Hajime Arima

Hyperosmolar Mannitol Stimulates Expression of Aquaporins 4 and 9 through a p38 Mitogen-activated Protein Kinase-dependent Pathway in Rat Astrocytes*

The membrane pore proteins, aquaporins (AQPs), facilitate the osmotically driven passage of water and, in some instances, small solutes. Under hyperosmotic conditions, the expression of some AQPs changes, and some studies have shown that the expression of AQP1 and AQP5 is regulated by MAPKs. However, the mechanisms regulating the expression of AQP4 and AQP9 induced by hyperosmotic stress are poorly understood. In this study, we observed that hyperosmotic stress induced by mannitol increased the expression of AQP4 and AQP9 in cultured rat astrocytes, and intraperitoneal infusion of mannitol increased AQP4 and AQP9 in the rat brain cortex. In addition, a p38 MAPK inhibitor, but not ERK and JNK inhibitors, suppressed their expression in cultured astrocytes. AQPs play important roles in maintaining brain homeostasis. The expression of AQP4 and AQP9 in astrocytes changes after brain ischemia or traumatic injury, and some studies have shown that p38 MAPK in astrocytes is activated under similar conditions. Since mannitol is commonly used to reduce brain edema, understanding the regulation of AQPs and p38 MAPK in astrocytes under hyperosmotic conditions induced with mannitol may lead to a control of water movements and a new treatment for brain edema.

Interleukin‐1β induces the expression of aquaporin‐4 through a nuclear factor‐κB pathway in rat astrocytes

Interleukin (IL)‐1β is known to play a role in the formation of brain edema after various types of injury. Aquaporin (AQP)4 is also reported to be involved in the progression of brain edema. We tested the hypothesis that AQP4 is induced in response to IL‐1β. We found that expression of AQP4 mRNA and protein was significantly up‐regulated by IL‐1β in cultured rat astrocytes, and that intracerebroventricular administration of IL‐1β increased the expression of AQP4 protein in rat brain. The effects of IL‐1β on induction of AQP4 were concentration and time dependent. The effects of IL‐1β on AQP4 were mediated through IL‐1β receptors because they were abolished by co‐incubation with IL‐1 receptor antagonist. It appeared that IL‐1β increased the level of AQP4 mRNA without involvement of de novo protein synthesis because cycloheximide, a protein synthesis inhibitor, did not inhibit the effects of IL‐1β. Inhibition of the nuclear factor‐κB (NF‐κB) pathway blocked the induction of AQP4 by IL‐1β in a concentration‐dependent manner. These findings show that IL‐1β induces expression of AQP4 through a NF‐κB pathway without involvement of de novo protein synthesis in rat astrocytes.

Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes

The water channel protein aquaporin (AQP) may play roles in the homeostasis of water content in the brain and brain edema. One possible mechanism of brain edema is glial swelling due to lactic acidosis associated with ischemia. Here, we investigated the effect of lactic acid on the expression and cellular distribution of AQP 4 in cultured rat astrocytes. After 24h of incubation, the AQP4 expression level increased maximally with 35mM lactic acid. The AQP4 expression levels also increased with hydrochloric acid or acetic acid. In contrast, with sodium lactate, the AQP4 levels did not increase. The increase in AQP4 expression level occurred without a significant increase in AQP4 mRNA expression level by lactic acid. Under the conditions of de novo protein synthesis inhibition with cycloheximide, lactic acid increased the AQP4 expression level. Furthermore, lactic acid increased the AQP4 expression level on the cell surface of the astrocytes, as determined by a cell surface biotinylation assay and immunocytochemical examination. The increase in AQP4 expression level on the cell membrane of astrocytes induced by lactic acid may be a new regulation mechanism of AQP4 in the brain.

Transient and reversible parkinsonism after acute organophosphate poisoning

Parkinsonism is a rare complication in patients with organophosphate poisoning. To date there have been two cases of transient parkinsonism after acute and severe cholinergic crisis, both of which were successfully treated using amantadine, an anti-parkinsonism drug. We report on an 81-year-old woman who was admitted for the treatment of acute severe organophosphate poisoning. Although acute cholinergic crisis was treated successfully with large doses of atropine and 2-pyridine aldoxime methiodide (PAM), extrapyramidal manifestations were noticed on hospital day 6. The neurological symptoms worsened, and the diagnosis of parkinsonism was made by a neurologist on hospital day 9. Immediately, biperiden (5 mg), an anti-parkinsonism drug, was administered intravenously, and her symptoms markedly improved. From the following day, biperiden (5 mg/day) was given intramuscularly for eight days. Subsequently, neurological symptoms did not relapse, and no drugs were required. Our patient is the third case of parkinsonism developing after an acute severe cholinergic crisis and the first case successfully treated with biperiden. Patients should be carefully observed for the presence of neurological signs in this kind of poisoning. If present, an anti-parkinsonism drug should be considered.

