Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 19 recordsLinked to original sources

PubMed1998

Effect of the endothelin family of peptides on human coronary artery smooth-muscle cell migration.

The migration of coronary artery medial smooth-muscle cells (SMCs) is one of the key events in the process of intimal thickening in coronary atherosclerotic lesions. The objectives of the present study were to determine whether any of the three isoforms of endothelin (ET), ET-1, ET-2, and ET-3, or an intermediate form of ET, big ET-1, induces migration of human coronary artery SMCs, and to investigate the possible interaction of ET peptides and well-known migration-stimulatory factors, platelet-derived growth factor (PDGF)-BB and angiotensin II (Ang II), on SMC migration by the Boyden's chamber method. None of the ET peptides alone induced SMC migration between 10(-9) and 10(-7) mol/L. In contrast, ET-1 and ET-2 significantly induced SMC migration in the presence of low concentrations of PDGF-BB (0.5 ng/mL) or Ang II (10(-9) mol/L), although ET-3 was less active (ET-1 = ET-2 > ET-3). In contrast, big ET-1 was without significant activity on PDGF-BB-or Ang II-induced SMC migration. The potentiation of SMC migration by ET peptides was clearly inhibited by the ETA receptor antagonist BG-123 in a concentration-dependent manner. These results suggest that the ET family of peptides, especially ET-1 and ET-2, can induce human coronary artery SMC migration in combination with PDGF-BB or Ang II, probably via ETA receptors. Taken together with the finding that the concentrations of ET, PDGF-BB and Ang II are locally increased at sites of endothelial injury, this indicates that ET may be an initial stimulus for human coronary artery medial SMC recruitment during coronary atherosclerosis, possibly in combination with PDGF-BB or Ang II.

Angiotensin II↗

PubMed1998

Heparin suppresses cyclosporine-induced endothelin-1 synthesis in rat endothelial cells.

Cyclosporine stimulates vasoconstrictor endothelin-1 (ET-1) synthesis. This study examined the effect of heparin on cyclosporine-induced ET-1 synthesis in Wistar rat aortic endothelial cells in culture. Cyclosporine (0.01-5 mumol/L) stimulated ET-1 mRNA expression in a dose-dependent manner. A nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA) (10(-5) mol/L), did not affect cyclosporine-induced ET-1 mRNA expression. Heparin (1-20 U/ml) suppressed cyclosporine-induced ET-1 mRNA expression in a dose-dependent manner. The inhibitory effect of heparin was blunted in the presence of either L-NMMA (10(-5) mol/L) or calmodulin inhibitors such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) (5 x 10(-5) mol/L) or calmidazolium (5 x 10(-5) mol/L) in the presence of the phosphodiesterase inhibitor 3-isobutyl 1-methylxanthine (0.1 mmol/L). These results suggest that heparin suppresses cyclosporine-induced ET-1 mRNA expression via both NO- and calmodulin-dependent pathways.

Animals↗

PubMed1998

Suppression of endothelin-3-induced nitric oxide synthesis by triglyceride in human endothelial cells.

Reduced endothelium-derived nitric oxide (NO) production characterizes several vascular diseases. This study examined the effect of triglyceride on NO production induced by endothelin-3 (ET-3) in cultured human umbilical vein endothelial cells. Triglyceride-rich human plasma obtained after a high-carbohydrate diet with white wine was used in an ex vivo study. The plasma triglyceride fraction was found to consist of large amounts of palmitic and oleic acids detected by gas-liquid chromatography. Therefore, the effect of synthetic tripalmitin and triolein emulsion on NO production was also examined. ET-3 stimulated NO and guanosine 3',5'-cyclic monophosphate production and increased cytosolic Ca2+ levels in the endothelial cells (ECs). After incubation of the ECs with the triglyceride-rich plasma for 2 h, these responses to ET-3 were ameliorated in a triglyceride concentration-dependent manner (50-200 mg/dl). A synthesized emulsion of tripalmitin (100 mg/dl) and triolein (100 mg/dl) also blunted the responses to ET-3. Neither endothelial constitutive NO synthase mRNA expression nor its protein level was affected by treatment with triglycerides. These results suggest that triglyceride suppresses ET-3-induced NO synthesis in human ECs by inhibiting cytosolic Ca2+ elevation.

