四种麻醉药物对食蟹猴麻醉效果分析和选择应用

目的分析比对速眠新、氯胺酮、异氟烷和利多卡因4种不同麻醉药对食蟹猴的麻醉效果。方法总结实际工作中分别使用四种不同麻醉药物对食蟹猴作用的麻醉特点。结果速眠新、氯胺酮、异氟烷均能获得较好的麻醉效果,能满足不同手术、采样需要;局麻药利多卡因对食蟹猴麻醉的实际应用不理想。结论食蟹猴的手术及其他侵犯性操作等都应该考虑生物安全和动物福利要求,实行麻醉,但应根据食蟹猴实验内容要求和不同麻醉药特点选择合适的麻醉方法,确保人员和动物安全,实验结果不受影响。     

Juvenile Rats Show Altered Gut Microbiota After Exposure to Isoflurane as Neonates

Neurochemical Research - Inhaled anesthetic agents may be neurotoxic to the developing brain of a neonatal rodent. Isoflurane is a commonly used volatile anesthetic agent for maintenance of general...     

Alzheimer’s Disease: Halothane Induces Aβ Peptide to Oligomeric Form—Solution NMR Studies

Alzheimer’s disease (AD) is a significant contributor to cognitive decline and is responsible for about half of the cases of dementia in later life. Although exact etiology of AD is not known, however, many risk factors for AD are identified. Anesthesia for elderly patients is considered as a risk factor in AD as they frequently experience deterioration in cognitive function with long exposure to anesthetics during surgery. Inhaled anesthetic agents remain the mainstay for patients undergoing major surgical operations. This study using multidimensional NMR spectroscopy provides the first direct evidence in vitro that inhaled anesthetic, halothane specifically interacts with Aβ40 and Aβ42 peptide. Halothane induces structural alternation of Aβ peptide from soluble monomeric α-helical form to oligomeric β-sheet conformation, which may hasten the onset of AD. Aβ42 is more prone to oligomerization compared to Aβ40 in the presence of halothane. The molecular mechanism of halothane induced structural alternation of Aβ peptide is discussed. An erratum to this article can be found at     

A core process in receptor function, general anesthesia, sleep, and aging

The diffusion of ligands and proteins was proposed to be guided by chreodes in water organized by protein-surface side chains with varying hydropathic states. These chreodes are proposed to be the target of volatile general anesthetic agents. The similarity between this effect and sleep deprivation leads to a proposal of an external agent responsible for sleep. This agent is elemental nitrogen. An extension of this effect is the concept that elemental nitrogen is a core factor in aging.     

Effect of anesthetic agents on lavage fluid parameters used as indicators of pulmonary injury

The effect of the anesthetic agent used in killing animals in an in vivo pulmonary toxicity screening test was examined in Fischer-344 rats and in Syrian hamsters. Using animals killed by cervical dislocation with no anesthesia as a baseline, two types of anesthetic agents (halothane, sodium pentobarbital) and carbon dioxide were tested. Carbon dioxide caused the greatest perturbance of baseline lavage fluid and tissue parameters normally used in the screening test. Halothane anesthesia caused the least perturbance in the screening test parameters and was selected as the anesthetic of choice for use in future pulmonary toxicity tests.     

New volatile anesthetic,desflurane, reduces vitamin E level in blood of operative patients via oxidative stress

It has been well known that some volatile anesthetic agents produce oxidative stress. Desflurane as a new volatile agent might have limited oxidative toxic effect because it is relatively a new short‐acting anesthetic characterized by a short duration of action and a quick postanesthetic recovery. We investigated effect of desflurane on serum glutathione peroxidase (GSH‐Px), lipid peroxidation (LP), vitamin E, and erythrocyte superoxide dismutase (SOD) values in patients. Fifteen adult patients are scheduled for elective surgery, ASA I or II physical status. Tidal volume and ventilation frequency were kept unchanged during the operation. Baseline values in venous blood samples were preoperatively taken and blood was also taken postoperatively at the 1st and the 12th hours of desflurane exposure. LP levels were significantly (p < 0.05) higher postoperatively at 1st hour than in preoperative values while α‐tocopherol concentration was significantly (p < 0.001) lower in postoperative period at 1st hour than in preoperative period. Erythrocyte SOD and serum GSH‐Px activities did not differ between pre‐ and postoperative periods. In conclusion, we observed that desflurane produced oxidative stress by decreasing α‐tocopherol levels. Use of vitamin E may be possible to reduce the oxidative effect of desflurane. Copyright © 2010 John Wiley & Sons, Ltd.     

Inactivation of the BSE agent

In the studies carried out so far, the BSE agent has proved to be just as resistant as other TSE agents to inactivation by procedures such as autoclaving or exposure to sodium hydroxide that are effective with conventional microorganisms. However, in common with other TSE agents, the BSE agent appears to be effectively inactivated by exposure to sodium hypochlorite solutions containing high levels of available chlorine. Not surprisingly, the BSE agent has been found to survive at least some of the rendering processes that were used to process tissues discarded by abattoirs in the EU during the early 1980s. Despite the survival of BSE infectivity after autoclaving or exposure to sodium hydroxide, it is known that combining these procedures results in a very reliable degree of inactivation for TSE agents generally. The combination of heat and alkali has also been shown to be effective with a mouse-passaged strain of BSE agent, even at a temperature of only 100 degrees C for a minute. Also, in carrying out BSE-spiked validation studies relating to the safety of bone-derived gelatin, it has also been found that the exposure of acid-treated bone (which is free from any obvious remains of fatty or proteinaceous tissue) to 0.3 M sodium hydroxide for two hours knocks out any residual BSE infectivity.     

Utilization of Neural Stem Cell-Derived Models to Study Anesthesia-Related Toxicity and Preventative Approaches

Early-life stress has been shown in both preclinical and clinical studies to cause neuroanatomical and biological alterations and disruptions in homeostasis. These alterations can lead to dysfunction in critical regulatory systems and concomitant increases in risk for the development of pathology. The existing data from research using in vivo animal models have implicated some general anesthetics as being toxic to the developing brain and causing cognitive deficits later in life. Because of obvious limitations, it is not possible to thoroughly explore the effects of early-life stress—e.g., prolonged exposure to anesthetic agents—on neurons in vivo in human infants or children. However, the availability of stem cell-derived models, especially human embryonic neural stem cells, along with their capacity for proliferation and ability to differentiate, has provided a potentially invaluable tool for examining the developmental effects of anesthetic agents in vitro. This review focuses on how embryonic neural stem cells, when combined with biochemical, pathological, and pharmacokinetic assessments, might serve as a bridging platform to provide the most expeditious approaches toward decreasing the uncertainty in extrapolating preclinical data to the human condition. This review presents key concepts in stem cell biology with respect to the nervous system, presents an overview of neural development, and summarizes the involvement of neural cell types in developmental neurotoxicity associated with anesthetic exposure.     

SYSTEMIC TOXIC REACTIONS TO LOCAL ANESTHETICS

The topical use of anesthetic agents involves an element of risk. Systemic toxic reactions are rare, but they do occur and may result in death. When a reaction occurs from a topical application, it usually progresses rapidly to respiratory and cardiovascular collapse, and thus therapy must be instituted with more haste to avoid deaths. Fatal systemic toxic reactions from topically administered anesthetic drugs are, in effect, usually not due to well informed use of the drug but to misuse owing to less than complete understanding of absorption.Emphasis is placed on the causes, prophylaxis and treatment of severe systemic toxic reactions which follow the topical application of local anesthetic drugs. If systemic toxic reactions resulting from a safe dose of a local anesthetic agent are correctly treated, there will usually follow an uneventful recovery rather than a catastrophe.     

Effect of diethyl ether on the biliary excretion of acetaminophen

The biliary and renal excretion of acetaminophen and its metabolites over 8 hr was determined in rats exposed to diethyl ether by inhalation for 1 hr. Additional rats were anesthetized with urethane (1 g/kg ip) while control animals were conscious throughout the experiment (surgery was performed under hexobarbital narcosis: 150 mg/kg ip; 30-min duration). The concentration of UDP-glucuronic acid was decreased 80% in livers from ether-anesthetized rats but was not reduced in urethane-treated animals when compared to that in control rats. The concentration of reduced glutathione was not affected by either urethane or diethyl ether. Basal bile flow was not altered by the anesthetic agents. Bile flow rate after acetaminophen injection (100 mg/kg iv) was increased slightly over basal levels for 2 hr in hexobarbital-treated control rats, was unaltered in urethane-anesthetized animals, and was decreased throughout the 8-hr experiment in rats exposed to diethyl ether for 1 hr. In control and urethane-anesthetized animals, approximately 30-35% of the total acetaminophen dose (100 mg/kg iv) was excreted into bile in 8 hr, while only 16% was excreted in rats anesthetized with diethyl ether. Urinary elimination (60-70% of the dose) was not altered by exposure to ether. Separation of metabolites by reverse-phase high-pressure liquid chromatography showed that ether decreased the biliary elimination of unchanged acetaminophen and its glucuronide, sulfate, and glutathione conjugates by 47, 40, 49, and 73%, respectively, as compared to control rats. Excretion of unchanged acetaminophen and the glutathione conjugate into bile was depressed in urethane-anesthetized animals by 45 and 66%, respectively, whereas elimination of the glucuronide and sulfate conjugates was increased by 27 and 50%, respectively. These results indicate that biliary excretion is influenced by the anesthetic agent and that diethyl ether depresses conjugation with sulfate and glutathione as well as glucuronic acid.     

Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia

It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE). Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon), in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35%) or xenon (35%) were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND) 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic) neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be tested in clinical trials in the future.     

Sevoflurane Modulates AKT Isoforms in Triple Negative Breast Cancer Cells. An Experimental Study

(1) Background: Triple negative breast cancer (TNBC) is a highly aggressive tumor, associated with high rates of early distant recurrence and short survival times, and treatment may require surgery, and thus anesthesia. The effects of anesthetic drugs on cancer progression are under scrutiny, but published data are controversial, and the involved mechanisms unclear. Anesthetic agents have been shown to modulate several molecular cascades, including PI3K/AKT/mTOR. AKT isoforms are frequently amplified in various malignant tumors and associated with malignant cell survival, proliferation and invasion. Their activation is often observed in human cancers and is associated with decreased survival rate. Certain anesthetics are known to affect hypoxia cell signaling mechanisms by upregulating hypoxia-inducible factors (HIFs). (2) Methods: MCF-10A and MDA-MB 231 cells were cultivated and CellTiter-Blue^® Cell Viability assay, 2D and 3D matrigel assay, immunofluorescence assays and gene expressions assay were performed after exposure to different sevoflurane concentrations. (3) Results: Sevoflurane exposure of TNBC cells results in morphological and behavioral changes. Sevoflurane differently influences the AKT isoforms expression in a time-dependent manner, with an important early AKT3 upregulation. The most significant effects occur at 72 h after 2 mM sevoflurane treatment and consist in increased viability, proliferation and aggressiveness and increased vimentin and HIF expression. (4) Conclusions: Sevoflurane exposure during surgery may contribute to cancer recurrence via AKT3 induced epithelial–mesenchymal transition (EMT) and by all three AKT isoforms enhanced cancer cell survival and proliferation.     

