Synthetic Ion Channels: A New Class of Membrane Disruptor and Efflux Pump Inhibitor for the Recovery of Antibiotic Potency

Antibiotic resistance has become a world-wide health care crisis. In 2013 there were 50,000 deaths in U.S. and EU, associated with hospital acquired bacterial infections. This problem is exacerbated by the lack of new antibiotics in development. Here, we report that synthetic amphiphiles represent a new class of adjuvants that rescue antibiotic potency against multidrug resistant bacteria. Hydraphiles are amphiphiles, designed and synthesized in Gokel lab, that show many of the same properties as protein ion channels. Hydraphiles were previously shown to have antimicrobial activity against Escherichia coli, Bacillus subtilis and Saccharomyces cerevisiae. Here, we report that hydraphiles recover the activity of tetracycline and fluoroquinolones (ciprofloxacin, norfloxacin) against E. coli, Klebsiella pneumoniae, Staphylococcus aureus bacteria. At sub-lethal concentrations, hydraphiles do not inhibit bacterial growth, show synergy with existing antibiotics and transport K+ ions. Controls confirmed that the structure and function of hydraphiles are critical for its activity. Our investigation shows that hydraphiles can inhibit antibiotic efflux pumps and increase the bacterial membrane permeability. The outer membranes of Gram negative bacteria provide for an attractive target for antibiotic development. We showed that benzyl C14 hydraphile localize in the cell membrane of E. coli and human embryonic kidney (HEK-293) cells. However, hydraphile only increases the permeability of bacterial membranes. An advantage of this approach is that bacteria cannot readily develop resistance to membrane-active amphiphiles as observed with benzyl C14 hydraphiles. Our results show that hydraphiles inhibited the activity of norA efflux pump in S. aureus. As a result, the accumulation of the substrate/antibiotic increases in the S. aureus cytoplasm. This increases the antibiotic potency. At sub-lethal concentration of benzyl C14 hydraphile, the survival of three different mammalian cells was 80-100%. Overall, we report a novel adjuvant platform that could be used to rescue the efficacy of existing antibiotics for the treatment of life-threatening bacterial infections

Compositions and methods for synthetic amphiphile-induced changes in plant root morphology

The disclosure provides a method for increasing the lateral root development of a plant by exposing said plant to a composition containing a synthetic amphiphile. By increasing the number of lateral roots, the surface area of the root structure is increased, making the plants better able to survive such stresses as drought or low nutrients. For the most up-to-date information about these patents, including the availability of Certificates of Correction, be sure to check the United States Patent and Trademark Office\u27s free, publicly accessible database: Patent Public Search https://ppubs.uspto.gov/pubwebapp/static/pages/landing.htmlhttps://irl.umsl.edu/patents/1006/thumbnail.jp

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF TAPENTADOL HCL, ACECLOFENAC AND PARACETAMOL IN TERNARY MIXTURE

Objective: To develop a accurate, precise and specific RP-HPLC method for simultaneous estimation of Tapentadol HCl (TAP), Aceclofenac (ACE) and Paracetamol (PCM) in its laboratory synthetic mixture.Methods: The optimized method uses C8 Thermo quest, hypersil division, 250*4.60 mm; 5 μ column, mobile phase consisting of phosphate buffer (pH 3) and acetonitrile in the ratio of 40:60, flow rate 0.8 ml/min. The detection wavelength was set at 217 nm.Results: The developed method resulted Paracetamol, Tapentadol HCl and Aceclofenac in eluting at 4.008 min 4.595 min and 6.073 min respectively. Linearity was observed over the concentration range of 52-130 µg/ml for PCM, 16-40 µg/ml forACE and 12-30 µg/ml forTAP. The percentage recovery was found to be in the range of 98-102% at three different levels of a standard addition. The precision (intra-day, inter-day) of the method was within the limit (RSD<2%).Conclusion: The proposed method was found to be accurate, precise, reproducible and specific and it can be used for qualitative and quantitative determination of Tapentadol HCl, Aceclofenac and Paracetamol in their combined dosage form in the pharmaceutical industry.Â

Dynamic heterogeneity in polydisperse systems: A comparative study of the role of local structural order parameter and particle size

In polydisperse systems, describing the structure and any structural order parameter (SOP) is not trivial as it varies with the number of species we use to describe the system, M . Depending on the degree of polydispersity, there is an optimum value of M = M0 where we show that the mutual information of the system increases. However, surprisingly the correlation between a recently proposed SOP and the dynamics is highest for M = 1. This effect increases with polydispersity. We find that the SOP at M = 1 is coupled with the particle size, {\sigma}, and this coupling increases with polydispersity and decreases with an increase in M . Careful analysis shows that at lower polydispersity the SOP is a good predictor of the dynamics. However, at higher polydispersity, the dynamics is strongly dependent on {\sigma}. Since the coupling between the SOP and {\sigma} is higher for M = 1 thus, it appears to be a better predictor of the dynamics. We also study the Vibrality an order parameter independent of structural information. Compared to SOP, at high polydispersity we find Vibrality to be a marginally better predictor of the dynamics. However, this high predictive power of Vibrality, which is not there at lower polydispersity, appears to be due to its stronger coupling with {\sigma}. Thus our study suggests that for systems with high polydispersity, the correlation of any order parameter and {\sigma} will affect the correlation between the order parameter and dynamics and need not project a generic predictive power of the order parameter.Comment: 14 pages, 41 figures, 1 tabl

