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Nitrosamines crisis in pharmaceuticals Insights on toxicological implications, root causes and risk assessment: A systematic review

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Journal of Pharmaceutical Analysis 2024年第5期14卷 639-652页

作者： Hemanth P.R.Vikram Tegginamath pramod kumar Gunjan kumar Narasimha M.Beeraka Rajashree Deka Sheik Mohammed Suhail Sandeep Jat Namitha Bannimath Gayatiri Padmanabhan Ravandur S.Chandan pramod kumar Bannimath Gurupadayya Department of Pharmaceutical Chemistry JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Xenone Healthcare Pvt.Ltd. New Delhi110076India Department of Pharmaceutics JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of Human Anatomy I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow119991Russian Federation Department of Pharmacology Raghavendra Institute of Pharmaceutical Education and Research(RIPER)Ananthapuramu515721India Herman B.Wells Center for Pediatric Research Department of PediatricsIndiana University School of MedicineIndianapolisIN46202USA Animal Physiology and Biochemistry Laboratory Department of ZoologyGauhati UniversityGuwahati781014India Department of Pharmacology JSS College of Pharmacy MysuruJSS Academy of Higher Education and Research(JSSAHER)Mysuru570015India Department of Pharmaceutical Analysis National Institute of Pharmaceutical Education and Research(NIPER)-GuwahatiChangsari781101India Department of Pharmacology University of GalwayGalwayH91 TK33Ireland

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic *** systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for *** review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological ***,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk *** comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

关键词： Carcinogenicity Genotoxicity Mutagenicity Molecular toxicity Nitrosamine impurities Nitrosamine drug substance-related impurities

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Overlap in oncogenic and pro-inflammatory pathways associated with areca nut and nicotine exposure

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Cancer Pathogenesis and Therapy 2024年第3期2卷 187-194页

作者： Krati Garg Anuj kumar Vidisha Kizhakkethil pramod kumar Shalini Singh Department of Biochemical Engineering and Biotechnology Indian Institute of Technology(IIT)DelhiDelhi 110016India Division of Molecular Biology ICMR-National Institute of Cancer Prevention and Research(ICMR-NICPR)Indian Council of Medical ResearchNoidaUttar Pradesh 201301India Department of Biotechnology Vellore Institute of Technology(VIT)VelloreTamil Nadu 632024India ICMR-National Institute of Cancer Prevention&Research(ICMR-NICPR) Indian Council of Medical ResearchNoidaUttar Pradesh 201301India

Background:Betel nut/areca nut/Areca catechu is one of the most commonly used psychoactive substance,and is also a major preventable cause of *** other psychoactive substances,such as nicotine,the mechanisms underlying addiction to areca nuts and related oncogenesis remain *** reports suggest a possible overlap in the mechanisms of action of nicotine and areca nuts in the human ***,this study aimed to investigate the interactome of human proteins associated with areca nut exposure and the intricate similarities and differences in the effects of the two psychoactive substances on ***:A list of proteins associated with areca nut use was obtained from the available literature using terms from Medical Subject Headings(MeSH).Protein-protein interaction(PPI)networks and functional enrichment were *** results obtained for both psychoactive substances were ***:Given the limited number of common proteins(36/226,16%)in the two sets,a substantial overlap(612/1176 nodes,52%)was observed in the PPI networks,as well as in Gene *** nuts mainly affect signaling pathways through three hub proteins(alpha serine/threonine-protein kinase,tumor protein 53,and interleukin-6),which are common to both psychoactive substances,as well as two unique hub proteins(epidermal growth factor receptor and master regulator of cell cycle entry and proliferative metabolism).Areca nut-related proteins are associated with unique pathways,such as extracellular matrix organization,lipid storage,and metabolism,which are not found in nicotine-associated ***:Areca nuts affect regulatory mechanisms,leading to systemic toxicity and *** nuts also affect unique pathways that can be studied as potential markers of exposure,as well as targets for anticancer therapeutic agents.