Plasma and cerebrospinal fluid concentration of neuropeptide Y, serotonin, and catecholamines in patients under propofol or isoflurane anesthesia

Propofol is a widely used anesthetic for both induction and maintenance of anesthesia during surgery. A strong feeling of hunger has been reported during the early recovery period after propofol anesthesia. We have investigated the effect of propofol on appetite in 10 patients undergoing a craniotomy and in parallel measured neuropeptide Y (NPY), catecholamines, and serotonin levels in the cerebrospinal fluid and plasma during anesthesia. Ten patients anesthetized with a volatile agent (isoflurane) served as a control group. Plasma NPY and catecholamines levels were not affected by surgery at any time. We observed a strong increase in NPY concentrations in the cerebrospinal fluid independently of the anesthetic technique agent used, whereas catecholamines were unchanged. We found that serotonin concentrations decreased significantly in the plasma (but not in the cerebrospinal fluid) of patients treated by propofol when compared with the control group; this decrease was associated with an increase of hunger early postoperatively. We concluded that the proappetite effect of propofol is mediated through a decrease of serotonin at the peripheral level.     

Effect of Vaccination in Environmentally Induced Diseases

Along with the constant improvement in hygiene in the last few decades there has been a continuous increase in the incidence of particular diseases, mainly of autoimmune or allergic etiology, but also of diseases caused by infectious agents, such as listeriosis. We here present a model for the effect of exposure to agents causing or inducing the disease on the incidence of morbidity. The proposed model is an expansion of the SIR model to non-contagious diseases and aims to estimate the balance between immunization and disease probability. The model results indicate that, paradoxically in a wide range of parameters, a decrease in exposure to the disease inducing agent results in an increase in disease incidence. This can occur if: (a) the probability of developing disease, given an exposure to the agent increases with age, (b) immunity to the agent is long. The inverse relation between exposure and disease incidence results from a decrease in the adult immunized population following a previous decrease in the exposure rate. Therefore, a lower exposure can lead to lower incidence in the short term but to higher incidence in the long term.     

Qualitative and quantitative procedures for health risk assessment.

Numerous reactive mutagenic electrophiles are present in the environment or are formed in the human body through metabolizing processes. Those electrophiles can directly react with DNA and are considered to be ultimate carcinogens. In the past decades more than 200 in vitro and in vivo genotoxic tests have been described to identify, monitor and characterize the exposure of humans to such agents. When the responses of such genotoxic tests are quantified by a weight-of-evidence analysis, it is found that the intrinsic potency of electrophiles being mutagens does not differ much for the majority of the agents studied. Considering the fact that under normal environmental circumstances human are exposed to low concentration of about a million electrophiles, the relation between exposure to such agents and adverse health effects (e.g., cancer) will become a 'Pandora's box'. For quantitative risk assessment it will be necessary not only to detect whether the agent is genotoxic, but also understand the mechanism of interaction of the agent with the DNA in target cells needs to be taken into account. Examples are given for a limited group of important environmental and carcinogenic agents for which such an approach is feasible. The groups identified are agents that form cross-links with DNA or are mono-alkylating agents that react with base-moieties in the DNA strands. Quantitative hazard ranking of the mutagenic potency of these groups of chemical can be performed and there is ample evidence that such a ranking corresponds with the individual carcinogenic potency of those agents in rodents. Still, in practice, with the exception of certain occupational or accidental exposure situations, these approaches have not be successful in preventing cancer death in the human population. However, this is not only due to the described 'Pandora's box' situation. At least three other factors are described. Firstly, in the industrial world the medical treatment of cancer in patients occurs with high levels of extremely mutagenic agents. Actually, both in number of persons and in exposure levels such medical treatment is the single largest exposure of humans to known carcinogens. Although such treatments are very effective in curing the tumor as present in the patient, the recurrence of cancer in those patients later in life is very high. In other words: "curing cancer is not the same as preventing cancer death in the human population". Secondly, the rate of cancer death in the human population is also determined by the efficacy in which other major causes of death are prevented. For instance, cardiovascular diseases are the major cause of death in humans in the industrialized world. There is evidence that the treatment of cardiovascular diseases is more successful than that of cancer. On a population level this will result in increase of cancer being the ultimate death cause. Finally, the improvement of medical treatment of diseases together with an improved quality of life will lead to increase average age of the population. Because the onset of most cancer is long after the exposure to carcinogens-in human often more than 30 years-cancer is predominantly a disease of the old age. This means that if the average age of human increases, there will be a selective preference of cancer becoming an even more important cause of death. This especially will be pronounced in those countries were the age distribution in a population is abnormal.     

