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Determination of possible genotoxic damage by comet assay in patients under treatment due to depression and anxiety disorders

Yıl 2022, Cilt: 24 Sayı: 2, 594 - 607, 08.07.2022

Öz

Anxiety and depression, very common disorders today, are often seen together. The present study was designed to detect DNA damage in patients diagnosed and treated with depression and anxiety using the Comet test. Thirty-eight patients who received pharmacological therapy (selective serotonin reuptake inhibitors-SSRIs, selective norepinephrine reuptake inhibitors-SNRIs, and antipsychotics) for anxiety and depression and twenty-eight healthy volunteers were included in the study. The comet test was used to evaluate the DNA damage in peripheral blood lymphocytes. As a result, DNA damage in patients in all the treatment groups was higher than those in the control group. It was determined that factors such as age, gender, initial or recurrent diagnosis, SNRI or SSRI use, and fluoxetine use did not cause a statistically significant difference in DNA damage in patient groups. This study revealed that both depression and anxiety disease and the treatment of the disease may present a risk factor for DNA damage.
This study revealed that both depression and anxiety and treatment used may have a risk for DNA damage.

Destekleyen Kurum

Gazi Üniversitesi (BAP)

Proje Numarası

05/2019-28.

Teşekkür

This study has been supported by Gazi University Scientific Research Projects Coordination Unit under grant number 05/2019-28.

