pH-Responsive Gallol-Functionalized Hyaluronic Acid-Based Tissue Adhesive Hydrogels for Injection and Three-Dimensional Bioprinting.

The major challenges of hyaluronic acid-based bioinks in extrusion-based three-dimensional bioprinting are poor printability and low printing accuracy. To tackle the challenges, we developed a bioink in which two components are blended: gallic acid-functionalized hyaluronic acid (HAGA) and hyaluronic acid methacrylate (HAMA). In the precursor phase, the blend's HAGA component enables pH-dependent viscosity modulation that results in improved injectability and printability at physiological temperature. Postprinting, the blend's HAMA component is photocrosslinked to create a true hydrogel with a complementary network of both HAGA and HAMA. The ready structures of the HAGA-HAMA hydrogel showed sufficient printing quality and accuracy compared to plain HAMA. The blend also displayed enhanced viscoelastic properties and stable swelling behavior. In addition to the pH tunability, the HAGA component also imparted tissue adhesion and antioxidant activity. This bioink has the potential to be printed directly on an infected wound site due to its adhesiveness to tissue and dimensional stability in situ.

Sequential Cross-linking of Gallic Acid-Functionalized GelMA-Based Bioinks with Enhanced Printability for Extrusion-Based 3D Bioprinting.

The printability of a photocross-linkable methacrylated gelatin (GelMA) bioink with an extrusion-based 3D bioprinter is highly affected by the polymer concentration and printing temperature. In this work, we developed a gallic acid (GA)-functionalized GelMA ink to improve the printability at room and physiological temperatures and to enable tissue adhesion and antioxidant properties. We introduced a sequential cross-linking approach using catechol-Fe3+ chelation, followed by photocross-linking. The results show that the ink formulation with 0.5% (w/v) Fe3+ in GelMA (30% modification) with 10% GA (GelMA30GA-5Fe) provided the optimum printability, shape fidelity, and structural integrity. The dual network inside the printed constructs significantly enhanced the viscoelastic properties. Printed cylinders were evaluated for their printing accuracy. The printed structures of GelMA30GA-5Fe provided high stability in physiological conditions over a month. In addition, the optimized ink also offered good tissue adhesion and antioxidant property. This catechol-based sequential cross-linking method could be adopted for the fabrication of other single-polymer bioinks.

Photocross-linkable Methacrylated Polypeptides and Polysaccharides for Casting, Injecting, and 3D Fabrication.

For modern tissue engineering, we need not only develop new hydrogels but also suitable processing methods for them. Polypeptides and polysaccharides are potential candidates because they can be methacrylated, processed before photocross-linking, and yielded into hydrogels with given shape and form. In this study, we successfully methacrylated collagen, gelatin, hyaluronan, and alginate to 30 and 60% degree of modification. We studied methacrylated compositions (i.e., precursors) to investigate their processability. The precursors of collagen and gelatin with 60% methacrylation exhibited suitable yield stress, shear-thinning properties, and fiber-forming capability for injecting and 3D bioprinting. On the contrary, the 30% methacrylated precursors had properties suitable for casting purposes. Our study also showed that the mechanical properties of hydrogels corresponded to the used photocross-linking conditions and the degree of modification. These results underline the importance of tunability of the precursors and resulting hydrogels according to the specific fabrication method and tissue engineering application.

Harnessing hyaluronic acid-based nanoparticles for combination therapy: A novel approach for suppressing systemic inflammation and to promote antitumor macrophage polarization.

Anti-inflammatory drugs such as dexamethasone (DEX) are commonly administered to cancer patients along with anticancer drugs, however, the effect of DEX on human cancers is poorly understood. In this article, we have tailored self-assembled nanoparticles derived from hyaluronic acid (HA) wherein, anti-inflammatory DEX was used as a hydrophobic moiety for inducing amphiphilicity. The HA-DEX micelles were subsequently loaded with chemotherapeutic agent, doxorubicin (DOX) (HA-DEX-DOX) and was utilized to deliver drug cargo to human cancer cells expressing different levels of CD44 receptors. We found that DEX suppressed the cytotoxicity of DOX in HCT116, while it synergistically enhanced cytotoxicity in MCF-7 cells. When we tested DOX and HA-DEX-DOX in an ex-vivo human whole blood, we found activation of complement and the coagulation cascade in one group of donors. Encapsulation of DOX within the nanoparticle core eliminated such deleterious side-effects. The HA-DEX-DOX also polarized bone-marrow-derived anti-inflammatory M2 macrophages, to pro-inflammatory M1 phenotype with the upregulation of the cytokines TNF-α, iNOS and IL-1ß.

