Home | About PM | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Pharmacognosy Magazine
Search Article 
Advanced search 

  Table of Contents  
Year : 2018  |  Volume : 14  |  Issue : 53  |  Page : 124-128  

Computational tool for immunotoxic assessment of pyrethroids toward adaptive immune cell receptors

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India

Date of Submission17-Feb-2017
Date of Acceptance08-Mar-2017
Date of Web Publication20-Feb-2018

Correspondence Address:
Kamal Kant
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi - 835 215, Jharkhand
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pm.pm_62_17

Rights and Permissions

Background: Pyrethroids have prominently known for their insecticidal actions worldwide, but recent reports as anticancer and antiviral applications gained a lot of interest to further understand their safety and immunotoxicity. Objective: This encouraged us to carry out our present study to evaluate the interactions of pyrethroids toward adaptive immune cell receptors. Materials and Methods: Type 1 and Type 2 pyrethroids were tested on T (CD4 and CD8) and B (CD28 and CD45) immune cell receptors using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). In addition, top-ranked tested ligands were too explored for toxicity prediction in rodents using ProTOX tool. Results: Pyrethroids (specifically type 2) such as fenvalerate (−5.534 kcal/mol: CD8), fluvalinate (−4.644 and − 4.431 kcal/mol: CD4 and CD45), and cypermethrin (−3.535 kcal/mol: CD28) have outcome in less energy or more affinity for B-cell and T-cell immune receptors which may later result in the immunosuppressive and hypersensitivity reactions. Conclusion: The current findings have uncovered that there is a further need to assess the Type 2 pyrethroids with wet laboratory experiments to understand the chemical nature of pyrethroid-induced immunotoxicity.
Abbreviations used: PDB: Protein Data Bank; AOFA: Amine oxidase (flavin-containing) A; PGH 1: Prostaglandin G/H synthase 1.

Keywords: Docking, immunotoxicity, pyrethroids, receptor

How to cite this article:
Kumar A, Behera PC, Rangra NK, Dey S, Kant K. Computational tool for immunotoxic assessment of pyrethroids toward adaptive immune cell receptors. Phcog Mag 2018;14:124-8

How to cite this URL:
Kumar A, Behera PC, Rangra NK, Dey S, Kant K. Computational tool for immunotoxic assessment of pyrethroids toward adaptive immune cell receptors. Phcog Mag [serial online] 2018 [cited 2022 Dec 3];14:124-8. Available from: http://www.phcog.com/text.asp?2018/14/53/124/225667


  • Fenvalerate showed apex glide score toward CD8 immune receptor, while fluvalinate confirmed top-ranked binding with CD4 and CD45 immune proteins
  • In addition, cypermethrin outcame in top glide score against CD28 immune receptor
  • Top dock hits (Type 2) pyrethroids have shown probable toxicity targets toward AOFA: Amine oxidase (flavin-containing) A and PGH1: Prostaglandin G/H synthase 1, respectively.

