Expansion and characterization of cells from surgically removed intervertebral disc fragments in xenogen-free medium.

Low back pain due to degeneration of intervertebral disc (IVD) is a major health problem resulting in significant disability as well as adding to the economic burden. Discectomy is a very common procedure done worldwide to relieve this pain. At present all the surgically removed disc tissue is mostly discarded. However, there are reports that state that progenitor cells in the IVD can be grown ex vivo and have the potential to be used for IVD repair and regeneration. We report here that viable cells can be harvested from surgically removed, herniated disc tissue and can be potentially used in cell based therapy. Further, we have successfully replaced xenogenic supplements such as foetal bovine serum with either autologous serum or human platelet lysate for culturing IVD cells from patient's surgically removed disc tissue, without loss of any cell characteristics, including cell surface markers, growth factor secretion in the conditioned medium and osteogenic and chondrogenic differentiation potential in vitro. The present work will not only contribute to overcoming some of the major barriers in carrying out human clinical trials, but also provide a cheap, alternate source of proteins and growth factors for growing IVD cells ex vivo for therapy.

STITCHLESS Percutaneous Endoscopic Cervical Discectomy: Are We Moving Towards Day Care Discectomy Procedure?

BACKGROUND: STITCHLESS percutaneous endoscopic cervical discectomy s[PECD] is safe, precise, targeted, and a complete endoscopic procedure to treat soft cervical disc herniation with unilateral radiculopathy. It allows direct visualization of herniated fragment and its removal, inspection of decompressed nerve root in an awake and aware patient. It reduces the risk related to general anesthesia and to the neurological structures. However, all the patients treated with PECD can be candidates for anterior cervical discectomy and fusion (ACDF). ACDF requires a longer period of stay, expense, and more risk to neurological structures and ultimately loss of the disc space by fusion. MATERIALS AND METHODS: Twenty consecutively treated patients by sPECD over a period of 2 years with soft cervical disc herniation and unilateral radiculopathy were included in the study. PECD enables removal of offending fragment under vision and irrigation and ablation of inflammation with few complications. All patients were followed for minimum of 6 months with visual analog score (VAS) and neck disability index (NDI). RESULTS: All treated patients had a good outcome in terms of pain relief (VAS) and functional recovery (NDI). One patient had episodes of cough lying in the supine position and another patient had transient hoarseness of voice, (both recovered). CONCLUSION: Potential benefits of sPECD include safety as it is done under local anesthesia, smaller incision, short hospitalization, fewer complications, avoidance of fusion, preservation of segmental motion, preventing the adjacent segment degeneration, and avoidance of the risk related to the hardware (nonunion and pseudarthrosis). sPECD is an effective treatment modality for soft cervical disc herniation.

Role of Transpedicular Percutaneous Vertebral Biopsy for Diagnosis of Pathology in Vertebral Compression Fractures.

STUDY DESIGN: Retrospective observational study. PURPOSE: To identify the role of percutaneous vertebral biopsy in histopathological diagnosis of vertebral compression fractures and to identify the frequency of unexpected malignancy in vertebral compression fractures. OVERVIEW OF LITERATURE: Vertebral compression fractures are common in the Indian population. Magnetic resonance imaging and nuclear imaging have some limitations in the diagnosis of definitive pathology of vertebral compression fractures. Therefore, histological confirmation is necessary for definitive diagnosis and to plan appropriate management for patient. METHODS: A retrospective observational study was conducted involving 84 patients who underwent percutaneous vertebral biopsy between 2010 and 2014. We performed C-arm guided percutaneous transpedicular core vertebral biopsy of vertebral compression fractures under combination of local anesthesia and intravenous conscious sedation. RESULTS: Sufficient biopsy material was obtained in 79 of the 84 cases. In the other five cases, biopsy material was not sufficient for reporting. Out of the 79 cases, osteoporotic pathology was detected in 69 patients, malignancy was detected in 8 patients and no pathology was found in 2 patients. Two patients with distant metastases to vertebra were identified. Primary spinal malignancy was detected in 6 patients (1 unsuspected plasmacytoma, 5 diagnosed malignancy preoperatively). So, the frequency of unsuspected malignancy of this study was 1.19% (1/84). None of the patients had any complications. CONCLUSIONS: C-arm guided percutaneous transpedicular vertebral biopsy is useful in obtaining definitive histopathological diagnosis of vertebral compression fractures, especially in differentiating malignant and non-malignant vertebral compression fractures and helping plan appropriate management of patients. The rate of unexpected malignancy in vertebral compression fracture was 1.19%.

