Effects of delayed intraventricular TLR7 agonist administration on long-term neurological outcome following asphyxia in the preterm fetal sheep.

In the preterm brain, accumulating evidence suggests toll-like receptors (TLRs) are key mediators of the downstream inflammatory pathways triggered by hypoxia-ischemia (HI), which have the potential to exacerbate or ameliorate injury. Recently we demonstrated that central acute administration of the TLR7 agonist Gardiquimod (GDQ) confers neuroprotection in the preterm fetal sheep at 3 days post-asphyxial recovery. However, it is unknown whether GDQ can afford long-term protection. To address this, we examined the long-term effects of GDQ. Briefly, fetal sheep (0.7 gestation) received sham asphyxia or asphyxia induced by umbilical cord occlusion, and were studied for 7 days recovery. Intracerebroventricular (ICV) infusion of GDQ (total dose 3.34 mg) or vehicle was performed from 1-4 hours after asphyxia. GDQ was associated with a robust increase in concentration of tumor necrosis factor-(TNF)-α in the fetal plasma, and interleukin-(IL)-10 in both the fetal plasma and cerebrospinal fluid. GDQ did not significantly change the number of total and immature/mature oligodendrocytes within the periventricular and intragyral white matter. No changes were observed in astroglial and microglial numbers and proliferating cells in both white matter regions. GDQ increased neuronal survival in the CA4 region of the hippocampus, but was associated with exacerbated neuronal injury within the caudate nucleus. In conclusion, our data suggest delayed acute ICV administration of GDQ after severe HI in the developing brain may not support long-term neuroprotection.

The Effect of Asphyxia Arrest Duration on a Pediatric End-Tidal CO2-Guided Chest Compression Delivery Model.

OBJECTIVES: To determine the effect of the duration of asphyxial arrest on the survival benefit previously seen with end-tidal CO2-guided chest compression delivery. DESIGN: Preclinical randomized controlled study. SETTING: University animal research laboratory. SUBJECTS: Two-week-old swine. INTERVENTIONS: After either 17 or 23 minutes of asphyxial arrest, animals were randomized to standard cardiopulmonary resuscitation or end-tidal CO2-guided chest compression delivery. Standard cardiopulmonary resuscitation was optimized by marker, monitor, and verbal feedback about compression rate, depth, and release. End-tidal CO2-guided delivery used adjustments to chest compression rate and depth to maximize end-tidal CO2 level without other feedback. Cardiopulmonary resuscitation for both groups proceeded from 10 minutes of basic life support to 10 minutes of advanced life support or return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: After 17 minutes of asphyxial arrest, mean end-tidal CO2 during 10 minutes of cardiopulmonary resuscitation was 18 ± 9 torr in the standard group and 33 ± 15 torr in the end-tidal CO2 group (p = 0.004). The rate of return of spontaneous circulation was three of 14 (21%) in the standard group rate and nine of 14 (64%) in the end-tidal CO2 group (p = 0.05). After a 23-minute asphyxial arrest, neither end-tidal CO2 values (20 vs 26) nor return of spontaneous circulation rate (3/14 vs 1/14) differed between the standard and end-tidal CO2-guided groups. CONCLUSIONS: Our previously observed survival benefit of end-tidal CO2-guided chest compression delivery after 20 minutes of asphyxial arrest was confirmed after 17 minutes of asphyxial arrest. The poor survival after 23 minutes of asphyxia shows that the benefit of end-tidal CO2-guided chest compression delivery is limited by severe asphyxia duration.

Placental clearance/synthesis of neurobiomarkers GFAP and UCH-L1 in healthy term neonates and those with moderate-severe neonatal encephalopathy.

BACKGROUND: Fetal concentrations of GFAP and UCH-L1 are elevated in umbilical arterial (UmA) blood of neonates with birth asphyxia plus neonatal encephalopathy (NE), but their source and role of placental clearance/synthesis is unknown. METHODS: Prospective cohort study of term neonates to (a) determine UmA and venous (UmV) blood concentrations of GFAP and UCH-L1 in term uncomplicated pregnancies and their placental synthesis and/or clearance and (b) compare UmA concentrations in uncomplicated pregnancies with those complicated by fetal hypoxia-asphyxia+NE. Three term groups were studied: uncomplicated cesarean delivery without labor (Group 1, n = 15), uncomplicated vaginal delivery with labor (Group 2, n = 15), and perinatal hypoxia-asphyxia+NE (Group 3, n = 8). RESULTS: UmA GFAP concentrations were lower in Group 1 vs. 2 (P = 0.02) and both demonstrated 100% placental clearance. In contrast, UmA and UmV UCH-L1 concentrations were not unaffected by labor. Group 3 UmA GFAP concentrations were 30- and 8-fold higher than Groups 1 and 2, respectively, P = 0.02, whereas UmA UCH-L1 concentrations were similar in all groups. CONCLUSIONS: UmA GFAP is derived from the fetus, and circulating levels, which are modulated by placental clearance, increase during uncomplicated labor and more so in the presence of fetal hypoxia-asphyxia+NE, providing a better biomarker than UCH-L1 for hypoxia-asphyxia+NE.

Perinatal Asphyxia and Brain Development: Mitochondrial Damage Without Anatomical or Cellular Losses.

Perinatal asphyxia remains a significant cause of neonatal mortality and is associated with long-term neurodegenerative disorders. In the present study, we evaluated cellular and subcellular damages to brain development in a model of mild perinatal asphyxia. Survival rate in the experimental group was 67%. One hour after the insult, intraperitoneally injected Evans blue could be detected in the fetuses' brains, indicating disruption of the blood-brain barrier. Although brain mass and absolute cell numbers (neurons and non-neurons) were not reduced after perinatal asphyxia immediately and in late brain development, subcellular alterations were detected. Cortical oxygen consumption increased immediately after asphyxia, and remained high up to 7 days, returning to normal levels after 14 days. We observed an increased resistance to mitochondrial membrane permeability transition, and calcium buffering capacity in asphyxiated animals from birth to 14 days after the insult. In contrast to ex vivo data, mitochondrial oxygen consumption in primary cell cultures of neurons and astrocytes was not altered after 1% hypoxia. Taken together, our results demonstrate that although newborns were viable and apparently healthy, brain development is subcellularly altered by perinatal asphyxia. Our findings place the neonate brain mitochondria as a potential target for therapeutic protective interventions.

Postmortem biochemical investigation results in situations of fatal mechanical compression of the neck region.

Biochemical investigations performed in cases of mechanical asphyxia have provided diverging information over time. The purpose of the study presented herein was threefold: to investigate the postmortem stability of a series of molecules (thyroglobulin, iodothyronines, calcitonin, and parathyroid hormone) in blood after death, to determine the same molecules in a series of cases of suicidal hangings for which antemortem serum samples were available, and to measure the same molecules in postmortem serum obtained from different sampling sites thereby evaluating the distribution of these molecules in the specific samples. Preliminary results indicated postmortem stability of thyroglobulin, calcitonin, and parathyroid hormone levels, decreasing total and free T4 levels, and increasing total and free T3 concentrations. Our findings also showed that antemortem mechanical force applied to the neck region (hanging cases) may be accompanied by increased thyroglobulin in peripheral (femoral) blood, though a certain number of cases with nonincreased thyroglobulin levels may be observed. Lastly, our results revealed that hanging, manual, and ligature strangulation cases may be accompanied by increased thyroglobulin, total T3, and free T3 values in postmortem serum specimens obtained from blood sampled at different sampling sites, even in the absence of microscopically identified thyroid gland tissue damage. Such increases are more constant and important in arterial and venous blood samples obtained from sampling sites located in close vicinity of the thyroid gland.

High serum serotonin in sudden infant death syndrome.

Sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality, likely comprises heterogeneous disorders with the common phenotype of sudden death without explanation upon postmortem investigation. Previously, we reported that ∼40% of SIDS deaths are associated with abnormalities in serotonin (5-hydroxytryptamine, 5-HT) in regions of the brainstem critical in homeostatic regulation. Here we tested the hypothesis that SIDS is associated with an alteration in serum 5-HT levels. Serum 5-HT, adjusted for postconceptional age, was significantly elevated (95%) in SIDS infants (n = 61) compared with autopsied controls (n = 15) [SIDS, 177.2 ± 15.1 (mean ± SE) ng/mL versus controls, 91.1 ± 30.6 ng/mL] (P = 0.014), as determined by ELISA. This increase was validated using high-performance liquid chromatography. Thirty-one percent (19/61) of SIDS cases had 5-HT levels greater than 2 SDs above the mean of the controls, thus defining a subset of SIDS cases with elevated 5-HT. There was no association between genotypes of the serotonin transporter promoter region polymorphism and serum 5-HT level. This study demonstrates that SIDS is associated with peripheral abnormalities in the 5-HT pathway. High serum 5-HT may serve as a potential forensic biomarker in autopsied infants with SIDS with serotonergic defects.

Evaluation of factors associated with elevated newborn 17-hydroxyprogesterone levels.

BACKGROUND: Measurement of 17-hydroxyprogesterone (17-OHP) in dried blood spots has been widely used as a newborn screening tool for congenital adrenal hyperplasia (CAH). Various maternal and neonatal factors can result in falsely high values of 17-OHP. There is a paucity of Indian studies in this regard because routine evaluation of newborn 17-OHP levels as a screening program is not widely practiced in India. Hence, this study was undertaken to evaluate the influence of various maternal and neonatal factors on newborn 17-OHP levels. The aim of the study was to determine the effect of various maternal and neonatal factors on the newborn 17-OHP values. METHODS: Retrospective data related to a total of 3080 newborn 17-OHP values and clinical characteristics were collected for 3 years (2013-2015). The data were analyzed to determine the influence of various factors on 17-OHP values. RESULTS: The mean value of 17-OHP in our study was 5.486±3.96 ng/mL. Gender and mode of delivery did not significantly affect the 17-OHP levels. The levels were significantly higher in preterm and low birth weight babies as compared to term babies and babies with normal birth weight. Stress factors like pregnancy induced hypertension (PIH), early onset sepsis (EOS), neonatal seizures and birth asphyxia significantly increase the neonatal 17-OHP levels. CONCLUSIONS: The levels of 17-OHP in newborns was measured around day 3 of life are very sensitive to the influence of gestational age, birth weight and presence of stress factors like maternal PIH, birth asphyxia, neonatal sepsis and neonatal seizures and should be interpreted cautiously.

The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers.

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO2 inhalation and decapitation. CO2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration.

Emergency endotracheal intubation under fluoroscopy guidance for patients with acute dyspnea or asphyxia.

OBJECTIVE: To evaluate the feasibility and effectiveness of emergency endotracheal intubation (EEI) under fluoroscopy guidance for patients with acute dyspnea or asphyxia. METHODS: From October 2011 to October 2014, of 1521 patients with acute dyspnea or asphyxia who required EEI in 6 departments, 43 patients who experienced intubation difficulty or failure were entered into this study. Data on technical success, procedure time, complications, and clinical outcome were collected. The pulse oxygen saturation and Hugh-Jones classification changes were analyzed. RESULTS: Fluoroscopy-guided EEI was technically successful in all patients. Acute dyspnea had resolved in all patients with clinical success rate 100% after the procedure. There were no serious complications during or after the procedure. The pulse oxygen saturation and Hugh-Jones classification showed significant increase after EEI (P < .05). Further treatments, including tracheal stents (n = 21), surgical resection (n = 16), palliative tracheotomy (n = 4), and bronchoscopic treatment (n = 2), were performed 1 to 72 hours after EEI. During a mean follow-up period of 13.2 months, 13 patients had died and 30 patients remained alive without dyspnea. CONCLUSIONS: Fluoroscopy-guided EEI is a safe and feasible procedure, and may serve as an alternative treatment option for patients when traditional EEI is unsuccessful.