Blotting, Northern↗

PubMed1998

Effects of hypertonic saline and dextran 70 on cardiac contractility after hemorrhagic shock.

OBJECTIVE: The effects of a bolus of 7.5% NaCl-6% dextran 70 (HSD) on cardiac contractility were evaluated in anesthetized sheep with hemorrhagic shock. BACKGROUND: HSD has been shown to be effective at resuscitation in cases of hypovolemia caused by hemorrhage. Common hemodynamic findings after the injection of HSD in hemorrhagic shock are the restoration of cardiac output, increased blood pressure, and improvement of peripheral circulation. Some mechanisms by which HSD maintains circulation in hemorrhagic shock have been proposed: rapid shift of fluid from intracellular to extracellular space, improved peripheral perfusion, and increased cardiac contractility. Conflicting data exist, however, regarding the positive effect of HSD on cardiac contractility after hemorrhagic shock. METHODS: Hemorrhagic shock was induced by shedding mean blood volume of 31.4 mL/kg, and mean blood pressure was maintained at 50 mm Hg for 30 minutes. The HSD group (n = 6) received HSD (4 mL/kg), and the saline group (n = 6) received normal saline (40 mL/kg) after shock. Cardiac functions were measured in both groups using the left ventricular end-systolic pressure-volume relationship and preload recruitable stroke work during the experimental period: before shock, immediately after the resuscitation, and 2 hours after resuscitation. RESULTS: Hemodynamic parameters in both groups demonstrated similar changes throughout the experimental period without significant difference between the two groups. Not only the slopes of end-systolic pressure-volume relationship and preload recruitable stroke work but also their placements did not result in any significant differences between the groups. CONCLUSION: HSD seems to be an effective resuscitation fluid after hemorrhagic shock because the volume required to maintain circulation is smaller than that of normal saline. Our data, however, show that HSD does not enhance cardiac contractility after hemorrhagic shock.

Animals↗

PubMed1997

Effect of a protein phosphatase inhibitor, okadaic acid, on thrombomodulin expression in cultured human umbilical vein endothelial cells.

We examined the effects of okadaic acid, a potent specific inhibitor of protein phosphatases 1 and 2A, on the expression of thrombomodulin (TM), a cell surface anti-thrombotic glycoprotein, on cultured human umbilical endothelial cells. Okadaic acid (2.5-10 nM) significantly increased TM antigen levels in parallel with its cofactor activity for thrombin-dependent protein C activation. Incubation of cells with 10 nM okadaic acid for 18 h induced an approximately 240% up-regulation of TM antigen levels that was accompanied by an increase in TM mRNA levels. Co-incubation of cells with okadaic acid and dibutyryl cyclic AMP further increased TM antigen levels. Furthermore, the effect of cAMP on TM expression was augmented by the pretreatment of cells with 10 nM okadaic acid for 18 h. These results provide evidence for the involvement of protein phosphatase in the cellular regulatory mechanisms for TM expression, which is distinct from that by cAMP.

Blotting, Northern↗

PubMed1997

Altered cardiac mechanism and sarcoplasmic reticulum function in pressure overload-induced cardiac hypertrophy in rats.

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we examined the hypothesis that alterations in SR function occur during the development of hypertrophy of the left ventricle (LV) induced in rats by pressure overload secondary to abdominal aortic coarctation. Ten days, 4 and 8 weeks after the operation, hemodynamic parameters were measured using a catheter-tip manometer. The SR vesicles of hypertrophic LV (group A) and sham-operated LV (group S) at each stage were used to study Ca2+ release and uptake, and to characterize the ryanodine receptor. Moderate hypertrophy was observed in group A even at the earliest stage. Systolic LV pressure and peak +dP/dt were significantly increased in group A. There were no significant change in diastolic LV pressure in either group at any stage. Hemodynamic data indicated that LV function in group A was enhanced during the development of the hypertrophy. The amount of Ca2+ release and uptake, and the number of ryanodine binding sites on the SR were higher in group A than in group S at both early and middle stages. However, 8 weeks after the operation, SR activity was normal, even though cardiac function was still augmented. Our results indicated that LV hypertrophy induced by pressure overload is associated with altered intracellular Ca2+ regulation, as reflected by the increased Ca2+ release and uptake functions of the SR and the quantitative change in the number of ryanodine receptors during the early stages of the development of hypertrophy. Therefore, alterations in the SR Ca2+ transport capacity could account, at least in part, for the alterations in E-C coupling seen in hypertrophy.

