Browsing by Author "Parul Sharma"

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5-hydroxytryptamine-evoked contractile activity of large gut in neonatal albino rats
(Scientific Scholar, 2023) Shuchita Singh; Maloy B. Mandal; Devarshi Dixit; Parul Sharma
Objectives: Serotonin, also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter. It is abundantly present in the gut of mammals. The extent to which it contributes to the contraction of the neonatal gut requires further investigation. This study aimed to assess the effect of 5-HT on the contractions of the large intestine in newborn albino rats. Materials and Methods: The colon and rectum samples were collected from neonatal and adult albino rats for analysis. Further, in an organ bath, isometric contractions of these isolated gut segments were recorded, in vitro, using a force transducer and a computerised chart recorder, with and without 5-HT in different groups. The 5-HT-induced contractions were also recorded in gut segments pre-treated with various antagonists. Results: 5-HT (0.01-10 M) caused a significantly (P < 0.05) greater contractile response (g/g wet tissue) in neonate rats as compared to adults. The response was greater in the rectum as compared to the colon in both neonates and adults. In neonate rats, ondansetron, a 5-HT3 antagonist, could not block the 5-HT-induced large gut contractions, while, in adult rats, it significantly blocked the 5-HT-evoked gut contractility. Methysergide, a 5-HT1/2/5-7 antagonist, blocked the response in both the adult and neonate rectum. Conclusion: The 5-HT-evoked response is mediated through 5-HT3 receptor subtypes in adults but not in neonate colon and rectum, indicating possible changes in the distribution of 5-HT receptors in the colon and rectum during development. Furthermore, atropine (a muscarinic cholinergic blocker) and hexamethonium (a ganglion blocker) could not affect the 5-HT-evoked responses in the neonate or adult rats' colons or rectum. The effect of 5-HT did not appear to involve cholinergic or enteric ganglionic elements. © 2023 Published by Scientific Scholar on behalf of Indian Journal of Physiology and Pharmacology.
A Deep Dive into PDE5 Inhibition: Innovative Discoveries via Virtual Screening
(Bentham Science Publishers, 2024) Abhijit Debnath; Hema Chaudhary; Parul Sharma; Rajesh Singh; Shikha Srivastava
Background: PDE5 inhibitors have had a surge in popularity over the last decade owing to their efficacy in the treatment of erectile dysfunction, coronary vasculopathy, and pulmonary arterial hypertension. These inhibitors exhibit competitive binding with phosphodiesterase type 5 and inhibit the hydrolysis of cyclic guanosine monophosphate, hence elevating the levels of cGMP in smooth muscle cells and prolonging the duration of an erection. However, due to production costs and side effects, further research is needed to discover new PDE5 inhibitors. Objectives: The study aimed to identify potent PDE5 inhibitors by employing the extensive application of computer-aided drug design. Methods: Three different databases, named Million Molecules Database, Natural Product Database, and NCI Database, have been screened, which has been followed by filtering based on various drug-likeness rules, docking, ADME, toxicity, consensus molecular docking, and 100 ns molecular dynamics simulation. Results: Three compounds (ZINC05351336, ZINC12030898, and ZINC17949426) have exhibited stable-binding characteristics at the active site of PDE5, demonstrating a robust binding affinity. These molecules have been found to possess drug-like capabilities, effective ADME features, low toxicity, and high stability. Conclusion: The study has delved into the realm of PDE5 inhibitors, which have been found to be effective in treating erectile dysfunction, but high production costs and side effects necessitate new ones. Through computer-aided drug design and screening, three compounds have been identified with promising binding characteristics, drug-appropriate properties, effective ADME profiles, mini-mal toxicity, and stability, making them potential candidates for future PDE5 inhibitors. © 2024 Bentham Science Publishers.
