Lysophosphatidic acid protects against acetaminophen-induced acute liver injury

We investigated the effect of lysophosphatidic acid (LPA) in experimental acetaminophen (APAP)-induced acute liver injury. LPA administration significantly reduced APAP-challenged acute liver injury, showing attenuated liver damage, liver cell death and aspartate aminotransferase and alanine aminotransferase levels. APAP overdose-induced mortality was also significantly decreased by LPA administration. Regarding the mechanism involved in LPA-induced protection against acute liver injury, LPA administration significantly increased the glutathione level, which was markedly decreased in APAP challenge-induced acute liver injury. LPA administration also strongly blocked the APAP challenge-elicited phosphorylation of JNK, ERK and GSK3β, which are involved in the pathogenesis of acute liver injury. Furthermore, LPA administration decreased the production of TNF-α and IL-1β in an experimental drug-induced liver injury animal model. Mouse primary hepatocytes express LPA₁(,)₃–₆, and injection of the LPA receptor antagonist KI16425 (an LPA₁(,)₃-selective inhibitor) or H2L 5765834 (an LPA₁(,)₃(,)₅-selective inhibitor) did not reverse the LPA-induced protective effects against acute liver injury. The therapeutic administration of LPA also blocked APAP-induced liver damage, leading to an increased survival rate. Collectively, these results indicate that the well-known bioactive lipid LPA can block the pathogenesis of APAP-induced acute liver injury by increasing the glutathione level but decreasing inflammatory cytokines in an LPA₁(,)₃(,)₅-independent manner. Our results suggest that LPA might be an important therapeutic agent for drug-induced liver injury.

The immune-stimulating peptide WKYMVm has therapeutic effects against ulcerative colitis

In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW, indicating the crucial role of FPR2 in this effect. Mechanistically, WKYMVm effectively decreases intestinal permeability by stimulating colon epithelial cell proliferation. WKYMVm also strongly decreases interleukin-23 and transforming growth factor-beta production in the colon of DSS-treated mice. We suggest that the potent immune-modulating peptide WKYMVm and its receptor FPR2 may be useful in the development of efficient therapeutic agents against chronic intestinal inflammatory diseases.

Changes in Hemodynamics and Plasma Catecholamine Levels following Midazolam Premedication / 대한마취과학회지

The present study atternpted. to expiore the new benzodiazepine, midazolam, which is water-soluble, shorter-acting, more potent, and less irritating to inject than diazepam, and which has been used as premedication before induction of anesthesia in various elective surgeries. Forty patients (aged 20 to 50 and in ASA class I or II ) about to undergo simple elective surgery under general anesthesia entered the study. The patients were divided into the study group (n=20) that recieved 0.07 mg/Kg i.m midazolan premedication and the control group (n= 20) that recieved normal saline as sham premedication. The changes in the values of various hemodynamic parameters, i.e., heart rate and systolic, diastolic, mean arterial pressures, were monitored first before tracheal intubation, then at the time of intubation and 5, 10 and 30 minutes after intubation. The concentrations of plasma catecholamines i.e., epinephrine and norepinephrine, were measured before intubation and 5, 30 minutes after intubation. Systolic pressure and plasma epinephrine concentration before induction was significantly low in the study compared with the controls. At the time of intubation, sytolic, diastolic & mean arterial pressures were significantly low in the study group compared with the controls. Heart rates measured at 10 and 30 minutes postintubation were significantly low at 30 minutes postintubation in the study group compared with the controls as was plasma epinephrine levels at each instance of its measurement. In conclusion, midazolam-premedicated patients appear to maintain stable hemodynamies and plasma catecholamine levels. Our findings support that midazolam premedication effectively reduces stress response during induction period making it suitable induction for elective surgery.

