ABSTRACT
This study uses annular circular rings to create multi-band applications using crescent-shaped patch antennas. It is designed to be made up of five circular, annular rings nested inside of each other. Three annular rings are positioned and merged on top of the larger rings, with two annular rings set along the bottom of the feed line. The factors that set them apart, such as bandwidths, radiation patterns, gain, impedance, and return loss (RL), are analysed. The outcomes show how compact the multi-band annular ring antenna is. The proposed circular annular ring antenna has return losses of -33 dB and operates at two frequencies: 3.1 GHz and 9.3 GHz. This design is modelled and simulated using ANSYS HFSS. The outcomes of the simulation and the tests agree quite well. The X band and WLAN resonant bands have bandwidth capacities of 500 and 4300 MHz, respectively. Additionally, the circular annular ring antenna design is advantageous for most services at these operating bands.
ABSTRACT
BACKGROUND: There are very few small-molecule drug candidates developed against SARS-CoV-2 that have been revealed since the epidemic began in November 2019. The typical medicinal chemistry discovery approach requires more than a decade of the year of painstaking research and development and a significant financial guarantee, which is not feasible in the challenge of the current epidemic. OBJECTIVE: This current study proposes to find and identify the most effective and promising phytomolecules against SARS-CoV-2 in six essential proteins (3CL protease, Main protease, Papain- Like protease, N-protein RNA binding domain, RNA-dependent RNA polymerase, and Spike receptor binding domain target through in silico screening of 63 phytomolecules from six different Ayurveda medicinal plants. METHODS: The phytomolecules and SARS-CoV-2 proteins were taken from public domain databases such as PubChem and RCSB Protein Data Bank. For in silico screening, the molecular interactions, binding energy, and ADMET properties were investigated. RESULTS: The structure-based molecular docking reveals some molecules' greater affinity towards the target than the co-crystal ligand. Our results show that tannic acid, cyanidin-3-rutinoside, zeaxanthin, and carbolactone are phytomolecules capable of inhibiting SARS-CoV-2 target proteins in the least energy conformations. Tannic acid had the least binding energy of -8.8 kcal/mol, which is better than the binding energy of its corresponding co-crystal ligand (-7.5 kcal/mol) against 3 CL protease. Also, it has shown the least binding energy of -9.9 kcal/mol with a more significant number of conventional hydrogen bond interactions against the RdRp target. Cyanidin-3-rutinoside showed binding energy values of -8.8 and -7.6 kcal/mol against Main protease and Papain-like protease, respectively. Zeaxanthin was the top candidate in the N protein RBD with a binding score of - 8.4 kcal/mol, which is slightly better when compared to a co-crystal ligand (-8.2 kcal/mol). In the spike, carbolactone was the suitable candidate with the binding energy of -7.2 kcal/mol and formed a conventional hydrogen bond and two hydrophobic interactions. The best binding affinity-scored phytomolecules were selected for the MD simulations studies. CONCLUSION: The present in silico screening study suggested that active phytomolecules from medicinal plants could inhibit SARS-CoV-2 targets. The elite docked compounds with drug-like properties have a harmless ADMET profile, which may help to develop promising COVID-19 inhibitors.
