Ampicillin, a beta-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G signifi cantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.
Ampicillin* ; Animals ; Astrocytes ; Brain Injuries ; Carotid Artery, Common ; Glial Fibrillary Acidic Protein ; Glutamic Acid ; Halothane ; Hippocampus ; Humans ; Ischemia* ; Lectins ; Male ; Matrix Metalloproteinases ; Mice* ; Microglia ; Neurons ; Neuroprotective Agents ; Penicillin G ; Prosencephalon*

INTRODUCTIONDraw-over anaesthesia remains an attractive option for conduct of anaesthesia in austere conditions. The Diamedica Draw-over Vaporiser (DDV) is a modern draw-over vaporiser and has separate models for isoflurane/halothane and sevoflurane.

MATERIALS AND METHODSA laboratory study was done to measure sevoflurane output in an isoflurane/ halothane DDV. We did 3 series of experiments with the isoflurane/halothane DDV. We measured anaesthetic agent output in both push-over and draw-over setups, and at minute ventilation of 6 L/min and 3 L/min. Series 1 experiment was done with isoflurane in the DDV at ambient temperature of 20°C. Series 2 experiment was done with sevoflurane in the DDV at ambient temperature of 20°C. Series 3 experiment was done with sevoflurane in the DDV and with the DDV placed in a water bath of 40°C.

RESULTSThe sevoflurane output was found to be two-thirds of the isoflurane/ halothane DDV dial setting at ambient temperature of 20°C. With the DDV in a 40°C water bath, the sevoflurane output was found to be about the isoflurane/ halothane DDV dial settings.

CONCLUSIONIn our experiment, we show that it is possible to use sevoflurane in an isoflurane/halothane DDV.

Anesthesia, Inhalation ; instrumentation ; methods ; Anesthetics, Inhalation ; administration & dosage ; Halothane ; Humans ; Isoflurane ; Methyl Ethers ; administration & dosage ; Nebulizers and Vaporizers ; Temperature

BACKGROUND: Malignant hyperthermia (MH) has a high mortality rate and a family history. Then, caffeine and halothane contracture test (CHCT), generally used to detect MH susceptibility, is needed for early detection. The aim of this survey is to collect the opinion about establishment of the center for CHCT in Korea. METHODS: A people who were anesthesiologists working in the training hospital of Korea participated the survey between January and March 2011. Usual anesthetic drug during general anesthesia including volatile agents, opioids, muscle relaxants, incidence, diagnoses and treatments of MH, and opinion about establishment of the center for CHCT, were investigated. RESULTS: A total of 105 people who were anesthesiologists working in Korea were registered, they answered that 33 anesthesiologists (32%) met MH patient, and MH occurred once in a decade. If there is a diagnostic method such as CHCT in Korea, 89 anesthesiologists (89%) will recommend the test for the patients and their family. CONCLUSIONS: Many anesthesiologists want to recommend the CHCT for patients and their family. But, in Korea, it is impossible because there is no laboratory available for CHCT. Now, we considered carefully to establish the laboratory available for CHCT.
Analgesics, Opioid ; Anesthesia, General ; Caffeine ; Contracture ; Halothane ; Humans ; Incidence ; Korea ; Malignant Hyperthermia ; Muscles ; Surveys and Questionnaires

BACKGROUNDMalignant hyperthermia (MH), manifesting as MH crisis during and/or after general anesthesia, is a potentially fatal disorder in response to volatile anesthetics and depolarizing muscle relaxants. Though typical features of MH episode can provide clues for clinical diagnosis, MH susceptibility is confirmed by in vitro caffeine-halothane contracture test (CHCT) in western countries. It is traditionally thought that MH has less incidence and fewer typical characteristics in Chinese population than their western counterparts because of the different genetic background. In this study, we investigated the clinical features of MH in Chinese cases and applied the clinical grading scale and CHCT for diagnosis of MH.

METHODSA cluster of three patients with MH, from January 2005 to December 2007, were included in the study. Common clinical presentations and the results of some lab examinations were reported in detail. The method of the clinical grading scale of diagnosis of MH was applied to estimate the qualitative likelihood of MH and predict MH susceptibility. Muscle fibers of femoral quadriceps of the patients were collected and CHCT was performed to confirm the diagnosis of MH.