Tissue adhesive hyaluronic acid hydrogels for sutureless stem cell delivery and regeneration of corneal epithelium and stroma.

Regeneration of a severely damaged cornea necessitates the delivery of both epithelium-renewing limbal epithelial stem cells (LESCs) and stroma-repairing cells, such as human adipose-derived stem cells (hASCs). Currently, limited strategies exist for the delivery of these therapeutic cells with tissue-like cellular organization. With the added risks related to suturing of corneal implants, there is a pressing need to develop new tissue adhesive biomaterials for corneal regeneration. To address these issues, we grafted dopamine moieties into hydrazone-crosslinked hyaluronic acid (HA-DOPA) hydrogels to impart tissue adhesive properties and facilitate covalent surface modification of the gels with basement membrane proteins or peptides. We achieved tissue-like cellular compartmentalization in the implants by encapsulating hASCs inside the hydrogels, with subsequent conjugation of thiolated collagen IV or laminin peptides and LESC seeding on the hydrogel surface. The encapsulated hASCs in HA-DOPA gels exhibited good proliferation and cell elongation, while the LESCs expressed typical limbal epithelial progenitor markers. Importantly, the compartmentalized HA-DOPA implants displayed excellent tissue adhesion upon implantation in a porcine corneal organ culture model. These results encourage sutureless implantation of functional stem cells as the next generation of corneal regeneration.

Practical Aspects and Avoidance of Complications in Microendoscopic Spine Surgeries: A Review.

INTRODUCTION: Although the indications for endoscopic procedures have increased in recent times, there are also some limitations. This review discusses the practical points to prevent and treat complications in microendoscopic spine surgery. MATERIAL AND METHODS: A literature search was conducted for the relevant articles after a topic search on PubMed, Google Scholar, and Medline. The review is based on the experience of 1,574 spinal endoscopic procedures performed by the senior author. RESULTS: Advantages of endoscopic surgery include better visualization, panoramic vision, and the ability to work around corners. Limitations with endoscopic procedures include proximal blind areas, obstruction in instrument handling due to a narrow corridor, disorientation, frequent lens fogging, loss of depth perception, and difficulty in achieving hemostasis, leading to complications and longer operative time during the learning curve. CONCLUSION: Surgeons need to learn endoscopic skills in addition to microsurgical ones to perform microendoscopic procedures properly. Attending live workshops, watching operative videos, visiting various departments, watching an experienced and accomplished endoscopic surgeon, proper case selection, a multidisciplinary team approach, practicing on models, hands-on cadaveric workshops, laboratory training, and simulators can improve results and shorten the learning curve.

Endoscopic surgery of spontaneous basal ganglionic hemorrhage.

INTRODUCTION: Although there are controversies about the optimal management of spontaneous intracerebral hemorrhage (ICH), benefits of endoscopic procedures in ICH have been reported. This study is aimed to evaluate the result of 270 patients undergoing endoscopic treatment of ICH. METHODS: This was a retrospective study from July 2008 to June 2017. All procedures were done with the endoscopic technique using a tubular retractor. Patients with the hematoma volume between 30 to 80 ml, with the Glasgow Coma Scale (GCS) between 5 to 14, and evidence of severe mass effect, were included in the study. RESULTS: The average stay in the intensive care unit was 6 days (range 1-17 days). The median pre-operative midline shift of 8.3 mm was reduced to 2.7 mm after surgery. The average hematoma removal ratio, the duration of surgery, and the blood loss was 90%, 90 min, and 60 ml, respectively. There was improvement in the average pre-operative GCS from 9.4 to 11.3 at seventh post-operative day. The post-operative mortality rate was 10.7%. A good outcome was observed in 71% patients at 6 months after surgery. Larger the volume of hematoma, more the operative time, more the pre-operative midline shift, and poorer the GCS, significantly higher was the association with mortality. The patients with a better pre-operative GCS were associated with a better Glasgow Outcome Score. The follow-up period ranged from 7 to 115 months. CONCLUSION: Endoscopic surgery with the help of a tubular retractor was effective and safe. It allowed for a good visualization of the hematoma and the surrounding brain, and helped in proper hemostasis. The hematoma may also be removed with the help of the microscope and the tubular retractor, in case any difficulty during the endoscopic technique is encountered.