Adaptation, Physiological↗

PubMed1997

Effect of aortic impedance on preload-afterload mismatch in canine hearts in situ.

The aim was to examine the influence of the independent increase of aortic wall characteristics from vascular resistance on global left ventricular (LV) function in intact hearts. In 11 anesthetized dogs, aortic stiffness was increased by a constriction of the thoracic aorta using a stiff tube, and then, in nine dogs, total systemic resistance (TSR) was increased by an infusion of angiotensin II. During the above procedures, aortic input impedance and LV dimension were measured. Aortic input impedance spectra revealed the steady increase in the moduli at high frequencies by aortic constriction, indicating the increase in aortic stiffness. At the stage of increased aortic characteristic impedance (Zc) (134% of control) without a change in TSR, both LV end-diastolic diameter (LVEDD, 99%, p < 0.01 and stroke volume (SV, 95%, p < 0.01) decreased significantly without a change in LV end-systolic diameter (LVESD). During the increase in TSR produced by angiotensin II (128% of control) without a change in Zc, LVEDD tended to increase and LVESD significantly increased (103%, p < 0.01) associated with a decrease in SV (94%, p < 0.01). LV systolic mean wall stress was increased by angiotensin II (118%, p < 0.01), whereas it was unchanged by aortic constriction. In conclusion, the isolated increase in aortic stiffness without a change in TSR was associated with a reduction in LV preload and SV.

Animals↗

PubMed1997

1 alpha,25-dihydroxyvitamin D3 induces very low density lipoprotein receptor mRNA expression in HL-60 cells in association with monocytic differentiation.

Expression of VLDL receptor mRNA during differentiation of HL-60 cells was investigated by Northern analysis. The expression induced in 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3)-treated cells was 3 times that in untreated cells, while LDL receptor mRNA expression was unchanged. VLDL receptor mRNA levels were not changed in macrophages caused to differentiate from HL-60 cells by treatment with phorbol 12-myristate 13-acetate (PMA). Treatment of sarcoma cells which possess the vitamin D receptor (MG-63 cell line) with 1 alpha,25(OH)2D3 did not affect VLDL receptor mRNA levels. Therefore, 1 alpha,25(OH)2D3 induces VLDL receptor mRNA in HL-60 cells through differentiation-dependent mechanisms.

Calcitriol↗

PubMed1997

Quantification of singlet oxygen from hematoporphyrin derivative by electron spin resonance.

The mechanism of the generation and the quantitative analysis of singlet oxygen (1O2) formed by the exposure of a hematoporphyrin derivative (HpD) to light was re-evaluated by electron spin resonance (ESR) combined with 2,2,6,6,-tetramethyl-4-piperidine (TMPD). The change from TMPD to 2,2,6,6,-tetramethyl-4-piperidine-N-oxide (TAN) has been reported to depend on singlet oxygen. However, we confirmed that this reagent also react with superoxide anion (O2-) and hydroxyl radicals (OH). Therefore, the reactions between TMPD and 1O2, O2- and OH were re-examined using a kinetic approach. We found that the generation of TAN was proportional to the concentration of TMPD and HpD, as well as to the duration and strength of the illumination. The generation of TAN was not inhibited by dimethyl-sulfoxide (DMSO) or superoxide dismutase (SOD). The reaction rate between TMPD and 1O2 was determined to be 5.0 x 10(-7) M min-1. The generation of 1O2 from HpD was 2.7 x 10(-7) M min-1 under our conditions. The competitive reaction observed between 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and TMPD for O2- or OH shows that TMPD reacts with both forms of active oxygen, but gave no ESR signal. The second-order reaction rate constant of TMPD between O2- and OH was calculated as 73 M-1 s-1 and 1.5 x 10(9) M-1 s-1, respectively. The photochemical generation of 1O2 from methylene blue, another sensitizer, was also demonstrated by this method. These results show that ESR signal of TAN can be used for the highly selective monitoring of 1O2.

