Electroencephalographic correlates of prenatal exposure to alcohol in infants and children: a review of findings and implications for neurocognitive development.

In this paper, we reviewed all existing studies using electroencephalography (EEG) in infants and children with known prenatal exposure to alcohol (PEA). The guiding purposes of the review were to determine if (1) EEG is a useful neuroimaging technique for investigating the brain correlates of PEA in infants and children, (2) there are indeed consistent EEG correlates of PEA in literature, and (3) these EEG correlates can be framed within a coherent picture of emerging implications for the study of PEA and its effects. The review confirms that EEG techniques have proven useful in indicating evidence of differential effects of patterns of PEA and timing in early fetal development and impairment of brain maturation in older children. In general, these techniques could be important in functional assessment of the brain of children affected by PEA, especially if used in conjunction with other neuroimaging techniques. The reviewed studies also suggest that although the impact on sensory and cognitive functions may involve extensive neural networks, there are EEG correlates of PEA which may in the future lead to the identification of neurophysiologic markers. A consistent aspect that emerges from the EEG data is that converging evidence from the study of different systems and processes suggests that PEA may almost invariably have consequences for later neurocognitive development.     

Relationship between maternal- and fetal-specific IgE

AIM: A positive correlation between maternal and cord-blood IgE levels is well documented for total IgEs, but not for specific IgEs. The difficulty in detecting specific cord-blood IgEs is due to their low concentrations, which hinder their dosage by low-sensitivity methods. The study aimed to correlate maternal and foetal specific IgEs against individual cow's milk proteins, detected by highly sensitive and specific techniques. METHODS: Cow's milk specific IgE detection was performed by chemiluminescence on 52 specimens of maternal and cord blood after cow's milk protein separation by 1D and 2D gel electrophoresis. Cow's milk protein (CMP) antigens were identified by mass spectrometry techniques. RESULTS: Specific IgEs for CMPs were found in 25/52 (48.1%) of maternal sera and in 19/52 (37%) of cord-blood sera. In order of decreasing frequency, the proteins found were BSA, IgG heavy chain, caseins and, in a single case, b-lactoglobulin. Positive cord-blood sera in all cases corresponded to a positive maternal result, and maternal and foetal immunoreactivity patterns were closely correlated. Moreover, in no case was there a positive cord-blood response with a negative maternal response. CONCLUSION: The study demonstrates a close relationship between maternal and cord-blood specific IgE patterns. The phenomenon observed could provide a model to elucidate the general production method of foetal IgEs, which might only be produced in the presence of both the corresponding maternal IgE and the related allergen.     

Different effects of the liver mitogens triiodo-thyronine and ciprofibrate on the development of rat hepatocellular carcinoma

Previous work has shown that treatment with thyroid hormone (T3) decreased the incidence of rat hepatocellular carcinoma (HCC). The present study was designed to determine whether the inhibitory effect of T3 on HCC development was limited to early steps of the carcinogenetic process or, whether a similar effect could also be exerted by starting T3 treatment at later stages. Hepatic nodules were induced in Fischer rats by a single dose of DENA, followed by a 2-week exposure of the animals to 2-AAF and partial hepatectomy. Rats were then divided into 3 groups: group 1 was maintained on basal diet: group 2 was fed a diet containing 4 mg/kg T3 for a week, every month/7 months, starting 9 weeks after DENA administration: group 3 was exposed to cycles of T3 starting 8 months after initiation. Results demonstrate that inhibition of HCC development was essentially similar in rats exposed to T3 starting either 9 weeks or 8 months after initiation (50% inhibition compared to control rats). We have previously shown that T3-induced nodule regression and HCC inhibition occurred in spite of its mitogenic effect. Therefore, we next wished to determine whether a similar antitumoral effect could be exerted by other liver mitogens, such as peroxisome proliferators. Rats exposed to the initiation-promotion protocol described previously, were subjected to 11 cycles of a T3 or a ciprofibrate-supplemented diet, each cycle consisting of 7 days/month: the incidence of HCC and lung metastases was determined 13.5 months after initiation. Results showed that although treatment with T3 strongly inhibited HCC development (only 31% of T3+ rats showed HCC vs 91% of controls), rats given ciprofibrate developed the same number of HCC as T3-untreated rats. In conclusion, the results of this study showed that the anticarcinogenic effect of T3 is maintained also when treatment begins late in the process, and its antitumoral property appears to be specific and may not be shared by other liver mitogens.     

Cloning and characterization of two catechol 1,2-dioxygenase genes from Acinetobacter radioresistens S13

Two novel catechol 1,2-dioxygenase (C 1,2-O) genes have been isolated from an Acinetobacter radioresistens strain that grows on phenol or benzoate as sole carbon and energy source. Designated as catA(A) and catA(B), they encode proteins composed of 314 and 306 amino acids, whose deduced sequences indicate that they have approximately 53% identity, whereas their NH2-terminal and COOH-terminal regions have no sequences in common. This may explain their different thermal and pH stability. Polyclonal antibodies raised against an amino-terminal CatA(A) peptide or the whole CatA(B) protein were used to establish their inducible and differential expression patterns upon bacterial growth in phenol or benzoate. The CatA(A) protein (IsoA) was induced by both phenol and benzoate though with different kinetics, whereas the catA(B) product (IsoB) was constitutively produced at low levels that increased only during growth in the presence of benzoate.     

Free Fatty Acids Signature in Human Intestinal Disorders: Significant Association between Butyric Acid and Celiac Disease

Altered circulating levels of free fatty acids (FFAs), namely short chain fatty acids (SCFAs), medium chain fatty acids (MCFAs), and long chain fatty acids (LCFAs), are associated with metabolic, gastrointestinal, and malignant diseases. Hence, we compared the serum FFA profile of patients with celiac disease (CD), adenomatous polyposis (AP), and colorectal cancer (CRC) to healthy controls (HC). We enrolled 44 patients (19 CRC, 9 AP, 16 CD) and 16 HC. We performed a quantitative FFA evaluation with the gas chromatography–mass spectrometry method (GC–MS), and we performed Dirichlet-multinomial regression in order to highlight disease-specific FFA signature. HC showed a different composition of FFAs than CRC, AP, and CD patients. Furthermore, the partial least squares discriminant analysis (PLS-DA) confirmed perfect overlap between the CRC and AP patients and separation of HC from the diseased groups. The Dirichlet-multinomial regression identified only strong positive association between CD and butyric acid. Moreover, CD patients showed significant interactions with age, BMI, and gender. In addition, among patients with the same age and BMI, being male compared to being female implies a decrease of the CD effect on the (log) prevalence of butyric acid in FFA composition. Our data support GC–MS as a suitable method for the concurrent analysis of circulating SCFAs, MCFAs, and LCFAs in different gastrointestinal diseases. Furthermore, and notably, we suggest for the first time that butyric acid could represent a potential biomarker for CD screening.     

Right Ventricle Dysfunction in Patients With Adult Cystic Fibrosis Enlisted for Lung Transplant

Knowledge of preoperative right heart function of adult patients with cystic fibrosis (CF) awaiting lung transplant (LUTX) is limited. The echocardiography of adult patients with CF enlisted for LUTX was retrospectively analyzed and compared with standards and invasive analyses (right heart catheterization, multigated radionuclide ventriculography). We included 49 patients (reported as mean ± standard deviation; 29 ± 9 years of age; forced expiratory volume in first second of expiration, 31% ± 11% predicted; lung allocation score, 36 ± 5; invasive mean pulmonary artery pressure, 17 ± 5 mm Hg; multigated radionuclide ventriculography right ventricle [RV] ejection fraction, 50% ± 9%). Patients had increased RV end-diastolic area, RV wall thickness, and increased pulmonary artery acceleration time with subnormal tricuspid annular plane systolic excursion, tissue Doppler positive peak systolic velocity, and fraction area change. Subnormal tricuspid annular plane systolic excursion (< 23 mm), tissue Doppler positive peak systolic velocity (< 14 cm/s), and fraction area change (< 49%) had high sensitivity and negative predictive value in predicting impaired RV.ejection fractionA good correlation between echocardiographic estimated and invasively measured systolic pulmonary artery pressure was observed (R² = 0.554, P < .001). Adults with CF awaiting LUTX have morphologic alterations of the right heart, with subclinical impairment of RV systolic function. Echocardiography may be used as a bedside, repeatable, and reliable noninvasive test to screen further deterioration in RV function while on the waiting list for LUTX. More prospective follow-up echocardiographic studies are necessary to confirm such a hypothesis.     

Clearing hepatitis C virus with direct antiviral agents reduces cardiovascular events in patients with prediabetes. Commentary to Sasso and colleagues

Liver health is a key determinant of cardiovascular risk (CVR). Hepatic fibrosis is the shared common result of chronic hepatitis, irrespective of aetiology. Fibrosis profoundly distorts liver tissue architecture and perturbs hepatic physiology, dictates the course of chronic liver disease and is increasingly recognized as a CVR factor. The relative weights of pre-diabetes and hepatic fibrosis as risk factors for major adverse cardiac events (MACE) in patients with HCV remain an open issue. Sasso and Colleagues answered this research question by treating approximately half of 770 HCV positive pre-diabetic patients with direct antiviral agents (DAAs), while the rest served as historical controls. Data have shown that achieving HCV clearance with DAAs was associated with a 60% reduced risk of MACE, thereby implying that this antiviral strategy is recommended in HCV positive pre-diabetic patients, regardless of the severity of liver disease and concurrent CVR factors. This study paves the way for additional studies addressing the molecular patho-mechanisms and changes in the clinical spectrum involved in cardio-metabolic protection following HCV eradication in patients with pre-diabetes.