Kaynakça

  • World Health Organization (WHO), Depression and other common mental disorders (2017).http://apps.who.int/iris/bitstream/handle /10665/254610/WHO-MSD-MER-2017.2-eng.pdf, (08.09.2021).
  • Alshawwa, I.A., Elkahlout, M., El-Mashharawi, H.Q. and Abu-Naser, S.S., An expert system for depression diagnosis, International Journal of Academic Health and Medical Research, 3, 4, 20-27, (2019).
  • Kroenke, K., Somatic symptoms and depression: a double hurt, The Primary Care Companion to The Journal of Clinical Psychiatry, 7, 4, 148–149, (2005).
  • Gupta, S., Nihalani, N. and Masand, P., Duloxetine: review of its pharmacology, and therapeutic use in depression and other psychiatric disorders, Annals of Clinical Psychiatry, 19, 125-132, (2007).
  • Cakır, S., Genel tıpta depresyon, Klinik Gelişim Dergisi İstanbul Tabip Odası, Süreli Bilimsel Yayını, 22, 461-464, (2009).
  • Annagür, B. and Tamam, L., Psychıatric disorder comorbidity in patients with major depression, Anatolian Journal of Clinical Investigation, 4, 2, 111-117, (2010).
  • Kessler, R.C., Berglund, P. and Demler, O., Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national Comorbidity survey replication, Archives Of General Psychiatry, 62, 593-602, (2005).
  • Karamustafalıoglu, O. and Yumrukca H., Depression and anxiety disorders, Medical Bulletin of Sisli Etfal Hospital, 45, 65-74, (2011).
  • Ingunn, R., Stian, L., Tricia L. L. and Bernhard, W., Developmental course of anxiety and depression from adolescence to young adulthood in a prospective Norwegian clinical cohort, European Child & Adolescent Psychiatry, 27, 1413–1423, (2008).
  • Saatcioglu, O., Yaygın anksiyete bozukluğunun tedavisi ve yeni yaklaşımlar, Bulletin of Clinical Psychopharmacology, 11, 1, (2001).
  • Andrews, G., Bell, C., Boyce P., Gale, C., Lampe, L., Marvat, O., Rapee, R. and Wilkins, G., Royal Australian and New Zealand college of psychiatrists clinical practice guidelines for the treatment of panic disorder, social anxiety disorder and generalised anxiety disorder, Australian & New Zealand Journal of Psychiatry, 52, 12, 1109-1172, (2018).
  • Baldwin, D., Generalized anxiety disorder in adults: epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis, (2018).https: //www.uptodate.com/contents/generalized-anxiety-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis, (04.09.2021).
  • McArt, D.G., McKerr, G., Saetzler, K., Howard, C.V., Downes, C.S. and Wasson, G.R., Comet sensitivity in assessing DNA damage and repair in different cell cycle stages, Mutagenesis, 25, 3, 299–303, (2010).
  • Möller, H.J., Bitter, I., Bobes, J., Fountoulakis, K., Höschl, C. and Kasper, S., Position statement of the european psychiatric association (EPA) on the value of antidepressants in the treatment of unipolar depression, European Psychiatry, 27, 114-128, (2012).
  • Rawat, G., Urs, A.B., Chakravarti, A. and Kumar, P., Evaluation of DNA damage in peripheral blood leukocytes in oral potentially malignant and malignant disorders by comet assay, Clinical Cancer Investigation Journal, 7, 2, 50-55, (2018).
  • Niu, C., Wang, C., Wu, G., Yang, J., Wen, Y., Meng, S., Lin, X., Pang, X. and An, L., Toxic effects of the emamectin benzoate exposure on cultured human bronchial epithelial (16HBE) cells, Environmental Pollution, 257, (2020).
  • Wang, P., Wan, R., Huo, W., Dong, H., Chang, Z. and Xia, X., Cytotoxicity, genotoxicity, oxidative stress and apoptosis in HepG2 cells induced by the imidazole ionic liquid 1-dodecyl-3-methylimidazolium chloride, Environmental Toxicology, 35, 6, 665-672, (2020).
  • Andreazza, A.C., Frey, B.N., Erdtmann, B., Salvador, M., Rombaldi, F., Santin, A., Gonçalves, C.A. and Kapczinski, F., DNA damage in bipolar disorder, Psychiatry Research, 153, 27-32, (2007).
  • Reed, L., Jarvis, IWH., Phillips, DH. and Arlt, VM., Deletion of cytochrome P450 oxidoreductase enhances metabolism and DNA adduct formation of benzo[a]pyrene in Hepa1c1c7 cells, Mutagenesis, 34, 5-6, 413-420, (2019).
  • Zeid, E.H.A., El Sharkawy, N.I., Moustafa, G.G., Anver, A.M. and Al Nady, A.G., The palliative effect of camel milk on hepatic CYP1A1 gene expression and DNA damage induced by fenpropathrin oral intoxication in male rats, Ecotoxicology and Environmental Safety, 207, 111296, (2021).
  • Benhusein G.M., Mutch E., Aburawi S. and Williams, F.M., Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay, Libyan Journal of Medicine, 13, 5, (2010).
  • Collins, A.R., Measuring oxidative damage to DNA and its repair with the comet assay, Biochimica et Biophysica Acta, 1840, 794–800, (2014).
  • Yuzbasıoglu, D., Yılmaz, A.E. and Unal, F., Antidepresan ilaçlar ve genotoksisite, TUBAV Journal of Science, 9, 1, 17-28, (2016).
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  • Solek, P., Koszla, O., Mytych, J., Badura, J., Chelminiak, Z., Cuprys, M., Fraczek, J., Tabecka-Lonczynska, A. and Koziorowski, M., Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies, Apoptosis, 24, 9-10,773–784, (2019).
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Depresyon ve anksiyete tedavisi gören hastalarda comet testi kullanılarak olası genotoksik hasarın belirlenmesi

