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Article ; Online: Animal models for the study of arterial hypertension.

Dornas, Waleska C / Silva, Marcelo E

2011 Volume 36, Issue 4, Page(s) 731–737

Abstract: Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided ... ...

Abstract	Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.
MeSH term(s)	Animals ; Denervation/adverse effects ; Diet/adverse effects ; Disease Models, Animal ; Humans ; Hypertension/etiology ; Hypertension/genetics ; Hypertension/physiopathology ; Hypertension, Renal/etiology ; Hypertension, Renal/genetics ; Hypertension, Renal/physiopathology ; Models, Animal ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/antagonists & inhibitors ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/metabolism ; Pressoreceptors/surgery ; Rats ; Rats, Inbred Dahl ; Rats, Inbred SHR ; Rats, Transgenic
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase (EC 1.14.13.39) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X)
Language	English
Publishing date	2011-08-21
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	756157-x
ISSN	0973-7138 ; 0250-5991
ISSN (online)	0973-7138
ISSN	0250-5991
DOI	10.1007/s12038-011-9097-y
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Article ; Online: Health implications of high-fructose intake and current research.

Dornas, Waleska C / de Lima, Wanderson G / Pedrosa, Maria L / Silva, Marcelo E

Advances in nutrition (Bethesda, Md.)

2015 Volume 6, Issue 6, Page(s) 729–737

Abstract: Although fructose consumption has dramatically increased and is suspected to be causally linked to metabolic abnormalities, the mechanisms involved are still only partially understood. We discuss the available data and investigate the effects of dietary ... ...

Abstract	Although fructose consumption has dramatically increased and is suspected to be causally linked to metabolic abnormalities, the mechanisms involved are still only partially understood. We discuss the available data and investigate the effects of dietary fructose on risk factors associated with metabolic disorders. The evidence suggests that fructose may be a predisposing cause in the development of insulin resistance in association with the induction of hypertriglyceridemia. Experiments in animals have shown this relation when they are fed diets very high in fructose or sucrose, and human studies also show this relation, although with conflicting results due to the heterogeneity of the studies. The link between increased fructose consumption and increases in uric acid also has been confirmed as a potential risk factor for metabolic syndrome, and insulin resistance/hyperinsulinemia may be causally related to the development of hypertension. Collectively, these results suggest a link between high fructose intake and insulin resistance, although future studies must be of reasonable duration, use defined populations, and improve comparisons regarding the effects of relevant doses of nutrients on specific endpoints to fully understand the effect of fructose intake in the absence of potential confounding factors.
MeSH term(s)	Animals ; Diet ; Dietary Sucrose/administration & dosage ; Fructose/administration & dosage ; Fructose/adverse effects ; Fructose/metabolism ; Humans ; Hypertension/etiology ; Hypertriglyceridemia/etiology ; Insulin/blood ; Insulin Resistance ; Lipid Metabolism ; Metabolic Diseases/etiology ; Mice ; Obesity/etiology ; Rats ; Risk Factors ; Uric Acid/blood ; Weight Gain
Chemical Substances	Dietary Sucrose ; Insulin ; Uric Acid (268B43MJ25) ; Fructose (30237-26-4)
Language	English
Publishing date	2015-11-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2583634-1
ISSN	2156-5376 ; 2156-5376
ISSN (online)	2156-5376
ISSN	2156-5376
DOI	10.3945/an.114.008144
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Article ; Online: Efficacy of the superoxide dismutase mimetic tempol in animal hypertension models: a meta-analysis.

Dornas, Waleska C / Silva, Maísa / Tavares, Ricardo / de Lima, Wanderson G / dos Santos, Rinaldo C / Pedrosa, Maria L / Silva, Marcelo E

Journal of hypertension

2015 Volume 33, Issue 1, Page(s) 14–23

Abstract: Objective: Considering the growing body of evidence that indicates the contribution of superoxide anions (O2) and other reactive oxygen species (ROS) to the development of hypertension, we assessed whether animal models of hypertension have a benefic ... ...

Abstract	Objective: Considering the growing body of evidence that indicates the contribution of superoxide anions (O2) and other reactive oxygen species (ROS) to the development of hypertension, we assessed whether animal models of hypertension have a benefic effect with tempol, a superoxide dismutase mimetic, to help augment the design of future studies. Methods: Studies published between July 1998 and December 2012 on blood pressure (BP) in different hypertensive models were obtained after an electronic and manual search of PubMed. In-depth analyses of the methodological quality of the studies and the mean arterial pressure (MAP) changes after treatment with tempol were performed, as well as the subgroup analyses on the route of tempol delivery. Results: Out of the 144 identified studies, 28 were included after screening. The data showed that tempol reduced MAP by computing the standardized mean difference with the value of 4.622 (95% confidence interval 3.24-5.99). The quality of studies included in the meta-analysis was category II; however, omission of details in the trials might have biased the results. There was substantial heterogeneity in the results with an I of 94.45%, which persisted after stratifying for the route of tempol delivery. Conclusion: In conclusion, this analysis shows that antioxidant treatment with tempol can reduce BP, suggesting that ROS plays a role in the pathogenesis of increased BP in the hypertension models used in the current research practice.
MeSH term(s)	Animals ; Antioxidants/therapeutic use ; Biomimetic Materials/pharmacology ; Biomimetic Materials/therapeutic use ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Cyclic N-Oxides/pharmacology ; Cyclic N-Oxides/therapeutic use ; Disease Models, Animal ; Hypertension/drug therapy ; Hypertension/metabolism ; Rats ; Spin Labels ; Superoxide Dismutase/pharmacology ; Superoxide Dismutase/therapeutic use ; Superoxides/metabolism
Chemical Substances	Antioxidants ; Cyclic N-Oxides ; Spin Labels ; Superoxides (11062-77-4) ; Superoxide Dismutase (EC 1.15.1.1) ; tempol (U78ZX2F65X)
Language	English
Publishing date	2015-01
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	605532-1
ISSN	1473-5598 ; 0263-6352 ; 0952-1178
ISSN (online)	1473-5598
ISSN	0263-6352 ; 0952-1178
DOI	10.1097/HJH.0000000000000422
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Article ; Online: Oxidative stress causes hypertension and activation of nuclear factor-κB after high-fructose and salt treatments.

Dornas, Waleska C / Cardoso, Leonardo M / Silva, Maísa / Machado, Natália L S / Chianca, Deoclécio A / Alzamora, Andréia C / Lima, Wanderson G / Lagente, Vincent / Silva, Marcelo E

Scientific reports

2017 Volume 7, Page(s) 46051

Abstract: There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent ... ...

Abstract	There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent hypertension yet remain largely unexplored. Here, we tested the role of oxidative state as an essential factor along with high salt and fructose treatment in causing hypertension. Fischer male rats were supplemented with a high-fructose diet (20% in water) for 20 weeks and maintained on high-salt diet (8%) associate in the last 10 weeks. Fructose-fed rats exhibited a salt-dependent hypertension accompanied by decrease in renal superoxide dismutase activity, which is the first footprint of antioxidant inactivation by reactive oxygen species (ROS). Metabolic changes and the hypertensive effect of the combined fructose-salt diet (20 weeks) were markedly reversed by a superoxide scavenger, Tempol (10 mg/kg, gavage); moreover, Tempol (50 mM) potentially reduced ROS production and abolished nuclear factor-kappa B (NF-κB) activation in human embryonic kidney HEK293 cells incubated with L-fructose (30 mM) and NaCl (500 mosmol/kg added). Taken together, our data suggested a possible role of oxygen radicals and ROS-induced activation of NF-κB in the fructose- and salt-induced hypertension associated with the progression of the renal disease.
MeSH term(s)	Antioxidants/metabolism ; Blood Pressure ; Body Weight ; Cyclic N-Oxides/pharmacology ; Diet ; Drinking Behavior ; Feeding Behavior ; Fructose/adverse effects ; Gene Expression Regulation/drug effects ; Glucose Tolerance Test ; HEK293 Cells ; Humans ; Hypertension/blood ; Hypertension/metabolism ; Hypertension/pathology ; Hypertension/physiopathology ; Kidney/drug effects ; Kidney/enzymology ; Kidney/pathology ; Lymphocytes/drug effects ; Lymphocytes/metabolism ; Monocytes/drug effects ; Monocytes/metabolism ; NF-kappa B/metabolism ; Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Sodium Chloride/adverse effects ; Spin Labels ; Superoxide Dismutase/metabolism
Chemical Substances	Antioxidants ; Cyclic N-Oxides ; NF-kappa B ; Reactive Oxygen Species ; Spin Labels ; Fructose (30237-26-4) ; Sodium Chloride (451W47IQ8X) ; Superoxide Dismutase (EC 1.15.1.1) ; tempol (U78ZX2F65X)
Language	English
Publishing date	2017-04-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep46051
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Article ; Online: Experimental atherosclerosis in rabbits.