关键词： Cancer Areca nut Nicotine Interactome Cell signaling

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Corrigendum to“Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review”[***.14(2024)100919]

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Journal of Pharmaceutical Analysis 2024年第6期14卷 934-936页

Original statement in the Section 2:*** search Our primary screening of 180 articles yielded the relevant data for this *** selection A total of 180 articles spanning from 1960 to the present day,including original research,reviews,case reports and studies reporting nitrosamine impurities above the no-observed-adverse-effect levels(NOAEL)established by regulatory agencies,were initially *** the primary screening,we considered factors such as relevance,publication date,access to the full article text,and content.

关键词： statement initially spanning

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Characteristic of Ionospheric foF2 and Solar Indices during the 23rd Solar Cycle over High Latitude Station, Syowa, Antarctica

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American Journal of Climate Change 2015年第5期4卷 408-416页

作者： Purushottam Bhawre Kamal Kishore Suresh kumar Dogra pramod kumar purohit Malik Abdul Waheed Prakash Khatarkar Roshni Atulkar Space Science Laboratory Department of Physics Barkatullah University Bhopal India Government Degree College Udhampur India National Institute of Technical Teachers’ Training & Research (NITTTR) Bhopal India

The behavior and dynamics of ionosphere are completely dependent on the solar activity. We have investigated the long term variability of ionospheric parameter foF2 with corresponding changes in the solar activity during the 23rd solar cycle. The variation of the critical frequency of ionospheric foF2 at Syowa Station Antarctica, (69°S, 39°E) is examined with four different solar activity indices characterizing the long term variability of solar activity wise Flare Index, relative sunspot number (Rz), solar flux F10.7 cm and CME occurrence index. We compared the dependency of foF2 and other solar activity indices on each other by using linear correlation investigation, and showed the qualitative similarity of the ionospheric foF2 with the solar indices. We notice that hysteresis of foF2 is lower for the growing branches of the solar cycle. The individual dissimilarity of critical frequency foF2 demonstrated the dependency on the solar cycle but this variation was different during the months, which depended on solar activity and polar ionospheric behavior. The peak to peak variation between monthly average of critical frequency foF2 and solar indices parameter is evidence for the absolute dependency for each other. The linear correlation between the solar indices and foF2 is very strong during the climbing and downward branches of the solar cycle. However the incline of their linear fits shows variations from index to index.

关键词： High Latitude foF2 Solar Cycle Solar Indices

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Viral hepatitis: A global burden needs future directions for the management

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World Journal of Gastroenterology 2022年第16期28卷 1718-1721页

作者： Henu kumar Verma Kiran Prasad pramod kumar Bhaskar Lvks Department of Immunopathology Institute of Lungs Biology and DiseaseComprehensive Pneumology CenterHelmholtz ZentrumMunich 80331BayrenGermany Department of Zoology Guru Ghasidas VishwavidyalayaBilaspur 495001ChhattisgarhIndia Department of Drug Delivery Institute of Lung Biology and DiseaseHelmholtz Research CenterMunich 80331BayrenGermany

Viral hepatitis is an acute or chronic liver disease due to the infection from Hepatitis A,B,C,D and E *** can cause severe liver damage such as cirrhosis,liver failure and liver *** avoid such fatal complications,hepatitis patients must be diagnosed,pathologized and treated as soon as ***,these hepatitis viruses infect through different routes,resulting in distinct disease pathologies,severity and even the need for specific treatment strategies to combat the infection.

关键词： Viral hepatitis Vaccination Chronic Acute Viral therapy

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Modelling reference evapotranspiration using gene expression programming and artificial neural network at Pantnagar,India

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Information Processing in Agriculture 2023年第4期10卷 547-563页

作者： Pangam Heramb pramod kumar Singh K.V.Ramana Rao A.Subeesh Division of Irrigation and Drainage Engineering ICAR-Central Institute of Agricultural EngineeringBhopal 462038India Department of Irrigation and Drainage Engineering G.B.Pant University of Agriculture and TechnologyPantnagar 263145India Division of Agricultural Mechanization ICAR-Central Institute of Agricultural EngineeringBhopal 462038India

Evapotranspiration is an essential component of the hydrological cycle that is of particular interest for water resource *** quantification is helpful in irrigation scheduling,water balance studies,water allocation,*** of reference evapotranspiration(ET0)using both gene expression programming(GEP)and artificial neural network(ANN)techniques was done using the daily meteorological data of the Pantnagar region,India,from 2010 to 2019.A total of 15 combinations of inputs were used in developing the ET0 *** model with the least number of inputs consisted of maximum and minimum air temperatures,whereas the model with the highest number of inputs consisted of maximum air temperature,minimum air temperature,mean relative humidity,number of sunshine hours,wind speed at 2mheight and extra-terrestrial radiation as inputs and with ET0 as the output for all the *** the GEP models were developed for a single functional set and pre-defined genetic operator values,while the best structure in each ANN model was found based on the performance during the testing *** was found that ANN models were superior to GEP models for the estimation *** was evident from the reduction in RMSE values ranging from 2%to 56%during training and testing phases in all the ANN models compared with GEP *** ANN models showed an increase of about 0.96%to 9.72%of R2 value compared to the respective GEP *** comparative study of these models with multiple linear regression(MLR)depicted that the ANN and GEP models were superior to MLR models.

关键词： Artificial Neural Networks Evolutionary algorithms Gene Expression Programming Machine Learning Regression Analysis Reference evapotranspiration models

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Theoretical investigation on mechanical,thermal,and ultrasonic properties of epitaxial nanostructured ZrN layers growth on MgO(001)substrate

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ChemPhysMater 2023年第3期2卷 253-258页

作者： Aadesh kumar Prajapati Sachin Rai Prashant Srivastav pramod kumar Yadawa Department of Physics Prof.Rajendra Singh(Rajju Bhaiya)Institute of Physical Sciences for Study and ResearchV.B.S.Purvanchal UniversityJaunpur 222003India

In the present study,we calculated the elastic,mechanical,and thermo-physical properties of Zirconium Nitride(ZrN)/Magnesium Oxide(MgO)(001)nanostructures in the temperature range of 50∼300 K using higher-order elastic *** two fundamental factors,nearest-neighbor distance and hardness parameter,in this tem-perature range,the second-and third-order elastic constants(SOECs and TOECs)are estimated using the Coulomb&Born-Mayer *** computed values of SOECs have been used to calculate Young’s modulus,thermal conductivity,Zener anisotropy,bulk modulus,thermal energy density,shear modulus,and Poisson’s ratio to as-sess the thermal and mechanical properties of the ZrN/MgO(001)nanostructured ***,SOECs are used to calculate the wave velocities for shear as well as longitudinal modes of propagation along crystalline orientations,,andin these temperature *** temperature-dependent Debye average velocity,hardness,melting temperature,and ultrasonic Grüneisen parameters(UGPs)were *** frac-ture/toughness(B/G)ratio in the current investigation was greater than 1.75,indicating that the ZrN/MgO(001)nanostructured layer was ductile in this temperature *** selected materials fully satisfied the Born me-chanical stability *** this ambient temperature,it has been computed how long thermal relaxation takes to complete and how ultrasonic waves are attenuated by thermo-elastic relaxation and phonon-phonon interaction *** results,in combination with other well-known physical properties,can be applied to the non-destructive testing of materials for various industrial applications such as microelectronic devices,optical coatings,batteries,and solar cells.

关键词： Nanostructured layers Elastic properties Thermal conductivity Mechanical properties Ultrasonic properties

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Effect of high shear homogenization on quality characteristics of bael fruit pulp

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Food Quality and Safety 2022年第1期6卷 81-92页

作者： Meenatai G.Kamble Anurag Singh pramod kumar Prabhakar Murlidhar Meghwal Sukh Veer Singh Ajay V.Chinchkar Department of Food Science and Technology National Institute of Food Technology Entrepreneurship and Management(NIFTEM)SonipatHaryana-131028India

