scholarly journals General anesthesia, germ cells and the missing heritability of autism: an urgent need for research

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Jill Escher ◽  
La Donna Ford
Keyword(s):  
Risk Assessment ◽  
Nervous System ◽  
General Anesthesia ◽  
Germ Cells ◽  
Volatile Anesthetic ◽  
Diagnostic Procedures ◽  
Scientific Communities ◽  
Critical Gap ◽  
Anesthetic Gases ◽  
Behavioral Pathology

Abstract Agents of general anesthesia (GA) are commonly employed in surgical, dental and diagnostic procedures to effectuate global suppression of the nervous system, but in addition to somatic targets, the subject’s germ cells—from the embryonic primordial stage to the mature gametes—may likewise be exposed. Although GA is generally considered safe for most patients, evidence has accumulated that various compounds, in particular the synthetic volatile anesthetic gases (SVAGs) such as sevoflurane, can exert neurotoxic, genotoxic and epigenotoxic effects, with adverse consequences for cellular and genomic function in both somatic and germline cells. The purpose of this paper is to review the evidence demonstrating that GA, and in particular, SVAGs, may in some circumstances adversely impact the molecular program of germ cells, resulting in brain and behavioral pathology in the progeny born of the exposed cells. Further, we exhort the medical and scientific communities to undertake comprehensive experimental and epidemiological research programs to address this critical gap in risk assessment.

scholarly journals Severe haemophilia a in a preterm girl with turner syndrome - a case report from the prenatal period to early infancy (part I)

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Agnieszka Berendt ◽  
Monika Wójtowicz-Marzec ◽  
Barbara Wysokińska ◽  
Anna Kwaśniewska
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Turner Syndrome ◽  
X Chromosome ◽  
Diagnostic Procedures ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Preterm Children ◽  
Initial Symptoms ◽  
The Central Nervous System

Abstract Background Bleedings are more frequent in the population of preterm children than among those born at term, much less in older children. The reasons for such bleedings in preterms include plasma factor deficiencies, immaturity of small vessels in the germinal matrix region, prenatal hypoxia or sepsis. They affect the brain tissue, the gastrointestinal tract and the respiratory system, or are manifested by prolonged bleedings from injection sites. Haemophilia is a rare cause of haemorrhages in the neonatal period, and in the female population it is even seen as an extremely rare disorder. Its aetiology in girls is diverse: inheriting defective genes from their parents, skewed X inactivation or a single X chromosome. Case presentation The article presents a case of a preterm girl born in the 28th week of pregnancy, who was diagnosed with severe haemophilia A stemming from the absence of the X chromosome. The girl’s father is healthy, but her mother’s brother suffers from haemophilia. On the second day of the child’s life, a prolonged bleeding from the injection site was observed. A coagulation profile revealed prolonged APTT which pointed to haemophilia A diagnosis. Moreover, a marked clinical dysmorphy, female sex and a negative family history on the father’s side led the treating team to extend the diagnostic procedures to encompass karyotype evaluation. The girl was diagnosed with Turner syndrome. No bleeding to the central nervous system was observed during her hospital stay. Conclusions Preterm children belong to the risk group of bleeding into the central nervous system or haemorrhages in the course of sepsis. Rare causes of such bleedings should also be borne in mind, including haemophilia. The initial symptoms of haemophilia in preterm children occur in the first days of their lives, which is connected with a number of invasive procedures required in that period. Genetic conditions may coexist with one another. Arriving at one diagnosis does not mean one should abandon further diagnostic procedures in cases where additional atypical symptoms are present which do not match the clinical image of a primary disease.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Time Course ◽  
Model Organism ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Effective Concentration ◽  
Forward Genetics ◽  
C Elegans ◽  
Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

scholarly journals An overview of travel-associated central nervous system infectious diseases: risk assessment, general considerations and future directions

