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Topic:Selenium

Selenium is an essential trace mineral that is important for various physiological processes in horses. It is a component of several enzymes and proteins, including glutathione peroxidase, which plays a role in protecting cells from oxidative damage. Selenium is also involved in thyroid hormone metabolism and immune function. Horses require selenium in their diet, but the required amounts can vary based on factors such as age, workload, and geographic location, as soil selenium content influences forage selenium levels. Both selenium deficiency and toxicity can lead to health issues in horses, with deficiency potentially resulting in muscle disorders and toxicity causing symptoms such as colic and neurological signs. This page compiles peer-reviewed research studies and scholarly articles that explore the metabolism, dietary requirements, and health implications of selenium in equine nutrition and management.
Selenium deficiency associations with gender, breed, serum vitamin E and creatine kinase, clinical signs and diagnoses in horses of different age groups: a retrospective examination 1996-2011.
Equine veterinary journal. Supplement    March 2, 2013   Issue 43 31-35 doi: 10.1111/j.2042-3306.2012.00643.x
Streeter RM, Divers TJ, Mittel L, Korn AE, Wakshlag JJ.Selenium and vitamin E deficiency have been associated with nutritional myopathy, more commonly known as white muscle disease (WMD) in horses. However, correlations between selenium concentrations and presenting clinical signs, age, breed, gender, serum vitamin E, creatine kinase (CK) and final diagnosis, have not previously been evaluated. Objective: To determine the number of hospitalised horses in 3 age groups that were selenium tested and the proportions of horses with categorised presenting clinical signs; the association/odds risk of final diagnosis with selenium deficiency and to examin...
Antioxidant trace elements in serum of draft horses with acute and chronic lower airway disease.
Biological trace element research    July 6, 2012   Volume 150, Issue 1-3 123-129 doi: 10.1007/s12011-012-9471-0
Youssef MA, El-Khodery SA, Ibrahim HM.The aim of the present study was to evaluate the oxidative stress level and antioxidant trace elements status associated with lower airway disease in draft horses. For this purpose, venous blood samples were obtained from draft horses exhibiting signs of lower respiratory tract disorders (n = 83) and from control group (n = 20). Serum trace elements including selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), and iron (Fe) were assayed. Serum malondialdehyde (MDA) and low-density lipoprotein (LDL) levels as well as plasma hydrogen peroxides (H₂O₂) concentration and activity of ...
[Seasonal and national differences in the selenium supply of horses across Europe].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    June 13, 2012   Volume 40, Issue 3 157-166 
Müller A, Bertram A, Moschos A.Evaluation of the differences in the selenium supply to horses across Europe. Methods: Serum samples from 137,152 horses all over Europe, which had been sent by veterinarians to IDEXX Vet Med Labor between January 1st 2006 and December 31st 2011, were routinely analyzed for the selenium concentration by means of ICP-analytic. Results: The selenium content of the soil appears to play a key role in the selenium supply to horses. Countries closer to the ocean provided a better selenium supply than countries in central Europe. The best selenium supply can be seen in Denmark and in the Netherlands....
Acute selenium toxicosis in polo ponies. Desta B, Maldonado G, Reid H, Puschner B, Maxwell J, Agasan A, Humphreys L, Holt T.Just prior to an international polo event, 21 horses from one team exhibited clinical signs of central nervous system disturbance, hyperexcitability, sweating, ataxia, tachycardia, dyspnea, pyrexia, and rapid death. The suspected cause of this peracute onset of illness and death included intentional contamination of feed or iatrogenic administration of performance-enhancing drugs resulting in a severe adverse reaction. Six horses were submitted to the Bronson Animal Disease Diagnostic Laboratory for necropsy and toxicological examination. The clinical signs and sudden death, the similarity to ...
A genetic variant near the equine interleukin 6 gene associated with copper:zinc ratio.
Veterinary journal (London, England : 1997)    February 16, 2011   Volume 190, Issue 2 e143-e145 doi: 10.1016/j.tvjl.2010.12.028
Beghelli D, Giacconi R, Mocchegiani E, Cipriano C, Malavolta M, Renieri C.The aim of this study was to validate an A/T single nucleotide polymorphism (SNP) corresponding to a LINE2 sequence located ∼1.1kb downstream of the IL-6 gene (SNP BIEC2-911738) and to determine if this variant is correlated with interleukin 6 (IL-6) modulation or with different plasma concentrations of Zn, Cu, Se and Fe. The frequency of the newly described variant T ranged from 0 to 23.1% among different breeds of horses. SBIEC2-911738 was not associated with changes in IL-6 plasma levels. Increased Cu:Zn ratios were observed in horses carrying the AT genotype independently of breed when s...
Effect of dietary antioxidant supplementation on fresh semen quality in stallion.
Theriogenology    February 4, 2011   Volume 75, Issue 7 1319-1326 doi: 10.1016/j.theriogenology.2010.12.003
Contri A, De Amicis I, Molinari A, Faustini M, Gramenzi A, Robbe D, Carluccio A.In this study, the effect of dietary supplementation of organic selenium, vitamin E, and zinc on raw semen characteristics was evaluated. Ten stallions with normal fertility were divided into two groups: a control group (CG), in which standard diet was provided, and a treated group (TG), in which the standard diet was supplemented with 1500 mg of α-tocopherol acetate, 360 mg of zinc, and 2.5 mg of organic selenium on a daily basis. Semen parameters on fresh semen were evaluated three times in all stallions before antioxidant supplementation (T0) and 30 (T1), 60 (T2), and 90 (T3) d after suppl...
The selenium and vitamin E status of horses in Prince Edward Island.
The Canadian veterinary journal = La revue veterinaire canadienne    December 2, 2010   Volume 51, Issue 9 979-985 
Muirhead TL, Wichtel JJ, Stryhn H, McClure JT.Serum selenium (Se), vitamin E, and resting thyroid hormone concentrations were measured in 201 horses in Prince Edward Island (PEI). Selenium concentrations were either marginal (0.0053 to 0.1200 ppm) or deficient (< 0.0053 ppm) in 79% of horses based on current reference ranges for Se in serum. Aged and young adult pleasure horses had a higher prevalence of inadequate Se concentrations compared to racehorses and broodmares (82% and 97% versus 45% and 72%, respectively). Overall, 13% of horses had inadequate (< 200 μg/dL) serum vitamin E concentrations; most of these were young pleasure hors...
Equine protozoal myeloencephalitis due to Neospora hughesi and equine motor neuron disease in a mule.
Veterinary ophthalmology    July 14, 2010   Volume 13, Issue 4 259-265 doi: 10.1111/j.1463-5224.2010.00790.x
Finno CJ, Eaton JS, Aleman M, Hollingsworth SR.A 23-year-old female mule was presented for bilateral ocular abnormalities and an abnormal pelvic limb gait. Results: Anisocoria, unilateral enophthalmos, medial strabismus, ptosis, pupillary light reflex deficits, and bilateral reticulated pigmentary retinopathy were observed on ophthalmic examination. Neurologic abnormalities included right-sided facial nerve paralysis, extensive symmetric muscle atrophy, and asymmetric pelvic limb ataxia with an abnormal pelvic limb gait. A positive titer (1:40) for equine protozoal myeloencephalitis (EPM) associated with Neospora hughesi was obtained from ...
Selenium in blood, semen, seminal plasma and spermatozoa of stallions and its relationship to sperm quality.
Reproduction, fertility, and development    May 11, 2010   Volume 22, Issue 5 886-891 doi: 10.1071/RD10032
Bertelsmann H, Keppler S, Höltershinken M, Bollwein H, Behne D, Alber D, Bukalis G, Kyriakopoulos A, Sieme H.The essential trace element selenium is indispensable for male fertility in mammals. Until now, little data existed regarding the relationship between selenium and sperm quality in the stallion. Selenium, or selenium-dependent glutathione peroxidase activity, was determined in red blood cells, semen, seminal plasma and spermatozoa, and the percentages of spermatozoa with progressive motility (PMS), intact membranes (PMI), altered (positive) acrosomal status (PAS) and detectable DNA damage, determined by the sperm chromatin structure assay, were evaluated in 41 healthy stallions (three samples ...
The effect of age on the immune response of horses to vaccination.
Journal of comparative pathology    December 1, 2009   Volume 142 Suppl 1 S85-S90 doi: 10.1016/j.jcpa.2009.10.010
Muirhead TL, McClure JT, Wichtel JJ, Stryhn H, Markham RJ, McFarlane D, Lunn DP.Few studies have investigated immunosenescence in the horse, but it is accepted that the primary and secondary (anamnestic) immune responses may differ between aged and younger horses. The aim of the present study was to determine whether aged horses have a protective immune response post-vaccination. Thirty-four aged healthy horses (> or =20 years) and 29 younger adult horses (4-12 years) of various breeds were vaccinated with commercially produced killed rabies and influenza vaccines. Rabies serum neutralizing antibody titres and equine influenza virus specific antibody subclasses (immunoglo...
Effect of selenium supplementation and plane of nutrition on mares and their foals: selenium concentrations and glutathione peroxidase.
Journal of animal science    November 6, 2009   Volume 88, Issue 3 991-997 doi: 10.2527/jas.2008-1743
Karren BJ, Thorson JF, Cavinder CA, Hammer CJ, Coverdale JA.To investigate the maternal plane of nutrition and role of Se yeast on muscle Se concentration, plasma glutathione peroxidase (Gsh-Px) activity, and colostrum Se concentration in mares and their foals, 28 Quarter Horse mares (465 to 612 kg of BW, and 6 to 19 yr of age) were used in a study with a randomized complete block design. Mares were blocked by expected foaling date and randomly assigned to dietary treatments within blocks. Dietary treatments were arranged as a 2 x 2 factorial with 2 planes of nutrition, pasture or pasture + grain mix (fed at 0.75% of BW on an as-fed basis) and 2 concen...
Metabolic and hematological profiles in mature horses supplemented with different selenium sources and doses.
Journal of animal science    November 6, 2009   Volume 88, Issue 2 650-659 doi: 10.2527/jas.2009-1855
Calamari L, Abeni F, Bertin G.This study was conducted to determine the effects of dietary Se source and dose on metabolic and hematological profiles, and their relationships with oxidative status in horses. Twenty-five mature horses were blocked by BW and randomly allocated to 1 of 5 dietary treatments: negative control (CTRL: 0.085 mg of Se/kg of DM), 3 different dietary concentrations of organic Se provided by Se yeast (SY02, SY03, and SY04 containing 0.2, 0.3, and 0.4 mg of total Se/kg of DM, respectively), and 1 positive control provided by sodium selenite (SS03 containing 0.3 mg of total Se/kg of DM). Horses were fed...
Effect of selenium supplementation and plane of nutrition on mares and their foals: foaling data.
Journal of animal science    November 6, 2009   Volume 88, Issue 3 982-990 doi: 10.2527/jas.2008-1646
Thorson JF, Karren BJ, Bauer ML, Cavinder CA, Coverdale JA, Hammer CJ.To investigate the maternal plane of nutrition and role of Se yeast on foaling variables and passive transfer of IgG, 28 Quarter Horse mares were used in a study with a randomized complete block design. Mares were blocked by expected foaling date and assigned randomly within block to dietary treatments. Dietary treatments were arranged as a 2 x 2 factorial with 2 planes of nutrition, pasture or pasture + grain mix (fed at 0.75% of BW on an as-fed basis) and 2 concentrations of Se yeast (0 or 0.3 mg/kg of DMI). This resulted in 4 treatments: pasture (PA), pasture + Se (PS), pasture + grain mix ...
Whole blood selenium concentrations in endurance horses.
Veterinary journal (London, England : 1997)    August 19, 2009   Volume 186, Issue 2 192-196 doi: 10.1016/j.tvjl.2009.07.017
Haggett E, Magdesian KG, Maas J, Puschner B, Higgins J, Fiack C.Exercise causes an increase in the production of reactive oxygen species, which can result in oxidant/antioxidant disequilibrium. Deficiency of antioxidants can further alter this balance in favor of pro-oxidation. Selenium (Se) is one of many antioxidant catalysts, as a component of the glutathione peroxidase enzymes. Soils and forages vary widely in Se concentration and a deficient diet can lead to sub-clinical or clinical deficiency in horses. Endurance horses are prone to oxidative stress during long periods of aerobic exercise and their performance could be affected by Se status. This stu...
