous arm exercise in both groups, but the effect of exercise was more pronounced in the SCI group than in the control group; 4) treating the platelet with L-arginine inhibited O(X)-LDL-potentiated platelet activation in both groups. The study concludes that individuals with SCI had more extensive resting and exercise-enhanced O(X)-LDL-potentiated platelet activation and greater amounts of preformed lipid peroxides than those without SCI. Therefore, supplementation therapy with antioxidants may be needed for patients with SCI, especially in a strenuous arm exercise period.

Topics: Adult; Arm; Arteriosclerosis; Calcium; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dinoprost; Exercise Test; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Platelet Activation; Platelet Aggregation; Platelet Count; Risk Factors; Spinal Cord Injuries; Thromboxane B2

As prostaglandin F2alpha is present in biological materials, and plays an important physiological role at trace level in the living body, then, highly sensitive determination of PGs is required. Various fluorescence derivatization reagents have been proposed for the determination of PGs. The 3-bromomethyl-6,7-methylenedioxyl-1-methyl-2(1H)-quinoxalinone was found to be a highly sensitive fluorescence derivatization reagent for PGF2alpha in HPLC with a detectable limit of 10-15 fmol for PGF2alpha. In this work we optimized its reaction conditions. Thus the PGF2alpha was extracted from the microdialysates with ethyl acetate at pH 3.0-3.5 following which the extracts were evaporated to dryness. The residue was derivatized by adding acetonitrile, KHCO3, Br-DMEQ and 18-crown-6-ether at 50 degrees C for 30min in the dark. The corresponding fluorescent derivatives produced were separated on a C8 column (Phase-Sep Ltd.), 5microm, 4.6mm x 150mm. Stepwise elution with different ratios of A and B was carried out. 30:10:60 of CHsCN:CH3OH:H2O constituted A solution and 35:30:35 made B solution. The A/B (97/3) was first run for 25 min and A/B (50/50) for the next 15min. Then the column was equilibrated with A/B (97/3) for 20min before the next sample injected. Fluorescence detector was used at lambdaEX 370nm and lambdaEM 455nm, and flow-rate of 2.0mL/min. Because the most evidence for a role of free radicals in tissue damage is indirect, we attempt to determine whether OH causes release of arachidonic acid products in vivo. We did this by (1) generating OH radical in vivo in rat spinal cord by administering H2O2 and FeCl2/EDTA through two parallel microdialysis fibers so they mixed in the cord, and (2) analyzing PGF2alpha in microdialysates in response to OH generation by HPLC. We utilized dialysis fibers of < or = 220microm external diameter including their coating except for a 2mm dialysis zone which was coated with a thin layer of silicon rubber. When the animal was clamped, two microdialysis fibers glued together were inserted through the cord until the dialysis zone just placed in the gray matters of the cord. The time course of changes in levels of PGF2alpha during OH generation by Fe/H2O2 is given. Typical chromatogram of the dialysate collected from one animal is illustrated. Prostaglandin F2alpha dramatically increased in response to hydroxyl radical generation from undetectable (basal level) to about 333 +/- 166nmol/L (SD, n = 5) in 90min, Prostaglandin F2alp

Topics: Animals; Chromatography, High Pressure Liquid; Dinoprost; Disease Models, Animal; Humans; Hydroxyl Radical; Male; Rats; Spinal Cord; Spinal Cord Injuries

Free radicals and some free fatty acids, such as arachidonic acid metabolites, have been hypothesized to be contributors to secondary damage to the spinal cord upon injury. These two types of species may form a feedback loop in which generation of one type leads to formation of the other. In this study, to determine whether hydroxyl radical causes generation of arachidonic acid metabolites in vivo, we generated hydroxyl radical, a most reactive oxygen radical, in the rat spinal cord and measured resulting changes in levels of prostaglandin F2 alpha, an arachidonic acid metabolite that rises following traumatic injury. The hydroxyl radical was generated in the rat spinal cord by administering H2O2 through one microdialysis fiber and FeCl2/EDTA through a parallel fiber. The prostaglandin F2 alpha in the collected microdialysates was measured by HPLC as its 3-bromomethyl-6,7-dimethoxy-1-methyl-2-(1H)-quinoxalinone derivative. Prostaglandin F2 alpha dramatically increased in response to hydroxyl radical generation, but declined substantially after 3 h of exposure. Prostaglandin F2 alpha was undetectable when either H2O2 or FeCl2/EDTA was administered alone in control experiments, demonstrating that its formation was caused by generated hydroxyl radical.

Topics: Animals; Arachidonic Acid; Dinoprost; Feedback; Hydroxyl Radical; Kinetics; Male; Microdialysis; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries