Analyze Diet

Topic:Microbiome

The equine microbiome refers to the diverse community of microorganisms, including bacteria, fungi, and viruses, residing in various parts of a horse's body, such as the gastrointestinal tract, skin, and respiratory system. These microorganisms are involved in numerous physiological processes, including digestion, metabolism, and immune function. The composition and diversity of the microbiome can be influenced by factors such as diet, environment, and health status. Research in this area explores the characterization of the equine microbiome, its impact on health and disease, and potential applications in managing equine health. This page compiles peer-reviewed research studies and scholarly articles that investigate the composition, function, and implications of the microbiome in horses.
Alterations in microbiota and fermentation products in equine large intestine in response to dietary variation and intestinal disease.
The British journal of nutrition    August 5, 2011   Volume 107, Issue 7 989-995 doi: 10.1017/S0007114511003825
Daly K, Proudman CJ, Duncan SH, Flint HJ, Dyer J, Shirazi-Beechey SP.We aimed to determine the effects of variations in dietary composition on equine gut microbiota and their fermentation products, and proposed that dietary modifications profoundly affect microbial ecosystems and their metabolites. Bacterial communities within the large intestine of three groups of horses were compared using oligonucleotide-RNA hybridisation methodology. Each group consisting of six horses was maintained on (1) a grass-only diet, (2) a concentrate diet (i.e. supplemented with hydrolysable carbohydrates) and (3) a concentrate diet but horses were affected by simple colonic obstr...
Intestinal ciliate composition found in the feces of the Turk rahvan horse Equus caballus, Linnaeus 1758.
European journal of protistology    June 8, 2011   Volume 47, Issue 4 245-255 doi: 10.1016/j.ejop.2011.04.005
Gürelli G, Göçmen B.Species composition and distribution of large intestinal ciliates were investigated in the feces from 15 Turk rahvan horses, living in the vicinity of Izmir, Turkey. Twenty-two ciliate genera consisting of 36 species were identified. This is the first report on intestinal ciliates in Turk rahvan horses and no previously unknown species were observed. The mean number of ciliates was 14.2±13.9×10(4) cells ml(-1) of feces and the mean number of ciliate species per host was 9.9±7.1. No ciliates were observed in 2 horses. Bundleia and Blepharocorys were considered to be the major genera since th...
Presence and distribution of fungi and bacteria in the reproductive tract of healthy stallions.
Theriogenology    May 6, 2011   Volume 76, Issue 3 464-470 doi: 10.1016/j.theriogenology.2011.02.023
Rota A, Calicchio E, Nardoni S, Fratini F, Ebani VV, Sgorbini M, Panzani D, Camillo F, Mancianti F.A saprophytic bacterial flora is present on the penis and the distal part of the urethra of stallions. Little is known about the fungal flora of their reproductive tract. As micro organisms play an important role in mares fertility, the aim of the study was to describe the distribution of fungi and bacteria in the normal genital apparatus of stallions. The microbic flora of the reproductive tract of 11 healthy, fertile stallions was evaluated, collecting samples from 5 different locations: urethral fossa, penis/internal lamina of the prepuce, urethra pre- and post-ejaculation, and semen. For f...
Changes in faecal bacteria and metabolic parameters in foals during the first six weeks of life.
Veterinary microbiology    March 26, 2011   Volume 151, Issue 3-4 321-328 doi: 10.1016/j.vetmic.2011.03.017
Kuhl J, Winterhoff N, Wulf M, Schweigert FJ, Schwendenwein I, Bruckmaier RM, Aurich JE, Kutzer P, Aurich C.Many foals develop diarrhoea within the first two weeks of life which has been suggested to coincide with postpartum oestrus in their dams. To analyse the pathogenesis of this diarrhoea we have determined faecal bacteria in foals and their dams (n=30 each), and serum IGF-1 and γ-globulins for 6 weeks after birth. In addition, effects of β-carotene supplementation to mares (group 1: 1000 mg/day, n=15, group 2: control, n=15) on diarrhoea in foals were studied. Diarrhoea occurred in 92 and 79% of foals in groups 1 and 2, respectively, but was not correlated with oestrus in mares. Beta-carotene...
Dynamic host-bacteria interactions during an acidotic state induction.