Sciatica: detection and confirmation by new method.

We need to overcome limitations of present assessment and also integrate newer research in our work about sciatica. Inflammation induces changes in the DRG and nerve root. It sensitizes the axons. Nociceptor is a unique axon. It is pseudo unipolar: both its ends, central and peripheral, behave in similar fashion. The nerve in periphery which carries these axons may selectively become sensitive to mechanical pressure--"mechanosensitized," as we coin the phrase. Many pain questionnaires are used and are effective in identifying neuropathic pain solely on basis of descriptors but they do not directly physically correlate nerve root and pain. A thorough neurological evaluation is always needed. Physical examination is not direct pain assessment but testing mobility of nerve root and its effect on pain generation. There is a dogmatic dominance of dermatomes in assessment of leg pain. They are unreliable. Images may not correlate with symptoms and pathology in about 28% of cases. Electrophysiology may be normal in purely inflamed nerve root. Palpation may help in such inflammatory setting to refine our assessment further. Confirmation of sciatica is done by selective nerve root block (SNRB) today but it is fraught with several complications and needs elaborate inpatient and operating room set up. We have used the unique property of the pseudo unipolar axon that both its ends have similar functional properties and so inject along its peripheral end sodium channel blockers to block the basic cause of the mechanosensitization namely upregulated sodium channels in the root or DRG. Thus using palpation we may be able to detect symptomatic nerve in stage of inflammation and with distal end injection, along same inflamed nerve we may be able to abolish and so confirm sciatica. Discussions of sciatica pain diagnosis tend to immediately shift and centre on the affected disc rather than the nerve. Theoretically it may be possible to detect the affected nerve by palpating the nerve and relieve pain moment we desensitize the nerve.

Falcipain inhibitors as potential therapeutics for resistant strains of malaria: a patent review.

INTRODUCTION: There is an urgent need to discover new antimalarial drugs due to emergence of resistance in the parasite to the existing drugs. Malarial cysteine proteases falcipin-2 (FP-2) and falcipain-3 (FP-3) are attractive targets for antimalarial chemotherapy. The structures and functions of FP-2/3, their binding domains and their interactions with small- and macro-molecules are well studied. These studies could provide important insight into rational designing of FP inhibitors as potential antimalarial drugs. AREAS COVERED: This review is focused on a selection of interesting patents published during 1999 - 2011 on peptidic and nonpeptidic chemotypes of the FP-2/FP-3 inhibitors. EXPERT OPINION: It is a known fact that malaria is a serious health problem worldwide due to the emergence of resistant strains. Hence, development of novel, potent and affordable antimalarial drugs devoid of side effects is of great significance and in great demand. FPs, the malarial cysteine proteases are potential targets for development of new antimalarial drugs. Assessing the available literature on FP-2/3 and their inhibitors it could be speculated that these inhibitors have the potential to enter the clinical stages of development for the treatment of malaria in the years to come.

Investigation of functionally liver selective glucokinase activators for the treatment of type 2 diabetes.

Type 2 diabetes is a polygenic disease which afflicts nearly 200 million people worldwide and is expected to increase to near epidemic levels over the next 10-15 years. Glucokinase (GK) activators are currently under investigation by a number of pharmaceutical companies with only a few reaching early clinical evaluation. A GK activator has the promise of potentially affecting both the beta-cells of the pancreas, by improving glucose sensitive insulin secretion, as well as the liver, by reducing uncontrolled glucose output and restoring post-prandial glucose uptake and storage as glycogen. Herein, we report our efforts on a sulfonamide chemotype with the aim to generate liver selective GK activators which culminated in the discovery of 3-cyclopentyl-N-(5-methoxy-thiazolo[5,4-b]pyridin-2-yl)-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionamide (17c). This compound activated the GK enzyme (alphaK(a) = 39 nM) in vitro at low nanomolar concentrations and significantly reduced glucose levels during an oral glucose tolerance test in normal mice.

Novel N-substituted 4-hydrazino piperidine derivative as a dipeptidyl peptidase IV inhibitor.

A novel class of N-substituted 4-hydrazino piperidine derivatives were designed, synthesized and evaluated for DPP IV inhibition. The SAR studies on the N-substituted piperidine led to the discovery of compound 22e as a potent DPP IV inhibitor (IC(50) 88nM), which is highly selective over other peptidases. In vivo efficacy indicates that compound 22e stimulates insulin release in response to glucose load and improves glucose tolerance in n5-STZ and Zucker Diabetic Fatty (ZDF) rats.