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Biomedical subjects

N Shimada

Publications and source records attributed to N Shimada.

At least 109 records · Page 6Linked to original sources
PubMed1999

Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes.

Azelastine, an antiallergy and antiasthmatic drug, has been reported to be metabolized mainly to desmethylazelastine and 6-hydroxyazelastine in mammals. In the present study, the inhibitory effects of azelastine and its two metabolites on human cytochrome P-450 (CYP) isoform-dependent reactions were investigated to predict the drug interactions of azelastine using microsomes from human B-lymphoblast cells expressing CYP. The specific activities for human CYP isoforms included: 7-ethoxyresorufin O-deethylation (CYP1A1), phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), 7-benzyloxyresorufin O-dealkylation (CYP2B6), S-warfarin 7-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and testosterone 6beta-hydroxylation (CYP3A4). In almost all the activities, desmethylazelastine exhibited stronger inhibition than azelastine and 6-hydroxyazelastine. Desmethylazelastine, but not azelastine and 6-hydroxyazelastine, uncompetitively inhibited CYP2B6 activity (Ki = 32.6 +/- 4.8 microM). Azelastine, desmethylazelastine, and 6-hydroxyazelastine competitively inhibited CYP2C9 activity (Ki = 13. 9 +/- 1.8, 15.0 +/- 3.1, and 17.0 +/- 4.1 microM, respectively), CYP2C19 activity (Ki = 21.9 +/- 2.2, 7.3 +/- 1.6, and 9.3 +/- 1.6 microM, respectively), and CYP2D6 activity (Ki = 1.2 +/- 0.1, 1.5 +/- 0.2, and 3.0 +/- 0.5 microM, respectively). Azelastine and desmethylazelastine competitively inhibited CYP3A4 activity (Ki = 23. 7 +/- 4.6 and 13.2 +/- 2.3 microM). 6-Hydroxyazelastine interfered with the determination of testosterone 6beta-hydroxylation by HPLC. CYP1A2, CYP2A6, and CYP2E1 activities were not significantly inhibited by azelastine and the two metabolites. Among the human CYPs tested, the inhibitory effects of azelastine and its two metabolites were the most potent on human CYP2D6. In consideration of the Ki values and the concentration of azelastine and desmethylazelastine in human livers after chronic oral administration of azelastine, the possibility of in vivo drug interaction of azelastine and other drugs that are mainly metabolized by CYP2D6 was suggested although it might not cause critical side effects. The inhibition of CYP2C9, CYP2C19, and CYP3A4 activity by azelastine and its two metabolites might be clinically insignificant.

Anti-Allergic Agents↗
PubMed1999

[Analysis of the long-term prognosis for conjunctival malignant melanomas in Japan].

PURPOSE: To investigate the long-term prognosis for primary conjunctival malignant melanomas in Japan. MATERIALS & METHODS: We conducted a survey of 61 cases which had been reported in a 38-year period (1959 to 1996). We gathered information regarding the survival of patients, the post-operative follow-up period, the causes of death, and recurrences. Answers were obtained segarding 51 cases (84%). Detailed progress was identified in 23 of these cases. The survival rates were calculated using the Kaplan-Meier method. RESULTS: The survival rates were 95.1% after 1 year, 72.9% after 3 years, and 53.4% after 5 years. These values are relatively low compared with those reported in Europe and the United States.

Adolescent↗
PubMed1999

Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes.

Phenacetin O-deethylation (POD) exhibits biphasic kinetics in human liver microsomes. Although cytochrome P-450 (CYP) 1A2 is responsible for the high-affinity component of POD, the enzyme(s) that catalyzes the low-affinity reaction is still unknown. We examined the roles of human CYPs in POD by using human liver microsomes and recombinant CYPs from baculovirus-infected insect cells. Of the recombinant CYPs studied, CYP1A2 showed the highest POD activity. CYP1A1, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 also showed POD activity at 500 microM phenacetin. K(M) values of recombinant CYP1A2 and CYP2E1 (28 +/- 2 microM and 785 +/- 125 microM, respectively) were similar to those of the high- and low-affinity components of POD in pooled human liver microsomes (15 +/- 5 and 894 +/- 189 microM, respectively). Fluvoxamine (10 microM) and anti-CYP1A2 antibodies potently inhibited POD activity at 500 microM phenacetin in pooled human liver microsomes to 22.8 and 34.2% of controls, respectively. CYP2E1 inhibitors diethyldithiocarbamate and aniline also reduced POD activity. The combination of fluvoxamine (10 microM) and aniline (1 mM) further inhibited the residual POD activity not inhibited by fluvoxamine alone. Microsomal POD activity in 12 human livers in the absence of fluvoxamine was correlated with immunoquantified CYP1A2 levels (r = 0.961, p <.001) and, in the presence of 10 microM fluvoxamine, was correlated with immunoquantified CYP2E1 levels (r = 0.589, p <.01) or chlorzoxazone 6-hydroxylase activity (r = 0.823, p <.001). These results suggest that CYP2E1 is responsible for the low-affinity component of POD in human liver microsomes.