Metabolomics in Newborns.

Metabolomics is the quantitative analysis of a large number of low molecular weight metabolites that are intermediate or final products of all the metabolic pathways in a living organism. Any metabolic profiles detectable in a human biological fluid are caused by the interaction between gene expression and the environment. The metabolomics approach offers the possibility to identify variations in metabolite profile that can be used to discriminate disease. This is particularly important for neonatal and pediatric studies especially for severe ill patient diagnosis and early identification. This property is of a great clinical importance in view of the newer definitions of health and disease. This review emphasizes the workflow of a typical metabolomics study and summarizes the latest results obtained in neonatal studies with particular interest in prematurity, intrauterine growth retardation, inborn errors of metabolism, perinatal asphyxia, sepsis, necrotizing enterocolitis, kidney disease, bronchopulmonary dysplasia, and cardiac malformation and dysfunction.

Serum potassium concentration predicts brain hypoxia on CT after avalanche-induced cardiac arrest.

BACKGROUND: Brain anoxia after complete avalanche burial and cardiac arrest (CA) may occur despite adequate on-site triage. PURPOSE: To investigate clinical and biological parameters associated with brain hypoxia in a cohort of avalanche victims with whole body computed tomographic (CT) scan. METHODS: Retrospective study of patients with CA and whole body CT scan following complete avalanche burial admitted in a level-I trauma center. MAIN FINDINGS: Out of 19 buried patients with whole body CT scan, eight patients had refractory CA and 11 patients had pre-hospital return of spontaneous circulation. Six patients survived at hospital discharge and only two had good neurologic outcome. Twelve patients had signs of brain hypoxia on initial CT scan, defined as brain edema, loss of gray/white matter differentiation and/or hypodensity of basal ganglia. No clinical pre-hospital parameter was associated with brain anoxia. Serum potassium concentration at admission was higher in patients with brain anoxia as compared to patients with normal CT scan: 5.5 (4.1-7.2) mmol/L versus 3.3 (3.0-4.2) mmol/L, respectively (P<.01). A threshold of 4.35 mmol/L serum potassium had 100% specificity to predict brain anoxia on brain CT scan. CONCLUSIONS: Serum potassium concentration had good predictive value for brain anoxia after complete avalanche burial. This finding further supports the use of serum potassium concentration for extracorporeal life support insertion at hospital admission in this context.

The effect of elapsed time on cardiac troponin-T (cTnT) degradation and its dependency on the cause of death.

PURPOSE: The aim of the present study is to evaluate the effect of elapsed time on cardiac troponin-T degradation and its dependency on the cause of death. METHODS: The cases included in this study were divided into six groups depending upon the cause of death without any prior history of disease that died in the hospital and their exact time of death was known. The analysis involves extraction of the protein, separation by denaturing gel electrophoresis and visualization by Western blot. RESULTS: Western blot data shows the rate of degradation of cTnT into lower molecular weight fragments with respect to time. In cases of control group the greatest amount of protein breakdown was observed within the first 64 h while in MI cases within first 6 h, the original band of cTnT (42 kDa) decreased markedly into seven major fragments, with 25 kDa & 20 kDa fragments being the most prominent. In burn group, at 41.40 h blot shows maximum fragmentation. In electrocution group the greatest amount of protein breakdown was observed within the first 50 Hrs. Within asphyxia cases, the original band of cTnT (42 kDa) decreased markedly into many major and minor fragments which continues up to 210 Hrs while the original band of cTnT (42 kDa) in poisoning cases decreased markedly into many major & minor fragments up to 140 h but after it blot shows only intact protein of very less intensity with few minor fragments. CONCLUSION: It can be observed that in case of death due to MI, the intact cTnI fragmented at a much faster rate than in burn, electrocution, control, poisoning and asphyxia group. Thus, the rate of fragmentation of intact cTnT into lower molecular weight fragments depends upon the cause of death.

Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration.

BACKGROUND: The Neonatal Resuscitation Program (NRP) recommends upper and lower limits of preductal saturations (SpO2) extrapolated from studies in infants resuscitated in room air. These limits have not been validated in asphyxia and lung disease. METHODS: Seven control term lambs delivered by cesarean section were ventilated with 21% O2. Thirty lambs with asphyxia with meconium aspiration were randomly assigned to resuscitation with 21% O2 (n = 6), 100% O2 (n = 6), or initiation with 21% O2 followed by variable FIO2 to maintain NRP target SpO2 ranges (n = 18). Hemodynamic and ventilation parameters were recorded for 15 min. RESULTS: Control lambs maintained preductal SpO2 near the lower limit of NRP target range. Asphyxiated lambs had low SpO2 (38 ± 2%), low arterial pH (6.99 ± 0.01), and high PaCO2 (96 ± 7 mm Hg) at birth. Resuscitation with 21% O2 resulted in SpO2 values below the target range with low pulmonary blood flow (Qp) compared to variable FIO2 group. The increase in PaO2 and Qp with variable FIO2 resuscitation was similar to control lambs. CONCLUSION: Maintaining SpO2 as recommended by NRP by actively adjusting inspired O2 leads to effective oxygenation and higher Qp in asphyxiated lambs with lung disease. Our findings support the current NRP SpO2 guidelines for O2 supplementation during resuscitation of an asphyxiated neonate.

Simultaneous measurement of cerebral hemoglobin oxygen saturation and blood volume in asphyxiated neonates by near-infrared time-resolved spectroscopy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) usually results in a poor clinical outcome even when treated with hypothermic therapy (HT). Early postnatal changes in cerebral blood oxygenation and hemodynamics may be critical determinants of brain injury and the efficacy of HT. OBJECTIVES: We measured cerebral hemoglobin oxygen saturation (ScO2) and cerebral blood volume (CBV) by near-infrared time-resolved spectroscopy (TRS) in HT-treated and non-HT-treated neonatal HIE patients to assess the influence of these parameters on clinical outcome. METHODS: We retrospectively compared ScO2, CBV, and clinical outcomes of 11 neonates with HIE: 5 were treated by HT (HT-treated; 33.5°C±0.5°C for 72h starting approximately 6h after delivery) and 6 were not (non-HT-treated). Both CBV and ScO2 were measured by TRS at 6, 24, 48, and 72h after birth. Magnetic resonance imaging (MRI) was performed 1-2weeks after birth to assess brain injury. RESULTS: Five neonates had adverse outcomes (3 HT-treated, 2 non-HT-treated). Of these, 1 died within 3days of birth and 4 had abnormal MRI findings, including basal ganglia, white matter, and/or thalamic lesions. The other 6 neonates had normal MRI findings (favorable outcome). At 6h after birth, CBV was significantly higher in neonates with adverse outcomes compared with those with a favorable outcome. At 24h after birth, ScO2 was significantly higher in neonates with adverse outcomes. Furthermore, we found that combined CBV at 24h after birth plus ScO2 had the best predictive ability for neurological outcome: sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. CONCLUSION: Early postnatal CBV and ScO2 elevations were predictive of a poor outcome in HIE. Therefore, measuring combined CBV plus ScO2 at 24h after birth can allow more precise prediction of neurological outcome. Control of postnatal CBV and ScO2 is critical for effective HIE treatment.

A preliminary study on postmortem interval estimation of suffocated rats by GC-MS/MS-based plasma metabolic profiling.