Evaluation of Pulmonary Ventiation Effects about pH , ( a-Et )PCO2 , K+ between Normal and Hyperventilation with Capnometric Control / 대한마취과학회지

Capnometer has been used in anesthesia for the evaluation of pulmonary ventilation because of its nonivasive and continuous monitoring advantges. We studied pulmonary ventilation effects with arterial blood gas parameter between normoventilation and hyperventilation with capnometric control during 1 hr duration. We devided two group. Control group was maintained PetCO2 38 mmHg and experimental group PetCO2 28 mmHg and four times arterial blood gas sample were done. The results were as follows. 1) Serum K+ concentration was decreased siginifcantly in hyperventilation group. 2) Arterial pH changes were observed respiratory alkalosis in experimental group and respiratory acidosis in control group. 3) (a-t)PCO2 differnce were increased in both group and especially control group with correlation of time duration. 4) No arrhythmia were detected in both group. We conclude that only capnometric control of pulmonary ventilation is not suffieient and it has to be combined periodic ABGS and resetting of ventilation mode.

A Clinical Study of Geriatric Anesthesia / 대한마취과학회지

It is widely believed that, compared with younger patients, elderly having surgery have a significantly high incidence of complications or death. So, we reviewed clinical records of 2094 patients aged over 65 out of 41,129 surgical cases performed at Catholic University Kang-Nam St. Mary Hospital from May 1980 to December 1989. The case were analysed statistically according to age, sex, department, preoperative physical status, operation site, anesthetic techniques and agents, duration of anesthesia, intraoperative transfusion, intraoperative complication, asaociated disease, postoperative complication and mor- tality. The results were as follows: 1) Of the total 41, 129 cases, 2,094 cases (5.1%) were over 65 years of age consisting of 1,039 male (49.6%) and 1,055 female (50.4%). 2) The most common age group for geriatric anesthesia (1, 164 cases) was 65~70 years of age (55.6%). 3) The rate of elective and emergency surgery was 90.2% (1,889 cases) and 9.8% (205 caaes). 4) Among the 2,094 cases, 1.029 cases were general surgry (49.1%), 373 cases were orthopedic surgery (20.7%) 5) The number of upper abdominal surgery cases were 643 cases (30.7%) and the number of lower abdominal surgery cases 433 cases (20. 7%). 6) The duration of anesthesia was within 1 hour in 286 case (13.1%), 1~2 hours in 755 cases (36.1%), 2~3 hours in 516 cases (24.6%). 7) The technique of anesthesia was done under the general anesthesia for 1,445 cases (69.0%) and epidural anesthesia for 433 cases (20.7%). 8) The anesthetics were halothane for 631 cases (30.1%), enflurane for 435 cases (20.8%) and fentanyl for 364 eases (17.8%), lidocaine and bupivacaine mixture for 254 cases (12.1%). 9) Among the 2.094 cases, 1,471 cases had preoperative disease (70.3%), which of the most common disease (24.1%) was the chronic obstructive pulmonary disease (545 cases). 10) The numbers of postoperative death were 40 cases (1.9%).

The Effect of Sodium Nitroprusside - Induced Hypotension on Plasma Renin Activity and Serum Aldosterone Level / 대한마취과학회지

The renin-angiotensin system plays an important role in maintaining blood pressure in various pathologic and physiologic states. To investigate the effects of the sodium nitroprusside (SNP)-induced hypotension on plasma renin activity and serum aldosterone level, SNP 2.0 mg/kg/min was infused to seven unanesthetized rabbits. The mean arterial pressure and heart rate were measured three times; at the start of, 15 and 30 minutes after SNP inusion and 30 minutes after the discontinuation of SNP infusion. The measurement of the plasma renin activity and the serum aldosterone levels during SNP infusion were done by means of radioimmunoassay. The results were as follows: 1) The mean arterial pressure was 117.6+/-6.9 mmHg at zero time ans decreased significantly to 84.0+/-19.6mmHg and 72.9+/-21.6mmHg at 15 and 30 minutes after SNP infusion, respectiely(P<0.01). 2) The heart rate was 124.8+/-9.3 beats/min at zero time and increased significantly to 139.7+/-6.4 beats/minute and 155.6+/-7.9 beats at 15 and 30 minutes after SNP infusion, respectively(P<0.05). 3) The plasma renin activity was 2.31+/-0.53 ng/ml/hr at zero time and increased significantly to 5.17+/-1.39 ng/ml/hr and 4.97+/-1.52 ng/ml/hr in 15 and 30 minutes after SNP infusion, respectively. 4) The serum aldosterone level was 28.8+/-13.5ng/dl at zero time and increased to 42.3+/-14.6ng/dl and 39.5+/-13.9ng/dl at 15 and 30 minutes after SNP infusion and it continued to increase up to 30 minutes after discontinuation of SNP infusion. In conclusion, it was postulated that the plasma renin activity and serum aldosterone level were closely related to the change of the mean arterial pressure and heart rate during SNP-induced hypotension.

