Koshi Makita

Receptor for advanced glycation end-products is a marker of type I lung alveolar cells.

Lung alveolar epithelial cells are comprised of type I (ATI) and type II (ATII) cells. AΤΙ cells are polarized, although they have very flat morphology. The identification of marker proteins for apical and basolateral membranes of ATI cells is important to investigate into the differentiation of ATI cells. In this paper, we characterized receptor for advanced glycation end‐products (RAGE) as a marker for ATI cells. RAGE was localized on basolateral membranes of ATI cells in the immunoelectron microscopy and its expression was enhanced in a parallel manner to the differentiation of ATI cells in vivo and in primary cultures of ATII cells. RAGE and T1α, a well‐known ATI marker protein, were targeted to basolateral and apical membranes, respectively, when expressed in polarized Madine Darby canine kidney cells. Moreover, RAGE was expressed in ATI cells after T1αin vivo and in ex in vivo organ cultures. In conclusion, RAGE is a marker for basolateral membranes of well‐differentiated ATI cells. ATI cells require some signal provided by the in vivo environment to express RAGE.

Using the Intubating Laryngeal Mask Airway (lma-fastrach™) for Blind Endotracheal Intubation in Patients Undergoing Cervical Spine Operation

T he intubating laryngeal mask airway (ILMA; LMA-Fastrach, Laryngeal Mask Company, Ltd., Henley on Thames, UK) has been recently introduced as a prototype of the laryngeal mask airway for blind endotracheal intubation (1–3). It allows for an endotracheal tube (ETT) of up to 8.0-mm inside diameter and does not require head and neck manipulations on insertion. The success rate of blind intubation using the ILMA was up to 99.3% in patients with or without airway problems (3). Therefore, the ILMA might be helpful for endotracheal intubation in patients with cervical spine disease. The purpose of this study was to investigate the utility of the ILMA for blind endotracheal intubation in patients undergoing cervical spine surgery.

Glutamate transporters GLAST and EAAT4 regulate postischemic Purkinje cell death : An in vivo study using a cardiac arrest model in mice lacking GLAST or EAAT4

Cerebellar Purkinje cells represent a group of neurons highly vulnerable to ischemia. Excitotoxicity is thought to be an important pathophysiological mechanism in Purkinje cell death following ischemia. The glutamate transporter is the only mechanism for the removal of glutamate from the extracellular fluid in the brain. Therefore, glutamate transporters are believed to play a critical role in protecting Purkinje cells from ischemia-induced damage. Two distinct glutamate transporters, GLAST and EAAT4, are expressed most abundantly in the cerebellar cortex. GLAST is expressed in Bergmann glia, whereas EAAT4 is concentrated in the perisynaptic regions of Purkinje cell spines. However, the in vivo functional significance of these glial and neuronal glutamate transporters in postischemic Purkinje cell death is largely unknown. To clarify the role of these glutamate transporters in the protection of Purkinje cells after global brain ischemia, we evaluated Purkinje cell loss after cardiac arrest in mice lacking GLAST or EAAT4. We found that Purkinje cells with low EAAT4 expression were selectively lost after cardiac arrest in GLAST mutant mice. This result demonstrates that GLAST plays a role in preventing excitotoxic cerebellar damage after ischemia in concert with EAAT4.

Proteolytic release of the receptor for advanced glycation end products from in vitro and in situ alveolar epithelial cells

