Histopathological safety evaluation of newly-developed MgO sealer.

We aimed to evaluate the subcutaneous tissue reaction to a newly-developed MgO Sealer for root canals. We injected the experimental material and three existing control materials into the dorsal area of 43 male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embedding sites was removed and histopathological examination was performed. The results demonstrate that the basic histopathological reaction is the formation of fibrous capsules consisting of granulation tissue around the experimental and control embedded materials. Based on our results, we believe that the newly-developed MgO Sealer is as safe as the existing control materials and can be considered for dental use as a root canal sealer.

Immunohistochemical expression of heat shock protein27 in the mouse dental pulp after immediate teeth separation.

AIM: After immediate teeth separation, expression of HSP27 in the mouse dental pulp was examined. Immunohistochemistry was performed to examine the incidence of HSP27 expression. MATERIALS AND METHODS: A total of 36 8-week-old ddY mice were used as experimental subjects and a wedge was inserted in between maxillary right molars. The wedge was removed 30 min or 3 h after insertion. Animals were immediately sacrificed after the removal of wedge or until 1 week later and serial sections from paraffin-embedded tissues were prepared. Immunohistochemistry was carried out to examine the expression of HSP27. The untreated side served as the control. RESULTS: In the control group, the endothelial cells and some pulp fibroblasts weakly expressed HSP27 suggesting that the expression is due to mechanical stress brought about by physiological masticatory force and pressure from the tongue. In both 30 min and 3 h experimental groups, HSP27 expression was highest at 24 h after wedge removal and the expression remained the same or started to decrease thereafter. The expression decreased at the same level as that of the control group 1 week after wedge removal. CONCLUSION: HSP27 may serve as an indicator of stimulus strong enough to show its expression.

Immunohistochemical expression of hard tissue related factors in the mouse dental pulp after immediate teeth separation.

We examined change of Runx2 and ALP expression in mouse tooth pulp which exposed to teeth separation experiment by immunohistochemistry as a model for conservative dentistry treatment. 8-week-old 36 male ddY mice were used and wedge was inserted between upper 1st and 2nd molars. The wedge was removed 30 minutes as well as 3 hours after the insertion and the samples were prepared extending up to 1 week of time period for regular histopathological and immunohistochemical examinations for ALP and Runx2 expression. The opposite sides without wedge insertion were taken as controls. In the control group pulp, weak expressions of Runx2 and ALP in the vessel endothelial cells as well as the pulp cells were revealed, suggesting the appearance of these genes upon mechanical stress induced by mastication and tongue pressure etc. On the other hand in the experiment group, Runx2 expression increased both in 30-minute and 3-hour teeth separation group. The expression became maximum at 24 hours. Then it gradually decreased and became similar level with the control group at 1-week after the wedge insertion. Similarly ALP expression increased after the wedge insertion and was maximum at 24 hours and then gradually decreased to the levels similar with the control group. These results suggest that when immunohistochemical expression of Runx2 as well as ALP was used as an index, no severe damage occur upon clinical application of wedge insertion.

Hard tissue formation in subcutaneously transplanted rat dental pulp.

While dental pulp appears to be able to form mineralized matrices that do not always resemble dentin, the precise characteristics of the hard tissue and the mechanism of its induction remain unknown. Therefore, we evaluated hard tissue induced by transplantation of pulp into subcutaneous tissue. Seven days after transplantation, initial hard tissue was formed at the inner periphery of the pulp. After 14 days, this hard tissue expanded inwardly. Mineralized matrix was immunopositive for osteocalcin, osteopontin, and bone sialoprotein, but negative for dentin sialoprotein. Transplantation of GFP-labeled pulp into wild-type rats showed these formative cells to have been derived from the transplant. TEM observation revealed apatite crystals within necrotic cells and matrix vesicles at the initial stage of calcification. These results indicate that pulp cells possess the ability to form a bone- or cementum-like matrix. Calcification of the matrix may occur in necrotic cells and matrix vesicles, followed by collagenous calcification.

