Exploring the role of antibiotics and steroids in managing respiratory diseases.

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.

STABILITY INDICATIVE HPLC DETERMINATION OF RELATED SUBSTANCES AND IDENTIFICATION OF POTENTIAL DEGRADANTS USING LC-MS IN TRIPLE COMBINATION ANTIRETROVIRAL TABLETS.

A rapid stability indicating liquid chromatography method was developed and validated for the simultaneous quantitation of related substances of antiretrovirals in combined oral dosage formulation. Separation was achieved using a Waters, Xterra RP-18 column (250 x 4.6 mm) with a mobile phase containing a gradient mixture of sodium acetate trihydrate solution and acetonitrile with a flow rate of 1 mL/min, detec- tion at 254 nm. A simple preparative and LC-MS method were applied for the isolation and identification of degradation products. The active drugs were subjected to stress studies and significant degradation was observed. The spectral purity of the active drugs was determined to establish the stability indicating power of the developed method. The developed chromatographic method was validated as per ICH guidelines and is capable to identify and quantify all the 17 impurities at a level of 0.01 and 0.03%, respectively, with respect to test concentration. The wide range of linearity and good resolution imply that the method is suitable for routine quantification of related substances as well as for the assay of the actives.

Identification of Phytoconstituents of Tragia Involucrata leaf Extracts and Evaluate their Correlation with Anti-inflammatory & Antioxidant Properties.

AIMS: The present investigation was aimed at exploring the phytoconstituents using Gas Chromatography Mass Spectroscopy and to evaluate antioxidant and anti-inflammatory properties of the leaf extracts. MATERIALS AND METHODS: The extracts were obtained sequentially with petroleum ether, ethyl acetate and water using Soxhlet apparatus. The anti-inflammatory property of the identified compounds using GC- MS spectroscopy was evaluated in silico. The antioxidant activity was performed by DPPH and H2O2 method whereas anti-inflammatory study was carried out by HRBC membrane stabilization method. Terpenoids were found to be a major constituents in petroleum ether extract while, phenols and flavonoids were predominantly found in ethyl acetate extract. RESULTS AND DISCUSSION: The GC-MS analysis of the extract revealed six major molecules including Squalene, 19ß, 28-epoxyleanan-3-ol and 2-tu-Butyl-5-chloromethyl-3-methyl-4-oxoimidazolidine- 1-carboxylic acid. The ethyl acetate extract showed a significant antioxidant activity (P<0.01) in both DPPH method (70.87%) and H2O2 method (73.58%) at 200 µg mL-1. Increased membrane stabilization of petroleum ether extract was observed in the in vitro anti-inflammatory activity study. A strong relationship between the terpenoid content and anti-inflammatory activity was obtained from the correlation (0.971) and docking study. CONCLUSION: These results justify T. involucrata to be a rich source of terpenoids with potent anti- inflammatory property.

Antibacterial and In Vitro Growth Inhibition Study of Struvite Urinary Stones Using Oxalis corniculata Linn. Leaf Extract and its Biofabricated Silver Nanoparticles.

