Calcium and magnesium physiology and nutrition in relation to the prevention of milk fever and tetany (dietary management of macrominerals in preventing disease).

Dairy cows may suffer events of hypocalcemia and hypomagnesemia, commonly known as milk fever and tetany. Milk fever is characterized by hypocalcemia at parturition as a consequence of a sudden increase in Ca demand and an unavoidable delay in Ca metabolism adaptation. Tetany is due to impaired Mg absorption from the rumen that cannot be compensated by absorptive or excretory adaptation, resulting in a net nutritional shortage of Mg and culminating in hypomagnesemia. Prevention strategies require triggering the activation of Ca gastrointestinal absorption and avoiding factors limiting ruminal Mg absorption.

[The process of eliminating neonatal Tetanus in Colombia, 1989-2005]. / Proceso de eliminación del Tétanos neonatal en Colombia 1989-2005.

OBJECTIVE: To describe the country's progress in eliminating neonatal tetanus based on the information obtained from epidemiologic surveillance. MATERIAL AND METHODS: A retrospective descriptive study of the epidemiological surveillance of neonatal tetanus in Colombia in the period ranging from 1989 to 2005. Available information was consulted regarding confirmations of this event of interest for Public Health. RESULTS: During the study period, a total of 830 cases of neonatal tetanus were reported. In 1989, the rate of neonatal tetanus in Colombia was 0.22 per 1000 live births. In 2005, this value was reduced to 0.01 cases per 1000 live births; a reduction of nearly 94 %. CONCLUSIONS: Given the information provided by epidemiological surveillance, Colombia has achieved the goal of maintaining a rate<1 case per 1000 live births. Nevertheless, even one case anywhere in the country should be considered a failure of the healthcare system.

Determinants of utilization of sufficient tetanus toxoid immunization during pregnancy: evidence from the Kenya Demographic and Health Survey, 2008-2009.

Although the effectiveness of tetanus toxoid (TT) immunization during pregnancy in preventing maternal and neonatal tetanus is well established, in many developing countries, TT immunization programs are underutilized. The objective of this study was to examine factors associated with sufficient TT immunization among postpartum women in Kenya. Population based secondary data analysis was conducted using de-identified data from the 2008-2009 Kenyan Demographic and Health Survey (KDHS) for 1,370 female participants who had a live birth during or within 12 months of the cross-sectional survey. Chi-square test and independent sample t test were conducted to assess bivariate associations and a multivariable logistic regression analysis was conducted to examine associations before and after adjustment for demographic, socioeconomic, cultural, and access to care factors. The main factors contributing to having been sufficiently immunized against tetanus were lower birth order, higher household wealth index, women's employment, making joint health-related decisions with a partner, and higher number of antenatal care visits. Implications for health care providers and other professionals involved in development of strategies and interventions aimed at improving immunization rates are discussed.

Cost-effectiveness analysis regarding postoperative administration of vitamin-D and calcium after thyroidectomy to prevent hypocalcaemia / Análisis de costo-efectividad de la administración postoperatoria de Vitamina D y calcio después de tiroidectomía para la prevención de la hipo calcemia

Objective Hypocalcaemia is a frequently arising complication following total thyroidectomy. Routine postoperative prophylactic administration of vitamin D or metabolites and calcium reduce the incidence of symptomatic hypocalcaemia; this article reports evaluating its cost-effectiveness in Colombia. Methods Meta-analysis was used for comparing the administration of vitamin D or metabolites to oral calcium or no treatment at all in patients following total thyroidectomy and a cost-effectiveness analysis was designed based on a decision-tree model with local costs. Results The OR value for the comparison between calcitriol and calcium compared to no treatment and to exclusive calcium treatment groups was 0.32 (0.13-0.79 95 %CI) and 0.31 (0.14-0.70 95 %CI), respectively. The most cost-effective strategy was vitamin D or metabolites and calcium administration, having a US $0.05 incremental cost-effectiveness ratio. Conclusion Prophylactic treatment of hypocalcaemia with vitamin D or metabolites + calcium or calcium alone is a cost-effective strategy.

Objetivos La hipo calcemia es la complicación más frecuente después de tiroidectomía. La administración profiláctica de vitamina D o metabolitos y calcio reduce la incidencia de hipocalcémia sintomática. Se evalúa su costo-efectividad en Colombia. Materiales y métodos Utilizamos la información de un meta-análisis que comparó la administración de vitamina D o metabolitos contra calcio no tratamiento en pacientes llevados a tiroidectomía total y diseñamos un análisis de costo-efectividad basados en un modelos de decisiones con costos locales. Resultados El valor del OR para la comparación entre calcitriol y calcio comparado con no tratamiento o calcio exclusivo fue de 0.32 (95 % IC, 0.13- 0.79) y 0.31 (95 % IC, 0.14-0.70), respectivamente. La estrategia más costo-efectiva fue la administración de vitamina D o metabolitos y calcio, con una relación de costo-efectividad incremental de US $0.05. Conclusiones El tratamiento profiláctico de la hipo calcemia con vitamina D o metabolitos y calcio o calcio exclusivo después de tiroidectomía total es una estrategia costo-efectiva.

