Biomedical subjects

Anuj Chauhan

Publications and source records attributed to Anuj Chauhan.

11 recordsLinked to original sources

PubMed2026

Long non-coding RNAs link DNA methylation to immune regulatory networks in bovine subclinical mastitis.

Long non-coding RNAs (lncRNAs) are emerging as important regulators of inflammatory and immune signaling, yet their contribution to bovine subclinical mastitis remains poorly defined. Here, we characterized the lncRNA expression landscape associated with disease in milk somatic cells of healthy and subclinical mastitic Vrindavani cattle. We identified 11,403 high-confidence lncRNAs, of which 104 were differentially expressed in subclinical mastitis (adjusted P < 0.05; |log2FC| ≥ 1), with the vast majority upregulated in mastitic samples. Predicted cis- and trans-associated target analyses identified 637 non-redundant genes, and KEGG analysis identified 8 significantly enriched cis-associated pathways and 152 significantly enriched trans-associated pathways (adjusted P < 0.05), predominantly enriched for immune and inflammation-related pathways. These findings prioritized a subset of mastitis-associated lncRNAs for subsequent methylation and interaction-network analyses. A subset of these lncRNAs further overlapped differentially methylated regions (DMRs), suggesting a potential association between lncRNA expression changes and DNA methylation alterations. Integration of lncRNA-miRNA and miRNA-mRNA interactions identified lncRNA-miRNA-mRNA interaction networks involving DMR-associated lncRNAs. Among the prioritized candidates, MSTRG.28878.1 showed overlap with a hypomethylated promoter-associated DMR, increased expression, and multiple connections within the predicted interaction network. Together, these findings identify candidate lncRNAs, methylation-associated loci, and predicted molecular interactions associated with bovine subclinical mastitis and provide a resource for future functional investigation of candidate non-coding RNA-associated mechanisms in disease.

Animals↗

PubMed2006

Sequestration of amitriptyline by liposomes.

We study the uptake of amitriptyline, which is a common cause of overdose-related fatalities, in aqueous solutions by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes and liposomes composed of a mixture of DMPC and 1,2-dioleoyl-sn-glycero-3-[phospho-rac(1-glycerol)] (DOPG) lipids. The effect of drug concentration, liposomal charge, pH, salt, and protein presence on the drug uptake is investigated using two different methodologies, a precipitation and a centrifugation method. Furthermore, the time scale of the drug uptake is studied through qualitative observations at high pH and through conductivity measurements at neutral pH and found to be <5 s. The results of the quantitative studies show that the fractional drug uptake decreases with increasing drug concentration, and for a given concentration it increases with the pH and decreases in the presence of salt. We find that a larger amount of drug is sequestered by negatively charged liposomes (those containing DOPG) than liposomes with no net charge (DMPC). We speculate that the mechanism of drug uptake is due to both electrostatic interactions as well as hydrophobic effects. The fractional uptake by DMPC:DOPG in a 70:30 ratio is as high as 95% in water and about 90% in physiological buffer. The fractional uptake is also measured in presence of 2% (w/w) bovine serum albumin (BSA), which is approximately the protein concentration in the intercellular fluid. In presence of protein the fractional uptakes by 70:30 DMPC:DOPG liposomes and 50:50 DMPC:DOPG liposomes are 82 and 90%, respectively, at 125 muM drug amitriptyline. In the absence of liposomes, 67% of the drug is taken up by the protein in a 2% (w/w) BSA, 125 muM amitriptyline solution. Thus, addition of 50:50 DMPC:DOPG liposomes reduces the free drug concentration by a factor of about 3.5, making them attractive candidates for drug detoxification.

Amitriptyline↗

PubMed2005

Influence of physical and chemical heterogeneity shape on thin film rupture.

It is known that the breakup times for thin liquid films on solid surfaces can be substantially smaller if the surface is heterogeneous, either chemically or physically. In this paper we explore issues related to the effect of the shape of the physical and chemical heterogeneities on the breakup time and the thinning behavior. We consider two shapes, sinusoidal and exponential, for both physical and chemical gradients and compare the breakup times for these two different forms of gradients. Furthermore, the wavelength of the sinusoidal gradients and the length scale of the exponential gradients are varied and the effects of these on the breakup times and the film evolution are determined. For the sinusoidal gradients, we also obtain analytical results for shape evolution that are valid at short times and for small amplitude perturbation of the physical/chemical heterogeneities. The fastest growing modes are determined for spinodal breakup and also for both shapes (sinusoidal and exponential) of physical and chemical heterogeneities. The breakup times for the fastest growing modes from the linear and the nonlinear studies are compared for spinodal breakup and these results are also compared with those for both chemical and physical heterogeneities, of both sinusoidal and exponential shapes. Results show that the presence of heterogeneities, in general, accelerates the breakup of the film. In the linear regime, the growth rates are the same for the chemical and physical heterogeneities and spinodal breakup, and the effect of the heterogeneities is manifested as increased amplitude of initial perturbation. The effect of the chemical and physical heterogeneities dominate the film dynamics at early times, becoming less important at later times. The growth rates and equivalently the breakup times for the films on heterogeneous surfaces depend on the length scale over which physical/chemical gradients occur, and as the length scale approaches zero, which implies that the gradients become very steep, the effect of the heterogeneities on the breakup times becomes small.