BACKGROUND: Herbal drugs are gaining exponential scientific recognition due to their distinct advantages. In the last 2-3 decades, a gradual increase in worldwide patents on herbal nanoformulations has been noted to address the solubility and bioavailability issues of phytoceuticals. Struvite or ammonium magnesium phosphate hexahydrate (NH4MgPO4.6H2O) is among the important urinary infection stones causing painful urological ailment. These smaller stones may bind together to form bigger staghorn calculus. Urinary tract infections caused by some gram positive and gram negative bacteria further enhance the chance of formation of such stones. Oxalis corniculata Linn. is an edible plant, traditionally used in the treatment of bacterial infections and kidney stones. However, there is no scientific evidence to relate the use of O. corniculata against struvite kidney stones. Hence, the antibacterial and struvite stones inhibition activity of the aqueous extract of Oxalis corniculata Linn. leaves and its biofabricated silver nanoparticles (AgNPs) was studied. METHODS: The aqueous extract of O. corniculata was prepared by Soxhlet extraction. AgNPs were synthesized using green technique and were characterized using UV and IR spectroscopy, XRD, TEM, DLS and zeta potential studies. Antibacterial activity of the aqueous extract and the silver nanoparticles was tested against E. coli (gram negative) and S. aureus (gram positive) species. Struvite stones were grown in a gel medium by in vitro single diffusion gel growth technique and its inhibition study was carried out using the extract and its biofabricated nanoparticles. RESULTS: The aqueous extract and its biofabricated AgNPs exhibited potent antibacterial activity against both gram positive and gram negative strains of bacteria. The aqueous extract also effectively repressed the growth of struvite stones and led to the dissolution of stones, but the inhibitory effect was further enhanced by its biofabricated AgNPs. CONCLUSION: The present work confirms the inhibitory activity of the aqueous extract of edible O. corniculata and its biofabricated silver nanoparticles against urinary tract infection (UTI) causing bacteria and urolithiasis. Therefore, the consumption of O. corniculata in our daily diet may reduce the risk of UTI and urolithiasis.

A clinical update on metformin and lung cancer in diabetic patients.

Diabetes mellitus (DM) is frequently increased in many countries and become a serious health problem worldwide. Diabetes is associated with dysfunction of different organs such as heart, eyes, blood vessels, nerves, and kidneys. There is a strong connection between diabetes and cancer. Metformin is one of the most commonly prescribed oral antidiabetic medicines and it is suggested as the first-line therapy due to its comparatively safe, inexpensive, effective and well-tolerated. Some of the in vitro and in vivo investigations proved that metformin may have a direct anticancer action by preventing the proliferation of malignant cells and formations of the colony, inducing arrest of cell cycle and apoptosis and suppressing tumor growth. The antiproliferative mechanism of metformin alone or in combination with various chemotherapeutic agents is complex and involves several beneficial roles. In this regard, clinical studies are required to explain these roles. In the coming future, the use of metformin, alone or in combination with current chemotherapy, might be a conventional approach to effectually manage lung cancer. This mini-review provides a critical overview of currently available clinical trials investigating the effects of metformin in lung cancer.

Biosynthesis of AgNPs using aqueous leaf extract of Ipomoea eriocarpa and their anti-inflammatory effect on carrageenan-induced paw edema in male Wistar rats.

Silver nanoparticles (AgNPs) were synthesised from aqueous Ag nitrate through a simple, competent and eco-friendly method using the leaf extract of Ipomoea eriocarpa as reducing as well as capping agent. Ultraviolet-visible absorption spectroscopy was used to confirm the formation of AgNPs which displayed the substantiation of surface plasmon bands at 425 nm. The NPs were also characterised using Fourier transformer infrared spectroscopy, X-ray diffraction method, transmission electron microscope and zeta potential. The characterisation study confirmed the formation of AgNPs, their spherical shape and average diameter of 12.85 ± 8.65 nm. Zeta potential value of -20.5 mV suggested that the AgNPs are stable in the suspension. The aqueous extract and the AgNPs were further screened for in vivo anti-inflammatory activity using carrageenan-induced paw edema in male Wistar rats. The study demonstrated that the AgNPs (1 ml kg-1) had a significant (p < 0.05) anti-edemic effect and inhibition was observed from the first hour (21.31 ± 1.34) until the sixth hour (52.67 ± 1.41), when the inhibitory effect was greatest and superior to the aqueous extract and the standard, diclofenac.

Evaluation of in vitro and in vivo anti-urolithiatic activity of silver nanoparticles containing aqueous leaf extract of Tragia involucrata.

