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1.
Mol Biol Rep ; 50(3): 2663-2683, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36536185

ABSTRACT

The past several decades have witnessed the emergence and re-emergence of many infectious viral agents, flaviviruses, influenza, filoviruses, alphaviruses, and coronaviruses since the advent of human deficiency virus (HIV). Some of them even become serious threats to public health and have raised major global health concerns. Several different medicinal compounds such as anti-viral, anti-malarial, and anti-inflammatory agents, are under investigation for the treatment of these viral diseases. These therapies are effective improving recovery rates and overall survival of patients but are unable to heal lung damage caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, there is a critical need to identify effective treatments to combat this unmet clinical need. Due to its antioxidant and immunomodulatory properties, stem cell therapy is considered a novel approach to regenerate damaged lungs and reduce inflammation. Stem cell therapy uses a heterogeneous subset of regenerative cells that can be harvested from various adult tissue types and is gaining popularity due to its prodigious regenerative potential as well as immunomodulatory and anti-inflammatory properties. These cells retain expression of cluster of differentiation markers (CD markers), interferon-stimulated gene (ISG), reduce expression of pro-inflammatory cytokines and, show a rapid proliferation rate, which makes them an attractive tool for cellular therapies and to treat various inflammatory and viral-induced injuries. By examining various clinical studies, this review demonstrates positive considerations for the implications of stem cell therapy and presents a necessary approach for treating virally induced infections in patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/therapy , Interferons , Lung , Stem Cell Transplantation
2.
Environ Res ; 234: 116555, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37419199

ABSTRACT

An easy synthesis of two 1,3,4-oxadiazole derivatives, namely, 2-phenyl-5-(pyridin-3-yl)-1,3,4-oxadiazole (POX) and 2-(4-methoxyphenyl)-5-(pyridin-3-yl)-1,3,4-oxadiazole (4-PMOX), and their corrosion-inhibition efficacy against mild steel corrosion in 1 N HCl, is evaluated using weight loss from 303 to 323 K, Electrochemical Impedance Spectroscopy (EIS), Potentiodynamic Polarization (PDP), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), UV-Vis spectroscopy, along with theoretical evaluation. Both POX and 4-PMOX exhibit excellent inhibition efficiency, with values reaching 97.83% and 98% at 500 ppm, respectively. The PDP analysis reveals that both derivatives act as mixed-type inhibitors. The Langmuir adsorption isotherm provides insights into the adsorption phenomena, demonstrating that 4-PMOX exhibits superior adsorption behavior on the mild steel surface compared to POX. This finding is further supported by SEM, DFT, RDF, and MSD analyses. Quantum mechanical parameters, including EHOMO, ELUMO, dipole moment (µ), energy gap (ΔE), etc., are in good agreement with the effectiveness of inhibition performance revealing ΔE values of 3.10 and 2.75 for POX and 4-PMOX, respectively. The results obtained from this study hold significant implications for researchers aiming to design more efficient organic inhibitors to combat metal corrosion.


Subject(s)
Oxadiazoles , Steel , Steel/chemistry , Corrosion , Pyridines
3.
J Biochem Mol Toxicol ; 35(7): e22785, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33860986

ABSTRACT

Azilsartan is found to be more potent than other angiotensin receptor blockers in reducing blood pressure. However, its effect on the heart following myocardial infarction remains to be established. For the first time, we investigated the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonistic and cardioprotective properties of azilsartan. Computational modeling studies of interactions between azilsartan and PPAR-γ revealed azilsartan as an agonist of PPAR-γ and showed the mechanism of azilsartan in cardioprotection. Our study compared the cardioprotective potential of telmisartan to that of azilsartan in a murine model of myocardial ischemia-reperfusion injury by comparing their antioxidant, ant apoptotic, anti-inflammatory, mitogen-activated protein kinase (MAPK)-modulating ability, and PPAR-γ agonistic activity. Male Wistar rats were grouped into four to receive vehicle (dimethyl sulfoxide [0.05%] 2 ml/kg) telmisartan (10 mg/kg p.o.), azilsartan (10 mg/kg p.o.) or azilsartan with specific PPAR-γ blocker, GW 9662 for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Telmisartan and azilsartan pretreatment significantly nearly normalized cardiac parameters and preserved structural changes. Both drugs inhibited oxidative burst, inflammation, as well as cell death by modulating apoptotic protein expression along with reduction in 4',6-diamidino-2-phenylindole/terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. An increment in pro-survival kinase ERK paralleled with a reduction in p38 and JNK was also revealed by MAPK pathway studies, after administration of these drugs. Interestingly, the aforementioned changes induced by both drugs were reversed by administration of the specific PPAR-γ antagonist, GW9662. However, we found that azilsartan upregulated PPAR-γ to a lesser extent as compared to telmisartan and the latter may be preferred in hypertensive patients at risk of myocardial infarction.


