Lack of correlation between central venous minus arterial PCO2 to arterial minus central venous O2 content ratio and respiratory quotient in patients with septic shock: A prospective observational study.

OBJECTIVE: Central venous-arterial PCO2 to arterial-central venous O2 content ratio (Pcv-aCO2/Ca-cvO2) is commonly used as a surrogate for respiratory quotient (RQ) and tissue oxygenation. Although Pcv-aCO2/Ca-cvO2 might be associated with hyperlactatemia and outcome, neither the interchangeability with RQ nor the correlation with conclusive variables of anaerobic metabolism has never been demonstrated in septic shock. Our goal was to compare Pcv-aCO2/Ca-cvO2 and RQ in patients with septic shock. DESIGN: Prospective, observational study. SETTING: Two adult ICUs. PATIENTS: Forty-seven patients with septic shock on mechanical ventilation with stable respiratory settings and vasopressor dose after initial resuscitation. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We measured arterial and central venous gases, Hb, and O2Hb. Pcv-aCO2/Ca-cvO2 and the ratio of central venous-arterial CO2 content to arterial-central venous O2 content (Ccv-aCO2/Ca-cvO2) were calculated. RQ was determined by indirect calorimetry. RESULTS: Pcv-aCO2/Ca-cvO2 and Ccv-aCO2/Ca-cvO2 were not correlated with RQ (R2 = 0.01, P = 0.50 and R2 = 0.01, P = 0.58, respectively), showing large bias and wide 95 % limits of agreement with RQ (1.09, -1.10-3.27 and 0.42, -1.53-2.37). A multiple linear regression model showed Hb, and central venous PCO2 and O2Hb, but not RQ, as Pcv-aCO2/Ca-cvO2 determinants (R2 = 0.36, P = 0.0007). CONCLUSIONS: In patients with septic shock, Pcv-aCO2/Ca-cvO2 did not correlate with RQ and was mainly determined by factors that modify the dissociation of CO2 from Hb. Pcv-aCO2/Ca-cvO2 seems to be a poor surrogate for RQ; therefore, its values should be interpreted with caution.

Signals for Muscular Protein Turnover and Insulin Resistance in Critically Ill Patients: A Narrative Review.

Sarcopenia in critically ill patients is a highly prevalent comorbidity. It is associated with a higher mortality rate, length of mechanical ventilation, and probability of being sent to a nursing home after the Intensive Care Unit (ICU). Despite the number of calories and proteins delivered, there is a complex network of signals of hormones and cytokines that affect muscle metabolism and its protein synthesis and breakdown in critically ill and chronic patients. To date, it is known that a higher number of proteins decreases mortality, but the exact amount needs to be clarified. This complex network of signals affects protein synthesis and breakdown. Some hormones regulate metabolism, such as insulin, insulin growth factor glucocorticoids, and growth hormone, whose secretion is affected by feeding states and inflammation. In addition, cytokines are involved, such as TNF-alpha and HIF-1. These hormones and cytokines have common pathways that activate muscle breakdown effectors, such as the ubiquitin-proteasome system, calpain, and caspase-3. These effectors are responsible for protein breakdown in muscles. Many trials have been conducted with hormones with different results but not with nutritional outcomes. This review examines the effect of hormones and cytokines on muscles. Knowing all the signals and pathways that affect protein synthesis and breakdown can be considered for future therapeutics.

Epigenetics in Obesity and Diabetes Mellitus: New Insights.

A long-term complication of obesity is the development of type 2 diabetes (T2D). Patients with T2D have been described as having epigenetic modifications. Epigenetics is the post-transcriptional modification of DNA or associated factors containing genetic information. These environmentally-influenced modifications, maintained during cell division, cause stable changes in gene expression. Epigenetic modifications of T2D are DNA methylation, acetylation, ubiquitylation, SUMOylation, and phosphorylation at the lysine residue at the amino terminus of histones, affecting DNA, histones, and non-coding RNA. DNA methylation has been shown in pancreatic islets, adipose tissue, skeletal muscle, and the liver. Furthermore, epigenetic changes have been observed in chronic complications of T2D, such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. Recently, a new drug has been developed which acts on bromodomains and extraterminal (BET) domain proteins, which operate like epigenetic readers and communicate with chromatin to make DNA accessible for transcription by inhibiting them. This drug (apabetalone) is being studied to prevent major adverse cardiovascular events in people with T2D, low HDL cholesterol, chronic kidney failure, and recent coronary events. This review aims to describe the relationship between obesity, long-term complications such as T2D, and epigenetic modifications and their possible treatments.

