Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada

IntroductionMetabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice.ObjectivesTo describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction.Material and methodsRetrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate < 22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were ≥ 22 mEq/l.ResultsThe study group consisted of 969 patients (age 65 ± 14 years, 507 males) with a mean GFR of 14.8 ± 4.5 ml/min/1.73 m². At baseline, 530 patients (55%) had serum bicarbonate < 22 mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR = 1.03; 95% CI 1.01 – 1.05), baseline GFR (OR = 1.07; 1.02 – 1.12), and treatment with proton-pump inhibitors (OR = 1.61; 95% CI 1.06 – 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67 ± 3.71 vs -4.36 ± 4.56 ml/min/1.73 m²/year, P < .0001), and lower average serum potassium concentration (5.1 ± 0.5 vs 5.3 ± 0.5, P < .0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate.ConclusionMA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched.     

Hyperpolarized product selective saturating‐excitations for determination of changes in metabolic reaction rates in real‐time

Investigation of hyperpolarized substrate metabolism has been showing utility in real‐time determination of in‐cell and in vivo enzymatic activities. Intracellular reaction rates may vary during the course of a measurement, even on the very short time scales of visibility on hyperpolarized MR, due to many factors such as the availability of the substrate and co‐factors in the intracellular space. Despite this potential variation, the kinetic analysis of hyperpolarized signals typically assumes that the same rate constant (and in many cases, the same rate) applies throughout the course of the reaction as observed via the build‐up and decay of the hyperpolarized signals. We demonstrate here an acquisition approach that can null the need for such an assumption and enable the detection of instantaneous changes in the rate of the reaction during an ex vivo hyperpolarized investigation, (i.e. in the course of the decay of one hyperpolarized substrate dose administered to a viable tissue sample ex vivo). This approach utilizes hyperpolarized product selective saturating‐excitation pulses. Similar pulses have been previously utilized in vivo for spectroscopic imaging. However, we show here favorable consequences to kinetic rate determinations in the preparations used. We implement this acquisition strategy for studies on perfused tissue slices and develop a theory that explains why this particular approach enables the determination of changes in enzymatic rates that are monitored via the chemical conversions of hyperpolarized substrates. Real‐time changes in intracellular reaction rates are demonstrated in perfused brain, liver, and xenograft breast cancer tissue slices and provide another potential differentiation parameter for tissue characterization.     

Ammonium accumulation and chemokine decrease in culture media of Gcdh−/− 3D reaggregated brain cell cultures

Glutaric Aciduria type I (GA-I) is caused by mutations in the GCDH gene. Its deficiency results in accumulation of the key metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body tissues and fluids. Present knowledge on the neuropathogenesis of GA-I suggests that GA and 3-OHGA have toxic properties on the developing brain.We analyzed morphological and biochemical features of 3D brain cell aggregates issued from Gcdh^?/? mice at two different developmental stages, day-in-vitro (DIV) 8 and 14, corresponding to the neonatal period and early childhood. We also induced a metabolic stress by exposing the aggregates to 10 mM l-lysine (Lys).Significant amounts of GA and 3-OHGA were detected in Gcdh^?/? aggregates and their culture media. Ammonium was significantly increased in culture media of Gcdh^?/? aggregates at the early developmental stage. Concentrations of GA, 3-OHGA and ammonium increased significantly after exposure to Lys. Gcdh^?/? aggregates manifested morphological alterations of all brain cell types at DIV 8 while at DIV 14 they were only visible after exposure to Lys. Several chemokine levels were significantly decreased in culture media of Gcdh^?/? aggregates at DIV 14 and after exposure to Lys at DIV 8.This new in vitro model for brain damage in GA-I mimics well in vivo conditions. As seen previously in WT aggregates exposed to 3-OHGA, we confirmed a significant ammonium production by immature Gcdh^?/? brain cells. We described for the first time a decrease of chemokines in Gcdh^?/? culture media which might contribute to brain cell injury in GA-I.     

