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Rifabutin reduces systemic exposure of an antimalarial drug 97/78 upon co-administration in rats:an in-vivo & in-vitro analysis

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Asian Pacific Journal of Tropical Medicine 2015年第8期8卷 620-625页

作者： Yeshwant Singh mahendra kumar Hidau Shio kumar Singh Pharmacokinetics & Metabolism Division CSIR-Central Drug Research Institute Academy of Scientific and Innovative Research

Objective: To determine the potential drug-drug interactions between anti-malarial candidate 97/78 and anti-tubercular drug rifabutin in-vivo in rats followed by in-vitro investigation of the underlying mechanisms of drug interaction. Methods: Single oral dose study was conducted in male and female rats at 40 mg/kg and 70 mg/kg for 97/78 and rifabutin respectively. Results: It was reported that rifabutin co-administration altered pharmacokinetics of 97/63(active metabolite of 97/78). A significant decrease was reported in the systemic exposure of 97/63 by a factor of 3-4. The AUC0-last values were(4.03 ± 0.60) and(5.44 ± 1.15) μg·h·m L-1 upon 97/78 administration alone, while the values were decreased to(1.13 ± 0.10) and(1.23 ± 1.13) μg·h·m L-1 upon rifabutin co-administration in male and female rats respectively. Statistically significant differences were also reported in Cmax and Tmax values upon rifabutin co-administration. In-vitro drug metabolism study in rat liver microsomes has shown that the metabolism of 97/63 was increased by 10%-12% upon rifabutin co-incubation. The extent of plasma protein binding of 97/63 was found to be decreased from 54%-55% to 6%-8% upon rifabutin addition. Conclusions: It was concluded that rifabutin co-administration altered PK parameters of 97/63 in SD rats. However, no intersex influences were reported in the interaction pattern. The results obtained in the in-vivo study were well correlated with the invitro findings and can further be applied to explore other aspects of potential drug interactions between these two drugs.

关键词： Accumulation Relative bioavailability Sex effect Pharmacokinetics

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In-depth investigation on physicochemical and thermal properties of magnesium(Ⅱ) gluconate using spectroscopic and thermoanalytical techniques

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Journal of Pharmaceutical Analysis 2017年第5期7卷 332-337页

作者： mahendra kumar Trivedi Neena Dixit Parthasarathi Panda Kalyan kumar Sethi Snehasis Jana Trivedi Global Inc. National Institute of Technology Trivedi Science Research Laboratory Pvt.Ltd.

Magnesium gluconate is a classical organometallic pharmaceutical compound used for the prevention and treatment of hypomagnesemia as a source of magnesium ion. The present research described the in-depth study on solid state properties viz. physicochemical and thermal properties of magnesium gluconate using sophisticated analytical techniques like Powder X-ray diffraction(PXRD), particle size analysis(PSA),Fourier transform infrared(FT-IR) spectrometry, ultraviolet–visible(UV–Vis) spectroscopy, thermogravimetric analysis(TGA)/differential thermogravimetric analysis(DTG), and differential scanning calorimetry(DSC).Magnesium gluconate was found to be crystalline in nature along with the crystallite size ranging from 14.10 to47.35 nm. The particle size distribution was at d(0.1)=6.552 μm, d(0.5)=38.299 μm, d(0.9)=173.712 μm and D(4,3)=67.122 μm along with the specific surface area of 0.372 m^2/g. The wavelength for the maximum absorbance was at 198.0 nm. Magnesium gluconate exhibited 88.51% weight loss with three stages of thermal degradation process up to 895.18 °C from room temperature. The TGA/DTG thermograms of the analyte indicated that magnesium gluconate was thermally stable up to around 165 °C. Consequently, the melting temperature of magnesium gluconate was found to be 169.90 °C along with the enthalpy of fusion of 308.7 J/***, the authors conclude that the achieved results from this study are very useful in pharmaceutical and nutraceutical industries for the identification, characterization and qualitative analysis of magnesium gluconate for preformulation studies and also for developing magnesium gluconate based novel formulation.

