Browsing by Author "Sharma N."

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    Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus
    (2023-01-01) Varghese G.M.; Dayanand D.; Gunasekaran K.; Kundu D.; Wyawahare M.; Sharma N.; Chaudhry D.; Mahajan S.K.; Saravu K.; Aruldhas B.W.; Mathew B.S.; Nair R.G.; Newbigging N.; Mathew A.; Abhilash K.P.P.; Biswal M.; Prasad A.H.; Zachariah A.; Iyadurai R.; Hansdak S.G.; Sathyendra S.; Sudarsanam T.D.; Prakash J.A.J.; Manesh A.; Mohan A.; Tarning J.; Blacksell S.D.; Peerawaranun P.; Waithira N.; Mukaka M.; Cheah P.Y.; Peter J.V.; Abraham O.C.; Day N.P.J.; Mahidol University
    Background: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. Methods: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. Results: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P=0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P=0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. Conclusions: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone.
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    Phosphatidylcholine-Specific Phospholipase C as a Promising Drug Target
    (2023-08-01) Eurtivong C.; Leung E.; Sharma N.; Leung I.K.H.; Reynisson J.; Mahidol University
    Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol (DAG) from phosphatidylcholine. Although PC-PLC has been linked to the progression of many pathological conditions, including cancer, atherosclerosis, inflammation and neuronal cell death, studies of PC-PLC on the protein level have been somewhat neglected with relatively scarce data. To date, the human gene expressing PC-PLC has not yet been found, and the only protein structure of PC-PLC that has been solved was from Bacillus cereus (PC-PLCBc). Nonetheless, there is evidence for PC-PLC activity as a human functional equivalent of its prokaryotic counterpart. Additionally, inhibitors of PC-PLCBc have been developed as potential therapeutic agents. The most notable classes include 2-aminohydroxamic acids, xanthates, N,N′-hydroxyureas, phospholipid analogues, 1,4-oxazepines, pyrido[3,4-b]indoles, morpholinobenzoic acids and univalent ions. However, many medicinal chemistry studies lack evidence for their cellular and in vivo effects, which hampers the progression of the inhibitors towards the clinic. This review outlines the pathological implications of PC-PLC and highlights current progress and future challenges in the development of PC-PLC inhibitors from the literature.
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    The antibiotic resistance profiles of Pseudomonas aeruginosa in the Asia Cornea Society Infectious Keratitis Study
    (2024-12-01) Khor W.B.; Lakshminarayanan R.; Periayah M.H.; Prajna V.N.; Garg P.; Sharma N.; Mehta J.S.; Young A.; Goseyarakwong P.; Puangsricharern V.; Tan A.L.; Beuerman R.W.; Tan D.T.H.; Khor W.B.; Mahidol University
    Purpose: To describe the prevalence and antibiotic resistance profiles of Pseudomonasaeruginosa isolated from the Asia Cornea Society Infectious Keratitis Study (ACSIKS). Methods: All bacterial isolates from ACSIKS underwent repeat microbiological identification in a central repository in Singapore. Minimum inhibitory concentration (MIC) determination was conducted for isolates of P. aeruginosa against thirteen antibiotics from 6 different classes, and categorized based on Clinical Laboratory Standard Institutes’ reference ranges. The percentage rates of resistance (non-susceptibility) to each antibiotic included isolates of both intermediate and complete resistance. Multi-drug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. Results: Of the 1493 unique bacterial specimens obtained from ACSIKS, 319 isolates were of P. aeruginosa. The majority of isolates were from centers in India (n = 118, 37%), Singapore (n = 90, 28.2%), Hong Kong (n = 31, 9.7%) and Thailand (n = 30, 9.4%). The cumulative antibiotic resistance rate was the greatest for polymyxin B (100%), ciprofloxacin (17.6%) and moxifloxacin (16.9%), and lowest for cefepime (11.6%) and amikacin (13.5%). Isolates from India demonstrated the highest antibiotic resistance rates of all the centers, and included moxifloxacin (47.5%) and ciprofloxacin (39.8%). Forty-eight of the 59 MDR isolates also originated from India. Antibiotic resistance rates were significantly lower in the other ACSIKS centers, and were typically less than 10%. Conclusions: The antibiotic resistance profiles of P. aeruginosa varied between different countries. While it was low for most countries, substantial antibiotic resistance and a significant number of multi-drug resistant isolates were noted in the centers from India.
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    Trends in functional beverages: Functional ingredients, processing technologies, stability, health benefits, and consumer perspective
    (2023-08-01) Gupta A.; Sanwal N.; Bareen M.A.; Barua S.; Sharma N.; Joshua Olatunji O.; Prakash Nirmal N.; Sahu J.K.; Mahidol University
    The World Health Organization's emphasis on the health benefits of functional foods and beverages that has contributed to the rise in its popularity globally. Besides these consumers have become more aware of the importance of their food composition and nutrition. Among the fastest-growing market segments within the functional food industries, the functional drinks market focuses on fortified beverages or products that are novel with improved bioavailability of bioactive compounds, and their implicated health benefits. The bioactive ingredients in functional beverages include phenolic compounds, minerals, vitamins, amino acids, peptides, unsaturated fatty acids, etc. which can be obtained from plant, animal and microorganisms. The types of functional beverages which are globally intensifying the markets are pre-/pro-biotics, beauty drinks, cognitive and immune system enhancers, energy and sports drink produced via several thermal and non-thermal processes. Researchers are focusing on improving the stability of the active compounds by encapsulation, emulsion, and high-pressure homogenization techniques to strengthen the positive consumer perspective in functional beverages. However, more research is needed in terms of bioavailability, consumer safety, and sustainability of the process. Hence, product development, storage stability, and sensory properties of these products are vital for consumer acceptance. This review focuses on the recent trends and developments in the functional beverages industry. The review provides a critical discussion on diverse functional ingredients, bioactive sources, production processes, emerging process technologies, improvement in the stability of ingredients and bioactive compounds. This review also outlines the global market and consumer perception of functional beverages with the future perspective and scope.