Effects of variation in superoxide dismutases (SOD) on oxidative stress and apoptosis in lens epithelium.

Among the critical antioxidant enzymes that protect the cells against oxidative stress are superoxide dismutases: CuZnSOD (Sod1) and MnSOD (Sod2). The latter is also implicated in apoptosis. To determine the importance of these enzymes in protection against reactive oxygen species (ROS) in the lens, we analysed DNA strand breaks in lens epithelium from transgenic and knockout (Sod1) mice following exposure to H2O2 in organ culture. Since Sod2 knockouts do not survive, comparison was made of lenses of partially-deficient (heterozygote) for Sod2 and the wild-type controls which have twice the enzyme level. Antioxidant potential of Sod2 was also studied in human lens epithelial cells (SRA01/04) in which the enzyme was up- and down-regulated by transfection with plasmids containing sense and antisense human cDNA for MnSOD. DNA strand breaks in the epithelium of Sod1 knockouts and Sod2 heterozygotes were much greater than in the corresponding wild-type or in transgenic mice over-expressing the enzymes when the lenses were exposed to H2O2. The functional role of Sod2 in apoptosis was examined in cultured human lens epithelial cells. Cells with higher enzyme levels were more resistant to the cytotoxic effects of H2O2, O2- and UV-B radiation. Furthermore, Sod2-deficient cells showed dramatic mitochondrial damage, cytochrome C leakage, caspase 3 activation and increased apoptotic cell death when they were challenged with O2-. Thus, mitochondrial enzyme (Sod2) deficiency plays an important role in the initiation of apoptosis in the lens epithelium.

Tributyltin interacts with mitochondria and induces cytochrome c release.

Although triorganotins are potent inducers of apoptosis in various cell types, the critical targets of these compounds and the mechanisms by which they lead to cell death remain to be elucidated. There are two major pathways by which apoptotic cell death occurs: one is triggered by a cytokine mediator and the other is by a mitochondrion-dependent mechanism. To elucidate the mechanism of triorganotin-induced apoptosis, we studied the effect of tributyltin on mitochondrial function. We found that moderately low doses of tributyltin decrease mitochondrial membrane potential and induce cytochrome c release by a mechanism inhibited by cyclosporine A and bongkrekic acid. Tributyltin-induced cytochrome c release is also prevented by dithiols such as dithiothreitol and 2,3-dimercaptopropanol but not by monothiols such as GSH, N-acetyl-L-cysteine, L-cysteine and 2-mercaptoethanol. Further studies with phenylarsine oxide agarose revealed that tributyltin interacts with the adenine nucleotide translocator, a functional constituent of the mitochondrial permeability transition pore, which is selectively inhibited by dithiothreitol. These results suggest that, at low doses, tributyltin interacts selectively with critical thiol residues in the adenine nucleotide translocator and opens the permeability transition pore, thereby decreasing membrane potential and releasing cytochrome c from mitochondria, a series of events consistent with established mechanistic models of apoptosis.

Ultraviolet irradiation of titanium dioxide in aqueous dispersion generates singlet oxygen.

We previously reported that irradiation of titanium dioxide (TiO2) in ethanol generates both singlet oxygen (1O2) and superoxide anion (O2*-) as measured by EPR spectroscopy. The present study describes the production of reactive oxygen species upon irradiation of TiO2 in aqueous suspension as determined by EPR spectroscopy using 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TMP) and 5,5-dimethyl-pyrroline-N-oxide (DMPO). Photoproduction of 1O2 by suspended TiO2, detected as 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (4-oxo-TEMPO), was measured in water and deuterium oxide (D2O) in the presence or absence of sodium azide (NaN3) and under air or argon atmospheres. Production of a DMPO-OH adduct was examined in 4-oxo-TMP containing medium in the presence or absence of dimethyl sulfoxide (DMSO). The signal for the DMPO spin adduct of superoxide anion was not observed in aqueous conditions. Kinetic analysis revealed that 1O2 was produced at the surface of irradiated TiO2 in aqueous suspension as was observed in ethanol. Kinetic analysis revealed that the formation of DMPO-OH adduct reflects oxidation of DMPO by 1O2 rather than the trapping of the hydroxyl radical produced by the reaction of photo-exited TiO2 and water. The production of large amounts of 1O2 by TiO2 in aqueous suspension as compared to those in ethanol and possible formation of hydroxyl radical in aqueous suspension but not in alcohol, suggest that irradiation of TiO2 in aqueous environments is biologically more important than that in non-aqueous media.