Subject(s)
Benzimidazoles/pharmacology , Cardiotonic Agents/pharmacology , MAP Kinase Signaling System/drug effects , Myocardial Reperfusion Injury , Myocardium , Oxadiazoles/pharmacology , Telmisartan/pharmacology , Animals , Disease Models, Animal , Male , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/prevention & control , Myocardium/metabolism , Myocardium/pathology , Rats , Rats, Wistar
4.
Arch Biochem Biophys ; 694: 108572, 2020 11 15.
Article in English | MEDLINE | ID: mdl-32926843

ABSTRACT

The methodology exploring the cardioprotective potential of the flavonoid Fisetin through its ability to modulate PPAR-γ was unraveled in the present study. Computational modelling through molecular docking based binding study of interactions between Fiestin and PPAR-γ revealed the potential role of Fisetin as an agonist of PPAR-γ. A murine model of cardiac ischemia-reperfusion injury was used to explore this further. Male Wistar Rats were randomly assigned to five groups. Fisetin (20 mg/kg; p. o) was administered for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Fisetin pretreatment upregulated the expression of PPAR-γ in heart tissue significantly Cardioprotection was assessed by measurement of hemodynamic parameters, infarct size, ELISA for oxidative stress, immunohistochemistry and TUNEL assay for apoptosis, and western blot analysis for MAPK proteins and inflammation. PPAR-γ activation by fisetin led to significantly reduced infarct size, suppression of oxidative stress, reduction of cardiac injury markers, alleviation of inflammation, and inhibition of apoptosis The MAPK-based molecular mechanism showed a rise in a key prosurvival kinase, ERK1/ERK2 and suppression of JNK and p38 proteins. The aforementioned beneficial findings of fisetin were reversed on the administration of a specific antagonist of PPAR-γ. In conclusion, through our experiments, we have proved that fisetin protects the heart against ischemia-reperfusion injury and the evident cardioprotection is PPAR-γ dependant. In conclusion, our study has revealed a prime mechanism involved in the cardioprotective effects of fisetin. Hence, Fisetin may be evaluated in further clinical studies as a cardioprotective agent in patients undergoing reperfusion interventions.


Subject(s)
Cardiotonic Agents/therapeutic use , Flavonoids/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/prevention & control , PPAR gamma/agonists , Animals , Cardiotonic Agents/metabolism , Flavonoids/metabolism , Flavonols , Heart/drug effects , Humans , MAP Kinase Signaling System/drug effects , Male , Mice , Molecular Docking Simulation , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/pathology , Myocardium/pathology , Oxidative Stress/drug effects , PPAR gamma/metabolism , Rats, Wistar , Up-Regulation
5.
Biomed Chromatogr ; 34(6): e4825, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32166756

ABSTRACT

Treatment through a combination of drugs involving cyclin D-dependent kinase inhibitors like abemaciclib and aromatase inhibitor like letrozole proved to be a potential therapeutic regimen and first-line treatment in estrogen receptor-positive breast cancer. In this study, we developed a simple and simultaneous RP-HPLC bioanalytical method for quantifying abemaciclib and letrozole in rat plasma. Abemaciclib and letrozole were separated on Zorbax Eclipse C18 column employing a gradient elution method comprising 10 mM ammonium acetate (pH 5) and acetonitrile as mobile phase. The method was found to have acceptable selectivity, accuracy (97.20-118.17%), precision (1.10-9.39%) and stability in the validation experiment performed as per the US Food and Drug Administration guidelines. The method sensitivity was low at a concentration level of 100 ng/ml. The applicability of the method has been verified through a single-dose oral pharmacokinetic study in rat. The developed method will be useful to quantitate the analytes in rat plasma samples of different preclinical studies including their pharmacokinetic drug-drug interactions in the future. To date, no method has been reported for the quantification of abemaciclib and letrozole simultaneously in any type of biological matrices. Therefore, this study makes a definite significant contribution in the field of bioanalytical research.


