Estimated risk for altered fetal growth resulting from exposure to fine particles during pregnancy: an epidemiologic prospective cohort study in Poland

The purpose of this study was to estimate exposure of pregnant women in Poland to fine particulate matter [less than or equal to 2.5 microm in diameter (PM 2.5)] and to assess its effect on the birth outcomes. The cohort consisted of 362 pregnant women who gave birth between 34 and 43 weeks of gestation. The enrollment included only nonsmoking women with singleton pregnancies, 18-35 years of age, who were free from chronic diseases such as diabetes and hypertension. PM 2.5 was measured by personal air monitoring over 48 hr during the second trimester of pregnancy. All assessed birth effects were adjusted in multiple linear regression models for potential confounding factors such as the size of mother (maternal height, prepregnancy weight), parity, sex of child, gestational age, season of birth, and self-reported environmental tobacco smoke (ETS). The regression model explained 35% of the variability in birth weight (beta = -200.8, p = 0.03), and both regression coefficients for PM 2.5 and birth length (beta = -1.44, p = 0.01) and head circumference (HC; beta = -0.73, p = 0.02) were significant as well. In all regression models, the effect of ETS was insignificant. Predicted reduction in birth weight at an increase of exposure from 10 to 50 microg/m3 was 140.3 g. The corresponding predicted reduction of birth length would be 1.0 cm, and of HC, 0.5 cm. The study provides new and convincing epidemiologic evidence that high personal exposure to fine particles is associated with adverse effects on the developing fetus. These results indicate the need to reduce ambient fine particulate concentrations. However, further research should establish possible biologic mechanisms explaining the observed relationship.     

Glutamate input to noradrenergic neurons plays an essential role in the development of morphine dependence and psychomotor sensitization

The brain's noradrenergic system is involved in the development of behaviours induced by drugs of abuse, e.g. dependence and withdrawal, and also reward or psychomotor effects. To investigate how noradrenergic system activity is controlled in the context associated with drug-induced behaviours, we generated a Cre/loxP mouse model in which the essential glutamate NMDA receptor subunit NR1 is ablated in cells expressing dopamine β-hydroxylase (Dbh). As a result, the noradrenergic cells in NR1DbhCre mice lack the NMDA receptor-dependent component of excitatory post-synaptic currents. The mutant mice displayed no obvious behavioural alterations, had unchanged noradrenaline content and mild increase in dopamine levels in the nucleus accumbens. Interestingly, NR1DbhCre animals did not develop morphine-induced psychomotor sensitization. However, when the morphine injections were preceded by treatment with RX821002, an antagonist of α2-adrenergic receptors, the development of sensitization was restored. Conversely, pretreatment with clonidine, an agonist of α2-adrenergic receptors, blocked development of sensitization in wild-type mice. We also found that while the development of tolerance to morphine was normal in mutant mice, withdrawal symptoms were attenuated. These data reveal that NMDA receptors on noradrenergic neurons regulate development of opiate dependence and psychomotor sensitization, by controlling drug-induced noradrenaline signalling.     

Opioids in neuropathic pain

Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opioid specific signaling. Endogenous opioid systems were found to be represented in the regions involved in the nociception and are implicated in chronic pain. Opioid peptides biosynthesis and opioid receptors density in the nociceptive pathways and their functions change under various conditions associated with neuropathic pain following damage to the spinal cord and injury of peripheral nerves. Identification of a role of opioid systems in neuropathic pain and molecular and cellular mechanisms underlying these processes are of importance to understanding of the opioid action in neuropathic pain that will hopefully facilitate development of therapeutic strategies in which effectiveness of opioids in alleviation neuropathic pain is increased.     

Ischemic tau protein gene induction as an additional key factor driving development of Alzheimer’s phenotype changes in CA1 area of hippocampus in an ischemic model of Alzheimer’s disease

Background

Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimer’s disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations.