RESULTSThe clinical grading scales of diagnosis of the disease for these cases were all ranked grade D6, suggesting almost diagnosed ones. And the results of caffeine test were positive correspondingly, indicating that the patients should be diagnosed as MH susceptibility (MHS) according to diagnostic criteria of the North America MH group, which were already confirmed by clinical presentations and biochemical results.

CONCLUSIONSThese Chinese cases manifest as MH crisis. The clinical grading scale of diagnosis of MH may provide clues for clinical diagnosis. CHCT can also be used in confirming diagnosis of MH in Chinese cases though they have different genetic background from their western counterparts.

Adolescent ; Adult ; Caffeine ; Child ; China ; Female ; Halothane ; Humans ; In Vitro Techniques ; Male ; Malignant Hyperthermia ; diagnosis ; Muscle Contraction ; drug effects ; Young Adult

BACKGROUND: The 5-hydroxytryptamine type 3 (5-HT3) receptor is a member of the Cys-loop superfamily of ligand-gated ion channels (LGICs) and modulated by pharmacologic relevant concentrations of volatile anesthetics or n-alcohols like most receptors of LGICs. The goal of this study was to reveal whether the site-directed single mutations of E-106, F-107 and R-222 in 5-HT3 receptor may affect the anesthetic modulation of halothane known as positive modulator. METHODS: The wild-type and mutant receptors, E106D, F107Y, R222F, R222V, were expressed in Xenopus Laevis oocytes and receptor function was assessed using two electrode voltage clamp techniques. RESULTS: E106D, F107Y, R222F, R222V mutant 5-HT3A receptors were functionally expressed. F107Y mutant 5-HT3A receptors displayed decreased sensitivity to 5-HT compared to the wild type 5-HT3A receptor (P < 0.05). Halothane showed positive modulation in both wild and F107Y mutant 5-HT3A receptors but F107Y mutant 5-HT3 receptor showed greater enhancing modulation comparing to wild-type receptor. Meanwhile, R222F and R222V mutant 5-HT3 receptor lost positive modulation with 1 and 2 MAC of halothane. Most interestingly, positive modulation by halothane was converted into negative modulation in E106D mutant 5-HT3A receptor. CONCLUSIONS: The present study implicate the amino acid residues known for agonist binding and linking agonist binding to channel gating might also have important role for anesthetic modulation in 5-HT3A receptor.
Anesthetics ; Electrodes ; Electrophysiology ; Halothane ; Ligand-Gated Ion Channels ; Oocytes ; Patch-Clamp Techniques ; Receptors, Serotonin, 5-HT3 ; Serotonin ; Xenopus laevis

BACKGROUNDThe mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.

METHODSMedian effective doses (ED(50)) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6 - 10 were cultured for breeding sensitive offspring (S(1)). So did median ones of percentile 48 - 52 for breeding median offspring (M(1)), resistant ones of percentile 91 - 95 for breeding resistant offspring (R(1)). Process was repeated through 31 generations, in the 37th generation, S(37), M(37) and R(37) were used to determine ED(50) for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED(50) values were correlated with minimum alveolar concentration (MAC) values in human.

RESULTSFrom a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED(50) values in three strains correlated directly with MAC values in human.

CONCLUSIONSThree Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED(50) are directly correlated with MAC in human for eight volatile anesthetics.

Anesthetics, Inhalation ; pharmacology ; Animals ; Chloroform ; pharmacology ; Drosophila melanogaster ; drug effects ; growth & development ; Enflurane ; pharmacology ; Female ; Halothane ; pharmacology ; Isoflurane ; analogs & derivatives ; pharmacology ; Male ; Methoxyflurane ; pharmacology ; Methyl Ethers ; pharmacology ; Trichloroethylene ; pharmacology

Halothane, isoflurane and desflurane are metabolized to hepatotoxic trifluoroacetyl proteins. But sevoflurane is metabolized to hexafluoroisopropanol. Hexafluoroisopropanol has a low binding affinity for liver protein and is therefore rapidly converted to glucuronidate that are excreted in the urine. Thus sevoflurane has been considered to have a very low potential for hepatotoxicity. We report a case of a 67 years old woman who developed acute hepatic dysfunction after sevoflurane anesthesia.
Anesthesia ; Female ; Halothane ; Humans ; Isoflurane ; Liver ; Methyl Ethers ; Propanols ; Proteins