关键词： Magnesium gluconate Solid state properties Particle size analysis Thermal analysis Spectroscopic analysis

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Carbon nanotubes:A review on risks assessment,mechanism of toxicity and future directives to prevent health implication

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BIOCELL 2021年第2期45卷 267-279页

作者： PIYOOSH kumar BABELE mahendra kumar VERMA RAVI KANT BHATIA College of Agriculture Rani Laxmi Bai Central Agriculture UniversityJhansi284003India Department of Biological Sciences Indian Institute of Science Education and Research Bhopal(IISERB)Bhopal462066India Department of Biotechnology Himachal Pradesh UniversityShimla171005India

Carbon nanotubes(CNTs)have tremendous applications in almost every walk of life;however,their harmful impacts on humans and the environment are not well *** have been used in various applications ranging from medical science to different engineering branches,to ease human ***,the toxicological profile of CNTs under laboratory conditions cannot be assessed primarily in medical science due to the inconsistent availability of cytotoxic study *** toxicity has been affected by many physicochemical properties(e.g.,size,type of functionalization),concentration,the extent of exposure,mode of exposure,and even the solvents/medium used to dissolve/disperse CNTs for their *** inconsistencies arise due to the variation in synthesis methods as well as the mode of their human *** their unlimited use in various fields,most of CNT toxicity aspects and mechanisms remain ***,in-depth knowledge of CNTs toxicity is scarce,and the available literature shows dissimilarities in experimental data and exposure *** understand the toxicological issues,it is the need of the hour to provide insight into the published data,post-exposure studies,and various factors that may damage the cells due to CNTs *** review article analyses the hazardous potential through toxicological implications and summarizes the detailed mechanism(s)of CNTs studied on the different model organisms,including human cell *** this review article,we hypothesized that thorough knowledge of various aspects,as mentioned above,helps us design and develop possible strategies to reduce the toxicity of nanomaterial to make them safer and secure for humanity’s betterment.

关键词： Nanotechnology CNTs Nanotoxicity Toxicity mechanism Drug delivery

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Solid and liquid state characterization of tetrahydrocurcumin using XRPD, FT-IR, DSC, TGA, LC-MS, GC-MS, and NMR and its biological activities

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Journal of Pharmaceutical Analysis 2020年第4期10卷 334-345页

作者： mahendra kumar Trivedi Parthasarathi Panda Kalyan kumar Sethi Mayank Gangwar Sambhu Charan Mondal Snehasis Jana Trivedi Global Inc. Henderson89052NevadaUSA Trivedi Science Research Laboratory Pvt.Ltd. Thane(W)-400604MaharashtraIndia

Tetrahydrocurcumin(THC)is one of the major metabolites of curcumin(CUR),an ancient bioactive natural polyphenolic *** research article describes both the solid and liquid state characterization of THC using advanced spectroscopic and thermo-analytical ***-inflammatory,anti-oxidant,and neuroprotective activities of THC were investigated using in vitro cell *** chromatography-mass spectrometry analysis revealed that our sample comprised 95.15%THC,0.51%tetrahydrodemethoxycurcumin(THDC),3.40%hexahydrocurcumin,and 0.94%*** chromatography-mass spectrometry analysis indicated the presence of 96.68%THC and 3.32%*** in solution existed as keto-enol tautomers in three different forms at different retention time,but the enol form was found to be dominant,which was also supported by nuclear magnetic resonance *** was thermally stable up to 335.55*** exhibited more suppression of cytokines(TNF-a,IL-1b,and MIP-1a)than CUR in a concentration-dependent manner in mouse splenocytes,while NK-cell and phagocytosis activity was increased in *** showed a significant reduction of free radicals(LPO)along with improved antioxidant enzymes(SOD and catalase)and increased free radical scavenging activity against ABTSt radicals in HepG2 *** displayed higher protection capability than CUR from oxidative stress and neuronal damage by improving cell viability against H2O2 induced HepG2 cells and MPPt induced SH-SY5Y cells,respectively,in a concentration-dependent ***,a variation of the biological activities of THC might rely on its keto-enol form and the presence of other THC analogs as *** present study could be advantageous for further research on THC for better understanding its physicochemical properties and biological variation.

关键词： Tetrahydrocurcumin Liquid chromatography-mass spectrometry Spectroscopic and thermal analysis Keto-enol tautomer Anti-inflammatory Antioxidant

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Management of proximal tibial stress fracture associated with advanced knee osteoarthritis:A systematic review

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Chinese Journal of Traumatology 2024年第3期27卷 147-152页

作者： Mukesh kumar Saini mahendra Singh Devendra Singh Prem Manohar Seervi Pera Jayavardhan Reddy Neelam Ramana Reddy Department of Orthopaedics Dr SN Medical CollegeJodhpur342011India Department of Orthopaedics Star HospitalsB Block Banjara HillsHyderabad500034India