Estimation of postmortem interval (PMI) is an important goal in judicial autopsy. Although many approaches can estimate PMI through physical findings and biochemical tests, accurate PMI calculation by these conventional methods remains difficult because PMI is readily affected by surrounding conditions, such as ambient temperature and humidity. In this study, Sprague-Dawley (SD) rats (10 weeks) were sacrificed by suffocation, and blood was collected by dissection at various time intervals (0, 3, 6, 12, 24, and 48 h; n = 6) after death. A total of 70 endogenous metabolites were detected in plasma by gas chromatography-tandem mass spectrometry (GC-MS/MS). Each time group was separated from each other on the principal component analysis (PCA) score plot, suggesting that the various endogenous metabolites changed with time after death. To prepare a prediction model of a PMI, a partial least squares (or projection to latent structure, PLS) regression model was constructed using the levels of significantly different metabolites determined by variable importance in the projection (VIP) score and the Kruskal-Wallis test (P < 0.05). Because the constructed PLS regression model could successfully predict each PMI, this model was validated with another validation set (n = 3). In conclusion, plasma metabolic profiling demonstrated its ability to successfully estimate PMI under a certain condition. This result can be considered to be the first step for using the metabolomics method in future forensic casework.

Neonatal encephalopathy and the association to asphyxia in labor.

OBJECTIVE: In cases with moderate and severe neonatal encephalopathy, we aimed to determine the proportion that was attributable to asphyxia during labor and to investigate the association between cardiotocographic (CTG) patterns and neonatal outcome. STUDY DESIGN: In a study population of 71,189 births from 2 Swedish university hospitals, 80 cases of neonatal encephalopathy were identified. Cases were categorized by admission CTG patterns (normal or abnormal) and by the presence of asphyxia (cord pH, <7.00; base deficit, ≥12 mmol/L). Cases with normal admission CTG patterns and asphyxia at birth were considered to experience asphyxia related to labor. CTG patterns were assessed for the 2 hours preceding delivery. RESULTS: Admission CTG patterns were normal in 51 cases (64%) and abnormal in 29 cases (36%). The rate of cases attributable to asphyxia (ie, hypoxic ischemic encephalopathy) was 48 of 80 cases (60%), most of which evolved during labor (43/80 cases; 54%). Both severe neonatal encephalopathy and neonatal death were more frequent with an abnormal, rather than with a normal, admission CTG pattern (13 [45%] vs 11 [22%]; P = .03), and 6 [21%] vs 3 [6%]; P = .04), respectively. Comparison of cases with an abnormal and a normal admission CTG pattern also revealed more frequently observed decreased variability (12 [60%] and 8 [22%], respectively) and more late decelerations (8 [40%] and 1 [3%], respectively). CONCLUSION: Moderate and severe encephalopathy is attributable to asphyxia in 60% of cases, most of which evolve during labor. An abnormal admission CTG pattern indicates a poorer neonatal outcome and more often is associated with pathologic CTG patterns preceding delivery.

Reliability of pulse oximetry in hypoxic newborn pigs.

OBJECTIVE: The reliability of pulse oximetry in the lower SaO2-ranges has not been fully investigated. We wanted to investigate pulse oximeter performance in a pig model of perinatal asphyxia. METHODS: Asphyxia was induced in 22 newborn pigs. Pulse oximetry-values for SpO2, as well as SaO2 from blood gas analyses were recorded multiple times before, during and after asphyxiation. The relationship between SpO2 and SaO2 in normoxia and hypoxia in this model was quantified. Calculations were made for 5% increments of SaO2 increasing successively from ≥95% to ≥20%. RESULTS: The pigs became severely hypoxic, acidotic and hypotensive. The bias in the total data was +13.7 (p < 0.001), i.e. SpO2 was on average higher than SaO2 for the entire interval of SaO2. However, bias was not significantly different from zero in most SpO2-ranges. Accuracy and precision were considerably higher than stated by the manufacturer in all SpO2-ranges, with both accuracy and precision increasing when SpO2-values down to 60% and lower were included. CONCLUSION: Pulse oximetry was less reliable at SaO2-values below 60%. Tissue acidosis and reduced peripheral perfusion may have contributed to this. It is unknown whether the difference between SpO2 and SaO2 is clinically relevant.

Thyroid hormone concentrations in foals affected by perinatal asphyxia syndrome.

The hypothalamus-pituitary-thyroid axis has specific functions, mostly related to metabolic activities, cell differentiation, and development. To the authors' knowledge, there are no studies about thyroid hormone (TH) concentrations in foals affected by perinatal asphyxia syndrome (PAS). Hence, the aims of the study are (1) to evaluate plasma TH concentrations (T3 and T4) in healthy foals during the first 7 days of life; (2) to evaluate plasma TH concentration (T3 and T4) in critically ill foals affected by PAS during the first 7 days of hospitalization; and (3) to compare TH concentrations between surviving and nonsurviving critically ill foals. Forty-five Standardbred foals were enrolled in this prospective observational study: 21 healthy foals (group 1) and 24 foals affected by PAS (group 2). Jugular blood samples were collected within 10 minutes from birth/admission and every 24 hours for 7 days (t0-t7). TH concentrations were analyzed by RIA. In both groups, T3 concentration was significantly lower at t4, t5, t6, and t7 compared with t1 (P < 0.05), and T4 concentration was significantly higher at birth than at all other time points (P < 0.01). No differences were found in TH concentrations at admission between surviving (n = 20) and nonsurviving (n = 4) foals. Statistical comparison between healthy and PAS foals divided into age groups showed significantly lower TH concentrations at t0 in PAS foals <12 hours old at admission (P < 0.01). In conclusion, PAS may cause lower T3 and T4 concentrations in affected foals than in age-matched healthy foals, as reported for other systemic illnesses, such as sepsis and prematurity. TH concentrations showed no prognostic value, which maybe due to the small number of nonsurviving foals in this study. Further studies are needed to find out if thyroid replacement therapy could be useful in the treatment of critically ill foals affected by PAS.

The effect of lactic acidosis on the generation and compensation of mixed respiratory-metabolic acidosis in neonatal calves.

Postnatal mixed respiratory-metabolic acidosis is common in calves, and depending on its severity can impair vitality or even cause death. Carbon dioxide accounts for the respiratory component and L-lactate for the metabolic component of the mixed acidosis, but it remains unclear which component determines the severity and duration of the acidosis. In a first attempt to clarify, this was investigated retrospectively in 31 calves during the first two hours of life, and in 13 calves during the first three days of life. Venous blood was collected for blood gas analysis and measurement of acid-base variables and L-lactate concentration. pH Was more strongly correlated with L-lactate concentration (r(2)=0.808) than with partial pressure of CO2 (pCO2, r(2)=0.418). Duration of parturition had a distinct effect on pH and L-lactate concentration but not on pCO2; calves born within six hours of rupture of the allantoic sac had a higher pH and lower L-lactate concentration than calves born after a longer duration of parturition (both P<0.01). Normalisation of pCO2 took four hours and normalisation of L-lactate took 48 hours. It was concluded that L-lactate is a more important factor in the pathogenesis of acidosis than pCO2, and that the duration of metabolic acidosis exceeds that of respiratory acidosis in perinatal asphyxia of calves.

Postmortem serum tenascin-C (TN-C) concentrations in forensic autopsy cases: A pilot study.

In forensic investigations, autopsy findings offer major clues for the diagnosis of the cause of death. Thus, various clinical biochemical markers are now being tested to complement conventional investigation in the field of forensic medicine. In this study, we focused on tenascin-C (TN-C), a glycoprotein present in the extracellular matrix and expressed in pathological states. We reviewed autopsy cases for a 4-year period (2006-2009) using autopsy records, and analyzed the blood serum concentrations of TN-C and C-reactive protein (CRP) in these cases (N=101). The TN-C levels were relatively higher in the postmortem serum samples than in the samples from healthy individuals, and in cases of head injury, both TN-C and CRP levels were high in the postmortem serum sample. Moreover, high TN-C levels were observed particularly in cases with a long survival period. These findings indicate that postmortem serum TN-C levels may represent a useful tool for identifying the cause of specific fatal traumas.