INTRODUCTION: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects. METHODS: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes. RESULTS: Although the administration of non-opioids, in general, had no effect on the development of delayed cerebral ischemia or hydrocephalus, the use of metamizole as the main analgesic was associated with a significantly lower chance of poor outcome at both 2-weeks and 6-months, as well as the development of delayed cerebral ischemia. As opioids were indicated primarily for analgosedation in mechanically ventilated patients with poor clinical status, their usage was associated with a significantly higher chance of poor outcome, delayed cerebral ischemia, and hydrocephalus. CONCLUSION: Our results suggest that the prescription of metamizole may be associated with better outcomes and a lower chance of delayed cerebral ischemia development in patients after subarachnoid hemorrhage. Considering the retrospective nature of our study and the limited worldwide availability of metamizole due to its prohibition in some countries, our results do not demonstrate a clear benefit but rather justify the need for subsequent prospective studies.
- MeSH
- Analgesics therapeutic use administration & dosage MeSH
- Anti-Inflammatory Agents, Non-Steroidal * therapeutic use administration & dosage MeSH
- Adult MeSH
- Hydrocephalus etiology MeSH
- Brain Ischemia drug therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Dipyrone * therapeutic use administration & dosage MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Subarachnoid Hemorrhage * drug therapy complications MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The fetus develops normally in a hypoxic environment but exaggerated hypoxia late in pregnancy is a worrisome sign often observed in hypertensive disorders of pregnancy, placental insufficiency, or fetal growth restriction (FGR). Serial fetal biometry and the cerebroplacental ratio (CPR, calculated as the middle cerebral artery [MCA] / the umbilical artery [UmbA] pulsatility indices [PI]), are commonly used to indicate fetal "brain sparing" resulting from exaggerated fetal hypoxia. But unclear is the extent to which a low CPR indicates pathology or is a physiological response for maintaining cerebral blood flow. We studied 31 appropriate for gestational age (AGA) pregnancies at low (LA, 1670 m) or high (HA, 2879 m) altitude, given the chronic hypoxia imposed by HA residence, and 54 LA women with a clinical diagnosis of FGR. At week 34, the MCA PI was lower in the LA-FGR than the LA-AGA group but lower still in the HA-AGA compared to either LA groups due to a trend toward higher end-diastolic velocity (EDV). We concluded that the lower MCA PI was likely due to greater cerebral vasodilation in the HA AGA group and an indication of physiological versus pathological fetal hypoxia. Future reporting of serial MCA and UmbA values and their determinants along with the CPR could improve our ability to distinguish between physiological and pathological fetal brain sparing. Keywords: Birth weight, Cerebroplacental ratio, Fetal physiology, HDP, High altitude.
- MeSH
- Middle Cerebral Artery * diagnostic imaging physiopathology MeSH
- Umbilical Arteries diagnostic imaging physiopathology MeSH
- Adult MeSH
- Fetal Hypoxia * physiopathology MeSH
- Hypoxia physiopathology MeSH
- Humans MeSH
- Brain physiopathology blood supply diagnostic imaging MeSH
- Cerebrovascular Circulation physiology MeSH
- Altitude MeSH
- Fetal Growth Retardation * physiopathology MeSH
- Pregnancy MeSH
- Ultrasonography, Prenatal methods MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Psychiatric and mood disorders may play an important role in the development and persistence of irritable bowel syndrome (IBS). Previously, we hypothesized that stress-induced implicit memories may persist throughout life via epigenetic processes in the enteric nervous system (ENS), independent of the central nervous system (CNS). These epigenetic memories in the ENS may contribute to developing and perpetuating IBS. Here, we further elaborate on our earlier hypothesis. That is, during pregnancy, maternal prenatal stresses perturb the HPA axis and increase circulating cortisol levels, which can affect the maternal gut microbiota. Maternal cortisol can cross the placental barrier and increase cortisol-circulating levels in the fetus. This leads to dysregulation of the HPA axis, affecting the gut microbiota, microbial metabolites, and intestinal permeability in the fetus. Microbial metabolites, such as short-chain fatty acids (which also regulate the development of fetal ENS), can modulate a range of diseases by inducing epigenetic changes. These mentioned processes suggest that stress-related, implicit, long-term epigenetic memories may be programmed into the fetal ENS during pregnancy. Subsequently, this implicit epigenetic stress information from the fetal ENS could be conveyed to the CNS through the bidirectional microbiota-gut-brain axis (MGBA), leading to perturbed functional connectivity among various brain networks and the dysregulation of affective and pain processes.