Subject(s)
Aminopyridines/blood , Aminopyridines/pharmacokinetics , Benzimidazoles/blood , Benzimidazoles/pharmacokinetics , Letrozole/blood , Letrozole/pharmacokinetics , Aminopyridines/chemistry , Animals , Benzimidazoles/chemistry , Chromatography, High Pressure Liquid/methods , Female , Letrozole/chemistry , Limit of Detection , Linear Models , Rats , Rats, Sprague-Dawley , Reproducibility of Results
6.
Biomed Chromatogr ; 33(12): e4672, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31386207

ABSTRACT

The combination of acebrophylline (ABP), levocetirizine (LCZ) and pranlukast (PRN) is used to treat allergic rhinitis, asthma, hay-fever and other conditions where patients experience difficulty in breathing. This study was carried out with the aim of developing and validating a reverse-phase high-performance liquid chromatographic bioanalytical method to simultaneously quantitate ABP, LCZ and PRN in rat plasma. The objective also includes determination of the pharmacokinetic interaction of these three drugs after administration via the oral route after individual and combination treatment in rat. Optimum resolution between the analytes was observed with a C18 Kinetex column (250 mm × 4.6 mm × 5 µm). The chromatography was performed in a gradient elution mode with a 1 mL/min flow rate. The calibration curves were linear over the concentration range of 100-1600 ng/mL. The intra- and inter-day precision and accuracy were found to be within acceptable limits as specified in US Food and Drug Administration guideline for bioanalytical method validation. The analytes were stable on the bench-top (8 h), after three freeze-thaw cycles, in the autosampler (8 h) and as a dry extract (-80°C for 48 h). The statistical results of the pharmacokinetic study in Sprague-Dawley rats showed a significant change in pharmacokinetic parameters for PRN upon co-administration of the three drugs.


Subject(s)
Ambroxol/analogs & derivatives , Cetirizine , Chromones , Theophylline/analogs & derivatives , Ambroxol/blood , Ambroxol/chemistry , Ambroxol/pharmacokinetics , Animals , Cetirizine/blood , Cetirizine/chemistry , Cetirizine/pharmacokinetics , Chromatography, High Pressure Liquid , Chromones/blood , Chromones/chemistry , Chromones/pharmacokinetics , Limit of Detection , Linear Models , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Theophylline/blood , Theophylline/chemistry , Theophylline/pharmacokinetics
7.
Pancreatology ; 18(5): 500-506, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29779831

ABSTRACT

BACKGROUND: Predicting severe acute pancreatitis (AP) is important for triage, prognosis, and designing therapeutic trials. Persistent systemic inflammatory response syndrome (SIRS) predicts severe AP but its diagnostic accuracy is suboptimal. Our objective was to study if cytokine levels could improve the predictive value of clinical variables for the development of severe AP. METHODS: Consecutive patients with AP were included in a prospective cohort study at a tertiary care center. Serum levels of IL-6, TNF-α, IL-10, MCP-1, GM-CSF and IL-1ß were measured at day 3 of onset of AP. Variables such as age, co-morbidity, etiology, SIRS, and cytokines were modeled to predict severe AP by multivariable regression analysis. Genotyping was done to correlate IL-6, TNF-α and MCP-1 gene polymorphisms with cytokine levels. RESULTS: Of 236 patients with AP, 115 patients admitted within 7 days of onset formed the study group. 37 of the 115 (32%) patients developed organ failure. Independent predictors of organ failure were persistent SIRS (OR 34; 95% CI: 7.2-159) and day 3 serum IL-6 of >160 pg/ml (OR 16.1; 95% CI:1.8-142). IL-6 gene (-174 G/C) GG genotype was associated with significantly higher levels of IL-6 compared to CC/CG genotype. Serum IL-6 >160 pg/ml increased the positive predictive value of persistent SIRS from 56% to 85% and specificity from 64% to 95% for predicting OF without compromising its sensitivity and negative predictive value. CONCLUSION: Serum IL-6 of >160 ng/ml added significantly to the predictive value of SIRS for severe AP.

