acidosis metabolic [keywords]
- Metabolic consequences of β-alanine supplementation during exhaustive supramaximal cycling and 4000-m time-trial performance. [JOURNAL ARTICLE]
- Appl Physiol Nutr Metab 2016 Aug; 41(8):864-871.
The present study investigated the effects of β-alanine supplementation on the resultant blood acidosis, lactate accumulation, and energy provision during supramaximal-intensity cycling, as well as the aerobic and anaerobic contribution to power output during a 4000-m cycling time trial (TT). Seventeen trained cyclists (maximal oxygen uptake = 4.47 ± 0.55 L·min(-1)) were administered 6.4 g of β-alanine (n = 9) or placebo (n = 8) daily for 4 weeks. Participants performed a supramaximal cycling test to exhaustion (equivalent to 120% maximal oxygen uptake) before (PreExh) and after (PostExh) the 4-week supplementation period, as well as an additional postsupplementation supramaximal cycling test identical in duration and power output to PreExh (PostMatch). Anaerobic capacity was quantified and blood pH, lactate, and bicarbonate concentrations were measured pre-, immediately post-, and 5 min postexercise. Subjects also performed a 4000-m cycling TT before and after supplementation while the aerobic and anaerobic contributions to power output were quantified. β-Alanine supplementation increased time to exhaustion (+12.8 ± 8.2 s; P = 0.041) and anaerobic capacity (+1.1 ± 0.7 kJ; P = 0.048) in PostExh compared with PreExh. Performance time in the 4000-m TT was reduced following β-alanine supplementation (-6.3 ± 4.6 s; P = 0.034) and the mean anaerobic power output was likely to be greater (+6.2 ± 4.5 W; P = 0.035). β-Alanine supplementation increased time to exhaustion concomitant with an augmented anaerobic capacity during supramaximal intensity cycling, which was also mirrored by a meaningful increase in the anaerobic contribution to power output during a 4000-m cycling TT, resulting in an enhanced overall performance.
- Single-site cannulation veno-venous extracorporeal CO2 removal as bridge to lung volume reduction surgery in end-stage lung emphysema. [JOURNAL ARTICLE]
- ASAIO J 2016 Jul 26.
Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we first describe the application of low-flow v-v extracorporeal CO2 removal (LFVV-ECCO2R) as bridge to LVRS in patients with end-stage lung emphysema experiencing severe hypercapnia due to acute failure of the breathing pump.Between March and October 2015, n = 4 patients received single-site LFVV-ECCO2R as bridge to LVRS.Indication for ECLS was severe hypercapnia with respiratory acidosis and acute breathing pump failure. Two patients required continuous mechanical ventilation over a temporary tracheostomy and were bed ridden. The other two patients were nearly immobile due to severe dyspnea at rest. Length of preoperative ECCO2R was 14 (1 - 42) days. All patients underwent unilateral LVRS. Anatomical resection of the right (n = 3) or left (n = 1) upper lobe was performed. Postoperatively, both patients with previous mechanical ventilatory support were successfully weaned.ECCO2R in patients with end-stage lung emphysema experiencing severe hypercapnia due to acute breathing pump failure is a safe and effective bridging tool to LVRS. In such patients, radical surgery leads to a significant improvement of the performance status and furthermore facilitates respiratory weaning from mechanical ventilation.
- NF-κB is involved in the LPS-mediated proliferation and apoptosis of MAC-T epithelial cells as part of the subacute ruminal acidosis response in cows. [JOURNAL ARTICLE]
- Biotechnol Lett 2016 Jul 22.
