Tini M Gruner

Acute and chronic stress

Tini M. Gruner — Mon, 06 Apr 2009 20:49:47 PDT

Stress triggers fight/flight response with physiological changes including: - upregulation of heart rate, BP, breathing, glycogenolysis and gluconeogenesis, cytokine production, immune response, and water and sodium retention - downregulation of digestion, GnRH, GH, LH and TSH Chronic stress (allostatic load) on the body leads to: - lack of hormonal inhibition through negative feedback - higher cortisol levels (with depletion in later stages) - higher disease burden Stress-related health problems range from addictions, anxiety, depression, panic attacks, sleep disorders, impairment of cognitive function and memory, heart disease, obesity, homonal disturbances, inflammation, auto-immune disorders, chronic fatigue syndrome and fibromyalgia to digestive disorders Stress management includes coping mechanisms such as plenty of good sleep, exercise, relaxation, wholesome diet and social support Therapies include CBT, physical therapies, nutritional and herbal medicine and miscellaneous therapies, such as art, music and light

MMA and cobalt deficiency diagnosis

Tini M. Gruner — Mon, 06 Apr 2009 20:49:47 PDT

Changes in serum concentration of methylmalonic acid and vitamin B12 in cobalt-supplemented ewes and their lambs on two cobalt deficient properties

Tini M. Gruner — Mon, 06 Apr 2009 20:49:46 PDT

AIM: To determine concurrent changes in serum methylmalonicacid (MMA) and vitamin B12 concentrations of ewes andtheir lambs on cobalt-defi cient properties, subsequent to cobaltsupplementation.METHODS: Three experiments were carried out on two farms.Groups of ewes (n=25-50) were either supplemented with cobaltbullets during late pregnancy, 23-47 days before the meanlambing date, or left unsupplemented. In two experiments,lambs from within each group were supplemented directly byvitamin B12 injection at 3-weekly intervals from birth, and inthe third experiment by injection with micro-encapsulated vitaminB12 at tailing and 3 months later. Pasture samples wereobtained for analysis of cobalt content at each sampling time.Blood samples were obtained and liveweight recorded from ewesand lambs at approximately monthly intervals. On one farm(two experiments), liver and milk samples were obtained fromewes and liver samples from lambs.RESULTS: Serum vitamin B12 concentrations in unsupplementedewes fell below 250 pmol/L during early lactation inall experiments and mean concentrations as low as 100 pmol/Lwere recorded. MMA concentration was maintained below2 μmol/L in serum from supplemented ewes but increased tomean concentrations ranging from 7 to14 μmol/L at the nadirof serum vitamin B12 concentration during peak lactation.A signifi cant liveweight response to supplementation was recordedin ewes on one property, and the vitamin B12 concentrationin the ewes' milk and in the livers of their lambs morethan doubled. No liveweight-gain response to supplementationwas observed in lambs on this property. Mean serum MMAconcentrations in lambs ranged from <2 in>supplemented, to19.2 μmol/L in unsupplemented lambs, and the latter had concurrentserum vitamin B12 concentrations of >300 pmol/L. Pasturecobalt concentration was lowest at 0.04-0.09 μg/kg drymatter (DM) on the property on which responses in lambs occurredbut considerably higher (>0.09 μg/kg DM) on the propertyon which responses in ewes occurred.On the second property, serum vitamin B12 concentrations inlambs at tailing were extremely low (100 pmol/L), irrespectiveof supplementation of dams with cobalt. Mean serum MMAconcentration was increased to 20 and 42 μmol/L in lambsfrom supplemented and non-supplemented ewes, respectively.Weight-gain response to direct supplementation of lambs withvitamin B12 occurred during suckling in the latter, but notthe former. Lambs from ewes supplemented with vitamin B12showed a much bigger increase in serum vitamin B12 concentrationsa month after supplementation than did lambs fromunsupplemented ewes (+1,400 pmol/L vs +650 pmol/L).CONCLUSIONS: Serum MMA concentration gave a more preciseindication of responsiveness to vitamin B12 or cobalt supplementationthan serum vitamin B12 concentrations in ewesand lambs. Neither very low serum vitamin B12 nor elevatedMMA concentrations were necessarily indicative of responsivenessto supplementation in suckling lambs, but the latter gavean early indication of impending responsiveness. Supplementationof the ewe with a cobalt bullet appeared to protect thegrowth performance of the lamb for 90 days and infl uence thesubsequent serum vitamin B12 response in the lamb to vitaminB12 supplementation.CLINICAL SIGNIFICANCE: Supplementing ewes with cobaltbullets in late pregnancy can improve the vitamin B12 status oftheir lambs, and modify their response to vitamin B12 supplementation.