Analgesics, Non-Narcotic↗
PubMed1999

[A case of acute renal failure with rhabdomyolysis caused by the interaction of theophylline and clarithromycin].

Theophylline toxicity has been recognized since its introduction into clinical medicine. Clarithromycin is a new oral macrolide antibiotic with excellent antibacterial activity and rare adverse effect. Patients with upper respiratory infection are often treated with theophylline and clarithromycin concurrently. We report a case of acute renal failure due to acute rhabdomyolysis caused by the interaction of theophylline and clarithromycin. A 72-year-old man visited our hospital because of coughing and a sore throat continuing for 1 week. He was diagnosed as having the common cold with a bronchial asthmatic symptom and was prescribed 200 mg/day of sustained-release theophylline for the treatment of asthma for 7 days. One week later, he visited our hospital again. Radiographic study of the chest revealed mild interstitial pneumonia and 200 mg/day of sustained-release theophylline and 400 mg/day of clarithromycin were administrated concomitantly. Five days after the second visit, the patient was admitted to our hospital because of generalized twitching, muscular weakness, high fever and serious general condition. He experienced generalized muscular twitching and tremor. Blood urea nitrogen was 106.1 mg/dl, serum creatinine was 7.4 mg/dl, serum creatinine kinase (CK) was 36,000 IU/l (normal 15-130 IU/l), CK isozyme revealed the following ratio: BB 0%, MB 1% and MM 99%. He was diagnosed as having acute renal failure with rhabdomyolysis caused by the interaction of theophylline and clarithromycin. Hemodialysis therapy was started. After 5 weeks, his serum creatinine was markedly decreased. It is well-known that clarithromycin enhances the serum concentration of theophylline by inhibition of the cytochrome P450-dependent pathway in hepatocytes. Theophylline toxicity may be enhanced when clarithromycin is administrated concomitantly, especially to elderly patients with dehydration.

Acute Kidney Injury↗
PubMed1999

Enhancement of cytochrome P-450 3A4 catalytic activities by cytochrome b(5) in bacterial membranes.

Activities of testosterone, nifedipine, and midazolam oxidation by recombinant cytochrome P-450 (P-450) 3A4 coexpressed with human NADPH-P-450 reductase (NPR) in bacterial membranes (CYP3A4/NPR membranes) were determined in comparison with those of other recombinant systems and of human liver microsomes with high contents of CYP3A4. Growth conditions for Escherichia coli transformed with the bicistronic construct affected expression levels of CYP3A4 and NPR; an excess of NPR over P-450 in membrane preparations enhanced CYP3A4-dependent testosterone 6beta-hydroxylation activities of the CYP3A4/NPR membranes. Cytochrome b(5) (b(5)) and apolipoprotein b(5) further enhanced the testosterone 6beta-hydroxylation activities of CYP3A4/NPR membranes after addition to either bacterial membranes or purified enzymes. NPR was observed to enhance catalytic activity when added to the CYP3A4/NPR membranes, either in the form of bacterial membranes or as purified NPR (in combination with cholate and b(5)). Apparent maximal activities of testosterone 6beta-hydroxylation in CYP3A4/NPR membranes were obtained when the molar ratio of CYP3A4/NPR/b(5) was adjusted to 1:2:1 by mixing membranes containing each protein. Testosterone 6beta-hydroxylation, nifedipine oxidation, and midazolam 4- and 1'-hydroxylation activities in CYP3A4/NPR membranes plus b(5) systems were similar to those measured with microsomes of insect cells coexpressing CYP3A4 with NPR and/or of human liver microsomes, based on equivalent CYP3A4 contents. These results suggest that CYP3A4/NPR membrane systems containing b(5) are very useful models for prediction of the rates for liver microsomal CYP3A4-dependent drug oxidations.

Anesthetics, Intravenous↗
PubMed1999

Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes.