Environmental microbiology reports    February 1, 2011   Volume 3, Issue 1 101-105 doi: 10.1111/j.1758-2229.2010.00193.x
Rudi K.Mainly due to the lack of time-series data, we know very little about the underlying interactions leading to adverse states in the gut. I therefore investigate the host-bacteria dynamic interactions in a recently published acidotic state induction time-series experiment. Too high levels of fermentation in the hindgut may lead to elevated serum lactate levels, which is a characteristic of the acidotic state. The acidotic state was induced through injection of oligofructose directly into the caecum of five horses, with subsequent temporal measurements of host serum lactate, and a range of caecum...
Understanding the equine cecum-colon ecosystem: current knowledge and future perspectives.
Animal : an international journal of animal bioscience    January 1, 2011   Volume 5, Issue 1 48-56 doi: 10.1017/S1751731110001588
Santos AS, Rodrigues MA, Bessa RJ, Ferreira LM, Martin-Rosset W.Having evolved as a grazing animal, a horse's digestive physiology is characterized by rapid gastric transit, a rapid but intense enzymatic digestion along the small intestine, and a long and intense microbial fermentation in the large intestine. The process of understanding and describing feed degradation mechanisms in the equine digestive system in general, and in the hindgut ecosystem in particular, is essential. Regardless of its importance for the nutritional status of the host, the significance of the cecum-colon ecosystem has not yet been fully understood, and few reports have focused d...
Do horses suffer from irritable bowel syndrome?
Equine veterinary journal    April 14, 2010   Volume 41, Issue 9 836-840 doi: 10.2746/042516409x474284
Hunter JO.Irritable bowel syndrome (IBS) in man is not a single entity but has several causes. One of the most common forms has similarities with colic and laminitis in horses. Undigested food residues may pass from the small intestine into the colon where bacterial fermentation produces chemicals that lead to disease. In horses the consequences may be disastrous, but in healthy humans such malabsorption may not be harmful. After events such as bacterial gastroenteritis or antibiotic treatment, an imbalance of the colonic microflora with overgrowth of facultative anaerobes may arise, leading to malferme...
Changes in faecal bacteria associated with concentrate and forage-only diets fed to horses in training.
Equine veterinary journal    April 14, 2010   Volume 41, Issue 9 908-914 doi: 10.2746/042516409x447806
Willing B, Vörös A, Roos S, Jones C, Jansson A, Lindberg JE.Diets rich in readily fermentable carbohydrates, fed traditionally to meet the increased energy requirements of the performance horse, are associated with a number of gastrointestinal disorders that involve disturbances in the intestinal microbiota, however, these changes are poorly understood. Objective: With the long-term objective of improving intestinal health and to increase understanding of the relationship between diet and microbiota, the effect of feeding Standardbred horses a high-energy forage-only (F) diet was studied compared to a more traditional forage-concentrate (C) diet on fae...
Microbial events in the hindgut during carbohydrate-induced equine laminitis.
The Veterinary clinics of North America. Equine practice    April 13, 2010   Volume 26, Issue 1 79-94 doi: 10.1016/j.cveq.2010.01.007
Milinovich GJ, Klieve AV, Pollitt CC, Trott DJ.Equine laminitis is the most serious foot disease of the horse, often resulting in death or euthanasia. Laminitis has long been recognized as an affliction of horses, as has the association of this condition with the ingestion of carbohydrates. Research into the pathophysiology of this condition has been facilitated by the development of reliable models for experimentally inducing laminitis, and DNA-based techniques for profiling complex microbiomes have dramatically increased the knowledge of the microbiology of this disease. Recent studies have provided substantial evidence showing equine hi...
Fecal microbiota of horses in the clinical setting: potential effects of penicillin and general anesthesia.
Veterinary microbiology    April 13, 2010   Volume 145, Issue 3-4 366-372 doi: 10.1016/j.vetmic.2010.03.023
Grønvold AM, L'Abée-Lund TM, Strand E, Sørum H, Yannarell AC, Mackie RI.Antimicrobial treatment is associated with the spread of antimicrobial resistance and disturbances in the ecological balance of intestinal microbiota. In horses, the main adverse effect of antimicrobial treatment is colitis. We used culture and 16S rRNA gene based molecular methods to monitor the prevalence of antimicrobial resistance and changes in predominant fecal populations during penicillin treatment and general anesthesia of horses in the clinical setting. After 5 days of parenteral administration of penicillin, fecal Escherichia coli were resistant to multiple unrelated antimicrobial a...