8.
J Minim Access Surg ; 14(4): 291-297, 2018.
Article in English | MEDLINE | ID: mdl-29319014

ABSTRACT

INTRODUCTION: The fear of pleural adhesions and densely stuck lymph nodes in India, a country where tuberculosis is endemic, is one major factor keeping our surgeons away from video-assisted thoracoscopic surgery (VATS) lobectomy. In this paper, we aim to report our experience with performing VATS lobectomy in 102 cases using a standardised three-port anterior approach. MATERIALS AND METHODS: Between March 2012 and September 2016, we performed 102 VATS lobectomies. Sixty patients (58.8%) were males and 42 females (41.2%), with a mean age of 42.02 years. Diagnoses were as follows: benign disease (72), lung cancer (27) and pulmonary metastases (3). Among the cases with primary lung cancer, twenty out of 27 (74%) were adenocarcinoma and 7 cases of squamous carcinoma (25.92%). All patients underwent lobectomy by a standardised three-port anterior approach. RESULTS: The overall conversion rate was 8.82% (n = 9). We observed no postoperative complications in 82 (80.4%) patients. The average blood loss was 211.37 ml. Mean operative time was 173 min. Median length of hospital stay was 5 with median chest tube duration of 4.9 days. There was no in hospital or 30-day mortality. The most common complication was prolonged air leak. CONCLUSION: From this first Indian series, it is clear that VATS lobectomy is feasible in both benign and malignant cases. It also shows that the fear of adhesions is unwarranted and properly selected benign cases can also undergo VATS lobectomy safely.

9.
Chem Commun (Camb) ; 60(36): 4838-4841, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38619439

ABSTRACT

Herein, we present an efficient Pd-catalysed method for stereoselective synthesis of chromone C-glycosides from various glycals. We successfully applied this method to various glycals with different protecting groups, yielding the corresponding glycosides in 41-78% yields. Additionally, we investigated the potential of this approach for the late-stage modification of natural products and pharmaceutical compounds linked to glycals, leading to the synthesis of their respective glycosides. Furthermore, we extended our research to gram-scale synthesis and demonstrated its applicability in producing various valuable products, including 2-deoxy-chromone C-glycosides. In summary, our work introduces a novel library of chromone glycosides, which holds promise for advancing drug discovery efforts.


Subject(s)
Chromones , Glycosides , Palladium , Palladium/chemistry , Catalysis , Glycosides/chemistry , Glycosides/chemical synthesis , Stereoisomerism , Chromones/chemistry , Chromones/chemical synthesis , Molecular Structure , Biological Products/chemical synthesis , Biological Products/chemistry
10.
World J Pediatr Congenit Heart Surg ; : 21501351231215257, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38263667

ABSTRACT

Background: Treatment of congenital heart disease (CHD), being the most common congenital anomaly, puts immense financial burden in low- and middle-income countries (LMICs) and contributes significantly to infant mortality. We report experiences of treatment of CHD in the Indian state of West Bengal by a public-private partnership (PPP) model. Methods: Under the Rashtriya Bal Swasthya Karyakram, the government of the state of West Bengal in India launched a program called the "Sishu Sathi Scheme" to provide free treatment to children who need heart surgeries, irrespective of economic status. Treatment was provided in selected private hospitals and some public hospitals in a reimbursement model where government compensated the hospitals. Data were collected on such procedures from 2013 to 2022 and analyzed. Results: A total of 27,844 patients with CHD received treatment under the Sishu Sathi Scheme from August 2013 to December 2022. The average number of patients per year was 3,093. Detailed data of procedures from January 2016 to December 2022 showed a total of 22,572 procedures (6,249 device interventions, 4,840 cardiac catheterizations, and 11,483 surgical interventions). The in-hospital mortality of surgical procedures and catheterization lab procedures were 5.2% and 0.9%, respectively. Conclusions: A large number of patients with CHD were successfully treated under a PPP in the state of West Bengal in India. In spite of its inherent challenges, this model is of special relevance in LMICs where access and affordability for treatment of CHD always remain a challenge.