Metabolic cooperation of ascorbic acid and glutathione in normal and vitamin C-deficient ODS rats.

Although the coordination of various antioxidants is important for the protection of organisms from oxidative stress, dynamic aspects of the interaction of endogenous antioxidants in vivo remain to be elucidated. We studied the metabolic coordination of two naturally occurring water-soluble antioxidants, ascorbic acid (AA) and reduced glutathione (GSH), in liver, kidney and plasma of control and scurvy-prone osteogenic disorder Shionogi (ODS) rats that hereditarily lack the ability to synthesize AA. When supplemented with AA, its levels in liver and kidney of ODS rats increased to similar levels of those in control rats. Hepato-renal levels of glutathione were similar with the two animal groups except for the slight increase in its hepatic levels in AA-supplemented ODS rats. Administration of L-buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, rapidly decreased the hepato-renal levels of glutathione in a biphasic manner, a rapid phase followed by a slower phase. Kinetic analysis revealed that glutathione turnover was enhanced significantly in liver mitochondria and renal cytosol of ODS rats. Administration of BSO significantly increased AA levels in the liver and kidney of control rats but decreased them in AA-supplemented ODS rats. Kinetic analysis revealed that AA is synthesized by control rat liver by some BSO-enhanced mechanism and the de novo synthesized AA is transferred to the kidney. Such a coordination of the metabolism of GSH and AA in liver and kidney is suppressed in AA-deficient ODS rats. These and other results suggest that the metabolism of AA and GSH forms a compensatory network by which oxidative stress can be decreased.

Fluvastatin normalizes the decreased turnovers of glutathione and ascorbic acid in Watanabe heritable hyperlipidaemic rabbits.

1. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to decrease the oxidizability of plasma lipids in hyperlipidaemic subjects. In order to elucidate one of the mechanisms of this in vivo, we investigated the effects of fluvastatin and pravastatin on the decreased turnovers of reduced glutathione (GSH) and ascorbic acid (AA) in Watanabe heritable hyperlipidaemic (WHHL) rabbits. 2. These drugs (30 mg/kg per day) equally decreased plasma levels of lipids after a 4 week treatment period. However, only fluvastatin significantly decreased thiobarbituric acid-reactive substances, which were increased in the plasma of WHHL. 3. Although these drugs did not affect the steady state levels of total glutathione and low molecular weight thiols in the liver and kidney, fluvastatin markedly normalized the rate of GSH turnover in these tissues, as determined by using L-buthionine-(S,R)-sulphoximine, a specific inhibitor of GSH synthesis. 4. Fluvastatin also increased the clearance of AA from the circulation in WHHL. 5. These results suggest that, in addition to its hypolipidaemic action, fluvastatin has the potential to improve the turnover of anti-oxidants, which is closely related to the amelioration of the redox status in the body.

[Clinical characteristics and indications for shunting in patients with idiopathic normal pressure hydrocephalus with brain atrophy (atypical idiopathic normal pressure hydrocephalus)].

PURPOSE: To clarify clinical characteristics of atypical idiopathic normal pressure hydrocephalus (AINPH) and indications for shunt operations. SUBJECTS AND METHODS: Subjects examined in the present study included 65 patients who satisfied the following 4 diagnostic criteria of AINPH and underwent V.P shunt with Medos type shunt system; set pressure: epidural standard pressure x 13.6 - 20 mmH2O (omission of a figure in the first place). The diagnostic criteria were: 1) no apparent history of intra- or extra-cranial disease; 2) dementia was present as a main complaint; 3) the presence of moderate to severe cerebral atrophy and ventricular enlargement and PVL around the anterior horn on CT scans; 4) normal cerebrospinal pressure and filling of ventricles or subarachnoid space with contrast medium at 24 hours on cisternography. The patients were aged 49-83 with the mean age of 62.9 years; the ratio of male to female was 37:28. They were categorized as shunt-effective (group E: 36 cases) or non-shunt-effective (group NE: 29 cases), and the following parameters in both groups were compared: 1. clinical characteristics: 2. the presence or absence of pressure wave (PW) during preoperative continuous epidural pressure measurement (EDPM) 3. CSF outflow resistance (Ro) 4. preoperative serum alpha-1-antichymotrpsin (alpha-1-ACT) 5. cerebral arteriovenous difference of oxygen content (c-AVDO2) before and after surgery 6. mean cerebral blood flow (mCBF; 99mTc-HMPAO-SPECT) before and after surgery. RESULTS AND CONCLUSIONS: 1. Group E had a shorter duration between symptom onset and hospital visit (within 16 months and showed hyporoluntary and hyporeactivity as their main complaints associated with gait disturbance; the time course of symptoms was classified as suddenly progressing and fluctuating in many cases. Group NE had a relatively longer duration between symptom onset and hospital visit and showed activeness, wandering, nervousness and quick temper as their main complaints; the time course of symptoms was classified as progressing in many cases. 2. PW-positive cases were all included in group E. but some PW-negative cases were also observed in group E. 3. Ro was significantly higher in group E (p < 0.01), and cases with a Ro value over 20 mmHg/ml/min. were all included in group E. 4. alpha-1-ACT was significantly lower in group E (p < 0.05), and cases with an alpha-1-ACT value over 55 mg/dl were all included in group NE. 5. Although preoperative c-AVDO2 was significantly higher in group E (p < 0.05), cases with a c-AVDO2 value over 8.5 ml% were all included in group NE. c-AVDO2 values were within 5-8.5 ml% in all cases of group E. 6. mCBF significantly increased after surgery in group E (p < 0.001). 7. It was confirmed that cerebral atrophy in group E on AINPH is caused by a cerebral circulation disturbance defined as a cerebral blood flow of penumbra or more due to cerebral arteriosclerosis, etc. 8. A flowchart of indications for shunt surgery for AINPH was prepared based on the results of the present study.

[A case of angiographically occult arteriovenous malformation with metaplasia (so-called brain stone)].

The patient was a 69-year-old female. Right hemiparesis occurred on April 25, 1996, and then was relieved a day later. Because headache (dull pain in the left) persisted subsequently, she consulted our department on April 26. Head CT showed, without enhancement effect, osseous high density on the surface of the left frontal area. MRI showed high intensity on T1 and low intensity on T2 with flow-void like findings. Cerebral angiography showed a pooling of contrast medium in the same region. 123I-IMP-SPECT revealed reduced cerebral blood flow in the left frontal and parietal lobes just under the same region. On June 11, the patient underwent surgery during which a tumor with arachnoid hypertrophy was extracted en block. Histopathologically, there were abnormal blood vessels with elastic fibers, expanding to an ossified site, and AVM accompanying ossification was thus diagnosed. Postoperative 123I-IMP-SPECT showed improved cerebral blood flow in the left frontal and parietal lobes. The patient was discharged on June 22. The TIA pathologic condition, a symptom of its onset, was considered attributable to cerebral blood flow steal due to AVM.

Indications for shunting in patients with idiopathic normal pressure hydrocephalus presenting with dementia and brain atrophy (atypical idiopathic normal pressure hydrocephalus).