The present investigation is focused on exploring the anti-urolithiatic potential of aqueous leaf extract of Tragia involucrata (TIA) and its silver nanoparticles (AgNPs) and to quantify the total phenol, flavonoid, terpenoid and sterol contents present in TIA. Quantification results suggested TIA to be a rich source of phenol, flavonoid and terpenoid and less of sterol content. The AgNPs were synthesized by a simple green method using aqueous extract of T. involucrata. The formation of AgNPs was confirmed through UV spectroscopy, particle size analysis, zeta potential, X-ray diffraction and transmission electron microscopy. The in vitro struvite growth inhibitory activity of the extract was performed using a single gel diffusion method. Samples incorporated with higher concentration of 2% TIA and AgNPs (200 µg mL-1) exhibited potent crystal growth inhibitory activity which was further supported by the dissolution of crystals in gel medium. Calcium oxalate stone formation was induced in rats by the oral administration of ethylene glycol in water. Stone formation was assessed by increase in the levels of calcium and phosphorous in the urine and accumulation of nitrogenous substances like urea, creatinine in renal tissues and blood. Prophylactic treatment with TIA and AgNPs showed significant anti-urolithiatic activity with normalization of the mineral contents of the urine and serum samples. Histopathological analysis of the kidney of TIA- and AgNP-treated animals showed no CaOx deposits and a normal architecture of the kidney cells. We conclude that aqueous extract of T. involucrata and its AgNPs has potential for the treatment of patients with recurrent stones.

Formation of struvite urinary stones and approaches towards the inhibition-A review.

BACKGROUND: Struvite is one of the most common urinary/kidney stones, composed of magnesium ammonium phosphate (MgNHPO4·H2O). They are also termed as infection stones as these are associated with urinary tract infections. Numerous studies have been carried out to examine the growth and inhibition of struvite stones. OBJECTIVE: This review summarizes various reports on the factors responsible for inducing struvite stones in the kidney and gives a detailed account of studies on inhibition of growth of struvite crystals. RESULTS: The presence of urea-splitting bacteria such as Proteus mirabilis and alkaline pH plays a crucial role in struvite formation. In vitro inhibition of struvite stones by various chemical agents were examined mainly in artificial urine whereas inhibition by herbal extracts was studied in vitro by gel diffusion technique. Herbal extracts of curcumin, Boerhaavia diffusa Linn, Rotula aquatica and many other plants, as well as some chemicals like pyrophosphate, acetohydroxamic acid, disodium EDTA and trisodium citrate, were reported to successfully inhibit struvite formation. CONCLUSION: The present review recapitulates various factors affecting the growth of struvite urinary stones and the inhibitory role of certain chemicals and herbal extracts. Most of the tested plants are edible hence can be easily consumed without any adverse effects whereas the side effects of chemicals are unknown due to lack of toxicity studies. Thus, the use of herbal extracts might serve as an alternate and safe therapy for prevention of struvite stones.

Antiurolithiatic activity of ethanol leaf extract of Ipomoea eriocarpa against ethylene glycol-induced urolithiasis in male Wistar rats.

OBJECTIVE: The objective of this study was to investigate the prophylactic and curative effect of the ethanol leaf extract of Ipomoea eriocarpa (Convolvulaceae) (IEE) in ethylene glycol-induced urolithiasis in rats. MATERIALS AND METHODS: Thirty male Wistar rats were divided into five groups (n = 6). All the groups received stone-inducing treatment till 28(th) day, comprising 1% ethylene glycol (v/v) with 1% ammonium chloride (w/v) for 4 days, followed by 1% ethylene glycol alone in water, except Group I (Control). Group II received only stone-inducing treatment till 28(th) day. Group III (Standard) received cystone (500 mg/kg) from 15(th) day till 28(th) day. Group IV (Prophylactic) received IEE (200 mg/kg) from 1(st) day till 28(th) day and Group V (Curative) received IEE (200 mg/kg) from 15(th) day till 28(th) day. Various biochemical parameters such as phosphorus, calcium, magnesium, urea, and creatinine levels were evaluated using urine, serum, and kidney homogenate. The kidneys were also sectioned and examined histopathologically under light microscope to study the kidney architecture and calcium oxalate deposits. RESULTS: The IEE treatment (prophylactic and curative) significantly (P < 0.001) restored the parameters in urine, serum, and kidney homogenate to near-normal level. The histopathological examinations revealed that calcium oxalate crystal deposits in the renal tubules and congestion and dilation of the parenchymal blood vessels were significantly reverted after IEE treatment. CONCLUSIONS: The leaf extract of I. eriocarpa reduces and inhibits the growth of urinary stones showing its effect as an antiurolithiatic agent.