- MeSH
- Epigenesis, Genetic * MeSH
- Humans MeSH
- Brain-Gut Axis physiology MeSH
- Stress, Psychological * metabolism MeSH
- Gastrointestinal Microbiome physiology MeSH
- Enteric Nervous System * MeSH
- Irritable Bowel Syndrome * metabolism MeSH
- Pregnancy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Nitroděložní či systémový mateřský zánět komplikuje zhruba 20% všech těhotenství. Epidemiologické studie naznačují, že mateřský zánět je zodpovědný za abnormální psychomotorický vývoj u potomků, včetně poruch autistického spektra, kognitivního zpoždění a schizofrenie. Buněčné/molekulární mechanismy tohoto fenoménu dosud nebyly plně objasněny. Recentní výzkumy naznačují, že prozánětlivé cytokiny (např. interferon gamma a interleukin 6) regulují expresi a aktivitu klíčových enzymů metabolismu tryptofanu v placentě a následně placentární produkci neuroaktivních metabolitů (např. serotonin, melatonin, kynurenin, kyselina kynurenová a kyselina chinolinová). Po uvolnění z placenty do fetálního oběhu mohou tyto metabolity ovlivnit vývoj a programování mozku plodu. V navrhovaném projektu se s pomocí řady experimentálních přístupů snažíme objasnit vazby mezi prenatálním zánětem, produkcí prozánětlivých cytokinů, placentárním metabolizmem tryptofanu a následným psychomotorickým vývojem kojenců s cílem identifikovat potenciální cesty k in utero prevenci rozvoje psychomotorických poruch u dětí.; Intrauterine or systemic inflammation occurs in ca. 20% of all pregnancies, and epidemiological observations indicate that they are associated with various neurodevelopmental disorders in the offspring, including autism spectrum disorders, cognitive delay, and schizophrenia. However, the underlying cellular and molecular mechanisms have not been fully elucidated. Recent research indicates that inflammatory cytokines (e.g. interferon gamma and interleukin 6) may modulate the expression and activity of key enzymes involved in placental tryptophan metabolism and hence production of neuroactive molecules (e.g. serotonin, melatonin, kynurenine, kynurenic acid and quinolinic acid). After release from the placenta into the foetal circulation, these neuroactive compounds may interfere with foetal brain development and programming. Thus, in the proposed project we aim to clarify links between prenatal inflammation, inflammatory cytokines, placental tryptophan metabolism and infant neurodevelopment, thereby identifying potential avenues for addressing neurological disorders in utero.
- Keywords
- pregnancy, zánět, inflammation, Metabolismus, Metabolism, tryptofan, tryptophan, Těhotenství, placenta, placenta, neurotoxicity, fetal development, neurotoxicita, vývoj plodu,
- NML Publication type
- závěrečné zprávy o řešení grantu AZV MZ ČR
Prenatal listening experience reportedly modulates how humans process speech at birth, but little is known about how speech perception develops throughout the perinatal period. The present experiment assessed the neural event-related potentials (ERP) and mismatch responses (MMR) to native vowels in 99 neonates born between 32 and 42 weeks of gestation. The vowels elicited reliable ERPs in newborns whose gestational age at time of experiment was at least 36 weeks and 1 day (36 + 1). The ERPs reflected spectral distinctions between vowel onsets from age 36 weeks + 6 days and durational distinctions at vowel offsets from age 37 weeks + 6 days. Starting at age 40 + 4, there was evidence of neural discrimination of vowel length, indexed by a negative MMR response. The present findings extend our understanding of the earliest stages of speech perception development in that they pinpoint the ages at which the cortex reliably responds to the phonetic characteristics of individual speech sounds and discriminates a native phoneme contrast. The age at which the brain reliably differentiates vowel onsets coincides with what is considered term age in many countries (37 weeks + 0 days of gestational age). Future studies should investigate to what extent the perinatal maturation of the cortical responses to speech sounds is modulated by the ambient language.