The indications for shunt operation in patients with idiopathic normal pressure hydrocephalus accompanied by brain atrophy (atypical idiopathic normal pressure hydrocephalus: AINPH) were investigated in 25 patients who satisfied the diagnostic criteria and underwent ventriculoperitoneal (VP) shunting. All patients had no apparent history of intra- or extracranial disease; dementia and gait disturbance as the main complaints; moderate to severe cerebral atrophy and ventricular dilatation and at least periventricular low density around the anterior horn on computed tomography; normal cerebrospinal fluid (CSF) pressure and filling of ventricles or cortical surface space with contrast medium at 24 hours on cisternography. The 15 male and 10 female patients were aged 47-83 years (mean 60.4 years). VP shunting was effective in 12 improved patients and not effective in 13 unimproved patients according to NPH grading. Pathological pressure wave on epidural pressure monitoring was observed in eight of 12 improved patients, but none of 13 unimproved patients. CSF outflow resistance was 35.33 +/- 11.16 mmHg/ml/min in improved patients and 9.12 +/- 3.51 mmHg/ml/min in unimproved patients. Preoperative serum alpha-1-antichymotrypsin value (alpha-1-ACT) was 42.02 +/- 8.64 mg/dl in improved patients and 61.72 +/- 11.03 mg/dl in unimproved patients. Alpha-1-ACT over 55 mg/dl occurred only in unimproved patients. Cerebral arteriovenous difference of oxygen content value (c-AVDO2) before and after surgery was 6.34 +/- 0.9 ml% and 5.91 +/- 0.78 ml% in improved patients and 4.75 +/- 1.85 ml% and 4.81 +/- 1.73 ml% in unimproved patients, respectively. The two cases with preoperative c-AVDO2 value over 8.5 ml% were both unimproved. Mean cerebral blood flow value before and after surgery was 23.51 +/- 4.20 ml/100 g/min and 45.22 +/- 8.11 ml/100 g/min in improved patients and 21.77 +/- 5.12 ml/100 g/min and 24.82 +/- 4.97 ml/100 g/min in unimproved patients, respectively. Cerebral atrophy in improved patients is caused by a cerebral circulation disturbance defined as a cerebral blood flow of penumbra or more due to cerebral arteriosclerosis, etc. A flow-chart of indications of shunt surgery for AINPH was prepared based on the results of the present study.

Decreased turnovers of glutathione and ascorbic acid in watanabe heritable hyperlipidemic rabbits.

Oxidative stress has been postulated to play important roles in the pathogenesis of various diseases such as atherosclerosis in hyperlipidemic subjects. Although the possible role of oxidation of low-density lipoprotein (LDL) in the etiology of atherosclerosis has been studied extensively, the turnover of endogenous antioxidants, which is an important protection system against oxidative stress, remains to be elucidated. The aim of our study was to determine the change of the turnover of endogenous antioxidants such as glutathione and ascorbic acid in case of hyperlipidemia, using Japanese white rabbits (JW) and Watanabe heritable hyperlipidemic rabbits (WHHL). The levels of total glutathione and low molecular weight thiols in the liver, kidney, and other organs in both strains of rabbits were similar. However, a kinetic analysis using L-buthionine-(S,R)-sulfoximine revealed that the rate of glutathione turnover in the liver and kidney of WHHL was about 50%) lower than that of JW. Furthermore, intravenously administered ascorbic acid disappeared more slowly in WHHL than in JW. These results indicate that the turnovers of both glutathione and ascorbic acid in WHHL are depressed in comparison with that in JW. These changes would be closely related to the increased oxidizability of lipids in the circulation of hyperlipidemic subjects.

Cross-talk between NO and oxyradicals, a supersystem that regulates energy metabolism and survival of animals.