Profound pain due to propofol injection triggered myocardial ischemia in a patient with a suspected pheochromocytoma.

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Effect of mild hypothermia on the expression of aquaporin family in cultured rat astrocytes under hypoxic condition

Aquaporins (AQPs) are a family of water-selective transporting proteins with homology to the major intrinsic protein (MIP) of lens, that increase plasma membrane water permeability in secretory and absorptive cells. In this study, we investigated the effect of mild hypothermia on the expression of AQP4, AQP5 and AQP9 in rat astrocytes cultured under hypoxic conditions. At 37 degrees C, a marked decrease in the expression of AQP4, AQP5 and AQP9 mRNAs was observed. However, at 32 degrees C (mild hypothermia), the expression of AQP5 mRNA was restored to its basal level. Interestingly, under mild hypothermia AQP4 mRNA expression transiently decreased and then increased about two-fold; while AQP9 mRNA expression decreased the same as at 37 degrees C. The changes in the expression of AQP4 and AQP9 proteins were confirmed by Western blot analysis. The restoration of the AQP4 and AQP5 expression at 32 degrees C from the hypoxia-induced decrease at 37 degrees C may play an important role in the reduction of brain edema under hypothermic conditions.

Airway obstruction associated with transesophageal echocardiography in a patient with a giant aortic pseudoaneurysm.

IMPLICATIONS Airway compression from insertion of a transesophageal echocardiography (TEE) probe has been mostly limited to pediatric patients. We present a case of TEE-associated airway obstruction in an adult patient undergoing surgery for repair of a giant ascending aortic pseudoaneurysm.

Difficult airway in a child with spinal muscular atrophy type I

Spinal muscular atrophy (SMA) type I is a relatively common inherited neuromuscular disease of hypotonic newborns, but is not associated with craniofacial abnormalities. There is nothing in the literature about difficult intubation in patients affected by this disease. We report a case of 34‐month‐old girl with SMA type I who was scheduled for emergency endoscopic laser treatment of tracheal stenosis caused by granulations. Tracheostomy was performed at 17 months of age and before this, the orotracheal tube was changed periodically without difficulty. For this laser treatment, orotracheal intubation was required. Preoperative physical examination revealed micrognathia and class II malocclusion. Opening her mouth was not difficult. Although difficult orotracheal intubation was predictable, we attempted to intubate her trachea as usual, but could not visualize the epiglottis. We decided to proceed with retrograde intubation, one of the standard techniques employed in a child with a difficult airway, via the tracheostome. A feeding nasogastric catheter was used as a guide catheter, and our strategy was successful. In this study we report a case of difficult airway in a child with SMA type I. The relationship between SMA type I with a tracheostome and difficult airway are discussed.

Ketamine reduces amyloid β-protein degradation by suppressing neprilysin expression in primary cultured astrocytes

Pathological accumulation of cortical amyloid β-protein (Aβ) is an early and consistent feature of Alzheimers disease (AD). Aβ levels in the brain are determined by production and catabolism. Previous studies have suggested that deficits in the brain expression of neprilysin (NEP) and the insulin-degrading enzyme (IDE), which are both proteases involved in amyloid degradation, may promote Aβ deposition in patients with sporadic late-onset AD. Because the incidence of AD increases after surgical intervention, we examined whether ketamine, which is a general anaesthetic with neuroprotective properties for excitotoxic ischaemic damage, is associated with Aβ degradation by inducing NEP and IDE expression. The non-competitive N-methyl-d-aspartate receptor antagonist ketamine and MK801 significantly decreased the expression of NEP, but not IDE, in a concentration- and time-dependent manner through the dephosphorylation of p38 mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Furthermore, NEP-reduced reagents significantly suppressed the degradation of exogenous Aβ in cultured astrocytes. These results suggested that ketamine suppresses the Aβ degradation of NEP by reducing p38 MAPK-mediated pathway activity.

Distorted perception of smell by volatile agents facilitated inhalational induction of anesthesia

Background:  Unpleasant smell of halogenated volatile agents is one of the frustrating factors for inhalational induction. We developed a new modification that might enable children to enjoy the smell itself while incrementally elevating sevoflurane concentration. Troposmia is usually a pathological quality change of smell perception and an olfactory stimulus is distortedly perceived in this state, which we applied to inhalational induction.