ABSTRACT
BACKGROUND: A limited number of small molecules against SARS-CoV-2 has been discovered since the epidemic commenced in November 2019. The conventional medicinal chemistry approach demands more than a decade of the year of laborious research and development and a substantial financial commitment, which is not achievable in the face of the current epidemic. OBJECTIVE: This study aims to discover and recognize the most effective and promising small molecules by interacting SARS-CoV-2 Mpro target through computational screening of 39 phytochemicals from five different Ayurvedic medicinal plants. METHODS: The phytochemicals were downloaded from Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) PubChem, and the SARS-CoV-2 protein (PDB ID: 6LU7; Mpro) was taken from the PDB. The molecular interactions, binding energy, and ADMET properties were analyzed. RESULTS: The binding affinities were studied using a structure-based drug design of molecular docking, divulging 21 molecules possessing greater to equal affinity towards the target than the reference standard. Molecular docking analysis identified 13 phytochemicals, sennoside-B (-9.5 kcal/mol), isotrilobine (-9.4 kcal/mol), trilobine (-9.0 kcal/mol), serratagenic acid (-8.1 kcal/mol), fistulin (-8.0 kcal/mol), friedelin (-7.9 kcal/mol), oleanolic acid (-7.9 kcal/mol), uncinatone (-7.8 kcal/mol), 3,4-di- O-caffeoylquinic acid (-7.4 kcal/mol), clemaphenol A (-7.3 kcal/mol), pectolinarigenin (-7.2 kcal/mol), leucocyanidin (-7.2 kcal/mol), and 28-acetyl botulin (-7.2 kcal/mol) from ayurvedic medicinal plants phytochemicals possess greater affinity than the reference standard Molnupiravir (-7.0 kcal/mol) against SARS-CoV-2-Mpro. CONCLUSION: Two molecules, namely sennoside-B, and isotrilobine with low binding energies, were predicted as most promising. Furthermore, we carried out molecular dynamics simulations for the sennoside-B protein complexes based on the docking score. ADMET properties prediction confirmed that the selected docked phytochemicals were optimal. These compounds can be investigated further and utilized as a parent core molecule to create novel lead molecules for preventing COVID-19.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Molecular Docking Simulation , Sennosides , Chemistry, Pharmaceutical , Molecular Dynamics Simulation , Protease InhibitorsABSTRACT
Monkeypox is a zoonotic viral disease that mainly affects tropical rainforest regions of central and west Africa, with sporadic exportations to other places. Since there is no cure, treating monkeypox with an antiviral drug developed for smallpox is currently acceptable. Our study mainly focused on finding new therapeutics to target monkeypox from existing compounds or medications. It is a successful method for discovering or developing medicinal compounds with novel pharmacological or therapeutic applications. In this study, homology modelling developed the Monkeypox VarTMPK (IMNR) structure. Ligand-based pharmacophore was generated using the best docking pose of standard ticovirimat. Further, molecular docking analysis showed compounds, tetrahydroxycurcumin, procyanidin, rutin, vicenin-2, kaempferol 3-(6''-malonylglucoside) were the top five binding energy compounds against VarTMPK (1MNR). Furthermore, we carried out MD simulations for 100 ns for the six compounds, including reference based on the binding energies and interactions. MD studies revealed that as ticovirimat interacted with residues Lys17, Ser18, and Arg45, all the above five compounds interacted with the same amino acids at the active site during docking and simulation studies. Among all the compounds, ZINC4649679 (Tetrahydroxycurcumin) was shown to have the highest binding energy -9.7 kcal/mol and also observed stable protein-ligand complex during MD studies. ADMET profile estimation showed that the docked phytochemicals were safe. However, further biological assessment through a wet lab is essential to measure the efficacy and safety of the compounds.Communicated by Ramaswamy H. Sarma.
Subject(s)
Mpox (monkeypox) , Humans , Drug Repositioning , Ligands , Molecular Docking Simulation , Pharmacophore , Molecular Dynamics SimulationABSTRACT
BACKGROUND: To date, very few small drug molecules are used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been discovered since the epidemic commenced in November 2019. SARS-CoV-2 RdRp and spike protein are essential targets for drug development amidst whole variants of coronaviruses. OBJECTIVE: This study aims to discover and recognize the most effective and promising small molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 39 phytochemicals from five different Ayurveda medicinal plants. METHODS: The phytochemicals were downloaded from PubChem, and SARS-CoV-2 RdRp and spike protein were taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed. RESULTS: Molecular docking analysis identified some phytochemicals, oleanolic acid, friedelin, serratagenic acid, uncinatone, clemaphenol A, sennosides B, trilobine and isotrilobine from ayurvedic medicinal plants possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely oleanolic acid and sennosides B, with low binding energies, were the most promising. Furthermore, based on the docking score, we carried out MD simulations for the oleanolic acid and sennosides B-protein complexes. CONCLUSION: Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike protein of SARS-CoV-2.