Advancements of Glucose Monitoring Biosensor: Current State, Generations of Technological Progress and Innovation Dynamics
(Bentham Science Publishers, 2025) Arpita Dua; Abhijit Debnath; Kunal Kumar; Rupa Mazumder; Avijit Mazumder; Rajesh Kumar Singh; Saloni Mangal; Jahanvi Sanchitra; Fahad Khan; Soumya Tripathi; Sukriti Vishwas; Hema Chaudhary; Parul Sharma; Shikha Srivastava
Glucose monitoring is essential for managing diabetes, and continuous glucose monitoring biosensors can offer real-time monitoring with little invasiveness. However, challenges remain in improving sensor accuracy, selectivity, and overall performance. This article aims to review current trends and recent advancements in glucose-monitoring biosensors while evaluating their benefits and limitations for diabetes monitoring. An analysis of current literature on transdermal glucose sensors was conducted, focusing on detection techniques, novel nanomaterials, and integrated sensor systems. Recent research has led to advancements in electrochemical, optical, electromagnetic, and sonochemical sensors for transdermal glucose detection. The use of novel nanomaterials and integrated sensor designs has improved sensitivity, selectivity, and accuracy. However, issues like calibration requirements, motion artifacts, and skin irritation persist. Transdermal glucose sensors show promise for non-invasive, convenient diabetes monitoring but require further enhancements to address limitations in accuracy, reliability, and biocompatibility. Continued research and innovation focusing on sensor materials, designs, and surface chemistry is needed to optimize biosensor performance and utility. The study offers a comprehensive analysis of the present status of technological advancement and highlights areas that need more research. © 2025 Bentham Science Publishers.
Assessment of awareness regarding health hazards of plastic chemicals and their warning label among a sample population of Varanasi City: A cross-sectional study
(Wolters Kluwer Medknow Publications, 2021) Parul Sharma; Priyanka Bhagat; M. Mandal; T. Singh
Background: Plastic containers are widely used to store and serve edibles. In the production of some types of plastic, chemicals such as bisphenol A (BPA) and bisphenol S (BPS) are used. These chemicals leach from the plastic containers into the edibles, get access into the biological systems, and cause a toxic impact on health. Aim: This cross-sectional survey was planned to assess the usage of food contact plastic and awareness regarding the health hazards of plastic chemicals and warning labels on plastic items among a sample population of Varanasi city. Materials and Methods: Data were collected by interviewing the 556 adult participants, using a prevalidated structured questionnaire. Chi-square test was used to test the association and P < 0.05 was considered as significant. Results: Most of the participants were found to be following routine practices during cooking and storage of edibles which may expose them to BPA and BPS through the gut. Although many participants were aware that plastic may contain some type of chemicals which may enter the human body and harm human health in some way, they lacked precise knowledge regarding warning label like 'BPA free plastic' 'plastic containing BPA' and 'food grade plastic.' Furthermore, none of the participants could recognize the 'resin identification codes' correctly. Conclusion: Most of the participants had only elementary awareness of health risk of plastic usage. A significant number of participants lacked crucial information that can help them to make healthy choices as a consumer and use safe alternatives of plastic. © 2021 Journal of Pharmacy and Bioallied Sciences. All rights reserved.