Dornas, Waleska C / Oliveira, Tânia T de / Augusto, Luis E Franklin / Nagem, Tanus J

Arquivos brasileiros de cardiologia

2010 Volume 95, Issue 2, Page(s) 272–278

Abstract: Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in ... ...

Abstract	Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.
MeSH term(s)	Animals ; Atherosclerosis/etiology ; Atherosclerosis/pathology ; Cholesterol/blood ; Cholesterol, Dietary/administration & dosage ; Cholesterol, Dietary/adverse effects ; Coronary Vessels/pathology ; Diet ; Diet, Atherogenic ; Disease Models, Animal ; Endothelium, Vascular/pathology ; Endothelium, Vascular/physiopathology ; Hypercholesterolemia/complications ; Hypercholesterolemia/metabolism ; Rabbits
Chemical Substances	Cholesterol, Dietary ; Cholesterol (97C5T2UQ7J)
Language	Portuguese
Publishing date	2010-09-24
Publishing country	Brazil
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	730261-7
ISSN	1678-4170 ; 0066-782X
ISSN (online)	1678-4170
ISSN	0066-782X
DOI	10.1590/s0066-782x2010001200020
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Article ; Online: Aterosclerose experimental em coelhos Experimental atherosclerosis in rabbits

Waleska C. Dornas / Tânia T. de Oliveira / Luis E. Franklin Augusto / Tanus J. Nagem

Arquivos Brasileiros de Cardiologia, Vol 95, Iss 2, Pp 272-

2010 Volume 278

Abstract: Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes ...

Abstract	Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose. Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.
Keywords	Aterosclerose ; colesterol ; hipercolesterolemia ; coelhos ; Atherosclerosis ; cholesterol ; hypercholesterolemia ; rabbits ; Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Cardiovascular ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2010-08-01T00:00:00Z
Publisher	Sociedade Brasileira de Cardiologia - SBC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Iron toxicity mediated by oxidative stress enhances tissue damage in an animal model of diabetes.

Sampaio, Ana Flávia S / Silva, Maisa / Dornas, Waleska C / Costa, Daniela C / Silva, Marcelo E / Dos Santos, Rinaldo C / de Lima, Wanderson G / Pedrosa, Maria Lúcia

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine

2014 Volume 27, Issue 2, Page(s) 349–361

Abstract: Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of ... ...