Troglitazone, a new oral antidiabetic drug, is reported to be mostly metabolized to its conjugates and not to be oxidized by cytochrome P-450 (P-450) enzymes. Of fourteen cDNA-expressed human P-450 enzymes examined, CYP1A1, CYP2C8, CYP2C19, and CYP3A4 were active in catalyzing formation of a quinone-type metabolite at a concentration of 10 microM troglitazone, whereas CYP3A4 had the highest catalytic activity at 100 microM substrate. In human liver microsomes, rates of the quinone-type metabolite formation (at 100 microM) were correlated well with rates of testosterone 6beta-hydroxylation (r = 0.98), but those at 10 microM troglitazone were not correlated with any of several marker activities of P-450 enzymes. Quercetin efficiently inhibited quinone-type metabolite formation (at 10 microM troglitazone) in human samples that contained relatively high levels of CYP2C, whereas ketoconazole affected these activities in liver microsomes in which CYP3A4 levels were relatively high. Anti-CYP2C antibodies strongly inhibited quinone-type metabolite formation (at 10 microM troglitazone) in CYP2C-rich human liver microsomes (by approximately 85%); the intensity of this effect depended on the human samples and their P-450 status. The results suggest that in human liver both CYP2C8 and CYP3A4 have major roles in quinone-type metabolite formation and that the hepatic contents of these two P-450 forms determine which P-450 enzymes play major roles in individual humans. CYP3A4 may be expected to play a role in formation of quinone-type metabolite from troglitazone even at a low concentration in humans.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs.

Azelastine, an antiallergy and antiasthmatic drug, has been reported to be mainly N-demethylated to desmethylazelastine in humans. In the present study, Eadie-Hofstee plots of azelastine N-demethylation in human liver microsomes were biphasic. In microsomes from human B-lymphoblast cells, recombinant cytochrome P-450 (CYP)2D6 and CYP1A1 exhibited higher azelastine N-demethylase activity than did other CYP enzymes. On the other hand, recombinant CYP3A4 and CYP1A2 as well as CYP1A1 and CYP2D6 in microsomes from baculovirus-infected insect cells were active in azelastine N-demethylation. The K(M) value of the recombinant CYP2D6 (2.1 microM) from baculovirus-infected insect cells was similar to the K(M) value of the high-affinity (2.4+/-1.3 microM) component in human liver microsomes. On the other hand, the K(M) values of the recombinant CYP3A4 (51.1 microM) and CYP1A2 (125.4 microM) from baculovirus-infected insect cells were similar to the K(M) value of the low-affinity (79.7+/-12.8 microM) component in human liver microsomes. Bufuralol inhibited the high-affinity component, making the Eadie-Hofstee plot in human liver microsomes monophasic. Azelastine N-demethylase activity in human liver microsomes (5 microM azelastine) was inhibited by ketoconazole, erythromycin, and fluvoxamine (IC(50) = 0.08, 18.2, and 17.2 microM, respectively). Azelastine N-demethylase activity in microsomes from twelve human livers was significantly correlated with testosterone 6beta-hydroxylase activity (r = 0.849, p<.0005). The percent contributions of CYP1A2, CYP2D6, and CYP3A4 in human livers were predicted using several approaches based on the concept of correction with CYP contents or relative activity factors (RAFs). Our data suggested that the approach using RAF(CL) (RAF as the ratio of clearance) is most predictive of the N-demethylation clearance of azelastine because it best reflects the observed N-demethylation clearance in human liver microsomes. Summarizing the results, azelastine N-demethylation in humans liver microsomes is catalyzed mainly by CYP3A4 and CYP2D6, and CYP1A2 to a small extent (in average, 76.6, 21.8, and 3.9%, respectively), although the percent contribution of each isoform varied among individuals.

Animals↗
PubMed1999

Role of human CYP2B6 in S-mephobarbital N-demethylation.

The role of cytochrome P-450s (CYPs) in S-mephobarbital N-demethylation was investigated by using human liver microsomes and cDNA-expressed CYPs. Among the 10 cDNA-expressed CYPs studied (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), only CYP2B6 could catalyze S-mephobarbital N-demethylation. The apparent K(m) values of human liver microsomes for S-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 microM). The N-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920, p<.001). Orphenadrine (300 microM), a CYP2B6 inhibitor, inhibited the N-demethylase activity of S-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzes S-mephobarbital N-demethylation in human liver microsomes.

Anticonvulsants↗
PubMed1999

[Transition of branched-chain amino acids and tyrosine ratio (BTR) in the blood of acute hepatitis patients].

