Fluid volume kinetics of dilutional hyponatremia; a shock syndrome revisited.

OBJECTIVE: To evaluate whether the pathophysiology of shock syndromes can be better understood by comparing central hemodynamics with kinetic data on fluid and electrolyte shifts. METHODS: We studied the dilutional hyponatremic shock that developed in response to overhydration with electrolyte-free irrigating fluid - the so-called 'transurethral resection syndrome' - by comparing cardiac output, arterial pressures, and volume kinetic parameters in 17 pigs that were administered 150 ml/kg of either 1.5% glycine or 5% mannitol by intravenous infusion over 90 minutes. RESULTS: Natriuresis appeared to be the key factor promoting hypovolemic hypotension 15-20 minutes after fluid administration ended. Excessive sodium excretion, due to osmotic diuresis caused by the irrigant solutes, was associated with high estimates of the elimination rate constant (k10) and low or negative estimates of the rate constant describing re-distribution of fluid to the plasma after translocation to the interstitium (k21). These characteristics indicated a high urinary flow rate and the development of peripheral edema at the expense of plasma volume and were correlated with reductions in cardiac output. The same general effects of natriuresis were observed for both irrigating solutions, although the volume of infused 1.5% glycine had a higher tendency to enter the intracellular fluid space. CONCLUSION: Comparisons between hemodynamics and fluid turnover showed a likely sequence of events that led to hypovolemia despite intravenous administration of large amounts of fluid.

Fluid volume kinetics of dilutional hyponatremia; a shock syndrome revisited

OBJECTIVE: To evaluate whether the pathophysiology of shock syndromes can be better understood by comparing central hemodynamics with kinetic data on fluid and electrolyte shifts. METHODS: We studied the dilutional hyponatremic shock that developed in response to overhydration with electrolyte-free irrigating fluid - the so-called ‘transurethral resection syndrome' - by comparing cardiac output, arterial pressures, and volume kinetic parameters in 17 pigs that were administered 150 ml/kg of either 1.5% glycine or 5% mannitol by intravenous infusion over 90 minutes. RESULTS: Natriuresis appeared to be the key factor promoting hypovolemic hypotension 15-20 minutes after fluid administration ended. Excessive sodium excretion, due to osmotic diuresis caused by the irrigant solutes, was associated with high estimates of the elimination rate constant (k10) and low or negative estimates of the rate constant describing re-distribution of fluid to the plasma after translocation to the interstitium (k21). These characteristics indicated a high urinary flow rate and the development of peripheral edema at the expense of plasma volume and were correlated with reductions in cardiac output. The same general effects of natriuresis were observed for both irrigating solutions, although the volume of infused 1.5% glycine had a higher tendency to enter the intracellular fluid space. CONCLUSION: Comparisons between hemodynamics and fluid turnover showed a likely sequence of events that led to hypovolemia despite intravenous administration of large amounts of fluid. .

Glycine intrastriatal administration induces lipid and protein oxidative damage and alters the enzymatic antioxidant defenses in rat brain.

AIMS: We investigated the effects of in vivo intrastriatal administration of glycine (Gly), which is found at high concentrations in the brain of patients affected by nonketotic hyperglycinemia (NKH), on important parameters of oxidative stress. MAIN METHODS: Thiobarbituric acid-reactive substances values (TBA-RS, lipid peroxidation), carbonyl formation (protein oxidative damage), sulfhydryl content, reduced glutathione concentrations, nitric oxide production and the activities of the antioxidant enzymes glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase and glucose-6-phosphate dehydrogenase (antioxidant defenses) were measured in striatum from 30-day-old rats after Gly injection. KEY FINDINGS: Gly administration significantly increased TBA-RS values, implying lipid oxidative damage. Furthermore, Gly-induced increase of TBA-RS was fully prevented by the NMDA receptor antagonist MK-801, indicating the involvement of the NMDA glutamate receptor in this effect. Gly injection also induced protein carbonyl formation, as well as elevation of the activities of glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase. In contrast, glutathione levels, sulfhydryl content, nitric oxide production and the activity of glucose-6-phosphate dehydrogenase were not modified by Gly. SIGNIFICANCE: The data shows that Gly in vivo administration causes lipid peroxidation, probably secondary to NMDA stimulation, induces protein oxidation and modulates the activities of important antioxidant enzymes in the striatum. In case these findings can be extrapolated to the human NKH, it is feasible that oxidative stress may be involved in the pathophysiology of the brain injury observed in patients with this neurometabolic disease.