Effects of vitamin E and selenium on serum trace and major elements in horses.
Biological trace element research    September 17, 2008   Volume 125, Issue 3 223-228 doi: 10.1007/s12011-008-8109-8
Yur F, Dede S, Deger Y, Kilicalp D.The combined effects of vitamin E and selenium were studied in native Anatolian horses subject to strenuous exercise. The concentrations of copper, zinc, iron, calcium, potassium, and magnesium were determined in serum by atomic absorption spectrometry in two study groups (n = 25 each), one of which served as untreated controls. After exercising the horses by running 1,500 m in about 7 min, only the copper level and the copper/zinc ratio significantly increased (p < 0.05), but the concentrations of calcium, potassium, iron, and magnesium remained unchanged. In horses treated with vitamin E ...
Effect of selenium source and dose on selenium status of mature horses.
Journal of animal science    September 12, 2008   Volume 87, Issue 1 167-178 doi: 10.2527/jas.2007-0746
Calamari L, Ferrari A, Bertin G.This study was conducted to determine the effects of either dietary Se source or dose on the Se status of horses. Twenty-five mature horses were blocked by BW and randomly allocated to 1 of 5 dietary treatments that comprised the same basal diet that differed only in Se source or dose. Treatments were as follows: negative control (0.085 mg of Se/kg of DM), 3 different dietary concentrations of supplemental organic Se (Se yeast; 0.2, 0.3, and 0.4 mg of total Se/kg of DM), and positive control (0.3 mg of total Se/kg of DM) supplemented with Na selenite. Horses initially received the control diet...
Investigation of blood oxidant/antioxidant markers in healthy competition horses of different breeds.
Equine veterinary journal. Supplement    April 4, 2007   Issue 36 239-244 doi: 10.1111/j.2042-3306.2006.tb05546.x
Kirschvink N, de Moffarts B, Farnir F, Pincemail J, Lekeux P.There is increasing evidence that the equine athlete is exposed to exercise-induced changes of its oxidant/antioxidant balance and antioxidant supplementation is frequently recommended. However, it is unknown whether there is a specific need for antioxidants according to performance, breed, gender or age. Objective: To assess whether breed-, gender- and age-related differences of blood oxidant/antioxidant markers occur in competition horses. Methods: Healthy horses (n = 493) underwent oxidant/ antioxidant blood marker determination. Vitamin E, lipophilic antioxidant capacity (ACL), ascorbic ac...
Is the distribution of selenium and zinc in the sublocations of spermatozoa regulated?
Annals of the New York Academy of Sciences    April 4, 2007   Volume 1095 204-208 doi: 10.1196/annals.1397.024
Bertelsmann H, Sieme H, Behne D, Kyriakopoulos A.In the sperm nuclei, of mammalian species selenium has been found only in the form of sperm nuclei glutathione peroxidase (snGPx) where it is most likely bound to the chromatin of spermatozoa. Over 80% of selenium in sperm is bound to the selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) in the midpiece of rat sperm. Zinc in sperm is mainly contained in the outer dense fiber (ODF) proteins of the flagella of mammalian spermatozoa. In the sperm nuclei, zinc is predominately located in the chromatin to the protamine proteins. In order to investigate if the insertion of zinc...
Effects of exercise and oral antioxidant supplementation enriched in (n-3) fatty acids on blood oxidant markers and erythrocyte membrane fluidity in horses.
Veterinary journal (London, England : 1997)    November 15, 2006   Volume 174, Issue 1 113-121 doi: 10.1016/j.tvjl.2006.06.001
De Moffarts B, Portier K, Kirschvink N, Coudert J, Fellmann N, van Erck E, Letellier C, Motta C, Pincemail J, Art T, Lekeux P.The aim of this study was to investigate in a placebo-controlled field study the effect of a (n-3)-vitamin supplementation on erythrocyte membrane fluidity (EMF), oxidant/antioxidant markers and plasmatic omega3/omega6 fatty acid ratio (FAR) in 12 eventing horses. Venous blood was sampled at rest before (PRE) and after (POST) a three week treatment period with either the supplement (group S, n=6) or a placebo (group P, n=6) as well as after 15min (POST E15') and 24h (POST E24h) after a standardised exercise test. The following markers were analysed: EMF, plasma antioxidant capacity of water an...
