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acidosis metabolic [keywords]
- Retinopathy of prematurity: risk factors and role of antenatal betamethasone in Indian preterm newborn babies. [Journal Article]
- J Clin Neonatol 2014 Jan; 3(1):20-4.
Increase in the survival of preterm neonates has led to increased incidence of retinopathy of prematurity (ROP). Among various risk factors, only prematurity is well-established and role of others is still not clear. Effect of antenatal betamethasone on ROP severity is also controversial. Available literature from India has a paucity of information.(a) The primary aim of the following study is to find the incidence and risk factors of ROP and (b) secondary aim is to assess the effect of antenatal betamethasone on ROP.prospective, observational cohort study.Tertiary level neonatal care unit.A total of 148 infants ≤ 34 weeks gestation at birth, completed the study protocol. Severe ROP was defined as stage II and higher (including plus disease) of ROP. Various perinatal factors including antenatal betamethasone were analyzed by univariate followed by multivariate analysis.overall incidence of ROP (any stage) was 44.6%. Severe ROP was mainly detected in <1200 g birth weight and/or <30 weeks gestational age. Antenatal betamethasone was associated with non-severe form of ROP (P < 0.05) on univariate analysis, but could not pass multivariate logistic regression analysis. Among other perinatal factors studied, low birth weight (<1200 g) (odds ratio [OR]: 19.699, 95% confidence interval [CI]: 2.42-160.17, P = 0.005), low gestational age (<30 weeks) (OR: 36.52, 95% CI: 3.76-354.3, P = 0.002), acidosis (OR: 6.932, 95% CI: 1.16-41.33, P = 0.034) and blood transfusion (OR: 14.11, 95% CI: 1.494-133.5, P = 0.021) were associated with babies in severe ROP in an independent manner.Low birth weight and low gestational age emerged as independent significant risk factors along with blood transfusion and acidosis. Antenatal betamethasone may be preventive for severe ROP. More studies are however recommended.
- Common and Novel TMEM70 Mutations in a Cohort of Italian Patients with Mitochondrial Encephalocardiomyopathy. [JOURNAL ARTICLE]
- JIMD Rep 2014 Apr 17.
ATP synthase or complex V (cV) of the oxidative phosphorylation system is responsible for the production of ATP, dissipating the electrochemical gradient generated by the mitochondrial respiratory chain. In addition to maternally transmitted cV dysfunction caused by mutations in mtDNA genes (MT-ATP6 or MT-ATP8), encoding cV subunits, recessive mutations in the nuclear TMEM70 are the most frequent cause of ATP synthase deficiency.We report on a cohort of ten Italian patients presenting with neonatal lactic acidosis, respiratory distress, hypotonia, cardiomyopathy and psychomotor delay and harbouring mutations in TMEM70, including the common splice mutation and four novel variants. TMEM70 protein was virtually absent in all tested TMEM70 patients' specimens.The exact function of TMEM70 is not known, but it is considered to impact on cV assembly since TMEM70 mutations have been associated with isolated cV activity reduction. We detected a clear cV biochemical defect in TMEM70 patients' fibroblasts, whereas the assay was not reliable in frozen muscle. Nevertheless, the evaluation of the amount of holocomplexes in patients with TMEM70 mutations showed a nearly absent cV in muscles and a strong decrease of cV with accumulation of sub-assembly species in fibroblasts. In our cohort we found not only cV deficiencies but also impairment of other OXPHOS complexes. By ultrastructural analysis of muscle tissue from one patient with isolated cV deficiency, we found a severely impaired mitochondrial morphology with loss of the cristae. These findings indicate that cV impairment could indirectly alter other respiratory chain complex activities by disrupting the mitochondrial cristae structure.
- Acid base, electrolyte, glucose, and lactate values during cardiopulmonary resuscitation in dogs and cats. [Journal Article]
- J Vet Emerg Crit Care (San Antonio) 2014 Mar; 24(2):208-14.