Vitamin C

Tini M. Gruner — Mon, 06 Apr 2009 20:49:45 PDT

Summary the first nutritional disease ever identified was scurvy, which was endemic in Europe in the 18th century. Vitamin C was subsequently recognised in 1928 as the 'antiscorbutic factor' in the citrus fruits that James Lind had fed his sailors. Since then, the research on this nutrient has ebbed and flowed, portraying it at different stages as both panacea and placebo. In light of the current evidence-based paradigm, it appears now that the true effect of vitamin C lies somewhere between the two. There is growing recognition by international authorities of the broader actions and applications of vitamin C, and the potentially profound long-term sequelae of suboptimal consumption. Due to an improved understanding of the pharmacokinetics of vitamin C, there is also renewed interest in studies assessing IV vitamin C in the treatment of cancer-- see JCM 2006;5(3):20-1.

A critical evaluation of serum methylmalonic acid and vitamin B12 for the assessment of cobalt deficiency of growing lambs in New Zealand

Tini M. Gruner — Mon, 06 Apr 2009 20:49:45 PDT

AIM: To derive reference ranges for serum methylmalonic acid(MMA) for the diagnosis of cobalt/vitamin B12-responsivenessin lambs and critique existing serum vitamin B12 referenceranges.METHODS: Individual animal data from earlier supplementationtrials, involving 225 ewes, 106 suckling lambs, 301 lambsduring the suckling and post-weaning periods and 414 weanedlambs, for which weight gain to supplementation was observed,were used to derive relationships between serum vitamin B12and MMA, and liveweight gain.RESULTS: Serum MMA concentrations were rarely elevatedabove the norm of <2 μmol/L when serum vitamin B12 concentrationswere >375 pmol/L, and not elevated into the rangewhere a liveweight response to supplementation occurred(>10 μmol/L) unless serum vitamin B12 concentrations were below200 pmol/L. Suckling lambs were able to maintain high growthrates despite elevated serum MMA concentrations (>20 μmol/L).CONCLUSIONS: The current reference ranges used in NewZealand for serum vitamin B12 are set conservatively high. SerumMMA concentrations appear to allow better differentiationof a responsive condition than vitamin B12 concentrations. SerumMMA concentrations >13 μmol/L indicate responsivenessto supplementation whilst concentrations <7 μmol/L indicateunresponsiveness. In the range 7-13 μmol/L, variation in responsewas observed and predictability of response is less certain,but supplementation is advisable.CLINICAL RELEVANCE: The current reference ranges forvitamin B12 responsiveness are conservatively high and leadto over-diagnosis of vitamin B12 defi ciency in ill-thriftiness ofsheep.

Vitamin B12: an undervalued vitamin

Tini M. Gruner — Mon, 06 Apr 2009 20:49:44 PDT

Development of a method for the separation of corrinoids in ovine tissues by HPLC

R J. Kelly — Mon, 06 Apr 2009 20:49:43 PDT

A method has been developed using a combination of high-performance liquid chromatography (HPLC) and a radioisotope dilution assay (RIDA) to routinely estimate the distribution of corrinoids (the cobalamins hydroxocobalamin, methylcobalamin and 5-deoxyadenosylcobalamin, and cobalamin analogues) in liver, plasma, milk, intestinal fluid and faeces. Corrinoids were extracted with a sodium acetate buffer, separated by HPLC and quantified by RIDA. Recoveries of corrinoids were 29% for hydroxocobalamin, 50% for 5-deoxyadenosylcobalamin and 64% for methylcobalamin. The method allows the routine analysis of many samples and maintains good standards of precision.

Metabolic consequences and metabolic indicators of vitamin B12 deficiency

Tini M. Gruner — Mon, 06 Apr 2009 20:49:43 PDT

The buccal cytome and micronucleus frequency is substantially altered in Down's syndrome and normal ageing compared to young healthy controls

Philip Thomas — Mon, 06 Apr 2009 20:49:42 PDT

The buccal micronucleus cytome assay was used to investigate biomarkers for DNA damage, cell death and basal cell frequency in buccal cells of healthy young, healthy old and young Down's syndrome cohorts. With normal ageing a significant increase in cells with micronuclei (P < 0.05, average increase +366%), karyorrhectic cells (P < 0.001, average increase +439%), condensed chromatin cells (P < 0.01, average increase +45.8%) and basal cells (P < 0.001, average increase +233%) is reported relative to young controls. In Down's syndrome we report a significant increase in cells with micronuclei (P < 0.001, average increase +733%) and binucleated cells (P < 0.001, average increase +84.5%) and a significant decrease in condensed chromatin cells (P < 0.01, average decrease −52%), karyolytic cells (P < 0.001, average decrease −51.8%) and pyknotic cells (P < 0.001, average decrease −75.0%) relative to young controls. These changes show distinct differences between the cytome profile of normal ageing relative to that for a premature ageing syndrome, and highlight the diagnostic value of the cytome approach for measuring the profile of cells with DNA damage, cell death and proportion of cells with proliferative potential (i.e., basal cells). Significant correlations amongst cell death biomarkers observed in this study were used to propose a new model of the inter-relationship of cell types scored within the buccal micronucleus cytome assay. This study validates the use of a cytome approach to investigate DNA damage, cell death and cell proliferation in buccal cells with ageing.

Analysis of corrinoids in ovine tissues

R J. Kelly — Mon, 06 Apr 2009 20:49:41 PDT

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.