Yıl 2022, Cilt: 24 Sayı: 2, 594 - 607, 08.07.2022

Öz

Anksiyete ve depresyon, günümüzde çok sık görülen rahatsızlıklar olup sıklıkla birlikte görülmektedir. Bu çalışma, comet testi kullanılarak depresyon ve anksiyete bozukluğu tanısı alan ve tedavi edilen hastalarda DNA hasarını ölçmek için tasarlanmıştır. Anksiyete ve depresyon nedeniyle farmakolojik tedavi (seçici serotonin geri alım inhibitörleri-SSRI'lar, seçici norepinefrin geri alım inhibitörleri-SNRI'lar ve antipsikotikler) alan otuz sekiz hasta ve yirmi sekiz sağlıklı gönüllü çalışmaya dahil edilmiştir. DNA hasarını değerlendirmek için periferal kan lenfositlerinde comet testi kullanılmıştır. Sonuç olarak tedavi gruplarındaki tüm hastalarda DNA hasarı kontrol grubuna kıyasla daha yüksek bulunmuştur. Hasta grubunda yaş, cinsiyet, ilk veya tekrarlayan tanı, SNRI veya SSRI kullanımı ve fluoksetin kullanımı gibi faktörlerin DNA hasarında anlamlı bir farklılığa neden olmadığı bulunmuştur. Bu çalışma, hem depresyon ve anksiyete hastalığının hemde hastalığın tedavisinin DNA hasarı açısından bir risk faktörü oluşturabileceğini ortaya çıkarmıştır.
Bu çalışma, hem depresyon ve anksiyete hastalığının hemde hastalığın tedavisinin DNA hasarı açısından bir risk faktörü oluşturabileceğini ortaya çıkarmıştır.

Proje Numarası

05/2019-28.