Anti-oxidative status and semen quality during cooled storage in stallions.
Journal of veterinary medicine. A, Physiology, pathology, clinical medicine    October 24, 2006   Volume 53, Issue 9 486-489 doi: 10.1111/j.1439-0442.2006.00879.x
Pagl R, Aurich C, Kankofer M.Activity of the anti-oxidative enzymes glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), content of thiobarbituric acid reactive substances (TBARS) and SH-groups were determined in native stallion semen (n = 8 stallions). Semen was then diluted in Kenney extender, EquiPro((R)) extender either with or without addition of N-acetyl cysteine or phosphate-buffered saline (PBS) and stored for 72 h at 5 degrees C. Correlations between initial activity of enzymes and development of semen motility and membrane integrity were calculated. Activities of GSH-Px, SOD and CAT im...
Effect of selenium supplementation and source on the selenium status of horses.
Journal of animal science    June 16, 2006   Volume 84, Issue 7 1742-1748 doi: 10.2527/jas.2005-413
Richardson SM, Siciliano PD, Engle TE, Larson CK, Ward TL.This study was conducted to determine the effect of Se supplementation and source on the Se status of horses. Eighteen 18-mo-old nonexercised horses were randomly assigned within sex to 1 of 3 treatments: 1) control (CTRL, no supplemental Se, 0.15 mg of Se/kg of total diet DM); 2) inorganic Se (INORG, CTRL + 0.45 mg of Se/kg of total diet DM from NaSeO3); or organic Se [ORG, CTRL + 0.45 mg of Se/kg of total diet DM from zinc-L-selenomethionine (Availa Se, Zinpro, Corp., Eden Prairie, MN)]. Horses were acclimated to the CTRL diet (7.1 kg of DM alfalfa hay and 1.2 kg of DM concentrate per horse ...
Double-blind placebo-controlled vitamin E or selenium supplementation of sport horses with unspecified muscle problems. An example of the potential of placebos.
The Journal of nutrition    June 15, 2006   Volume 136, Issue 7 Suppl 2045S-2047S doi: 10.1093/jn/136.7.2045S
Kienzle E, Freismuth A, Reusch A.No abstract available
Evaluation of the risk of motor neuron disease in horses fed a diet low in vitamin E and high in copper and iron.
American journal of veterinary research    January 24, 2006   Volume 67, Issue 1 120-126 doi: 10.2460/ajvr.67.1.120
Divers TJ, Cummings JE, de Lahunta A, Hintz HF, Mohammed HO.To determine whether equine motor neuron disease (EMND) could be induced in adult horses fed a diet low in vitamin E and high in copper and iron. Methods: 59 healthy adult horses. Methods: Horses in the experimental group (n = 8) were confined to a dirt lot and fed a concentrate low in vitamin E and high in iron and copper in addition to free-choice grass hay that had been stored for 1 year. Control horses (n = 51) were fed a concentrate containing National Research Council-recommended amounts of copper, iron, and vitamin E. The hay fed to control horses was the same as that fed to experimenta...
Correlation between 25 element contents in mane hair in riding horses and atrioventricular block.
Biological trace element research    December 6, 2005   Volume 108, Issue 1-3 127-136 doi: 10.1385/BTER:108:1-3:127
Asano K, Suzuki K, Chiba M, Sera K, Matsumoto T, Asano R, Sakai T.The influence of atrioventricular block (AV-block) on the trace elemental status in a horse hair was studied. The particle-induced X-ray emission (PIXE) method has provided a reliable, rapid, easy, and relatively inexpensive diagnostic method. Twenty-five elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Hg, K, Mg, Mn, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, Y, and Zn) in mane hair and serum were measured by the PIXE method. A horse hair with first- and second-degree AV-block contained significantly greater amounts of Br, Ca, Sr, and Zn than those of horses without electrocardiographic abnormalities...
Selenium contents in equine semen and semen fractions and their relations with chromatin integrity and foal birthing rate.