Capsaicin fails to produce changes in contractile tension in large gut of neonate rats
(Scientific Scholar, 2023) Shuchita Singh; Parul Sharma; Devarshi Dixit; Maloy B. Mandal
Objectives: Capsaicin, the most pungent constituent of chilli pepper (Capsicum annuum L.), is known to alter the physiological activity of the gut. Capsaicin mediates its action through a transient receptor potential vanilloid type 1 (TRPV1) channel. The action of capsaicin on gut smooth muscle varies from segment to segment in different species. The earlier studies were carried out in adult animals only, and its status in the neonate gut, which is in a development stage, is not known. Objective: Therefore, the present study was done to assess the effect of capsaicin on the large gut of neonates. Materials and Methods: In an organ bath preparation, isometric contractions were recorded from segments of dissected rat colon and rectum. The gut segments were exposed to cumulative concentrations of capsaicin (0.01 nM–3 µM) and a capsaicin-induced contractile response was observed. TRPV1 receptor antagonist capsazepine (1 µM) and a nitric oxide synthase inhibitor, L-NAME (100 µM), were used to assess their blocking effect on capsaicin-induced contractile response. Results: Capsaicin raised contractile tension in the colon and rectum of adult rats but not in neonate rats. In adult rats, capsazepine pre-treatment (1 µM) failed to block the capsaicin-induced response in the colon, but in the lower concentrations, it increased contractile tension in the rectum. Pre-application of L-NAME (100 µM) potentiated capsaicin-induced response in the adult rectum and neonate’s colon but had no effect in the neonate rectum and adult colon. Capsaicin with a low concentration (0.01 nM–0.01 µM) increased contractile frequency in both the colon and rectum of adult rats. However, the effect of capsaicin on frequency was abolished at higher concentrations (0.01 µM–3 µM). A capsaicin-evoked change in contractile frequency in adult rats was blocked by capsazepine and L-NAME. At lower concentrations (0.01 nM–0.01 µM), capsaicin did not show any change in frequency in the neonatal colon, while a decrease in contractile frequency was observed with the higher concentrations (0.1 µM–3 µM) of capsaicin. In neonates, capsazepine pre-treatment produced changes in frequency for both the colon and rectum. However, pre-application of L-NAME decreased frequency in the neonate rectum but not in the colon. Conclusion: Capsaicin-induced changes in contractile activity may or may not involve TRPV1 or the Nitric Oxide (NO) pathway, depending on the part of the large gut and developmental maturity. © 2023 Association of Physiologists and Pharmacologists of India. All rights reserved.
Characterization of oleic acid-induced acute respiratory distress syndrome model in rat
(National Institute of Science Communication, 2014) Aparna Akella; Parul Sharma; Ratna Pandey; Shripad B. Deshpande
Animal studies using oleic acid (OA) model to produce acute respiratory distress syndrome (ARDS) have been inconsistent. Therefore, the present study was undertaken to establish an acute model of ARDS in rats using OA and to characterize its effect on cardio-respiratory parameters and lethality. The trachea, jugular vein and femoral artery of anesthetized adult rats were cannulated. A dose of OA (30-90 μL; iv) was injected in each animal and changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were recorded. Minute ventilation and PaO2/FiO2 (P/F) ratio were also determined. At the end, lungs were excised for determination of pulmonary water content and histological examination. At all doses of OA, there was immediate decrease followed by increase in RF, however at 75 and 90 μL of OA, RF decreased abruptly and the animals died by 63 ± 8.2 min and 19 ± 6.3 min; respectively. In all the groups, HR and MAP changes followed the respiratory changes. The minute ventilation increased in a dose-dependent manner while the values of P/F ratio decreased correspondingly. Pulmonary edema was induced at all doses. Histological examination of the lung showed alveolar damage, microvascular congestion, microvascular injury, infiltration of inflammatory cells, pulmonary edema and necrosis in a dose-dependent manner. With these results, OA can be used to induce different grades of ARDS in rats and OA doses of 50, 60 and 75 μL resemble mild, moderate and severe forms of ARDS respectively. Hence, OA model serves as a useful tool to study the pathophysiology of ARDS.