2014 ◽  
Vol 4 (8) ◽  
pp. 589-596
Author(s):  
Morteza Izadi ◽  
Arman Is'haqi ◽  
Mohammad Ali Is'haqi ◽  
Nematollah Jonaidi Jafari ◽  
Fatemeh Rahamaty ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Central Nervous System ◽  
Nervous System ◽  
Infectious Diseases ◽  
Future Directions

REFRACTIVE INDICES FOR VOLATILE ANESTHETIC GASES

1992 ◽  
Vol 77 (Supplement) ◽  
pp. A522
Author(s):  
C. F. Wallroth ◽  
K. L. Gippert ◽  
M. Ryschka ◽  
W. Falb ◽  
H. D. Hattendorff ◽  
...  
Keyword(s):  
Volatile Anesthetic ◽  
Refractive Indices ◽  
Anesthetic Gases

Effects of Temperature and Volatile Anesthetics on GABAAReceptors 

1999 ◽  
Vol 90 (2) ◽  
pp. 484-491 ◽  
Author(s):  
Andrew Jenkins ◽  
Nicholas P. Franks ◽  
William R. Lieb
Keyword(s):  
Body Temperature ◽  
General Anesthesia ◽  
Volatile Anesthetic ◽  
Gaba Concentration ◽  
Normal Body Temperature ◽  
Gaba A ◽  
Normal Body ◽  
Anesthetic Agents ◽  
Receptor Channel

Background Potentiation of the activity of the gamma-aminobutyric acid type A (GABA(A)) receptor channel by volatile anesthetic agents is usually studied in vitro at room temperature. Systematic variation of temperature can be used to assess the relevance of this receptor to general anesthesia and to characterize the modulation of its behavior by volatile agents at normal body temperature. Methods Potentiation of the GABA(A) receptor by halothane, sevoflurane, isoflurane, and methoxyflurane was studied at six temperatures in the range 10-37 degrees C using the whole-cell patch-clamp technique and mouse fibroblast cells stably transfected with defined GABA(A) receptor subunits. Results Control GABA concentration-response plots showed small and physically reasonable changes in the GABA concentration required for a half-maximal effect, the Hill coefficient, and maximal response over the range 10-30 degrees C. Potentiations of GABA (1 microM) responses by aqueous minimum alveolar concentrations of the volatile anesthetic agents decreased with increasing temperature from 10-37 degrees C in an agent-specific manner (methoxyflurane > isoflurane > sevoflurane > halothane) but tended to equalize at normal body temperature (37 degrees C). These findings are in line with published results on the temperature dependence of anesthetic potencies in animals. Conclusions These results are consistent with direct binding of volatile anesthetic agents to the GABA(A) receptor channel playing an important role in general anesthesia. The finding that the degree of anesthetic potentiation was agent-specific at low temperatures but not at 37 degrees C emphasizes the importance of doing in vitro experiments at normal body temperature.

scholarly journals Is It Feasible of Prophylactic Alpha-5 GABA(A) Receptor Blockade for Preventing POCD?

2013 ◽  
Vol 3 (3) ◽  
pp. 61-62
Author(s):  
Fuzhou Wang
Keyword(s):  
Nervous System ◽  
General Anesthesia ◽  
Neuronal Excitability ◽  
Underlying Mechanism ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
Inhalational Anesthetics ◽  
Exploratory Data

GAMMA-AMINOBUTYRIC ACID (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system (CNS). It plays a role in regulating neuronal excitability throughout the nervous system. Also GABA activation is considered as the basis of general anesthesia including intravenous and inhalational anesthetics. Meanwhile, cumulating evidence indicated that GABA is the underlying mechanism of post-operative cognitive dysfunction (POCD). Based on these findings, researchers are beginning to focus on GABA as the target to treat POCD, but they ignored the role of GABA in the performance of general anesthesia, especially when the blockade of GABA was given prior to surgery. It is undoubtedly risking our patients in intra-operative awareness. Our exploratory data also verified our hypothesis in which the GABA inhibition would reduce the efficacy of inhalational anesthetics.

Sign in / Sign up

Export Citation Format

Share Document