Gloriosa superba Mediated Synthesis of Platinum and Palladium Nanoparticles for Induction of Apoptosis in Breast Cancer.

Green chemistry approaches for designing therapeutically significant nanomedicine have gained considerable attention in the past decade. Herein, we report for the first time on anticancer potential of phytogenic platinum nanoparticles (PtNPs) and palladium nanoparticles (PdNPs) using a medicinal plant Gloriosa superba tuber extract (GSTE). The synthesis of the nanoparticles was completed within 5 hours at 100°C which was confirmed by development of dark brown and black colour for PtNPs and PdNPs, respectively, along with enhancement of the peak intensity in the UV-visible spectra. High-resolution transmission electron microscopy (HRTEM) showed that the monodispersed spherical nanoparticles were within a size range below 10 nm. Energy dispersive spectra (EDS) confirmed the elemental composition, while dynamic light scattering (DLS) helped to evaluate the hydrodynamic size of the particles. Anticancer activity against MCF-7 (human breast adenocarcinoma) cell lines was evaluated using MTT assay, flow cytometry, and confocal microscopy. PtNPs and PdNPs showed 49.65 ± 1.99% and 36.26 ± 0.91% of anticancer activity. Induction of apoptosis was most predominant in the underlying mechanism which was rationalized by externalization of phosphatidyl serine and membrane blebbing. These findings support the efficiency of phytogenic fabrication of nanoscale platinum and palladium drugs for management and therapy against breast cancer.

Endoscopic Anterior Approach for Cervical Disc Disease (Disc Preserving Surgery).

OBJECTIVE: To report our experience of endoscopic disc removal by anterior approach for management of cervical myelopathy in 210 patients. METHODS: A retrospective study of 187 cases of single- and 23 cases of double-level disc disease was performed. Cases of myelopathy with or without unilateral or bilateral radiculopathy and unilateral radiculopathy with either soft or hard disc prolapse were included. Patients with ≥3 disc levels, unstable spine, infections, trauma, significant posterior compression, congenital canal stenosis, disc extending more than half the vertebral body height, and prior surgery at the same level were excluded. RESULTS: C5-6 (n = 119 patients), C6-7 (n = 58 patients), C4-5 (n = 49 patients), C3-4 (n = 6 patients), and C2-3 (n = 1 patient) levels were represented. Visual analog scale and Nurick grading system were used to assess severity of neck and arm pain and functional outcomes, respectively. Preoperative mean visual analog scale scores for arm and neck pain were 6.7 and 3.2, respectively, which improved to 1.7 and 1.1 at 3 months after surgery. The average preoperative Nurick grade improved from 2.64 to 0.81 at 6 months postoperatively. Follow-up was 6-54 months. CONCLUSIONS: Endoscopic anterior discectomy (disc preserving surgery) is an effective and safe alternative in cervical disc disease. Although there was reduction in disc height, clinical outcome was good at an average 29 months of follow-up. Long-term follow-up is required to assess any progressive disc degeneration and clinical results.

Full Endoscopic Vascular Decompression in Trigeminal Neuralgia: Experience of 230 Patients.

