Cobalt deficiency in cattle and its impact on production / Deficiência de cobalto em bovinos e seu impacto na produção

Two outbreaks of cobalt deficiency in beef cattle were diagnosed in Midwestern Brazil. We discuss the clinical, epidemiological, pathological features, therapeutic measures, and impact aspects of the production system associated with these outbreaks occurring outbreaks in two farms of extensive cattle raising-system in the state of Mato Grosso do Sul. Seven affected cattle were euthanized and necropsied. Tissues for histopathology and microelements dosage were secured. At Farm A, 3100 cattle of all ages got sick, and 396 died; at Farm B, 148 were affected, and 110 died. In both farms, cattle were fed the same mineral supplement. The main clinical signs were weight loss and weakness, even though a good supply of forage was available in the paddocks. Many cattle stop grazing and chew at tree barks, wood chips from fence posts, and bones. In addition to the deaths, there was a compromised growth, and the reproductive rates fell sharply. The necropsied cattle were thin, with rough hair coat and pale mucous membranes. The liver was diffusely orange and showed a lobular pattern. The bone marrow was gelatinous and diffusely yellow. Histological changes included hemosiderosis in the liver and spleen, hepatocellular vacuolar degeneration, and myeloid and erythroid hypoplasia of the bone marrow. In the white matter of four cattle's brains, the myelin sheath was markedly distended (spongy degeneration). Proliferative parasitic abomasitis was observed in three cattle. The presumptive diagnosis was based on the association of the clinical picture, the necropsy findings, and the ruling out of other possible causes. The diagnosis was confirmed by the favorable response to treatment with cobalt and vitamin B12 orally and by mineral supplementation.(AU)

Dois surtos de deficiência de cobalto em bovinos de corte foram diagnosticados. Os aspectos clínicos, epidemiológicos, anatomopatológicos, terapêuticos e impactos no sistema de produção são descritos e discutidos. Os surtos ocorreram em duas fazendas de criação extensiva estado de Mato Grosso do Sul, Centro-Oeste brasileiro. Sete bovinos afetados foram eutanasiados e necropsiados. Na necropsia foram colhidas amostras para exames histopatológicos e dosagem de microelementos. Na Fazenda A, 3100 bovinos de todas as idades adoeceram e 396 morreram e na Fazenda B, 148 bovinos adoeceram e 110 morreram. Ambas as fazendas utilizavam o mesmo suplemento mineral. Os principais sinais clínicos observados foram emagrecimento e fraqueza, apesar da boa oferta de forragem nos piquetes, muitos bovinos deixaram de pastejar e comiam cascas de árvores, madeira das porteiras e ossos. Além das mortes, tiveram crescimento comprometido e os índices reprodutivos tiveram queda acentuada. Os bovinos necropsiados estavam magros, com os pelos arrepiados e mucosas pálidas. O fígado estava difusamente alaranjado e com evidenciação do padrão lobular. A medula óssea estava de consistência gelatinosa e difusamente amarelada. Alterações histológicas incluíam degeneração vacuolar hemossiderose que era moderada no fígado e marcada no baço. Hipoplasia mieloide e eritoide era vista na medula óssea. Na substância branca do encéfalo de quatro bovinos, a bainha de mielina estava marcadamente distendida (degeneração esponjosa). Abomasite parasitária proliferativa foi observada em três bovinos. O diagnóstico presuntivo baseou-se na associação do quadro clínico, nos achados de necropsia e na eliminação de outras possíveis causas. O diagnóstico foi confirmado pela resposta favorável ao tratamento com cobalto e vitamina B12 por via oral, e a suplementação mineral.(AU)

ATTENTION DEFICIT HYPERACTIVITY DISORDER AND HAIR HEAVY METAL AND ESSENTIAL TRACE ELEMENT CONCENTRATIONS. IS THERE A LINK?