Effect of misoprostol treatment on oleic acid-induced ARDS in rats
(Research Journal of Pharmaceutical, Biological and Chemical Sciences, 2016) Parul Sharma; Ratna Pandey; Shripad B. Deshpande
Adult respiratory distress syndrome (ARDS) is a clinical condition associated with high mortality. Prostaglandins are involved in the pathophysiology of ARDS but the results of earlier studies are not conclusive. Therefore, this study was aimed to determine the role of misoprostol (Prostaglandin E1 agonist) in oleic acid (OA)-induced ARDS in rats. Anaesthetized animals were divided in to three groups. In group I (control group), rats were treated with saline. In group II (OA only group), OA was injected to induce ARDS. In group III (OA + M group), misoprostol was administered after OA injection and the dose was repeated after every 20 min. In all groups respiratory frequency (RF), pulmonary water content, mean arterial pressure (MAP), heart rate (HR), P/F ratio, and survival time were determined. OA produced ARDS as indicated by ventilatory changes, decreased P/F ratio, pulmonary edema, and death within 90 min. Severe changes in heart rate and mean arterial pressure were also observed. Misoprostol post-treatment prevented pulmonary edema and initial tachypnea and also improved P/F ratio in OA-induced ARDS but overall survival time was not altered. The MAP changes were reversed initially but not the heart rate changes. The results indicate that misoprostol post treatment ameliorates the OA-induced ARDS in the initial phase but can not prevent the lethality. © 2010 RJPBCS.
Effects of endometriosis, fibroids, and other pathological conditions on muscular contractions in the human fallopian tube
(Oxford University Press, 2025) Richa S. Singh; Sakshi Agarwal; Parul Sharma; Sanjeev Kumar Mahto
Background: Ectopic pregnancy and tubal endometriosis directly affect the fallopian tube structure and function, while ovarian cysts and uterine fibroids may indirectly influence tubal physiology. These conditions are associated with infertility, but their impact on fallopian tube mechanical contractions remains unclear. This study aimed to assess the effects of these pathologies on fallopian tube contractility. Method: Ampulla samples were obtained from women undergoing salpingectomy for benign causes. Based on the menstrual phases, samples were divided into two groups: proliferative (normal proliferative, tubal endometriosis, ovarian cysts, and uterine fibroids) and secretory (normal secretory and ectopic pregnancy). Normal proliferative considered control for the proliferative group, while normal secretory for the ectopic pregnancy. Contractile parameters, maximum contractile force, basal tone, frequency, and amplitude were measured using an isometric force transducer, while in another set of experiments; the oxytocin doses (1 and 10 μM) response was assessed. Smooth muscle organization and structural changes were analyzed through hematoxylin and eosin staining. Result: Compared to the normal proliferative, the tubal endometriosis and ovarian cysts groups showed significantly lower maximum contractile force, basal tone, frequency, and amplitude, along with damaged smooth muscle layers, while uterine fibroids showed decreased frequency and amplitude, with organized muscle structure. Ectopic pregnancy showed higher maximum contractile force and basal tone than normal secretory, with increased frequency and amplitude and disorganized smooth muscle. Oxytocin increased contractility at 1 μM and reduced it at 10 μM in most groups. Conclusion: This study demonstrated that fallopian tube contractions and tissue structure were differentially affected across groups, with increased contractility observed in the ectopic pregnancy group and reduced contractility in the uterine fibroids, ovarian cysts, and tubal endometriosis groups. © The Author(s) 2025. Published by Oxford University Press on behalf of the Society for the Study of Reproduction. All rights reserved.