Chemical Phenomena↗

PubMed2005

DNA separation by EFFF in a microchannel.

This paper theoretically explores the application of electric field flow fractionation (EFFF) for the size-based separation of DNA strands in a microchannel. An axial electric field cannot separate DNA strands in solution because the electrical mobility of the strands is independent of the length. However, lateral electric fields coupled with an axial Poiseuille flow can separate the DNA strands of different sizes. By using regular perturbation analysis, we obtain the effective diffusivity and the mean velocity of the DNA molecules that are undergoing a pressure driven Poiseuille flow in a 2D channel in presence of a lateral electric field. The mean velocities and the dispersion coefficients are then utilized to determine the scaling for length of the channel and the time required for separation of DNA molecules in different parameter regimes. The results show that EFFF can separate DNA strands in the range of 10 kbp that differ in size by about 2.5 kbp in about half an hour in a 1 cm long channel. While DNA strands can be separated by EFFF, the performance of devices based on EFFF seems to be at best comparable to other techniques such as entropic trapping.

DNA↗

PubMed2005

Separation of charged colloids by a combination of pulsating lateral electric fields and poiseuille flow in a 2D channel.

Separation of colloidal particles of different sizes is becoming increasingly important due to rapid developments in the area of proteomics, genetic engineering, drug discovery, etc. In particular, there is a need to accomplish these separations on a microscale in 'lab-on-a-chip' devices. In this paper, we propose a new method for accomplishing separation of charged colloids of different sizes in a microchannel. This method involves a combination of pulses of lateral electric fields and Poiseuille flow in the axial direction. We develop a model for this separation technique and obtain closed form solutions for the mean velocity and the dispersion coefficient for a pulse of molecules introduced into the channel. These expressions are then utilized to determine the channel length and the separation time. For reasonable value of design constants, the proposed technique can separate molecules of different sizes that have diffusivities of 10(-10) and 0.5 x 10(-10) m2/s in 15.7 s in a 3.7 mm long channel. The length and the time increase to 5.45 cm and 231 s if the ratio of the diffusivities is reduced from 2 to 1.2, i.e., the latter diffusivity is increased to 0.835 x 10(-10) m2/s, while keeping all the other parameters the same. If the diffusivities are about 10(-9) m(2)/s, the length and the time for separation are 1 cm and 17.5 s for D1/D2=2, and 16 cm and 269 s for D1/D2=1.2.

Journal Article↗

PubMed2005

Dispersion of microemulsion drops in HEMA hydrogel: a potential ophthalmic drug delivery vehicle.

Approximately 90% of all ophthalmic drug formulations are now applied as eye-drops. While eye-drops are convenient and well accepted by patients, about 95% of the drug contained in the drops is lost due to absorption through the conjunctiva or through the tear drainage. A major fraction of the drug eventually enters the blood stream and may cause side effects. The drug loss and the side effects can be minimized by using disposable soft contact lenses for ophthalmic drug delivery. The essential idea is to encapsulate the ophthalmic drug formulations in nanoparticles, and disperse these drug-laden particles in the lens material. Upon insertion into the eye, the lens will slowly release the drug into the pre lens (the film between the air and the lens) and the post-lens (the film between the cornea and the lens) tear films, and thus provide drug delivery for extended periods of time. This paper focuses on dispersing stabilized microemulsion drops in poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels. The results of this study show that the p-HEMA gels loaded with a microemulsion that is stabilized with a silica shell are transparent and that these gels release drugs for a period of over 8 days. Contact lenses made of microemulsion-laden gels are expected to deliver drugs at therapeutic levels for a few days. The delivery rates can be tailored by controlling the particle and the drug loading. It may be possible to use this system for both therapeutic drug delivery to eyes and the provision of lubricants to alleviate eye problems prevalent in extended lens wear.

Algorithms↗

PubMed2005

Dispersion of DMPC liposomes in contact lenses for ophthalmic drug delivery.

Approximately 90% of all ophthalmic drug formulations are now applied as eyedrops. Although eyedrops are convenient and well accepted by patients, about 95% of the drug contained in the drops is lost due to absorption through the conjunctiva or through the tear drainage. A major fraction of the drug eventually enters the bloodstream and may cause side effects. To reduce drug loss and side effects, it is proposed to encapsulate the ophthalmic drug formulations in liposomes and to disperse the drug-laden liposomes in the lens material. Upon insertion into the eye, the liposome-laden lens will slowly release the drug into the pre-lens (the film between the air and the lens) and the post-lens (the film between the cornea and the lens) tear films and thus provide drug delivery for extended periods of time. This paper focuses on dispersing dimyristoyl phosphatidylcholine (DMPC) liposomes in poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels, which are a common contact lens material. The results of this study show that the p-HEMA gels loaded with liposomes are transparent and that these gels release drugs for a period of about 8 days. Contact lenses made of particle-laden gels are expected to deliver drugs at therapeutic levels for a few days. The delivery rates can be tailored by controlling the particle and the drug loading.

