Preventive and Therapeutic Vaccines against Human Papillomaviruses Associated Cervical Cancers
Nayereh
Khadem Ghaebi
Women’s Health Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Zahra
Meshkat
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
text
article
2012
eng
Cervical cancer is, globally known to be, one of the most common cancers among women especially indeveloping countries. More than 90% of cervical cancers are associated with high-risk humanpapillomaviruses (HPVs) particularly HPV types 16 and 18. Two major strategies have been developed forprevention and treatment of cervical cancer and other HPV-associated malignancies; the first one is based onHPV virus-like particles (VLPs) containing HPV structural proteins. VLP based vaccines can inducegenotype specific virus neutralizing antibodies for preventing HPV infections. The other strategy is based onHPV early genes especially E6 and E7 for eliminating the established HPV infections; therefore they areclassified as HPV therapeutic vaccines. This article reviews the preventive and therapeutic vaccines againstHPV infections and cervical cancer.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
585
601
https://ijbms.mums.ac.ir/article_4828_f2fdef9e9493adee58c6809a9c130e92.pdf
dx.doi.org/10.22038/ijbms.2012.4828
Plasma Nitric Oxide and Acute Phase Proteins after Moderate and Prolonged Exercises
Akinwande
Kazeem
Department of Chemical Pathology and Immunology, Faculty of Basic Medical Sciences, Olabisi Onabanjo
University, Ago-iwoye, Nigeria
author
Akinosun
Olubayo
Department of Chemical Pathology and Immunology, University College Hospital, Ibadan, Nigeria
author
Arinola
Ganiyu
Department of Chemical Pathology and Immunology, University College Hospital, Ibadan, Nigeria
author
text
article
2012
eng
Objective(s)The aim of this study was to evaluate plasma levels of nitric oxide (NO) and certain acute phase proteins(caeruloplasmin, transferrin, haptoglobin, C-reactive protein) in Nigerian subjects after short and prolonged exercises.Materials and MethodsA total of 57 subjects (34 males and 23 females) between ages of 19 and 45 years participated in this study and weredivided into three groups: Group 1 (Prolonged exercise) consisted of footballers (10 males and 9 females) who playedfootball for at least two hrs daily; Group II (Moderate exercise) consisted of individuals (14 males and 5 females) whoplayed football for 30 min 3 times a week; Group III (10 males and 9 females) were sedentary workers, who rarely hadany form of physical exercise. The plasma samples were assayed for NO, C-reactive protein (CRP), caeruloplasmin,haptoglobin, and transferrin using spectrophotometer and immunoplates. Statistical analysis was done using thestudent’s-t-test.ResultsThe result showed that there was a significant reduction in the level of NO in prolonged exercise (P<0.05) whencompared with control subjects while the increase of NO in subjects with moderate exercise was not statisticallysignificant when compared with control subjects. C-reactive protein was significantly increased (P< 0.01) whiletransferrin and haptoglobin were significantly reduced (P< 0.001 and P< 0.01 respectively) in subjects with prolongedexercise when compared with control subjects. In moderate exercise, haptoglobin was significantly reduced (P< 0.05)while the reduction in the levels of caeruloplasmin and transferrin was not statistically significant when compared withcontrol subjects. The mean level of CRP was significantly raised in prolonged exercise compared with controls ormoderate exercise while the level of caeruloplasmin was significantly reduced in prolonged exercise compared withcontrols or moderate exercise.ConclusionModerate exercises should be encouraged.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
602
607
https://ijbms.mums.ac.ir/article_4829_cc83071b4451964629963e6b08f6f7d7.pdf
dx.doi.org/10.22038/ijbms.2012.4829
Theophylline-Ethylcellulose Microparticles: Screening of the Process and Formulation Variables for Preparation of Sustained Release Particles
Mitra
Jelvehgari
Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
author
Siavoush
Dastmalch
Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
author
Nazila
Derafshi
Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
author
text
article
2012
eng
Objective(s)
The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of
theophylline using ethylcellulose as the retardant material with high entrapment efficiency.
Materials and Methods
Microspheres were prepared by water-in-oil-in-oil (W/O1/O2) emulsion-solvent diffusion (ESD). A mixed
solvent system consisting of acetonitrile and dichloromethane in a 1:1 ratio and light liquid paraffin were
chosen as primary and secondary oil phases, respectively. In the current study formulations with different
drug/polymer ratios were prepared and characterized by drug loading, loading efficiency, scanning electron
microscopy (SEM), X-ray diffraction (XRD), Fourier Transform infrared spectroscopy (FTIR) and
differential scanning calorimetry (DSC).