11.
Article in English | MEDLINE | ID: mdl-38446299

ABSTRACT

A convenient synthesis of a novel 1,3,4-oxadiazole derivative, specifically known as, 2-(5-methylthiophen-2-yl)-5-(pyridin-3-yl)-1,3,4-oxadiazole (MTPO), is reported along with a comprehensive evaluation of its ability to inhibit the corrosion of mild steel (MS) in a 1 N HCl environment using weight loss, EIS, PDP, SEM, EDX, and UV-Vis spectroscopy. The investigated inhibitor expressed excellent inhibition efficiency (99.05% at 500 ppm, 298 K) with a mixed-type inhibitory mechanism as demonstrated by the PDP technique. Furthermore, MTPO followed Langmuir adsorption isotherm, which provides insights into the adsorption phenomena, demonstrating that it exhibits superior adsorption behavior on the MS surface compared. In silico investigations, using DFT computation and MD simulation complements the experimental outcomes revealing strong adsorbing attributes of the MTPO hybrid with the ω - and ω + values of 8.8882 eV and 4.4787 eV, respectively. In addition, the radial distribution function also addressed the chemisorption behavior of MTPO. This article also takes into consideration the various ways in which the inhibitor interacts with the mild steel, offering potential insights for developing strategies to mitigate metal dissolution in acidic environments.

12.
Arch Med Res ; 55(6): 103037, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38981342

ABSTRACT

Human life and health have interacted reciprocally with the surrounding environment and animal fauna for ages. This relationship is evident in developing nations, where human life depends more on the animal population for food, transportation, clothing, draft power, and fuel sources, among others. This inseparable link is a potent source of public health issues, especially in outbreaks of zoonotic diseases transmitted from animals to humans. Zoonotic diseases are referred to as diseases that are naturally transmitted between vertebrate animals and humans. Among the globally emerging diseases in the last decade, 75% are of animal origin, most of which are life-threatening. Since most of them are caused by potent new pathogens capable of long-distance transmission, the impact is widespread and has serious public health and economic consequences. Various other factors also contribute to the transmission, spread, and outbreak of zoonotic diseases, among which industrialization-led globalization followed by ecological disruption and climate change play a critical role. In this regard, all the possible strategies, including advances in rapid and confirmatory disease diagnosis and surveillance/monitoring, immunization/vaccination, therapeutic approaches, appropriate prevention and control measures to be adapted, and awareness programs, need to be adopted collaboratively among different health sectors in medical, veterinary, and concerned departments to implement the necessary interventions for the effective restriction, minimization, and timely control of zoonotic threats. The present review focuses on the current scenario of zoonotic diseases and their counteracting approaches to safeguard their health impact on humans.

13.
FEBS J ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38975839

ABSTRACT

The protein-protein interaction (PPI) network of the Mediator complex is very tightly regulated and depends on different developmental and environmental cues. Here, we present an interactive platform for comparative analysis of the Mediator subunits from humans, baker's yeast Saccharomyces cerevisiae, and model plant Arabidopsis thaliana in a user-friendly web-interface database called MediatorWeb. MediatorWeb provides an interface to visualize and analyze the PPI network of Mediator subunits. The database facilitates downloading the untargeted and unweighted network of Mediator complex, its submodules, and individual Mediator subunits to better visualize the importance of individual Mediator subunits or their submodules. Further, MediatorWeb offers network visualization of the Mediator complex and interacting proteins that are functionally annotated. This feature provides clues to understand functions of Mediator subunits in different processes. In an additional tab, MediatorWeb provides quick access to secondary and tertiary structures, as well as residue-level contact information for Mediator subunits in each of the three model organisms. Another useful feature of MediatorWeb is detection of interologs based on orthologous analyses, which can provide clues to understand the functions of Mediator complex in less explored kingdoms. Thus, MediatorWeb and its features can help the user to understand the role of Mediator complex and its subunits in the transcription regulation of gene expression.