Kaynakça

  • World Health Organization (WHO), Depression and other common mental disorders (2017).http://apps.who.int/iris/bitstream/handle /10665/254610/WHO-MSD-MER-2017.2-eng.pdf, (08.09.2021).
  • Alshawwa, I.A., Elkahlout, M., El-Mashharawi, H.Q. and Abu-Naser, S.S., An expert system for depression diagnosis, International Journal of Academic Health and Medical Research, 3, 4, 20-27, (2019).
  • Kroenke, K., Somatic symptoms and depression: a double hurt, The Primary Care Companion to The Journal of Clinical Psychiatry, 7, 4, 148–149, (2005).
  • Gupta, S., Nihalani, N. and Masand, P., Duloxetine: review of its pharmacology, and therapeutic use in depression and other psychiatric disorders, Annals of Clinical Psychiatry, 19, 125-132, (2007).
  • Cakır, S., Genel tıpta depresyon, Klinik Gelişim Dergisi İstanbul Tabip Odası, Süreli Bilimsel Yayını, 22, 461-464, (2009).
  • Annagür, B. and Tamam, L., Psychıatric disorder comorbidity in patients with major depression, Anatolian Journal of Clinical Investigation, 4, 2, 111-117, (2010).
  • Kessler, R.C., Berglund, P. and Demler, O., Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national Comorbidity survey replication, Archives Of General Psychiatry, 62, 593-602, (2005).
  • Karamustafalıoglu, O. and Yumrukca H., Depression and anxiety disorders, Medical Bulletin of Sisli Etfal Hospital, 45, 65-74, (2011).
  • Ingunn, R., Stian, L., Tricia L. L. and Bernhard, W., Developmental course of anxiety and depression from adolescence to young adulthood in a prospective Norwegian clinical cohort, European Child & Adolescent Psychiatry, 27, 1413–1423, (2008).
  • Saatcioglu, O., Yaygın anksiyete bozukluğunun tedavisi ve yeni yaklaşımlar, Bulletin of Clinical Psychopharmacology, 11, 1, (2001).
  • Andrews, G., Bell, C., Boyce P., Gale, C., Lampe, L., Marvat, O., Rapee, R. and Wilkins, G., Royal Australian and New Zealand college of psychiatrists clinical practice guidelines for the treatment of panic disorder, social anxiety disorder and generalised anxiety disorder, Australian & New Zealand Journal of Psychiatry, 52, 12, 1109-1172, (2018).
  • Baldwin, D., Generalized anxiety disorder in adults: epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis, (2018).https: //www.uptodate.com/contents/generalized-anxiety-disorder-in-adults-epidemiology-pathogenesis-clinical-manifestations-course-assessment-and-diagnosis, (04.09.2021).
  • McArt, D.G., McKerr, G., Saetzler, K., Howard, C.V., Downes, C.S. and Wasson, G.R., Comet sensitivity in assessing DNA damage and repair in different cell cycle stages, Mutagenesis, 25, 3, 299–303, (2010).
  • Möller, H.J., Bitter, I., Bobes, J., Fountoulakis, K., Höschl, C. and Kasper, S., Position statement of the european psychiatric association (EPA) on the value of antidepressants in the treatment of unipolar depression, European Psychiatry, 27, 114-128, (2012).
  • Rawat, G., Urs, A.B., Chakravarti, A. and Kumar, P., Evaluation of DNA damage in peripheral blood leukocytes in oral potentially malignant and malignant disorders by comet assay, Clinical Cancer Investigation Journal, 7, 2, 50-55, (2018).
  • Niu, C., Wang, C., Wu, G., Yang, J., Wen, Y., Meng, S., Lin, X., Pang, X. and An, L., Toxic effects of the emamectin benzoate exposure on cultured human bronchial epithelial (16HBE) cells, Environmental Pollution, 257, (2020).
  • Wang, P., Wan, R., Huo, W., Dong, H., Chang, Z. and Xia, X., Cytotoxicity, genotoxicity, oxidative stress and apoptosis in HepG2 cells induced by the imidazole ionic liquid 1-dodecyl-3-methylimidazolium chloride, Environmental Toxicology, 35, 6, 665-672, (2020).
  • Andreazza, A.C., Frey, B.N., Erdtmann, B., Salvador, M., Rombaldi, F., Santin, A., Gonçalves, C.A. and Kapczinski, F., DNA damage in bipolar disorder, Psychiatry Research, 153, 27-32, (2007).
  • Reed, L., Jarvis, IWH., Phillips, DH. and Arlt, VM., Deletion of cytochrome P450 oxidoreductase enhances metabolism and DNA adduct formation of benzo[a]pyrene in Hepa1c1c7 cells, Mutagenesis, 34, 5-6, 413-420, (2019).
  • Zeid, E.H.A., El Sharkawy, N.I., Moustafa, G.G., Anver, A.M. and Al Nady, A.G., The palliative effect of camel milk on hepatic CYP1A1 gene expression and DNA damage induced by fenpropathrin oral intoxication in male rats, Ecotoxicology and Environmental Safety, 207, 111296, (2021).
  • Benhusein G.M., Mutch E., Aburawi S. and Williams, F.M., Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay, Libyan Journal of Medicine, 13, 5, (2010).
  • Collins, A.R., Measuring oxidative damage to DNA and its repair with the comet assay, Biochimica et Biophysica Acta, 1840, 794–800, (2014).
  • Yuzbasıoglu, D., Yılmaz, A.E. and Unal, F., Antidepresan ilaçlar ve genotoksisite, TUBAV Journal of Science, 9, 1, 17-28, (2016).
  • Paz, M.F.C.J., Alencar, M.V.O.B., Lima, R.M.P., Sobral, A.L.P., Nascimento, G.T.M., Reis, AM., Coêlho, MPSS., Nascimento, MLLB., Júnior, ALG., Machado, K.C., Menezes, A.P.M., Lima, R.M.T., Filho, J.W.G.O., Dias, A.C.S., Reis, A.C., Mata, A.M.O.F., Machado, S.A., Sousa, C.D.C., Silva, F.C.C., Islam, MT., Sousa, J.M.C. and Cavalcante, A.C.M., Pharmacological effevts and toxicogenetic impacts of omeprazole: genomic instability and cancer, Oxidative Medicine and Cellular Longevity, 21, (2020).