BACKGROUND: Although most surgeons are using endoscopy as an adjunct to microscopy in microvascular decompression, a full endoscopic technique is less commonly performed. The present study is aimed to evaluate results of 230 patients of endoscopic vascular decompression. METHODS: A retrospective study was carried out in a tertiary care hospital. Patients with typical neuralgia, with or without preoperatively detected vascular compression, were advised to undergo vascular decompression. RESULTS: Maxillary and mandibular division were involved in 116 and 93 patients, respectively. Superior cerebellar (n = 174) artery was most common vascular conflict followed by anterior inferior cerebellar artery (n = 96). Tortuous basilar artery and small veins were possible causes of neuralgia in 1 and 2 patients, respectively. Single- and double-vessel conflict were observed in 173 and 50 patients, respectively. The compressing vessel was placed anterior to the trigeminal nerve in 39 patients. An arterial loop was in contact with the nerve, producing grooving, and displacing the nerve in 215, 35, and 21 patients, respectively. Complete, satisfactory, and no relief of pain were observed in 204 (88.7%), 11 (5.8%), and 15 (6.5%) patients, respectively. Recurrence was observed in 25 patients at an average follow-up of 60 months. Temporary complications included trigeminal dysesthesia, vertigo, facial paresis, CSF leak, and reduced hearing in 9, 8, 8, 7, and 3 patients, respectively. CONCLUSION: Endoscopic vascular decompression is a safe and efficient alternative technique to endoscopic assisted microvascular decompression provided surgeon is experienced in endoscopic surgery. It is helpful in identification of all offending vessels including the double vessel, and anterior compression without brain and nerve retraction.

Endoscopic Management of Arnold-Chiari Malformation Type I with or without Syringomyelia.

INTRODUCTION: Several different surgical techniques have been used in the treatment of patients with symptomatic Arnold-Chiari malformation type 1 (ACM-1) with or without syrinx. Endoscope-assisted decompression of the posterior fossa has been found to be safe and effective. We report our initial experience of endoscopic management of ACM-I. MATERIAL AND METHODS: This was a prospective study of 15 symptomatic patients. Pre- and postoperative clinical status and computed tomography and magnetic resonance imaging findings were recorded. Suboccipital bone of ∼ 3 cm distance from the foramen of magnum and posterior arch of atlas was removed. Partial splitting of the dura mater with preservation of the inner portion and the arachnoid membrane was performed. Any change in axial and sagittal length of the syrinx, tonsillar ascension, shape of the tonsil tip, appearance of cerebrospinal fluid posterior to the tonsil, and formation of the cisterna magna were recorded. Patients with atlantoaxial instability, tethered cord, associated myelomeningocele, hydrocephalus, or elevated intracranial pressure were excluded. RESULTS: Age of patients ranged from 26 to 48 years. There were nine female patients. There were six patients with ACM-I without and nine with ACM-I with syrinx. Average pre- and postoperative Karnofsky performance score was 78 and 93, respectively. Average operative time was 130 minutes (110-190 minutes), and blood loss was 30 mL (20-180 mL). Follow-up ranged from 9 to 21 months. CONCLUSION: Although the study is limited by the small number of patients with a short follow-up, endoscopic decompression in selected patients of ACM-I with or without syrinx with dural splitting was a safe and effective alternative to microsurgical treatment.

Extent of Decompression of Lumbar Spinal Canal after Endoscopic Surgery.

