Progressive hemorrhage and myotoxicity induced by echis carinatus venom in murine model: neutralization by inhibitor cocktail of n,n,n `,n `-tetrakis (2-pyridylmethyl) ethane-1,2-diamine and silymarin

Viperbite is often associated with severe local toxicity, including progressive hemorrhage and myotoxicity, persistent even after the administration of anti-snake venom (ASV). In the recent past, investigations have revealed the orchestrated actions of Zn2+ metalloproteases (Zn(2+)MPs), phospholipase A(2)s (PLA(2)s) and hyaluronidases (HYs) in the onset and progression of local toxicity from the bitten site. As a consequence, venom researchers and medical practitioners are in deliberate quest of potent molecules alongside ASV to tackle the brutal local manifestations induced by aforesaid venom toxins. Based on these facts, we have demonstrated the protective efficacy of inhibitor cocktail containing equal ratios of N,N,N', N'-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and silymarin (SLN) against progressive local toxicity induced by Echis carinatus venom (ECV). In our previous study we have shown the inhibitory potentials of TPEN towards Zn(2+)MPs of ECV (IC50: 6.7 mu M). In this study we have evaluated in vitro inhibitory potentials of SLN towards PLA(2)s (IC50: 12.5 mu M) and HYs (IC50: 8 mu M) of ECV in addition to docking studies. Further, we have demonstrated the protection of ECV induced local toxicity with 10 mM inhibitor cocktail following 15, 30 min (for hemorrhage and myotoxicity); 60 min (for hemorrhage alone) of ECV injection in murine model. The histological examination of skin and thigh muscle sections taken out from the site of ECV injection substantiated the overall protection offered by inhibitor cocktail. In conclusion, the protective efficacy of inhibitor cocktail is of high interest and can be administered locally alongside ASV to treat severe local toxicity

Advances in Social Media Research:Past, Present and Future

Social media comprises communication websites that facilitate relationship forming between users from diverse backgrounds, resulting in a rich social structure. User generated content encourages inquiry and decision-making. Given the relevance of social media to various stakeholders, it has received significant attention from researchers of various fields, including information systems. There exists no comprehensive review that integrates and synthesises the findings of literature on social media. This study discusses the findings of 132 papers (in selected IS journals) on social media and social networking published between 1997 and 2017. Most papers reviewed here examine the behavioural side of social media, investigate the aspect of reviews and recommendations, and study its integration for organizational purposes. Furthermore, many studies have investigated the viability of online communities/social media as a marketing medium, while others have explored various aspects of social media, including the risks associated with its use, the value that it creates, and the negative stigma attached to it within workplaces. The use of social media for information sharing during critical events as well as for seeking and/or rendering help has also been investigated in prior research. Other contexts include political and public administration, and the comparison between traditional and social media. Overall, our study identifies multiple emergent themes in the existing corpus, thereby furthering our understanding of advances in social media research. The integrated view of the extant literature that our study presents can help avoid duplication by future researchers, whilst offering fruitful lines of enquiry to help shape research for this emerging field

The Role of Antibiotics in Nasal Fractures after Closed Reduction

Background:. Nasal fractures represent the most common fracture in facial trauma. The role of prophylactic antibiotics in these injuries is debated, given low infection rates and demonstrated risks of antibiotics. We studied the isolated effect of prophylactic antibiotics on infection rate in patients with nasal fracture after closed reduction. Methods:. Retrospective cohort study of a prospectively maintained facial trauma database was conducted. Demographics, comorbidities, fracture classifications, and management of patients who received antibiotics at the time of closed nasal reduction were compared against those who did not receive antibiotics. Infection rates between groups were analyzed. Multivariate analysis was conducted to control for confounding variables. Qualitative analysis was performed for patients who experienced infection following nasal fracture. Results:. A total of 282 patients met inclusion criteria (n = 144, antibiotic; n = 138, nonantibiotic). Six patients experienced infection. There was no difference in infection rate between antibiotic and nonantibiotic groups (2.0% versus 2.2%; P = 0.90). On multivariate regression, antibiotics did not significantly decrease odds of infection (OR 1.7 [0.17–13.6]; P = 0.64). Moreover, patients with open nasal fractures did not have significantly higher odds of infection (OR 1.9 [0.08–20.8]; P = 0.64). Similarly, increasing severity of injury based on Rohrich classification did not significantly impact odds of infection (OR 0.68 [0.23–1.9]; P = 0.46). All six infections were managed at the bedside, with zero infections following operating room management (P = 0.32). Conclusions:. Prophylactic antibiotics do not decrease infection rates following nasal fractures managed by closed reduction. Bedside management may be a risk factor for the development of infection; however, this finding requires further evaluation