Clinical Evaluation of the Neruomuscular Blocking Effect of Isoflurane / 대한마취과학회지

Isoflurane, which has only recently been introduced into clinical practice, is a nonflammable halogenated ether used as an inhalation anesthetic. It has pharmacological, physical, and clinical properties similar to those of halothane and enflurane: however, it differs from botn in several important aspecs. The potent neuromuscular blocking action of sioflurane in desirable, because it reduces the requirement for muscle relaxants and allows lower doses of anesthesis. To quantitatively clarify the neuromuscular blocking effect of isoflurane, neuromuscular function was monitored by "Train of Four" stimulus with and without administration of muscle relaxants under halothane and isoflurane anesthesis, respectively, in 60 patients. The patients were divided into 4 groups(halothane anesthesia without muscle relaxants, halothane anesthesis with muscle relaxants, isoflurane anesthesia without muscle relaxants and isoflurane anesthesia with muscle relaxants). Twich responses of thenar muscle were monitored and analysed for the value of maximaum twich depression by halothane and isoflurane anesthesia, respectively, and the onset time, degree of maximal neuromuscular blockade, duration of action and recovery index of pnscuronium bromide under halothane and isoflurane anesthesia, respectively. The results were as follows: 1) Isoflurane exhibited a neuromuscular blocking effect 2,3 times more potent than halothane. 2) Neuromuscular depression by halothane and isoflurane was not accompanied by "fade". 3) The recovery time from nuromuscular blockade by succinylcholine in isoflurane anesthesia was increased significantly compared with halothane anesthesia. 4) The duration of action and the recovery index were increased significantly in isoflurane anesthesia compared with halothane anesthesia.

The Neuromuscular Responses of Atracurium in Myasthenia Patieats / 대한마취과학회지

Myasthenia gravis is now considered as one of autoimmune disease eintities and characterized by progressive muscle weakness upon exertion and high sensitivity to the motor end plate. Special considerations are required in the anesthetic management of the myasthenic patient undergoing surgery under general anesthesia. The myasthenic patient is generally highly sensitve to non-depolarising agents and resistant to depolarizing agents. it is advisable to avoid the non-depolarzing agents or use only small dose during anesthesia, if neccessary. Atractrium is an intermediate acting bisquatenary ammonium compound and it's effects are well dissipated by hofmann elimination and ester hydrolysis. We have had myasthenic patient undergo thymectomy. Muscle relaxation was obtained by using a small dose of atracurium during anesthesia. Patient's perianesthetic course was not remarkable except slow spontaneous recovery, but it was well reversed by anticholinesterase.

Anesthetic Management for a Patient with a Silicon Tracheal T-tube / 대한마취과학회지

The silicon tracheal T-tube was designed to maintain an adequate tracheal airway as well as to provide support in the stenotic trachea which has been reconstructed. Replacement of the T-tube was obviously undesirable following recent reconstruction of an unstable fracture of the airway. The loss of anesthetic gas through a T-tube while it is in place during anesthesia has been a problem. This report describes a simple method of establishing a satisfactory airway in a patient with a tracheal T-tube, and reviews the anesthesia aspects of modern surgical reconstruction of the larynx and cervical traches.