Introduction Endoscopic techniques are being used in lumbar disk disease and lumbar canal stenosis to decompress the spinal canal. The present study analyzed pre- and postoperative magnetic resonance imaging (MRI) measurements of the lumbar canal. Material and Methods This was a prospective study of 30 lumbar levels. Patients < 18 years of age with unilateral compression, previous surgery at the same level, and spinal instability were excluded. Endoscopic posterior decompression was used. Pre- and postoperative MRIs of all the patients were performed. Anteroposterior (AP), transverse, interfacet diameter, canal surface area, and height and angle of the lateral recess were measured. Results Mean ages of male and female patients were 42.1 ± 10.3 and 45.0 ± 9.9 years, respectively. Pathologies were at L4-L5, L5-S1, and L2-L3 levels in 16, 13, and 1 patient, respectively. There was significant improvement in AP diameter (4.75 ± 1.75 mm to 10.33 ± 2.11 mm), interfacet distance (12.70 ± 4.86 mm to 18.92 ± 3.53 mm), and canal surface area (76.45 ± 25.36 mm2 to 187.13 ± 41.04 mm2) after decompression. Significant improvement was noted in mean height and angle of lateral recess after surgery of both sides suggesting that effective decompression of the bilateral canal was possible using a unilateral approach. Most of the patients (90%) showed excellent and good improvement after surgery. Postoperative canal surface area and AP diameter in patients who did not have any pain after surgery or had pain requiring occasional medication was higher compared with patients who continued to complain of pain and required continuous pain medication. Conclusion Although the number of patients was small with a short follow-up, the endoscopic technique was effective in improving AP diameter, interfacet distance, canal surface area, lateral recess height, and lateral recess angle, suggesting that an endoscopic technique using a unilateral approach is effective in bilateral decompression of neural elements.

Endoscopic Management of Spinal Intradural Extramedullary Tumors.

Introduction Posterior midline laminectomy is associated with risks of postoperative instability, spinal deformity, extensive bilateral subperiosteal muscle stripping, partial or total facetectomy especially in foraminal tumor extension, increased cerebrospinal fluid leakage, and wound infection. Minimally invasive approaches with the help of a microscope or endoscope using hemilaminectomy have been found to be safe and effective. We report our initial experience of 18 patients using the endoscopic technique. Material and Methods A retrospective study of intradural extramedullary tumors extending up to two vertebral levels was studied. Pre- and postoperative clinical status, magnetic resonance imaging was done in all patients. The Destandau technique was used, and resection of ipsilateral lamina, medial part of the facet joint, base of the spinous process, and undercutting of the opposite lamina was performed. Dura repair was done using an endoscopic technique. Fibrin glue was used to reinforce repair in the later part of the study. Results The sagittal and axial diameter of tumor ranged from 21 to 41 mm and 12 to 18 mm, respectively. There were four cervical, two cervicothoracic, five thoracic, three thoracolumbar, and four lumbar tumors, respectively. All 18 patients improved after total excision of tumor. Average duration of surgery and blood loss was 140 minutes and 60 mL, respectively. Postoperative stay and follow-up ranged from 3 to 7 days and 9 to 24 months, respectively. Conclusion Although the study is limited by the small number of patients with a short follow-up and is a technically demanding procedure, endoscopic management of intradural extramedullary tumors was an effective and safe alternative technique to microsurgery in such patients.

Microendoscopic Removal of Deep-Seated Brain Tumors Using Tubular Retraction System.

Background Retraction of the overlying brain can be difficult without causing significant trauma when using traditional brain retractors with blades. These retractors may produce focal pressure and may result in brain contusion or infarction. Tubular retractors offer the advantage of low retracting pressure that is less likely to be traumatic. Low retraction pressure in the tubular retractor is due to the distribution of retraction force in all directions in a larger area. Material and Methods We conducted a retrospective study of 100 patients with deep-seated tumors operated on from January 2010 to December 2014. Tumor removal was accomplished with the help of a microscope and/or endoscope. Tubular brain retractors sizes 23, 18, and 15 mm were used. Folding of the tubular retractor after making a longitudinal cut allowed a small corticectomy. Larger retractor sizes were used in the earlier part of the study and in larger tumors. All the patients were evaluated postoperatively by computed tomography scan on the first postoperative day, and subsequent scans were done as and when needed. Any brain contusion or infarctions and the amount of tumor removal were recorded. Results A total of 74 patients had astrocytomas; 12, meningiomas; 4, colloid cyst of the third ventricle; 4, metastases; 4, primitive neuroectodermal tumor; 1, neurocytoma; and 1, ependymoma. Pure endoscopic excision without using a microscope was performed in 12 patients. Lesions were in the frontal (n = 34), parietal (n = 22), intraventricular (n = 16), basal ganglion or thalamic (n = 14), occipital (n = 10), and cerebellar (n = 4) areas. Total, near-total, and partial excision was achieved in 49, 29, and 22 patients, respectively. Use of a conventional retractor for excision of peripheral and superficial parts of a large tumor, small brain contusions, and technical failure were observed in 7, 4, and 1 patient, respectively. The low incidence of contusion may be partly due to the nonavailability of magnetic resonance imaging in the early postoperative period because of financial constraints. Conclusion Removal of deep-seated tumors was safe and effective using our simple tubular retractor. It also helped minimize bleeding during surgery. A tubular brain retractor and conventional retractor can be used to complement each other if required.