N-Acetyl cysteine improves cellular growth in respiratory-deficient yeast.

BACKGROUND: Reactive oxygen species (ROS) is a main factor that alters cellular physiology and functionality. Many strategies are used in order to control excessive oxidative stress. One strategy includes the use of antioxidants like N-acetyl cysteine (NAC). The aim of this study was to compare the effect of this antioxidant on ROS production and cellular growth of a wild-type and a respiratory-deficient Saccharomyces cerevisiae strain. METHODS: Using a simple system such as yeast allows oxidative stress investigations on which numerous factors are more manageable or circumscribed than in a higher organism. We grew cells in a complex medium and incubated them during 72 h. Later, cellular viability and ROS production was evaluated. ROS level was estimated by use of fluorescence signal with 2',7'-dichlorofluorescein diacetate (DCFH-DA). RESULTS: As it is found in the present work, a reducing environment exerted by NAC presence during incubation of the cells allows a respiratory-deficient Saccharomyces cerevisiae strain to improve its cellular growth. CONCLUSIONS: It seems likely that the energy production or the phenotype which characterizes a deficient strain is incapable of palliating ROS growth inhibition while NAC helps to overcome this limitation.

[Muscle assessment methods for the diagnosis of sarcopenia in cirrhotic patients]. / Métodos de evaluación muscular para el diagnóstico de sarcopenia en pacientes cirróticos.

Sarcopenia is the loss of muscle mass and function. Its presence darkens the prognosis of cirrhotic patients. The gold standard for the description of sarcopenia is the Skeletal Muscle Index (SMI). Thirty-four cirrhotic patients were included. Measurement was carried out through CT of both psoas separately that were then added obtaining the so called "sum of area of 2 psoas", in addition total muscular area, SMI and total area of psoas were measured. Ultrasonography was also performed and the transverse area of the quadriceps rectus anterior was measured by ultrasound and Hand Grip (HG). The correlation between the different measurements was analyzed comparing with the total muscle area, with quadriceps area (r = 0.39; p = 0.019), with total psoas area (r = 0.71; p <0.01), with sum of area of 2 psoas (r = 0.72; p <0.001) and with HG (r = 0.45; p = 0.0069). Compared with SMI, in women HG had 86% sensitivity and 66% specificity (AUC = 0.89). In men, the sum of 2 psoas had 91.7% sensitivity and specificity (AUC = 0.82) and the total area of psoas had 83.3% sensitivity and 76.9% specificity (AUC = 0.8). There was a very good correlation between the tomography methods with the gold standard. The correlation with ultrasound and strength was good. In the evaluation of sensitivity, specificity and AUC, it was not found a useful method when comparing with the SMI.

La sarcopenia es la pérdida de masa y función muscular. Su presencia ensombrece el pronóstico de los pacientes cirróticos. El gold standard para la descripción de sarcopenia es el Skeletal Muscle Index (SMI). Se incluyeron 34 pacientes cirróticos. Se realizó medición a través de tomografía computarizada de ambos psoas por separado, que luego fueron sumados obteniendo lo que se denominó "suma de área de 2 psoas", además se midió área muscular total, SMI y área total de psoas. También se realizó ecografía y se midió el área transversal de recto anterior del cuádriceps por ecografía y Hand Grip (HG). Se analizó la correlación entre las distintas mediciones comparando con el área muscular total, con área de cuádriceps (r = 0.39; P = 0.019), con área total de psoas (r = 0.71; P < 0.01), con suma de área de 2 psoas (r= 0.72; P < 0.001) y con HG (r = 0.45; P = 0.0069). Comparado con el SMI, en mujeres el HG tuvo 86% sensibilidad y 66% especificidad (AUC = 0.89). En hombres la suma de 2 psoas tuvo 91.7% de sensibilidad y especificidad (AUC = 0.82) y el área total de psoas tuvo 83.3% de sensibilidad y 76.9% de especificidad (AUC = 0.8). Hubo muy buena correlación entre los métodos de tomografía con el gold standard, y la correlación con la ecografía y la fuerza fue buena. Evaluando sensibilidad, especificidad y AUC, no se consideró un método útil para ambos sexos, comparado con el SMI.