Results
The best drug to polymer ratio was 0.5:1 (F2 formulation). F2 Formulation showed 29.53% of entrapment,
loading efficiency of 88.59%, and mean particle size of 757.01 μm. SEM studies showed that the
microspheres were spherical. FTIR, SEM, XRD and DSC showed that drug in the microspheres was stable
and revealed crystallinity form.
Conclusion
The results showed that, generally, an increase in the ratio of drug to polymer resulted in a reduction in the
release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The release of
theophylline was found to be diffusion controlled and was influenced by the drug to polymer ratio, loading
efficiency, and particle size. The in vitro release profile could be modified by changing various processing
and formulation parameters (as stirring rate, the volume of dispersing medium, and non-solvent
concentration) to give a controlled release of drug from the microparticules.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
608
622
https://ijbms.mums.ac.ir/article_4830_77ea64fec1f31e163885d5b8e16a2ce8.pdf
dx.doi.org/10.22038/ijbms.2012.4830
The Ultrastructural Changes of the Sertoli and Leydig Cells Following Streptozotocin Induced Diabetes
Davoud
Kianifard
Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
author
Rajab Ali
Sadrkhanlou
Department of Basic Sciences, Histology and Embryology Sections, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
author
Shapour
Hasanzadeh
Department of Basic Sciences, Histology and Embryology Sections, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
author
text
article
2012
eng
Objective(s)
This investigation was conducted to evaluate the effects of diabetes on the structure and function of testicular tissue.
Materials and Methods
Diabetes was induced in male adult rats by a single intraperitoneal injection of streptozotocin. Body and testicular weight, hormonal analyses, histological and ultrastructural analyses were measured.
Results
The body and testicular weights were dropped significantly (P< 0.05) in diabetic rats in comparison with control rats. On the other hand, in diabetic rats, the blood glucose level increased significantly (P< 0.05). The blood plasma levels of testosterone, 17-β estradiol, progesterone, FSH and LH were reduced in diabetic rats. Histomorphological studies were revealed reduction in diameter of seminiferous tubules and germinal epithelium height, edema in interstitial tissue, germ cell depletion, decrease in cellular population and activity with disruption of spermatogenesis in diabetic rats. Ultrastructural study showed the mitochondrial change and reduction of smooth endoplasmic reticulum in Sertoli and presence of lipid droplets in Leydig cells of diabetic rat’s testes.
Conclusion
The results of the present study confirmed that, the ultrastructural changes of Sertoli and Leydig cells, brought about by streptozotocin induced diabetes, because of the alterations in pituitary gonadotropins, and these changes influence the normal spermatogenesis in rats.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
623
635
https://ijbms.mums.ac.ir/article_4831_5e4ad5635c2f4c42fb7b6693823b6e56.pdf
dx.doi.org/10.22038/ijbms.2012.4831
Investigation of Toxic Metals in the Tobacco of Different Iranian Cigarette Brands and Related Health Issues
Alireza
Pourkhabbaz
Department of Environmental Science, Agriculture Faculty, Birjand University, Birjand, Iran
author
Hamidreza
Pourkhabbaz
Department of Environmental Science, Natural Resources Faculty, Behbahan University, Behbahan, Iran
author
text
article
2012
eng
Objective(s)
The primary objective of this study was to determine whether local and imported cigarette brands used in Iran, have elevated levels of metals or not. The produced data of cigarette brands are compared both with each other and with the existing brands in different countries.
Materials and Methods
In present study, nineteen various cigarettes brands were randomly purchased from the commercially available cigarettes in Iranian market (Birjand city) including local Iranian branded and imported cigarettes. All samples were analyzed for heavy metals, viz. Cd, ,Cu ,Co Ni, Zn and Pb by graphite furnace atomic absorption spectrophotometer after microwave-assisted wet digestion method with nitric and perchloric acids.
Results
The observed average metals concentrations for cadmium in all cigarette brands was 2.71 and ranging 1.76 to 3.20, copper 9.7 (5.18-17.6), cobalt 4.42 with range of 2.57-6.49, nickel 17.93 (10.0-30), zinc 27.02 (18.1-42.2) and value for lead was 2.07 with range of 1.05 to 3.10 (µg/g dry weight) and mean metals content per cigarette was also measured. The produced data of imported and local cigarette brands are discussed and compared together and with studies from elsewhere.
Conclusion
The investigation may confirm that the level of metal contents in Iranian cigarettes is similar to the other parts of the world. However, the concentration of these metals was slightly higher in comparison with other investigation.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
636
644
https://ijbms.mums.ac.ir/article_4832_9c45d6f817a528e40895cb7c78a33dc7.pdf
dx.doi.org/10.22038/ijbms.2012.4832
Safety Assessment of Ocimum Basilicum Hydroalcoholic Extract in Wistar Rats: Acute and Subchronic Toxicity Studies
Hamid Reza
Rasekh
School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Leila
Hosseinzadeh
School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
author
Soghra
Mehri
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mohammad
Kamli-Nejad
School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Majid
Aslani
School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
Farahnaz
Tanbakoosazan
School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
author
text
article
2012
eng
Objective(s)
Ocimum basilicum L. is widely used in folk medicine of many countries including Iran. Both O. basilicum and its oil extract have received considerable attention for their potential medicinal properties, but there are a few reports about possible toxicity of this plant. Therefore, in the present study, acute and subchronic toxicity of O. basilicum hydroalcohlic extract have been evaluated in Wistar rats.
Materials and Methods
For the acute toxicity assessment, five groups of 10 animals (5 male, 5 female) received four different single dose of extract orally, the animals were, then, kept under observation for 14 days. For subchronic toxicity, the animals were divided into four groups (5 male, 5 female) and were gavaged daily by 50, 200 and 500 mg/kg of extract. Mortality, clinical signs, body weight changes, food and water consumption, and hematological and biochemical parameters were monitored during the study period. On the 45th day, animals were sacrificed and gross findings, weight of liver and left kidney and liver histological markers were assessed.
Results
The results of acute study indicated that LD50 of O. basilicum is higher than 5 mg/kg. In subchronic study, no adverse effects were observed on serum parameters in male and female rats. The hematological results showed a reduction in the hematocrit, platelets and RBC in both sexes. No abnormalities were observed in other parameters.
Conclusion
Based on the results of this study, present data suggest that hematologic system could serve as a target organ in oral toxicity of this plant.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
645
653
https://ijbms.mums.ac.ir/article_4833_9f71d6cb80db080ef5e6005ecc49391d.pdf
dx.doi.org/10.22038/ijbms.2012.4833
The Prevalence of TEM and SHV Genes among Extended-Spectrum Beta-Lactamases Producing Escherichia Coli and Klebsiella Pneumoniae
Fatemeh
Riyahi Zaniani
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Zahra
Meshkat
Women's Health Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mahboubeh
Naderi Nasab
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mehrangiz
Khaje-Karamadini
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Kiarash
Ghazvini
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Abdolrahim
Rezaee
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Habibollah
Esmaily
Department of Biostatistics in Health Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
author
1Maryam Sadat
Nabavinia
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
Mahboubeh
Darban Hoseini
Microbiology and Virology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
author
text
article
2012
eng
Objective(s)
Production of extended-spectrum beta-lactamases (ESBLs) by enteric bacteria continues to be a major problem in hospitals and community. ESBLs producing bacteria cause many serious infections including urinary tract infections, peritonitis, cholangitis and intra-abdominal abscess. The aim of this study was to determine the prevalence of ESBLs producing Escherichia coli and Klebsiella pneumoniae bacteria isolated from clinical samples of patients attending Imam Reza and Ghaem University Hospitals, Mashhad, Northeast of Iran.
Materials and Methods
During 2009 and 2010, 82 strains of E. coli and 78 strains of K. pneumoniae were isolated from out-patients and hospitalized patients and they were examined by Oxoid combination disk test and PCR methods.
Results
We found that 43.9% of E. coli and 56.1% of K. pneumoniae produced ESBLs. The frequency of SHV and TEM among the ESBLs producing isolates were 14.4% and 20.6%, respectively. Ratios of ESBLs positive isolates from out-patients to hospitalized patients were 24/33.
