Acute and Subacute Toxicity Assessment of Andrographolide-2-hydroxypropyl-ß-cyclodextrin Complex via Oral and Inhalation Route of Administration in Sprague-Dawley Rats.

Objective: Acute and subacute toxicity analysis of AND-2-HyP-ß-CYD complex was conducted in Sprague-Dawley (SD) rats following oral and inhalation routes of administration. Methods and Results: Single dose acute toxicity was carried out at 2000 mg/kg of AND-2-HyP-ß-CYD complex, while the doses of 200, 400, and 666 mg/kg were administered, over a period of 28 days under repeated dose oral toxicity study. Hence, LD50 (lethal dose) was found to be >2000 mg/kg in addition to NOAEL (no observed adverse effect level) of 666 mg/kg. Correspondingly, single dose acute inhalation toxicity of AND-2-HyP-ß-CYD complex was carried out at 5 mg/L/4 h/day and subacute inhalation toxicity at 0.5, 1, and 1.66 mg/L/4 h/day over a period of 28 days. The NOAEL and LOAEL (lowest observed adverse effect level) were estimated to be 0.5 mg/L/4 h/day and 1 mg/L/4 h/day, respectively. Conclusion: The findings of the present study would further be useful in assessing and utilizing the medicinal and therapeutic benefits of AND-2-HyP-ß-CYD complex.

Molecular encapsulation of andrographolide in 2-hydroxypropyl-ß-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and in vitro antiviral activity analysis against SARS-CoV-2.

In present investigation, AND-2-HyP-ß-CYD (Andrographolide-2-Hydroxypropyl-ß-cyclodextrin) complex was synthesized and characterized for antiviral and pharmacokinetic profile. The linear host-guest relation suggested synthesis of a 1:1 complex of AND with 2-HyP-ß-CYD by inclusion mode. The Kc, stability constant of the two phase system of AND with 2-HyP-ß-CYD computed to be 38.60 x 10-3M. 1H NMR spectrum of AND indicated the presence of triplet at 6.63-ppm which was up-fielded in AND-2-HyP-ß-CYD complex at 6.60-ppm (doublet) confirmed the insertion of AND in cavity of 2-HyP-ß-CYD through lactone ring. AND-2-HyP-ß-CYD complex exhibited the IC50 of 0.1-µg.mL-1 (E gene) and 0.29-µg.mL-1 (N gene) against SARS-CoV-2 infected Vero6 cells. Moreover, a 1.5-fold increment in extent of absorption of AND was noticed post complexation. The bioavailability was estimated to be 15.87 ± 3.84% and 23.84 ± 5.46%, respectively for AND and AND-2-HyP-ß-CYD complex. AND-2-HyP-ß-CYD complex may be a prospective candidate for further studies to evolve as a clinically viable formulation against SARS-CoV-2.

Minimally Invasive Surgical Approach for Odontoid Lesions: A Technical Description in a Case of High Cervical Osteomyelitis and Abscess.

BACKGROUND: Cervical approaches to the dens are limited by the presence of several structures, including the spinal cord, vertebral arteries, C1 articular pillars, and C2 nerves. Surgical approaches to access the high anterior cervical spine classically encompass the extended anterior retropharyngeal route, transoral route, and extreme lateral route, each of which has its own pattern of morbidity or complications. Percutaneous procedures to drain infections in this area have a limited yield. Osteomyelitis of the dens is a rare but serious condition that is associated with significant mortality. Patients with cervical osteomyelitis and epidural abscess are likely to have significant coexistent medical comorbidities and are often poor candidates for extensive surgical procedures. A minimally invasive approach that gives access to the entire odontoid process would allow for more aggressive treatments and potentially even a complete odontoidectomy without resection of the C1 anterior arch. CASE DESCRIPTION: We describe a minimally invasive approach to drainage and debridement of an atlantoaxial epidural abscess and osteomyelitis. Using minimally invasive techniques from a posterolateral trajectory in a cadaveric specimen, we were able to safely access the anterior epidural space, odontoid, and retropharynx. We then performed this approach in our patient who was unable to tolerate a large surgical procedure. CONCLUSIONS: We developed, tested, and then applied a minimally invasive approach that combined tubular retractors with positioning of the head and neck to optimize the exposure in a patient with a complex abscess that involved the ventral epidural space, odontoid process, and retropharyngeal space. The abscesses were successfully drained along with local tissue debridement without complication. A posterolateral minimally invasive approach is a safe alternative in patients with an atlantoaxial epidural abscess, odontoid osteomyelitis, or retropharyngeal abscess with significant medical comorbidities who are unlikely to tolerate a more extensive surgery. It can also be used for resections of lesions of an oncologic nature and could even be used to resect pannus or os odontoideum, without necessitating an anterior approach or resection even of the C1 arch.

Arachnoiditis ossificans.