Purpose:Tibial stress fracture associated with knee osteoarthritis is an unusual and difficult clinical *** is no clear existing treatment guideline for this uncommon clinical *** aim of this study is to review the impact of various treatment options for patients with advanced knee osteoarthritis associated with proximal tibial stress ***:The study was performed using the databases of PubMed and *** index for non-randomized studies score was used to evaluate the included studies’*** concluded data included the treatment approach,reported outcome measure,and time to fracture *** literature search was started in December 2021 and accomplished in January 2022.A narrative description of the different methods and comparison of their results were ***:Out of total assessed 69 studies,9 studies were included in our *** commonest treatment approach used was total knee arthroplasty by long tibial stem *** mean preoperative knee society score and knee functional score were 30.62 and 23.17,*** mean postoperative knee society knee score was 86.87,while the functional score was *** average reported time to achieve fracture union was 4 months(a range of 2.07-5.50 months).Conclusion:The optimal clinical outcome for treating either acute or mobile tibial stress fracture in patients with advanced knee osteoarthritis can be achieved with long stem total knee ***,due to heterogeneity of data,comparison of different treatment options for chronic proximal tibial stress fracture mal-union/non-union coexisting with knee osteoarthritic and such inferences need to be judged cautiously.

关键词： Tibial stress fracture Knee osteoarthritis Total knee arthroplasty

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Improved dielectric and electro-optical parameters of nematic liquid crystal doped with magnetic nanoparticles

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Chinese Physics B 2019年第3期28卷 223-229页

作者： Geeta Yadav Govind Pathak Kaushlendra Agrahari mahendra kumar Mohd Sajid Khan V S Chandel Rajiv Manohar Liquid Crystal Research Laboratory Department of PhysicsUniversity of LucknowLucknow 226007India

This study investigates the effect of magnetic nanoparticles(NPs) on the weakly polar nematic liquid crystal(NLC).Different parameters of dielectric data were measured for both the homeotropic and planar aligned samples as a function of frequency and temperature and the substantial changes have been noticed for the doped systems. Dielectric permittivity has been increased after the dispersion of magnetic NPs in the pure NLC. Dielectric anisotropy has also been influenced by incorporating the magnetic NPs with the NLC molecules. These results were attributed to the dipole–dipole interaction between the magnetic nanoparticles and nematic liquid crystal molecules. Electro-optical study indicated the faster rise time and fall time of the doped systems as compare to pure NLC. Threshold voltage has been calculated and found to be decreased for the doped systems. Moreover, we have also calculated the rotational viscosity and the splay elastic constant for pure and the doped systems. Both the rotational viscosity and splay elastic constant of the doped systems are found to be considerably lower than those of pure NLC. Change in these properties has been explained on the basis of molecular disturbances created by the interaction between the magnetic nanoparticle and LC director. This study reveals that the inclusion of magnetic NPs in weakly polar NLC can be useful to enhance the basic properties of the weakly polar NLC and make it a promising material for many display applications.

关键词： magnetic nanoparticles dielectric permittivity response time rotational viscosity

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Comment on: Observation of peripheral refraction in myopic anisometropia in young adults

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1385-1386页

作者： Suraj kumar Chaurasiya mahendra Singh Pradeep Agarwal Yu-Qin Du Yue-Hua Zhou Ming-Wei Ding Ming-Xu Zhang Yu-Juan Guo Shan-Shan Ge Department of Optometry and Vision Science CL Gupta Eye InstituteRam Ganga Vihar Phase II(Extn.)MoradabadUttar Pradesh 244001India Department of Paediatric and Neuro Ophthalmology CL Gupta Eye InstituteRam Ganga Vihar Phase II(Extn.)MoradabadUttar Pradesh 244001India Eye School of Chengdu University of TCM Ineye Hospital of Chengdu University of TCMChengdu 610036Sichuan ProvinceChina Beijing Ming Vision and Ophthalmology Beijing 100010China

Dear Editor,We read with great interest the recently published article titled“Observation of peripheral refraction in myopic anisometropia in young adults”by Du et al[1].The study conducted at the InEye Hospital of Chengdu University of TCM provides valuable insights into the relationship between anisometropia and peripheral refraction in myopic young *** commend the authors for their thorough investigation and adherence to ethical *** the study contributes significantly to our understanding of myopic anisometropia,we would like to draw attention to some limitations that merit consideration for a comprehensive interpretation of the findings.