Conclusion
This study shows that the prevalence of ESBLs producing E. coli and K. pneumoniae is high in both study groups (out-patients and hospitalized patients). Therefore it seems that continuous surveillance is essential to monitor the ESBLs producing microorganisms in hospitals and community.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
654
660
https://ijbms.mums.ac.ir/article_4834_d70215a6fe97d02e2e06a9c7e0971ffe.pdf
dx.doi.org/10.22038/ijbms.2012.4834
Molecular Identification of Rare Clinical Mycobacteria by Application of 16S-23S Spacer Region Sequencing
Hasan
Shojaei
Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
author
Abodolrazagh
Hashemi
Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
author
Parvin
Heidarieh
Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Iran
author
Fazel
Pourahmad
Microbiology Group, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
author
Abass
Daei Naser
School of Veterinary Medicine, Ilam University, Ilam, Iran
author
text
article
2012
eng
Objective(s)
In addition to several molecular methods and in particular 16S rDNA analysis, the application of a more discriminatory genetic marker, i.e., 16S-23S internal transcribed spacer gene sequence has had a great impact on identification and classification of mycobacteria. In the current study we aimed to apply this sequencing power to conclusive identification of some Iranian clinical strains of mycobacteria.
Materials and Methods
The test strains consisted of nineteen mycobacterial isolates which were initially identified by the use of conventional phenotypic techniques and molecular methods and subjected to further definitive identification using the 16S-23S internal transcribed spacer gene sequencing.
Results
Out of 19 studied strains, 7 isolates were found to be rapidly growing and 12 isolates as slowly growing mycobacteria. With the exception of one isolate, i.e., the isolate HNTM87, which yielded a distinct ITS sequence incomparable with all previously identified mycobacteria, the remaining isolates produced the sequences similar to the established mycobacteria and were clearly identified and differentiated from closely related taxa. A phylogenetic tree based on maximum parsimony analysis of 16S-23S internal transcribed spacer gene sequences constructed showing the relatedness of Iranian clinical isolates with the closely related type species of mycobacteria.
Conclusion
This study showed that the 16S-23S internal transcribed spacer gene of the genus Mycobacterium exhibits a high variation which is of value for discriminating closely related taxa and could be used independently or in combination with 16S rDNA sequencing to delineate the true identity of rare mycobacterial species.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
661
668
https://ijbms.mums.ac.ir/article_4835_f851e2cc983dd8d58a317983417a23fe.pdf
dx.doi.org/10.22038/ijbms.2012.4835
Different Expression of Extracellular Signal-Regulated Kinases (ERK) 1/2 and Phospho-Erk Proteins in MBA-MB-231 and MCF-7 Cells after Chemotherapy with Doxorubicin or Docetaxel
Aliakbar
Taherian
Kashan Anatomical Research Centre, Kashan University of Medical Science, Kashan, Iran
author
Tahereh
Mazoochi
Kashan Anatomical Research Centre, Kashan University of Medical Science, Kashan, Iran
author
text
article
2012
eng
Objective(s)
Curative treatment of breast cancer patients using chemotherapy often fails as a result of intrinsic or acquired resistance of the tumor to the drug. ERK is one of the main components of the Ras/Raf/MEK/ERK cascade, which mediates signal from cell surface receptors to transcription factors to regulate different gene expression. In this study, cytotoxicity and the expression of Erk1/2 and phospho-ERK was compared in MDA-MB-231 (ER-) and MCF-7 (ER+) cell lines after treatment with doxorubicin (DOX) or docetaxel (DOCT).
Materials and Methods
Cell cytotoxicity of DOX or DOCT was calculated using MTT assay. Immonofluorescent technique was used to show MDR-1 protein in MDA-MB-231 and MCF-7 cells after treatment with DOX or DOCT. The expression of ERK1/2 and phpspho-ERK was assayed with immunoblotting.
Results
Comparing IC50 values showed that MDA-MB-231 cells are more sensitive than MCF-7 cells to DOX or DOCT. Immonofluorescent results confirmed the expression of MDR-1 in these two cell lines after DOX or DOCT treatment. In MDA-MB-231 cells the expression of ERK1/2 and phospho-ERK was decreased after DOX treatment in a dose-dependent manner. In contrast in MCF-7 cells the expression of ERK1/2 and phospho-ERK was increased after DOX treatment. DOCT treatment demonstrated the same result with less significant differences than DOX.
