Acute, subacute and chronic sequelae of horses accidentally exposed to monensin-contaminated feed.

BACKGROUND: Monensin is highly toxic to horses and inadvertent ingestion can result in cardiac injury and death. OBJECTIVES: To describe sequelae of monensin ingestion and to determine clinical predictors of outcome. STUDY DESIGN: Observational clinical study. METHODS: Physical examination, electrocardiogram and echocardiography were performed on 76 horses accidentally exposed to monensin-contaminated feed. Four horses were examined within 14 days of exposure (acute period), 29 horses were examined between 15 and 45 days post-exposure (subacute period) and 70 horses were examined 4-10 months after exposure (chronic period). Follow-up information was obtained for 56 horses by telephone interviews approximately 16 months after exposure. RESULTS: Cardiac abnormalities were detected in 4/4, 19/29 and 31/70 horses during the acute, subacute and chronic periods, respectively. Sixteen months post-exposure, 34 of the 64 horses (53%) for which the outcome was known had returned to their previous use, 13 (20%) were reported to be exercise intolerant, three (5%) were retired and 14 (22%) were dead (two deaths, 12 euthanasia). Thinning of the myocardium observed at any point in time was associated with a negative outcome. Heterogeneity of the myocardium observed in the acute/subacute period was associated with a negative outcome while subjective contractile intraventricular dyssynchrony, cardiac chamber dilation, decreased fractional shortening and multiple premature ventricular complexes observed in the chronic period were associated with a negative outcome. Some horses with significant changes associated with a negative outcome in the chronic phase still returned to their previous work. MAIN LIMITATIONS: No control group and only 27 horses were examined more than once. CONCLUSIONS: Clinical outcome of horses exposed to sublethal doses of monensin is highly variable. The presence of heterogeneity and thinning of the myocardium shortly after intoxication were associated with a negative outcome.

The physiological response of broiler chickens to the dietary supplementation of the bacteriocin nisin and ionophore coccidiostats.

The aim of this study was to investigate the effect of dietary supplementation with nisin alone or in combination with salinomycin or monensin on broiler chickens in terms of growth performance, selected blood parameters, digestive enzyme activity, apparent nutrient digestibility, and tibiotarsus mineralization, as well as selected gastrointestinal tract (GIT) organ weights, intestinal length, and central immune organ weights. Two independent experiments, each including 400 one-day-old female Ross 308 chicks differing in ionophore coccidiostats, i.e., salinomycin and monensin supplementation, were conducted. The following treatments were applied: experiment 1: NA-no additives, SAL-salinomycin (60 mg/kg diet), NIS-nisin (2,700 IU/kg diet), SAL+NIS-salinomycin (60 mg/kg diet) and nisin (2,700 IU/kg diet); experiment 2: NA-no additives, MON-monensin (100 mg/kg diet), NIS-nisin (2,700 IU/kg diet) and MON+NIS-monensin (100 mg/kg diet) and nisin (2,700 IU/kg diet). The addition of nisin with or without ionophores to the birds' diet improved broiler growth performance in terms of BWG and FCR (days 1 to 14) and BWG and FI (15 to 35 d; 1 to 35 d). Salinomycin showed effects similar to those of nisin influence on growth performance (1 to 35 d), while monensin supplementation resulted in lower BWG. Moreover, no additive effect between nisin and ionophores was observed. Nisin and salinomycin had no influence on the serum concentration of selected hormones and other blood biochemical parameters except glucose, which was reduced by nisin. A decrease in lipase activity was observed during nisin and salinomycin supplementation, while the apparent ileal digestibility of fat was not affected. However, the digestibility of crude protein increased with nisin administration. Additionally, the effects of nisin on decreasing the weight and length of GIT segments were observed. Supplementation with nisin and monensin was not associated with a negative impact on tibiotarsus mineralization and the immune organ index. This study suggests that nisin may be used in broiler nutrition as a growth promotor, with no negative influence on the bird's metabolism or immune status.

How Metabolic Diseases Impact the Use of Antimicrobials: A Formal Demonstration in the Field of Veterinary Medicine.

Decreasing the use of antimicrobials has become a primary objective for both human and veterinary medicine in many countries. Medical prevention and good nutrition are seen as key parameters for reducing antimicrobial use. However, little consideration has been given to how metabolic diseases may influence the use of antimicrobials in humans and animals through limiting the prevalence and severity of infectious diseases. To quantify this relationship using the example of a common metabolic disease in dairy cows (subclinical ketosis, SCK), we constructed a stochastic model reporting the total quantity of curative antimicrobials for a given population with the prevalence of cows at risk for SCK. We considered the prevalence of SCK, the relative risk of the disease in cases of SCK compared to no SCK and the use of antimicrobials to treat SCK-induced infectious diseases. Reducing the percentage of cows at risk for SCK from 80% to 10% was associated with an average decrease in the use of antimicrobials of 11% (prevalence of SCK from 34% to 17%, respectively) or 25% (prevalence of SCK from 68% to 22%, respectively), depending on the relative risk to contract SCK if risk was present. For a large percentage of the cows at risk for SCK, using a preventive bolus of monensin reduced the use of curative antimicrobials to the same level that was observed when the percentage of cows at risk for SCK was low. The present work suggests similar approaches for obesity and diabetes.

Serum, milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation.

Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the Cmax , Tmax, and t1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low-dose group. The cTnI concentrations in the high-dose group were 2.1 times that of cTnI in the low-dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.

Salinomycin and other ionophores as a new class of antimalarial drugs with transmission-blocking activity.

The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads.

[The use of monensin premix in dairy cows: simple and essential steps for ensuring its proper use]. / L'utilisation du prémélange de monensin chez les vaches laitières: un suivi simple et essentiel pour s'assurer d'une utilisation adéquate.

The use of monensin premix in dairy cows: Simple and essential steps for ensuring its proper use. Dietary monensin, containing monensin sodium as active ingredient, is frequently used on dairy farms in Canada. Although the use of monensin is safe, some overdose situations have been reported following consumption of higher than recommended doses. A regular monitoring of bulk tank milk fat percentage should be performed to ensure quick detection of a potential overdose situation. Diarrhea and sudden drop in dry matter intake are other potential clinical signs of monensin overdose. Quick detection of such cases will allow rapid correction of the situation.(Translated by the authors).

Parâmetros digestivos e produção de proteína microbiana em novilhas em crescimento compensatório / Digestive parameters and protein microbial production in heifers under compensatory growth

Avaliaram-se o manejo para crescimento compensatório e o efeito da suplementação com ionóforo na dieta sobre os parâmetros digestivos e sobre a produção de proteína microbiana de novilhas leiteiras. Foram utilizadas 20 animais puros da raça Pardo-Suíça, com média de peso inicial de 200kg aos cinco meses de idade. Os tratamentos foram arranjados em um esquema fatorial 2x2x2, e os animais foram alocados, aleatoriamente, em cada uma das combinações. O fator 1 consistiu dos sistemas de alimentação (convencional e crescimento compensatório), o fator 2, da utilização (200mg de monensina/animal/dia) ou não de ionóforo e o fator 3, dos períodos de alimentação (P1 e P2). A inclusão de ionóforo na dieta aumentou os coeficientes de digestibilidade total da matéria seca, da matéria orgânica, dos carboidratos totais e da fibra em detergente neutro. Não houve efeito do sistema de alimentação, da adição de ionóforo à dieta e do período sobre a produção microbiana. A eficiência microbiana (g PB microbiana/kg de NDT consumido) no período de restrição foi maior que no período de realimentação.

The effects of compensatory growth and ionophore supplementation of diet of dairy heifer on digestive parameters and protein microbial production were evaluated. Twenty five-month-old Brown-Swiss heifers averaging 200kg b.w. were used. The treatments were arranged in a factorial design (2x2x2) with the animals randomly allocated to each of the combinations. Factor 1 was based on the feeding systems (conventional and compensatory growth), factor 2 on ionophore supplementation option (200mg of monensin/animal/day or not) and factor 3, on the feeding periods (P1 and P2). The diet supplemented with ionophore increased the total digestibility coefficients of dry matter, organic matter, total carbohydrates, and neutral detergent fiber. No effect of feeding systems, ionophore supplementation, or feeding periods based on microbial production was oberved. The microbial efficiency (g of microbial crude protein/kg of NDT intake) during the restriction period was higher than the re-feeding period.

Interaction of ionophore and vitamin E in knockdown syndrome of turkeys.

Monensin and vitamin E concentrations, as well as histopathology of skeletal muscles and myocardium, were evaluated in broad-breasted white turkeys kept in commercial facilities. Turkeys with knockdown syndrome had myopathy of skeletal muscles, but no lesions in the myocardium. Generally, concentration of monensin in serum was highest in turkeys diagnosed with knockdown syndrome given more than 90 mg/kg of monensin in the diet, followed by turkeys diagnosed with knockdown syndrome given <90 mg/kg of monensin in the diet, healthy turkeys fed a diet that contained <90 mg/kg of monensin, and finally healthy turkeys fed a diet free of monensin (not detectable). However, the concentration of monensin was highly variable within each group, and the median was lower than the average. Vitamin E concentrations in the livers varied from low-normal to below normal and were statistically higher in healthy turkeys fed a diet free of monensin than in the livers of birds from the 3 groups exposed to monensin. This suggests that the concentration of monensin in serum positively correlates to the severity of clinical signs and pathology and to the amount of monensin in the feed. Although the methodology developed to detect serum monensin concentrations is beneficial and accurate for case investigations, it is recommended that several samples from each flock be evaluated because of variation within a flock. The current study also suggests that monensin in the feed could induce lower concentrations of vitamin E in the liver of turkeys and can predispose the turkeys to knockdown syndrome.

A meta-analysis of the impact of monensin in lactating dairy cattle. Part 3. Health and reproduction.

A meta-analysis of the impact of monensin on health and reproductive outcomes in dairy cattle was conducted. A total of 16 papers were identified with sufficient data and quality to evaluate health and reproductive outcomes for monensin. The available trials provided approximately 9,500 cows with sufficient data for analysis. This provided good statistical power to examine the effects of monensin on health and reproduction. Over all the trials analyzed, monensin decreased the risk of ketosis [relative risk (RR) = 0.75], displaced abomasums (RR = 0.75), and mastitis (RR = 0.91). No significant effects of monensin were found for milk fever, lameness, dystocia, retained placenta, or metritis. Monensin had no effect on first-service conception risk (RR = 0.97) or days to pregnancy (hazard ratio = 0.93). However, the impact of monensin on dystocia, retained placenta, and metritis was heterogeneous for all 3 outcome measures and random effect models were utilized. Causes of the heterogeneity were explored with meta-regression. Days of treatment with monensin before calving increased the risk of dystocia. Delivery method of monensin influenced the incidence of retained placenta and metritis, with risk being lower with controlled release capsule treatment compared with delivery in either topdress or in a total mixed ration. Days of treatment before calving also influenced retained placenta with an increase in risk with more days treated before calving. Improvements in ketosis, displaced abomasums, and mastitis with monensin were achieved. Exposure to prolonged treatment in the dry period with monensin may increase the risk of dystocia and retained placenta.

Atividade ovariana de vacas leiteiras em dietas com propilenoglicol ou monensina no período de transição / Ovarian activity of dairy cows receiving diets with propylene glycol or monensin during the transition period

Avaliou-se o efeito da adição de propilenoglicol ou de monensina na dieta de vacas leiteiras no período de transição sobre o retorno à atividade ovariana cíclica. Foram utilizadas 42 vacas pluríparas, da raça Holandesa, com produção de leite semelhante na lactação anterior (média de 8.000kg). Os animais, distribuídos em um delineamento inteiramente ao acaso, foram divididos em grupos que receberam dieta-controle e dietas acrescidas com 300ml de propilenoglicol ou 30ppm da matéria seca da dieta/dia de monensina. Avaliaram-se os ovários, por ultra-sonografia, entre os dias quatro e 46 pós-parto, e a concentração plasmática de progesterona, nos dias 10, 20, 25, 30, 35, 40 e 45 pós-parto. A adição de propilenoglicol mostrou-se eficiente em acelerar o retorno à ciclicidade após o parto. Os animais dos grupos que receberam propilenoglicol só no pré-parto, ou no pós-parto e no período de transição apresentaram intervalos parto-primeira ovulação de 29,0, 44,0 e 27,2 dias, respectivamente. Os intervalos parto-concepção para esses mesmos grupos foram de 98,3, 90,8, e 100,0 dias. A adição de monensina não se mostrou eficiente em acelerar o retorno à atividade ovariana cíclica após o parto. As vacas dos grupos que receberam monensina só no pré-parto, ou pós-parto, ou no período de transição apresentaram intervalos parto-primeira ovulação de 43,6, 39,3 e 42,8 dias, respectivamente. Os intervalos parto-concepção para os grupos pré e pós parto foram de 173,2, e 126,1 dias, respectivamente.

