Foram utilizados neste experimento quatro garrotes Jersey (J) e quatro Gir (G), providos de cânula ruminal. Dois meses antes da indução da acidose láctica ruminal (ALR), os animais foram alimentados com dieta padronizada a base de feno e concentrado. A ALR foi induzida experimentalmente por meio da administração de sacarose intraruminal, correspondente ao peso metabólico corrigido, segundo técnica descrita por ORTOLANI (l995). Colheitas de sangue, suco de rúmen, urina, fezes e exames clínicos foram realizados nos seguintes momentos após a indução: zero, 14, 16, 18, 20, 22 e 24 horas. O pH e as concentrações de ácido láctico total, D e L e de seus sais foram determinados em todos os materiais biológicos colhidos. No sangue foram avaliados o hematócrito, os exames gasométricos e a concentração de creatinina; esta última substância também foi determinada na urina. Após a última colheita, todo o conteúdo ruminal foi completamente retirado para a determinaçãodo seu volume. Os bovinos de ambas as raças apresentaram marcante e idêntica acidose ruminal, não ocorrendo diferença no pH e na concentração de ácido láctico total, L e D no suco de rúmen. A acidose metabólica sistêmica foi moderada em ambas as raças, porém esta foi mais intensa nos bovinos J, confirmada pelas menores concentrações médias de bicarbonato e TCO2 (P < 0,00001) e pelo menor pH sangüíneo, (p < 0,025). Os garrotes J absorveram maiores quantidades de ácido láctico total e do isômero D; este último apresentou correlação negativa com o pH sangüíneo nesta raça (r = -O,78). Os garrotes G apresentaram maior capacidade homeostática de manutenção de pH sangüíneo no final da indução, provavelmente pela maior metabolização do lactato-L. Entretanto, os mesmos animais tiveram maior grau de desidratação, evidenciado pelas maiores porcentagens de hematócrito e de déficit de volume plasmático (p < 0,00001). Nessa raça ocorreu uma menor filtração glomerular, demonstrada pela maior concentração sérica de creatinina (p < 0,00001), menor depuração deste catabólito (p < 0,003) e menor volume urinário estimado (p < 0,05). Não ocorreram diferenças significativas no pH fecal entre as raças estudadas. Houve correlação negativa entre a concentração de lactato total fecal e o correspondente pH (r = - 0,65). / Four Jersey (J) and four Gir (G) rumen-cannulated steers were used. The steers were fed, for two months before the beginning of the rumen lactic acidosis (RLA) induction, a standard diet of hay and concentrates. The RLA was induced experimentally through the administration of sucrose into the rumen, according to the corrected metabolic weight, after ORTOLANI (1995). Blood, rumen fluid, urine, and fecal samples were collected and clinical examination carried out in the following times after the induction: zero, 14, 16, 18, 20, 22 and 24 hours. The pH, the total lactic acid and its L and D isomers were determined in all samples. The hematocrit, acid-base variables and the creatinine concentration were determined in the blood samples; creatinine was also determined in the urine samples. All the rumen content was evacuated in order to evaluate its volume at the 24th h. A intense rumen acidosis was reached; no differences in the rumen fluid pH and in the concentration of the total lactic acid and its isomers were found in both studied breeds. A moderate level of systemic metabolic acidosis was reached in both breeds, but lower overall mean of bicarbonate and TCO2 (p < 0.0001) as well as blood pH (p < 0.025) were found in the J steers. These steers absorbed higher amounts of total lactic and its D isomer than the G animals; the higher the blood D-lactate concentration, the lower the blood pH (r = - O.78) in the former breed. Better blood pH homeostasis were kept, at the end of induction, by the G steers, probably by their higher efficiency to metabolize L-lactate. However, the G steers exhibited a higher level of dehydration as seen by the greater hematocrit and plasma volume deficit (p < 0.00001). They also presented a lower glomerular filtration as evidenced by the higher creatinine serum levels (p < 0.00001), its lower urinary clearance (p < 0.003) and the lower estimated urinary volume (p < 0.05). There were no differences in the fecal pH values presented by both breeds. There was a negative correlation between the fecal total lactate concentration and the fecal pH (r = - 0.65).