  • Ayabaktı, S. and Kocaman, A.Y., Cytogenotoxic effects of venlafaxine hydrochloride on cultured human peripheral blood lymphocytes, Drug and Chemical Toxicology, 43, 2, 192-199, (2018).
  • Ahmadimanesh, M., Abbaszadegan, M.R., Rad D.M., Moallem, S.A., Mohammadpour, A.H., Ghahremani, M.H., Hosseini, F.F., Behdani, F., Manteghi, A.A., Jowsey, P., Behbahani, F.S., Moallem, S.M.H. and Etemad, L., Effects of selective serotonin reuptake inhibitors on DNA damage in patients with depression, Journal of Psychopharmacology, 33, 11, 1364-1376, (2019).
  • Solek, P., Koszla, O., Mytych, J., Badura, J., Chelminiak, Z., Cuprys, M., Fraczek, J., Tabecka-Lonczynska, A. and Koziorowski, M., Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies, Apoptosis, 24, 9-10,773–784, (2019).
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  • Avuloglu, Y.E., Unal, F. and Yüzbasioglu, D., Evaluation of cytogenetic and DNA damage induced by the antidepressant drug-active ingredients, trazodonee and milnacipran, in vitro, Drug and Chemical Toxicology, 40, 1, 57-66, (2017).
  • Bozkurt, G., Abay, E., Ates, I., Karabogaz, G., Ture, M., Savran, FO., Palanduz, S., Temocin, K. and Algunes, C., Clastogenicity of selective serotonin-reuptake inhibitors, Mutation Research, 14, 558, 137-144, (2004).
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  • Battal, D., Aktas, A., Sungur, M.A., Kadioglu, E., Eker, E.D., Sahin, N.O. and Saygi, S., In vivo genotoxicity assessment of sertraline by using alkaline comet assay and the cytokinesis-block micronucleus assay, Basic and Clinical Pharmacology and Toxicology, 113, 5, 339-346, (2013).
  • Donbak, L., Dal, O. and Celik, M., Genotoxic effects of antidepressant reboxetine in human peripheral lymphocytes, Advance Laboratory Medicine International, 4, 3, 93–102 (2014).
  • Cobanoglu, H., Coskun, M., Cayir, A. and Coskun, M., In vitro genotoxic and cytotoxic effects of doxepin and escitalopram on human peripheral lymphocytes, Drug and Chemical Toxicology, 41, 2, 238-244, (2018).
  • Sakin, M.T. and Kamal, Y.M., Cytotoxic effect of nefazodone on HepG2 cell line and the reliability of comet assay to determine genotoxicity, Al-Mustansiriyah Journal for Pharmaceutical Sciences, 2, 30-36, (2019).
  • Togar, B., Turkez, H., Tatar, A., Kirkpinar, I., Hacimuftuoglu, A., Geyikoglu, F., Keles, M.S. and Dirican, E., The genotoxic potentials of some atypical antipsychotic drugs on human lymphocytes, Toxicology and Industrial Health, 28, 4, 327-333, (2012).
  • Zaki, M.E., El-Bassyouni, H.T., Yousef, W., Mohamed, R., El Toukhy, S. and Ismail, S., Body image, anxiety, depression and DNA damage in obese Egyptian women, Middle East Journal of Medical Genetics, 8, 42-47, (2019).
  • Dunnick, J.K. and Hailey, J.R., Experimental studies on the long-term effects of methylphenidate hydrochloride, Toxicology, 103, 2, 77-84, (1995).
  • Andreazza, A.C., Frey, B.N., Valvassori, S.S., Zanotto, C., Gomes, K.M., Comim, C.M., Cassini, C., Stertz, L., Ribeiro, L.C., Quevedo, J., Kapczinski, F., Berk, M. and Gonçalves, C.A., DNA damage in rats after treatment with methylphenidate, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 31, 6, 1282-1288, (2007).
  • Bendele, R.A., Adams, E.R., Hoffman, W.P., Gries, C.L. and Morton D.M., Carcinogenicity studies of fluoxetine hydrochloride in rats and mice, Cancer Research, 52, 24, 6931-6935, (1992).
  • Kelly, JP., Rosenberg, L., Palmer, JR., Rao, R.S., Strom, B.L., Stolley, P.D., Zauber, A.G. and Shapiro, S., Risk of breast cancer according to use of antidepressants, phenothiazines, and antihistamines, American Journal of Epidemiology, 150, 8, 861-868, (1999).
  • Cotterchio, M., Kreiger, N., Darlington, G. and Steingart, A., Antidepressant medication use and breast cancer risk, American Journal of Epidemiology, 151, 10, 951-957, (2000).
  • Moorman, P.G., Grubber, J.M., Millikan, R.C. and Newman, B., Antidepressant medications and their association with invasive breast cancer and carcinoma in situ of the breast, Epidemiology, 14, 307-314, (2003).
  • Fulton-Kehoe, D., Rossing, M.A., Rutter, C., Mandelson, M.T. and Weiss, N.S., Use of antidepressant medications in relation to the incidence of breast cancer, British Journal of Cancer, 94, 1071-1078, (2006).
  • Hininger, I., Chollat-Namy, A., Sauvaigo, S., Osman, M., Faure, H., Cadet, J., Favier, A. and Roussel, A.M., Assessment of DNA damage by comet assay on frozen total blood: method and evaluation in smokers and non-smokers, Mutation Research, 558, 1-2, 75-80, (2004).
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  • Erikel, E., Yuzbasıoglu, D. and Unal, F., Genotoxic and antigenotoxic potential of amygdalin on isolated human lymphocytes by the comet assay, Journal of Food Biochemistry, 44, 10, (2020).
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  • Araldi, R.P., Melo, T.C, Mendes, T.B., Junior, P.L., Nozima, B.H.N., Ito, E.T., Carvalho, R.F., Souza, E.B. and Stocco, RC., Using the comet and micronucleus assays for genotoxicity studies: a review, Biomedicine & Pharmacotherapy,72, 74-82, (2015).
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Toplam 68 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Araştırma Makalesi
Yazarlar