Cyclic N-Oxides↗

PubMed1997

Endothelin production in cultured vascular smooth muscle cells--modulation by the atrial, brain, and C-type natriuretic peptide system.

We examined the regulatory mechanisms of endothelin-1 (ET-1) production in cultured rat vascular smooth muscle cells (VSMC) with a special focus on the roles of protein kinase C (PKC)- and cyclic guanosine-3',5'-monophosphate (GMP)-mediated signaling systems. Effects of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) on angiotensin II (Ang II)-, and arginine vasopressin (AVP)-induced production of ET-1 were examined in cultured rat aortic VSMC. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner through angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1) receptors, respectively. The stimulatory effects of Ang II and AVP were markedly abolished in PKC-depleted cells. Rat ANP (1-28), rat BNP-45, and rat CNP-22 potently inhibited Ang II- and AVP-stimulated ET-1 production in a concentration-dependent manner, respectively. The inhibitory effect by CNP on ET-1 production was paralleled by an increase in the cellular level of cyclic GMR.8-Bromo cyclic GMP reduced the stimulated ET-1 production by Ang II and AVP. These results indicate that Ang II and AVP stimulate ET-1 production in cultured rat VSMC through AT1 and V1 receptors by a mechanism probably involving activation of PKC, and that ANP, BNP, and CNP inhibit this stimulated production through a cyclic GMP-dependent process.

Angiotensin II↗

PubMed1997

Improvement of erythrocyte deformability by cholesterol-lowering therapy with pravastatin in hypercholesterolemic patients.

Erythrocyte deformation is an important regulatory factor of the microcirculation. The present study was designed to examine whether erythrocyte deformability is altered in hypercholesterolemic patients and, if so, whether cholesterol-lowering therapy affects this parameter in these patients. The erythrocyte deformability of 37 hypercholesterolemic patients was evaluated before and after 1 year of therapy with pravastatin, an inhibitor of hepatic hydroxymethyl glutaryl coenzyme A reductase, under various shear stresses (4.7, 9.5, 23.6, 47.3, 118.1, and 236.2 dyne/cm2) using laser diffractometry. At study entry, erythrocyte deformability under 4.7 and 9.5 dyne/cm2 shear stress, which is actually observed in human vessels, was reduced compared with that in 20 age-matched normocholesterolemic subjects and was inversely correlated with serum cholesterol and low-density lipoprotein (LDL) cholesterol. Pravastatin therapy for 1 year, which reduced serum cholesterol from 288 +/- 28 to 223 +/- 20 mg/dL, significantly improved erythrocyte deformability by approximately 20%. There was a significant relation between the improvement of erythrocyte deformability and the reduction of serum cholesterol or LDL cholesterol. The results suggest that erythrocyte deformability is reduced in hypercholesterolemic patients, and that long-term cholesterol-lowering therapy can improve reduced erythrocyte deformability, which may contribute to the improvement of organ perfusion.

Adult↗

PubMed1997

Renoprotective effects of a combined endothelin type A/type B receptor antagonist in experimental malignant hypertension.

We previously showed that plasma endothelin-1 (ET-1) concentration was increased in deoxycorticosterone acetate (DOCA)-salt-induced malignant hypertension in spontaneously hypertensive rats (SHR). In contrast, in normal SHR, this value is similar to that seen in Wistar-Kyoto (WKY) rats. The purpose of this study was to examine the effects of the new combined ET type A/type B (ETA/B) receptor antagonist, TAK-044, on the development of hypertension in this model of malignant hypertension. TAK-044 10 mg/kg, which effectively blocks both ETA and ETB receptors, was administered intraperitoneally once per day for 4 weeks in DOCA-salt SHR, and the effects on ET-1 and other parameters were compared with the same values in untreated WKY rats, untreated DOCA-salt SHR, and hydralazine-treated DOCA-salt SHR. DOCA-salt caused marked increases in blood pressure, blood urea nitrogen (BUN), serum creatinine, and plasma ET-1 concentrations in SHR. Both TAK-044 and hydralazine significantly suppressed the increase in blood pressure in DOCA-salt SHR to the same extent. Both treatments also suppressed the increase in BUN and serum creatinine, but this attenuation was less marked with hydralazine than with TAK-044. Neither TAK-044 nor hydralazine affected plasma ET-1 concentration in this model. TAK-044 significantly reduced kidney weight in DOCA-salt SHR, whereas the decrease seen with hydralazine was less marked. Prevention of DOCA-salt-induced renal structural injury (mesangial hypercellularity, glomerular sclerotic changes, and tubulointerstitial damage) in this model was clearly greater with TAK-044 treatment than with hydralazine treatment. These results suggest that endogenous ET-1 may, at least in part, contribute to renal functional and structural damage in malignant DOCA-salt SHR. Our results raise the possibility of renoprotective effects of ETA/B receptor blockers in certain forms of malignant hypertension.

Animals↗

PubMed1997

Postmyelographic computerized tomographic scan in the differential diagnosis of radiculomeningeal arteriovenous malformation: technical note.

BACKGROUND: The differential diagnosis of radiculomeningeal arteriovenous malformation (AVM) includes spinal intramedullary tumor and spinal cord myelitis. In making the diagnosis of radiculomeningeal AVM, clinical features of the history and magnetic resonance (MR) imaging findings are important initially, followed by selective spinal arteriography with or without myelography to confirm the diagnosis. The differential diagnosis, however, is not always easy. METHODS: We encountered five radiculomeningeal AVM and 14 intramedullary thoracolumbar tumors that were accurately diagnosed preoperatively. We performed postmyelographic computerized tomography (CT) in all five patients with radiculomeningeal AVM and five patients with intramedullary thoracolumbar tumors that were not able to exclude radiculomeningeal AVM with only MR imaging. RESULTS: In all our patients with radiculomeningeal AVM, postmyelographic CT demonstrated the dilated coronal venous plexus on the dorsal aspect of the spinal cord in contrast with a single swelling of the spinal cord in the patients with intramedullary tumor. CONCLUSIONS: We believe that this finding is useful when the serpentine dilated coronal venous plexus is not clearly identified on myelogram and selective spinal arteriography is not apparently indicated.

Aged↗

PubMed1997

Preoperative and postoperative magnetic resonance imaging (MRI) findings of radiculomeningeal arteriovenous malformations: important role of gravity in the symptoms and MRI.

BACKGROUND: The symptoms of radiculomeningeal arteriovenous malformations (AVMs) are reported to be uniform, which suggests it to be a conus medullaris syndrome, and in fact, the lesions on magnetic resonance imaging (MRI) images usually include the conus medullaris. However, the reason why the conus medullaris is always involved in the lesion has not been discussed. METHODS: We encountered seven patients with spinal radiculomeningeal AVMs and operated on all of them. We evaluated the preoperative and postoperative MRI findings in these patients. Postoperative MRI was followed ranging from 6-32 months (mean: 21 months) after surgery. RESULTS: All of our patients showed swelling of the spinal cord, including the conus medullaris, on the preoperative magnetic resonance image. Postoperatively, MRI showed that the swelling of the spinal cord had resolved but that it had finally deteriorated into an atrophic condition. In all of five patients who could be followed up using multiple postoperative MRI scans, sequential T2-weighted images showed that the most rostral level of areas with increased signal in the spinal cord moved in a caudal direction with time. CONCLUSIONS: This and the fact that the conus medullaris was included in the swelling of the spinal cord regardless of the level of the nidus in all our patients, suggested that gravity played an important role in the etiology of radiculomen-ingeal AVM in these patients.

Aged↗

PubMed1997

Tropism of human herpesvirus 8 for peripheral blood lymphocytes in patients with Castleman's disease.