Tumor metabolism is a highly dysregulated process that is identified as a unique target for therapy. Current philosophy proposes that tumor metabolism is a plastic and flexible process which sustains proliferative and survival advantages. Tumors employ an anaerobic glycolytic pathway resulting in the overproduction of lactate. Additional thinking suggests that the conversion of pyruvate to lactate regenerates the NAD+ pool in the cell, maintaining a sustainable oxidative environment. Regardless of the reasons for lactate overproduction, its excretion and build up in the microenvironment results in acidic tumor microenvironments. Tumor acidosis has been measured with several different methods, but consistently averages from pH 6.6 to 7.0. Tumor acidity can thus be measured as a biomarker for tumor metabolism. This work examines the commonly explored energy pathways available to the cancer cell and a non-invasive MRI method to measure the efficacy of the tumor metabolism targeting agent. Appendix A is an introduction to tumor metabolism pathways and the large list of candidate therapies in interfering with energy production. Glucose, fatty acid, and glutamine metabolisms are all discussed along with PI3K/AKT/mTOR and HIF growth signals and ion transport. Magnetic resonance imaging and positron emission tomography are examined as imaging methods for non-invasively interrogating tumor acidosis. Appendix B presents the findings in a study where tumor metabolism was targeted with an mTOR inhibitor, where tumor growth rate was initially decreased and accompanied by an early, acute increase in tumor extracellular pH with acidoCEST MRI. Chapter 2 discusses the combination of a lactate dehydrogenase inhibitor in conjunction with doxorubicin in a breast cancer model. Tumor extracellular pH was shown to increase when measured with acidoCEST MRI, and an increase in cell death was measured. Chapter 4 discusses the studies and experimental designs that can be done in the near future.

Muscle wasting and increased proteolysis is a major problem in chronic kidney disease (CKD). Exercise is potentially beneficial, but has been under-investigated in pre-dialysis CKD and could theoretically worsen acidosis through exercise-induced lactic acid generation. We therefore investigated effects of 6 months walking exercise with and without additional alkali therapy. 40 patients were recruited (23 male and 17 female, median age 58, range 20-83, mean eGFR±SEM 25.7±1.2ml/min/1.73m2). 20 undertook walking exercise at a Borg Rating of Perceived Exertion Rate (RPE) of 12-14 for at least 30 minutes, 5 times a week. The other 20 continued with normal physical activity (non-exercising controls). In addition to standard oral bicarbonate therapy (STD), 10 patients in each group were randomised to receive additional bicarbonate (XS). Blood and vastus lateralis muscle biopsies were drawn at baseline, one and six months. 18 exercisers (including 8 in XS group) and 14 controls (6 in XS group) completed the 6 month study. Exercise tolerance increased after 1 and 6 months in the exercisers, but not the controls, accompanied by a reduced acute lactate response in the XS, but not the STD exercising group. After 6 months of exercise, 9 intramuscular free amino acids showed striking depletion in the STD, but not XS bicarbonate group. This suggests an inhibition of active amino acid transporters, possibly the SNAT2 transporters that are inhibited by acidosis. Studies with cultured myotubes identified glucocorticoid as a possible mediator of acid s inhibitory effect on SNAT2. The preservation of amino acid concentrations in the XS exercising group was accompanied by strong suppression of ubiquitin E3-ligases MuRF-1 and MAFbx which activate proteolysis through the ubiquitin-proteasome pathway. However, other anabolic indicators (Protein Kinase B activation and suppression of the 14kDa actin fragment) were unaffected in the exercising XS group. Possibly because of this, overall suppression of myofibrillar proteolysis (3-methyl histidine excretion) and increased lean body mass (DEXA) were not observed in the exercising patients. As XS alkali had no effect in non-exercisers, it is concluded that alkali effects in the exercisers arose by countering exercise-induced acidosis. Sulphuric acid produced from the catabolism of sulphur-containing amino acids ingested in the diet is the main contributor to the daily titratable acid load and hence acidosis in CKD. In these patients the amount of sulphate excreted in urine over 24h varied widely between individuals. This directly correlated with 3-methyl histidine excretion suggesting that sulphate excretion may be a better clinical indicator of acidotic patients at long-term risk of cachexia than conventional measures such as venous bicarbonate. Studies with cultured myotubes confirmed that skeletal muscle is a source of sulphuric acid and showed that production of this acid is partly suppressed by L-Glutamine a potential novel way to control acidosis in CKD.