The molar ratio of branched-chain amino acids to tyrosine (BTR) correlates well with the Fischer ratio, and can be measured in a short period of time. It is regarded as the method of analysis that will eventually replace the Fischer ratio. But clinical significance of BTR in terms of acute liver disorders has not been examined thoroughly as of yet. In this study, we measured BTR of 34 patients with acute hepatitis, and examined the transition of the acute period of acute hepatitis and its recovery process. Thirty-four patients diagnosed with acute viral hepatitis became subjects of examination (16 patients of A type, 15 patients of B type, 1 patient of C type, 2 patients of non-A, non-B, non-C type). Out of the 34 patients, 11 were in serious stages (HPT under 40%), including 3 in fulminant condition. By using preserved serum obtained during the acute period (within 1 week of the highest transaminase value), recovery period (within 4 weeks), and treatment period (3 months and later), measurements were conducted with Diacolor:BTR (enzymatic analysis, ONO Pharmaceutical Co., Ltd.), and the results were compared with those of 50 healthy subjects (25 men, 25 women). BTR correlated well with the Fischer ratio for chronic hepatic patients, and with albumin (Alb), PT, and ICGR15 as well, proving that it is useful as an indicator of hepatic reserve ability. But BTR has not been thoroughly examined as it relates to acute liver disorders. In this study, BTR fell in the acute period, correlating with the serious period, proving that it is a useful indicator. For acute liver damage, BTR supports conventional indicators (Alb, Ch-E, HGF, etc.) for assessing serious damage. Also, it has been suggested that measuring the passage of BTR could be the indicator of true recovery, including amino acid metabolism for liver disorders.

Acute Disease↗
PubMed1998

Changes in plasma erythropoietin and interleukin-6 concentrations in patients with septic shock after hemoperfusion with polymyxin B-immobilized fiber.

OBJECTIVE: To find out whether polymyxin B-immobilized fiber (PMX-F) treatment affects the clinical parameters and plasma concentrations of erythropoietin (EPO) and interleukin (IL)-6. DESIGN: A prospective case series study. SETTING: Intensive care unit of the Department of Internal Medicine, Misato Junshin Hospital, Saitama, and Koto Hospital, Tokyo, Japan. PATIENTS: 17 consecutive patients (10 men, 7 women; mean age 54.6 years) with clinically defined septic shock and 20 healthy volunteers (12 men, 8 women; mean age 52.2 years). MAIN RESULTS: Of the 17 patients with septic shock, 9 (53 %) survived. The systolic blood pressure increased significantly from 78+/-6 to 106+/-8 mm Hg 2 h after PMX-F treatment in patients with septic shock. Plasma endotoxin levels decreased significantly after treatment, from 40+/-6 to 12+/-4 pg/ml. The pretreatment plasma concentrations of EPO and IL-6 were significantly higher in the 8 nonsurviving patients with septic shock (EPO: 400+/-36 mlU/ml; IL-6: 6260+/-1180 pg/ml) than in the 9 surviving patients (EPO: 120+/-22 mlU/ml; IL-6: 680+/-138 pg/ml) and the 20 control subjects (EPO, 12+/-6 mlU/ml; IL-6, 8+/-2 pg/ml). Plasma concentrations of EPO and IL-6 in patients with septic shock decreased significantly after PMX-F treatment (EPO, nonsurviving: 320+/-28 mlU/ml, p < 0.05; survivors: 26+/-8 mlU/ ml, p < 0.001; IL-6, nonsurviving: 3860+/-840 pg/ml, p < 0.01; survivors: 84+/-20 pg/ml, p < 0.001). CONCLUSIONS: Plasma concentrations of EPO and IL-6 may be prognostic indicators in patients with septic shock: PMX-F treatment may be effective in reducing the plasma concentrations of EPO and IL-6 in patients with septic shock.

Adult↗
PubMed1998

Effects of hemoperfusion with polymyxin B-immobilized fibre on serum neopterin and soluble interleukin-2 receptor concentrations in patients with septic shock.