The influence of the addition of propylene glycol or monensin to diets of dairy cows during the transition period on return to ovarian cyclicity was evaluated. Forty two multiparous Holstein cows with an average milk production of 8,000kg were distributed in a split-plot design and were divided into groups receiving either control diets or diets increased with 30ppm of monensin or 300ml of propylene glycol during the transition period. Ovaries were evaluated by ultrasonography between days 4 and 46 post-partum. On days 10, 20, 25, 30, 35, 40, and 45 post-partum, blood samples were taken to assay progesterone. The addition of propylene glycol showed to be more efficient in accelerate the return to cyclic ovarian activity. Cows that received propylene glycol just during pre-partum, post-partum or during the hole transition period showed intervals from parturition to first ovulation of 29.0, 44.0 and 27.2 days, respectively. The intervals from parturition to conception for the same groups were 98.3, 90.8, and 100.0 days, respectively. The addition of monensin to diets did not show positive effects on post-partum return to ovarian cyclicity. Cows that received monensin just during pre-partum, post-partum or during the hole transition period showed intervals from parturition to first ovulation of 43.6, 39.3, and 42.8 days, respectively. The interval from parturition to conception for cows that received monensin pre and post-partum were 173.2 and 126.1 days, respectively.

Propileno-glicol ou monensina na dieta de vacas leiteiras no período de transição: saúde do úbere, produção e composição do leite / Propylene glycol or monensin on diets of dairy cows during the transition period: udder health, milk yield and composition

Avaliou-se o efeito do propileno-glicol e da monensina na dieta de vacas leiteiras no período de transição sobre a produção e composição do leite. Foram utilizadas 42 vacas da raça Holandesa com média de produção na lactação anterior de 8.000kg. Os animais, distribuídos em sete tratamentos segundo um delineamento inteiramente ao acaso, receberam dietas basais pré e pós-parto ou dietas basais acrescidas com 300ml de propileno-glicol ou 30ppm de monensina sódica na matéria seca da dieta. Nos dias 10 e 20 pós-parto, avaliou-se a produção de leite seguida de coleta de amostras para estudo dos constituintes do leite - gordura, proteína, lactose e extrato seco e de uréia e contagem de células somáticas. A inclusão de propileno-glicol apenas no período pós-parto resultou em diminuição da produção de leite e da quantidade total de gordura e proteína nos tempos de coleta estudados (P<0,05). A adição de propileno-glicol no pré-parto resultou em aumento da porcentagem de gordura, extrato seco e lactose nos tempos de coleta estudados (P<0,05). A inclusão de monensina tanto no pré quanto no pós-parto reduziu a porcentagem de proteína em relação aos outros tratamentos.

The influence of the addition of propylene glycol or monensin to diets of dairy cows during the transition period on milk production and milk composition was studied. Forty-two multiparous Holstein cows with an average milk production of 8,000 kg in the previous lactation were distributed in a complete randomized design and were divided into seven groups receiving either control diets or diets with 30ppm of monensin or 300ml of propylene glycol during the transition period. Milk production was recorded on days 10th and 20th post-partum and milk samples were taken on the same days to analyse milk components such as fat, protein, lactose, urea and somatic cells (10Õ/ml). The addition of propylene glycol in the post-partum diet decreased milk production as well as total the fat and protein production on the sampling times (days 10th and 20th post-partum) (P<0.05). The adition of propylene glycol during pre- partum increased fat and lactose percentage on the sampling times (P<0.05). The use of monensin during pre and post-partum periods decreased the protein percentage.

Oxidative effects of Na+--specific ionophore monensin on the rat epididymis.

The carboxylic antibiotic ionophore monensin is well-known for the Na+/H+ exchanger activity across the biological membranes. The current study has been designed to investigate the effect of monensin on spermatozoal concentration, motility, and oxidative stress-related parameters in the rat epididymis. Monensin was administered orally at a dose of 3.5 mg/kg body weight daily for 70 days, a duration that coincides with the completion of the spermatogenic cycle. At the end of the respective treatment, the epididymis was isolated into three separate regions--the capitum, corpus, and the cauda--successively away from the head of the testis. Marked changes were noted in the body weight, organ (epididymis) weight, sperm concentration and motility, as well as the morphologic observations of the sperm and the histologic architecture of the epididymal epithelium. Significant alterations were also recorded in the oxidative stress parameters such as the lipid peroxidation product, malonyldialdehyde, and the activity of superoxide dismutase, glutathione sulfotransferase, glutathione reductase, and catalase. The nonenzymatic thiol content such as the total, oxidized, and reduced glutathione showed significant changes and the tissue phosphatases such as alkaline and acid phosphatase were increased, indicative of the interference of the drug in lysosomal and Golgi membrane complex. The findings of the current study indicate interactions during the spermatozoal maturational process in the epididymis, and a significant potential use of monensin in male contraception may be suggested.