Although the receptor for advanced glycation end products (RAGE) has been used as a biological marker of alveolar epithelial cell injury in clinical studies, the mechanism for release of soluble RAGE from lung epithelial cells has not been well studied. Therefore, these studies were designed to determine the mechanism for release of soluble RAGE after lipopolysaccharide (LPS) challenge. For these purposes, alveolar epithelial cells from rat lungs were cultured on Transwell inserts, and LPS was added to the apical side (500 μg/ml) for 16 h on day 7. On day 7, RAGE was expressed predominantly in surfactant protein D-negative cells, and LPS challenge induced release of RAGE into the medium. This response was partially blocked by matrix metalloproteinase (MMP) inhibitors. Transcripts of MMP-3 and MMP-13 were upregulated by LPS, whereas RAGE transcripts did not change. Proteolysis by MMP-3 and MMP-13 resulted in soluble RAGE expression in the bronchoalveolar lavage fluid in the in situ rat lung, and this reaction was inhibited by MMP inhibitors. In human studies, both MMP-3 and -13 antigen levels were significantly correlated with the level of RAGE in pulmonary edema fluid samples. These results support the conclusion that release of RAGE is primarily mediated by proteolytic damage in alveolar epithelial cells in the lung, caused by proteases in acute inflammatory conditions in the distal air spaces.

Endothelin-1 and atrial natriuretic peptide in septic shock

utes are being utilized. 4 Although a recent randomized trial of s tandard and high-dose epinephrine for cardiac arrest outside the hospital failed to reveal a survival advantage for the higher dose protocol, there was a t rend toward improved survival when high-dose epinephrine was administered within 10 minutes after the onset of cardiac arrest, as can be achieved in the catheterizat ion laboratory. 5 There are obvious l imitat ions to this report. I t is not randomized and it is retrospective. The dose of intracoronary epinephrine adminis tered to these pat ients was arbi t rar i ly selected and may not have resulted in the opt imal hemodynamic response. Int racoronary epinephrine was generally selected as a t rea tment of last resort and may have been more effective given earlier during the episode of hypotension. Fur thermore , it was often adminis tered simultaneously with other therapies, and its precise benefit, or even potent ia l harm to pat ients 5 through 8, is impossible to define. However, based on our observations in most pat ients of a rapid increase in arterial blood pressure after the adminis t ra t ion of intracoronary epinephrine, it would seem reasonable to consider its use in cases of refractory hypotension occurring during PTCA when other measures prove ineffective.

Delayed emergence from anesthesia resulting from cerebellar hemorrhage during cervical spine surgery

Cerebellar hemorrhage is an unpredictable complication of spinal surgery. We encountered a case of cerebellar hemorrhage presenting with delayed emergence from anesthesia and hemiplegia after resection of an intradural extramedullar tumor from the cervical spine. Postoperative brain computed tomography revealed hematoma in the cerebellar vermis and right cerebellar hemisphere. The patient made a gradual recovery with conservative treatment. Although the mechanism of cerebellar hemorrhage remains speculative, loss of cerebrospinal fluid may play an important role. Cerebellar hemorrhage must therefore be considered in patients with unexplained neurological deterioration or disturbance on emergence from anesthesia after spinal surgery.

Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine tolerance

Morphine is the drug of choice to treat intractable pain, although prolonged administration often causes undesirable side‐effects including analgesic tolerance. It is speculated that voltage‐dependent Ca2+ channels (VDCCs) play a key role in morphine analgesia and tolerance. To examine the subtype specificity of VDCCs in these processes, we analysed mice lacking N‐type (Cav2.2) or R‐type (Cav2.3) VDCCs. Systemic morphine administration or exposure to warm water swim‐stress, known to induce endogenous opioid release, resulted in greater analgesia in Cav2.3−/− mice than in controls. Moreover, Cav2.3−/− mice showed resistance to morphine tolerance. In contrast, Cav2.2−/− mice showed similar levels of analgesia and tolerance to control mice. Intracerebroventricular (i.c.v.) but not intrathecal (i.t.) administration of morphine reproduced the result of systemic morphine in Cav2.3−/− mice. Furthermore, i.c.v. administration of an R‐type channel blocker potentiated morphine analgesia in wild‐type mice. Thus, the inhibition of R‐type Ca2+ current could lead to high‐efficiency opioid therapy without tolerance.

