The effect of halothane on the action of alcuronium in the dog

Summary The effect of halothane on the action of alcuronium on neuromuscular transmission was studied in the intact dog. Electrical and mechanical evoked responses from stimulation of the ulnar nerve were recorded. The administration of 0.5% halothane prolonged the duration of action of alcuronium by about 50%.We are indebted to Professor A. Mueller for facilities, help and encouragement. R.S. Jones was the holder of a Royal Society European Exchange Fellowship.     

Influence of ventilatory and circulatory changes on the pharmacokinetics of halothane and isoflurane

In two groups of dogs, uptake and elimination of halothane and isoflurane were studied using a closed-loop anesthesia system which automatically controlled end-tidal halothane or isoflurane partial pressure at minimal alveolar concentration (MAC) equivalent levels. Hemodynamic and respiratory variables were recorded and the anesthetic partial pressure was measured in the inspired and expired air, as well as in the arterial, cerebrovenous and mixed venous blood. Data were recorded during wash-in, hyperventilation, hypercirculation, hypotension and wash-out. For halothane, the controller delivered a higher inspired partial pressure than for isoflurane to compensate for the higher blood/gas partition coefficient. This was especially pronounced during the wash-in and the hypercirculation periods. Smaller differences between halothane and isoflurane partial pressures occurred during hyperventilation, hypotension and the wash-out period and could be explained by the lower solubility of isoflurane. These results show that even under unstable ventilatory and hemodynamic conditions, the inspired concentration of isoflurane has to be adjusted less often and to a smaller degree than that of halothane if end-tidal concentrations are to be maintained constant.     

The effects of naloxone on the analgesic activities of general anaesthetics

Summary Inhaled concentrations of nitrous oxide (80%), halothane (0.5%), trichloroethylene (0.5%) and s.c. ethanol (1 ml/kg) caused similar degrees of excitation and ataxia in mice. Nitrous oxide, tricholoroethylene and ethanol caused analgesia (hot plate and writhing tests), but only that caused by nitrous oxide was antagonized by naloxone (20 mg/kg). Halothane lacked analgesic activity.     

Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane

Adult rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3',5'-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3',5'-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.     

The effect of halothane on in vitro human neutrophil chemotaxis

Summary Increasing concentrations of halothane were shown to sequentially inhibit directed (chemotactic) and random movement of human peripheral blood neutrophils. No influence on neutrophil movement was apparent at clinically important concentrations, halothane may effect neutrophil microtubule and actomyosin microfilament systems.Acknowledgments. We thank Mr Lous Matej for his skillful technical assistance.     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin.

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

Cell-to-cell coupling studied in isolated ventricular cell pairs

Cell pairs isolated from adult rat and guinea pig ventricles were used to study the electrical properties of the nexal membrane. Each cell of a pair was connected to a voltage-clamp system so as to enable whole-cell, tight-seal recording. The current-voltage relationship of the nexal membrane was found to be linear, revealing a resistance rn of 2-4 M omega. rn was insensitive to the sarcolemmal membrane potential (range: -90 to +30 mV), and exerted no time-dependent gating behavior (range: 0.1 to 10 s). Lowering pHi yielded a small increase in rn. Vigorous elevations in [Ca2+]i gave rise to an increase in rn which was associated with a cell shortening. Uncoupling caused by aliphatic alcohols or halothane did not produce cell shortening. Cell pairs were also used to study action potential transfer.     

Der Einfluss von Halothan und Chloroform auf die Feinstruktur und Proteinsynthese der Rattenleber

Summary Examinations by electron microscopic and autoradiographic techniques of whether chloroform and halothane alter protein synthesis in rat liver, demonstrate, that chloroform causes an early destruction of the granular endoplasmatic reticulum accompanied by a marked decrease of the protein synthesis in the centre of the acini. After anaesthesia with halothane, the granular endoplasmatic reticulum and the protein synthesis proved to remain unaffected.     

Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane

Summary Adults rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3,5-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3,5-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.Acknowledgments. This research was supported by Public Health Service Grant NS-14355.     

Inhibition by the enterotoxin of Vibrio cholerase of meiosis reinitiation of the Xenopus laevis oocyte induced in vitro by progesterone]

Progesterone reinitiates in vitro meiosis in Xenopus laevis oocytes. This action of the hormone can be abolished by the exotoxin of vibrio cholerae. The concentration of toxin which inhibits 50% of the progesterone (10 muM) action in about 2.5 pM. Binding experiments using 125I labelled toxin demonstrated the existence of high affinity binding sites (KD approximately 0.2 nM) located probably on the surface of the oocytes.     

The effect of surgery and anesthetic agents on granulocyte-chemiluminescence in whole blood

Summary The effect of anesthesia and major abdominal surgery on zymosan-induced chemiluminescence (CL) of neutrophil granulocytes was evaluated. CL was measured in diluted whole blood taken at distinct intervals within the perioperative period. In addition, blood samples from healthy volunteers were supplemented with ether and halothane to investigate the in vitro effect of these agents. The phagocytosis-induced CL was not found to be depressed by anesthesia and surgery. Only at supranarcotic concentrations was CL reduced. Surgery and anesthesia, therefore, do not appear to impair this defense system significantly under the conditions of this investigation.     