Salih Özden 0000-0002-2248-825X

Deniz Yüzbaşıoğlu 0000-0003-2756-7712

Gülnur Özdamar Bu kişi benim 0000-0001-7325-8860

Fatma Ünal 0000-0002-7468-6186

Proje Numarası 05/2019-28.
Yayımlanma Tarihi 8 Temmuz 2022
Gönderilme Tarihi 12 Ekim 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 24 Sayı: 2

Kaynak Göster

APA Özden, S., Yüzbaşıoğlu, D., Özdamar, G., Ünal, F. (2022). Determination of possible genotoxic damage by comet assay in patients under treatment due to depression and anxiety disorders. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 24(2), 594-607.
AMA Özden S, Yüzbaşıoğlu D, Özdamar G, Ünal F. Determination of possible genotoxic damage by comet assay in patients under treatment due to depression and anxiety disorders. BAUN Fen. Bil. Enst. Dergisi. Temmuz 2022;24(2):594-607.
Chicago Özden, Salih, Deniz Yüzbaşıoğlu, Gülnur Özdamar, ve Fatma Ünal. “Determination of Possible Genotoxic Damage by Comet Assay in Patients under Treatment Due to Depression and Anxiety Disorders”. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi 24, sy. 2 (Temmuz 2022): 594-607.
EndNote Özden S, Yüzbaşıoğlu D, Özdamar G, Ünal F (01 Temmuz 2022) Determination of possible genotoxic damage by comet assay in patients under treatment due to depression and anxiety disorders. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi 24 2 594–607.
IEEE S. Özden, D. Yüzbaşıoğlu, G. Özdamar, ve F. Ünal, “Determination of possible genotoxic damage by comet assay in patients under treatment due to depression and anxiety disorders”, BAUN Fen. Bil. Enst. Dergisi, c. 24, sy. 2, ss. 594–607, 2022.
ISNAD Özden, Salih vd. “Determination of Possible Genotoxic Damage by Comet Assay in Patients under Treatment Due to Depression and Anxiety Disorders”. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi 24/2 (Temmuz 2022), 594-607.
JAMA Özden S, Yüzbaşıoğlu D, Özdamar G, Ünal F. Determination of possible genotoxic damage by comet assay in patients under treatment due to depression and anxiety disorders. BAUN Fen. Bil. Enst. Dergisi. 2022;24:594–607.
MLA Özden, Salih vd. “Determination of Possible Genotoxic Damage by Comet Assay in Patients under Treatment Due to Depression and Anxiety Disorders”. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, c. 24, sy. 2, 2022, ss. 594-07.
Vancouver Özden S, Yüzbaşıoğlu D, Özdamar G, Ünal F. Determination of possible genotoxic damage by comet assay in patients under treatment due to depression and anxiety disorders. BAUN Fen. Bil. Enst. Dergisi. 2022;24(2):594-607.