Molecules that inhibit efflux pumps in multi-drug resistant bacteria and uses thereof

Methods and compositions are provided for increasing or enhancing the efficacy of antibiotics, such as by increasing antimicrobial activity, against a variety of microbes by co-administration with synthetic amphiphiles, including lariat ethers and hydraphiles. Methods and compositions for overcoming antibiotic resistance are also provided. For the most up-to-date information about these patents, including the availability of Certificates of Correction, be sure to check the United States Patent and Trademark Office\u27s free, publicly accessible database: Patent Public Search https://ppubs.uspto.gov/pubwebapp/static/pages/landing.htmlhttps://irl.umsl.edu/patents/1025/thumbnail.jp

Retrospective analysis of oral cavity squamous cell carcinoma treated with surgery and adjuvent radiotherapy

Background: Oral cavity cancer is one of the leading causes of cancer related deaths in developing countries. Most of the failures occur due to locoregional recurrence. The present study was conducted to find out the pattern of recurrences and factors responsible for that in oral cavity squamous cell carcinoma (SCC).Methods: The study was conducted at Gujarat cancer and research institute Ahmedabad, India. Total 260 patients were evaluated in study from year January 2013 to December 2013 retrospectively. Two year follow up was studied to find out the pattern of failure in terms of local, regional (nodal) and systemic.Results: Oral cavity SCC has high chances of local failure when removed inadequately during surgery. Perineural spread, lymphovascular involvement and perinodal spread are important prognostic factors.Conclusions: Most patients of oral cavity cancer present in advanced stages. Close margins and perineural involvement are responsible for local recurrences while perinodal spread and lymphovascular involvement contributes to nodal recurrences. Tobacco consumption is important responsible factor.

Enhancement of antibiotic efficacy

Methods and compositions are provided for increasing or enhancing the efficacy of antibiotics, such as by increasing antimicrobial activity, against a variety of microbes by co-administration with synthetic amphiphiles, including lariat ethers and hydraphiles. Methods and compositions for overcoming antibiotic resistance are also provided. For the most up-to-date information about these patents, including the availability of Certificates of Correction, be sure to check the United States Patent and Trademark Office\u27s free, publicly accessible database: Patent Public Search https://ppubs.uspto.gov/pubwebapp/static/pages/landing.htmlhttps://irl.umsl.edu/patents/1012/thumbnail.jp

Bis-amino acid based compound and use thereof

Compositions comprising bis(tryptophan) derivatives are provided that act as antimicrobials. Also provided are methods for reversing antibiotic resistance in a bacterium, or recovering or enhancing antimicrobial activity of an antibiotic against a variety of microbes, by co-administration with a bis(tryptophan) derivative.https://irl.umsl.edu/patents/1004/thumbnail.jp

Comparative study of tension band wiring and pre contoured locking compression plate fixation in olecranon fractures in adults

Background: Olecranon fractures are about 10% of all proximal forearm fractures.Mostly intra articular fractures, require anatomical reduction and internal fixation for satisfactory clinical outcomes. The most commonly used techniques are still tension band wiring (TBW) and plate fixation (PF). The aim of the current study is to discuss whether TBW or PF technique of internal fixation is better in the treatment of olecranon fractures.Methods: This is a comparative study including 30 adult patients of olecranon fracture classified by Mayo classification and operated upon by tension band plating (group A) and tension band wiring (group B) at Department of Orthopaedics, Sri Aurobindo Medical College and PG Institute, Indore. All operated cases between the period of January 2018 to August 2019 with follow up of 1 year were assessed on the basis of functional outcome using Mayo elbow performance score (MEPS).Results: The MEPS, 73% of the patients in group A achieved a good to excellent results in comparison to 60% in group B. no significant differences between the two groups could be detected regarding the clinical and radiographic outcome.Conclusions: Both TBW and PF interventions had treatment benefit in OFs. The current study reveals that there are no significant differences in MEPS, improvement rate and ROM between TBW and PF for OFs. More high-quality studies are required to further confirm our results as most of the cases included in study belonged to Mayo type IIA category

Global Pandemic Conditions and List of Possible Medications and Vaccines for the Treatment of COVID-19: A Review

At the end of December 2019, a novel coronavirus was identified which caused severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a disease known as coronavirus disease 2019 (COVID-19). The virus first originated in the city of Wuhan in China, causing symptoms such as pneumonic plague, which began in the Wuhan and then spread throughout the world with high transmission efficiency. Special precautions and care are needed such as leaving the public area, covering your mouth with a mask, not shaking hands, washing hands, and sanitation from time to time. Infection due to SARS-CoV-2 shows several symptoms, one of which is very often the patient shows difficulty breathing. Currently, COVID-19 has been declared a global pandemic and has almost attacked all countries in the world, including in India which has one of the largest human populations in the entire world. One of the challenges in handling COVID-19 is the unavailability of drugs or special vaccines to treat the disease, so clinical practitioners and academics are currently testing various drugs to see how they affect the COVID-19 patients. Some of the drugs tested provide effective mechanisms against SARS-CoV-2, such as chloroquine, remdesivir, lopinavir, and vaccines under development. These drugs are still being tested and are now at the forefront to combat the effects of SARS-CoV-2 infection. This review article will discuss all kinds of ins and outs of SARS-CoV-2 and COVID-19, including the transmission method, how to prevent it, as well as various drugs and vaccines currently used in handling COVID-19