Cost-effectiveness analysis regarding postoperative administration of vitamin-D and calcium after thyroidectomy to prevent hypocalcaemia.

OBJECTIVE: Hypocalcaemia is a frequently arising complication following total thyroidectomy. Routine postoperative prophylactic administration of vitamin D or metabolites and calcium reduce the incidence of symptomatic hypocalcaemia; this article reports evaluating its cost-effectiveness in Colombia. METHODS: Meta-analysis was used for comparing the administration of vitamin D or metabolites to oral calcium or no treatment at all in patients following total thyroidectomy and a cost-effectiveness analysis was designed based on a decision-tree model with local costs. RESULTS: The OR value for the comparison between calcitriol and calcium compared to no treatment and to exclusive calcium treatment groups was 0.32 (0.13-0.79 95 %CI) and 0.31 (0.14-0.70 95 %CI), respectively. The most cost-effective strategy was vitamin D or metabolites and calcium administration, having a US $0.05 incremental cost-effectiveness ratio. CONCLUSION: Prophylactic treatment of hypocalcaemia with vitamin D or metabolites + calcium or calcium alone is a cost-effective strategy.

Differential effects of neuromuscular blockers on twitches and tetani in the isolated rat muscle: a multiple comparison study using simultaneous confidence intervals.

In the present work a comparative quantitative evaluation of the differential effects of neuromuscular blockers on twitches and tetani was performed, encompassing: atracurium, cisatracurium, mivacurium, pancuronium, rocuronium and vecuronium. The sciatic nerve-extensor digitorum longus muscle of the rat was used, in vitro. Twitches were evoked at 0.1 Hz and tetani at 50 Hz. The differential effects of the studied compounds on twitches and tetani were statistically compared using simultaneous confidence intervals for the ratios between mean IC(50) for the block of twitches and mean IC(50) for the block of tetani. The results of ratios of mean IC(50) together with their corresponding 95% simultaneous confidence intervals were: vecuronium: 2.5 (1.8-3.5); mivacurium: 3.8 (3.0-4.9); pancuronium: 3.9 (2.0-7.6); rocuronium: 6.1 (3.8-9.9); atracurium: 9.0 (6.4-12.6); cisatracurium: 13.1 (6.0-28.4). Using the criteria that neuromuscular blockers displaying disjunct confidence intervals for the ratios of mean IC(50) differ statistically with regard to differential effects on twitches and tetani, significant differences in ratios of IC(50) were detected in the following cases: vecuronium vs. rocuronium, vs. atracurium and vs. cisatracurium and mivacurium vs: cisatracurium and vs. atracurium. The results show that the magnitude of the differential effects of neuromuscular blockers on twitches and tetani, as evaluated in the present work in the form of ratios of mean IC(50), does not depend on the chemical structure (comparing steroidal and isoquinolinic compounds), but seems to depend on differential pre- and post-synaptic effects of the compounds. It is also suggested that the greater the ability of a compound to block twitches and tetani in a differential manner, the safer is the compound from the clinical anesthesiology viewpoint.

Randomized study on oral administration of calcitriol to prevent symptomatic hypocalcemia after total thyroidectomy.

BACKGROUND: Symptomatic hypocalcemia remains the main postoperative complication after total thyroidectomy. The aim of the present study was to evaluate the role of oral supplementation of calcitriol and calcium salts in preventing severe postoperative hypocalcemia after total thyroidectomy. METHODS: A consecutive series of patients undergoing total thyroidectomy followed by administration of 500 mg of calcium salts 3 times per day were randomized to 3 different postoperative medical treatments: in group A, .5 microg of calcitriol twice per day was administered to 104 patients; in group B, 1 mmicrog of calcitriol twice per day was administered to 111 patients; and in group C, 202 patients did not receive calcitriol. RESULTS: The rate of postoperative tetany in group A was 2.9%, in group B was 0%, and in group C was 7.4% (P=.03) and the rate of paresthesias was 28.8%, 17.1%, and 22.3%, respectively (P=.19). At discontinuation of calcitriol/calcium salts treatment, intact parathyroid hormone levels did not significantly differ from the preoperative levels. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve for serum concentration of calcium in predicting postoperative tetany was .749, .858 and .862 on the first, second, and third postoperative day, respectively. The best cut-off value of calcemia for prediction tetany was 7.5 mg/dL, and the rate of severe hypocalcemia on the third postoperative day was 23.1% in group A, 9.9% in group B, and 27.2% in group C (P=.001). CONCLUSIONS: Oral administration of 1 microg of calcitriol twice per day and 500 mg of calcium salts 3 times per day after total thyroidectomy significantly decreases the risk of severe postoperative hypocalcemia.