C-N Coupling of Amides with Alcohols Catalyzed by N-Heterocyclic Carbene-Phosphine Iridium Complexes.

N-Heterocyclic carbene-phosphine iridium complexes (NHC-Ir) were developed/found to be a highly reactive catalyst for N-monoalkylation of amides with alcohols via hydrogen transfer. The reaction produced the desired product in high isolated yields using a wide range of substrates with low catalyst loading and short reaction times.

Quaternary Indolizidine and Indolizidone Iminosugars as Potential Immunostimulating and Glycosidase Inhibitory Agents: Synthesis, Conformational Analysis, Biological Activity, and Molecular Docking Study.

New quaternary indolizidine iminosugars, with hydroxymethyl group at the ring junction, namely, C-8a-hydroxymethyl-1-deoxycastanospermine congeners 1a, 2a, 3a and their 3-oxo analogs 1b, 2b, and 3b were synthesized by using intramolecular reductive aminocyclization/lactamization of d-mannose/D-glucose derived C5-γ-azido esters as a key step wherein both the rings of the indolizidine skeleton were built up in one pot following the cascade reaction pathway. The conformations ((5)C8 or (8)C5) of 1-3 were assigned on the basis of the (1)H NMR studies. All compounds were found to be potent inhibitors of various glycosidase enzymes with Ki and IC50 values in the micromolar/nanomolar concentration range and further substantiated by molecular docking studies. The effect of synthesized iminosugars 1-3 on the cytokine secretion of IL-4, IL-6, and IFN-γ was evaluated. All compounds were found to be TH1 bias increasing the TH1/TH2 cytokines ratio (IL-6 and IL-4) indicating their potency as immunostimulating agents. Our study suggests that immunomodulatory activity of indolizidine iminosugars can be tuned by minor structural/stereochemical alterations.

Avoiding Complications in Endoscopic Third Ventriculostomy.

Endoscopic neurosurgical techniques hold the potential for reducing morbidity. But they are also associated with limitations such as the initial learning curve, proximal blind spot, visual obscurity, difficulty in controlling bleeding, disorientation, and loss of stereoscopic image. Although some of the surgical techniques in neuroendoscopy and microsurgery are similar, endoscopy requires additional skills. A thorough understanding of endoscopic techniques and their limitations is required to get maximal benefit. Knowledge of possible complications and techniques to avoid such complications can improve results in endoscopic third ventriculostomy (ETV). The surgeon must be able to manage complications and have a second strategy such as a cerebrospinal fluid shunt if ETV fails. It is better to abandon the procedure if there is disorientation or a higher risk of complications such as bleeding or a thick and opaque floor without any clear visualization of anatomy. Attending live workshops, practice on models and simulators, simpler case selection in the initial learning curve, and hands-on cadaveric workshops can reduce complications. Proper case selection, good surgical technique, and better postoperative care are essential for a good outcome in ETV. Although it is difficult to make a preoperative diagnosis of complex hydrocephalus (combination of communicating and obstructive), improving methods to detect the exact type of hydrocephalus before surgery could increase the success rate of ETV and avoid an unnecessary ETV procedure in such cases.

Modified twist drill technique in the management of chronic subdural hematoma.