The aim of our study was to assess hair micro-elemental status in children with attention deficit hyperactivity disorder, determine micro-elemental misbalances and heavy metal concentrations and evaluate its impact on child behavior. Case-control study was conducted at Child Development Center of M. Iashvili Children's Central Hospital in 2015-2017years (Tbilisi, Georgia). We studied 70 children, mean age from 6 to 8 year. Target group involved 35 children with Attention Deficit Hyperactivity Disorder . Control group include 35 children of same age with normal behavior. Groups were homogenous based on different characteristics. To diagnose behavioral problems multi-profile group (pediatrician, neurologist, psychologist) assessment was used and final diagnostic was based on DSM V (Diagnostic and Statistical Manual of Mental Disorders from the American Psychiatric Association) and ICD-10 (International Clasiffication of Desease-10) criteria. Micro-elemental status was detected in the hair, with roentgen-fluorescence spectrometer method (Method MBИ 081/12-4502-000, Apparatus ELVAX-CIP, USA-UKRAIN). We study the content of 27 microelements (Zn, Fe, Cu, Mn, Co, Se, K, Cr, S , Cl, ,Ag ,V, Ni, Rb, Sr, Mo, Sr,, Pb, Hg, Br, Ti, Ba, As, Zr, Sb, Sn, Cd) in the hair in target and control groups. Computer program SPSS - 21 (Statistical Package for the Social Science - 21; Independent Samples T-Test,) was used for statistical analysis. The results of our study revealed deficiency of major elements (Fe, Mn, Co, Se), in target group and deficiency of zinc and cooper in both (control and target) groups,but the mean concentrations of manganese (sig 0,200; p>0,05), cooper(sig 0,813; p>0,05) and selenium(sig 0,320;p>0,05) does not show significant difference between control and target groups. Only in case of zinc (sig 0,000; p<0,05), iron (sig0,000;p<0,05) and cobalt (sig 0,000; p<0,05) deficiency we got significant values and meaningful associations between microelement's deficiency and ADHD.Our research didn't reveal any changes in other 17 elements (K, Cr, S, Cl, Ag, V, Ni, Rb, Sr, Mo, Sr, Ba, As, Zr, Sb, Sn, Cd) levels. We detected contamination with Pb (lead), Hg(mercury) and Ti (titanium) in both groups , but there were significant difference in Pb (sig 0,000; p<0,05) and Hg (sig 0,000; p<0,05) values between control and study groups, while difference of Ti (sig 0,177; p>0,05) level was not significant. Our study suggests that zinc, iron and cobalt deficiency as well as contamination with high lead and mercury are associated with attention deficit hyperactivity disorder.

The effect of alcohol consumption on maternal and cord blood electrolyte and trace element levels.

BACKGROUND: Earlier studies demonstrated that alcoholism significantly alters electrolyte and trace element homeostasis. However, the existing data on the interplay between maternal alcohol consumption and fetal trace element status are contradictory. Therefore, the primary objective of the present study was to assess the influence of alcohol consumption on maternal and cord blood trace elements. METHODS: A total of 30 pregnant women (15 women consuming alcohol and 15 controls) were examined. Assessment of electrolyte and trace elements concentration in maternal (1 and 3 trimesters) and umbilical cord blood was performed using inductively-coupled plasma mass spectrometry. RESULTS: In the first trimester of pregnancy alcohol consumption is associated with increased whole blood Ca and Na levels. In the third trimester of pregnancy, women consuming alcohol are characterized by significantly increased Co levels. Conversely, the level of Co and Mn in the cord blood of offspring maternally exposed to ethanol is decreased. A significant correlation between first trimester blood and cord blood concentrations of K was revealed both in control women and those consuming alcohol. In the third trimester of pregnancy in the control women, a significant correlation with cord blood was detected for Fe, Mg, P, and Pb. Oppositely, in the third trimester in women consuming alcohol we detected a close association between maternal whole blood and cord blood levels for Ca, Cd, and Pb. CONCLUSIONS: The data obtained demonstrate that maternal alcohol consumption results in fetal Co and Mn deficiency.

High-level production of ethylmalonyl-CoA pathway-derived dicarboxylic acids by Methylobacterium extorquens under cobalt-deficient conditions and by polyhydroxybutyrate negative strains.

Bio-based production of dicarboxylic acids is an emerging research field with remarkable progress during the last decades. The recently established synthesis of the ethylmalonyl-CoA pathway (EMCP)-derived dicarboxylic acids, mesaconic acid and (2S)-methylsuccinic acid, from the alternative carbon source methanol (Sonntag et al., Appl Microbiol Biotechnol 98:4533-4544, 2014) gave a proof of concept for the sustainable production of hitherto biotechnologically inaccessible monomers. In this study, substantial optimizations of the process by different approaches are presented. Abolishment of mesaconic and (2S)-methylsuccinic acid reuptake from culture supernatant and a productivity increase were achieved by 30-fold decreased sodium ion availability in culture medium. Undesired flux from EMCP into polyhydroxybutyrate (PHB) cycle was hindered by the knockout of polyhydroxyalkanoate synthase phaC which was concomitant with 5-fold increased product concentrations. However, frequently occurring suppressors of strain ΔphaC lost their beneficial properties probably due to redirected channeling of acetyl-CoA. Pool sizes of the product precursors were increased by exploiting the presence of two cobalt-dependent mutases in the EMCP: Fine-tuned growth-limiting cobalt concentrations led to 16-fold accumulation of mesaconyl- and (2S)-methylsuccinyl-CoA which in turn resulted in 6-fold increased concentrations of mesaconic and (2S)-methylsuccinic acids, with a combined titer of 0.65 g/l, representing a yield of 0.17 g/g methanol. This work represents an important step toward an industrially relevant production of ethylmalonyl-CoA pathway-derived dicarboxylic acids and the generation of a stable PHB synthesis negative Methylobacterium extorquens strain.

Effect of cobalt on parameters of the cardiovascular system in elementary school children.

High incidence of cobalt deficiency (89%) was found in 7-8-year-old girls residents of the Republic of Tatarstan. Significant correlations were revealed between parameters of physical development and cardiovascular system and hair cobalt content. These data suggest that positive balance of cobalt is essential for normal growth and development of child's body and function of the cardiovascular system.

Effects of cobalt/vitamin B12 status in ewes on ovum development and lamb viability at birth.

Scottish Blackface ewes from cobalt-deficient farmland were fed a diet containing 0.06 mg cobalt per kg dry matter from approximately 30 days before embryo recovery/transfer until lambing. Ewes remained untreated (-Co; n = 82) or were given an intraruminal cobalt-containing bolus to compensate for the dietary deficit (+Co; n = 82). Ewes used as embryo donors (-Co, n = 17; +Co, n = 16) were artificially inseminated with semen from a single Suffolk sire. Day 6 embryos obtained from -Co and +Co donors were transferred in singleton to -Co and +Co recipients in a 2 x 2 factorial-designed experiment to determine the effects of cobalt/vitamin B12 status during the periconception period (factor 1) and pregnancy (factor 2) on lamb viability at birth. Mean (+/- s.e.m.) circulating concentrations of vitamin B12 in -Co and +Co donors at ovum recovery were 182 +/- 10 and 1288 +/- 64 pmol L(-1), respectively (P < 0.001), and the number of corpora lutea per ewe ovulating was 9.9 +/- 1.6 and 14.4 +/- 1.3, respectively (P < 0.05). Treatment did not affect the proportion of recovered ova that contained >32 cells (viable) or the median stage of development (late morula), but viable ova recovered from -Co v. +Co ewes had a better morphological grade (2.0 +/- 0.1 v. 2.20 +/- 0.04, respectively; P < 0.01). There was no effect of treatment on the proportion of recipient ewes that became pregnant. Circulating concentrations of vitamin B12 were lower in -Co than +Co ewes during pregnancy (P < 0.001) and at birth in lambs born to -Co ewes compared with those born to +Co ewes (P < 0.001). There was no effect of donor or recipient cobalt/vitamin B12 status on lamb birthweight, neonatal vigour or neonatal rectal temperatures, but lambs derived from +Co v. -Co embryo donors were more active in the first 3 days after birth (P < 0.05). Results show that sub-clinical cobalt/vitamin B12 deficiency reduces ovulatory response in superovulated ewes and that periconception nutrition can affect neonatal lamb behaviour.

Analysis of corrinoids in ovine tissues.

Corrinoids from various ovine tissue samples (liver, blood, small intestinal fluid and faeces) were analysed using a combination of high-performance liquid chromatography (HPLC) and a radioisotope dilution assay (RIDA) to estimate the distribution of corrinoids--the cobalamins hydroxocobalamin (OH-cbl), methylcobalamin (me-cbl) and 5'-deoxyadenosylcobalamin (ado-cbl), and cobalamin analogues--in these tissues. Samples were taken from either cobalt-deficient or cobalt-replete ewes, and ruminant and pre-ruminant lambs. In liver, ado-cbl predominated, followed by analogues, OH-cbl and me-cbl. Supplementation with either cobalt (ruminant) or vitamin B12 injections (pre-ruminant) increased the amount of ado-cbl and decreased analogues. In blood, OH-cbl predominated, followed by ado-cbl, analogues and me-cbl, respectively. In small intestinal fluid, the distribution from largest to smallest percentage was analogues, ado-cbl, OH-cbl and me-cbl. In faeces, analogues constituted the greatest proportion, followed by OH-cbl, ado-cbl and me-cbl, respectively. Owing to the small sample sizes only cautionary interpretations can be made. In contrast to humans, where me-cbl constitutes the highest proportion of corrinoids in plasma and ado-cbl in the liver, in sheep the amount of ado-cbl was consistently higher than me-cbl in all tissues. This may be due to the higher metabolic need of sheep for ado-cbl due to gluconeogenesis. Analogues and OH-cbl were found in each tissue, contrary to previous postulations. The much higher amount of vitamin B12 in small intestinal fluid compared with faeces indicates that a large proportion of the vitamin is absorbed by the gastro-intestinal tract.

Hepatic cobalt and copper levels in lambs in Norway.

Cobalt and copper concentrations were measured in 599 lamb livers collected at slaughter from 58 sheep flocks in 6 different parts of Norway in 1993. Information about pasture, additional feeding and mineral supplements in the flocks was obtained through a questionnaire. Average hepatic levels of cobalt in the lamb flocks varied from < 0.003 to 0.22 microg/g ww, and of copper from 5 to 240 microg/g ww. Flocks with deficient or marginal cobalt status were found in all parts of southern Norway, but primarily in the west and south-west. Some flocks with marginal copper status were found in the south-west, while flocks with signs of excessive hepatic copper concentrations were found mainly in inner parts of central and northern Norway. Hepatic copper concentrations were significantly higher in lambs that had grazed mountain pastures than in those that had grazed lowland pastures in the summer.

Caprine hepatic lipidosis induced through the intake of low levels of dietary cobalt.

Forty-one, 10-week-old newly weaned goats were randomly allocated into two groups, namely control (n=22) and treated (n=19). Kids in both groups were fed Rhodegrass hay ad libitum that contained < 0.1 mg/kg DM cobalt and 150 g/day of a commercially prepared ruminant concentrate that contained approximately 0.12 mg/kg DM cobalt. This diet provided the minimum daily requirement of cobalt as specified for sheep. The treated goats were supplemented with bi-monthly subcutaneous injections of 2000 microg of hydroxycobalamin. All goats were weighed and blood samples collected monthly for haematological, clinical biochemical and serum vitamin B12 analysis. After a 10-month experimental period the goats were slaughtered. The control animals exhibited significantly (P<0.05) lower weight gains, and had dry scruffy hair coats. In addition, there was a decline in erythrocyte counts, mean haemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. Controls also exhibited significantly (P<0.05) lower levels of total serum proteins and elevated levels of serum alkaline phosphatase compared to treated goats. Fourteen (63.6%) of the control goats developed pathology consistent with reported field cases of hepatic lipidosis associated with low liver levels of cobalt. Only one (5.3%) of the treated goats developed hepatic lipidosis. Contrary to previous reports that suggested that goats are less sensitive to low levels of dietary cobalt than sheep, it is apparent that this is not the case with Omani goats. This is the first report of the induction of hepatic lipidosis in goats due to feeding low levels of cobalt in their diet.

Nova Scotia moose mystery--a moose sickness related to cobalt- and vitamin B12 deficiency.

A wasting, debilitating disease with uncertain aetiology affecting moose (Alces alces americana) in Eastern North America has been reported repeatedly ever since the 1910s. Despite the intensive studies during 1930-1960s the cause of the sickness could not be established. In the 1960s a parasitic nematode (Parelaphostrongylus tenuis) was reported as constituting a probable explanation for the sickness, although several clinical and pathological signs remained unexplained. In Sweden, a moose disease with similar signs, has been shown to be caused by molybdenosis resulting from a nutritional imbalance. The findings of this investigation were applied in Nova Scotia to determine trace element concentrations in tissues from indigenous moose. Co deficiency was found in about half of the cases and the investigation was complemented by determining the vitamin B12 level, which proved nutritional Co/vitamin B12 deficiency, further verified by an increased MMA (methylmalonic acid) level in plasma. Deficiencies were found mainly in the Tobeatic and Cape Breton Highland regions. No indications of molybdenosis or other trace element disturbances were found in Nova Scotia. Otherwise, extremely high Cd levels (148 mg Cd/kg kidney wet wt., maximum) were found, though probably not contributing to the moose sickness. The Cd burden of moose on mainland Nova Scotia was more than 50% higher than that of moose in Huntville and Alonquin (Ontario, Canada) and five- to six-fold is higher than the highest Cd levels found in Sweden. To counteract the bio-geochemical effects of Co deficiency in the moose environment, provision of Co-containing salt licks is suggested.

Predicting the risk of cobalt deprivation in grazing livestock from soil composition data.

The objective was to derive predictive equations for acetic acid-extractable cobalt (A-ECo) in soils so that extensive national databases for total (T) Co in soils and stream sediments could be converted to 'plant available' concentrations for the purpose of predicting risk of Co deficiency in grazing livestock. Data on the chemical and physical properties of 103 soils from 15 different parent materials and 54 soil series in England and Wales were used. Ranges for the mean values for parent materials were: TCo, 5.0-20.4 and A-ECo, 0.20-1.30 mg kg-1; percentage (P) A-ECo, 3.4-13.5; soil manganese (Mn) 268-1174 mg kgDM-1; pH, 3.7-8.0. There were significant effects of parent material on all parameters with Chalks, Old and New Red Sandstones particularly low in A-ECo. Multiple linear regression yielded the following equation for predicting A-ECo, which accounted for 56% of the variance with 12 outliers, including the lowest pH values, omitted: [figure: see text] REML was used on the complete, unbalanced, log-transformed data set to fit a Generalised Mixed Model with parent material as random effect and soil Mn and pH as fixed effects; the effect of parent material was no longer significant. It was concluded that A-ECo can be satisfactorily predicted for most soils in England and Wales from TCo, TMn and soil pH.

Cobalt-deficiency-induced hyperhomocysteinaemia and oxidative status of cattle.

In ruminants, Co is required for the synthesis of vitamin B12, which in turn is needed for the resynthesis of methionine by methylation of homocysteine and thus, cobalamin deficiency may induce hyperhomocysteinaemia which is brought into context with perturbations of the antioxidative-prooxidative balance. The present study was conducted to explore whether Co deficiency in cattle is also associated with homocysteine-induced disturbances of oxidative status. Co deficiency was induced in cattle by feeding two groups of animals on either a basal maize-silage-based diet that was moderately low in Co (83 micrograms Co/kg DM), or the same diet supplemented with Co to a total of 200 micrograms Co/kg DM, for 43 weeks. Co deficiency was apparent from a reduced vitamin B12 status in serum and liver and an accumulation of homocysteine in plasma which was in excess of 4.8 times higher in Co-deprived cattle than in controls. The much increased level of circulating homocysteine did not indicate severe disturbances in antioxidant-prooxidant balance as measured by individual markers of lipid peroxidation, protein oxidation, and the antioxidative defence system. There were no quantitative difference in plasma thiol groups, nor were there significant changes in concentrations of alpha-tocopherol, microsomal thiobarbituric acid-reactive substances and carbonyl groups in liver. However, there was a trend toward increased plasma carbonyl levels indicating a slight degradation of plasma proteins in the hyperhomocysteinaemic cattle. Analysis of the hepatic catalase (EC 1.11.1.6) activity revealed an 11% reduction in Co-deficient cattle relative to the controls. These results indicate that long-term moderate Co deficiency may induce a severe accumulation of plasma homocysteine in cattle, but considerable abnormalities in oxidative status failed to appear.

Micronutrients and immune function in cattle.

Complex inter-relationships exist between certain micronutrients, immune function and disease resistance in cattle. Several micronutrients have been shown to influence immune responses. The relationship between deficiencies of some micronutrients and disease resistance is less clear. A number of studies have indicated that Cr supplementation may improve cell-mediated and humoral immune response as well as resistance to respiratory infections in stressed cattle. With respiratory-disease challenge models Cr generally does not affect disease resistance. Deficiencies of Cu, Se, vitamin E and Co in cattle reduce the ability of isolated neutrophils to kill yeast and/or bacteria. Cu deficiency reduces antibody production, but cell-mediated immunity is generally not altered. However, Cu deficiency appears to reduce production of interferon and tumour necrosis factor by mononuclear cells. Numerous studies have linked low vitamin E and/or Se status to increased susceptibility of dairy cows to intramammary infections. In contrast to findings in laboratory animals, marginal Zn deficiency does not appear to impair antibody production or lymphocyte responsiveness to mitogen stimulation in ruminants. Co deficiency has been associated with reduced resistance to parasitic infections. It is well documented that vitamin A-deficient animals are more susceptible to various types of infections. beta-Carotene, possibly via its antioxidant properties, may affect immune function and disease resistance independent of its role as a precursor of vitamin A.

Hepatic lipidosis associated with cobalt deficiency in Omani goats.

Livers from 36 of 684 (5.3%) apparently healthy goats examined at an abattoir in the greater Muscat area of Oman exhibited gross pathological findings characterized by extremely pale, friable, fatty livers encompassing the entire organ. Histopathologically, diffuse hepatic lipidosis and occasional bile duct proliferation were observed. Periodic acid Schiff-positive, diastase-resistant pigment was observed in the macrophages lining the sinusoids. These histopathological lesions were consistent with those characteristic of ovine white liver disease. Cobalt analysis revealed that normal livers had six times more cobalt and a 3-fold less fat content than those measured in the fatty livers. This is the first report of an association between cobalt deficiency and hepatic lipidosis in Omani goats.