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Intrathecal Infusion (intrathecal + infusion)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Therapeutic benefits of intrathecal protein therapy in a mouse model of amyotrophic lateral sclerosis

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2008
Yasuyuki Ohta
Abstract When fused with the protein transduction domain (PTD) derived from the human immunodeficiency virus TAT protein, proteins can cross the blood,brain barrier and cell membrane and transfer into several tissues, including the brain, making protein therapy feasible for various neurological disorders. We have constructed a powerful antiapoptotic modified Bcl-XL protein (originally constructed from Bcl-XL) fused with PTD derived from TAT (TAT-modified Bcl-XL), and, to examine its clinical effectiveness in a mouse model of familial amyotrophic lateral sclerosis (ALS), transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) bearing a G93A mutation were treated by intrathecal infusion of TAT-modified Bcl-XL. We demonstrate that intrathecally infused TAT-fused protein was effectively transferred into spinal cord neurons, including motor neurons, and that intrathecal infusion of TAT-modified Bcl-XL delayed disease onset, prolonged survival, and improved motor performance. Histological studies show an attenuation of motor neuron loss and a decrease in the number of cleaved caspase 9-, cleaved caspase 3-, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in the lumbar cords of TAT-modified Bcl-XL -treated G93A mice. Our results indicate that intrathecal protein therapy using a TAT-fused protein is an effective clinical tool for the treatment of ALS. © 2008 Wiley-Liss, Inc. [source]

Chemical Stability of an Admixture Combining Ziconotide and Bupivacaine During Simulated Intrathecal Administration

NEUROMODULATION, Issue 2007
David Shields PhD
ABSTRACT Objective., To determine the stability of an admixture combining ziconotide with bupivacaine hydrochloride during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods., An admixture containing ziconotide (25 µg/mL) and bupivacaine hydrochloride (5 mg/mL) was stored in SynchroMed® II pumps at 37° and in control vials at either 37° or 5°. Using high-performance liquid chromatography, drug concentrations were determined from samples obtained at varying intervals during the 30-day study. Results., After 30 days, pump ziconotide and bupivacaine hydrochloride concentrations measured an average of 86.9% and 99.4% of their initial concentrations, respectively. Control vials displayed similar degradation rates for both drugs. Statistical evaluation of the ziconotide 95% confidence interval indicated that the ziconotide concentration would meet or exceed 90% and 80% of initial concentration for 22 days and 45 days, respectively. Conclusions., An admixture containing 25 µg/mL ziconotide and 5 mg/mL bupivacaine hydrochloride was 90% stable for 22 days and 80% stable for 45 days (extrapolated) in SynchroMed® II infusion pumps. [source]

Chemical Stability of Ziconotide-Clonidine Hydrochloride Admixtures With and Without Morphine Sulfate During Simulated Intrathecal Administration

NEUROMODULATION, Issue 2007
David Shields PhD
ABSTRACT Objective., To determine the stability of ziconotide,clonidine hydrochloride admixtures with and without morphine sulfate during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods., Admixtures of ziconotide (25 µg/mL) and clonidine hydrochloride (2 mg/mL) with and without morphine sulfate (35 mg/mL) were stored in Medtronic SynchroMed® II pumps at 37°. Pumps were sampled immediately after filling and at four additional time points over the course of 28 (ziconotide,clonidine hydrochloride admixture) or 20 (ziconotide,clonidine hydrochloride,morphine sulfate admixture) days. Drug concentrations were determined using high-performance liquid chromatography. Results., Ziconotide concentration exceeded 97% of initial at all time points when combined with clonidine alone; statistical evaluation indicated that both ziconotide and clonidine concentrations would remain above 90% of initial for more than 60 days. When compounded with both clonidine and morphine, ziconotide and clonidine concentrations declined; statistical evaluation indicated that the ziconotide concentration was 70% of initial after 20 days, and that clonidine would remain 90% stable for 42 days. Morphine was stable in the presence of ziconotide and clonidine. Conclusions., A ziconotide-clonidine admixture was 90% stable for 60 days (extrapolated), and a ziconotide-clonidine-morphine admixture was 70% stable for 20 days. [source]

Intrathecal Catheter Granuloma Associated with Continuous Sufentanil Infusion

PAIN MEDICINE, Issue 6 2010
Anita Gupta DO, PharmD
Abstract Intrathecal sufentanil is a minimally utilized opioid for patients with intractable pain refractory to traditional intrathecal medications. We present an 86-year-old female with a history of multiple spine surgeries who eventually progressed to having chronic, intractable, and diffuse low back pain. After failing medical management, she underwent a successful intrathecal trial of opioid therapy and was subsequently treated with an implantable drug delivery system (IDDS) or intrathecal pump. We describe the first reported case of formation of a catheter tip granuloma associated with intrathecal infusion of sufentanil. Due to increasing opioid requirements and gradually escalating pain, a computed tomography myelogram was performed to explore neuraxial etiologies of her symptoms. This investigation revealed the presence of a catheter tip-associated inflammatory mass (granuloma). All patients receiving intrathecal medications, including sufentanil, must be considered for the possibility of catheter-associated granuloma, particularly with symptoms of altered neurological function and/or increasing medication requirements associated with worsening pain. [source]

Activation of metabotropic glutamate receptor 5 improves recovery after spinal cord injury in rodents,

ANNALS OF NEUROLOGY, Issue 1 2009
Kimberly R. Byrnes PhD
Objective Activation of metabotropic glutamate receptor 5 (mGluR5) has neuroprotective properties in vitro and has been reported to limit postischemic lesion volume in vivo. Previously, mGluR5 has been identified on microglia in vitro, but the effects of mGluR5 activation on inflammation in vivo or on recovery after spinal cord injury is unknown. Methods Rats received intrathecal infusion of the selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) for 7 days after moderate impact spinal cord injury at T9. Complementary studies examined CHPG effects on activated spinal microglia cultures. Results Functional motor recovery was significantly increased by CHPG treatment up to 28 days after injury, with improvements in weight bearing, step taking, and coordination of stepping behavior. CHPG treatment significantly reduced lesion volume and increased white matter sparing at 28 days after injury. Administration of CHPG attenuated microglial-associated inflammatory responses in a dose-dependent fashion, including expression of ED1, Iba-1, Galectin-3, NADPH oxidase components, tumor necrosis factor-,, and inducible nitric oxide synthase. Because mGluR5 is expressed by microglial cells in the rat spinal cord, such effects may be mediated by direct action on microglial cells. mGluR5 stimulation also reduced microglial activation and decreased microglial-induced neurotoxicity in spinal cord microglia cultures; the latter effects were blocked by the selective mGluR5 antagonist MTEP. Interpretation These data demonstrate that mGluR5 activation can reduce microglial-associated inflammation, suggesting that the protective effects of mGluR5 agonists may reflect this action. Ann Neurol 2009;66:63,74 [source]