Plastic Change of N-type Ca Channel Expression after Preconditioning Is Responsible for Prostaglandin E2-induced Long-lasting Allodynia

Background Although considerable evidence indicates neuronal Ca channels play significant roles in pain perception, their possible importance in hypersensitization after acute inflammation has not been investigated. Methods Using carrageenan for inducing hypersensitization, the authors investigated the analgesic effects of intrathecally administered N- and P/Q-type channel blockers, &ohgr;-conotoxin GVIA and &ohgr;-agatoxin IVA, respectively, and also examined the level of N-type channel expression. Results Acute inflammation, produced by carrageenan injection in a rat hind paw, caused mechanical hypersensitivity that resolved within several days. Injection of prostaglandin E2 into the same hind paw after resolution caused a markedly prolonged mechanical allodynia lasting more than 4 h. Similar but less potent prolonged allodynia was also induced in the contralateral hind paws. Intrathecal administration of &ohgr;-conotoxin GVIA (0.03–0.3 &mgr;g) produced dose-dependent inhibition of the allodynia in both control and carrageenan-preconditioned rats. However, the potency of &ohgr;-conotoxin GVIA was significantly lower in carrageenan-preconditioned paws than in those in the contralateral and saline-preconditioned paws. In contrast, &ohgr;-agatoxin IVA (0.01–0.1 &mgr;g) did not reduce the allodynia. Significant up-regulation of N-type channel expression was observed in both dorsal root ganglia and the spinal cord ipsilateral to the carrageenan-preconditioned hind paw. Conclusions The results suggest an aggravating role of the N-type channel in pain sensation and a selective plastic change of this channel expression that could underlie the mechanism of hypersensitization after acute inflammation.

Recovery of post‐tetanic count and train‐of‐four responses at the great toe and thumb

We have studied the recovery of post‐tetanic count and train‐of‐four responses at the great toe and thumb accelerographically after the administration of vecuronium 0.2 mgkg−1. Sixty adult patients scheduled for anaesthesia with nitrous oxide and isoflurane were studied. The times to the return of the first post‐tetanic twitch were comparable at the great toe and thumb (mean (SD) times: 30.0 (6.5) min and 35.0 (8.5) min, respectively). Recovery of post‐tetanic count followed similar time courses at the great toe and thumb. Also, time to the return of the first twitch of the train‐of‐four did not differ significantly at the great toe and thumb (47.5 (9.6) min vs. 49.7 (10.5) min). Similarly, time to the return of the second, third and fourth twitches of the train‐of‐four did not significantly differ at the great toe and the thumb. However, the value of the first twitch of the train‐of‐four, expressed as a proportion of control twitch, was significantly higher than that at the thumb between 50 min and 110 min after the vecuronium injection, and the train‐of‐four ratio at the great toe was significantly higher than that at the thumb between 60 min and 100 min after the vecuronium injection.

Medication errors in anesthesia: an 8-year retrospective analysis at an urban university hospital.

PurposeThe Japanese Society of Anesthesiologists (JSA) has investigated critical events in several fields of anesthesiology. However, the types, frequency, and characteristics of medication errors related to anesthesia have not been investigated. By analyzing incident reports retrospectively, we investigated medication errors that occurred during anesthetic practice over the past 8 years at our institution.MethodsIncident reports related to medication errors that occurred between May 1999 and March 2007 were analyzed retrospectively using a questionnaire published by the JSA in the “Survey of medication errors related to anesthesia”. During these 8 years, 233 incidents were reported, in a total of 27454 anesthesia cases conducted during this period. Of these incidents, 61 (26.2%) were anesthetic drug administration errors. In these 61 incidents, clerical error (e.g., erroneous prescription writing), and pre-error (defined as any incident with the potential to become an error) were excluded from the analysis. Consequently, 13 incidents were excluded and 48 incidents were analyzed.ResultsMedication errors due to overdose were the most frequent kind of error (25%), followed by substitution (23%), and omission (21%). Errors due to an incorrect route of administration were rare. The drugs most frequently involved in these errors were antibiotics and muscle relaxants. Most of the patients involved in the incidents were, fortunately, not harmed seriously. The total frequency of medication errors in the survey period was 0.175% (48 incidents in 27 454 total anesthesia cases).ConclusionWe found that overdose, substitution, and omission were the main causes of anesthesia-related medication errors in our department.