[Maternal and childhood immunization in developing countries: success, problems and new approaches]. / Vaccinations de la mère et de l'enfant dans les pays en développement: succès, problèmes et nouvelles orientations.

A quarter century after implementation of the Expanded Program of Immunization by the WHO, partner organizations and member states, significant progress has been made towards eradication of poliomyelitis, elimination of neonatal tetanus, and control of measles. Problems remain due to difficulties involved in extending immunization coverage to some regions (Africa), integrating new vaccines into routine immunization schedules and securing sufficient funding for programs. Injection safety is also a major problem that should be resolved by utilization and proper disposal of single-use auto-disabling syringes. The forthcoming availability of new vaccines on the market and the action of the Global Alliance for Vaccines and Immunization hold reasonable hope for the future.

Cooling abolishes neuronal network synchronization in rat hippocampal slices.

PURPOSE: We sought to determine whether cooling brain tissue from 34 to 21 degrees C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission. METHODS: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450-500 microm) from Sprague-Dawley male rats, maintained in an air-fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34 degrees C, reduced to 21 degrees C within 20 min. RESULTS: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a gamma-aminobutyric acid (GABA)A-receptor antagonist. Cooling from 34 to 21 degrees C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse-evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner. CONCLUSIONS: Tetany-induced neuronal network synchronization by GABAA-sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity.

Pathophysiology of grass tetany and other hypomagnesemias. Implications for clinical management.

Magnesium is an essential mineral with many physiologic and biochemical functions. Surprisingly, Mg homeostasis is not regulated by a hormonal feedback system, but simply depends on inflow (absorption) from the gastrointestinal tract and outflow (endogenous secretion, requirement for milk production, uptake by tissues). Any surplus (inflow greater than outflow) is excreted via urine. Conversely, if the outflow (mainly milk secretion and endogenous loss) exceeds inflow, hypomagnesemia occurs because of the lack of hormonal mechanisms of homeostasis. The major reason for insufficient inflow is a reduced absorption of Mg from the forestomachs. Recent studies from our laboratory and data from the literature permit the proposal of a putative transport model for the secondary active transport of Mg across the rumen epithelium. This model includes two uptake mechanisms across the luminal membrane (PD-dependent and PD-independent) and basolateral extrusion via a Na/Mg exchange. The well-known negative interaction between ruminal K concentration and Mg absorption can be explained on the basis of this model: an increase of ruminal K depolarizes the potential difference of the luminal membrane, PDa, and as the driving force for PD-dependent (or K-sensitive) Mg uptake. Because Na deficiency causes an increase of K concentration in saliva and ruminal fluid, Na deficiency should be considered a potentially important risk factor. The data obtained from in vitro and in vivo studies on the association of Mg transport, changes of ruminal K concentration, and PDa are extensive and confirm the model, if the ruminal Mg concentrations are below 2 to 3 mM. It is further proposed by the model that the PD-independent Mg uptake mechanism is primarily working at high ruminal Mg concentration (above 2 mM). Mg absorption becomes more and more independent of ruminal K with increasing Mg concentration, which can be considered as an explanation for the well-known prophylaxis of hypomagnesemia by increasing oral Mg intake. Fermentation products, NH4+ and SCFA, influence Mg absorption. The possible meaning regarding the pathogenesis of hypomagnesemia is not quite clear. A sudden increase of ruminal NH4+ should be avoided, because high NH4+ concentrations transiently reduce Mg absorption. The most prominent signs of hypomagnesemia are excitations and muscle cramps, which are closely correlated with the Mg concentration in the CSF. It is suggested that the clinical signs are caused by spontaneous activation of neurons in the CNS at low Mg concentrations, which leads to tetany. Prophylactic measures are discussed in context with the known effects on ruminal Mg absorption.

Time courses of plasma magnesium concentrations and urinary magnesium excretion in cows subjected to acute changes in potassium intake.

Hypomagnesaemic tetany in cows develops occasionally after an acute increase in K intake such as can occur when cows are transferred to spring grass. There is evidence that under these conditions plasma Mg concentrations are only transiently decreased. In this study the questions addressed were whether the plasma Mg concentration, indeed adapts to a high K intake as only dietary variable, and whether urinary Mg excretion is associated with this adaptation. Dry cows were fed rations containing either 26 or 50 g K/kg dm, the extra K being in the form of KHCO3. When the cows were acutely transferred from the low to the high K ration, plasma Mg concentrations fell slightly, but significantly from 0.86 to 0.76 mmol/l within five days, but rose again to 0.80 mmol/l after another 23 days, this rise being also statistically significant. None of the animals developed tetany. The decrease in plasma Mg concentration in individual animals after five days on the high-K ration ranged from 6 to 21%. The time course of urinary Mg excretion resembled that of plasma Mg concentration; minimum Mg excretion was seen after four to six days on the high-K ration with a subsequent increase thereafter. To explain the transient lowering of plasma Mg concentration, it is suggested that the K-induced decrease in Mg status caused a delayed increase in the carrier-mediated component of Mg absorption, which in turn caused an increase in urinary Mg excretion. When the cows were acutely switched from the high to the low K ration, plasma Mg concentration and urinary Mg excretion rose, but no transient changes were seen.

Ability of Acidaminococcus fermentans to oxidize trans-aconitate and decrease the accumulation of tricarballylate, a toxic end product of ruminal fermentation.

Mixed ruminal bacteria convert trans-aconitate to tricarballylate, a tricarboxylic acid which chelates blood divalent cations and decreases their availability (J. B. Russell and P. J. Van Soest, Appl. Environ. Microbiol. 47:155-159, 1984). Decreases in blood magnesium in turn cause a potentially fatal disease known as grass tetany. trans-Aconitate was stoichiometrically reduced to tricarballylate by Selenomonas ruminantium, a common ruminal bacterium in grass-fed ruminants (J. B. Russell, Appl. Environ. Microbiol. 49:120-126, 1985). When mixed ruminal bacteria were enriched with trans-aconitate, a trans-aconitate-oxidizing bacterium was also isolated (G. M. Cook, F. A. Rainey, G. Chen, E. Stackebrandt, and J. B. Russell, Int. J. Syst. Bacteriol. 44:576-578, 1994). The trans-aconitate-oxidizing bacterium was identified as Acidaminococcus fermentans, and it converted trans-aconitate to acetate, a nontoxic end product of ruminal fermentation. When S. ruminantium and A. fermentans were cocultured with trans-aconitate and glucose, tricarballylate never accumulated and all the trans-aconitate was converted to acetate. Continuous-culture studies (dilution rate, 0.1 h-1) likewise indicated that A. fermentans could outcompete S. ruminantium for trans-aconitate. When mixed ruminal bacteria were incubated in vitro with 10 mM trans-aconitate for 24 h, 45% of the trans-aconitate was converted to tricarballylate. Tricarballylate production decreased 50% if even small amounts of A. fermentans were added to the incubation mixes (0.01 mg of protein per mg of mixed bacterial protein). When A. fermentans (2 g of bacterial protein) was added directly to the rumen, the subsequent conversion of trans-aconitate to tricarballylate decreased 50%, but this effect did not persist for more than 18 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus.

Cytokines such as interleukin-1 beta (IL-1 beta) are released in the nervous system following inflammation or infection. Recently, IL-1 beta was shown to enhance synaptic inhibitory mechanisms. We therefore investigated the effect of IL-1 beta superfusion on long-term potentiation (LTP), the cellular model of memory and learning, evoked in the CA1 region by tetanic stimulation of the stratum radiatum in the rat hippocampal slice. IL-1 beta (150 pM-1.5 nM) superfused 10 min before tetanic stimulation significantly reduced LTP of the slope of the population excitatory postsynaptic potential (pEPSP) and the population spike (PS) amplitude in CA1 in a concentration-dependent manner. IL-1 beta (1.5 nM) applied for 10 min 1 h before tetanus significantly inhibited LTP of the PS amplitude and pEPSP slope and reduced pEPSP and PS values before tetanus as well, although the PS returned to control values before tetanus. Heat-inactivated IL-1 beta had no effect on pre-tetanus pEPSP or PS values or the induction of LTP. These data demonstrate that IL-1 beta modulates synaptic potentials and reduces LTP. These findings have important implications for the role of IL-1 beta in neuronal disorders following infection, perhaps best exemplified by HIV-1-associated dementia.

[Tetany crisis]. / La crise de tétanie.

The acute crisis of tetany appears generally on spasmophilic backgrounds, triggered most often by stress and anxiety. Always benign, it can however be quite annoying because of its length. The authors study that crisis successively from an etiological, therapeutical and preventive point of view.