Animal reproduction science    November 2, 2005   Volume 89, Issue 1-4 212-215 
Bertelsmann H, Bollwein H, Sieme H, Alber D, Kyriakopoulos A, Behne D.No abstract available
Twenty-eight element concentrations in mane hair samples of adult riding horses determined by particle-induced X-ray emission.
Biological trace element research    October 12, 2005   Volume 107, Issue 2 135-140 doi: 10.1385/BTER:107:2:135
Asano K, Suzuki K, Chiba M, Sera K, Asano R, Sakai T.The concentrations of 28 elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, V, Y, and Zn) were measured in mane hair by the particle-induced X-ray emission method. Except for Br, Cl, K, S, and P, the trace element concentrations in mane hair of horses are similar to literature values for human hair. The values obtained are not dependent on the horse's age, breed, and sex and could be used as reference values in the assessment of diseases and nutritional status in equines.
Determination of glutathione peroxidase and superoxide dismutase-like activities in equine spermatozoa, seminal plasma, and reproductive tissues.
American journal of veterinary research    September 22, 2005   Volume 66, Issue 8 1415-1419 doi: 10.2460/ajvr.2005.66.1415
Baumber J, Ball BA.To determine glutathione peroxidase (GPX) and superoxide dismutase (SOD)-like activities in spermatozoa, seminal plasma, and reproductive tissues (ie, testis, epididymis, bulbourethral gland, prostate, vesicular gland, and ampulla) in horses. Methods: Seminal plasma from 17 stallions, spermatozoa from 5 stallions, and reproductive tissues from 3 stallions. Methods: Activity of GPX was determined by use of assays measuring oxidation of NADPH in the presence of exogenous glutathione, cumene hydroperoxide, and glutathione reductase. Activity of SOD-like enzymes was determined by use of the nitrob...
Digestible energy intake, dry matter digestibility and mineral status of grazing New Zealand Thoroughbred yearlings.
New Zealand veterinary journal    July 21, 2005   Volume 50, Issue 2 63-69 doi: 10.1080/00480169.2002.36252
Grace ND, Gee EK, Firth EC, Shaw HL.To measure the nutritive value of pasture in terms of digestible energy intake (DEI) and dry matter (DM) digestibility, and to determine the effect of Ca, P, Cu, Zn, and Se supplementation on growth rate and degree of physeal swelling in Thoroughbred yearlings grazed on pasture. Methods: Fourteen yearling horses were randomly allocated to 1 of 2 groups and rotationally grazed on a ryegrass/white clover pasture for 7 months. One group was supplemented daily with a mineral mix. Liveweight changes were recorded at fortnightly intervals and pasture mineral composition determined at monthly interva...
The effect of injectable barium selenate on the selenium status of horses on pasture.
New Zealand veterinary journal    July 21, 2005   Volume 46, Issue 5 186-190 doi: 10.1080/00480169.1998.36087
Wichtel JJ, Grace ND, Firth EC.To examine the effect of intramuscular barium selenate on the blood selenium concentration of horses with marginal selenium status. Methods: Eighteen mares were assigned to one of six groups. The mares in groups 1-4 received barium selenate at 0.5, 0.75, 1.0 and 1.5 mg Se/kg, respectively, injected into the right pectoral muscle mass. The mares in group 5 received sodium selenate at 0.05 mg Se/kg orally at 8-week intervals. The mares in group 6 were left untreated. Blood samples were collected at 0, 1, 2, 5, 10, 30, 60, 90, 120, 180, 240, 300 and 360 days after the initial treatment for assay ...
Masseter myodegeneration as a cause of trismus or dysphagia in adult horses.
The Veterinary record    May 17, 2005   Volume 156, Issue 20 642-646 doi: 10.1136/vr.156.20.642
Pearson EG, Snyder SP, Saulez MN.The medical records of eight horses with histological evidence of myodegeneration of the masseter muscles were examined. While they were alive their most common clinical signs had included difficulty in eating or opening their mouths, weight loss, difficulty in moving, and noticeable atrophy of the masseter muscles. The serum activities of muscle enzymes were abnormally high in all of the horses. Whole blood and/or liver selenium and vitamin E concentrations were less than the reference ranges in some of the horses. The lesions varied with the stage of the disease and consisted of swelling and...