Microemulsion synthesis of silver nanoparticles using biosurfactant extracted from Pseudomonas aeruginosa MKVIT3 strain and comparison of their antimicrobial and cytotoxic activities.

In the present study, an efficient biosurfactant producing bacterial strain Pseudomonas aeruginosa MKVIT3 was isolated from an oil logging area in Vellore district of Tamil Nadu, India. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was performed for the identification of different congeners present in the extracted biosurfactant. The column purified biosurfactant was used to stabilise the formation of silver nanoparticles (NP) using borohydrate reduction in reverse micelles. The silver NP were characterised using UV-vis absorption spectroscopy, Powder-XRD TEM analysis and zeta potential. A comparative study of the antimicrobial activity and cytotoxic efficacy was done for the extracted purified biosurfactant and the silver NP. The LC-MS/MS analysis of the biosurfactant revealed the presence of five rhamnolipid congeners. The synthesised silver NP showed the characteristic absorption peak in UV-vis at 440 nm. Powder-XRD and TEM analysis revealed the average particle size of the NP as 17.89 ± 8.74 nm as well as their cubic structure. Zeta potential value of -30.9 mV suggested that the silver NPs are stable in the suspension. Comparative study of the antimicrobial activity revealed that the silver NP are more potent than the biosurfactant in inhibiting the growth of microbes. Cytotoxic activity revealed that the biosurfactant are more effective than the synthesised silver NP.

Preparative isolation and high-resolution mass identification of 10 stressed study degradants of nicorandil tablets.

Nicorandil is a potent drug with a dual mechanism of action which results in its wide application in treating angina patients. Since the literature review showed no single preparative method for isolation and liquid chromatography-mass spectrometry (LC-MS) compatible [high-performance liquid chromatography (HPLC) or ultra performance liquid chromatography (UPLC)] method for identification for the impurities generated in process and by force degradation was reported. Thus an attempt was made to develop a single preparative method for isolation and HPLC and UPLC methods for identification of impurities of nicorandil in tablet dosage form. Ten degradants were found in the formulated drug under the stress conditions, [40°C/75% relative humidity for 2 months] in an LC-MS compatible method. A cost effective and high-throughput simple gradient preparative HPLC method was developed with a runtime of 30 min to isolate all the degradants. The method is capable and can be used to isolate further degradants. To detect these degradants, rapid and effecient HPLC and UPLC methods were developed and the same were identified by UPLC-time of flight mass spectrometry (TOF MS). The crux of this work involves a single preparative isolation method and UPLC identification method for all degradants with a very short runtime, i.e., 13.8 min, and, furthermore, the method has the potential to separate a wide range of degradants.

Comparative evaluation of transdermal formulations of norfloxacin with silver sulfadiazine cream, USP, for burn wound healing property.

OBJECTIVE: In an attempt to find a better treatment for bacterial infections and burn wounds, various semisolid formulations containing 5% w/w of norfloxacin were prepared and evaluated for physicochemical parameters, in vitro drug release through cellophane membrane, antimicrobial activity, and burn wound healing properties. The prepared formulations were compared with silver sulfadiazine 1% cream, USP. METHODS: Various semisolid formulations were prepared with different bases like Carbopol, polyethylene glycol, and hydroxypropylmethyl cellulose, using standard procedures. The antimicrobial activity of these semisolid norfloxacin formulations, against various strains of aerobic and anaerobic microorganisms, was evaluated by using a standard cup-plate method. The wound healing property was evaluated by measuring the wound contraction and expressed as percentage of contraction of original wound size for each animal group. RESULTS: Antimicrobial activity of norfloxacin semisolid formulations was found to be equally effective against both aerobic and anaerobic bacteria in comparison to a formulation of silver sulfadiazine 1% cream, USP, available on the market. CONCLUSION: The burn wound healing property of the prepared norfloxacin semisolid formulations was found to be in good agreement with silver sulfadiazine 1% cream, USP, available on the market.