Antimicrobial resistance in equine faecal Escherichia coli isolates from North West England.
Annals of clinical microbiology and antimicrobials    April 7, 2010   Volume 9 12 doi: 10.1186/1476-0711-9-12
Ahmed MO, Clegg PD, Williams NJ, Baptiste KE, Bennett M.Escherichia coli isolates of equine faecal origin were investigated for antibiotic resistance, resistance genes and their ability to perform horizontal transfer. Methods: In total, 264 faecal samples were collected from 138 horses in hospital and community livery premises in northwest England, yielding 296 resistant E. coli isolates. Isolates were tested for susceptibility to antimicrobial drugs by disc diffusion and agar dilution methods in order to determine minimum inhibitory concentrations (MIC). PCR amplification was used to detect genes conferring resistance to: ampicillin (TEM and SHV b...
Lactobacillus hayakitensis, L. equigenerosi and L. equi, predominant lactobacilli in the intestinal flora of healthy thoroughbreds.
Animal science journal = Nihon chikusan Gakkaiho    February 19, 2010   Volume 80, Issue 3 339-346 doi: 10.1111/j.1740-0929.2009.00633.x
Morita H, Nakano A, Shimazu M, Toh H, Nakajima F, Nagayama M, Hisamatsu S, Kato Y, Takagi M, Takami H, Akita H, Matsumoto M, Masaoka T, Murakami M.To detect the predominant lactobacilli in the intestinal flora of healthy thoroughbreds, we isolated lactobacilli from the feces of nine thoroughbreds (five males and four females; 0-15-year-old). The isolated lactobacilli comprise 17 species (37 strains), and they were classified into five groups: Lactobacillus salivarius (6 species), L. reuteri (6 species), Lactobacillus delbrueckii (3 species), L. buchneri (1 species) and L. vitulinus (1 species). On the basis of 16S rRNA gene sequences, we identified 3 other phylogenetic relatives belonging to the genus Lactobacillus. These results suggest...
Lactobacillus and Bifidobacterium diversity in horse feces, revealed by PCR-DGGE.
Current microbiology    September 5, 2009   Volume 59, Issue 6 651-655 doi: 10.1007/s00284-009-9498-4
Endo A, Futagawa-Endo Y, Dicks LM.Lactobacillus equi, Lactobacillus hayakitensis, Lactobacillus johnsonii, and Weissella confusa/cibaria were the dominant species in 12 South African horses. The Bifidobacterium-group was detected in the feces of only one of the 12 horses. Sequencing of the nested-PCR amplicon identified the Bifidobacterium-group as Parascardovia denticolens. Cell numbers of L. equi, L. hayakitensis, and W. confusa/cibaria were consistent in all samples. P. denticolens, Bifidodobacterium pseudolongum, and a phylogenetic relative of Alloscardovia omnicolens were rarely detected. L. equigenerosi, a dominant speci...
The bacterial community of the horse gastrointestinal tract and its relation to fermentative acidosis, laminitis, colic, and stomach ulcers.
The Veterinary clinics of North America. Equine practice    July 8, 2009   Volume 25, Issue 2 199-215 doi: 10.1016/j.cveq.2009.04.005
Al Jassim RA, Andrews FM.The gastrointestinal tract of the horse has unique characteristics that make it well suited for the ingestion and utilization of roughage. The horse is considered a simple-stomached herbivore and is classed as a hindgut fermenter. The upper segments of the gastrointestinal tract resemble those of a typical simple-stomached animal. The lower have undergone modification to become voluminous and host to a large number of microbial populations similar to those of the compartmental stomach of ruminant animals. The main advantage of this arrangement is the ability of the horse to extract valuable nu...
Effect of live yeast culture supplementation on hindgut microbial communities and their polysaccharidase and glycoside hydrolase activities in horses fed a high-fiber or high-starch diet.