Mammalian tissues have large amounts of available ATP which are generated by oxidative phosphorylation in mitochondria. For the maintenance of the human body, a large amount of oxygen is required to regenerate these ATP molecules. A small fraction of the inspired oxygen is converted to superoxide radical and related metabolites even under physiological conditions. Most reactive oxygen species react rapidly with a variety of molecules thereby interfering with cellular functions and induce various diseases. Nitric oxide (NO) is an unstable gaseous radical with high affinity for various molecules, such as hemeproteins, thiols, and related radicals. NO easily penetrates through cell membrane/lipid bilayers, forms dissociable complexes with these molecules and modulates cellular metabolism and functions. Because NO has an extremely high affinity for the superoxide radical, the occurrence of the latter might decrease the biological function of NO. Thus, superoxide radicals in and around vascular endothelial cells play critical roles in the pathogenesis of hypertension and vasogenic tissue injury. Because NO also reacts with molecular oxygen, it rapidly loses its biological activity, particularly under ambient atmospheric conditions where the oxygen tension is unphysiologically high. Thus, biological functions of NO are determined by the local concentrations of molecular oxygen and superoxide radicals.

Irradiation of titanium dioxide generates both singlet oxygen and superoxide anion.

Although photoexcited TiO2 has been known to initiate various chemical reactions, such as the generation of reactive oxygen species, precise mechanism and chemical nature of the generated species remain to be elucidated. The present work demonstrates the generation of singlet oxygen by irradiated TiO2 in ethanol as measured by ESR spectroscopy using 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TMP) as a 1O2-sensitive trapping agent. Under identical conditions, the superoxide ion was also detected by spin trapping agent 5,5-dimethyl-pyrroline-N-oxide (DMPO). Kinetic analysis in the presence of both 4-oxo-TMP and DMPO revealed that singlet oxygen is produced directly at the irradiated TiO2 surface but not by a successive reaction involving superoxide anion. The basis for this view is the fact that DMPO added in the mixture increased the signals responsible for 4-oxo-2,2,6,6-tetramethyl-1-piperidinyloxy (4-oxo-TEMPO), a reaction product of 4-oxo-TMP and 1O2. The detailed mechanism for the generation of 1O2 and superoxide ion by irradiated TiO2 and reactions between these species and DMPO are discussed.

Fates and vascular action of S-nitrosoglutathione and related compounds in the circulation.

To know the metabolism of low-molecular-weight S-nitrosothiols (RS-NO) in the circulation, we analyzed the stability and depressor effects of S-nitrosoglutathione (GS-NO) and the l- and d-forms of S-nitrosocysteine (Cys-NO). Although half-lives of these RS-NO in fresh plasma were longer than 50 min, their depressor effects disappeared within 5 min after intravenous administration of these compounds. Acivicin (AT-125), an inhibitor of gamma-glutamyltransferase (gamma-GTP), prolonged the depressor effect of GS-NO but not of Cys-NO. The depressor effect of GS-NO disappeared in AT-125-treated rats within 10 min after administration, which is still shorter than its half-life in vitro. Although S-conjugates of l-cysteine, but not of d-cysteine, rapidly enter into cells via an active transport system and disappear from the circulation, both forms of Cys-NO exhibited similar activity to decrease blood pressure to that of NO. Thus, NO might be rapidly released from Cys-NO in the circulation and shortly exhibited its depressor action. These observations suggested that the circulating GS-NO is rapidly decomposed by gamma-GTP to form Cys-NO and that the release of NO from both GS-NO and Cys-NO is enhanced significantly in the circulation.

Role of superoxide, NO and oxygen in the regulation of energy metabolism and suppression of senile diseases.

Although nitric oxide (NO) rapidly reacts with molecular oxygen under air atmospheric conditions, thereby losing its biological functions, the lifetime of this gaseous radical increases under physiologically low intracellular oxygen tensions. To understand the pathophysiological roles of NO and related molecules in aerobic life, we analyzed the effect of oxygen tensions on the NO-dependent processes in resistance arteries, isolated mitochondria, intact cells and enteric bacteria. Kinetic analysis revealed that NO enhanced the generation of cGMP and induced vasorelaxation of resistance arteries more potently under physiologically low oxygen tensions than under hyperbaric conditions. NO reversibly inhibited the respiration of isolated mitochondria, intact cells and Escherichia coli; the inhibitory effect was more marked under hypoxic conditions than under hyperbaric conditions. Kinetic analysis revealed that NO has pivotal action to increase arterial supply of molecular oxygen for the generation of ATP in peripheral tissues and to suppress energy production in mitochondria and cells in an oxygen-dependent manner. These functions of NO are enhanced by decreasing oxygen tension in situ and suppressed by locally generated superoxide radicals. Thus, cross-talk of NO, superoxide and molecular oxygen constitutes a supersystem by which the energy metabolism in cells and tissues is beautifully regulated in a site-specific manner depending on the relative concentrations of these three radical species.