Biological Availability↗

PubMed2005

A mathematical model for tear drainage through the canaliculi.

PURPOSE: Tear drainage through the canaliculi has been extensively studied experimentally but there has been no attempt to develop a quantitative model for this process. In this paper, we develop a mathematical model for the tear drainage through the canaliculi. METHODS: The mathematical model is based on the experimental findings of Doane, according to which the muscle action during a blink drives the tear drainage. In this paper, mathematical models are developed for the tear flow and the canalicular deformation, and the model equations are solved to predict the tear drainage rates. RESULTS: The drainage rates depend on various physiological parameters. The time to attain a steady state during the drainage process can vary from about 0.0010 s to 0.0546 s, and the tear drainage rate can vary from 0.10 microl/min to 4.00 microl/min for a normal tear film, for physiologically reasonable values of various system parameters. CONCLUSIONS: The model predictions agree with various physiological experiments, at least qualitatively. The model also helps resolve the differences between various tear drainage experiments.

Blinking↗

PubMed2005

A mathematical model for ocular tear and solute balance.

PURPOSE: In this paper we develop a mathematical model that can predict the steady-state tear film thickness and the dynamic tear film thickness and the solute concentration after instillation of a solute-laden fluid in the eye. METHODS: The mathematical model developed in this paper is based on a balance between the inflow and outflow of tears into the tear film. It incorporates a tear drainage model and a model that relates the tear film thickness to the meniscus radius of curvature. To predict the solute concentrations, the tear balance is coupled with the solute balance. The differential equations for the unsteady balances are solved numerically. RESULTS: The model predicts that the tear film thickness depends on a number of physiological factors, such as rates of tear production and evaporation, geometry and modulus of the canaliculi, and surface tension and viscosity of tears, and varies from about 3 to 15 microm. The model also predicts that the drainage time for an instilled volume of 15 microl is 1283 s. Additionally, the time required for the tracer concentration to decay to 1% of the value immediately after instillation of a drug-laden 40 microl drop is about 2480 s. Similarly, the time for intensity decay for a radioactive tracer after 25 microl instillation is about 1566 s. Also, the model predicts that the fraction of the instilled drug that reaches the cornea is about 1.3% for topical application of timolol. CONCLUSIONS: The predicted results agree reasonably with the reported experimental results, at least qualitatively. The model developed here can serve as a useful tool to develop a more precise understanding of various issues related to tears and also evaluate the effect of various parameters on the tear volume.

Eye↗

PubMed2004

A physiologically-based pharmacokinetic model of drug detoxification by nanoparticles.

Nanoparticles (NPs) may be capable of reversing the toxic effects of drug overdoses in humans by adsorbing/absorbing drug molecules. This paper develops a model to include the kinetic effects of treating drug overdoses by NPs. Depending on the size and the nature of the NPs, they may either pass through the capillary walls and enter the tissue space or remain only inside the capillaries and other blood vessels: models are developed for each case. Furthermore, the time scale for equilibration between the NP and the blood will vary with the specific type of NP. The NPs may sequester drug from within the capillaries depending on whether this time scale is larger or smaller than the residence time of blood within the capillary. Models are developed for each scenario. The results suggest that NPs are more effective at detoxification if they are confined to the blood vessels and do not enter the tissues. The results also show that the detoxification process is faster if drug uptake occurs within the capillaries. The trends shown by the model predictions can serve as useful guides in the design of the optimal NP for detoxification.

Drug Overdose↗

PubMed2004

Ophthalmic drug delivery through contact lenses.

PURPOSE: Currently available ophthalmic drug delivery systems are inefficient and may lead to side effects. To increase efficiency and reduce side effects, the authors propose disposable particle-laden soft contact lenses for ophthalmic drug delivery. METHODS: The essential idea is to encapsulate the ophthalmic drug formulations in nanoparticles and to disperse these drug-laden particles in the lens material, such as poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels. The drug-laden p-HEMA hydrogels were synthesized by free radical solution polymerization of the monomers in presence of nanoparticles. The particle-laden hydrogels were characterized by light-transmission and electron microscopy studies. Release profiles of lidocaine, a model hydrophobic drug, were measured by UV-Vis spectrophotometry. RESULTS: Microemulsions of hexadecane in water stabilized with a silica shell around the particles produced transparent hydrogels. Contact lenses made with particle-laden hydrogels released therapeutic levels of drug for a few days. CONCLUSIONS: Particle-laden hydrogels are promising candidates for ophthalmic drug delivery. They are transparent and can release drugs for extended periods. The drug delivery rates can be controlled by varying the loading of nanoparticles in the gel.

Anesthetics, Local↗