OBJECTIVE: the aim of the present study was to determine whether serum neopterin and soluble interleukin (IL)-2 receptor levels were related to the development of septic shock and whether polymyxin B-immobilized fibre (PMX-F) treatment affects these levels. METHODS: we examined 24 patients admitted to our intensive care unit with Gram-negative septic shock. Serum neopterin and soluble IL-2 receptor levels were measured using commercially available test kits. Patients were treated with direct hemoperfusion using PMX-F columns. RESULTS: fifteen out of 24 patients (63%) survived and were discharged from our hospitals within 30 days after PMX-F treatment. Blood endotoxin levels decreased significantly from 49.2+/-8.6 pg/ml to 13.2+/-4.4 pg/ml after PMX-F treatment. The pretreatment serum concentrations of neopterin and IL-2 receptor were significantly higher in the nine non-surviving patients with septic shock than in the 15 surviving patients (P<0.01) and 20 control subjects (P<0.001). Serum concentrations of neopterin and IL-2 receptor in patients with septic shock decreased significantly after PMX-F treatment (P<0.01). CONCLUSIONS: these data suggest that serum neopterin and IL-2 receptor concentrations may be prognostic indicators in patients with septic shock. PMX-F treatment may be effective for reducing serum neopterin and IL-2 receptor concentrations.

Adult↗
PubMed1998

Increased plasma metalloproteinase-9 concentrations precede development of microalbuminuria in non-insulin-dependent diabetes mellitus.

We determined plasma metalloproteinase-9 (MMP-9) concentrations in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM) at an initial examination (baseline) and on three separate occasions during a 48-month follow-up period. All patients had normal urinary albumin excretion (<20 microg/min) at the first three examinations. At the fourth examination (48 months after the first examination), 22 patients had normal urinary albumin excretion and eight had microalbuminuria (median, 36.4 microg/min; range, 20.2 to 46.6 microg/min). Compared with patients with normal urinary albumin excretion, patients with microalbuminuria had significantly higher plasma levels of MMP-9 at the second (56+/-14 microg/L v36+/-12 microg/L; P < 0.05), third (88+/-23 microg/L v 39+/-14 microg/L; P < 0.01), and fourth (117+/-30 microg/L v 44+/-16 microg/L; P < 0.01) examinations, but not at the first examination (34+/-12 microg/L v 33+/-14 microg/L; P=NS). An increase in plasma MMP-9 concentrations preceded the occurrence of microalbuminuria within 4 years. The groups did not differ with regard to age, sex, duration of NIDDM, blood pressure, or mean glycated hemoglobin. In addition, the eight patients with microalbuminuria were treated with an angiotensin-converting enzyme inhibitor (cilazapril; 0.5 mg once daily) for 6 months. Microalbuminuria was reduced to within the normal range, and plasma MMP-9 concentrations were significantly decreased with the cilazapril treatment (52+/-18 microg/L; P < 0.01). However, serum MMP-1 and tissue inhibitor of MMP-1 showed no change during the study period. These data suggest that plasma MMP-9 concentrations preceded and may predict the development of microalbuminuria in NIDDM.

Adult↗
PubMed1998

Effect of hemoperfusion with polymyxin B-immobilized fiber on plasma endothelin-1 and endothelin-1 mRNA in monocytes from patients with sepsis.

Hemoperfusion using polymyxin B-immobilized fiber (PMX-F) is reported to be an effective treatment for sepsis. The aim of the present study is to assess whether plasma endothelin-1 (ET-1) and ET-1 messenger RNA (mRNA) levels in peripheral-blood monocytes are altered in patients with sepsis and whether PMX-F treatment affects plasma ET-1 and monocyte ET-1 mRNA levels. Sixteen patients with sepsis and 20 healthy volunteers were included in this study. Plasma ET-1 concentration was measured by radioimmunoassay (RIA), and plasma levels of transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA). Sixteen patients with sepsis were treated with direct hemoperfusion using PMX-F columns. Blood endotoxin levels decreased significantly from 35 to 10 pg/mL after two treatments of direct hemoperfusion, each for 2 hours. Patients with sepsis showed significantly increased levels of plasma ET-1 (P < 0.001) and monocyte ET-1 mRNA (P < 0.001) compared with healthy volunteers. However, no differences in plasma levels of TGF-beta, TNF-alpha, and IL-1beta existed between patients with sepsis and healthy volunteers. Increased plasma ET-1 levels and monocyte ET-1 mRNA levels in patients with sepsis decreased significantly after PMX-F treatment (P < 0.01). These data suggest that the secretion of ET-1 from peripheral-blood monocytes may be stimulated by endotoxin, and PMX-F treatment may be effective in reducing ET-1 secretion in patients with sepsis.

APACHE↗
PubMed1998

Involvement of CYP1A2 in mexiletine metabolism.