Indomethacin exacerbates oleic acid-induced acute respiratory distress syndrome in adult rats
(Association of Physiologists and Pharmacologists of India, 2016) Parul Sharma; Ratna Pandey; Shripad B. Deshpande
Acute respiratory distress syndrome (ARDS) is an acute fulminant condition associated with acute lung injury and inflammation leading to hypoxemia, pulmonary edema and respiratory failure. Even though prostaglandins are inflammatory mediators, the role of prostaglandins in ARDS is still not clear. Therefore, we examined the involvement of prostaglandin in experimentally induced ARDS by using prostaglandin synthesis inhibitor, indomethacin. Experiments were conducted on anesthetized adult rats (total n=15). Cannulation of trachea, jugular vein and carotid artery was done in these rats. Recording of respiratory excursions (for respiratory frequency; RF), ECG (for heart rate; HR) and blood pressure, before and after lethal dose of oleic acid (75 μL i.v.) was done for 120 min or till death of the animals. Arterial blood sample was collected 15 min after oleic acid injection to determine PaO2/FiO2 ratio. Lungs were excised at the end of experiment for estimation of pulmonary water content. Administration of oleic acid produced progressive increase in the RF up to 45 min followed by decrease. Subsequently, the respiration stopped and all the animals died by 75 min (mean survival time = 64±8.2 min). HR and mean arterial pressure (MAP) exhibited an immediate decrease followed by an increase up to 45 min. Thereafter, the HR and MAP progressively decreased. PaO2/FiO2 ratio in this group was 182±2.6 mm Hg and pulmonary water content was significantly greater than saline control group. However in indomethacin pretreated rats, injection of oleic acid produced instantaneous decrease in RF and all the animals died within 10 min (mean survival time = 6.6±1.07 min). HR and MAP followed the same pattern as seen with RF. Pulmonary water content in indomethacin pretreated animals was also significantly greater than control group. These observations indicate that indomethacin exacerbates the OA-induced ARDS. Thus, prostaglandins play an important role in the pathophysiology of OA-induced ARDS. © 2016, Association of Physiologists and Pharmacologists of India. All Rights reseved.
miRNA-Targeted Vaccines: A Promising Approach for Viral Attenuation and Immunogenicity Enhancement
(Bentham Science Publishers, 2025) Abhijit Debnath; Rupa Mazumder; Avijit Mazumder; Soumya Tripathi; Arpita Dua; Rajesh Kumar Singh; Saloni Mangal; Jahanvi Sanchitra; Pratibha Pandey; Biplab Pal; Hema Chaudhary; Parul Sharma; Shikha Srivastava
MicroRNAs (miRNAs) have emerged as a significant tool in the realm of vaccinology, offering novel approaches to vaccine development. This study investigates the potential of miRNAs in the development of advanced vaccines, with an emphasis on how they regulate immune response and control viral replication. We go over the molecular features of miRNAs, such as their capacity to direct post-transcriptional regulation toward mRNAs, hence regulating the expression of genes in diverse tissues and cells. This property is harnessed to develop live attenuated vaccines that are tissue-specific, enhancing safety and immunogenicity. The review highlights recent advancements in using miRNA-targeted vaccines against viruses like influenza, poliovirus, and tick-borne encephalitis virus, demonstrating their attenuated replication in specific tissues while retaining immunogenicity. We also explored the function of miRNAs in the biology of cancer, highlighting their potential to develop cancer vaccines through targeting miRNAs that are overexpressed in tumor cells. The difficulties in developing miRNA vaccines are also covered in this work, including delivery, stability, off-target effects, and the requirement for individualized cancer treatment plans. We wrap off by discussing the potential of miRNA vaccines and highlighting how they will influence the development of vaccination techniques for cancer and infectious diseases in the future. © 2025 Bentham Science Publishers.
