We present the results of the determination of eight aromatic microbial metabolites, phenylcarboxylic acids (PhCAs), by gas chromatography–mass spectrometry after their liquid–liquid extraction from ...serum samples and derivatization. The analytical range for the analytes is 0.5–40 μM. The concentration of phenylcarboxylic acids in the serum of healthy donors (
n
= 40) and the time profile of the concentration of different PhCAs in serum samples of four patients from the intensive care unit (ICU) are studied. The results correlated with the severity of the clinical state of patients.
Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient’s blood due to increased endogenous and microbial phenylalanine and tyrosine ...biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6 μM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈
p
-hydroxyphenyllactic >
p
-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota.
The development of accurate and applicable methods to assess the severity of patient condition is an urgent need in critical care medicine.The goal of the study was to determine whether the ...quantitave evaluation of phenylcarboxylic acids (PhCAs) concentrations in blood might be employed to assess the severity of patient condition and treatment efficiency intensive care unit.Materials and methods. Clinical and laboratory findings in patients (n=58) with acute surgical diseases of abdominal organs were registered on the day of admission to intensive care unit and during follow-up control including lactate level and blood serum PhCA concentrations of phenyllactic (PhLA), p#hydroxyphenyllactic (p-HPhLA) and phydroxyphenylacetic (p#HPhAA) acids. Patients' condition was assessed using APACHE II and SOFA international scales. PhCA concentrations were determined by gas chromatography. The reference group included healthy blood donors (n=25).Results. PhLA, p-HPhAA, p-HPhLA levels and total concentration of the three PhCAs were shown to be in direct correlation with APACHE II score (rs: 0.624; 0.757; 0.763 and 0.804, respectively; P<0.001). When testing PhCAs as a molecular prognostic criteria, areas under ROC#curves (AUC) were within the range of 0.800—0.900 (P<0.001). Therewith the molecular prognostic criteria were comparable with APACHE II multi#parameter scale by accuracy: AUCAPACHE II was 0.897 (P<0.001). Lactate level dynamics as a prognostic criterion was inferior in accuracy to the dynamics of PhCA total concentration: AUCС lactate, % 0.667 (P=0.071) vs AUCС 3PhCAs, % 0.862 (P<0.001). In patients with documented bacterial inflammatory complications PhCA level was 2.5 times higher (P<0,001, n=35) and p#HPhLA level was 1.5 times higher than in patients without infectious complications (P=0.048, n=23).Conclusion. The findings provide evidence for the inclusion of PhCAs (PhLA, p-HPhAA, p-HPhLA, 3PhCAs) in clinical practice as biomarkers of the severity of condition in patients with surgical diseases of abdominal organs. The study showed that change in PhCA serum concentrations reflected the dynamics of patient condition and might be used for objective monitoring of the treatment.
A search for low molecular weight biomarkers to objectively evaluate the efficiency of extracorporeal detoxification methods is extremely relevant. For this purpose, the investigation is to verify ...whether metabolites, the production of which from aromatic amino acids in the human body can be of microbial ori gin, may be used. Objective: to evaluate the efficiency of extracorporeal detoxification methods on the serum level of phenyl carboxylic acids in patients with sepsis associated renal failure. Subjects and methods. Ten patients with acute or chronic (end stage) renal failure that had developed in the presence of severe sepsis, infective and toxic shock, long term extracorporeal circulation, postresuscitation disease, etc. were prospectively examined and treated. All the patients underwent extracorporeal detoxification; the choice of its technique was determined from their past medical history and intoxication patterns. The investigators eval uated organ dysfunctions using the Sequential Organ Failure Assessment (SOFA) scale, estimated body tempera ture, leukocyte count, and leukocyte index of intoxication, and assessed the results of a procalcitonin test. Hemodiafiltration was done as extrarenally indicated to ameliorate a systemic inflammatory response in septic shock, by applying an EMiC2 superhigh permeability dialyzer. Low flux Diacap LO PS dialyzers were employed for hemodialysis. Blood samples were taken to estimate changes in the serum concentrations of phenylcarboxylic acid, benzoic acid, 3 phenylpropionic acid, phenyllactic acid, para hydroxyphenylacetic acid (p HPAA), and para hydroxyphenyllactic acid (p HPLA) directly before and immediately after extracorporeal detoxification. Results. The severity of organ dysfunctions by SOFA score was 10—22 (mean 16 scores); 10 day mortality rates were 40%. In all the patients, the baseline serum levels of some phenylcarboxylic acids were considerably above normal. After hemodiafiltration, the serum concentrations of p HPAA and p HPLA decreased (by an aver age of 1.7 and 1.85 fold, respectively). Conclusion. In sepsis associated renal failure, the clearance rate of microbial aromatic acid metabolites (p HPAA and p HPLA) is promising potential biomarker to evaluate the efficiency of extracorporeal detoxification methods.