L'acidose ruminale latente (ou acidose sub-clinique) est une préoccupation majeure pour la nutrition des ruminants à haut potentiel de production. Cet état se caractérise par une instabilité du microbiote et des fermentations ruminales qui s’orientent variablement vers le propionate et/ou le butyrate. L’une des stratégies de prévention de l’acidose latente consiste à distribuer dans l’alimentation des ruminants des probiotiques capables de rééquilibrer le microbiote et les fermentations ruminales (dans un sens favorable pour l’animal). L’analyse de la bibliographie montre toutefois que l’effet des probiotiques, et plus particulièrement des bactéries probiotiques (BP), est variable et parfois contradictoire ce qui serait probablement lié à l’instabilité du microbiote. Afin d’étudier la possibilité de prévenir l’acidose latente par les bactéries propioniques et/ou lactiques, nous avons émis l’hypothèse que leur efficacité dépend des orientations fermentaires dans le rumen. Des acidoses latentes butyrique et propionique caractérisées par des profils fermentaires et microbiens distincts ont été développées chez le mouton non productif et la vache laitière pour étudier l’effet et le mode d’action de la bactérie propionique P63 seule ou associée aux lactobacilles Lb. plantarum ou Lb. rhamnosus (P63, Lp + P63 et Lr + P63) sur le fonctionnement de l’écosystème ruminal et les performances animales. Chez le mouton en situation d’acidose propionique, les BP utilisées ont amélioré le pH ruminal via une réduction de la proportion en lactobacilles. Chez la vache laitière, la stabilisation du pH a été associée à une moindre disponibilité en hydrogène susceptible d’être transformé en protons, suite à une augmentation de la propionogenèse et/ou de la densité bactérienne, deux voies consommatrices d’hydrogène. Au cours de l’acidose latente butyrique, l’amélioration du pH n’a été observée que chez les moutons supplémentés avec Lp + P63. Cet effet semblait être dû à une diminution des acides gras volatils et de la proportion en S. bovis mais aussi à un pH initial faible (pH < 5,5) probablement optimal pour l’action des BP ; ce qui n’était pas le cas chez les vaches pour lesquelles le pH initial était compris entre 5,9 et 6,1. En revanche, l’efficacité digestive a été augmentée par l’association de P63 aux lactobacilles chez la vache laitière. L’association Lp + P63 a augmenté les activités fibrolytiques (cellulase, xylanase) et la digestibilité de la matière organique, tandis que Lr + P63 a amélioré la digestion des fibres et a diminué la production de méthane de 25%. Nous n’avons pas observé d’effet sur les performances zootechniques, ce qui serait probablement dû au dispositif expérimental en carré Latin qui n’est peut-être pas optimal pour mettre en évidence l’effet des BP. Nos résultats sont les premiers à démontrer l’efficacité des bactéries probiotiques pour sécuriser et/ou améliorer la digestion des rations et réduire la production de méthane chez le ruminant en acidose, et l’association de P63 avec les souches de Lactobacillus sont les plus efficaces. Enfin, nous avons validé notre hypothèse selon laquelle l’effet et le mode d’action des bactéries probiotiques pour prévenir l’acidose dépendent des orientations fermentaires dans le rumen. / Subacute ruminal acidosis (SARA) is a major concern for the nutrition of high-producing ruminants. This digestive disorder is characterized by the instability of the microbial ecosystem and fermentations which are oriented towards propionate and/or butyrate at the expense of acetate (propionic or butyric SARA). Among the strategies used to prevent SARA, supplementation with direct-fed microbials (DFMs) is thought to be able to balance the ruminal microbiota and fermentation. The analysis of the literature shows that the effect of DFMs, especially bacterial ones, is variable and sometimes contradictory which is probably related to the instability of the microbiota. To investigate the possibility of preventing SARA by propionibacteria and/or lactobacilli based DFMs, we hypothesized that their effectiveness depends on the ruminal fermentation patterns. Butyric and propionic SARA, characterized by distinct microbial and fermentation profiles, have been developed in non-productive sheep and lactating dairy cows to investigate the effects and mode of action of the Propionibacterium P63 alone or in conjunction with the lactobacilli strains Lb. plantarum or Lb. rhamnosus (P63, P63 and Lp + Lr + P63) on the ruminal ecosystem and animal performances. During the propionic SARA induced in sheep, the DFMs used increased the ruminal pH with a concomitant reduction in the lactobacilli population. In dairy cows, the pH stabilization was associated with a lower availability of hydrogen capable of being transformed into protons, following a stimulation of propionogenesis and/or bacterial growth that consume hydrogen. During butyric SARA, improvement in pH was observed only in sheep supplemented with Lp + P63. This effect appeared to be due to a decrease in VFA production and S. bovis proportion. Moreover, the lower initial pH (pH <5.5) was probably optimal for DFMs action, which was not the case for the dairy cows for which the initial pH was between 5.9 and 6.1. For the dairy cows, diet digestion was improved when P63 and lactobacilli association were fed. Indeed, Lp + P63 increased the fibrolytic activities (cellulase, xylanase) and digestibility of organic matter, while Lr + P63 improved fiber digestion and decreased methane production by 25%. We did not observe any effect on animal performances, which was probably due to the Latin square design that is not the best to evaluate the DFMs effects on animal performances. Our results are the first to demonstrate the effectiveness of bacterial DFMs to secure and/or improve diet digestion and reduce methane production in ruminants. Moreover, it seems that the association of P63 with the lactobacilli strains is more effective. Finally, we validated our hypothesis that the effect and mode of action of bacterial DFMs to prevent SARA is conditioned by ruminal fermentation patterns.

O presente trabalho avaliou a possibilidade de duas diferentes quantidades de melão, com alto teor de açúcares, em causar acidose ruminal em ovinos não adaptados. Foram utilizados 12 ovinos mestiços Santa Inês, machos, providos de cânula ruminal, com 25 kg de P.V. e 8 m de idade, que nunca receberam rações concentradas, frutas ou raízes, anteriormente. Os animais foram mantidos em baias coletivas com dieta basal composta de volumoso (feno de capim Cynodon dactylon - Coast cross) na base de 2,3% de seus pesos vivos, providos de água e sal mineralizado à vontade. Após 30 dias de adaptação, os ovinos foram distribuídos aleatoriamente em dois grupos iguais, assim constituídos: G1: 25% da M.S. de melão e G2: 75% de melão. O melão inteiro, sem as sementes, com 12º Bx de grau Brix (120 g sacarose/kg polpa e 7,8 % M.S.) foi triturado administrando-se pela cânula ruminal 130 g e 389,4 g de sacarose no G1 e G2, respectivamente, após os animais permanecerem em jejum por 12 horas. Foram realizados exames físicos, coletadas amostras de fluido ruminal e sangue nos seguintes tempos após a administração do substrato: zero, 3, 6, 12, 18 e 24 h. Os animais do G1 apresentaram durante a 3ª a 6ª h quadro de acidose ruminal por AGVs (subaguda) caracterizado por pH ruminal ligeiramente inferior a 5,6; discreto aumento no teor de ácido láctico-L, no potencial de oxirredução (POR) e no tempo de redução do azul de metileno (RAM) ruminais, sem que os animais manifestassem quaisquer sintomatologia clínica. Os animais do G2 desenvolveram quadro de acidose láctica ruminal, evidenciado pelo baixo pH (< 5,0), altos teores de lactato-L, valores de POR e da RAM, aumento temporário de osmolaridade ruminal, porém os animais não se tornaram desidratados, e apresentaram uma intensa diurese enquanto perdurou marcada hiperglicemia. Os animais evoluíram para uma moderada acidose metabólica sistêmica. A taquicardia e a taquipnéia foram provocadas pelo aumento da circunferência abdominal, devido ao grande volume de conteúdo administrado pela cânula, não sendo no caso da taquicardia gerada pelo aumento do volume globular, oriunda da desidratação e encontrada classicamente nesse tipo de acidose. A diminuição dos movimentos do rúmen foi correspondente a queda no pH ruminal e elevação dos teores de lactato-L no rúmen. O baixo pH e os altos valores de POR interferiram no aumento do tempo da RAM. Não se recomenda o oferecimento de altas quantidades de melão (75% da M.S.), porém acredita-se que os ovinos não terão problema de ingerir a quantia de 25% da M.S., desde que se tomem cuidados para a adaptação gradual dos animais ao substrato. / The present study evaluated the possibility of ruminal acidosis being caused by two distinct amounts of melon with high sugar content on non-adapted sheep. Twelve crossbreed Santa- Inês sheep with rumen cannula were used. Animals were male, 8 months old, 25 kg B. W., and had never eaten concentrated feed, fruits or roots of any kind before. They were kept in collective pens and their basal diet was composed on 2.3% of their B. W. of Coast cross (Cynodon dactylon) hay, water, and mineral salt Ad libitum. After 30 days of adaption, animals were divided in two groups: G1: 25% of D. M. of melon; and G2: 75% of D. M. of melon. The animals fasted for 12 hours. Then the whole melon, without seeds, 12º Bx (120 g sucrose/kg pulp and 7.8% D. M.) was crushed and administered through the rumen cannula, it represented 130 g and 389.4 g of sucrose on G1 and G2, respectively. Physical examinations along with the collection of ruminal fluid and blood were done after the administration of the substrate at: 0, 3, 6, 12, 18, and 24 h. G1 sheep presented VFAs ruminal acidosis (sub-acute) between the 3ª and 6ª h, characterized by rumen pH slightly inferior to 5.6, discrete lactic-L acid content increase, increased redox potential (RP) and methylene blue redox (MBR) time of the ruminal fluid, and lack of clinical signs. G2 presented lactic ruminal acidosis, ruminal fluid pH < 5.0, high lactate-L content, increased RP and MBR time, increased ruminal fluid osmolarity, no dehydration, and increased diuresis during hypoglycemic period. Animals had moderate systemic acidosis. Tachycardia and tachypnea were caused by an increase on abdominal circumference, resultant of the large amount of melon administrated through the cannula. Therefore these conditions were not caused by the increased globular volume and dehydration typically found on this type of acidosis. Reduced ruminal movements frequency corresponded to decreased ruminal pH and increased Lactate-L ruminal content. Reduced rumen pH and increased RP caused the increase on MBR time. Therefore, it is not recommended offering of large amounts of melon (75% da D.M.) on the diet, though it is believed that sheep will have no problems ingesting 25% of D.M. of melon, whenever the proper gradual adaptation is performed previously.