Journal of animal science    May 22, 2009   Volume 87, Issue 9 2844-2852 doi: 10.2527/jas.2008-1602
Jouany JP, Medina B, Bertin G, Julliand V.Four cecum and right ventral colon-fistulated horses were assigned in a 4 x 4 Latin square design and fed a high-fiber (HF) or a high-starch (HS) diet with or without 10 g of Saccharomyces cerevisiae (SC; CBS 493.94) containing 4.5 x 10(9) cfu/g. The HF and HS diets consisted of pelleted feeds and long wheat straw (18.0 and 3.5 g of DM.kg(-1) of BW.d(-1), respectively) given in 2 equal meals to provide an NDF:starch ratio of 3.5 and 1.0, respectively. After a 21-d adaptation period intestinal contents were collected 4 h after the morning meal on d 23 and 25 to determine bacterial and SC concen...
Dietetic effects of oral intervention with mare’s milk on the Severity Scoring of Atopic Dermatitis, on faecal microbiota and on immunological parameters in patients with atopic dermatitis.
International journal of food sciences and nutrition    May 21, 2009   Volume 60 Suppl 7 41-52 doi: 10.1080/09637480802249082
Foekel C, Schubert R, Kaatz M, Schmidt I, Bauer A, Hipler UC, Vogelsang H, Rabe K, Jahreis G.In a double-blind, placebo-controlled crossover trial, 23 patients consumed 250 ml mare's milk or placebo for 16 weeks. The aim was to examine the effects of mare's milk on the characteristics of atopic dermatitis (AD), on faecal microbiota and on clinical and immunological parameters. The intensity of AD was examined using the Severity Scoring of Atopic Dermatitis (SCORAD) index. During the mare's milk period, the mean SCORAD value of patients (n=23; 17 females, 6 males) decreased from 30.1 to 25.3 after 12 weeks (P<0.05) and to 26.7 after 16 weeks (P<0.1). In a subgroup (n=7) the SCORA...
Effects on the equine colon ecosystem of grass silage and haylage diets after an abrupt change from hay.
Journal of animal science    March 27, 2009   Volume 87, Issue 7 2291-2298 doi: 10.2527/jas.2008-1461
Muhonen S, Julliand V, Lindberg JE, Bertilsson J, Jansson A.The objective of this study was to investigate the effect of an abrupt change from grass hay (81% DM) to grass silage (36% DM) or grass haylage (55% DM), fed at similar DM intakes, and to compare the effects of silage and haylage on the composition and activities of the colon microflora. The forages were from the same swath harvested on the same day. Four adult colon-fistulated geldings were randomly assigned to diets in a crossover design. The study started with a preperiod when all 4 horses received the hay diet, followed by an abrupt feed change to the haylage diet for 2 horses and the sila...
The role of nutrition in colic.
The Veterinary clinics of North America. Equine practice    March 24, 2009   Volume 25, Issue 1 67-vi doi: 10.1016/j.cveq.2008.11.003
Durham AE.Nutritional intolerances manifesting as colic in the horse may be largely explained by divergence from the diet and ingestive behaviors to which the feral ancestors of modern domesticated equids had become accustomed and adapted. High-starch diets and abrupt dietary changes are probably foremost in the risk factors for diet-associated colic in the horse and have their basis in disruption of the stability of microbial populations resident within the equine hindgut. Although some general associations between colic and diet may be inferred from several epidemiologic studies, data derived from stu...
Biofilm evidence and the microbial diversity of horse wounds.
Canadian journal of microbiology    March 20, 2009   Volume 55, Issue 2 197-202 doi: 10.1139/w08-115
Freeman K, Woods E, Welsby S, Percival SL, Cochrane CA.Evidence of biofilms in human chronic wounds are thought to be responsible for preventing healing in a timely manner. However, biofilm evidence in horse wounds has not yet been documented. Consequently, this study aimed to determine whether biofilms could be detected in wounds, and to investigate the microbiology of chronic wounds in horses. Prior to analysis, wound surfaces were irrigated with 5 mL of sterile saline to remove debris. All wounds were swabbed twice (1 cm2 area) using sterile cotton-tipped swabs. In addition to this, 2 tissue biopsies were taken to investigate evidence of biofil...
Sharpea azabuensis gen. nov., sp. nov., a Gram-positive, strictly anaerobic bacterium isolated from the faeces of thoroughbred horses.