Enhanced Recovery after Surgery (ERAS) Protocol Is a Safe and Effective Approach in Patients with Gastrointestinal Fistulas Undergoing Reconstruction: Results from a Prospective Study

Background and Aims: An enterocutaneous fistula (ECF) poses a major surgical problem. The definitive surgical repair of persistent fistulas remains a surgical challenge with a high rate of re-fistulation and mortality, and the reasons for that is not the surgical technique alone. Enhanced Recovery after Surgery (ERAS^®) is an evidence-based multimodal perioperative protocol proven to reduce postoperative complications. The aim of the study was to assess the clinical value of the ERAS protocol in surgical patients with ECF. Methods: ERAS protocol was used in all patients scheduled for surgery for ECF at the Stanley Dudrick’s Memorial Hospital in Skawina between 2011 and 2020. A multidisciplinary team (MDT) was in charge of the program and performed annual audits. A consecutive series of 100 ECF patients (44 females, 56 males, mean age 54.1 years) were evaluated. Postoperative complications rate, readmission rate, length of hospital stay, prevalence of postoperative nausea and vomiting were assessed. Registered under ClinicalTrials.gov Identifier no. {"type":"clinical-trial","attrs":{"text":"NCT04771832","term_id":"NCT04771832"}}NCT04771832. Results: ERAS protocol was successfully introduced for ECF surgeries; however, eight modifications to the ERAS program was performed in 2015. They led to improvement of surgical outcomes: reduction of postoperative nausea and vomiting (15 vs. 17% patients, p = 0.025), overall complication rate (11 vs. 10, p = 0.021), median length of hospital stay (overall and after surgery, p = 0.022 and 0.002, respectively). Conclusions: ERAS protocol can be successfully used for ECF patients. Prescheduled audits can contribute to the improvement of care.     

What Role Does the Endocannabinoid System Play in the Pathogenesis of Obesity?

The endocannabinoid system (ECS) is an endogenous signaling system formed by specific receptors (cannabinoid type 1 and type 2 (CB₁ and CB₂)), their endogenous ligands (endocannabinoids), and enzymes involved in their synthesis and degradation. The ECS, centrally and peripherally, is involved in various physiological processes, including regulation of energy balance, promotion of metabolic process, food intake, weight gain, promotion of fat accumulation in adipocytes, and regulation of body homeostasis; thus, its overactivity may be related to obesity. In this review, we try to explain the role of the ECS and the impact of genetic factors on endocannabinoid system modulation in the pathogenesis of obesity, which is a global and civilizational problem affecting the entire world population regardless of age. We also emphasize that the search for potential new targets for health assessment, treatment, and the development of possible therapies in obesity is of great importance.     

LIPID PEROXIDATION AND ANTIOXIDANT STATUS IN THE LIVER,ERYTHROCYTES, AND SERUM OF RATS AFTER METHANOL INTOXICATION

Lipid peroxidation products measured as a malondialdehyde and activities of superoxide dism utase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), and concentrations of ascorbic acid,-tocopherol, and glutathione (GSH) were measured in the liver, erythrocytes, and serum of rats 6, 14, and 24 h and 2, 5, and 7 d after treatment with 3 g methanol/ kg. GSH-Px and GSSG-R activities, GSH level, and ascorbate concentration in the liver, erythrocytes, and blood serum were significantly decreased. In addition, SOD and-tocopherol in erythrocytes were diminished, while malondialdehyde (MDA) in liver, erythrocytes, and serum were elevated. Further, erythrocyte counts, hemoglobin levels, hematocrit, and mean corpuscular volume (MCV) were reduced. These results indicate that methanol intoxication in rats leads to an increase in the lipid peroxidation and impairment in the antioxidant mechanisms in liver, erythrocytes, and blood serum.     

Environmental enrichment reverses behavioral alterations in rats prenatally exposed to valproic acid: issues for a therapeutic approach in autism.

Environmental enrichment has been repeatedly shown to affect multiple aspects of brain function, and is known to improve cognitive, behavioral, and histopathological outcome after brain injuries. The purpose of the present experiments was to determine the effect of an enriched environment on behavioral aberrations observed in male rats exposed to valproic acid on day 12.5 of gestation (VPA rats), and proposed on the basis of etiological, anatomical, and behavioral data as an animal model of autism. Environmental enrichment reversed almost all behavioral alterations observed in the model. VPA rats after environmental enrichment (VPA-E) compared to VPA rats reared in standard conditions have higher sensitivity to pain and lower sensitivity to nonpainful stimuli; stronger acoustic prepulse inhibition; lower locomotor, repetitive/stereotypic-like activity, and enhanced exploratory activity; decreased anxiety; increased number of social behaviors; and shorter latency to social explorations. In comparison with control animals (Con), VPA-E rats exhibited increased number of pinnings in adolescence and social explorations in adulthood, and were less anxious in the elevated plus maze. Similar differences in social behavior and anxiety were observed between control rats exposed to environmental enrichment (Con-E) and control group reared in standard conditions. These results suggest that postnatal environmental manipulations can counteract the behavioral alterations in VPA rats. We propose environmental enrichment as an important tool for the treatment of autism spectrum disorders.