Evidence of self-protonation on the electrodic reduction mechanism of an anti-Helicobacter pylori metronidazole isotere

The electrochemical reduction mechanism of 1-(2-ammoniumethyl)-2-methyl-5-nitroimidazole bromide (2) in DMSO + 0.1 mol l^?1 TBAP has been investigated by cyclic voltammetry and macroscale electrolysis, on a glassy carbon electrode, in comparison with metronidazole (1). The cyclic voltammogram of 2 is represented by three reduction waves, one of them at less negative potential, when compared to the first wave of metronidazole which indicates that it undergoes easier reduction. There is evidence for a self-protonation mechanism in the electroreduction of 2, represented by the absence of the first wave in the successive cyclic voltammogram, by the disappearance of the first reduction wave upon addition of base and increase of the same wave in the presence of exogenous proton donors. The stoichiometry of the reaction, at the first reduction wave, involves 0.8 mol electron mol^?1 and yields 0.2 mol of 4e^?/4H⁺ reduced derivative (probably an unstable hydroxylamine) and 0.8 mol of the amine derivative, the conjugated base of 2. The second and third waves are typical for nitroaromatic reduction and are related to the reduction of the nitro group in this aminoderivative.     

Do buffered local anesthetics provide more successful anesthesia than nonbuffered solutions in patients with pulpally involved teeth requiring dental therapy?: A systematic review

Background

The authors conducted a systematic review that addresses the following population, intervention, comparison, outcome question: “In adults requiring dental therapy with pulpally involved teeth, what is the comparative efficacy of buffered local anesthetics (LAs) compared with that of nonbuffered LAs in achieving anesthetic success?”

The role of the succinate pathway in sorbitol fermentation by oral Actinomyces viscosus and Actinomyces naeslundii

The sorbitol fermentation by Actinomyces viscosus and Actinomyces naeslundii was studied with washed sorbitol-grown cells. The fermentation was followed by titration of acids produced at pH 7.0 under anaerobic conditions. Metabolic end-products and intracellular levels of NAD, NADH and glycolytic intermediates during the fermentation were also analyzed. Cell extracts were examined for certain enzyme activities. Bicarbonate was required for acid production from sorbitol and from a mixture of glucose and sorbitol. Malate and fumarate could also support the acid production of A. viscosus. The main end-products were succinate and lactate but not ethanol. Cell extracts showed no activities of alcohol and aldehyde dehydrogenases, but they had activities of malate dehydrogenase and fumarate reductase. In the absence of bicarbonate, malate or fumarate, the intracellular NADH/NAD ratio increased and the levels of 3- and 2-phospho-glycerate and phosphoenolpyruvate decreased. The results indicate that oral sorbitol-fermenting actinomyces lack the ethanol pathway that can contribute to NADH oxidation. To maintain intracellular redox balance during anaerobic sorbitol fermentation, these bacteria can oxidize surplus NADH through a succinate pathway.     

碳酸氢铵溶液增效HIFU消融新鲜离体牛肝的研究

目的 研究碳酸氢铵溶液增效HIFU消融离体牛肝的作用。方法 用HIFU以不同功率消融离体牛肝,比较不同浓度的碳酸氢铵溶液的实验组与注射PBS的对照组在灰度差值、灰度区域面积及凝固性坏死体积的差别并进行统计学分析。结果 当HIFU消融功率为150w时,各浓度碳酸氢铵溶液组在灰度差值、灰度面积及凝固性坏死体积方面均显著高于PBS对照组（P＜0.05）;而以其他功率进行HIFU消融时,情况并不完全一致。结论 在功率合适时,碳酸氢铵溶液具备增效HIFU消融离体牛肝的作用。     

维生素B6碳酸氢钠经阴道超声子宫输卵管造影临床应用

目的 观察应用维生素B6加碳酸氢钠作为声学造影剂，判断不孕症病人的输卵管通畅性和造影剂的应用效果。方法 对68例不孕症妇女采用维生素B6注射液300mg加5％碳酸氢钠5ml的混合液作声学造影剂，在阴道超声直视下观察输卵管通畅情况。结果 双侧输卵管通畅31例；双侧通而不畅8例；一侧通畅20例；一侧通而不畅，一侧阻塞3例；二侧阻塞6例。9例施行DSA下再通，符合率100％，同时检出子宫内疾病4例。结论 维生素B6加碳酸氢钠作为声学造影剂，具有直观、可靠、反应小、效果好、副作用少的优点。