Action of Bacillus thuringiensis preparation against larch bud moth, Zeiraphera diniana (Gn.), enhanced by beta-exotoxin and DDT.

Addition of either DDT or the supernatant of a centrifuged liquid culture of Bacillus thuringiensis, serotype H1, containing beta-exotoxin, enhanced the action of the bacterial preparation Thuricide 90 T against larvae of the larch pest Zeiraphera diniana, increasing mortality from 53% to more than 80%. Since DDT alone produced 57% mortality, its combined action corresponds to independent action. The preparation of beta-exotoxin, on the other hand, had only little effect alone but synergized the action of the bacterial preparation considerably.     

The effect of surgery and anesthetic agents on granulocyte-chemiluminescence in whole blood

The effect of anesthesia and major abdominal surgery on zymosan-induced chemiluminescence (CL) of neutrophil granulocytes was evaluated. CL was measured in diluted whole blood taken at distinct intervals within the perioperative period. In addition, blood samples from healthy volunteers were supplemented with ether and halothane to investigate the in vitro effect of these agents. The phagocytosis-induced CL was not found to be depressed by anesthesia and surgery. Only at supranarcotic concentrations was CL reduced. Surgery and anesthesia, therefore, do not appear to impair this defense system significantly under the conditions of this investigation.     

Cell-to-cell coupling studied in isolated ventricular cell pairs

Summary Cell pairs isolated from adult rat and guinea pig ventricles were used to study the electrical properties of the nexal membrane. Each cell of a pair was connected to a voltage-clamp system so as to enable whole-cell, tight-seal recording. The current-voltage relationship of the nexal membrane was found to be linear, revealing a resistance r_n of 2–4 M. r_n was insensitive to the sarcolemmal membrane potential (range:–90 to +30 mV), and exerted no time-dependent gating behavior (range: 0.1 to 10 s). Lowering pH_i yielded a small increase in r_n. Vigorous elevations in [Ca²⁺]_i gave rise to an increase in r_n which was associated with a cell shortening. Uncoupling caused by aliphatic alcohols or halothane did not produce cell shortening. Cell pairs were also used to study action potential transfer.     

The effects of continuous chloroform and halothane anesthesia on plasma prolactin levels in ovariectomized estrogen-treated rats

Summary In ovariectomized, estrogen-treated rats bearing indwelling aortic catheters, continuous inhalation of chloroform or halothane resulted in increases in plasma prolactin levels 10 min after the exposure to the anesthetics. The plasma prolactin levels over the subsequent 2 h, however, were not significantly different from that of the control animals.Supported by NSF Research Grant BMS 74-17332.The authors wish to express their appreciation to Mrs Cynthia Van De Walle for her outstanding assistance in the performance of the prolactin RIA and the art work.     

Dissolution of the pulmonary collagen of the normal rat by repeated pepsin action]

A non-denaturating method of extracting collagen from Rat lungs was developed. It consists in dissolving the collagen by repeated action of pepsin. Depending on the age of the animal, efficiency values between 50 and 90% are obtained.     

Post-transcriptional gene silencing of ribosomal protein S6 kinase 1 restores insulin action in leucine-treated skeletal muscle

Excessive nutrients, especially amino acids, impair insulin action on glucose metabolism in skeletal muscle. We tested the hypothesis that the branched-chain amino acid leucine reduces acute insulin action in primary myotubes via a negative feedback mechanism involving ribosomal protein S6 kinase 1 (S6K1). The effect of S6K1 on glucose metabolism was determined by applying RNA interference (siRNA). Leucine (5 mM) reduced glucose uptake and incorporation to glycogen by 13% and 22%, respectively, compared to the scramble siRNA-transfected control at the basal level. Leucine also reduced insulin-stimulated Akt phosphorylation, glucose uptake and glucose incorporation to glycogen (39%, 39% and 37%, respectively), and this reduction was restored after S6K1 silencing. Depletion of S6K1 enhanced basal glucose utilization and protected against the development of impaired insulin action, in response to excessive leucine. In conclusion, S6K1 plays an important role in the regulation of insulin action on glucose metabolism in skeletal muscle. Received 22 December 2008; received after revision 19 February 2009; accepted 23 February 2009     

Teratogenic effect of tolbutamide on the development of the sea urchin embryo (Paracentrotus lividus lamarck)

Summary The hypoglycemic agent tolbutamide was tested for its action on the cleavage and differentiation of the sea urchin embryo. Tolbutamide effects a strong selective action on the endoderm which becomes suppressed.     

Role of extracellular matrix molecules in the development of the sodium current in quail mesencephalic neural crest cells

The occurrence of the voltage-dependent sodium current has been studied in developing neurons from quail mesencephalic neural crest on different substrates, using the whole-cell patch clamp technique. Explants from 9–12 somite embryos were cultured on dishes coated with type I collagen, fibronectin, laminin or on plastic dishes in a chemically defined medium. After 18 h of culture the sodium current was observed in 70% of the neurons tested, and at 24 h some of these neurons were able to generate an action potential. After 18–25 h cells grown on fibronectinor collagen I-coated dishes showed a significantly higher occurrence of the sodium current (83% and 84% respectively) as compared to cells grown on uncoated plastic dishes (51%). Moreover, in the presence of fibronectin, the current density of the sodium current was more than doubled in comparison with cells grown on other substrates.