Response surface methodology was used to investigate the influence of high shear homogenization speed(A:3000-12000 r/min)and processing time(B:30-120 min)on bael fruit pulp quality *** experimental results were best fitted in the suggested quadratic model to delineate and envision the responses in terms of color(values of L^(*),meaning brightness to blackness,1oo-0;a^(*),meaning green-a^(*)to red+a^(*);and b^(*),meaning blue-b^(*)to yellow+b),total soluble solids,ascorbic acid,viscosity,andβ-carotene content with the highest coefficients of determination(R2)ranging from 0.80 to ***(P<0.05)change in the L^(*)value,total soluble solids,ascorbic acid,andβ-carotene content was found with change in homogenization *** interaction effect of homogenization showed a significant difference in a^(*)value and total soluble solid content of the *** best homogenization conditions were determined via multiple response optimization as 10682 r/min speed and 43.18 min process *** quality parameters of the pulp at optimized conditions were observed as L^(*)15.35,a^(*)4.51,b^(*)10.25,ascorbic acid 18.64 mg/100 g,viscosity 5349 cP,andβ-carotene 4.14μg/100 *** addition,total phenolic content,flavonoid content,and antioxidant content of homogenized bael fruit pulp was found to significantly(P<0.05)increase from(83.76±1.24)to(119.21±1.35)mg gallic acid equivalent(GAE)/100 mL,(147.39±0.69)to(156.10±1.11)mg quercetin equivalent(QE)/100 mL,and(41.77%±0.60%)to(66.53%±0.41%),***,this strategy could be used in fruit processing industries to process highly fibrous fruits and nonuniform-textured fruit pulptoavoid sedimentation whileretaining functionality.

关键词： Aegle marmelos L. underutilized fruit viscosity bioactive compounds color values

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Unified Understanding of Cosmological Energy Fields: Exploring Gravitation, Repulsion, and More

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Natural Science 2023年第11期15卷 263-284页

作者： pramod kumar Agrawal Universal Theory Research Centre Jaipur India

First, we develop a unitary process that can explain all four physical activations: electromagnetic wave, electromagnetic force, repulsion, and attraction. Second, it is clarified that cosmological and physical entities relate to different levels of existence in the universe and, hence, cannot be considered under the same paradigm. We know that biological entities use physical substances as executants;analogously, physical entities use cosmological substances as executants. Therefore, we have introduced new terms for the cosmological substances used as executants in physical activities. Third, this study introduces the primary elements of the cosmological world, such as visibility, forcibility, fullness, and hollowness, and defines them according to their attributes. This study explains how different combinations and placements of primary elements create different cosmological fields. These fields are used in all physical activations. Finally, we explain the entity model and how all physical activations occur. This study concludes that all physical activations use primary elements and follow the same universal law. Therefore, this study addresses the untouched subject of the creation of repulsion and attraction (gravitation). Furthermore, it addresses several cosmic mysteries that are yet to be resolved.

关键词： Cause of Gravitation Cause of Repulsion Model of Entity Unified Theory Multi-Disciplinary Approach

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Evolution and Structure of Elementary Physical Particles

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Natural Science 2022年第8期14卷 328-342页

作者： pramod kumar Agrawal Universal Theory Research Centre Jawaharlal Nehru Marg Jaipur India

This paper is presented in two parts. The first part provides a glimpse of the long-awaited unified theory, which explains the parallel activation of different levels of the universe: intellectual (humans), psychological (animals), biological (vegetation), physical (matter), and cosmological (energies) levels, whereas in the conventional approach, the physical and cosmological levels are grouped into the same category. This paper explains the evolution and structure of elementary physical particles (EPPs) based on the evolution and structure of elementary biological particles (cells). The second part of the paper explains the structure and ingredients of the PPE, which are responsible for the creation of the following four fields, as suggested by the author: visibility, forcibility (magnetism), the fullness field, and the hollowness field. All these fields comprise different unknown cosmological substances. These cosmological fields are present in all physical entities and are responsible for all kinds of physical activations. Finally, the paper explains the evolution of electromagnetic waves, electromagnetic fields, gravitation, and repulsion (repulsive gravitation). The theory is consistent with all previously conducted experiments and systematically unfolds several mysteries, thereby demonstrating the validity of the proposed theory.

关键词： Dark Matter Dark Energy Evolution of Elementary Physical Particle Repulsive Gravity Space Fabric

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