Abstract	Although iron is a first-line pro-oxidant that modulates clinical manifestations of various systemic diseases, including diabetes, the individual tissue damage generated by active oxidant insults has not been demonstrated in current animal models of diabetes. We tested the hypothesis that oxidative stress is involved in the severity of the tissues injury when iron supplementation is administered in a model of type 1 diabetes. Streptozotocin (Stz)-induced diabetic and non-diabetic Fischer rats were maintained with or without a treatment consisting of iron dextran ip at 0.1 mL day(-1) doses administered for 4 days at intervals of 5 days. After 3 weeks, an extensive increase (p < 0.001) in the production of reactive oxygen species (ROS) in neutrophils of the diabetic animals on iron overload was observed. Histological analysis revealed that this treatment also resulted in higher (p < 0.05) tissue iron deposits, a higher (p < 0.001) number of inflammatory cells in the pancreas, and apparent cardiac fibrosis, as shown by an increase (p < 0.05) in type III collagen levels, which result in dysfunctional myocardial. Carbonyl protein modification, a marker of oxidative stress, was consistently higher (p < 0.01) in the tissues of the iron-treated rats with diabetes. Moreover, a significant positive correlation was found between ROS production and iron pancreas stores (r = 0.42, p < 0.04), iron heart stores (r = 0.54, p < 0.04), and change of the carbonyl protein content in pancreas (r = 0.49, p < 0.009), and heart (r = 0.48, p < 0.02). A negative correlation was still found between ROS production and total glutathione content in pancreas (r = -0.50, p < 0.03) and heart (r = -0.45, p < 0.04). In conclusion, our results suggest that amplified toxicity in pancreatic and cardiac tissues in rats with diabetes on iron overload might be attributed to increased oxidative stress.
MeSH term(s)	Animals ; Diabetes Mellitus, Experimental/chemically induced ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 1/chemically induced ; Diabetes Mellitus, Type 1/metabolism ; Diabetes Mellitus, Type 1/pathology ; Disease Models, Animal ; Iron Overload/chemically induced ; Iron Overload/complications ; Iron Overload/metabolism ; Iron-Dextran Complex/administration & dosage ; Iron-Dextran Complex/pharmacokinetics ; Iron-Dextran Complex/toxicity ; Male ; Oxidative Stress/drug effects ; Rats ; Rats, Inbred F344 ; Reactive Oxygen Species/metabolism ; Streptozocin ; Tissue Distribution
Chemical Substances	Reactive Oxygen Species ; Streptozocin (5W494URQ81) ; Iron-Dextran Complex (9004-66-4)
Language	English
Publishing date	2014-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1112688-7
ISSN	1572-8773 ; 0966-0844
ISSN (online)	1572-8773
ISSN	0966-0844
DOI	10.1007/s10534-014-9717-8
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Article ; Online: Antidiabetic effects of the medicinal plants Efeitos antidiabéticos de plantas medicinais

Waleska C. Dornas / Tânia T. de Oliveira / Rosana G. R. Dores / Mary Helen A. Fabres / Tanus J. Nagem

Revista Brasileira de Farmacognosia, Vol 19, Iss 2a, Pp 488-

2009 Volume 500

Abstract: Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemy that has a significant impact for their patients. Its incidence is raising leading to an increase in the cost of the cares of the disease and of its complications. The ... ...

Abstract	Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemy that has a significant impact for their patients. Its incidence is raising leading to an increase in the cost of the cares of the disease and of its complications. The treatment involves, besides dietary control and physical activity, the use of drugs that cause side effects to reach wanted pharmacological actions. However, products of plants are, frequently, considered less poisonous and with fewer side effects than synthetic drugs and widely used by the population. In this paper, several species of plants, used experimentally or in the popular medicine, acting by different ways to control glycemia and/or to inhibit symptoms and characteristic complications of the diabetes, they will be reviewed for evaluation of their supposed therapeutic effects. Diabetes mellitus (DM) é uma doença metabólica crônica caracterizada por hipeglicemia que tem impacto significante em seus pacientes. Sua incidência está crescendo rapidamente conduzindo para aumento no custo dos cuidados da doença e de suas complicações. O tratamento envolve, além de controle dietético e atividade física, o uso de fármacos que ocasionam efeitos colaterais para atingir ações farmacológicas desejadas. Entretanto, produtos de plantas são, freqüentemente, considerados menos tóxicos e com menos efeitos colaterais que drogas sintéticas e amplamente utilizadas pela população. Nesse trabalho várias espécies de plantas utilizadas experimentalmente ou na medicina popular, agindo de diferentes formas de modo a controlar glicemia e/ou inibir sintomas e complicações características da diabetes serão revisadas para avaliação de seus supostos efeitos terapêuticos.
Keywords	Diabetes ; glicose ; hipoglicemia ; colesterol ; estresse oxidativo ; glucose ; hypoglycaemia ; cholesterol ; oxidative stress ; Pharmacy and materia medica ; RS1-441 ; Medicine ; R ; DOAJ:Pharmacy and materia medica ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	Portuguese
Publishing date	2009-06-01T00:00:00Z
Publisher	Sociedade Brasileira de Farmacognosia
Document type	Article ; Online
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Article ; Online: Endotoxin regulates matrix genes increasing reactive oxygen species generation by intercellular communication between palmitate-treated hepatocyte and stellate cell.