International journal of systematic and evolutionary microbiology    December 9, 2008   Volume 58, Issue Pt 12 2682-2686 doi: 10.1099/ijs.0.65543-0
Morita H, Shiratori C, Murakami M, Takami H, Toh H, Kato Y, Nakajima F, Takagi M, Akita H, Masaoka T, Hattori M.Four bacterial strains, designated ST18(T), HM244, HM250 and DI49, were isolated from the fresh faeces of four thoroughbred horses in Japan. Cells were Gram-positive, strictly anaerobic, catalase-negative, non-spore-forming, non-motile rods that occurred in chains. They were placed in the same subcluster based on 16S rRNA gene sequence analysis, phenotypic characteristics and levels of DNA-DNA relatedness. Their DNA G+C content ranged from 36 to 38 mol%. Lactobacillus catenaformis, Lactobacillus vitulinus and Catenibacterium mitsuokai belong to cluster XVII of the Clostridium subphylum. Strain...
Effects of crude protein intake from grass silage-only diets on the equine colon ecosystem after an abrupt feed change.
Journal of animal science    August 1, 2008   Volume 86, Issue 12 3465-3472 doi: 10.2527/jas.2007-0374
Muhonen S, Connysson M, Lindberg JE, Julliand V, Bertilsson J, Jansson A.The objective of this study was to investigate the effect of CP intake from 2 grass silage-only diets, differing in CP concentration, fed at similar DMI on the equine colon ecosystem after an abrupt feed change between the diets. Four adult right ventral colon-fistulated geldings were fed one silage-only diet high in CP (HP, 873 g of CP/d) and one diet providing recommended intakes (RP, 615 g of CP/d). An adaptation period of 15 d on either the HP or the RP diet was followed by 2 experimental periods when the diets were fed for 22 d each in a crossover design. Colon samples were taken before a...
Microbial ecology of the equine hindgut during oligofructose-induced laminitis.
The ISME journal    June 26, 2008   Volume 2, Issue 11 1089-1100 doi: 10.1038/ismej.2008.67
Milinovich GJ, Burrell PC, Pollitt CC, Klieve AV, Blackall LL, Ouwerkerk D, Woodland E, Trott DJ.Alimentary carbohydrate overload is a significant cause of laminitis in horses and is correlated with drastic shifts in the composition of hindgut microbiota. Equine hindgut streptococcal species (EHSS), predominantly Streptococcus lutetiensis, have been shown to be the most common microorganisms culturable from the equine caecum prior to the onset of laminitis. However, the inherent biases of culture-based methods are estimated to preclude up to 70% of the normal caecal microbiota. The objective of this study was to evaluate bacterial population shifts occurring in the equine caecum throughou...
Effects of dietary short-chain fructooligosaccharides on the intestinal microflora of horses subjected to a sudden change in diet.
Journal of animal science    October 16, 2007   Volume 86, Issue 2 316-323 doi: 10.2527/jas.2006-782
Respondek F, Goachet AG, Julliand V.Prebiotic compounds, such as short-chain fructooligosaccharides (scFOS), have been shown to improve health, welfare, or both, in several species, but few studies have been conducted in horses, despite the sensitivity of their hindgut microflora. We hypothesized that prebiotic oligosaccharides, known to be able to stabilize the intestinal microflora in other species, would be of importance in horses. Our study was designed to evaluate the effect of scFOS supplementation on the equine intestinal microflora and to assess its effectiveness in reducing hindgut microbial disturbances related to sudd...
Molecular profiling of Lactobacillus, Streptococcus, and Bifidobacterium species in feces of active racehorses.
The Journal of general and applied microbiology    August 30, 2007   Volume 53, Issue 3 191-200 doi: 10.2323/jgam.53.191
Endo A, Okada S, Morita H.Diversity and compositions of the Lactobacillus, Streptococcus, and Bifidobacterium group in the feces of six healthy, actively racing horses (Thoroughbreds) were analyzed by using PCR-denaturing gradient gel electrophoresis (DGGE) and real-time PCR with primer sets specific for each group. PCR-DGGE analysis of the feces showed that Lactobacillus equi, Lactobacillus johnsonii, a phylogenetic relative of Lactobacillus salivarius, a phylogenetic relative of Lactobacillus gastricus, and Weissella confusa were predominant in almost all of the feces tested, and Streptococcus bovis/Streptococcus equ...
The diversity of coliphages and coliforms in horse feces reveals a complex pattern of ecological interactions.
Applied and environmental microbiology    August 17, 2007   Volume 73, Issue 19 5975-5981 doi: 10.1128/AEM.01145-07
Golomidova A, Kulikov E, Isaeva A, Manykin A, Letarov A.The diversity of coliphages and indigenous coliform strains (ICSs) simultaneously present in horse feces was investigated by culture-based and molecular methods. The richness of coliforms (as estimated by the Chao1 method) is about 1,000 individual ICSs distinguishable by genomic fingerprinting present in a single sample of feces. This unexpectedly high value indicates that some factor limits the competition of coliform bacteria in the horse gut microbial system. In contrast, the diversity of phages active against any selected ICS is generally limited to one to three viral genotypes present in...
Fluorescence in situ hybridization analysis of hindgut bacteria associated with the development of equine laminitis.
Environmental microbiology    July 20, 2007   Volume 9, Issue 8 2090-2100 doi: 10.1111/j.1462-2920.2007.01327.x
Milinovich GJ, Trott DJ, Burrell PC, Croser EL, Al Jassim RA, Morton JM, van Eps AW, Pollitt CC.Carbohydrate-induced laminitis in horses is characterized by marked changes in the composition of the hindgut microbiota, from a predominantly Gram-negative population to one dominated by Gram-positive bacteria. The objective of this study was to monitor changes in the relative abundance of selected hindgut bacteria that have previously been implicated in the pathophysiology of equine laminitis using fluorescence in situ hybridization (FISH). Caecal cannulae were surgically implanted in five Standardbred horses and laminitis induced by oral administration of a bolus dose of oligofructose. Caec...
[Diversity and dynamics of bacteriophages in horse feces].
Mikrobiologiia    June 23, 2007   Volume 76, Issue 2 271-278 
Kulikova EE, Isaeva AS, Rotkina AS, Manykin AA, Letarov AV.The complex cellulolytic microbial community of the horse intestines is a convenient model for studying the ecology of bacteriophages in natural habitats. Unlike the rumen of the ruminants, this community of the equine large intestine is not subjected to digestion. The inner conditions of the horse gut are much more stable in comparison to other mammals, due to the fact that the horse diet remains almost unchanged and the intervals between food consumption and defecation are much shorter than the whole digestive cycle. The results of preliminary analysis of the structure and dynamics of the vi...
Vaginal lactic acid bacteria in the mare: evaluation of the probiotic potential of native Lactobacillus spp. and Enterococcus spp. strains.
Antonie van Leeuwenhoek    June 21, 2007   Volume 93, Issue 1-2 71-78 doi: 10.1007/s10482-007-9180-4
Fraga M, Perelmuter K, Delucchi L, Cidade E, Zunino P.Lactic acid bacteria (LAB) are important members of the human vaginal microbiota and their presence is considered beneficial. However, little is known about native vaginal bacteria in other animal species such as the horse. The aim of this work was to quantify the vaginal lactic acid bacteria and lactobacilli of mares and to establish if selected equine vaginal lactic acid bacteria, particularly Lactobacillus and Enterococcus spp. strains, could exhibit potential as probiotics. The vaginal lactic acid bacteria and lactobacilli of 26 mares were quantified by plate counts. Five strains (three La...
Fermentative gases in breath indicate that inulin and starch start to be degraded by microbial fermentation in the stomach and small intestine of the horse in contrast to pectin and cellulose.
The Journal of nutrition    June 15, 2006   Volume 136, Issue 7 Suppl 2108S-2110S doi: 10.1093/jn/136.7.2108S
Coenen M, Mösseler A, Vervuert I.No abstract available
Changes in equine hindgut bacterial populations during oligofructose-induced laminitis.
Environmental microbiology    April 21, 2006   Volume 8, Issue 5 885-898 doi: 10.1111/j.1462-2920.2005.00975.x
Milinovich GJ, Trott DJ, Burrell PC, van Eps AW, Thoefner MB, Blackall LL, Al Jassim RA, Morton JM, Pollitt CC.In the horse, carbohydrate overload is thought to play an integral role in the onset of laminitis by drastically altering the profile of bacterial populations in the hindgut. The objectives of this study were to develop and validate microbial ecology methods to monitor changes in bacterial populations throughout the course of experimentally induced laminitis and to identify the predominant oligofructose-utilizing organisms. Laminitis was induced in five horses by administration of oligofructose. Faecal specimens were collected at 8 h intervals from 72 h before to 72 h after the administration ...