   Introduction Top

During the past decades, pesticides have recognized as a major environmental chemical pollution in agriculture which eventually resulting in serious health concern.[1],[2],[3] Pyrethroid class of pesticides (insecticides) is often in use due to their low tendency to accumulate in organisms and short biodegradation period.[4] Type 1 and Type 2 pyrethroids are basically synthetic analogs derived from main nucleus pyrethrins, an imperative phytochemical entity isolated from the flowering part of Chrysanthemum cinerariaefolium. The division of pyrethroids into two classes is based on chemical structural differences and toxicological and neurophysiological actions. The chemical difference showed that Type 2 pyrethroids contain an α-cyano-phenoxy-benzyl moiety while Type 1 pyrethroids devoid of an α-cyano component which in turns relates to the types of poisoning syndrome. Mostly, synthetic pyrethroids exist in different forms of enantiomers due to their chiral nature.[5],[6],[7] The Type 1 compounds symptoms include increased reactivity to whole-body tremor, whereas salivation, choreoathetosis, and chronic seizures are quite common with Type 2 pyrethroids.[8],[9] The pyrethroids are toxic to insects due to their depolarization action on nerve membranes.[10],[11],[12] Photostability, high efficacy at low concentrations, easy disintegration, and low toxicity to birds and mammals are the key rewards of pyrethroid insecticides.[13],[14] The products containing pyrethroid insecticides are used for the control of pests such as mites, ants, weevils, and beetles on various crops, including cotton, corn, cereals, soybeans, and vegetables and also for the control of endo- and ecto-parasites on animals.[15] Pyrethroid insecticides are a product of choice in many countries due to their expeditious metabolism rate and low toxicity to humans and other nontarget animals. Due to their high potency on a huge number of pests, these have become a premier choice for the control of malaria and other vector-borne diseases.[16],[17],[18] For the last two decades, diminution on the sales of organophosphorus insecticides researchers has developed pyrethroids with the merits of more promising insecticidal and antiparasitic formulation.[19],[20] Globally, use of pyrethroids has resulted in contamination problem, and moreover, even their metabolites possess a significant role in polluting food and water which ultimately leads to health problems.[17],[21] Humans have exposed to pyrethroid insecticides by their well-built use in personal protection such as mosquito nets drenched with pyrethroid insecticides, disinfection of aircraft, in agriculture and public health, respectively.[22],[23],[24] Numerous manifestations have observed in the nervous, respiratory, cardiovascular, and gastrointestinal systems which ultimately resulting in allergic reactions, myocardial impairment, and even death due to respiratory failure by the minute subjection of pyrethroids to the human beings.[25] Immunotoxicity of pyrethroid insecticides is still unclear specifically on the adaptive immune system. T- and B-cells play the vital role to provide adaptive immunity against pathogens by producing various cytokines and antibodies. CD4 and CD8 are the surface markers which are present on T-cell receptors whereas CD28 and CD45 are present on B-cell receptors. As the immunotoxicity of pyrethroid insecticides on an adaptive immune system is still unexplored, it is essential to first observe their binding affinity towards the adaptive immune cell receptors. Chiral transformation of pyrethroid compounds may have a different potential toward adaptive immune system receptors. Molecular docking has provided an important tool for estimating the interaction of compounds toward specific receptors along with its pharmacokinetic properties. Outstandingly, ProTOX online tool has too shown promising toxicity prediction output in the form of LD50 value against rodents.[26],[27] Thus, the main aim of this study is to predict the binding affinity of pyrethroid insecticides toward T-cell (CD4, CD8) and B-cell receptors (CD28, CD45).

   Materials and Methods Top

Docking simulations were run on core TM processor with 4 GB RAM and 220 GB with center Linux Enterprise version as the operating system using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA) while toxicity prediction was carried out online through the ProTOX tool. The chemical structures of tested pyrethroids (Type 1 and Type 2) were retrieved from PubChem database.

Protein preparation

The immune proteins crystal structures (1BQH-2.8 Š; 1GC1-2.5 Š; 1YGR-2.9 Š; 1YGR-2.7 Š) were obtained from RCSB Protein Bank. The crystal structure of CD8 (PDB: 1BQH) and CD4 (PDB: 1GC1) glycoprotein was reported to complex with NAG and NDG; NAG, NDG, and α-L-fucose, respectively. Another immune receptors such as CD45 and CD28 (PDB: 1YGR and 1YJD) were found in complex with MET, TYR, and NAG, respectively. Protein preprocess and ionization steps were executed to receptors molecule, a crucial step to the correct geometry of receptors.

Ligand library

The tested compounds preparations highlighting energy minima were completed using least square OPLS_2005 force field. The conformers were too generated and filtered to their energy minima with probable state creation at pH 7 ± 2.0.

Grid generation and docking calculation

The sitemap option was employed (immune proteins) to generate the possible binding site for hydrophobic, hydrophilic, and H-bond donor/acceptor regions. Extra precision (XP) Glide docking was employed and finally docking pose examined through XP Visualizer, indicating possible interactions of the tested entities with the diverse residues of immune receptors.

   Results and Discussion Top

The ranking of screened pyrethroid derivatives was evaluated by the binding energy of the ligands. [Table 1] reveals that fenvalerate (−5.534 kcal/mol) possess a higher binding affinity with CD8 (1BQH) immune receptor while [Table 2] and [Table 3] show a higher binding affinity for fluvalinate (−4.644 kcal/mol and −4.431 kcal/mol) against CD4 (1GC1) and CD45 (1YGR) immune receptor, correspondingly. Moreover, cypermethrin (−3.535 kcal/mol) showed greater glide score toward CD28 (1YJD) immune protein [Table 4]. The estimated free energy of binding should not be used as an only criterion for the selection of top hits but visual inspections of docking pose can too serve as an important predecessor for enhancing accomplishment of our docking screening results.[28] The best hit ligands were taken into the account for further toxicity prediction in rodents using ProTOX online tool. [Table 5] results also illustrated that fenvalerate, fluvalinate, and cypermethrin have probable toxicity targets such as AOFA: Amine oxidase (flavin-containing) A and PGH1: Prostaglandin G/H synthase 1, respectively.
Table 1: Glide score, number of hydrogen bonds, and residues involved in hydrogen bonding interaction of pyrethroids with immune receptor (PDB: 1 BQH)

Click here to view
Table 2: Glide score, number of hydrogen bonds, and residues involved in hydrogen bonding interaction of pyrethroids with immune receptor (PDB: 1GC1)

Click here to view
Table 3: Glide score, number of hydrogen bonds, and residues involved in hydrogen bonding interaction of pyrethroids with immune receptor (PDB: 1 YGR)

Click here to view
Table 4: Glide score, number of hydrogen bonds, and residues involved in hydrogen bonding interaction of pyrethroids with immune receptor (PDB: 1 YJD)

Click here to view
Table 5: Toxicity prediction of top-ranked glide score pyrethroids using ProTOX tool

Click here to view

Apex-graded pyrethroid hits

CD8 (PDB: 1BQH) immune receptor


Fenvalerate has positioned the apex hit toward CD8 receptor as indicated in [Table 1]. This ligand was bound strongly to the binding site by nitrile group (CN) hydrogen bonding interactions with Asn70. Moreover, Tyr159, Leu156, Tyr45, Tyr7, Tyr22, Val9, Val97, Tyr116, and Phe74 were concerned in the hydrophobic interactions. It also showed two π–π stacking interactions with Tyr7 and Tyr159.


Cypermethrin has engaged hydrophobic in pocket of Phe74, Val97, Val9, Tyr116, Tyr22, Tyr7, Tyr159, Leu5, Trp167, Cys164, Tyr167, Tyr59, and Tyr45, and moreover, two hydrogen bonds between Asn70 with CN group and Trp159 with the oxygen of phenyl-linked ring are also studied. Interestingly, ligand phenyl ring illustrated π–cation, π–π interactions with Lys66 and Trp167.


The hydrophobic surface was occupied via Leu156, Val97, Tyr22, Val9, Phe74, Tyr159, Tyr7, Tyr167, Leu5, Tyr171, Cys164, Tyr59, and Tyr45 residues. Furthermore, Tyr159 had involved in hydrogen bonding interaction while π–cation (Lys166) and π–π interactions (Trp167) were also observed.

CD4 (PDB: 1GC1) immune receptor


Overall, fluvalinate resulted in the top most capable hit with a CD4 immune receptor. This compound has revealed promising hydrogen bonding of CN and NH groups with Thr236 while oxygen (other phenyl ring linked) moiety against Phe277. The hydrophobic interactions were also examined (Val275, Trp96, Phe233, Cys239, Pro238, and Phe277).


The compound was capable of wide-ranging hydrophobic bonding with Ile232, Phe353, Val271, Pro238, Phe233, Phe277, Cys239, Val275, and Trp96. Conspicuously, one hydrogen bond of CN group with Lys348 and π–π stacking with Phe277 was also analyzed.


Tralomethrin was linked with the binding pocket via hydrogen bonding interactions of CN and carbonyl group with Lys348. Interestingly, Val271, Phe353, Ile272, Phe277, Phe233, Pro238, and Cys239 were involved in hydrophobic interactions while π–π interaction was also seen.

CD45 (PDB: 1YGR) immune receptor


This compound was resulted as top strike and involved in hydrophobic interaction with Tyr658, Val659, Val832, Ile661, Leu869, and Ala830 along with hydrogen bonding interactions with Arg657 (-NH group) and Arg734(C=O group).