AIM: Burr-hole craniostomy is the most efficient and safe choice for surgical drainage of chronic subdural hematoma (CSDH). Although the twist-drill drainage is also relatively safe and time-saving, it carries the risk of inadequate drainage, brain penetration and hematoma formation. Our modified technique helps in avoiding bleeding and brain penetration. MATERIAL AND METHODS: The preferred sites for twist drill were the most curved parts on the cranium. Normal drilling at about 90 degree angle was done on the most curved surfaces while it was at about 60 degree angles on flat surface. This angled drilling and the curved guide wire (hooked in the distal blind end of infant feeding tube), helped to guide infant feeding tube in the hematoma cavity. Dura matter was coagulated using insulated wire. RESULTS: There was no procedure related hematoma, brain penetration and mortality in any of the 50 patients managed by the modified technique. Infant feeding tube was properly positioned in all the cases. Burr hole evacuation was done in 7 cases (14%) due to inadequate evacuation of the hematoma after TDC. CONCLUSION: Our modified technique of twist drill drainage is inexpensive, simple, safe and effective alternative technique in the treatment of CSDH.

Endoscopic transoral excision of odontoid process in irreducible atlantoaxial dislocation: our experience of 34 patients.

BACKGROUND: The endoscopic excision of the odontoid process in irreducible atlantoaxial dislocation (AAD) can be achieved by transnasal, transoral, and transcervical approaches. Endoscopic transoral technique has been found to be effective and safe. It avoids palatal splitting or prolonged retraction. We are reporting our experience of 34 cases. The relevant literature is reviewed. MATERIAL AND METHODS: This was a prospective study of 34 patients treated during the past 5 years. Detailed history was taken and a thorough physical examination was made to record preoperative status. X-ray cervical spine lateral view (in neutral, flexion, and extension), anteroposterior (AP), and transoral view for the odontoid process were taken. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) scans and postoperative CT scans were done in all cases. Postoperative status at 1, 6, and 12 months was recorded. RESULTS: Age ranged from 15 to 56 years. There were 22 male and 12 female patients. Symptom duration ranged from 6 to 18 months.Preoperatively, there were 26 and 8 patients in Ranawat grades 3A and 3B, respectively. Five patients had tenth cranial nerve paresis. There were 23, 10, and 1 cases of AAD, AAD with basilar invasion, and tuberculosis, respectively. Palatal splitting was not required in any of the cases. All patients improved after surgery. No deaths occurred. One patient had cerebrospinal fluid (CSF) leak, which stopped after external lumbar drainage. Follow-up ranged from 12 to 65 months. CONCLUSION: Endoscopic transoral odontoidectomy is a safe and effective alternative technique for odontoid excision. It can be performed in patients with small oral openings. Angled scopes improved exposure of clivus and palatal splitting was not required even in basilar invasion.

α-Geminal dihydroxymethyl piperidine and pyrrolidine iminosugars: synthesis, conformational analysis, glycosidase inhibitory activity, and molecular docking studies.

The Jocic-Reeve and Corey-Link type reaction of dichloromethyllithium with suitably protected 5-keto-hexofuranoses followed by treatment with sodium azide and sodium borohydride reduction gave 5-azido-5-hydroxylmethyl substituted hexofuranoses 7a-c with required geminal dihydroxymethyl group. Removal of protecting groups and converting the C-1 anomeric carbon into free hemiacetal followed by intramolecular reductive aminocyclization with in situ generated C5-amino functionality afforded corresponding 5C-dihydroxymethyl piperidine iminosugars 2a-c. Alternatively, removal of protecting groups in 7b and 7c and chopping of C1-anomeric carbon gave C2-aldehyde that on intramolecular reductive aminocyclization with C5-amino gave 4C-dihydroxymethyl pyrrolidine iminosugars 1b and 1c, respectively. On the basis of the (1)H NMR studies, the conformations of 2a/2b were assigned as (4)C(1) and that of 2c as (1)C(4). The glycosidase inhibitory activities of all five iminosugars were studied with various glycosidase enzymes and compared with natural d-gluco-1-deoxynojirimycin (DNJ). All the five compounds were found to be potent inhibitors of rice α-glucosidase with K(i) and IC(50) values in the nanomolar concentration range. Iminosugars 2b and 1b were found to be more potent inhibitors than their parent iminosugar. These results were substantiated by in silico molecular docking studies.