To determine the effect of NF-κB on cell proliferation and apoptosis, we investigate the expression of inflammation and apoptosis-related factors in the bovine mammary epithelial cell line, MAC-T.MAC-T cells were cultured in vitro and MTT and LDH assays used to determine the effects of lipopolysaccharide (LPS) on proliferation and cytotoxicity respectively. RT-PCR and western blotting were used to evaluate the effect of LPS and NF-κB inhibition [pyrrolidine dithiocarbamate (PDTC) treatment] on the expression of inflammation and apoptosis-related factors. LPS significantly inhibited MAC-T cell proliferation in a dose- and time-dependent manner. Furthermore, LPS promoted apoptosis while the NF-кB inhibitor PDTC attenuated this effect. After LPS treatment, the NF-кB signaling pathway was activated, and the expression of inflammation and apoptosis-related factors increased. When PDTC blocked NF-кB signaling, the expression of inflammation and apoptosis-related factors were decreased in MAC-T cells.LPS activates the TLR4/NF-κB signaling pathway, inhibits proliferation and promotes apoptosis in MAC-T cells. NF-кB inhibition attenuates MAC-T cell apoptosis and TLR4/NF-κB signaling pathway. NF-кB inhibitor alleviating MAC-T cell apoptosis is presumably modulated by NF-кB.
- pH-sensitive MRI demarcates graded tissue acidification during acute stroke - pH specificity enhancement with magnetization transfer and relaxation-normalized amide proton transfer (APT) MRI. [JOURNAL ARTICLE]
- Neuroimage 2016 Jul 18.
pH-sensitive amide proton transfer (APT) MRI provides a surrogate metabolic biomarker that complements the widely-used perfusion and diffusion imaging. However, the endogenous APT MRI is often calculated using the asymmetry analysis (MTRasym), which is susceptible to an inhomogeneous shift due to concomitant semisolid magnetization transfer (MT) and nuclear overhauser (NOE) effects. Although the intact brain tissue has little pH variation, white and gray matter appears distinct in the MTRasym image. Herein we showed that the heterogeneous MTRasym shift not related to pH highly correlates with MT ratio (MTR) and longitudinal relaxation rate (R1w), which can be reasonably corrected using the multiple regression analysis. Because there are relatively small MT and R1w changes during acute stroke, we postulate that magnetization transfer and relaxation-normalized APT (MRAPT) analysis increases MRI specificity to acidosis over the routine MTRasym image, hence facilitates ischemic lesion segmentation. We found significant differences in perfusion, pH and diffusion lesion volumes (P<0.001, ANOVA). Furthermore, MRAPT MRI depicted graded ischemic acidosis, with the most severe acidosis in the diffusion lesion (-1.05±0.29%/s), moderate acidification within the pH/diffusion mismatch (i.e., metabolic penumbra, -0.67±0.27%/s) and little pH change in the perfusion/pH mismatch (i.e., benign oligemia, -0.04±0.14%/s), providing refined stratification of ischemic tissue injury.
- Letter to the Editor: Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis. [Comment, Journal Article]
- Ann Pediatr Endocrinol Metab 2016 Jun; 21(2):109-10.
- The Author Reply: Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis. [Journal Article]
- Ann Pediatr Endocrinol Metab 2016 Jun; 21(2):111-2.
- Metformin associated lactic acidosis in Auckland City Hospital 2005 to 2009. [Journal Article]
- World J Nephrol 2016 Jul 6; 5(4):367-71.
To determine the incidence, clinical characteristics and outcomes of patients with metformin associated lactic acidosis (MALA).Auckland City Hospital drains a population of just over 400000 people. All cases presenting with metabolic acidosis between July 2005 and July 2009 were identified using clinical coding. A retrospective case notes review identified patients with MALA. Prescribing data for metformin was obtained from the national pharmaceutical prescribing scheme.There were 42 cases of metabolic lactic acidosis over 1718000 patient years. There were 51000 patient years of metformin prescribed to patients over the study period. There were thirty two cases of lactic acidosis due to sepsis, seven in patients treated with metformin. Ten cases of MALA were identified. The incidence of MALA was estimated at 19.46 per 100000 patient year exposure to metformin. The relative risk of lactic acidosis in patients on metformin was 13.53 (95%CI: 7.88-21.66) compared to the general population. The mean age of patients with MALA was 63 years, range 40-83 years. A baseline estimated glomerular filtration rate was obtained in all patients and ranged from 23-130 mL/min per 1.73 m(2). Only two patients had chronic kidney disease G4. Three patients required treatment with haemodialysis. Two patients died.Lactic acidosis is an uncommon but significant complication of use of metformin which carries a high risk of morbidity.