Orientador: Danilo Domingues Millen / Resumo: O objetivo deste estudo foi avaliar a redução do tempo de adaptação à rações com alto teores de energia para bovinos Nelore canulados em confinamento com a utilização de virginiamicina (VM) como aditivo alimentar, em que foram avaliadas as seguintes variáveis: pH, temperatura, e potencial de óxido-redução do rúmen, taxa de desaparecimento, digestibilidade total e degradabilidade ruminal de nutrientes, seletividade da ração e comportamento ingestivo, produtos da fermentação ruminal, assim como dados de ingestão de matéria seca. O delineamento experimental foi em quadrado latino 5x5, e cada período durou 21 dias, com 7 dias de washout entre o final e o início de um novo período. Foram utilizados 5 bovinos inteiros, com peso vivo aproximado de 414.86 ± 21.71 kg e com 17 meses de idade. Neste estudo os animais foram divididos em cinco tratamentos: 1) Monensina (MON; 30 mg/kg) com adaptação por 14 dias; 2) MON (30 mg/kg) + VM (25 mg/kg) com adaptação por 14 dias; 3) VM (25 mg/kg) com adaptação por 14 dias; 4) VM (25 mg/kg) com adaptação por 9 dias; e 5) VM (25 mg/kg) com adaptação por 6 dias. Bovinos que consumiram apenas MON tiveram menor concentração de butirato (P=0,02) e maior concentração de propionato (P=0,04), quando comparados aos que consumiram VM e foram adaptados por 14 dias. E animais que consumiram VM e foram adaptados por 14 dias tiveram maiores proporções AGCC quando comparados com animais que consumiram VMMON (P= 0,05) e quando comparados com animais que consumiram... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this study was to evaluate the reduction of adaptation length to the high-energy diet offered to cannulated Nellore cattle using Virginiamycin (VM) as sole feed additive, in which the following variables were assessed: pH, temperature,and ox-redox potential of the rumen, rate of disappearance, total tract digestibility and rumen nutrient degradability, feed particles sorting and feeding behavior, ruminal fermentation end-products, as well as dry matter intake. It was adopted the experimental design in a 5 x 5 Latin square, where each period lasted 21 days, with 7-day washout between the end and the beginning of a new period. Were used 5 Nellore yearling bulls,with approximately 414.86 ± 21.71 kg of body weight and 17 mo-old. In this study, the animals were divided into five treatments: 1) MON (30 mg/kg) adapted by 14 days; 2) MON (30 mg/kg) + VM (25 mg/kg) adapted by 14 days; 3) VM (25 mg/kg) adapted by 14 days; 4) VM (25 mg/kg) adapted by 9 days and 5) VM (25 mg/kg) adapted by 6 days.Bovine animals that consumed only MON had lower concentration of butyrate (P = 0.02)and higher concentration of propionate (P = 0.04) when compared to those that consumed VM and were adapted for 14 days. Animals that consumed VM and were adapted for 14 days had higher AGCC ratios when compared to animals that consumed VMMON (P = 0.05) and when compared to animals that consumed only MON (P = 0.04). As the adaptation time increased for animals that consumed VM, the dry matter inta... (Complete abstract click electronic access below) / Mestre

Theses (Msc.(Med.)(Pharmacy))--University of Limpopo, 2010. / With the availability of Highly Active Antiretroviral Therapy (HAART), one of the limitations of treatment safety is the occurrence of adverse events associated with antiretroviral agents. The aim of this study was to establish whether stavudine dosage reduction prevents toxicity from developing and minimizes the incidence of symptomatic hyperlactataemia/lactic acidosis (LA) in adults female HIV/AIDS infected patients. This retrospective study covered adult patients treated at the adult ARV clinic, Dr George Mukhari Hospital. The records of 88 patients aged between 27 and 59 years, initiated and treated from August 2004 to January 2006, were analyzed ( 67 females and 21 males). Twenty nine females started their treatment on a regimen containing 40 mg stavudine while 38 females were started on 30 mg stavudine. A group of male patients (n=21) were included for comparison. Seven males started on 40 mg stavudine and 14 were on 30 mg stavudine. Ten out of twenty nine females who started treatment on 40 mg stavudine developed elevated lactate levels while nineteen received 30 mg stavudine as reduced dose. Eight out of nineteen further developed elevated lactate levels when on 30 mg stavudine but eleven out of nineteen remained stable on treatment with 30 mg stavudine as reduced dose. In the group started on 30 mg stavudine, thirteen females out of thirty seven developed elevated lactate levels while twenty four were stable on their treatment. Key words: stavudine, dosage reduction, lactate levels, hyperlactataemia, lactic acidosis.

Bibliography: p. 137-154. / 154 p. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis details a series of studies in patients, in human volunteers and in large animals. Haemodynamics and left ventricular systolic and diastolic mechanics are reported during lactic acidosis, during therapies for lactic acidosis, and during hyperdynamic and hypovolemic shock. The study has the unifying hypothesis that cardiac dysfunction is important in hyperdynamic and hypovolemic shock and is not caused by lactic acidosis. / Thesis (M.D.)--University of Adelaide, Dept. of Anaesthesia and Intensive Care, 1997?