Efetividade de diferentes estratégias de intervenção com ferro nos níveis de hemoglobina e ferritina em escolares de Teresina, Piauí, Brasil / Effectiveness of different iron supplementation strategies on hemoglobin and ferritin levels among schoolchildren in Teresina, Piauí State, Brazil

O estudo avaliou o efeito das intervenções com sulfato ferroso e com ferro bisglicina quelato nas concentrações de hemoglobina e ferritina sérica em escolares de 7-11 anos, de ambos os sexos, de Teresina, Piauí, Brasil. Foi desenvolvido ensaio clínico-comunitário, randomizado, envolvendo 138 escolares, com níveis de hemoglobina < 11,5g/dL, alocados, individualmente, em dois grupos de tratamento. Um grupo (n = 71) recebeu 40mg de sulfato ferroso, uma vez/semana, e o outro (n = 67) 3,8mg de ferro bisglicina quelato, fracionados em biscoitos consumidos três vezes/semana, durante oito semanas. Houve um incremento (p < 0,01) médio, nas concentrações de hemoglobina, de 1,1g/dL entre os escolares que receberam sulfato ferroso e de 0,9g/dL para aqueles que receberam ferro bisglicina quelato, embora sem diferença (p > 0,05) na comparação intergrupos. Nenhum impacto foi observado (p > 0,05) nas reservas corporais de ferro. Entretanto, escolares que apresentaram depleção das reservas corporais de ferro (< 15ng/mL), no início dos tratamentos, tiveram aumento (p < 0,01) nas concentrações médias de ferritina sérica, após a intervenção, embora com efeito similar (p > 0,05) entre os grupos de tratamento. Os resultados confirmam a efetividade das intervenções e ratificam o uso do esquema semanal com sulfato ferroso e com ferro bisglicina quelato no tratamento da deficiência do mineral e da anemia ferropriva.

This study evaluated the effectiveness of supplementation with ferrous sulfate and iron bis-glycinate chelate on hemoglobin and serum ferritin levels among schoolchildren (7-11 years) of both sexes. A randomized community-based trial including 138 anemic children (hemoglobin < 11.5g/dL) was conducted in Teresina, Piauí State, Brazil. Children were assigned to two treatment groups on an individual basis. One group (n = 71) received 40mg iron as ferrous sulfate once weekly and the other group (n = 67) received 3.8mg of iron bis-glycinate chelate-enriched cookies, 3x/week, for 8 weeks. The interventions showed a significant increase (p < 0.01) in hemoglobin levels (1.1g/dL) for children who received ferrous sulfate and 0.9g/dl in those who received iron bis-glycinate chelate, although not significant in the inter-group comparison (p > 0.05). No effect was observed on body iron for either intervention (p > 0.05). Children with depleted iron stores (< 15ng/mL) at the beginning of interventions showed increased serum ferritin concentrations after 8 weeks (p < 0.01), although no difference between treatments (p > 0.05) was observed. The results confirm the effectiveness of the iron supplementation interventions and corroborate the use of iron salts or ferrous bisglycinate chelate on a weekly basis to overcome iron deficiency and anemia.

[Effectiveness of different iron supplementation strategies on hemoglobin and ferritin levels among schoolchildren in Teresina, Piauí State, Brazil]. / Efetividade de diferentes estratégias de intervenção com ferro nos níveis de hemoglobina e ferritina em escolares de Teresina, Piauí, Brasil.