Silver carboxylate-TiO2/polydimethyl siloxane is a safe and effective antimicrobial with significant wound care potential

Abstract. Introduction:. With the rise in antibiotic resistance, new methodologies are needed to combat musculoskeletal infections. Silver is an antimicrobial that can be synthesized in different forms, but its pharmacokinetics are difficult to control. This study details the antibacterial efficacy and cellular cytotoxicity of a formulation consisting of silver carboxylate (AgCar) released through a titanium dioxide/polydimethylsiloxane matrix with a predictable release profile on Pseudomonas aeruginosa, Acinetobacterium baumannii, and human-derived primary osteoblasts. Methods:. Through an Institutional Animal Care and Use Committee and IRB-approved protocol, AgCar was applied to live Yucatan porcine skin and histologically analyzed for skin penetration. Graphite Furnace Atomic Absorption Spectroscopy (GFAAS) was used to measure elution of AgCar. Dose–response curves were generated through optical density to assess potency. Finally, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to quantify the cellular cytotoxicity of the novel formulation. The results were subject to statistical analysis using analysis of variance and post hoc Tukey tests. Results:. The silver carboxylate coating demonstrated deep penetration into the epithelium at the level of the deep pilosebaceous glands in animal models. GFAAS testing demonstrated the extended elution profile of silver carboxylate over 96 hours, while 100% silver with no titanium dioxide-polydimethylsiloxane matrix fully eluted within 48 hours. 10x silver carboxylate demonstrated superior antimicrobial activity to antibiotics and other silver formulations and showed minimal cytotoxicity compared with other silver formulations. Discussion/Clinical Relevance:. Current antimicrobial therapies in wound care and surgical antisepsis, such as chlorhexidine gluconate, have pitfalls including poor skin penetration and short duration of efficacy. The broad antimicrobial activity, extended elution, and deep skin penetration of this AgCar formulation show great promise for surgical site infection and wound care treatment. Novel technology to fight the growing threat of microbial resistance should be at the forefront of orthopaedic surgical site infection prevention and treatment

Characterization of Major Zinc Containing Myonecrotic and Procoagulant Metalloprotease `Malabarin' from Non Lethal Trimeresurus malabaricus Snake Venom with Thrombin Like Activity: Its Neutralization by Chelating Agents

A major myonecrotic zinc containing metalloprotease `malabarin' with thrombin like activity was purified by the combination of gel permeation and anion exchange chromatography from T. malabaricus snake venom. MALDI-TOF analysis of malabarin indicated a molecular mass of 45.76 kDa and its N-terminal sequence was found to be Ile-Ile-Leu-Pro(Leu)-Ile-Gly-Val-Ile-Leu(Glu)-Thr-Thr. Atomic absorption spectral analysis of malabarin raveled the association of zinc metal ion. Malabarin is not lethal when injected i.p. or i.m. but causes extensive hemorrhage and degradation of muscle tissue within 24 hours. Sections of muscle tissue under light microscope revealed hemorrhage and congestion of blood vessel during initial stage followed by extensive muscle fiber necrosis with elevated levels of serum creatine kinase and lactate dehydrogenase activity. Malabarin also exhibited strong procoagulant action and its procoagulant action is due to thrombin like activity; it hydrolyzes fibrinogen to form fibrin clot. The enzyme preferentially hydrolyzes A alpha followed by B beta subunits of fibrinogen from the N-terminal region and the released products were identified as fibrinopeptide A and fibrinopeptide B by MALDI. The myonecrotic, fibrinogenolytic and subsequent procoagulant activities of malabarin was neutralized by specific metalloprotease inhibitors such as EDTA, EGTA and 1, 10-phenanthroline but not by PMSF a specific serine protease inhibitor. Since there is no antivenom available to neutralize local toxicity caused by T. malabaricus snakebite, EDTA chelation therapy may have more clinical relevance over conventional treatment