OBJECTIVE: Arachnoiditis ossificans is an uncommon clinical entity in which arachnoid ossification leads to clinical symptomatology. In this case report, we describe the case of a myelopathic patient with arachnoid ossifications, an arachnoid cyst, and syringomyelia coexisting with a herniated thoracic disc at the same levels. CASE DESCRIPTION: An 81-year-old woman presented with rapidly progressive leg weakness, dysesthetic pains, and urinary incontinence. RESULTS: The patient underwent thoracic laminectomy with costotransversectomy for resection of ossified arachnoid and re-establishment of cerebrospinal fluid pathways. CONCLUSION: Altered cerebrospinal fluid dynamics secondary to the obstruction in subarachnoid flow may predispose to the formation of an arachnoid cyst, and the cyst itself may be the proximate cause of the myelopathy.

Surgical treatment of metastatic spinal tumors.

Spinal metastases represent a significant cause of morbidity in patients diagnosed with malignancies. Metastases to the spine can cause severe pain, paralysis, and impairment of activities of daily living. The treatment paradigm for spinal metastases involves a cohesive multidisciplinary approach that allows treatment plans to be made in the context of a patient's overall condition. There have been significant advances in the surgical treatment of spinal metastases that can significantly improve a patient's quality of life.

Novel fluoroscopic technique for localization at cervicothoracic levels.

STUDY DESIGN: To use a novel modified intraoperative fluoroscopic view for spinal level localization. OBJECTIVE: To evaluate the safety and utility of the modified oblique fluoroscopic technique for intraoperative localization of distal cervical and proximal thoracic spinal levels. SUMMARY OF BACKGROUND INFORMATION: Operative radiographic localization of the cervicothoracic spine using standard anterior-posterior and lateral views is made difficult by its anatomic relationship to the shoulder and upper chest, which produce radiographic shadowing obscuring the spine. Additional image degradation can be caused by muscular patients or those with a high body mass index. An oblique modification of the standard cross table lateral can be used to accurately identify pathologic levels at or across the cervicothoracic junction. This method distinctly demonstrates the bony lamina, which can then be used to count spinal levels. The unique feature of this technique is that the oblique angle removes the shoulder and the majority of the ribs from the active field of view, thereby producing a cleaner and more distinct image. When the gantry angle of the fluoroscope is parallel to the plane of the opposite lamina, it gives a type of "target sign" similar to the trans-pedicular image commonly used in pedicle screw placement. This radiographic sign can be easily identified and recognized across the cervicothoracic junction, even in those patients with a large body mass index or large musculature. METHODS: Spinal level was determined intraoperatively through our oblique technique and confirmed in the same patient through standard views with retrograde counting. Postoperative imaging confirmed correct level surgery. RESULTS: Correct spinal level identification was achieved in the distal cervical and proximal thoracic spine by implementation of our novel oblique fluoroscopy technique. CONCLUSIONS: The modified oblique cross table fluoroscopy technique allows accurate operative localization across the cervicothoracic junction and well into the thoracic spine.

Treatment of primary vertebral tumors.

Advances in the treatment of disease and detection through advanced imaging have led to an increase in the discovery of vertebral tumors. Although the majority of symptomatic spinal lesions are metastatic in origin, a significant number of them arise primarily in the spine. These lesions encompass a wide variety of tumor types classified by their cell of origin: bony tumors, cartilaginous tumors, vascular tumors, plasma cell dyscrasias, and tumors that arise from embryonic rests. Further classification of these tumors into malignant or benign subtypes is based on their clinical progression, histopathological evidence of invasiveness, and response to therapy. We provide a brief overview and description of primary tumors as well as treatment paradigms for the individual tumor types. Mt Sinai J Med 76:499-504, 2009. (c) 2009 Mount Sinai School of Medicine.

Golf-associated head injury in the pediatric population: a common sports injury.

OBJECT: Golf-related injuries constitute a common type of sports injury in the pediatric population. The increase in the frequency of these injuries is largely attributed to the increase in the popularity of golf and greater use of golf carts by children. METHODS: The purpose of this study was to investigate the mechanisms and complications associated with golf-related injuries in the pediatric population and, by doing so, assist in the prevention of such injuries. We reviewed the charts of 2546 pediatric patients evaluated by the neurosurgery service at the authors' institution over a 6-year period. There were 64 cases of sports-related injuries. Of these, 15 (23%) were golf-related, making these injuries the second-largest group of sports-related injuries. Depressed skull fracture was the most common injury observed. Neurosurgical intervention was required in 33% of the cases. With rare exceptions, patients made good recoveries during a mean follow-up period of 22.2 months. One death occurred due to uncontrollable cerebral edema following a golf cart accident. One child required shunt placement and several revisions following an injury sustained from a golf ball. CONCLUSIONS: Children should be advised on the proper use of golf equipment as a preventive measure to avoid these injuries. Precautionary guidelines and safety training guidelines should be established. The institution of a legal minimum age required to operate a golf cart should be considered.

History of posterior thoracic instrumentation.

The term "backbone" appears in many expressions used in modern day society. In any scenario, it has one central meaning: stability. Best defined as a foundation that is able to sustain multiple stressors without adversely affecting integrity, the commonly and appropriately termed backbone of humans is the spinal column. As the central focus of stability in our species, the spine is subject to a great degree of trauma and mechanical forces. A variety of methods have been developed throughout history in the treatment of spinal column injury. Initial treatment involved the use of simple traction devices for the reduction of spinal fractures; these have evolved to include the current insertion of spinal instrumentation. The authors review the historical treatment and development of posterior instrumentation for thoracic spinal injury.