Two trials were conducted to evaluate effects of grain adaptation protocol on subacute acidosis, feeding behaviour and ADG of cattle. In trial one, 12 crossbred heifers (384 ¡À 25 kg) were stepped from 40% to 90% dietary concentrate by either rapid adaptation (RA; one step-up diet fed for 3 d) or by gradual adaptation (GA; five step-up diets fed for 3 d each). Mean daily ruminal pH variables did not differ (P > 0.10) between treatments but variances of a number of ruminal pH variables were greater (P < 0.05) for RA than GA during adaptation to 65% and 90% concentrate. Mean hourly pH did not differ over the first 24 h of adaptation to 65% concentrate, but variance of hourly pH tended (P < 0.10) to be greater for RA than GA for eight of the first 24 h of adaptation to 90% concentrate. Increased variance in ruminal pH parameters was associated with detection of acidosis in certain individuals. On d 1 of 90% concentrate, ruminal pH tended (P = 0.07) to be lower at 11 and 12 h post-feeding with RA than with GA. Ruminal volatile fatty acids (VFA) and osmolality were similar between treatments. In trial two, 120 crossbred heifers (366 ¡À 23 kg) were adapted from 40% to 90% concentrate. A protocol identical to trial one was used with the addition of moderate adaptation (MA; three step-up diets fed for 3 d each). The increase to 65% concentrate caused reduced daily bunk attendance and increased maximum intermeal interval for RA compared to MA and GA cattle but the increase to 90% did not. ADG was reduced for RA compared to MA or GA during adaptation but over day 1 to 69 ADG did not differ between treatments (P ¡Ý 0.41). Current management strategies for preventing acidosis in pens of cattle are based on responses of the most susceptible individuals. Improved understanding of individual responses to acidotic challenge may allow development of more effective acidosis prevention practices.

Organic acids, including L- and D-lactate, explain most but not the entire elevated anion gap in diarrhea-associated metabolic acidosis. Also, D-lactate has been implicated in the neurological symptoms associated with this condition. Less-common organic compounds may influence the anion gap and neurological symptoms. This research aimed to characterize and attempt to identify a previously unidentified compound, Compound X, first noted in diarrheic acidotic calves with elevated anion gap (Omole, 1999).<p> High performance liquid chromatography (HPLC) was used to measure Compound X in biological fluids from diarrheic and healthy calves; diarrheic piglets, foals, and human infants; and calves experimentally infused with saline or acid. Attempts were made to identify Compound X using HPLC with tandem and Fourier-transform mass spectrometry.<p> Compound X was significantly higher in diarrheic calf serum (p<0.001) and lower in feces (p<0.001) and rumen fluid (p<0.001) than those fluids from healthy calves. Compound X in serum from acid-infused calves (median peak area ratio = 1.5 1.9) was lower than that of diarrheic calves (median = 4.8) and only slightly greater than that of healthy calves (median = 1.2). Serum Compound X correlated with serum D-lactate in diarrheic and healthy calves combined; however, no such correlation was observed in acid-infused calves. Conversely, a relationship between Compound X and neurological disturbance was present in acid-infused calves, but not in diarrheic calves. In other species, Compound X was highest in diarrheic infants and lowest in diarrheic piglets. Although mass spectrometry and database library searches revealed several compounds as putative matches for Compound X, none of the compounds made sense within the context of acidosis and mammalian biological fluids. Therefore, the identity of Compound X remains unknown.<p> Compound X has been established as a ubiquitous compound(s) present in the biological fluids of mammals. Compound X may be a normal intestinal compound or bacterial metabolite that crosses the intestinal epithelium during diarrhea. In spite of this, Compound X was associated with the neurological manifestations of D-lactic acidosis. Compound X`s identity was not determined, and some reasons for this and future directions are discussed.