Inhibition of discoidin domain receptors by imatinib prevented pancreatic fibrosis demonstrated in experimental chronic pancreatitis model

Abstract Discoidin domain receptors (DDR1 and DDR2) are the collagen receptors of the family tyrosine kinases, which play significant role in the diseases like inflammation, fibrosis and cancer. Chronic pancreatitis (CP) is a fibro-inflammatory disease in which recurrent pancreatic inflammation leads to pancreatic fibrosis. In the present study, we have investigated the role of DDR1 and DDR2 in CP. The induced expression of DDR1 and DDR2 was observed in primary pancreatic stellate cells (PSCs) and cerulein-induced CP. Subsequently, the protective effects of DDR1/DDR2 inhibitor, imatinib (IMT) were investigated. Pharmacological intervention with IMT effectively downregulated DDR1 and DDR2 expression. Further, IMT treatment reduced pancreatic injury, inflammation, extracellular matrix deposition and PSCs activation along with inhibition of TGF-β1/Smad signaling pathway. Taken together, these results suggest that inhibition of DDR1 and DDR2 controls pancreatic inflammation and fibrosis, which could represent an attractive and promising therapeutic strategy for the treatment of CP

Microsurgical excision of intracranial epidermoids: a short surgical series of 12 cases

Background: Intracranial epidermoids are rare congenital cystic lesions where total excision is often difficult resulting in recurrence. In the current series we tried to analyze and report, the clinical findings, imaging criteria for diagnosis, surgical management strategy to achieve radical resection and outcomes were studied prospectively. Here we report our short experience with intracranial epidermoids as a whole.Methods: 12 cases of intracranial epidermoids confirmed radiologically between Feb 2009 and Dec 2013 were operated by different surgical approaches according to the location of the lesion by micro neurosurgical techniques to achieve total resection. All these patients were followed up for various periods and results analyzed.Results: Of the 12 epidermoids 5 were in CP angle, 4 were in supratentorial location. Of these 2 patients died and Transient facial palsy was observed in two cases and lower cranial nerve palsy in another case which improved later. 2 patients required VP shunt and there were no recurrences in the series. Total resection of the lesion was achieved in majority of the patients (83.3%) by microsurgical techniques.Conclusions: With the availability of good imaging techniques and modern micro neurosurgical techniques it is possible to achieve total or near total excision where ever possible to avoid recurrence of the lesions, resulting in total cure of the patient.

Clinical outcome following micro-vascular decompression for trigeminal neuralgia

Background: Trigeminal neuralgia is the most common facial pain syndrome characterized by severe, brief recurrent episodes of electric shock like pain in the distribution of one or more branches of trigeminal nerve on one side of the face. In the present paper we present our experience with MVD for trigeminal neuralgia in a series of 20 patients during the last 4 years.Methods: All the patients presented to the neurosurgery department with features suggestive of Trigeminal Neuralgia during the last 4 years were evaluated with 3D FIESTA imaging. All those patients eligible for surgical decompression underwent a standard MVD in the form of a small retromastoid suboccipital craniotomy and Microvascular decompression done using a sheet of Teflon to intervene between the vessel and the Vth nerve. Any arachnoid bands across the nerve were carefully divided. Standard post-operative care given. The results were evaluated and tabulated. Results: 65% (N=13) of the patients had immediate postoperative relief. 15% (N=3) showed delayed but good pain relief in 3 weeks period. 20% (N=4) 20% pts did not show any pain relief at all post operatively. There were no mortalities in the series and no redo surgeries were performed in the series.Conclusion: Micro-vascular decompression is safe and effective in producing good pain relief over a long term in patients with Trigeminal neuralgias refractive to medical treatment.

Table S7: Osteopontin and osteocalcin protein levels

Background The receptor activator of nuclear factor kappa-B (RANK)/RANK ligand/osteoprotegerin (OPG) system plays a critical role in bone remodelling by regulating osteoclast formation and activity. OPG has been used systemically in the treatment of bone diseases. In searching for more effective and safer treatment for bone diseases, we investigated newly formulated OPG-chitosan complexes, which is prepared as a local application for its osteogenic potential to remediate bone defects. Methods We examined high, medium and low molecular weights of chitosan combined with OPG. The cytotoxicity of OPG in chitosan and its proliferation in vitro was evaluated using normal, human periodontal ligament (NHPL) fibroblasts in 2D and 3D cell culture. The cytotoxicity of these combinations was compared by measuring cell survival with a tetrazolium salt reduction (MTT) assay and AlamarBlue assay. The cellular morphological changes were observed under an inverted microscope. A propidium iodide and acridine orange double-staining assay was used to evaluate the morphology and quantify the viable and nonviable cells. The expression level of osteopontin and osteocalcin protein in treated normal human osteoblast cells was evaluated by using Western blot. Results The results demonstrated that OPG in combination with chitosan was non-toxic, and OPG combined with low molecular weight chitosan has the most significant effect on NHPL fibroblasts and stimulates proliferation of cells over the period of treatment