Subject(s)
COVID-19 , Oleanolic Acid , Plants, Medicinal , SARS-CoV-2 , Molecular Docking Simulation , RNA, Viral , Sennosides , Spike Glycoprotein, Coronavirus , Antiviral Agents/pharmacology , Molecular Dynamics SimulationABSTRACT
Dengue virus enters the cell by receptor-mediated endocytosis followed by a viral envelope (DENVE) protein-mediated membrane fusion. A small detergent molecule n-octyl-ß-D-glucoside (ßOG) occupies the hydrophobic pocket which is located in the hinge region plays a major role in the rearrangement. It has been reported that mutations occurred in this binding pocket lead to the alterations of pH threshold for fusion. In addition to this event, the protonation of histidine residues present in the hydrophobic pocket would also impart the conformational change of the E protein evidence this pocket as a promising target. The present study identified novel cinnamic acid analogs as significant blockers of the hydrophobic pocket through molecular modeling studies against DENVE. A library of seventy-two analogs of cinnamic acid was undertaken for the discovery process of DENV inhibitors. A Molecular docking study was used to analyze the binding mechanism between these compounds and DENV followed by ADMET prediction. Binding energies were predicted by the MMGBSA study. The Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. The compounds CA and SCA derivatives have been tested against HSV-1 & 2 viruses. From the computational results, the compounds CA1, CA2, SCA 60, SCA 57, SCA 37, SCA 58, and SCA 14 exhibited favorable interaction energy. The compounds have in-vitro antiviral activity; the results clearly indicate that the compounds showed the activity against both the viruses (HSV-1 & HSV-2). Our study provides valuable information on the discovery of small molecules DENVE inhibitors.Communicated by Ramaswamy H. Sarma.
Subject(s)
Antiviral Agents , Dengue Virus , Viral Envelope Proteins , Antiviral Agents/chemistry , Dengue Virus/chemistry , Glucosides , Molecular Docking Simulation , Molecular Dynamics Simulation , Viral Envelope Proteins/chemistryABSTRACT
Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor's (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of evidence reports that selective long chain polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to transcriptional activation. We, therefore, hypothesize that selective PUFAs would modulate the dynamics and kinetics of VDRs, irrespective of the deficiency of vitamin-D. The spatial arrangements of the selected PUFAs in VDR active site were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR (PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.
Subject(s)
Fatty Acids, Unsaturated/metabolism , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Animals , Docosahexaenoic Acids/metabolism , Eicosapentaenoic Acid/metabolism , Humans , Ligands , Retinoid X Receptors/metabolism , Vitamin D/metabolism , Vitamins/metabolismABSTRACT
Coronavirus disease of 2019 (COVID-19) is a zoonotic disease caused by a new severe acute respiratory syndrome (SARS-CoV-2) which has quickly resulted in a pandemic. Recent anti-COVID-19 drug discoveries are leaning towards repurposing phytochemicals which have been previously reported for SARS and MERS-CoV outbreaks. However, they have been either virtually screened or tested so far against mono targets and the potent derivatives of virtually sorted lead molecules remain elusive. We aimed to identify the phytochemicals having potentials to inhibit SARS CoV-2 infection via multiple targets. The selected 132 phytochemicals were virtually screened using a structure based in silico technique against main protease (Mpro) which is a potential target of SARS CoV-2. Six compounds were selected based on the LibDock scores and further subjected to induced fit docking using the CDOCKER module of DS. Two compounds namely cinnamtannin-B and gallocatechin gallate were identified as top HITS against main protease (Mpro). Based on the Lipinski rule of five (L-ROF) and synthetic feasibility, gallocatechin gallate was taken for our further studies. Six analogues of gallocatechin gallate were screened against the next important targets such as RNA-dependent RNA polymerase (RdRp), angiotensin converting enzyme-2 (ACE2), transmembrane protease serine -2 (TMPRSS2) and interleukin-6 (IL-6) along with main protease (Mpro). Our molecular docking results reveal that a gallocatechin analogue (GC-2) namely (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate has shown potential to inhibit multiple targets of SARS CoV-2. Further, the molecular dynamics study was carried out to ascertain the stability of the GC-2 and RdRp complex.