AIMS: Mexiletine has been reported to be hydroxylated by cytochrome P450 2D6 (CYP2D6) in humans. However, the involvement of CYP1A2 in the metabolism of mexiletine has been proposed based on the interaction with theophylline which is mainly metabolized by CYP1A2. The aim of this study was to clarify the role of human CYP1A2 in mexiletine metabolism. METHODS: Human CYP isoforms involved in mexiletine metabolism were investigated using microsomes from human liver and B-lymphoblastoid cells expressing human CYPs. The contributions of CYP1A2 and CYP2D6 to mexiletine metabolism were estimated by the relative activity factor (RAF). RESULTS: Mexiletine p- and 2-hydroxylase activities in human liver microsomes were inhibited by ethoxyresorufin and furafylline as well as quinidine. Mexiletine p- and 2-hydroxylase activities in microsomes from nine human livers correlated significantly with bufuralol 1'-hydroxylase activity (r = 0.907, P < 0.001 and r = 0.886, P < 0.01, respectively). Microsomes of B-lymphoblastoid cells expressing human CYP1A2 exhibited lower mexiletine p- and 2-hydroxylase activities than those expressing human CYP2D6. It was estimated by RAF that the major isoform involved in mexiletine metabolism was CYP2D6, and the contribution of CYPIA2 to both mexiletine p- and 2-hydroxylase activities was 7-30% in human liver microsomes. However, the Km values of the expressed CYP1A2 (approximately 15 microM) were almost identical with those of the expressed CYP2D6 (approximately 22 microM) and human liver microsomes. CONCLUSIONS: Mexiletine is a substrate of CYP1A2. The data obtained in this study suggest that the interaction of mexiletine with theophylline might be due to competitive inhibition of CYP1A2.

Anti-Arrhythmia Agents↗
PubMed1998

Temperature distribution produced by laser irradiation in a ventricle model. The use of airflow in neuroendoscopic surgery.

The changes in intraventricular temperature during potassium titanyl phosphate laser irradiation were investigated using a ventricle configuration model. The laser had an output of 3 to 20 watts in 1 second pulse mode. The model ventricular cavity was filled with still air or saline, or irrigated with air or saline. The laser irradiation in a continuous mode with the output of 15 or 20 watts was also examined under air flow or saline irrigation. In pulse-mode irradiation, the temperature increase was less than 5.0 degrees C under all conditions with the outputs up to 10 watts. With 20 watts pulse irradiation, the temperature increase was within 7 degrees C with air flow, and over 20 degrees C in still air. The later condition occasionally induced a plume of steam resulting in excessive temperature elevation at a remote point. With the continuous irradiation of 15 or 20 watt, the temperature increased by about 4.0 degrees C even under saline irrigation, which required over 30 sec to return to the pre-irradiation level. These results indicate the possible use of pulse mode laser irradiation and air flow endoscopic surgery within the ventricular system. With continuous mode laser irradiation, however, the importance of saline irrigation and proper cooling interval is suggested.

Air Movements↗
PubMed1998

Elevated levels of erythropoietin in cerebrospinal fluid of depressed patients.

To investigate the role of erythropoietin (EPO) in the central nervous systems, we assayed EPO concentrations in the cerebrospinal fluid (CSF) of patients with depression or old cerebrovascular injuries and controls. Concentrations of EPO in the CSF were significantly higher in 13 patients with depression (3.21+/-0.46 mU/mL) than in 10 patients with old cerebrovascular diseases (1.80+/-0.32 mU/mL, P < 0.01), and in 10 healthy controls (0.98+/-0.26 mU/mL, P < 0.01). Serum EPO concentrations did not differ among these three groups. In the patients with depression, 5 months of treatment with imipramine and/or nortriptyline significantly reduced EPO concentrations in the CSF (1.56+/-0.34 mU/ mL, P < 0.01). Results suggest that the brain of patients with depression may be in an hypoxic state, and that the increased EPO in the CSF may act to limit hypoxia-induced damage to neurons in these patients.

Antidepressive Agents, Tricyclic↗
PubMed1998

Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment.

The authors measured plasma metalloproteinase (MMP)-9 and corresponding monocyte mRNA in 20 patients with septic shock. Plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels were significantly higher in the 10 nonsurviving patients with septic shock than in 10 surviving patients and 25 normal controls. Hemoperfusion using polymyxin B immobilized on fibers (PMX-F), a reportedly effective treatment for septic shock, was studied for effects on MMP-9 in the patients. Increases in plasma MMP-9 concentrations and corresponding monocyte mRNA levels were attenuated significantly by PMX-F treatment in both nonsurviving and surviving patients. These data suggest that plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels may be useful prognostic markers in septic shock, and that PMX-F treatment affects MMP-9.

Adult↗