subpial-adeno-associated-virus-9-aav9-vector-delivery-in-adult-mice

Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice

The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. ...

University of California, San Diego

In this case report, we describe recurrent spasms of the right coronary artery with no apparent preexisting abnormal angiogram that caused second-degree atrioventricular (AV) block and inferior wall hypokinesis. These hemodynamic changes were induced by mechanical compression of the right coronary artery by a pericardium drain tube. From our experience, we should be aware that mechanical compression may trigger an exaggerated vasomotor response, leading to severe coronary artery spasms.

Right coronary artery spasms triggered by mechanical compression during off-pump coronary artery bypass grafting surgery.

We investigated how various effectsite concentrations of fentanyl could affect breathing pattern and postoperative analgesia.

[Breathing pattern and postoperative analgesia at various effect-site concentrations of fentanyl].

This retrospective study compared remifentanil-sevoflurane anesthesia (RG) with fentanyl-sevoflurane anesthesia (FG) to determine which is accompanied with the lower incidence of intraoperative movement during tympanoplastic surgery under intraoperative facial nerve monitoring.

[Remifentanil can reduce intraoperative movement during tympanoplastic surgery--a retrospective analysis].

Decompression illness (DCI) develops during or after diving. Pulmonary decompression illness ('Chokes') is rarely seen because the affected individual usually dies in the water. We encountered a rare and interesting case. A 60-year-old man complained of leg pain after diving. Despite rapid transfer to a nearby hospital, advanced respiratory failure and shock had set in. He was then transferred to our hospital for hyperbaric oxygen therapy (HBOT). On account of his poor general condition, we initially treated him in the intensive care unit without HBOT, where he showed extreme hyperpermeability and a high level of serum procalcitonin (PCT; 20.24 ng/mL). Despite large-volume fluid therapy, severe intravascular dehydration and shock status remained. We assume that the injured endothelial cells induced vascular hyperpermeability and increased levels of inflammatory cytokines leading to the high serum PCT level. PCT might be a useful stress marker of endothelial damage and severity in DCI, including Chokes.

Vascular hyperpermeability in pulmonary decompression illness: 'the chokes'.

The fentanyl infusion rate was controlled by employing a target controlled infusion (TCI) technique under anticoagulant therapy for postoperative pain management. A 59-year-old woman with atrial fibrillation and mitral stenosis was scheduled for open cholecystectomy. Heparin was continuously infused for anticoagulant therapy. Sevoflurane and remifentanil were used for induction and maintenance of anesthesia. At completion of the operation, her consciousness was checked and the endotracheal tube was then removed under fentanyl TCI (effect-site concentration: Ce = 2.0 ng x ml(-1)). In this case, the spontaneous breathing rate was stable (10-12 x min(-1)) under fentanyl TCI. She had no complaints of pain(pain at rest: VAS 20 mm). The breathing rate in this case provided indication for postoperative pain management. The TIVAtrainer simulation makes the exchange from TCI infusion to continuous infusion easy. And the spontaneous breathing monitoring is useful for postoperative pain measurement of laparotomy cases.

[Utility of target controlled infusion technique for deciding the fentanyl infusion rate for post-cholecystectomy pain management in a patient on anticoagulant therapy].

We experienced management of general anesthesia in a patients with Coffin-Siris syndrome (CS syndrome) which is an autosomal dominant disorder characterized by mental retardation, growth failure, hypoplasia of the fifth finger's distal phalanx and limb, and syndrome-specific facial appearance. Anesthesia was induced by sevoflurane by mask. After obtaining muscle relaxation by rocuronium, laryngoscopy by Machintosh #2 failed to reveal the vocal cord. However, the vocal cord was revealed by AirwayScope (AWS) for the pediatrics and then tracheal intubation was successful. Surgical procedures and anes-thetic management were performed uneventfully. This case demonstrates usefulness of AWS in pediatric patients with difficult intubation.

[Case report : usefulness of the airwayscope for difficult intubations in a pediatric patients with Coffin-Siris syndrome].

A 39-year-old man with a history of transsphenoidal surgery was scheduled for sagittal split ramus osteotomy. Nasal intubation was successfully performed using a bronchoscope (BF) and a gum elastic bougie (GB). inserted using a BE The BF was then replaced with a GB. We widened his nasal cavity using the nasal airway. Finally, intubation was performed with an endotracheal tube (7.0 mm) using a GB and a Macintosh laryngoscope. Thus, BF and GB could be safely used for nasal intubation in a patient with a history of transsphenoidal surgery.

[Utility of a bronchoscope and a gum elastic bougie for nasal intubation in a patient with a history of transsphenoidal surgery].

We studied retrospectively amount of bleeding, clamping time, and the presence or absence of ischemia-reperfusion injury in all seven cases of IABO performed for placenta accreta from 2007 to 2012 at our hospital. We also examined rSO2 change before and after clamping in four cases in which lower-limb rSO2 monitoring was performed with NIRS (near-infrared spectroscopy). There was no case suspected of ischemia-reperfusion injury during and after clamping with the amount of bleeding around 1,580-10,973 ml (mean 4,536 ml) and clamping time of 10-83 min (mean 44 min). No significant decrease was observed in lower-limb rSO2 with 73.5 ± 5.9% before clamping and 70.8 ± 5.6% (mean ± SD) after clamping.

[Anesthetic management of intra-aortic balloon occlusion (IABO) for seven cases of placenta accreta--a six year experience at our institute].

The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity.

Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.

Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients.

Kota Kamizato

Neuroregeneration Laboratory,
Department of Anesthesiology,
Neuroregeneration Laboratory, Department of Anesthesiology

University of California, San Diego

Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice

Kota Kamizato

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Neuroregeneration Laboratory,Department of Anesthesiology,Neuroregeneration Laboratory, Department of Anesthesiology

University of California, San Diego

Subpial Adeno-associated Virus 9 (AAV9) Vector Delivery in Adult Mice

Neuroregeneration Laboratory,
Department of Anesthesiology,
Neuroregeneration Laboratory, Department of Anesthesiology