A method has been developed for the determination of phenylcarboxylic acids (benzoic,
p
-hydroxyphenyllactic,
p
-hydroxyphenylacetic, phenyllactic, 3-phenylpropanoic, and phenylacetic) in blood serum ...by gas chromatography with a flame-ionization detector (
FID
). The quantitative characteristics of analysis obtained with the FID and mass spectrometric detectors are in the same range and exhibit common trends for different groups of samples. It has been shown that the reproducibility of the results increases with the addition of a stage of salting out to the sample preparation procedure. The accuracy of the results is estimated using the added-found method. A possibility of the application of widely used FID to the quantitative determination of phenylcarboxylic acids in blood serum has been demonstrated for routine clinical practice.
Background Actuality of the problem of infection in critically ill patients remains high. Addition a local infectious processes have a tendency to rapid generalization and sepsis. Neutrophilsfunction ...failure plays a key role in the patho- genesis of infectious complications and sepsis. The hypothesis about the role of microbial metabolites in the formation of immunosuppression, in particular in the inhibition of phagocytic activity of neutrophils as the first line of defense against bacteria is acquiring more and more supporters. Among the microbial metabolites aromatic compounds, such as phenylcarbinol acid (PCA) are of particular interest. Their concentration in the blood reaches a maximum in case of generalized infection, and correlates with mortality in patients in critical conditions, and PCA biological activity confirmed by earlier researches in vitro. The purpose of the study was to reveal the relationship of the PCA with the severity of bacterial infections and to assess the effect of PCA on neutrophils phagocytic activity.
At the first stage the levels of PCA (GCh-FID method) in the serum ofpatients (n=57) with a documented bacterial infection of varying severity, confirmed APACHE II and SOFA scales were analyzed comparing with healthy donors (n=72). During the second stage the effect of clinically-relevant concentrations of PCA on neutrophils phagocytic activity ofperipheral blood was analyzed in vitro.
The levels ofphenylacetic (PAA), phenyllactic (PLA), hydroxyphenylacetic (p-HPAA) and hydroxyphenyllactic (p-HPLA) acids in patients were significantly higher than in healthy donors, reaching the highest values in severe infection. High direct correlation of PCA levels with the indicators ofscales APACHE II and SOFA was detected. A significant decrease in the number ofphagocytic neutrophils under the influence PAA, p-HPAA and PLA was identified in vitro experiment on average 11%. The most significant influence p-HPAA, PLA and p-HPLA have made on the intensity of the neutrophils absorption capacity reducing this parameter by an average of 26%. Also noted that phenylpropionic acid (PPC) which is in blood of healthy donors, disappears in critical ill patients.
Phenolcarbonic acids level in the blood serum shows the severity of bacterial inflammatory process. Ex- periment in vitro shows that the PCA in clinically-relevant concentrations is able to suppress the neutrophilsphagocytic activity.
INTRODUCTION:We hypothesized that aromatic microbial metabolites (AMM), such as phenyllactic (PhLA), p-hydroxyphenylacetic (p-HPhAA), and p-hydroxyphenyllactic (p-HPhLA) acids, contribute to the ...pathogenesis of septic shock.
METHODS:Clinical and laboratory data of patients with community-acquired pneumonia were obtained on intensive care unit admission and the next day. Patients were divided into two groups based on septic shock presence or absence. The levels of AMM (PhLA, p-HPhAA, p-HPhLA, and their sum, ∑3AMM), catecholamine metabolites (3,4-dihydroxymandelic DHMA, 3,4-dihydroxyphenylacetic DOPAC, and homovanillic HVA acids), lactate, N-terminal pro-brain natriuretic peptide (NT-proBNP), inducible nitric oxide synthase (iNOS), and procalcitonin (PCT) were compared. Correlations between AMM and clinical and laboratory data were calculated.
RESULTS:There were 20 patients in the septic shock group and 21 in the nonseptic shock group. On admission, the septic shock patients demonstrated significantly higher levels of PhLA (2.3 vs. 0.8 μmol/L), p-HPhAA (4.6 vs. 1.4 μmol/L), p-HPhLA (7.4 vs. 2.6 μmol/L), HVA, lactate, and significantly lower levels of iNOS. The next day, the two groups also showed significant differences in the levels of PCT and NT-proBNP. The correlation between ∑3AMM and presence of shock, levels of lactate, HVA, and NT-proBNP on admission was 0.44, 0.67, 0.57, and 0.38, respectively, and the correlation on the next day was 0.59, 0.73, 0.76, and 0.6, respectively (P < 0.01). These findings can be explained by the ability of AMM to reduce tyrosine hydroxylase activity, thus limiting the synthesis of catecholamines.
CONCLUSIONS:AMM are involved in the pathogenesis of septic shock.