14.
Ann Pediatr Cardiol ; 16(5): 378-380, 2023.
Article in English | MEDLINE | ID: mdl-38766452

ABSTRACT

We report a unique intraoperative finding of an additional double left atrial appendage (LAA) during an arterial switch operation with ventricular septal defect closure in a 4-month-old girl. Immediately after the procedure, a prolapsing mass within the left atrium (LA) on the transesophageal echocardiogram raised concerns of a possible thrombus. The LAA was clearly visible with a pressure monitoring line which was put intraoperatively. To investigate further, cardiopulmonary bypass was resumed, and the heart was arrested and explored. There was an appendage-like structure, separate from the one that had the pressure monitoring line, which was inverted inside. It was pulled out from outside clearly establishing a double LAA. This report illustrates an example of a diagnostic dilemma caused by a double atrial appendage which was invaginated into LA masquerading as a mass or thrombus.

15.
Biosens Bioelectron ; 219: 114783, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36257116

ABSTRACT

The outbreak of pandemics (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 in 2019), influenza A viruses (H1N1 in 2009), etc.), and worldwide spike in the aging population have created unprecedented urgency for developing new drugs to improve disease treatment. As a result, extensive efforts have been made to design novel techniques for efficient drug monitoring and screening, which form the backbone of drug development. Compared to traditional techniques, microfluidics-based platforms have emerged as promising alternatives for high-throughput drug screening due to their inherent miniaturization characteristics, low sample consumption, integration, and compatibility with diverse analytical strategies. Moreover, the microfluidic-based models utilizing human cells to produce in-vitro biomimetics of the human body pave new ways to predict more accurate drug effects in humans. This review provides a comprehensive summary of different microfluidics-based drug sensing and screening strategies and briefly discusses their advantages. Most importantly, an in-depth outlook of the commonly used detection techniques integrated with microfluidic chips for highly sensitive drug screening is provided. Then, the influence of critical parameters such as sensing materials and microfluidic platform geometries on screening performance is summarized. This review also outlines the recent applications of microfluidic approaches for screening therapeutic and illicit drugs. Moreover, the current challenges and the future perspective of this research field is elaborately highlighted, which we believe will contribute immensely towards significant achievements in all aspects of drug development.

16.
Curr Drug Deliv ; 19(2): 170-181, 2022.
Article in English | MEDLINE | ID: mdl-33797368

ABSTRACT

Unprincipled use of antibiotics has led to antimicrobial resistance (AMR) against mostly available compounds, and has now become a major cause of concern for the scientific community. However, in the past decade, green synthesized silver nanoparticles (AgNPs) have received greater attention for the development of newer therapies as antimicrobials by virtue of their unique physico- chemical properties. Unlike traditional antibiotics, AgNPs exert their action by acting on multiple mechanisms, which make them potential candidates against AMR. Green synthesis of AgNPs using various medicinal plants has demonstrated a broader spectrum of action against several microbes in a number of attempts. The present paper provides an insight into the scientific studies that have elucidated the positive role of plant extracts/phytochemicals during the green synthesis of AgNPs and their future perspectives. The studies conducted so far seem promising; still, a few factors like the precise mechanism of action of AgNPs, their synergistic interaction with biomolecules, and industrial scalability, need to be explored further till effective drug development using green synthesized AgNPs in healthcare systems against AMR is established.


Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Plants, Medicinal , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Silver
17.
Bioanalysis ; 14(15): 1051-1065, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36148926

ABSTRACT

Background: Ribociclib (RIBO), approved in 2017 for HR-positive and HER-2-negative metastatic breast cancer treatment is reported to have the potential to induce hepatobiliary toxicity in patients. Oleanolic acid (OLA) has hepatoprotective potential that can be beneficial if coadministered with RIBO. Methodology & results: The primary scope of this study was to develop quantitative bioanalytical methods for RIBO and OLA. Two methods (for +ve electrospray ionization [ESI] and -ve ESI) were developed and validated according to USFDA bioanalytical guidelines. Discussion/conclusion: A single and simple sample preparation method was developed with >75% recovery. The accuracy and precision for RIBO and OLA were within acceptable limits over the calibration range of 5-500 ng/ml. This work reports, for the first time, the drug-drug interaction potential between RIBO and OLA.