ABSTRACT
Mucin networks are lubricous biofunctional coats formed through the continuous deposition of mucin glycoproteins. Previously, we demonstrated the synthesis of a mucin mimic using biotinylated-filomicelles crosslinked via streptavidin using a layer-by-layer approach. These networks recreate the fibrous nature of mucin and can serve as a drug-releasing network. In this work, the ability to vary the network properties by blending filomicelles with spherical micelles is demonstrated. In addition, the deposition of a dense polymer coating on the mucin network was shown to act as a barrier to control diffusion and improved the structural stability under simulated oral chemical conditions. These biomimetic coatings can be utilized as a delivery system, providing a tunable drug release for oral applications.
Subject(s)
Biomimetic Materials , Micelles , Biomimetic Materials/chemical synthesis , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacokinetics , Biomimetic Materials/pharmacology , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Mucins/chemistry , Streptavidin/chemistryABSTRACT
Mucin networks are viscoelastic fibrillar aggregates formed through the complex self-association of biopolymeric glycoprotein chains. The networks form a lubricious, hydrated protective shield along epithelial regions within the human body. The critical role played by mucin networks in impacting the transport properties of biofunctional molecules (e.g., biogenic molecules, probes, nanoparticles), and its effect on bioavailability are well described in the literature. An alternate perspective is provided in this paper, presenting mucin's complex network structure, and its interdependent functional characteristics in human physiology. We highlight the recent advances that were achieved through the use of mucin in diverse areas of bioengineering applications (e.g., drug delivery, biomedical devices and tissue engineering). Mucin network formation is a highly complex process, driven by wide variety of molecular interactions, and the network possess structural and chemical variations, posing a great challenge to understand mucin's bulk behavior. Through this review, the prospective potential of polymer based analogs to serve as mucin mimic is suggested. These analog systems, apart from functioning as an artificial model, reducing the current dependency on animal models, can aid in furthering our fundamental understanding of such complex structures.
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PßAE polymers have emerged as highly promising candidates for biomedical and drug delivery applications owing to their tunable, degradable and pH sensitive properties. These polymeric systems can serve as prodrug carriers for the delivery of bioactive compounds which suffer from poor aqueous solubility, low bioavailability and are biologically unstable, such as the antioxidant, quercetin. Using acrylate functionalized quercetin, it is possible to incorporate the polyphenol into the backbone of the polymer matrix, permitting slow release of the intact molecule which is perfectly timed with the polymer degradation. While formulating these quercetin conjugated PßAE matrix into nanocarriers would allow for multiple delivery routes (oral, intravenous, inhalation etc.), well known oil-water nano-emulsion formulation methods are not amenable to the crosslinked hydrolytically sensitive nanoparticle/nanogel. In this work, a single-phase reaction-precipitation method was developed to formulate quercetin conjugated PßAE nanogels (QNG) via reaction of acrylated quercetin (4-5 acrylate groups) with a secondary diamine under dilute conditions using acetonitrile as the reaction medium, resulting in a self-stabilized suspension. The proposed approach permits the post synthesis modification of the spherical nanogels with a PEGylated coating, enhancing their aqueous stability and stealth characteristics. Nanogel size was controlled by varying feed reactant concentrations, achieving drug loadings of 25-38wt%. Uniform release of quercetin over 45-48h was observed upon PßAE ester hydrolysis under physiological conditions with its retained antioxidant activity over the extended times. STATEMENT OF SIGNIFICANCE: Here we present the first demonstration of using poly(beta amino ester) chemistry to form nanogels composed of a bioactive polyphenol for the control of cellular oxidative stress. Previous nanogel and nanoparticle approaches, which use a water phase, are not readily amenable to PBAE chemistry due to their hydrolytic sensitivity. Here we demonstrate a simple approach to control particle size, modify surface chemistry and achieve highly regulated controlled release of active antioxidants, which can protect cells against external oxidative stress signals. This work has importance in the area of controlling material biocompatibility through augmenting the antioxidant status of cells.