This ranked entity was minimally able of hydrophobic interactions such as Ile661, Tyr658, Phe632, Val873, Ala830, Leu867, and Val832 with a CD45 immune receptor.


Fenvalerate was capable of H-bonding interaction of CN group with Lys736 residue. In addition, Val832, Ala830, Leu869, Tyr658, and Ile661 residues were also occupied in hydrophobic interactions.

CD28 (PDB: 1YJD) immune receptor


This apex hit compound has revealed two hydrogen bonding interactions with Gln59 (C=O group) and Asn53 (oxygen-phenyl linked).


The different amino acid residues such as Tyr61, Tyr51, Tyr54, and Tyr100 had resulted in hydrophobic interactions while C=O group and oxygen (phenyl ring linked) were too involved in hydrogen bonding interactions with Gln59 and Asn53, respectively. Conspicuously, a π–π interaction with Tyr54 was too seen.


This compound was an outcome in good hydrogen bonding interactions of C=O group and oxygen (phenyl ring linked) with Asn53 and Gln56, consequently. Moreover, flucythrinate showed hydrophobic interactions with different receptor residues such as Tyr51, Tyr54, and Tyr100 [Figure 1], [Figure 2], [Figure 3], [Figure 4].
Figure 1: Binding interactions of Type 2 pyrethroid (fenvalerate) with CD8 immune cell receptor (PDB: 1BQH)

Click here to view
Figure 2: Binding interactions of Type 2 pyrethroid (fluvalinate) with CD4 immune cell receptor (PDB: 1GC1)

Click here to view
Figure 3: Binding interactions of Type 2 pyrethroid (fluvalinate) with CD45 immune cell receptor (PDB: 1YGR)

Click here to view
Figure 4: Binding interactions of Type 2 pyrethroid (cypermethrin) with CD28 immune cell receptor (PDB: 1YJD)

Click here to view

Consequences of the interaction of pyrethroid insecticides toward immune cell receptor

Remarkably, due to high sensitivity, the immune system is most easily concern with the toxicity of pyrethroids. Previous studies have shown that any alteration in the immune system serves as a vital predecessor for making an individual immunocompromised and more susceptible to serious health hazards.[29] The current findings have revealed that Type 2 pyrethroids exposed good interactions with immune cell proteins which may be linked to different pathways such as no alteration, autoimmune diseases, declined in the immune response, and development of hypersensitivity reactions [Figure 5].
Figure 5: Probable immune reactions of pyrethroids with immune receptors

Click here to view

   Conclusion Top

Type 2 pyrethroids such as fenvalerate (1BQH), fluvalinate (1GC1 and 1YGR), and cypermethrin (1YJD) have outcome in apex-graded immunotoxicity ligands. Interestingly, toxicity of top-ranked docked pyrethroids has also been analyzed with LD50 value plus possible toxic targets. Although pyrethroids have become popular due to their promising applications in different fields, current in-silico immunotoxic assessments of type 2 pyrethroids have put a big question mark pertaining to human health issues. This tool may further quite helpful for future researchers to validate the results with wet laboratory experiments.


The authors are enormously obliged to the Head, Department of Pharmaceutical Sciences & Technology for providing the software facility to carryout out our Docking work.

Financial support and sponsorship

We feel greatly privileged to UGC, New Delhi for their financial assistance in the form of UGC- BSR fellowship (F.7-36/2007).

Conflicts of interest

There are no conflicts of interest.