To report acid base, electrolyte, glucose, and lactate values collected during or immediately after cardiopulmonary resuscitation (CPR) in dogs and cats.Retrospective study.University Teaching Hospital.Thirty-two dogs and 10 cats.None.Blood gas, electrolyte, glucose, and lactate values measured during CPR or within 5 minutes of return of spontaneous circulation (ROSC) were retrospectively evaluated. The time of blood collection with respect to the occurrence of cardiopulmonary arrest (CPA), the initiation of CPR or ROSC was noted. Forty-two venous blood samples were analyzed, 24 collected during CPR and 18 samples were collected within 5 minutes of ROSC. Metabolic acidosis and hyperlactatemia were evident in all samples in the study while an increased PvCO2 occurred in 88% of samples collected during CPR and in 61% of samples collected following ROSC. Hyperkalemia occurred in 65% of all cases, decreased ionized calcium was evident in 18%, hypoglycemia was evident in 21% while hyperglycemia was evident in 62%. There was no significant difference in any parameter evaluated between dogs and cats during CPR. There was no significant difference of any variable measured during the first 15 minutes of CPA versus those measured more than 15 minutes following CPA. When the values measured during the first 5 minutes of ROSC were compared to those measured during CPR, the pH and PvO2 were significantly lower in the CPR group.Biochemical abnormalities including metabolic acidosis, hyperkalemia, ionized hypocalcemia, hypoglycemia, and hyperglycemia can be identified during CPR and immediately following ROSC. The therapeutic and prognostic relevance of these changes are yet to be defined and may prove to be useful to guide patient management in the future.
- Energy metabolism and regeneration impaired by seawater acidification in the infaunal brittlestar, Amphiura filiformis. [JOURNAL ARTICLE]
- J Exp Biol 2014 Apr 15.
Seawater acidification due to anthropogenic release of CO2 as well as the potential leakage of pure CO2 from sub-seabed carbon capture storage sites (CCS) may impose a serious threat to marine organisms. Although infaunal organisms can be expected to be particularly impacted by decreases in seawater pH, due to naturally acidified conditions in benthic habitats, information regarding physiological and behavioral responses is still scarce. Determination of pO2 and pCO2 gradients within the burrows of the brittlestar Amphiura filiformis during environmental hypercapnia demonstrated that besides hypoxic conditions, increases of environmental pCO2 are additive to the already high pCO2 (up to 0.08 kPa) within the burrows. In response to up to 4 weeks exposure to pH 7.3 (0.3 kPa pCO2) and pH 7.0 (0.6 kPa pCO2), metabolic rates of A.filiformis were significantly reduced in pH 7.0 treatments accompanied by increased ammonium excretion rates. Gene expression analyses demonstrated significant reductions of acid-base (NBCe and AQP9) and metabolic (G6PDH, LDH) genes. Determination of extracellular acid-base status indicated an uncompensated acidosis in CO2 treated animals, which could explain depressed metabolic rates. Metabolic depression is associated with a retraction of filter feeding arms into sediment burrows. Regeneration of lost arm tissues following traumatic amputation is associated with significant increases in metabolic rate, and hypercapnic conditions (pH 7.0, 0.6 KPa) dramatically reduce the metabolic scope for regeneration reflected in 80% reductions in regeneration rate. Thus, the present work demonstrates that elevated seawater pCO2 significantly affects the environment and the physiology of infaunal organisms like A. filiformis.
- Inhibition of ASICs reduces rat hepatic stellate cells activity and liver fibrosis: An in vitro and in vivo study. [JOURNAL ARTICLE]
- Cell Biol Int 2014 Apr 16.
Hepatic fibrosis is a chronic inflammation-associated disease, which is involved in the infiltration of inflammatory cells and releasing of proinflammatory cytokines. In the pathological process, protons are released by damaged cells and acidosis is considered to play a critical role in cell injury. Although the underlying mechanism (s) remain ill-defined, ASICs (acid-sensing ion channels) are assumed to be involved in this process. The diuretic, amiloride, is neuroprotective in models of cerebral ischemia, a property attributable to the inhibition of central ASICs by the drug. However, the effect of inhibition of ASICs by amiloride in the liver fibrotic process remains unclear. We found that amiloride (25, 50, or 100 μM) could restrain acid-induced HSCs at pH6 in vitro. In vivo experiments showed that amiloride could significantly alleviate liver injury, decreasing levels of profibrogenic cytokines, collagen deposition and reducing pathological tissue damage. In summary, amiloride inhibits hepatic fibrosis in vivo and in vitro, which is probably associated with the downregulation of ASICs.