Subject(s)
Endothelial Cells/physiology , Gels/chemistry , Nanocapsules/chemistry , Oxidative Stress/physiology , Polymers/chemistry , Quercetin/administration & dosage , Antioxidants/administration & dosage , Antioxidants/chemistry , Cells, Cultured , Diffusion , Endothelial Cells/drug effects , Humans , Nanocapsules/administration & dosage , Nanocapsules/ultrastructure , Nanoconjugates/administration & dosage , Nanoconjugates/chemistry , Nanoconjugates/ultrastructure , Oxidative Stress/drug effects , Particle Size , Quercetin/chemistry , Treatment OutcomeABSTRACT
We investigated mass mortalities of koi, Cyprinus carpio Linnaeus, 1758, experienced in South Indian fish farms by virus isolation, electron microscopy, PCR detection, sequencing of capsid protein gene and transmission studies. Samples of moribund koi brought to the laboratory suffered continuous mortality exhibiting swimming abnormalities, intermittent surfacing and skin darkening. Irido-like virus was isolated from the infected fish in the indigenous snakehead kidney cell line (SNKD2a). Icosahedral virus particles of 100 to 120 nm were observed in the infected cell cultures, budding from the cell membrane. Virus transmission and pathogenicity studies revealed that horizontal transmission occurred associated with mortality. PCR analysis of infected fish and cell cultures confirmed the presence of Ranavirus capsid protein sequences. Sequence analysis of the major capsid protein gene showed an identity of 99.9% to that of largemouth bass virus isolated from North America. Detection and successful isolation of this viral agent becomes the first record of isolation of a virus resembling Santee-Cooper Ranavirus from a koi and from India. We propose the name koi ranavirus to this agent.
Subject(s)
DNA Virus Infections/veterinary , Fish Diseases/virology , Animals , Capsid Proteins/genetics , Carps , Cell Line , DNA Virus Infections/diagnosis , DNA Virus Infections/pathology , DNA Virus Infections/transmission , DNA Virus Infections/virology , Fish Diseases/diagnosis , Fish Diseases/genetics , Fish Diseases/pathology , Fish Diseases/transmission , Fisheries , India , Microscopy, Electron, Transmission , Molecular Sequence Data , Ranavirus/genetics , Ranavirus/isolation & purification , Ranavirus/ultrastructureABSTRACT
Mucin networks are formed in the oral cavity by complexation of glycoproteins with other salivary proteins, yielding a hydrated lubricating barrier. The function of these networks is linked to their structural, chemical, and mechanical properties. Yet, as these properties are interdependent, it is difficult to tease out their relative importance. Here, we demonstrate the ability to recreate the fibrous like network through a series of complementary rinses of polymeric worm-like micelles, resulting in a 3-dimensional (3D) porous network that can be deposited layer-by-layer onto any surface. In this work, stability, structure, and microbial capture capabilities were evaluated as a function of network properties. It was found that network structure alone was sufficient for bacterial capture, even with networks composed of the adhesion-resistant polymer, poly(ethylene glycol). The synthetic networks provide an excellent, yet simple, means of independently characterizing mucin network properties (e.g., surface chemistry, stiffness, and pore size).