Dornas, Waleska / Glaise, Denise / Bodin, Aude / Sharanek, Ahmad / Burban, Audrey / Le Guillou, Dounia / Robert, Sacha / Dutertre, Stephanie / Aninat, Caroline / Corlu, Anne / Lagente, Vincent

Journal of cellular physiology

2018 Volume 234, Issue 1, Page(s) 122–133

Abstract: Previous studies have shown that gut-derived bacterial endotoxins contribute in the progression of simple steatosis to steatohepatitis, although the mechanism(s) remains inaccurate to date. As hepatic stellate cells (HSC) play a pivotal role in the ... ...

Abstract	Previous studies have shown that gut-derived bacterial endotoxins contribute in the progression of simple steatosis to steatohepatitis, although the mechanism(s) remains inaccurate to date. As hepatic stellate cells (HSC) play a pivotal role in the accumulation of excessive extracellular matrix (ECM), leading to collagen deposition, fibrosis, and perpetuation of inflammatory response, an in vitro model was developed to investigate the crosstalk between HSC and hepatocytes (human hepatoma cell) pretreated with palmitate. Bacterial lipopolysaccharide (LPS) stimulated HSC with phosphorylation of the p38 mitogen-activated protein kinase/NF-κB pathway, while several important pro-inflammatory cytokines were upregulated in the presence of hepatocyte-HSC. Concurrently, fibrosis-related genes were regulated by palmitate and the inflammatory effect of endotoxin where cells were more exposed or sensitive to reactive oxygen species (ROS). This interaction was accompanied by increased expression of the mitochondrial master regulator, proliferator-activated receptor gamma coactivator alpha, and a cytoprotective effect of the agent N-acetylcysteine suppressing ROS production, transforming growth factor-β1, and tissue inhibitor of metalloproteinase-1. In summary, our results demonstrate that pro-inflammatory mediators LPS-induced promote ECM rearrangement in hepatic cells transcriptionally committed to the regulation of genes encoding enzymes for fatty acid metabolism in light of differences that might require an alternative therapeutic approach targeting ROS regulation.
MeSH term(s)	Cell Communication/drug effects ; Cell Communication/genetics ; Cytokines/genetics ; Extracellular Matrix/drug effects ; Extracellular Matrix/genetics ; Fatty Liver/genetics ; Fatty Liver/microbiology ; Fatty Liver/pathology ; Fibrosis/genetics ; Fibrosis/pathology ; Hepatic Stellate Cells/drug effects ; Hepatic Stellate Cells/metabolism ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Humans ; Lipopolysaccharides/toxicity ; Palmitates/pharmacology ; Phosphorylation/drug effects ; Reactive Oxygen Species/metabolism ; Tissue Inhibitor of Metalloproteinase-1/genetics ; Transforming Growth Factor beta1/genetics ; p38 Mitogen-Activated Protein Kinases/genetics
Chemical Substances	Cytokines ; Lipopolysaccharides ; Palmitates ; Reactive Oxygen Species ; TGFB1 protein, human ; Tissue Inhibitor of Metalloproteinase-1 ; Transforming Growth Factor beta1 ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2018-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.27175
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