Duchenne muscular dystrophy (DMD) is an eventually fatal disorder that is characterized by rapidly progressive muscle weakness and atrophy of muscle tissue. The clinical manifestations of DMD vary depending on the stages of the disease. Succinylcholine-induced hyperkalemia and the administration of volatile anesthetic agents, - particularly halothane, - during acute rhabdomyolysis are more likely to result in cardiac arrest and unsuccessful resuscitation in DMD patients than in the general public. This is a case report of a 10-year-old boy who underwent elective strabismus revision under general anesthesia. Anesthesia was induced and maintained with intravenous propofol and remifentanil, which was started at the targeted effect concentration of 3.0micrometer/ml and 3.5 ng/ml respectively via target controlled infusion (TCI). No inhaled anesthetic was used. In addition, an initial dose 0.4 mg/kg of atracurium was injected intravenously over 15s. The results of this case report found intravenous infusion of propofol, remifentanil and atracurium to be safe because the malignant hyperthermia did not occur.
Anesthesia ; Anesthesia, General ; Anesthetics ; Atracurium ; Atrophy ; Child ; Halothane ; Heart Arrest ; Humans ; Hyperkalemia ; Infusions, Intravenous ; Malignant Hyperthermia ; Muscle Weakness ; Muscles ; Muscular Dystrophy, Duchenne ; Piperidines ; Propofol ; Resuscitation ; Rhabdomyolysis ; Strabismus

OBJECTIVETo explore the application of caffeine-halothane contracture test (CHCT) in the confirmation of malignant hyperthermia (MH).

METHODSOne patient who underwent radical gastrectomy presented with clinical manifestations of MH during routine intravenous-inhalation anesthesia process. Isoflurane inhalation and the operation were ceased immediately and emergency management approaches such as physical cooling therapy were taken. Meanwhile, the levels of serum creatine kinase (CK), serum myoglobin, and urinary myoglobin were examined and rectus abdominis was taken and then CHCT was performed to confirm the clinical diagnosis. Total genome was extracted from the patient and then exons 2-18, 39-46, and 90-104 of ryanodine receptor 1 (RYR1) gene were screened to detect mutations using DNA sequencing technique.

RESULTSThe patient was diagnosed as MH episode by clinical characteristics and postoperatively continuous elevation of the levels of CK, serum myoglobin, and urinary myoglobin (30 times higher than normal level). Despite halothane test was negative, the diagnosis of MH was verified by the positive result of caffeine test. DNA sequencing of RYR1 gene of the patient revealed c. 6724C > T (p. T 2 206M).

CONCLUSIONCHCT can be used to confirm the diagnosis of MH.

Anesthetics, Inhalation ; therapeutic use ; Caffeine ; Creatine Kinase ; blood ; Enzyme-Linked Immunosorbent Assay ; Halothane ; Humans ; Isoflurane ; therapeutic use ; Malignant Hyperthermia ; blood ; diagnosis ; genetics ; Muscle, Skeletal ; drug effects ; physiopathology ; Myoglobin ; blood ; Ryanodine Receptor Calcium Release Channel ; genetics

Ampicillin, a beta-lactam antibiotic, has been reported to induce astrocytic glutamate transporter-1 which plays a crucial role in protecting neurons against glutamate excitotoxicity. We investigated the effect of ampicillin on neuronal damage in the mouse hippocampus and neostriatum following transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery for 40 min. Ampicillin was administered post-ischemically (for 3 days) and/or pre-ischemically (for 3~5 days until one day before the onset of ischemia). Pre- and post-ischemic treatment with ampicillin (50 mg/kg/day or 200 mg/kg/day) prevented ischemic neuronal death in the medial CA1 area of the hippocampus as well as the neostriatum in a dose-dependent manner. In addition, ischemic neuronal damage was reduced by pre-ischemic treatment with ampicillin (200 mg/kg/day). In summary, our results suggest that ampicillin plays a functional role as a chemical preconditioning agent that protects hippocampal neurons from ischemic insult.
Ampicillin ; Animals ; Carotid Artery, Common ; Glutamic Acid ; Halothane ; Hippocampus ; Humans ; Ischemia ; Male ; Mice ; Neostriatum ; Neurons ; Prosencephalon