Decrease in the size of tetanic responses produced by nitrendipine or by extracellular calcium ion removal without blocking twitches or action potentials in skeletal muscle.

The effects of removing extracellular Ca++ ions or of adding the organic calcium channel antagonist, nitrendipine, were tested on twitches and tetani (100 Hz for 2 sec) in frog toe muscles. Under conditions that did not reduce or that potentiated twitches, both procedures reduced the size of the tetanic responses. This depression was seen as an inability to maintain the maximum tetanic tension for more than 0.5 sec. Intracellular microelectrode recordings showed that the muscle fibers were depolarized (mean about 23 mV) during the stimulus train and the fiber only slowly repolarized after the train. The latter effect is the "late negative afterpotential" and it is produced by the accumulation of K+ ions in the t-tubules during the action potential train. Neither the depolarization nor the late negative afterpotentials were decreased in amplitude by nitrendipine. These results indicate that the voltage-sensitive, slow Ca++ channels are opened by the accumulation of K+ ions in the t-tubules during the tetanus and that the Ca++ ions entering via these channels are required to maintain the full strength of the tetanic contraction. It is suggested that this is a function of these Ca++ channels concentrated in the t-tubules of skeletal muscle fibers.

Effect of magnesium administration route on plasma minerals in Holstein calves receiving either adequate or insufficient magnesium in their diets.

Rates of increase in plasma Mg following rectal or oral administration of solutions containing 30 g MgCl2.6H2O were compared in 10 Holstein bull calves receiving wheat straw (.07% Mg) and concentrates (.04 or .24% Mg) fed separately for ad libitum consumption. Treatments were administered in a sequence, which involved each calf with all combinations of MgCl2.6H2O dosing routes and dietary Mg within a 6-wk period. Plasma Mg concentration averaged 1.95 mg/dl initially but fell below 1 mg/dl within 2 wk after supplemental Mg was omitted. Maximum increases in plasma Mg concentration following oral or rectal dosing were 16 or 47% when dietary Mg was adequate and 48 or 124% when Mg was deficient. Calves fed either diet responded maximally to rectal infusion within 10 min, but plasma Mg of deficient calves increased throughout 160 min after oral dosing. Plasma Mg of deficient calves responded quicker and reached higher concentrations after rectal infusion, but the response was sustained longer after oral administration.

Use of animal breeds and breeding to overcome the incidence of grass tetany: a review.

British breeds of cattle are not so effective as Zebu in extracting nutrients from low-quality roughages, and these breeds differ in their nutrient metabolism and animal physiology. Breeds of cattle may differ in their requirements for Mg. Brahman cows are less susceptible to death from disease and metabolic disorders than are British breeds of cattle, whereas cows with 50% or greater dairy breeding (Holstein and Jersey) are more susceptible than British or Brahman breeds when maintained in beef production herds. Brahman or Brahman crossbred cows are less susceptible than other breeds to metabolic disorders such as grass tetany. Magnesium absorption has been shown to be greater in Brahman than in Jersey, Holstein and Hereford cows. These differences in the efficiency of Mg absorption between different breeds of cows may be due to genetic variation in the absorptive mechanisms of Mg, in feeding behavior, in gastrointestinal tract motility, in gastrointestinal tract fill or to some combination.

Management practices to overcome the incidence of grass tetany.

To minimize the incidence of grass tetany, winter pastures should be established on soils containing Mg-rich minerals, drainage should be improved on five-textured soils, legumes should be included in the sward and soil pH should be at least 5.5. Liming acid soils with dolomitic lime increases forage Mg by supplying Mg and by raising soil pH. Calcitic lime applications also can increase Mg availability to plants on soils with adequate Mg. Low rates of application of soluble Mg salts (less than 100 kg/ha of Mg) effectively increase Mg uptake from noncalcareous soils with low cation exchange capacity. Potassium levels in soils and plants should be kept in the lower range of recommended values. Nitrogen application should be regulated to provide the desired level of forage production. Nitrogen fertilizers, especially the nitrate form, stimulate plant Mg uptake if Mg is available in the soil. The most practical and cost-efficient method of supplementing dietary Mg intake is to provide free-choice Mg. Supplements must be palatable and placed in locations frequently used by cow herds. Including a high-energy feed in the supplement may at times increase its preventive effectiveness by increasing Mg absorption and reducing lipolysis. Regardless of the supplement formulation, Mg intake should be monitored on a regular basis, and formulation or management changes should be initiated if Mg consumption is below required levels. In severe grass tetany outbreaks, foliar application of Mg or administration of Mg via the drinking water may be warranted.