The aim of the present work was to evaluate changes in brain bioelectrical activity using electroencephalography (EEG) data in children with acute viral encephalitis. A total of 26 children were ...studied at the Pediatric Scientific Clinical Center for Infectious Diseases, Russian Federal Medical Biological Agency, with clinically confirmed diagnoses of “viral encephalitis.” Boys dominated the sex ratio of 18:8; mean age was 12 ± 2.1 years. All patients were in the acute period (first 14 days). The reference group for EEG analysis consisted of 10 healthy children. The groups were uniform in terms of sex and age. EEG recordings were made in all patients using a Neuron Spectrum 3 encephalograph (Ivanovo, Russia), with visual analysis of the EEG and spectral frequency analysis. Spectral power was evaluated in the α, θ, and δ frequency ranges, and the α/θ, α/δ ratios were also determined. Visual analysis of the EEG showed that 100% of children in the acute period of viral encephalitis showed diffuse slowing with recording of δ and θ frequencies. Focal changes in the form of sharp waves were recorded in 85% of cases (21 patients). Periodic activity was not recorded in even a single case in the study group of patients. Quantitative analysis of the results of statistical processing identified statistically significant decreases in the α/θ ratio (
p
= 0.035), maximum α (
p
= 0.046) and minimum θ (
p
= 0.044) in encephalitis patients as compared with the healthy children group. These data lead to the conclusion that pediatric patients during the acute period of viral encephalitis show significant impairments to the normal α/θ EEG power ratio. This impairment was apparent as a reduction in the power of the α and θ rhythms. It can be suggested that the cause of this reduction is suppression of the functional activity of the thalamus and thalamocortical pathways, as well as the reticular formation of the brain.
We have presented the first description of acute bilateral neuropathy of the abducens nerve associated with COVID-19 in a child.
A boy aged 2 years 2 months acutely developed bilateral convergent ...strabismus, the next day fatigue, drowsiness, and a single vomiting not associated with food intake, were joined. A differential diagnosis was performed between brainstem encephalitis, other organic (non-inflammatory) lesions of the brain stem, and idiopathic bilateral neuropathy of the abducens nerves. According to laboratory data, mild lymphocytosis, mild eosinophilia were detected, according to polymerase chain reaction DNA of the herpes virus type 1/2, cytomegalovirus, herpes virus type 6, Epstein-Barr, tick-borne encephalitis, borrelia, anaplasma, RNA ehrlichia were not detected. IgM and IgG to tick-borne encephalitis were not detected. Neurophysiological and neuroimaging examinations did not reveal any pathology. On the 6th day of the disease, SARS-CoV-2 RNA was detected by polymerase chain reaction of the nasopharynx and oropharynx discharge. The final diagnosis was formulated. — bilateral neuropathy of the abducens nerves. Bilateral convergent paralytic strabismus. Concomitant diagnosis: new coronavirus infection, subclini-cal form (positive by polymerase chain reaction in the discharge from the throat and nose of the 2019-nCoV coronavirus (SARS-CoV-2) RNA). Decrease in the severity of strabismus was noted over time against the background of the therapy.
Clinicians dealing with the COVID-19 should also pay attention to its ophthalmological manifestations and take into account that it can debut with them, as was in our case.
Purpose: to assess the functional state of the brain in critically ill encephalopathy in children with infectious diseases.
Materials and methods: 75 patients aged from 1 month to 17 years 11 months ...with infectious diseases, who were in the intensive care unit of the clinic, were examined, divided into two groups: the main group and the comparison group. Exclusion criteria: patients with cerebral palsy, organic lesions of the central nervous system, neuroinfections and epilepsy. Conducted daily clinical and neurological examination; study of the level of neurospecific proteins (NSE, protein S100) in blood serum; electroencephalography; study of evoked potentials of various modalities; ultrasound examination of the optic nerves, neuroimaging.
Results: All patients had general infectious manifestations, the development of sepsis syndrome, cerebral systemic disorders with impaired consciousness, as well as convulsive syndrome. In the acute period of the disease in the main group, NSE values in 87.5% of children were within the upper limit of normal, S100 protein levels were many times higher than those in the comparison group. In dynamics, all patients showed an increase in the level of NSE, which correlated with persistent neurological symptoms in the form of irritability, weakness, and cognitive decline. In the comparison group, an increase in NSE occurred in 53% of children, an increase in S100 - in 83%. By the time of discharge, 47% of patients had an increase NSE and S100 protein. Visual evoked potentials in 84% of the children of the main group in the acute period, had a decrease the amplitude of the N2-P2 cortical response was revealed without significant dynamics in the future, which was accompanied by pronounced clinical manifestations, which made it possible to substantiate the expediency of dispensary observation of children who underwent a critical condition against the background of severe infectious pathology.
Conclusion: in infectious diseases in children that are not accompanied by inflammatory processes in the nervous system, but proceed with the development of a critical condition, there is a neuropsychiatric deficit in the outcomes, which necessitates follow-up follow-up of such patients in the future.
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