Root canal system of the mandibular incisor.

To better assess the efficiency of the mechanical preparation of root canals, 1085 transparent specimens of extracted mandibular incisors were examined for canal configuration, thickness and curvature of the root canals, condition of any accessory canals, and location of the apical foramen. Greater than 85% of the root canals possessed a single canal (Type I). Of specimens in which furcation was observed, only 3% possessed two separate canals (Type III and IV). Fewer than 30% of the specimens showed accessory canals that were mechanically impossible to clean. The majority of the lateral branches were small, greater than 80% of the specimens were smaller than a #15 reamer, and none of the branches were larger than a #30 reamer. Although apical foramina located distal to the apex were observed in about 50% of the specimens, 83.6% of all apical foramina were within 0.5 mm of the apex, and 99.5% were within 1.0 mm. Data on the thickness of the root and main canal in the apical portion and curvature of the root canal suggest that for adequate apical preparation, a #40 reamer must be able to reach the apical constriction.

[Terson's syndrome which arose from ruptured right superior cerebellar artery aneurysm: a case report and 32 series investigations].

The case reported here was a 50-year-old woman with the onset of generalized convulsions and vomiting on November 22, 1993. At admission, her neurological sings and symptoms were classified as Hund & Hess grade IV, and precise examination revealed subarachnoid hemorrhage by rupture of aneurysm at the branching of the right superior cerebellar artery. Thus neck clipping was performed on the same day. Although her consciousness level gradually improved after operation, she complained of left vision disturbance on December 5 (14 days after onset). The visual acuity of the left eye was manual valve of 30 cm. It was precisely examined using fundoscopic examination and B mode ultrasonography making the diagnosis of left vitreous hemorrhage (Terson's syndrome). The visual acuity of the left eye began to improve on December 12, and was found to be 1.0 on November 18, 1994, about 1 year after onset. The hemorrhage was also determined to be almost completely absorbed by fundoscopic examination. In this report, the results of statistical analysis of 32 previous cases, in addition to our case, are described, together with the discussion on the pathogenesis of Terson's syndrome.

Ascorbic acid and reducing agents regulate the fates and functions of S-nitrosothiols.

Although S-nitrosoglutathione (GS-NO) and other S-nitrosothiols (RS-NO) exhibit activity attributable to nitric oxide (NO), the dynamic aspects of their metabolism remain to be elucidated. To determine the fates and functions of RS-NO, the stability of GS-NO was analyzed in plasma, and various fractions of liver and kidney. GS-NO was fairly stable under physiological conditions in plasma and buffer solutions. However, GS-NO was rapidly decomposed in the presence of either homogenates of rat liver and kidney or their supernatant fractions. The ability of the supernatants to decompose GS-NO remained unchanged after the removal of proteins and large molecular weight compounds. Physiological levels of reducing agents, such as reduced glutathione (GSH), ascorbic acid (AsA), and cysteine, also enhanced the decomposition of RS-NO; the order of their potency was AsA > cysteine >GSH. Considering their intra-cellular concentrations and potency, AsA might principally be responsible for the enhanced decomposition of GS-NO. NO, GS-NO, and related RS-NO inhibited the respiration of Ehrlich ascites tumor cells. The inhibitory effect of GS-NO was enhanced by the reducing agents (cysteine>AsA>GSH). Intravenously administered GS-NO exhibited a depressor action through some ascorbic acid enhancable mechanism. Thus, the metabolism and biological function of GS-NO and related RS-NO might be affected by AsA and other reducing agents.