Oviduct contractility in non-pregnant rats: changes in estrous cycle and effects of estrogen and progesterone antagonists
(BioScientifica Ltd., 2025) Richa S. Singh; Parul Sharma; Shristi Modanwal; Himanshu Ranjan; Amaresh Kumar Singh; Sakshi Agarwal; Sanjeev Kumar Mahto
This study aimed to systematically characterize oviduct contractility across the estrous cycle and to examine the regulatory roles of estradiol and progesterone using receptor antagonists and molecular docking to explore both receptor-mediated and ion channel pathways. Female Wistar rats (n = 48) were used for this purpose. Oviducts were collected during proestrus, estrus, metestrus, and diestrus, and spontaneous contractions were recorded using an isometric force transducer. Serum levels of estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and prolactin were measured through enzyme-linked immunosorbent assay (ELISA). To understand hormonal regulation, tamoxifen (10 mg/kg) was administered during proestrus, and mifepristone (5 mg/kg) was administered during metestrus. Immunofluorescence (IF) study was performed to evaluate expression of the estrogen, progesterone, and glucocorticoid receptors (ER, PR, and GR). Molecular docking analysis assessed interactions of the antagonists with estrogen and progesterone receptors and ion channels. Oviduct contractility was observed noticeably highest during proestrus (high estradiol) and lowest in metestrus and diestrus phases (high progesterone). Tamoxifen significantly reduced contraction parameters (P < 0.001) and estradiol levels, while mifepristone notably increased contraction force (P < 0.01), elevated estradiol levels (P < 0.001), and decreased the proportion of progesterone hormone. The IF study indicated suppression of ER, PR, and GR expression following treatment with mifepristone. Docking analysis revealed that tamoxifen interacted with potassium channels and ERβ, while mifepristone showed high affinity for PR, GR, and calcium channels. These findings highlight that oviduct contractility is dynamically regulated across the estrous cycle through both receptor-mediated and potential non-receptor and non-genomic pathways involving ion channels. © 2025 the author(s)
Plastic toxin Bisphenol-A depresses the contractile activity of rat ileum and colon in vitro
(Association of Physiologists and Pharmacologists of India, 2018) Kumari Nirja; Parul Sharma; Anil Kumar Tiwari; M.B. Mandal
Bisphenol A (BPA), a plastic toxin, is required in the production of various plastic items including water bottles, baby feeding bottles and other food and beverage containers. Since, the primary source of human exposure to BPA is the leachate from food and beverage containers, gastro intestinal tissues are particularly susceptible to BPA-induced changes. Therefore, the present study was undertaken to explore the possible effects of BPA on contractility in adult rat ileum and colon. In an organ bath preparation, isometric contractions were recorded from segments of dissected out colon and ileum, with the help of force transducer and digitized data acquisition system. The results indicated that BPA (1-100 μM) significantly (p<0.05) depresses contractile tension and frequency of ileum and colon in a dose dependent manner. Further, the exploration of possible mechanisms for BPA-induced decline in contractile responses revealed that the decrease in contractility was independent of estrogen receptors, nitric oxide and cholinergic system. © 2018, Association of Physiologists and Pharmacologists of India. All rights reserved.
Protective role of prostaglandin E1 analog in indomethacin-induced deterioration in acute respiratory distress syndrome in rats
(Mr Bhawani Singh, 2017) Parul Sharma; Ratna Pandey; Shripad B. Deshpande
Background: Acute respiratory distress syndrome (ARDS) is a severe inflammatory condition. Our earlier studies have characterized oleic acid (OA)-induced rat model of ARDS which was exacerbated by indomethacin (prostaglandin [PG] synthesis inhibitor). Aim and Objectives: The role of PGs in ARDS is ill defined as the results of earlier studies are conflicting. This study was undertaken to determine the effect of PGE1 analog (misoprostol) in indomethacin-induced exacerbation of ARDS in rats. Materials and Methods: The rats were anesthetized with urethane. Tracheal and jugular vein cannulation was done to keep the respiratory tract patent and deliver drugs, respectively. Respiratory excursions were recorded with the help of force displacement transducer. Cannulated carotid artery was connected to pressure transducer for recording of blood pressure. Electrocardiographic potentials were recorded by needle electrodes. Animals were divided into four groups. In Group I, OA (75 µl) was used to induce ARDS in rats. In Group II, OA was injected in indomethacin-pretreated rats. In Group III (control group), animals were treated with ethanol. In Group IV, OA was administered after indomethacin + misoprostol pretreatment. Misoprostol treatment was repeated after OA injection at 20 min interval. Cardiorespiratory parameters (respiratory frequency, heart rate, mean arterial pressure, and pulmonary water content) were determined, and histological examination of the lung was done in all groups. Results: Indomethacin pretreatment drastically advanced the OA-induced ARDS. Misoprostol protected against the deterioration as indicated by improvement in all the parameters and increase in survival time. Conclusion: Results of this study indicate that PGs have protective role in ARDS. © 2017 Ratna Pandey et al.