Conclusion
The heterogeneity seen in cell lines actually reflects the heterogeneity of breast cancers. That is why, patients categorized in one group respond differently to a single treatment. These results emphasize the importance of a more accurate classification and a more specific treatment of breast cancer subtypes.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
669
677
https://ijbms.mums.ac.ir/article_4836_5b130a6ccb2b082e45507524a86837d2.pdf
dx.doi.org/10.22038/ijbms.2012.4836
Prevalence of PER-1- type Extended-Spectrum Beta-Lactamaes in Clinical Strains of Pseudomonas aeruginosa Isolated from Tabriz, Iran
Mohammad Taghi
Akhi
Department of Microbiology, Faculty of Medicine, and *Research Center of Infectious Diseases and Tropical Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
author
Yones
Khalili
Department of Microbiology, Faculty of Medicine, and *Research Center of Infectious Diseases and Tropical Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
author
Reza
Ghottaslou
Department of Microbiology, Faculty of Medicine, and *Research Center of Infectious Diseases and Tropical Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
author
Mohammad
Aghazadeh
Department of Microbiology, Faculty of Medicine, and *Research Center of Infectious Diseases and Tropical Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
author
Mohammad hosein
Seroush Bar Haghi
Department of Microbiology, Faculty of Medicine, and *Research Center of Infectious Diseases and Tropical Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
author
Saber
Yousefi
Department of Clinical Laboratory Sciences, Faculty of Paramedicine, Urmia University of Medical Science
author
text
article
2012
eng
Objective(s) The aim of this study was to investigate the presence of PER-1-type ESBLs in drug resistant Pseudomonas aeruginosa isolates. Materials and Methods During one-year period (2008-2009), following isolation and identification of 56 P. aeruginosa, the E-test method was performed for determination of minimal inhibitory concentration of ceftazidim. The isolates that they had MIC≥16 µg/ml against ceftazidim were used for determination of ESBL-producing by combined disk test (CDT) and double disk synergy test (DDST) methods. Bla PER-1genewas investigated by PCR.P. aeruginosa KOAS was used as positive control. Results Twenty-nine (51.78%) out of fifty six isolates had MIC≥16 µg/ml to ceftazidime, twenty two (75.86%) of them were ESBL producers. Some isolates (27.5%) contained bla PER-1 gene. Conclusion PER-1-type ESBLs producing P.aeruginosa has not been reported previously in Tabriz but there has been a rather high prevalence of it.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
678
682
https://ijbms.mums.ac.ir/article_4837_5c53f606ad6a15dbe1e4636399d9e262.pdf
dx.doi.org/10.22038/ijbms.2012.4837
Mutation Analysis of TP53 Tumor Suppressor Gene in Colorectal Cancer in Patients from Iran (Kerman Province)
Azadeh
Lohrasbi Nejad
Department of Biotechnology, Research Institute for Environmental Sciences, International Centre for Science, High Technology and Environmental Sciences, Kerman, Iran
author
Mohammad Mehdi
Yaghoobi
Department of Biotechnology, Research Institute for Environmental Sciences, International Centre for Science, High Technology and Environmental Sciences, Kerman, Iran
author
text
article
2012
eng
Objective(s)
P53 is an important tumor suppressor, which is mutated in later stages of many cancers and leads to resistance to chemotherapy. The aim of this study was to reveal mutations of TP53 in colorectal cancer in Kerman province.
Materials and Methods
A total of Forty-three colon cancer specimens as paraffin block or fresh tissues, which passed stage IIIA, were selected. Three exons 5, 7 and 8 of P53 were amplified by PCR technique and sequenced directly.
Results
The results showed two deletions at codon 140 and 142 in one tumor sample. GAT→AAT mutation at codon 184, and CGG→TGG mutation at codon 248 were seen in some tumor samples. Some mutations were also observed in middle of intron 7 in some tumor or normal tissues.
Conclusion
Some of those patients with mutation in P53 gene had metastasis in other organs. Therefore, genetic test before chemotherapy is helpful for successful treatment.
Iranian Journal of Basic Medical Sciences
Mashhad University of Medical Sciences
2008-3866
15
v.
1
no.
2012
683
690
https://ijbms.mums.ac.ir/article_4838_7af6b2d7fcd7f8000bf8a570af265ecf.pdf
dx.doi.org/10.22038/ijbms.2012.4838