Subject(s)
Oleanolic Acid , Aminopyridines , Chromatography, Liquid/methods , Humans , Purines , Reproducibility of Results , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods
18.
Indian J Thorac Cardiovasc Surg ; 38(4): 403-407, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35756557

ABSTRACT

Late presentation of aortopulmonary window (APW) beyond infancy is uncommon and many of these cases are inoperable due to development of progressive pulmonary hypertension and Eisenmenger syndrome. Outcome data in this cohort is thus sparse and the aim of this study was to analyze the outcomes in patients with APW operable beyond 1 year of age. Between September 2016 and March 2020, in a single center, 12 consecutive patients older than 1 year, undergoing surgery for APW, were included in the study. The median age and weight at presentation were 7.5 years (interquartile range (IQR) 4-9.5) and 15 kg (IQR 11.7-19.5). Ten (83.3%) patients had type 1 APW (proximal type) and 2 (16.6%) had a type 2 APW (distal type). Eight (66.6%) patients had associated lesions. Transaortic patch closure of APW was done in all cases. Seven (58.3%) patients were extubated within 3.5 h of admission in intensive care. There were no early deaths or during follow-up. The median follow-up duration was 20.5 months (IQR 7.5-24), and all patients were in New York Heart Association (NYHA) class I at last follow-up. Follow-up echocardiography did not reveal any significant residual shunts necessitating any additional procedure and a consistent decrease in pulmonary artery pressures. Surgery in patients with APW beyond 1 year of age is possible in selected patients. The early and intermediate surgical outcomes in patients who remain operable are excellent.

19.
Article in English | MEDLINE | ID: mdl-34735976

ABSTRACT

A systematic metabolite profiling approach has paramount importance in detecting, identifying, and characterizing drug metabolites. Till date, there is no report published on the comprehensive metabolic fate of flibanserin (FLB). In this study, the structure of entire potential metabolites of FLB has been elucidated by execution of in silico tool and high resolution mass spectrometry based metabolite profiling strategy employing data-dependent and data-independent approaches. In vitro metabolism profile was investigated after incubating FLB with liver microsomes (rat and human) and S9 fractions in presence of their respective co-factors. In vivo metabolites were identified from rat plasma, urine, feces, and brain tissue samples. An efficient extraction technique was developed that made it possible to identify the metabolites generated even in extremely low concentrations. Extraction was carried out by precipitating protein and thereafter solid-phase extraction to enrich their concentration in the sample before analysis. Fourteen new metabolites have been identified and characterized. Most of the metabolites of FLB were generated due to hydrolysis and oxidation followed by glucuronide, sulfate, and methyl conjugation. Additionally, a spiking study was employed to confirm the presence of N-oxide metabolite in human liver S9 fraction and rat urine samples. Moreover, we have established the probable biotransformation pathway of FLB and successfully analyzed the toxicity potential of the metabolites using Pro Tox-II software.


Subject(s)
Benzimidazoles/chemistry , Benzimidazoles/metabolism , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Animals , Benzimidazoles/isolation & purification , Biotransformation , Feces/chemistry , Humans , Male , Microsomes, Liver/chemistry , Microsomes, Liver/metabolism , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Solid Phase Extraction
20.
Ann Pediatr Cardiol ; 14(2): 244-246, 2021.
Article in English | MEDLINE | ID: mdl-34103872

ABSTRACT

We report a case of 8-year-old boy with unexplained desaturation and clubbing. Echocardiography showed anomalous drainage of right superior vena cava into left atrium. He did not have any neurological symptoms preoperatively. Some perioperative observations and subtle postoperative behavioral changes prompted us to investigate him further. He was found to have extensive cerebral arteriovenous malformations and hemiatrophy of brain.

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