Comparación del Efecto de la adición de malato vs monensina sobre parámetros bioquímicos en terneros en crecimiento / Comparison between malate vs monensin adition on biochemicals parameters in growing steers

El objetivo del presente trabajo fue evaluar “ in vivo ” las repercusiones que tiene la adición de malato sódico sobre parámetros del medio interno, comparándolos con los resultados obtenidos al aplicar monensina sódica. Los parámetros sanguíneos estudiados fueron: glucosa, colesterol, triglicéridos, ácidos grasos libres, y las enzimas aspartato amino transferasa (ASAT), amilasa y gamma glutamil transpeptidasa (GGT). El estudio fue realizado con 13 animales, 8 de ellos recibieron malato sódico y 5 animales monensina sódica, extrayendo 6 muestras a cada animal, una toma basal (toma 1), y a los 3 (toma 2), 7 (toma 3), 21 (toma 4), 46 (toma 5) y 57 días (toma 6). Los resultados obtenidos muestran muy pocas diferencias entre ambos grupos y evoluciones parecidas, con variaciones entre grupos en el día 3 (ácidos grasos libres), día 7 (GGT), en el día 21 (amilasa) y en el día 46 (amilasa y GGT). En cuanto a las evoluciones de los parámetros a lo largo del experimento, colesterol, triglicéridos, amilasa y ASAT son los cuatro parámetros que presentan cambios estadísticos, con evoluciones similares en ambos grupos.

Effects of sodium malate addition on selected blood parameters, compared with the monensin addition were evaluated in this study. Serum glucose, triglycerides, cholesterols, free fatty acids (FFA), and the enzymes aspartate amino transferase (ASAT), amylase and gamma glutamyl transpeptidase (GGT) were studied. Thirteen steers, distributed in two different groups were used, one group (n=8) received sodium malate, and another group (n=5) received monensin and considered for us as a control group. Six samplings were obtained for each animal, at day 0 (before addition), and at days 3; 7; 21; 46 and 57 (after addition), respectively. Results obtained showed a similar evolution in both groups with small differences between them, at day 3 (FFA), at day 7 (GGT), at day 21 (amylase) and at day 46 (GGT and amylase). In relation with the evolution, we have seen similar statistical changes in both groups for cholesterol, triglycerides, amylase and ASAT assays.

Effect of administration of a controlled-release monensin capsule on incidence of calving-related disorders, fertility, and milk yield in dairy cows.

OBJECTIVE: To determine the effect of a controlled-release monensin capsule administered at cessation of lactation on incidence of calving-related disorders, fertility, and milk yield in dairy cows. ANIMALS: 290 dairy cows treated with monensin and 290 untreated control cows. PROCEDURE: Treated cows received a capsule that released monensin at 335 mg/d for 95 days. Incidence of calving-related disorders; daily milk yield up to 20 days postpartum; test-day milk yield, fat, protein, and mature-equivalent 305-day milk production; and body condition score at calving were determined. Reproductive variables were conception rate at first service, pregnancy rate, and calving-to-conception interval. RESULTS: Cows treated with monensin were 2.1 times as likely to develop dystocia and 0.8 times as likely to develop metritis as control cows. For milk yield, there was an interaction of treatment X time X parity. In multiparous cows, monensin significantly improved milk yield at test days 4 and 7. In addition, monensin increased body condition score at calving. CONCLUSIONS AND CLINICAL RELEVANCE: Despite increasing the likelihood of developing dystocia and metritis, administration of monensin improved the lactational performance of multiparous cows and may be a promising additive for use at the time of cessation of lactation.

Effects of monensin and stage of lactation on variation of blood metabolites within twenty-four hours in dairy cows.