Alpha-chloralose suppression of neuronal activity

Alpha-chloralose, an anesthetic agent widely used in neurophysiologic studies, caused a significant and long-lasting suppression of single neuron activity recorded from two areas of the central nervous system in decerebrate cats. A 50 mg/kg dose (an average anesthetic dose used in many neurophysiologic studies) caused suppression of spontaneous and evoked activity of neurons in the dorsal horn of the spinal cord and greater suppression of neurons in the nucleus reticularis gigantocellularis (NRGC) of the medial medullary reticular formation. Many researchers are of the opinion that alpha-chloralose causes less suppression of the central nervous system (CNS) than other commonly used anesthetic agents. The neuronal suppression recorded in this study appears similar in many ways to suppression caused by other anesthetic agents in the same two areas of the CNS. The results of the present study suggest that alpha-chloralose may be capable of producing significant suppression of neurons in the dorsal horn of the spinal cord and NRGC. Its ability to influence other areas of the CNS should not be inferred from these results, but the data do indicate the importance of evaluating the effects of anesthetics upon neurophysiologic systems under study.     

Comparison of Isoflurane and Carbon Dioxide Anesthesia in Chilean Rose Tarantulas (Grammostola rosea)

This study investigated the use of two anesthetic agents, isoflurane and carbon dioxide, in Chilean rose tarantulas (Grammostola rosea). We compared the onset, duration of anesthesia, and recovery time with both gases, and made observations regarding the effects of the anesthetic protocols. Subjectively, episodes for the isoflurane animals were uneventful. The spiders were calm throughout and did not respond adversely to gas exposure. Conversely, animals anesthetized with carbon dioxide experienced violent inductions and recoveries; the tarantulas appeared agitated when the carbon dioxide flow began. Seizure‐like activity and defecation would frequently be noted prior to induction with carbon dioxide. Neither isoflurane nor carbon dioxide seemed to have any clinically apparent short‐ or long‐term impact. The animals were all normal for at least 1‐year postexperiment. Future studies should focus on defining the impact, if any, that these anesthetic agents have on the health of invertebrate species. Zoo Biol. 32:101‐103, 2013. © 2012 Wiley Periodicals, Inc.     

Single-strand breaks in DNA of hamster and human cells exposed to methyl methanesulfonate and ultraviolet light

The number of single-strand breaks produced in DNA after exposure to UV light or to methyl methanesulfonate (MMS) was additive when cells were exposed to both agents in close succession. Repair of the damage from either agent was partially inhibited by cytosine arabinoside, resulting in higher break frequencies under all conditions of exposure. Exposure to both agents followed by growth in cytosine arabinoside resulted in break frequencies that were approximately the same as the sum of those from each agent individually. These findings contrast with previous results in which pyrimidine dimer excision and repair replication after exposure to UV light were inhibited by MMS. These observations are not due to cell permeability changes after alkylation, but can be explained if the complex of excision-repair proteins is only partially inactivated by alkylation. Initial incisions to start repair would still occur but only limited amounts of repair replication would ensue without actual removal of the pyrimidine dimers.     

The membrane volume occupied by anesthetic molecules: A reinterpretation of the erythrocyte expansion data

Seeman and coworkers (Seeman, P. (1972) Pharmacol. Rev. 24, 583–655) calculated that anesthetic agents exapnd membrane volume ten times more than the van der Waals volume of the agent alone. Their calculation was based on the assumption that the thickness of the erythrocyte membrane expands at the same rate as the surface area. However, recent data on bilayer membranes demonstrate that an expansion of membrane surface area is accompanied by a decrease in membrane thickness. A reinterpretation of their erythrocyte area expansion data using an appropriate contraction of membrane thickness suggests the volume in a membrane occupied by anesthetic molecules is approximately equal to their van der Waals volume.