- MeSH
- Acoustic Stimulation * methods MeSH
- Electroencephalography * MeSH
- Evoked Potentials physiology MeSH
- Phonetics * MeSH
- Gestational Age * MeSH
- Humans MeSH
- Infant, Premature physiology MeSH
- Infant, Newborn MeSH
- Speech Perception * physiology MeSH
- Evoked Potentials, Auditory physiology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Souhrn: Souhrnný článek o předčasném porodu jako nezávislém rizikovém faktoru rozvoje duševního onemocnění matky. Metodika: Přehled publikované literatury k danému tématu použitím databáze PubMed. Výsledky: Perinatální duševní zdraví ovlivňuje zásadně život matky a vývoj dítěte, a proto jde v širší souvislosti o celospolečenskou problematiku. Samostatnou vysoce rizikovou skupinou, kde lze očekávat deterioraci psychického stavu, jsou ženy, kterým se narodí nezralý novorozenec <32+0 týden těhotenství Very Low Birth Weight (VLBW) a <28+0 týden těhotenství Extremely Low Birth Weight (ELBW). Závěr: Mezi nejčastější duševní poruchy tohoto období patří poporodní deprese (PPD) a úzkostná porucha (AD). Cílem je shrnout současné poznatky o vzájemném působení předčasného porodu a rozvoje psychických poruch a zdůraznit návaznost perinatální a duševní péče.
ntroduction and Objective: Folate (vitamin B9) supplementation during pregnancy to prevent neural tube defects (NTDs) in the fetus is a widely accepted standard of care. Folate is also vital for maintaining proper brain function. Additionally, folic acid works in conjunction with vitamin B12 ro produce red blood cells and aids in the proper functioning of iron in the body. The most effective form of folate supplementation remains a topic of ongoing discussion. This review aims to collect information on the effects of folic acid and its derivatives on reproductive health. Review and Methods: Review and summary of available studies found in open-access formats on Google Scholar and PubMed. State of Knowledge: Folic acid is well-established as a preventive measure against NTDs during pregnancy. However, the debate persists over the most effective form of folate supplementation, with a focus on addressing individual genetic variations and specific health needs. Individuals with MTHFR gene variants, which can impair the conversion of folic acid to its active form, 5-MTHF, may experience greater benefits from direct 5-MTHF supplementation rather than traditional folic acid. Studies aim to optimize supplementation strategies, ensuring that they are tailored to enhance efficacy and improve health outcomes for diverse populations. Conclusions: Folic acid is essential for fetal development and overall health. MTHFR polymorphisms can hinder folate metabolism, raising deficiency risk. In such cases, 5-MTHF supplementation is recommended over folic acid for better absorption and lower cardiovascular risks. Ongoing research is vital for optimizing folate-related health.
- MeSH
- Cannabis MeSH
- Mental Processes drug effects MeSH
- Humans MeSH
- Young Adult MeSH
- Brain embryology physiopathology growth & development MeSH
- Alcohol Drinking adverse effects MeSH
- Alcohol-Induced Disorders * embryology physiopathology prevention & control congenital MeSH
- Pregnancy MeSH
- Fetal Development * MeSH
- Health Education MeSH
- Drug Misuse MeSH
- Check Tag
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
- Newspaper Article MeSH
The chondrocranium provides the key initial support for the fetal brain, jaws and cranial sensory organs in all vertebrates. The patterns of shaping and growth of the chondrocranium set up species-specific development of the entire craniofacial complex. The 3D development of chondrocranium have been studied primarily in animal model organisms, such as mice or zebrafish. In comparison, very little is known about the full 3D human chondrocranium, except from drawings made by anatomists many decades ago. The knowledge of human-specific aspects of chondrocranial development are essential for understanding congenital craniofacial defects and human evolution. Here advanced microCT scanning was used that includes contrast enhancement to generate the first 3D atlas of the human fetal chondrocranium during the middle trimester (13 to 19 weeks). In addition, since cartilage and bone are both visible with the techniques used, the endochondral ossification of cranial base was mapped since this region is so critical for brain and jaw growth. The human 3D models are published as a scientific resource for human development.
- MeSH
- Cartilage diagnostic imaging embryology MeSH
- Skull diagnostic imaging embryology MeSH
- Humans MeSH
- Fetus diagnostic imaging MeSH
- X-Ray Microtomography MeSH
- Pregnancy MeSH
- Imaging, Three-Dimensional * MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Dataset MeSH
Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (lipopolysaccharides/LPS) and viral (polyinosinic:polycytidylic acid/poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or poly I:C. Conversely, the rate-limiting enzyme in the kynurenine pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the kynurenine (KYN) pathway. Furthermore, we observed that treatment with LPS or poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.
- MeSH
- Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism MeSH
- Kynurenine * metabolism MeSH
- Humans MeSH
- Lipopolysaccharides toxicity MeSH
- Placenta * metabolism MeSH
- Poly I metabolism MeSH
- Serotonin metabolism MeSH
- Pregnancy MeSH
- Tryptophan metabolism MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH