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Biomedical subjects

N Aikawa

Publications and source records attributed to N Aikawa.

At least 37 records · Page 2Linked to original sources
PubMed2000

Importance of interleukin-8 in the development of reexpansion lung injury in rabbits.

Reexpansion of a collapsed lung induces increased microvascular permeability leading to reexpansion pulmonary edema (REPE). This study was designed to prove the hypothesis that local overproduction of interleukin-8 (IL-8) induces inflammatory cell accumulation which leads to the induction of REPE. Initially, we examined the detailed characteristics of a rabbit model of REPE in association with IL-8 production and its mRNA expression. The lung tissue to plasma ratio of radiolabeled albumin (T/P ratio), the lung wet to dry ratio, and bronchoalveolar lavage (BAL) neutrophil counts were significantly increased in the reexpanded lung. IL-8 concentrations and mRNA expression were significantly increased in the reexpanded lung homogenate. Immunohistochemically, alveolar macrophages (AMs) and epithelial cells in the reexpanded lung and AMs in the collapsed lung were positive for IL-8. Second, we examined the effect of pretreatment with a specific monoclonal anti-IL-8 antibody (Ab) or control IgG on the development of REPE. The T/P ratio and BAL neutrophil counts were conspicuously decreased by pretreatment with anti-IL-8 Ab, but not with control IgG. On a histopathological study, lung injury and leukocyte infiltration were attenuated by the pretreatment with anti-IL-8 Ab. In conclusion, IL-8 production is enhanced in the reexpanded lung, and contributes to the development of REPE. The pretreatment with anti-IL-8 antibody may be useful as a novel protective therapy for this disease.

Animals↗
PubMed2000

The effect of zaldaride maleate, an antidiarrheal compound, on acetylcholine-induced intestinal electrolyte secretion.

The effect of zaldaride on acetylcholine-induced colonic electrolyte secretion was examined. The short-circuit current response to acetylcholine was partially reduced by tetrodotoxin, a neuronal blocker, and was completely inhibited by atropine, an acetylcholine M receptor antagonist, in the rat colonic preparations. The tetrodotoxin sensitive effect was significantly inhibited by zaldaride, whereas the tetrodotoxin insensitive effect was not affected. Acetylcholine release from synaptosomes of submucosal nerves of guinea-pig colon was significantly reduced by zaldaride. Zaldaride may reduce colonic electrolyte secretion by acetylcholine due to the inhibition of acetylcholine release from synaptosomes of colonic submucosal nerves.

Acetylcholine↗
PubMed2000

Gender differences in the antidiarrheal effect of zaldaride maleate in rats.

The amelioration of secretory diarrhea has been reported after the administration of zaldaride maleate (ZAL), a selective calmodulin inhibitor, to male rodents. In this study, the antidiarrheal effect of ZAL in female rats was compared with that in male rats. In female and male rats, ZAL significantly ameliorated 16,16-dimethyl prostaglandin E2-induced diarrhea at doses of 1 and 3 mg/kg (p.o.), respectively, with ID50 values of 0.7 mg/kg (p.o.) in the females and 10.3 mg/kg (p.o.) in males. In castor oil-induced diarrhea, ZAL also significantly reduced the incidence of diarrhea in female and male rats at doses of 10 and 30 mg/kg (p.o.), respectively. When the same dose of ZAL was given orally to female and male rats, the maximum plasma level of this compound was approximately 3 times higher in female rats than in male rats. In contrast, after intravenous administration of the same dose of ZAL to female and male rats, the total clearance of this compound was similar. In an Ussing chamber experiment, the inhibitory action of ZAL on vasoactive intestinal polypeptide-induced ion secretion in the colon showed no difference between female and male rats. In conclusion, the antidiarrheal effect of ZAL in female rats is more potent than that in males, and could be due to the difference in plasma levels of this compound between female and male rats after oral administration.

16,16-Dimethylprostaglandin E2↗
PubMed2000

Comparison of the antidiarrheal effects of zaldaride maleate and its optical isomers in rats.

Zaldaride maleate (ZAL), a calmodulin inhibitor, that ameliorates secretory diarrhea in rodents, has a racemic structure. In this study, we compared the antidiarrheal and antisecretory effects of ZAL and its optical isomers, R(-)-isomer and S(+)-isomer, in rats. In Ussing chamber experiments, the inhibitory action of ZAL on acetylcholine-induced ion transport in the rat colonic mucosa was equipotent for both optical isomers, with IC50 values of approximately 3--4 micromol/l. In castor-oil-induced diarrhea, ZAL and its S(+)-isomer inhibited the incidence of diarrhea, whereas the R(-)-isomer had no effect. In 16,16-dimethyl prostaglandin E2-induced diarrhea, ZAL, the S(+)-isomer and the R(-)-isomer significantly ameliorated diarrhea at doses of 30, 10 and 30 mg/kg (p.o.), respectively; the ED50 values were 25, 10 and above 30 mg/kg (p.o.), respectively. The pharmacokinetic parameters after administration of 30 mg/kg (p.o.) of each compound were as follows: ZAL (Cmax: 378 ng/ml, AUC0-12: 1650 ng-h/ml); S(+)-isomer (Cmax: 565 ng/ml, AUC0-12: 2230 ng-h/ml) and R(-)-isomer (Cmax: 271 ng/ml, AUC0-12: 613 ng-h/ml) (mean, N=4). In conclusion, despite the fact that the antisecretory actions of ZAL and its optical isomers are the same, the antidiarrheal actions of ZAL and its S(+)-isomer are more potent than that of the R(-)-isomer. The antidiarrheal actions of ZAL and its optical isomers may be related to plasma levels.

Animals↗
PubMed2000

Effect of zaldaride maleate, an antidiarrheal compound, on fecal pellet output induced by hyperpropulsion in gastrointestine of rats.

The effect of zaldaride, a calmodulin inhibitor, on fecal pellet output in rats was compared with that of loperamide, an antidiarrheal drug. 5-Hydroxytryptamine (10 mg/kg, s.c.), neostigmine (0.3 mg/kg, s.c.) and nicotine (1.0 mg/kg, s.c.) increased fecal pellet output. Zaldaride (> or = 30 mg/kg, p.o.) reduced these increases in fecal pellet outputs. Loperamide (10 mg/kg, p.o.) inhibited fecal pellet output induced by 5-hydroxytryptamine and neostigmine but not nicotine. Under normal conditions, zaldaride and loperamide did not affect fecal pellet output at doses used in these studies. In conclusion, zaldaride may inhibit increases in fecal pellet output induced by hyperpropulsion of the gastrointestinal tract without causing constipation as a side effect.

Animals↗
PubMed2000

Effect of zaldaride maleate, an antidiarrheal compound, on 16,16-dimethyl prostaglandin E2-induced intestinal ion secretion in rats.

The effect of zaldaride, a calmodulin inhibitor, on 16,16-dimethyl prostaglandin E2 (dmPGE2)-induced intestinal ion secretion was investigated in rats. Zaldaride inhibited the dmPGE2-induced increase in water content in the colon, but not that in the small intestine. In the colonic mucosa, zaldaride attenuated the dmPGE2-induced short-circuit current; however, it did not affect the forskolin or dibutyryl cAMP-induced effect. These results suggest that zaldaride inhibits dmPGE2-induced intestinal ion secretion by reducing the activity of Ca2+/calmodulin-dependent adenylate cyclase linked to a receptor, and the colon may be an important site in the action of zaldaride.

16,16-Dimethylprostaglandin E2↗
PubMed2000

Effects of zaldaride maleate, an antidiarrheal compound, on intracellular Ca2+-mediated short-circuit current response in the rat colonic mucosa.

The effect of zaldaride maleate (ZAL) on intracellular Ca2+-mediated short-circuit current (Isc) response in rat colonic mucosa was investigated. The Isc response to acetylcholine was partially reduced by the neuronal blocker tetrodotoxin. The tetrodotoxin-sensitive Isc response to acetylcholine was inhibited by ZAL. The tetrodotoxin-insensitive effect, which indicates direct stimulation of acetylcholine in colonic mucosa, was not affected by ZAL. The Isc response to the Ca2+ ionophore A23187 was reduced by ZAL in the presence of tetrodotoxin. These results suggest that ZAL reduces colonic ion secretion by inhibiting a tetrodotoxin-sensitive neuronal pathway and an intracellular Ca2+ pathway in epithelium.

Acetylcholine↗
PubMed2000

Diagnostic value of a bedside test for cardiac troponin T in the patient with chest pain presenting to the emergency room.

Identification of patients with acute chest pain due to acute coronary syndrome is a common and difficult challenge for emergency physicians. A prospective study was conducted to assess the diagnostic value of a bedside test of cardiac troponin T in the emergency room setting. Forty-nine consecutive patients, who visited the emergency room within 6 hours of the onset of acute chest pain, were enrolled. Of the 26 patients who were ultimately diagnosed as having acute coronary syndrome, seven patients (27%) had positive cardiac troponin T assay results, whereas none of the patients without acute coronary syndrome had positive results (0%). For patients with acute coronary syndrome who presented later than 3 hours after the onset (n = 4), the test was positive in all cases (positive predictive value: 100%, negative predictive value: 100%, p < 0.01). However, the positive rate was only 14% for those who presented earlier than 3 hours after the onset (n = 22) (positive predictive value: 100%, negative predictive value: 47%, p = 0.84). In conclusion, bedside troponin T test results should be evaluated considering the time interval from the onset of chest symptoms.

Adult↗
PubMed2000

A 35-year-old man with cerebral hemorrhage and pheochromocytoma: the second brain-dead organ donor in Japan.

A 35-year-old man was brought into the emergency room of Keio University Hospital by ambulance because of a sudden onset of coma. His Glasgow Coma Scale was 3 and his blood pressure 150/100 mmHg. CT scanning revealed a subcortical hemorrhage 8 cm in diameter. His respiration deteriorated rapidly, and an emergency craniotomy was performed for hematoma removal and cerebral decompression. Postoperatively the patient remained in a deep coma (GCS = 3) requiring respiratory support. The family presented an organ donor card previously signed by the patient, and brain death was confirmed in accordance with Japan's transplant law. As a result of two tests conducted six hours apart brain death was confirmed on the 5th postoperative day. With the family's consent, the donor's heart, kidneys and skin were removed for organ transplantation to be performed in other institutions. An autopsy was performed after the removal of the organs and skin. An extensive subgaleal hemorrhage was found in the left cerebral hemisphere, and microscopic examination revealed extensive necrosis with karyolysis of neuronal cells, but no viable neuronal cells were found in the cerebrum. The brain stem was marked by edema, hemorrhage, infarction necrosis and neuronal cell loss. The cerebellum was swollen and congested and showed autolysis of the granular layer. These findings suggested brain death syndrome with respirator brain. Other autopsy findings included a huge pheochromocytoma in the right adrenal gland, bilateral bronchopneumonia, liver congestion and fatty metamorphosis with four cavernous hemangiomas, and mild chronic lymphocytic thyroiditis. This patient was the second brain-dead organ donor and the first brain-dead patient to undergo postmortem examination in Japan.

Adrenal Gland Neoplasms↗
PubMed2000

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1997 and March 1998].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 19 facilities in Japan since July 1982. This paper describes the results obtained during the period from April 1997 to March 1998. The number of cases investigated as objectives was 215 for one year. A total of 420 strains (170 strains from primary infections and 250 strains from postoperative infections) were isolated from 174 cases (80.9% of total cases). In primary infections, the isolation rate of anaerobic bacteria was higher than in postoperative infections, while in postoperative infections, those of aerobic Gram-positive bacteria and Pseudomonas aeruginosa were higher than in primary infections. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus, which was frequently isolated from postoperative infections. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by P. aeruginosa, Klebsiella pneumoniae in this order, and from postoperative infections, P. aeruginosa was most predominantly isolated, followed by E. coli and K. pneumoniae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. We found neither vancomycin nor arbekacin resistant strains of S. aureus, and found no vancomycin resistant strains of Enterococcus spp. The susceptibility of P. aeruginosa against carbapenems did not decline in the year 1997, while resistance of B. fragilis group against cephems advanced increasingly.

Anti-Bacterial Agents↗
PubMed1999

A case of traumatic shock complicated by methamphetamine intoxication.

A case of a 38-year-old male with traumatic shock complicated by methamphetamine intoxication is presented. The patient was involved in an assault which resulted in cardiac tamponade and right ventricular outflow laceration. Pericardiocentesis was immediately performed. However, profound metabolic acidosis greatly in excess of that expected from the short duration of the shock was revealed by arterial blood gas analysis. Another cause of the metabolic acidosis was suspected. The patient subsequently admitted to intravenous use of methamphetamine. Following hemodynamic and metabolic stabilization by continuous pericardial drainage and intravenous administration of sodium bicarbonate, the patient underwent cardiac surgery. His postoperative course was uneventful. There is a substantial association between methamphetamine users and traumatic accidents. In such cases, early identification of drug use is important. Marked metabolic acidosis, which conflicts with the diagnosed cause of shock, may be a clinical clue to methamphetamine intoxication.

Acidosis↗
PubMed1999

Effect of zaldaride maleate, an antidiarrheal compound, on visceral pain reflex induced by small intestinal distention in anesthetized rats.

Using distention of the small intestine as a visceral pain model, we investigated the effect of zaldaride maleate (ZAL), a selective inhibitor of calmodulin, on the depressor response. In pentobarbital-anesthetized rats, small intestine distention was induced by rapid application of intraluminal pressures of 40 cmH2O causing a reflex fall in arterial blood pressure. The depressor response to intestinal distention was abolished by intraperitoneal administration of capsaicin (5 mg/rat), which depletes neuropeptides such as substance P from the sensory neurons, on the mesenteric stalk and by neonatal pretreatment with capsaicin (50 mg/kg, s.c.). Morphine (20 mg/kg, s.c.) reduced the depressor response following intestinal distention. At doses of 3 mg/kg (i.v.) and higher, ZAL significantly reduced depressor response. The effect of morphine was reversed by naloxone (5 mg/kg, i.v.); the effect of ZAL was not affected. These results suggest that ZAL helps reduce the visceral pain induced by noxious stimulus and that the antinociceptive effect of ZAL is not mediated by opioid receptors.

Adrenergic alpha-Antagonists↗
PubMed1999

Antidiarrheal effects of zaldaride maleate after oral, intravenous and subcutaneous administration to rats.

The antidiarrheal action of zaldaride maleate (ZAL) after oral, intravenous and subcutaneous administration was examined to determine whether ZAL acts systemically or locally in the intestine of rats. Oral administration of ZAL inhibited castor oil- and 16,16-dimethyl prostaglandin E2-induced diarrhea; however, intravenous or subcutaneous administration of ZAL was ineffective. When ZAL was orally administered, the area under the plasma concentration time curve of the compound was lower than that of ZAL following intravenous or subcutaneous administration at the maximum doses studied. The antidiarrheal effect of ZAL was not dependent on its plasma concentration level. These results suggest that ZAL acts locally in the intestinal tract in rats.

16,16-Dimethylprostaglandin E2↗
PubMed1999

The natural history of the systemic inflammatory response syndrome and the evaluation of SIRS criteria as a predictor of severity in patients hospitalized through emergency services.

Based on the concept of the systemic inflammatory response syndrome (SIRS), a one-year retrospective study was carried out among a total of 2389 patients transported to the emergency room by ambulance. With respect to 351 patients who had all data necessary for evaluating SIRS criteria in 369 hospitalized patients, 200 met SIRS criteria within 24 hours of admission (24h-SIRS). The mortality rate for 24h-SIRS patients was significantly higher than that of non-SIRS patients. The mortality rate for 24h-SIRS patients increased sequentially as more SIRS criteria were met. In 235 patients who met SIRS criteria during hospitalization (overall-SIRS), 108 had sepsis. Of these, 60 developed severe sepsis, and 50 developed septic shock. The mortality rate for patients who had 3 or more consecutive days of SIRS was significantly higher than that for those with less than 3 consecutive SIRS days. Among 153 patients who had all data necessary for APACHEIII scoring within 24 hours of admission, the mortality rate for SIRS patients whose APACHEIII score was 50 or higher was 40.7%, significantly higher than that of other patients. In conclusion, SIRS criteria were demonstrated to be useful as indicators of severity and for predicting outcome in patients hospitalized through emergency services. Patients who met the following criteria were found to be a high-risk population among hospitalized emergency patients with SIRS: (1) Those who had three or more consecutive days of SIRS. (2) Those whose APACHEIII score was 50 or higher.

Adolescent↗
PubMed1999

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents: special references to bacteria isolated between July 1996 and June 1997].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 20 facilities in Japan since July 1982. This paper describes the results obtained during period from July 1996 to June 1997. The number of cases investigated as objectives was 217 for one year. A total of 406 strains were isolated from 177 cases (81.6% of total cases). From primary infections 162 strains were isolated, and from postoperative infections 244 strains were isolated, respectively. From primary infections, anaerobic bacteria were predominant, while from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was the highest. In postoperative infections, the majority of them were Enterococcus faecalis, while in primary infections, many of them were Enterococcus avium. The isolation rate of Staphylococcus spp., especially from postoperative infections, followed that of Enterococcus spp. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli and Enterobacter cloacae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. The isolation rate of aerobic Gram-negative bacillus has decreased with time, while those of anaerobes like B. fragilis group and of aerobic Gram-positive bacteria have gradually increased in both types of infections. We found vancomycin-resistant strains of neither Staphylacoccus aureus nor Enterococcus spp.; however, the MIC of arbekacin for one of strains of S. aureus was 100 micrograms/ml. Both the MIC90's of meropenem and imipenem/cilastatin against P. aeruginosa isolated in this term were 25 micrograms/ml, which were higher than those against the strains isolated in the previous years. Compared with the isolated strains in the year 1995, progress of resistance against carbapenem antibiotics was confirmed.

Anti-Bacterial Agents↗
PubMed1999

[Recent advances in the management of severely burned patients].

With recent advances in the systemic care of burns, patients with burns covering 80% of their body surface can frequently survive. The percentage of total body surface area burn for an expected 50% mortality rate has improved to 98% for children and 72% for adults in one burn center in the USA. From the results of 11 burn units in Tokyo, the mortality rate of burn patients with a prognostic burn index of 90-100 was 51.4%. The improvement is attributable to advances in the understanding of the pathophysiology of severe burns as a systemic inflammatory response syndrome. Improved cardiopulmonary management of extensive burns and respiratory tract burns has also played a part in reducing the mortality rate. Individualized fluid resuscitation programs based on hemodynamic monitoring have reduced the incidence of burn shock and acute renal failure. Early eschar excision and wound closure by immediate grafting have further reduced the mortality rate from extensive full-thickness burns. The use of bilayer artificial skin has improved the survival and cosmetic results of early eschar excision in patients with massive full-thickness burns. Cultured autologous epidermal sheets hold promise if used on an appropriate dermal bed.

Adolescent↗