Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thomson, a known immunomodulatory agent extensively used in ayurveda, has not been effectively validated for the mechanisms involved in immunomodulation and the identification of the active principles. The bioactive fraction of T. cordifolia (TBF) in methanol was used for nitric oxide (NO) radical scavenging activity, lipoxygenase (LOX) and cyclooxygenase (COX) dual inhibition and cytotoxicity studies. Production of the proinflammatory cytokines, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in dendritic cell (DC) suspensions treated with lipopolysaccharide (LPS) was also studied. The bioactive principles involved were identified with ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometric (UPLC-Q-ToF MS/MS) system. The results indicate significantly higher potency of TBF as compared to positive standards for LOX/COX inhibition with moderate NO radical scavenging activity and the fraction was also found to be non-cytotoxic to monocyte cells. A significant inhibition was also observed in TNF-α and IL-1β production in LPS-treated DC suspensions as compared to standards, rolipram and dexamethasone, respectively. 11 compounds were identified from TBF by MS/MS system. The potent inhibition of LOX and COX enzymes with moderate NO scavenging was indicative of a free radical scavenging-independent mechanism of immunomodulation. Further investigations into the active principles identified would result in the development of lead candidates with potent therapeutic implications.
1. Tumors arise and progress through the accumulation of serial genetic changes, including successive mutations, which involve activation of proto-oncogenes and inactivation of tumour suppressor genes, leading to the uncontrolled proliferation of progeny cells. The human body is continuously and unavoidably exposed to structurally diverse chemicals with established carcinogenic activity in animal models and/or mutagenic activity in short-term tests. 2. Celecoxib, a non-steroidal anti-inflammatory drug that specifically inhibits the enzyme cyclo-oxygenase-2, has been reported to be effective against certain types of cancers. The in vitro anti-oxidant and antimutagenic activities of the celecoxib were investigated in the present study using standard procedures. 3. The antimutagenic activity of celecoxib was determined using histidine mutant Salmonella typhimurium strains TA98, TA100, TA102 and TA1535 against directly acting mutagens (sodium azide (NaN3), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitro-o-phenylenediamine (NPDA) and doxorubicin) and mutagens needing activation (2-acetamidofluorene (2-AF) and 7,12-dimethylbenz [a] anthracene (DMBA)). 4. Celecoxib inhibited NaN3-, MNNG- and NPDA-induced mutations of TA100. The antimutagenicity of celecoxib (0.2 mg/plate) against the NaN3-induced mutation of TA1535 was 39.8% (P < 0.001). The MNNG-induced mutation of TA1535 was also inhibited by 0.3 mg/plate celecoxib (46.0%; P < 0.05). At concentrations of 0.2 mg/plate, celecoxib significantly inhibited NPDA- and doxorubicin-induced mutations of TA98 by 52.5 and 58.0%, respectively (P < 0.001 and P < 0.05, respectively). 5. The antimutagenic activity of 0.3 mg/plate celecoxib against 2-AF- and DMBA-induced mutations of TA98 was 81.76 and 98.1%, respectively (P < 0.001). 6. The anti-oxidant activity of celecoxib was determined by the inhibition of lipid peroxidation and superoxide and hydroxyl radical-scavenging activities. 7. The IC50 values of celecoxib for hydroxyl radical-scavenging and the inhibition of lipid peroxidation were 1.97 +/- 0.06 and 1.99 +/- 0.05 micromol/mL, respectively. Celecoxib had no superoxide radical scavenging-activity up to a concentration of 2.6 micromol/mL. 8. The in vitro antimutagenic and anti-oxidant activities of celecoxib indicate its possible therapeutic use as a cancer chemopreventive agent.
Introduction: The posterior interosseous nerve (PIN) is at risk of injury when surgical procedures are undertaken in the proximal forearm. The aim of the present study was to determine the relationship of the PIN to adjacent anatomical landmarks, which can be used to prevent iatrogenic injury to the nerve. Material and Methods: Forty upper extremities were used for this study. The landmarks used to measure the required parameters were intercondylar reference point, styloid process of ulna, proximal and distal borders of superficial layer of supinator muscle, and head of radius. The number of trunks of PIN and the innervation pattern of supinator muscle were studied. Results: The mean values and standard deviations of the measurements obtained were determined. There was no statistical difference of data between right and left sides. Discussion and Conclusion: The data obtained in the study will be of use to surgeons and orthopedicians during interventional procedures on the proximal part of radius and in decompression procedures of the PIN.
Introduction: Compression of the Posterior Interosseous Nerve (PIN) can cause pain on the lateral aspect of the proximal forearm and weak extension of the wrist and fingers. The distal arcade of the superficial layer of the supinator muscle can entrap the PIN, as it passes beneath it. Knowing the exact location of the distal arcade in relation to adjacent anatomical landmarks can help in decompression of the PIN. Aim: The aim of the study was to describe the morphology of the distal arcade of the supinator muscle and its relation with the PIN. Materials and Methods: An anatomic dissection of 40 upper extremities was conducted and the distances of the distal arcade and the PIN from adjacent landmarks were determined from Jan 2016 to Jun 2017. The mean, standard deviation and range were calculated for each of the measurements. The comparison of the parameters between sides was done using paired t-test. Data obtained was tabulated and analysed in Statistical Package For Social Sciences (SPSS) Software version 16.0. Results: A muscular distal arcade was the most common type seen in 17 (42.5%) upper limb. Distances between the distal arcade and the humero-radial and trans-epicondylar lines were 90.27 mm and 105.62 mm, respectively. The distance from the lateral epicondyle and the entrance and exit of the PIN from supinator was 61.47 mm and 85.60 mm, respectively. The distance between the proximal and distal arcades showed statistically significant difference (p-value=0.041). Conclusion: Knowledge of the anatomic findings of the distal arcade of the superficial layer of the supinator and the localisation of the PIN are important in the surgical management of PIN entrapment.
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