   References Top

Yonar ME, Sakin F. Ameliorative effect of lycopene on antioxidant status in Cyprinus carpio during pyrethroid deltamethrin exposure. Pestic Biochem Physiol 2011;99:226-1.  Back to cited text no. 1
Sondhia S, Dubey RP. Determination of terminal residues of butachlor and pendimethalin in onion. Pestic Res J 2006;18:85-6.  Back to cited text no. 2
Sondhia S, Singhai B. Persistence of sulfosulfuron under wheat cropping system. Bull Environ Contam Toxicol 2008;80:423-7.  Back to cited text no. 3
Laskowski DA. Physical and chemical properties of pyrethroids. Reviews of Environmental Contamination and Toxicology. New York: Springer-Verlag; 2002. p. 49-70.  Back to cited text no. 4
Saillenfait AM, Ndiaye D, Sabaté JP. Pyrethroids: Exposure and health effects – An update. Int J Hyg Environ Health 2015;218:281-92.  Back to cited text no. 5
Gammon DW, Lawrence LJ, Casida JE. Pyrethroid toxicology: Protective effects of diazepam and phenobarbital in the mouse and the cockroach. Toxicol Appl Pharmacol 1982;66:290-6.  Back to cited text no. 6
Gray AJ. Pyrethroid structure-toxicity relationships in mammals. Neurotoxicology 1985;6:127-37.  Back to cited text no. 7
Verschoyle RD, Aldridge WN. Structure-activity relationships of some pyrethroids in rats. Arch Toxicol 1980;45:325-9.  Back to cited text no. 8
Ray DE. The contrasting actions of two pyrethroids (deltamethrin and cismethrin) in the rat. Neurobehav Toxicol Teratol 1982;4:801-4.  Back to cited text no. 9
Miller TA, Salgado VL. The mode of action of pyrethroid on insects. In: Leahy JP, editor. The Pyrethroid Insecticide. London: Taylor and Francis; 1985. p. 43-7.  Back to cited text no. 10
Salgado VL, Irving SN, Miller TA. Depolarization of motor nerve terminals by pyrethroids in susceptible and kdr-resistant house flies. Pestic Biochem Physiol 1983;20:100-4.  Back to cited text no. 11
Salgado VL, Irving SN, Miller TA. The importance of nerve terminal depolarization in pyrethroid poisoning of insects. Pestic Biochem Physiol 1983;20:169-2.  Back to cited text no. 12
Bradbury SP, Coats JR. Comparative toxicology of the pyrethroid insecticides. Reviews of Environmental Contamination and Toxicology. New York: Springer; 1989. p. 133-7.  Back to cited text no. 13
Maund SJ, Hamer MJ, Wariton JS. Aquatic toxicology of the pyrethroid insecticide lambda cyhalothrin; consideration for higher-tier aquatic risk assessment. Pestic Sci 1998;54:408-7.  Back to cited text no. 14
Di Muccio A, Pelosi P, Barbini DA, Generali T, Ausili A, Vergori F. Selective extraction of pyrethroid pesticide residues from milk by solid-matrix dispersion. J Chromatogr A 1997;765:51-60.  Back to cited text no. 15
WHO. Deltamethrin. Health and Safety Guide No. 30. Geneva: WHO; 1989. Available from: http://www.inchem.org/documents/ehc/ehc/ehc97.htmArticle. [Last accessed on 2016 Oct 17].  Back to cited text no. 16
Barlow SM, Sullivan FM, Lines J. Risk assessment of the use of deltamethrin on bednets for the prevention of malaria. Food Chem Toxicol 2001;39:407-22.  Back to cited text no. 17
Chargui I, Grissa I, Bensassi F, Hrira MY, Haouem S, Haouas Z, et al. Oxidative stress, biochemical and histopathological alterations in the liver and kidney of female rats exposed to low doses of deltamethrin (DM): A molecular assessment. Biomed Environ Sci 2012;25:672-83.  Back to cited text no. 18
Muhammad M, Hossain J, Richardson R. Mechanism of pyrethroid pesticide – Induced apoptosis: Role of calpain and the ER stress pathway. Toxicol Sci 2011;122:512-5.  Back to cited text no. 19
Mestres R, Mestres G. Deltamethrin: Uses and environmental safety. Rev Environ Contam Toxicol 1992;124:1-18.  Back to cited text no. 20
Food and Agriculture Organization of the United Nations (FAO/WHO). Pesticide Residues in Food-1998 Evaluations. Part II. Toxicological. [WHO/PCS/99/18]. Geneva: World Health Organization; 1999.  Back to cited text no. 21
Luo D, Lu D, Yao R, Li P, Huo X, Li A, et al. Alphamethrin-impregnated bed nets for malaria and mosquito control in China. Trans R Soc Trop Med Hyg 1994;88:625-8.  Back to cited text no. 22
Jana-Kara BR, Jihullah WA, Shahi B, Dev V, Curtis CF, Sharma VP. Deltamethrin impregnated bednets against Anopheles minimus transmitted malaria in Assam, India. J Trop Med Hyg 1995;98:73-83.  Back to cited text no. 23
Moyou-Somo R, Lehman LG, Awahmukalah S, Ayuk Enyong P. Deltamethrin impregnated bednets for the control of urban malaria in Kumba Town, South-West Province of Cameroon. J Trop Med Hyg 1995;98:319-24.  Back to cited text no. 24
Hallenbeck WH, Cunningham-Burns KM. Pesticides and Human Health. New York: Springer-Verlag; 1985.  Back to cited text no. 25
Kumar A, Sasmal D, Sharma N. Deltamethrin induced an apoptogenic signalling pathway in murine thymocytes: Exploring the molecular mechanism. J Appl Toxicol 2014;34:1303-10.  Back to cited text no. 26
Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R. ProTox: A web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Res 2014;42:W53-8.  Back to cited text no. 27
Kumar M, Dagar V, Gupta VK, Sharma A. In silico docking studies of bioactive natural plant products as putative DHFR antagonists. Med Chem Res 2014;23:810-7.  Back to cited text no. 28
Kumar A, Bhaskar A, Chandra S, Sasmal D, Mukhopadhyay KM, Sharma N, et al. Mechanism of deltamethrin induced immunotoxicity: Current and future perspectives. Recept Clin Investig 2015;2:578-85.  Back to cited text no. 29


