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Akio Shigematsu

Publications and source records attributed to Akio Shigematsu.

44 records · Page 3Linked to original sources

Alphaxalone, a neurosteroid anesthetic, inhibits norepinephrine transporter function in cultured bovine adrenal medullary cells.

UNLABELLED: We studied the effects of alphaxalone, a neurosteroid anesthetic, on norepinephrine transporter (NET) function in cultured bovine adrenal medullary cells and the effect of a bolus injection of alphaxalone on blood pressure and serum norepinephrine (NE) levels in anesthetized rats. Alphaxalone (10-100 micro M) inhibited the desipramine-sensitive uptake of [(3)H]-NE by bovine adrenal medullary cells in a concentration-dependent manner. Eadie-Hofstee analysis of [(3)H]-NE uptake showed that alphaxalone increased the apparent Michaelis constant without altering the maximal velocity, indicating that inhibition occurred via competition for the NET. Alphaxalone inhibited the specific binding of [(3)H]-desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [(3)H]-desipramine binding revealed that alphaxalone increased the apparent dissociation constant for binding without altering maximal binding, indicating competitive inhibition. Bolus IV administration of alphaxalone had little effect on blood pressure but slightly, and significantly, increased the serum NE levels in anesthetized rats. These findings suggest that alphaxalone competitively inhibits NET function by interfering with both desipramine binding and NE recognition on the NET in adrenal medullary cells and probably in sympathetic neurons. IMPLICATIONS: Alphaxalone inhibited the desipramine-sensitive uptake of [(3)H]-norepinephrine (NE) by interfering with desipramine binding in bovine adrenal medullary cells. A bolus IV administration of alphaxalone slightly and significantly increased the serum NE levels in anesthetized rats. These findings suggest that alphaxalone competitively inhibits NE transporter function probably in sympathetic neurons.

Adrenal Medulla↗

Thioredoxin is associated with endotoxin tolerance in mice.

OBJECTIVE: Oxidative stress and subsequent lipid peroxidation appear to be central to the lethal effect of lipopolysaccharide. We hypothesized that induction of an antioxidant protein, thioredoxin, would play an important role in the development of endotoxin tolerance and reduce mortality rates in lipopolysaccharide-treated mice. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Adult, male, ddy mice. INTERVENTIONS: In survival-curve experiments, mice were pre-treated intravenously with a low dose of Escherichia coli lipopolysaccharide (20 microg/mouse, pretreatment group) or saline (control group). A large dose of lipopolysaccharide (200 microg/mouse) subsequently was injected into the tail vein 16 hrs after pretreatment. In experiments to measure the expression of thioredoxin after lipopolysaccharide challenge, mice were injected intravenously with different concentrations of lipopolysaccharide (between 20 and 200 microg/mouse, designated the lipopolysaccharide group) or with saline (control group). MEASUREMENTS AND MAIN RESULTS: The survival rate during the 72-hr observation period was significantly higher in the pretreatment group (82%) than in the control group (30%; p = .025 by Mantel-Cox log rank analysis). After lipopolysaccharide challenge, thioredoxin concentrations in the lung, heart, and liver of mice in the pretreated group were about 1.5- to 2-fold higher than those in the control group. Enhancement in these organs became apparent about 6 hrs after lipopolysaccharide challenge and lasted until at least 24 hrs. The levels of accumulation of 4-hydroxy-2-nonenal modified proteins after a large dose of lipopolysaccharide challenge were lower in the pretreatment group than in the control group. CONCLUSIONS: These results demonstrate that mice with an increased concentration of thioredoxin, induced by pretreatment with a low dose of lipopolysaccharide, had increased survival when given a subsequent high-dose challenge of lipopolysaccharide. Thus, thioredoxin is associated with the development of endotoxin tolerance in mice.

Animals↗

Inhibitory effects of ethanol on rat mesangial cell proliferation via protein kinase C pathway.

A large body of evidence has shown that ethanol inhibits the cell growth and cell proliferation in a variety of cell types. However, it has not been studied whether ethanol inhibits the proliferation of mesangial cells (MC) in the kidney. We examined the effects of ethanol on cell proliferation in cultured rat MC. Treatment with ethanol (10-200 mM) for 48 hr inhibited [(3)H]thymidine incorporation into MC in a concentration-dependent manner. The same concentrations of ethanol also inhibited the increase in cell number of MC. GF109203X and chelerythrine chloride, inhibitors for protein kinase C, eliminated the inhibitory effects of ethanol; and protein kinase C activator, PMA, mimicked the effects of ethanol. In contrast, neither the protein kinase A inhibitor H-89 nor the protein kinase G inhibitor KT5823 had any effect. These findings suggest that ethanol has inhibitory effects on the proliferation of MC, probably via activation of the protein kinase C pathway.

Animals↗

[Preliminary report: dissolving effect of 8% lidocaine pump spray on the print mark of the Trachlight wand].

In the use of 8% lidocaine pump spray as a lubricant on the Trachlight wand, its print mark was found to have dissolved. We therefore studied this dissolving effect on the print mark with three different types of lubricant (2% lidocaine jelly, 8% lidocaine pump spray and glycerin). One of these lubricants was painted or sprayed on the wand, and after five minutes the surface was wiped with a swab. Both lidocaine jelly and glycerin showed no effect on the print mark, but when lidocaine spray was used, the mark vanished almost completely. The manufacturer recommends that any topical anesthetics or other active ingredients should not be contained in a lubricant used on the Trachlight wand. We conclude that lidocaine pump spray should not be used as a lubricant on the Trachlight wand.

Intubation↗

Intramuscular tramadol increases gastric pH during anesthesia.

PURPOSE: Tramadol, [(1RS, 2RS)-2-dimethylamino) methyl-1-(3-methoxyphenyl)-cyclohexanol hydrochloride], is an analgesic in clinical use. It has been reported that tramadol inhibits muscarinic type 3 receptor function, which primarily mediates smooth muscle contraction and glandular secretion. We investigated the effects of tramadol on the pH of gastric juices during anesthesia to determine whether tramadol inhibits secretion from the gastric glands. METHODS: ASA physical status I or II adult patients (n = 30) presenting for major elective orthopedic surgery of the upper extremities or mastectomy were enrolled. Patients were randomly assigned to receive treatment with tramadol (n = 10), famotidine (n = 10), or saline (n = 10). General anesthesia was then induced using propofol, vecuronium bromide, and fentanyl. After inducing anesthesia, the gastric pH was measured using pH test paper and, then, 100 mg tramadol, 20 mg famotidine, or saline were injected into the deltoid muscle. Three hours after starting the operation, gastric juice was again aspirated and its gastric pH measured. RESULTS: There were no differences in the pH before anesthesia between the three groups. By contrast, gastric pH was increased in the tramadol group by the same amount as it was in the famotidine group three hours after administering the drugs. Gastric pH of the saline, famotidine, and tramadol groups was 2.6 +/- 2.5, 6.3 +/- 2.0, and 6.4 +/- 0.8, respectively. CONCLUSION: These results suggest that tramadol inhibits the secretion of gastric acid.

Adult↗

The gum elastic bougie eases tracheal intubation while applying cricoid pressure compared to a stylet.

PURPOSE: To compare the ease of tracheal intubation facilitated by the gum elastic bougie or the malleable stylet while applying cricoid pressure. METHODS: Sixty American Society of Anesthesiologists I-III adult patients undergoing elective surgeries participated in this study. After induction of anesthesia with 2.5 mg x kg(-1) propofol and vecuronium 0.1 mg x kg(-1), the laryngeal view was assessed without and with cricoid pressure. Patients were allocated randomly into two groups: a gum elastic bougie or stylet group. One of the two devices was used for tracheal intubation while applying cricoid pressure. The duration and ease of tracheal intubation was recorded. MAIN RESULTS: In 58 patients, the trachea was intubated at the first attempt. In the stylet group, tracheal intubation was difficult and needed more time, especially when the glottic opening was not visible. In the bougie group, the duration and ease of intubation was not influenced by laryngeal view. In the remaining two patients with Cook's modified 3b laryngeal view, it was impossible to intubate the trachea with these devices. CONCLUSIONS: Applying cricoid pressure worsened laryngeal view. The use of a gum elastic bougie was more effective than the use of a stylet to facilitate intubation.

Adult↗