Subject(s)
Biomimetics/methods , Micelles , Mucins/chemical synthesis , Polymers/chemistry , Curcumin/chemistry , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Polyethylene Glycols/chemistry , Porosity , Staphylococcus aureus/drug effects , Streptavidin/pharmacologyABSTRACT
Oral mucositis, a painful and debilitating ulcerative wound condition, is a frequently occurring complication following chemo- and/or radiotherapy. While the current standards of therapy (e.g., gels and mouth rinses) provide temporary relief, there is still an unmet need for a robust, long acting barrier that can provide lubricating protection in oral wounds, thereby enhancing the wound healing response. It is proposed that an affinity based layer-by-layer (LBL) self-assembly that can be administered as a series of mouth rinses could permit the formation of protective barriers, providing a modular approach to regenerative oral therapy. In this study, biotinylated poly(acrylic acid) was synthesized for developing LBL assemblies using biotin-streptavidin affinity linkages. To explore the ability of developed LBL assemblies to potentially resist the harsh intraoral environment, in vitro chemical and ex vivo mechanical tests were performed. The stability results demonstrated significant LBL barrier stability with wear resistance. From statistical analyses, it was deduced that polymer MW and the number of LBL layers contributed significantly to chemical barrier stability. Also, the extent of biotin conjugation played a key role for LBL development and in mechanical barrier stability. Thus, the proposed affinity based LBLs with their excellent barrier properties offer a modular treatment approach in oral mucosal injuries.
Subject(s)
Bandages , Mouth Diseases/therapy , Polymers , Wounds and Injuries/therapy , Humans , Multivariate Analysis , SalivaABSTRACT
BACKGROUND: It is well known that quite a large number of apparently healthy donors are not able to donate blood successfully because of varied reasons. AIM: We want to analyze the rate and various reasons for deferrals. MATERIALS AND METHODS: A retrospective analysis of records of the donors, for 3 years, from January 2005 to December 2007 was done, in order to find out the rate and causes of deferral in four categories of age groups, both in male and female, in our Transfusion Medicine Centre, Bangalore, India. RESULT: There were 16,706 donors, of which 976 donors were deferred (5.84%) for various reasons. Of the 16,706 donors registered for donation, females constituted only 11.27%. And deferral rate was about five times more for female (19.85%) compared to male (4.06%). The three most common reasons for deferral in female were low hemoglobin levels, low body weight, and hypotension. The deferral rate was higher in the age group of 18-25 years and most common cause was low hemoglobin level. In male, the three most common reasons for deferral were hypertension, under weight, and low hemoglobin levels. The deferral rate varied from 4 to 15% as reported in the literature. The most common cause of deferral in our study and in several studies available in the literature is the same.
ABSTRACT
BACKGROUND & OBJECTIVES: Although many infections can be transmitted through blood transfusion, it is not possible to carry out screening tests for all. Among the protozoal diseases transmitted by blood transfusion in India the most important is malaria, followed by toxoplasmosis. Screening for malaria is mandatory in India. We evaluated the seroprevalence of Toxoplasma gondii in healthy adult population of blood donors in Karnataka, south India. METHODS: A total of 1000 serum samples collected in two batches (500 each) in the years 2004 and 2005 from healthy voluntary blood donors were tested for T. gondii antibodies by ELISA method, in addition to the other five mandatory tests. RESULTS: Overall 20.3 per cent were positive for T. gondii IgG antibody, of which, 63 per cent had high and 7 per cent low avidity, 3.6 per cent IgM positive. IgG titre ranged from 18-362 IU/ml. INTERPRETATION & CONCLUSION: Our study showed a high prevalence of T. gondii antibodies in healthy voluntary blood population. It may be appropriate to include screening for T. gondii also in the pretransfusion blood testing schedule.
Subject(s)
Antibodies, Protozoan/blood , Blood Donors , Toxoplasma/immunology , Toxoplasmosis/epidemiology , Adult , Animals , Female , Humans , India/epidemiology , Male , Seroepidemiologic StudiesSubject(s)
ABO Blood-Group System , Blood Donors , Brain Neoplasms/blood , Glioma/blood , Humans , India , Meningioma/blood , Neurilemmoma/blood , Neurocytoma , Risk FactorsABSTRACT
This is the first report of secondary resistance to rifampin following MDT in a patient with prolonged, but irregular treatment. Repeated mouse foot-pad studies demonstrated resistance to dapsone after several years of monotherapy, and following subsequent MDT the studies demonstrated the development of resistance to rifampin.