Effects of prepartum administration of a monensin controlled release capsule (CRC) and stage of lactation on variation of blood metabolites within 24 h were determined in 16 dairy cows. Cows were fed a total mixed ration ad libitum twice daily at 0700 and 1300 h. At calving, cows were switched from a close-up dry cow diet to a lactating cow diet. Cows were blood sampled every 3 h for 24 h at 3 stages of lactation, including 1 wk before calving (wk -1), 1 wk after calving (wk 1), and 6 wk after calving (wk 6). Serum concentrations of glucose, beta-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), and urea exhibited significant variation within 24 h. Glucose and NEFA were, respectively, 0.09 and 0.08 mM lower between 1030 and 2230 h than between 2230 and 1030 h. beta-Hydroxybutyrate and urea were, respectively, 95.1 and 0.49 mM higher between 1030 and 2230 h than between 2230 and 1030 h. Monensin did not significantly affect glucose, NEFA, and urea in this study. Monensin reduced BHBA at wk 1, but not at wk -1 or wk 6. Glucose was lower and BHBA and NEFA were higher at wk 1 compared with wk -1 and wk 6. Urea was higher at wk 6 compared with wk -1. The variation within 24 h of glucose, BHBA, and NEFA were not affected by monensin and stage of lactation. Diurnal variation of urea was affected by stage of lactation, but not by monensin.

Short communication: Effects of a monensin premix on milk fatty acid content during subacute ruminal acidosis in dairy cows.

The effects of a monensin premix on milk fatty acid content during grain-induced subacute ruminal acidosis (SARA) in Holstein cows receiving a total mixed ration was investigated. Six multiparous, rumen-fistulated Holstein cows were used in a two-treatment, two-period crossover design with 6-wk periods. Experimental treatments were either a monensin premix or a placebo premix. At the beginning of wk 4, SARA was induced in experimental cows for a 10-d period using a grain challenge model. The administration of a monensin premix elevated milk fat proportion of total short-chain saturated fatty acids (sum of C4 to C15). Milk fat proportions of conjugated linoleic acid isomers were unaffected. Linolenic acid (C18:3n3) proportion in milk fat of monensin-treated cows were lower when compared with placebo-treated cows during the SARA period. Results from this study indicate that dietary supplementation with monensin during SARA had little effect on milk fatty acid content.

Rhabdomyolysis, acute renal failure, and death after monensin ingestion.

We report a case of human monensin intoxication; to our knowledge, this is the first reported case in the medical literature. The patient took a dose of monensin three times higher than a dose considered lethal for cattle and developed a clinical picture similar to that reported in veterinary medicine. There was an early and extremely severe rhabdomyolysis followed by acute renal failure, heart failure, and death. The main changes observed at autopsy were extensive skeletal muscle necrosis, complement deposition at the myocardial level, pulmonary edema, and acute tubular damage.

Heat shock protein synthesis is affected by intracellular pH: inhibition by monensin-induced alkalosis in C6 rat glioma cells.

The effect of intracellular pH (pHi) on heat shock protein (HSP) synthesis was investigated in C6 rat glioma cells. pHi changes were analysed by means of fluorescence spectroscopy in a perfused monitoring system allowing continuous measurements before, during and after treatments. HSP induction was determined by means of Western blots and autoradiographs. A 20 min heat shock (HS) of 44 degrees C decreased the pHi from 7.36 to 7.05 during exposure [17] and elicited the synthesis of heat shock proteins 2-8 h later. A pHi decrease, brought about by low extracellular pH (pHe) of 4.5 and 5.0 or 5.5, induced HSP synthesis after 1 h or 3 h, respectively. During these treatments, pHi decreased to values significantly lower than that caused by HS. Three h exposure to pHe 6.2, however, was not inductive. These results indicate that the heat shock-induced pHi decrease alone is not sufficient to stimulate HSP synthesis. In order to investigate the effect of alkaline pHi on the induction of HSP by heat, pHi was increased prior to HS treatments. Preincubation of cells at pHe ranging from 6.8 to 8.0 had little effect on pHi and on HSP synthesis. A shift of pHi to more alkaline values was achieved by adding the H+/Na+ exchanger monensin at alkaline pHe. Twenty microM monensin raised the pHi and inhibited the HSP induction depending on the pHe values: as pHe was increased from pH 7.2 to 8.0 HSP synthesis was increasingly inhibited. Monensin also diminished the HS-induced drop of pHi particularly at higher pHe. The result showed that neither a lower pHi nor a drop of pHi during HS is a necessary prerequisite for the induction, whereas alkalosis inhibits the synthesis of HSP.