This study evaluated the effectiveness of supplementation with ferrous sulfate and iron bis-glycinate chelate on hemoglobin and serum ferritin levels among schoolchildren (7-11 years) of both sexes. A randomized community-based trial including 138 anemic children (hemoglobin < 11.5 g/dL) was conducted in Teresina, Piauí State, Brazil. Children were assigned to two treatment groups on an individual basis. One group (n = 71) received 40 mg iron as ferrous sulfate once weekly and the other group (n = 67) received 3.8 mg of iron bis-glycinate chelate-enriched cookies, 3x/week, for 8 weeks. The interventions showed a significant increase (p < 0.01) in hemoglobin levels (1.1g/dL) for children who received ferrous sulfate and 0.9 g/dl in those who received iron bis-glycinate chelate, although not significant in the inter-group comparison (p > 0.05). No effect was observed on body iron for either intervention (p > 0.05). Children with depleted iron stores (< 15 ng/mL) at the beginning of interventions showed increased serum ferritin concentrations after 8 weeks (p < 0.01), although no difference between treatments (p > 0.05) was observed. The results confirm the effectiveness of the iron supplementation interventions and corroborate the use of iron salts or ferrous bisglycinate chelate on a weekly basis to overcome iron deficiency and anemia.

Taurine in the anterior cingulate cortex diminishes neuropathic nociception: a possible interaction with the glycine(A) receptor.

Taurine is an inhibitory amino-acid which has been proposed as a nociceptive process neuromodulator. The glycine(A) receptor (glyR(A)) has been postulated as a receptor in which taurine exerts its function. Functional image studies have documented the role of the anterior cingulate cortex (ACC) in the affective component of pain. The aim of this study was to investigate the role of taurine as a glycinergic agonist in the ACC using a neuropathic pain model related to autotomy behaviour (AB). In order to test whether glyR(A) is responsible for taurine actions, we microinjected strychnine, a glyR(A) antagonist. We used taurine microinjected into the ACC, followed by a thermonociceptive stimulus and a sciatic denervation. Chronic nociception was measured by the autotomy score, onset and incidence. The administration of taurine 7 days after denervation modifies the temporal course of AB by inhibiting it. Our results showed a decreased autotomy score and incidence in the taurine groups, as well as a delay in the onset. Those experimental groups in which strychnine was microinjected into the ACC, either on its own or before the microinjection of taurine, showed no difference as compared to the control group. When taurine was microinjected prior to strychnine, the group behaved as if only taurine had been administered. Our results evidence a significant neuropathic nociception relief measured as an AB decrease by the microinjection of taurine into the ACC. Besides, the role of the glyR(A) is evidenced by the fact that strychnine antagonises the antinociceptive effect of taurine.

Is glycine effective against elevated blood pressure?

PURPOSE OF REVIEW: Glycine, a non-essential amino acid, has been found to protect against oxidative stress in several pathological situations, and it is required for the biosynthesis of structural proteins such as elastin. As hypertension is a disease in which free radicals and large vessel elasticity are involved, this article will examine the possible mechanisms by which glycine may protect against high blood pressure. RECENT FINDINGS: The addition of glycine to the diet reduces high blood pressure in a rat model of the metabolic syndrome. Also, glycine supplemented to the low protein diet of rat dams during pregnancy has a beneficial effect on blood pressure in their offspring. The mechanism by which glycine decreases high blood pressure can be attributed to its participation in the reduction of the generation of free radicals, increasing the availability of nitric oxide. In addition, as glycine is required for a number of critical metabolic pathways, such as the synthesis of the structural proteins collagen and elastin, the perturbation of these leads to impaired elastin formation in the aorta. This involves changes in the aorta's elastic properties, which would contribute to the development of hypertension. SUMMARY: The use of glycine to lower high blood pressure could have a significant clinical impact in patients with the metabolic syndrome and with limited resources. On the other hand, more studies are needed to explore the beneficial effect of glycine in other models of hypertension and to investigate possible side-effects of treatment with glycine.