- Proton modulation of cardiac I na: a potential arrhythmogenic trigger. [Journal Article]
- Handb Exp Pharmacol 2014.:169-81.
Voltage-gated sodium (NaV) channels generate the upstroke and mediate duration of the ventricular action potential, thus they play a critical role in mediating cardiac excitability. Cardiac ischemia triggers extracellular pH to drop as low as pH 6.0, within just 10 min of its onset. Heightened proton concentrations reduce sodium conductance and alter the gating parameters of the cardiac-specific voltage-gated sodium channel, NaV1.5. Most notably, acidosis destabilizes fast inactivation, which plays a critical role in regulating action potential duration. The changes in NaV1.5 channel gating contribute to cardiac dysfunction during ischemia that can cause syncope, cardiac arrhythmia, and even sudden cardiac death. Understanding NaV channel modulation by protons is paramount to treatment and prevention of the deleterious effects of cardiac ischemia and other triggers of cardiac acidosis.
- HYPERLACTEMIA INDUCTION MODES AFFECT THE LACTATE MINIMUM POWER AND PHYSIOLOGICAL RESPONSES IN CYCLING. [JOURNAL ARTICLE]
- J Strength Cond Res 2014 Apr 14.
The aim of this study was to verify the influence of hyperlactemia and blood acidosis induction on lactate minimum intensity (LMI). Twenty recreationally trained males who were experienced in cycling (fifteen cyclists and five triathletes) participated in this study. The athletes underwent three lactate minimum tests (LMT) on an electromagnetic cycle ergometer. The hyperlactemia induction methods used were: graded exercise test (GXT), Wingate test (WAnT) and two consecutive Wingate tests (2×WAnTs).The LMI at 2×WAnTs (200.3 ± 25.8 W) was statistical higher than the LMI at GXT (187.3 ± 31.9 W) and WAnT (189.8 ± 26.0 W), with similar findings for blood lactate, oxygen uptake and pulmonary ventilation at LMI. The venous pH after 2×WAnTs was lower (7.04 ± 0.24) than in (p< 0.05) the GXT (7.19±0.05) and WAnT (7.19±0.05), whereas the blood lactate response was higher. In addition, similar findings were observed for bicarbonate concentration ([HCO3]) (2×WAnTs lower than WAnT; 15.3±2.6 mmol·L and 18.2±2.7 mmol·L respectively (p<0.05). However, the maximal aerobic power and total time measured during the incremental phase also did not differ. Therefore, we can conclude that the induction mode significantly affects; pH, blood lactate and [HCO3] and consequently they alter the lactate minimum intensity and physiological parameters at LMI.
- Isotonic crystalloid solutions: a structured review of the literature. [JOURNAL ARTICLE]
- Br J Anaesth 2014 Apr 15.
/st>Several different crystalloid solutions are available for i.v. fluid administration but there is little information about their specific advantages and disadvantages./st>We performed a systematic search of MEDLINE, EMBASE, and CENTRAL up until May 17, 2012, selecting all prospective human studies that directly compared any near-isotonic crystalloids and reported any outcome./st>From the 5060 articles retrieved in the search, only 28 met the selection criteria. There was considerable heterogeneity among the studies. Several articles reported an increased incidence of hyperchloraemic acidosis with the use of normal saline, and others an increase in blood lactate levels when large amounts of Ringer's lactate solutions were infused. From the limited data available, normal saline administration appears to be associated with increased blood loss and greater red blood cell transfusion volumes in high-risk populations compared to Ringer's lactate. Possible effects of the different solutions on renal function, inflammatory response, temperature, hepatic function, glucose metabolism, and splanchnic perfusion are also reported. The haemodynamic profiles of all the solutions were similar./st>Different solutions have different effects on acid-base status, electrolyte levels, coagulation, renal, and hepatic function. Whether these differences have clinical consequences remains unclear.
- Fialuridine Induces Acute Liver Failure in Chimeric TK-NOG Mice: A Model for Detecting Hepatic Drug Toxicity Prior to Human Testing. [Journal Article]
- PLoS Med 2014 Apr; 11(4):e1001628.
Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers.Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers.FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology studies could improve the safety of candidate medications selected for testing in human participants. Please see later in the article for the Editors' Summary.