关键词： Observation young insight

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ER<i>β</i>interacting protein ERAP 140 shows age dependent alteration in its interaction and expression in male mouse brain

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World Journal of Neuroscience 2013年第1期3卷 1-9页

作者： Vijay Paramanik mahendra kumar Thakur Biochemistry and Molecular Biology Laboratory Centre of Advanced Study Department of Zoology Banaras Hindu University Varanasi India

Estrogen mediates multiple functions in the brain through the interaction of estrogen receptor (ER)α and ERβ with a host of nuclear proteins that regulate specific gene transcription. We have identified ERAP 140, AIB 1, Trk A, Src, pCREB and CREB as ERβ interacting proteins in the mouse brain. Earlier we showed that the interaction of ERβ with ERAP 140 decreased whereas its expression increased with aging in the brain of female mice. Here we report that the pattern of interaction and expression is different in male mice as compared to females. The interaction of ERAP 140 with ERβ decreased in adult male mouse brain as compared to young and remained almost similar in old whereas its expression was higher in adult than young and old, which were almost similar. Further in silico secondary structure analysis by self-optimized prediction method alignment (SOPMA) and PSIPRED revealed that ERβ interacting proteins were rich in alpha helices and coils. Such findings might help to design ER modulators which can regulate specific functions of estrogen in the brain during aging and degenerative diseases.

关键词： Estrogen Receptor β Alpha Helices and Coils Interacting Proteins SOPMA PSIPRED Aging Brain

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Thyroid Function and Depression in HIV-1 Infection

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World Journal of AIDS 2012年第4期2卷 279-285页

作者： Raymond L. Ownby Drenna Waldrop-Valverde Adarsh kumar mahendra kumar Department of Psychiatry and Behavioral Medicine Nova Southeastern University Fort Lauderdale USA Department of Psychiatry and Behavioral Sciences Miller School of Medicine University of Miami Miami USA Nell Hodgson Woodruff School of Nursing Emory University Atlanta USA

Thyroid abnormalities have been reported in persons with HIV infection, although data have been inconsistent with respect to its frequency and association with specific medications. The purpose of this study was to explore thyroid system response to thyroid releasing hormone stimulation in persons with and without HIV infection and determine the extent to which their response was associated with depression. As part of a larger study of neuroendocrine response persons with HIV-1 infection, control and HIV-1 infected individuals were evaluated. Participants' response to TRH stimulation was evaluated via TSH, total T3, and T4 levels at baseline and 15, 30, 45, and 60 minutes after TRH stimulation. Participants with HIV infection had a more robust response to TRH stimulation as measured by higher levels of TSH, lower levels of T4 and modestly higher levels of T3. Depressed persons had a reduced TSH response to stimulation and lower levels of both T4 and T3, although the effect of depression on T4 was not statistically significant. These results suggest that TSH response to TRH-stimulation may be exaggerated in individuals with HIV infection but reduced in those with depression. They also suggest that the effects of depression and HIV infection may interact, and may provide a partial explanation for observed thyroid abnormalities in HIV-infected individuals. Results thus provide a partial explanation for findings on thyroid and depression in those affected by HIV infection.

关键词： Thyroid HIV Depression

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Nadi Yantra: a robust system design to capture the signals from the radial artery for assessment of the autonomic nervous system non-invasively

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Journal of Biomedical Science and Engineering 2009年第7期2卷 471-479页

作者： A bhinav Meghna Sareen mahendra kumar Jayashree Santhosh Ashok Salhan Sneh Anand 不详

Ayurvedic and other alternative medical practi-tioners throughout the world have been using pulse diagnosis to detect disease and the organ at distress by feeling the palpations at three close yet precise positions of the radial artery. This paper presents a robust electro-mechanical system, ‘Nadi Yantra’ which uses piezoelectric based pressure sensors to capture the signals from the radial artery. Morphology of the waveforms obtained from our system concurs with standard physiological arterial signals. Reproducibility and stability of the system has been verified. Signal processing techniques were applied to obtain features such as amplitude, power spectral density, bandpower and spectral centroid to reflect variations in signals from the three channels. Further, wavelet based techniques were used to process the pressure signals and percussion peaks were identified. The interval between the percussion peaks was used to calculate Heart Rate Varibility (HRV), a useful tool for assessing the status of the autonomic nervous system of the human body non-invasively. Time domain indices were calculated from direct measurement of peak-peak (PP) intervals and from differences between the PP intervals. Frequency domain indices such as very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power, LF/HF ratio were also calculated. Thereafter, nonlinear Poincare analysis was carried out. A map of consecutive PP intervals was fitted to an ellipse using least squares method. Results from 7 datasets are depicted in this paper. A novel pressure pulse recording instrument is deve loped for the objective assessment of the ancient sci-ence of pulse diagnosis. The features calculated using multi resolution wavelet analysis show potential in the evaluation of the autonomic nervous system of the human body.

关键词： Radial Artery Pulse Diagnosis Power Spectral Density Spectral Centroid Multi Resolution Wavelet Autonomic Nervous System Heart Rate Variability Time Domain Frequency Domain Poincare

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