Multicentric Castleman's disease (MCD), also called multicentric angiofollicular lymphoid hyperplasia, is a systemic lymphoproliferative disorder causing fever, lymphadenopathy and splenomegaly. Recently, Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) DNA sequences have been detected in cases of MCD. We examined HHV-8 DNA sequences in the peripheral blood mononuclear cells (PBMCs) of two HIV-negative patients with MCD and in PBMCs and the lymph node of a HIV-negative patient with localized Castleman's disease (LCD) by the polymerase chain reaction. The novel sequences were detected in all DNA samples. Furthermore, the sequences were detected in only the CD19+ B-lymphocyte fraction of the patient with LCD as previously reported. However, the sequences were detected in CD19+ B-lymphocyte and CD2+ T-lymphocyte fractions of two patients with MCD. These results suggest that HHV-8 has tropisms for both B lymphocytes and T lymphocytes in Castleman's disease.

Blotting, Southern↗

PubMed1997

Protection by alpha2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1.

Tissue plasminogen activator (tPA) is widely used in the treatment of acute myocardial infarction (MI). However, its thrombolytic efficacy does not correlate with the dose administered. The interactions between tPA, alpha2-macroglobulin (alpha2-M), and plasminogen activator inhibitor-1 (PAI-1) were investigated both in vitro and in patients undergoing tPA therapy for MI in an attempt to identify variables that might affect the clinical efficacy of tPA. Purified alpha2-M (5.4 mg/ml) protected 16.0% or 22.4% of tPA (12.5 IU/ml) activity from inhibition by PAI-1 at 4 or 8 IU/ml in vitro. Of nine patients treated with 5-20 mega IU of tPA for MI, the plasma activity of tPA remained increased for 15-30 min after the cessation of infusion in eight; the patient who failed to exhibit a persistent increase in tPA activity had a low plasma concentration of alpha2-M. Total tPA activity, derived from the area under the activity-versus-time curve (AUC), showed a significant inverse correlation with the ratio of the plasma PAI-1 activity to the plasma alpha2-M concentration. Total tPA activity did not correlate with plasma PAI-1 activity or plasma alpha2-M concentration alone. Results suggest that alpha2-M, by binding to tPA, protects the latter against inhibition by PAI-1.

Aged↗

PubMed1997

Hydroxyl and superoxide anion radical scavenging activities of natural source antioxidants using the computerized JES-FR30 ESR spectrometer system.

Free radical scavenging activities of water-soluble extracts from some natural sources, health foods, and antioxidant substances were measured using the JES-FR30 JEOL spectrometer. The objective was to develop a standardized method whereby comparison could be made between the radical scavenging activities of complex mixtures. Scavenging of hydroxyl radical was determined using DMPO. Activity was calibrated using a standard material, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1), an analog of vitamin C and vitamin E which is water soluble and stable at room temperature. The order of greatest hydroxyl radical scavenging activity was green tea extract, pine bark extract (Pycnogenol), Ginkgo Biloba extract (EGb 761), a flavonoid blend of several fruit and vegetable extracts (GNLD), and Bio-Normalizer (Sun-O Corp). Activity was determined after treatment of samples with ascorbic acid oxidase. This treatment revealed the presence of ascorbate in some natural extracts and commercial preparations. The pine bark extract was the most heat resistant and had ascorbate-like activity in the preparations. Scavenging of superoxide anion was determined using the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and analyzed by comparison with a standard curve made with superoxide dismutase. Comparison of the water solubilized components of natural source antioxidants showed that filtrates fractionated using centrifuge type Millipore filter tubes (M.W. < 100,000; M.W. < 10,000) also had almost the same SOD-like activity. Samples were also treated with ascorbate oxidase or by heating (100 degrees C for 10 min). The order of activity, from greatest to least, was Ginkgo biloba extract EGb 761, pycnogenol, beta-catechin, tea and BioNormalizer.

Antioxidants↗

PubMed1997

Free radicals in the cerebrospinal fluid are associated with neurological disorders including mitochondrial encephalomyopathy.

The free radical levels in the cerebrospinal fluid of 8 patients with neurological diseases and 9 undergoing lumbar anesthesia for surgery were measured. The ascorbate free radical level 10 min after lumbar puncture showed a positive correlation with the hydroxyl radical level. In the patient with mitochondrial encephalomyopathy, the levels of hydroxyl and ascorbate free radicals increased upon discontinuation of treatment and decreased upon its resumption, and the ascorbate free radical levels without therapy fell after lumbar puncture. The free radical levels in the cerebrospinal fluid may reflect the degree of oxidative stress in the central nervous system.

Aged↗