- Trauma Survival Margin Analysis: A Dissection of Trauma Center Performance through Initial Lactate. [Journal Article]
- Am Surg 2016 Jul; 82(7):649-53.
Measurement of trauma center performance presently relies on W-score calculation and comparison to national data sets. A limitation to this practice is a skewing of the W score, as it determines overall performance of a trauma population that is often heavily weighted by patients of low acuity. The University of Virginia relative mortality metric (RMM) was formulated to provide higher resolution in identifying areas of performance improvement within subpopulations of a trauma center using traditional Trauma Injury Severity Score methodology. Lactic acidosis has been established as a risk factor for mortality in the setting of trauma. This study aims to compare survival margin, defined as the area between actual and predicted mortality curves, in patients with either normal or elevated initial lactate. W score and RMM were calculated and compared in these cohorts. Whereas the W score suggested increased survival within the high initial lactate group, the RMM demonstrated the expected finding of increased survival margin in the normal lactate cohort. The RMM is a potentially valuable tool for trauma centers to monitor and improve performance. In addition, these findings validate the use of lactate as a triage and risk adjustment tool in the trauma setting.
- Gentisic acid sodium salt, a phenolic compound, is superior to norepinephrine in reversing cardiovascular collapse, hepatic mitochondrial dysfunction and lactic acidemia in Pseudomonas aeruginosa septic shock in dogs. [Journal Article]
- Intensive Care Med Exp 2016 Dec; 4(1):24.
The development of lactic acidemia (LA) in septic shock (SS) is associated with an ominous prognosis. We previously showed that the mechanism of LA in SS may relate to impaired hepatic uptake of lactate, but the mechanism was not clear. Uptake of lactate by the liver occurs by a membrane-associated, pH-dependent, antiport system known as the monocarboxylate transporter. In the hepatocyte, lactate can then be metabolized by oxidative phosphorylation or converted to glucose in the cytosol. In the present study, we examined (1) whether hepatic mitochondrial dysfunction accounted for decreased uptake of lactate in a canine model of Pseudomonas aeruginosa SS, (2) whether norepinephrine (NE) treatment by increasing mean arterial pressure (MAP) could improve mitochondrial dysfunction and LA in this model, and (3) whether gentisic acid sodium salt (GSS), a novel phenolic compound, was superior to NE in these effects.In anesthetized/ventilated dogs, we infused the bacteria over ~10 h and measured hemodynamics in various treatment groups (see below). We then euthanized the animal and isolated the hepatic mitochondria. We measured hepatic mitochondrial oxygen consumption rates using the novel Seahorse XF24 analyzer under conditions that included: basal respiration, after the addition of adenosine- diphosphate to produce coupled respiration, and after the addition of a protonophore to produce maximal respiration.We found that in the septic control group, mean arterial pressure decreased over the course of the study, and that mitochondrial dysfunction developed in which there was a reduction in maximal respiration. Whereas both NE and GSS treatments reversed the reduction in mean arterial pressure and increased maximal respiration to similar extents in respective groups, only in the GSS group was there a reduction in LA.Hepatic mitochondrial dysfunction occurs in SS, but does not appear to be required for the development of LA in SS, since NE improved mitochondrial dysfunction without reversing LA. GSS, a phenolic compound restored mean arterial pressure, mitochondrial dysfunction, and LA in SS. This reduction in LA may be independent of its effect on improving hepatic mitochondrial function.
- Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement. [JOURNAL ARTICLE]
- J Nephrol 2016 Jul 25.
Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research.A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved.Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients.This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.