Métodos de evaluación muscular para el diagnóstico de sarcopenia en pacientes cirróticos / Muscle assessment methods for the diagnosis of sarcopenia in cirrhotic patients

Resumen La sarcopenia es la pérdida de masa y función muscular. Su presencia ensombrece el pronóstico de los pacientes cirróticos. El gold standard para la descripción de sarcopenia es el Skeletal Muscle Index (SMI). Se incluyeron 34 pacientes cirróticos. Se realizó medición a través de tomografía computarizada de ambos psoas por separado, que luego fueron sumados obteniendo lo que se denominó "suma de área de 2 psoas", además se midió área muscular total, SMI y área total de psoas. También se realizó ecografía y se midió el área transversal de recto anterior del cuádriceps por ecografía y Hand Grip (HG). Se analizó la corre lación entre las distintas mediciones comparando con el área muscular total, con área de cuádriceps (r = 0.39; P = 0.019), con área total de psoas (r = 0.71; P < 0.01), con suma de área de 2 psoas (r= 0.72; P < 0.001) y con HG (r = 0.45; P = 0.0069). Comparado con el SMI, en mujeres el HG tuvo 86% sensibilidad y 66% especificidad (AUC = 0.89). En hombres la suma de 2 psoas tuvo 91.7% de sensibilidad y especificidad (AUC = 0.82) y el área total de psoas tuvo 83.3% de sensibilidad y 76.9% de especificidad (AUC = 0.8). Hubo muy buena correlación entre los métodos de tomografía con el gold standard, y la correlación con la ecografía y la fuerza fue buena. Evaluando sensibilidad, especificidad y AUC, no se consideró un método útil para ambos sexos, comparado con el SMI

Abstract Sarcopenia is the loss of muscle mass and function. Its presence darkens the prognosis of cirrhotic patients. The gold standard for the description of sarcopenia is the Skeletal Muscle Index (SMI). Thirty-four cirrhotic patients were included. Measurement was carried out through CT of both psoas separately that were then added obtain ing the so called "sum of area of 2 psoas", in addition total muscular area, SMI and total area of psoas were measured. Ultrasonography was also performed and the transverse area of the quadriceps rectus anterior was measured by ultrasound and Hand Grip (HG). The correlation between the different measurements was analyzed comparing with the total muscle area, with quadriceps area (r = 0.39; p = 0.019), with total psoas area (r = 0.71; p <0.01), with sum of area of 2 psoas (r = 0.72; p <0.001) and with HG (r = 0.45; p = 0.0069). Compared with SMI, in women HG had 86% sensitivity and 66% specificity (AUC = 0.89). In men, the sum of 2 psoas had 91.7% sensitivity and specificity (AUC = 0.82) and the total area of psoas had 83.3% sensitivity and 76.9% specificity (AUC = 0.8). There was a very good correlation between the tomography methods with the gold standard. The correlation with ultrasound and strength was good. In the evaluation of sensitivity, specificity and AUC, it was not found a useful method when comparing with the SMI.

Parenteral Succinate Reduces Systemic ROS Production in Septic Rats, but It Does Not Reduce Creatinine Levels.

In sepsis, reactive oxygen species (ROS) production is increased. This process takes place mainly within the electron transport chain. ROS production is part of the pathophysiology of multiple organ failure in sepsis. Succinate yields Dihydroflavine-Adenine Dinucleotide (FADH2), which enters the chain through complex II, avoiding complex I, through which electrons are lost. The aim of this work is to determine if parenteral succinate reduces systemic ROS production and improves kidney function. Rats with cecal ligation and puncture were used as model of sepsis, and 4 groups were made: Control group; Succinate group, which only received parenteral succinate; Sepsis group; and Sepsis which received parenteral succinate. Systemic ROS are measured 24 hours after the procedure. Rats subjected to cecal puncture treated with succinate had less systemic ROS than Septic untreated rats (p = 0.007), while there were no differences in creatinine levels (p = 0.07). There was no correlation between creatinine and systemic ROS levels (p = 0.3). We concluded that parenteral succinate reduces ROS levels, but it does not reduce creatinine levels. Since there is no correlation between both levels, the processes would not be related.

Biochemical study of idebenone effect on mitochondrial metabolism of yeast.

The aim of this work was to study the effect of the drug idebenone on the growth of a strain of Saccharomyces cerevisiae yeast and its respiratory-deficient mutant (rho(0)). We took this yeast as a model system of the interaction of the drug with mammalian cells. The effect of idebenone was evaluated in rich and minimal media. In the S288c strain, idebenone exerted a growth inhibitory effect in concentrations higher than 50 microM in media containing a carbon source consumed at mitochondrial level. In conditions of low oxygen supply, idebenone allows yeast to keep a cellular yielding comparable with conditions of normal oxygen supply. Also, the presence of idebenone in the growth media increased by 50% the fluorescence signal of rhodamine 123, indicating a higher mitochondrial membrane potential. The results could explain the effect of idebenone in the treatment of diseases in which oxygen deficiency alters the energetic metabolism of the cell.