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

This article has been cited by
1 Screening cyclooxygenase-2 inhibitors from Allium sativum L. compounds: in silico approach
Morteza Sadeghi, Mehran Miroliaei, Fatemeh Fateminasab, Mohammad Moradi
Journal of Molecular Modeling. 2022; 28(1)
[Pubmed] | [DOI]
2 Potential Therapeutic Candidates against Chlamydia pneumonia Discovered and Developed In Silico Using Core Proteomics and Molecular Docking and Simulation-Based Approaches
Roqayah H. Kadi, Khadijah A. Altammar, Mohamed M. Hassan, Abdullah F. Shater, Fayez M. Saleh, Hattan Gattan, Bassam M. Al-ahmadi, Qwait AlGabbani, Zuhair M. Mohammedsaleh
International Journal of Environmental Research and Public Health. 2022; 19(12): 7306
[Pubmed] | [DOI]
3 Computational identification of natural product leads that inhibit mast cell chymase: an exclusive plausible treatment for Japanese encephalitis
Kamal Kant, Ravi Rawat, Vipin Bhati, Shailesh Bhosale, Dalchand Sharma, Subham Banerjee, Anoop Kumar
Journal of Biomolecular Structure and Dynamics. 2021; 39(4): 1203
[Pubmed] | [DOI]
4 Cypermethrin induces Sertoli cell apoptosis through mitochondrial pathway associated with calcium
Heng-Xue Wang, Rui Zhang, Zheng Li, Lu-Shan Wang, Yue Yu, Qi Wang, Zhen Ding, Jin-Peng Zhang, Mei-Rong Zhang, Li-Chun Xu
Toxicology Research. 2021; 10(4): 742
[Pubmed] | [DOI]
5 Enhanced mosquitocidal efficacy of pyrethroid insecticides by nanometric emulsion preparation towards Culex pipiens larvae with biochemical and molecular docking studies
Nehad E. M. Taktak, Mohamed E. I. Badawy, Osama M. Awad, Nadia E. Abou El-Ela, Salwa M. Abdallah
Journal of the Egyptian Public Health Association. 2021; 96(1)
[Pubmed] | [DOI]
6 Virtual screening for potential inhibitors of (1,3)-D-glucan synthase as drug candidates against fungal cell wall
Zinat Farhadi, Tayebeh Farhadi, Seyed MohammadReza Hashemian
Journal of Drug Assessment. 2020; 9(1): 52
[Pubmed] | [DOI]


    Similar in PUBMED
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Materials and Me...
    Results and Disc...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded171    
    Comments [Add]    
    Cited by others 6    

Recommend this journal