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Biomedical subjects

S Mesaros

Publications and source records attributed to S Mesaros.

18 recordsLinked to original sources
PubMed2004

Primary progressive multiple sclerosis: clinical and paraclinical characteristics with application of the new diagnostic criteria.

The aim of our study was to analyse clinical and paraclinical characteristics of patients with multiple sclerosis (MS) with previous diagnosis of primary-progressive (PP) MS according to the Poser's criteria and further investigate if they fulfil the McDonald's diagnostic criteria for this disorder. A total of 561 MS patients were registered in the database at the Institute of Neurology, Belgrade, from 1 January 1997 to 31 December 2000 and 63 of them (11.2%) with previous diagnosis of PPMS were analysed retrospectively. Male/female ratio was 1.3:1 and mean age at onset 33.2 years. Most frequent at onset were pyramidal (in 73% of patients) and sensory symptoms (in 41% of patients); 74.6% of patients had greater than or equal to nine brain magnetic resonance imaging (MRI) lesions. Intrathecal oligoclonal immunoglobulin G (IgG) was detected in 96.7% and prolonged visual evoked potentials (VEP) P100 latency in 82.4% of patients. Of the total study group of 561 patients, 10.2% fulfilled the recently recommended McDonald's diagnostic criteria for the diagnosis of PPMS. Our findings further support the significance of the brain/spinal cord MRI, cerebrospinal fluid and VEP findings for precise diagnostic assessment in patients with suspected PP form of MS.

Adult↗
PubMed2002

Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients.

Interleukin-6 (IL-6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 patients with MS and 23 control subjects. Mean CSF IL-6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL-6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL-6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL-6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.

Adult↗
PubMed2001

Uric acid levels in sera from patients with multiple sclerosis.

The levels of uric acid (UA), a natural peroxynitrite scavenger, were measured in sera from 240 patients with multiple sclerosis (MS) and 104 sex- and age-matched control patients with other neurological diseases (OND). The mean serum UA concentration was lower in the MS than in the OND group, but the difference did not reach the level of statistical significance (P = 0.068). However, the mean serum UA level from patients with active MS (202.6 + 67.1 mumol/l) was significantly lower than that in inactive MS patients (226.5 + 78.6 mumol/l; P = 0.046) and OND controls (P = 0.007). We found a significant inverse correlation of serum UA concentration with female gender (P = 0.0001), disease activity (P = 0.012) and duration (P = 0.017), and a trend towards an inverse correlation with disability as assessed by EDSS score, which did not reach statistical significance (P = 0.067). Finally, multivariate linear regression analyses showed that UA concentration was independently correlated with gender (P = 0.0001), disease activity (P = 0.014) and duration of the disease (P = 0.043) in MS patients. These findings suggest that serum UA might serve as a possible marker of disease activity in MS. They also provide support to the potential beneficial therapeutic effect of radical-scavenging substances in MS.

Adolescent↗
PubMed2001

Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel.

BACKGROUND: Adapalene is a naphthoic acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris. OBJECTIVE: This study assessed the cumulative irritation potential of adapalene gel (0.1%) and adapalene cream (0.1%) compared with that of erythromycin (4%)/tretinoin (0.025%) solution, erythromycin (4%)/tretinoin (0.025%) gel, erythromycin (2%)/isotretinoin (0.05%) gel, and white petrolatum (negative control). METHODS: This was a single-center, randomized, controlled, investigator-blinded, intraindividual comparison study in healthy subjects with normal skin. The cumulative irritation assay (patch test) was used to assess the potential for irritation (including erythema) of the treatments. Each subject received all study treatments, randomly applied under occlusion (patch), to sites on either side of the midline on the mid-thoracic area of the back. All patches were applied to the same sites throughout the study, unless the degree of reaction to the treatment or adhesive necessitated removal. For 3 weeks, each test material was applied daily, Monday through Friday, for approximately 24 hours; the Friday patches were left in place over the weekend for approximately 72 hours. RESULTS: All 36 subjects (26 men, 10 women; age, 18-49 years [mean, 30 years]) completed the study. In the course of the study, all subjects had > or =1 application discontinued prematurely on > or =1 site due to intolerance. There were no discontinuations with white petrolatum. All erythromycin/tretinoin gel patches were discontinued at day 10; 35 of 36 erythromycin/isotretinoin gel patches were discontinued at day 9; and 35 of 36 erythromycin/tretinoin solution patches were discontinued at day 11 or day 17. The adapalene products, although slightly more irritating (mean cumulative irritation index, 0.25-1) than white petrolatum, were significantly less irritating than the erythromycin/tretinoin and erythromycin/isotretinoin products (P < 0.01). CONCLUSIONS: Adapalene gel and cream were well tolerated, with possible benefits for compliance. Their low irritation potential should be considered when prescribing a topical retinoid for the treatment of acne vulgaris.

Adapalene↗
PubMed2001

Seizures in multiple sclerosis.

PURPOSE: In patients with multiple sclerosis (MS), epileptic seizures occur more frequently than in the general population. The aim of this study was to analyze clinical characteristics of epilepsy in patients with MS, potential correlation between the semiology of seizures, EEG and magnetic resonance imaging (MRI) findings in these patients, as well as to examine the response to anticonvulsant therapy. METHODS: In a series of 268 consecutive patients with definite MS hospitalized at the Institute of Neurology, Belgrade, we identified 20 (7.5%) patients with seizures or epilepsy. All patients with seizures or epilepsy were submitted to standard EEG and brain MRI with gadopentetate dimeglumine. RESULTS: In four patients, epilepsy occurred 1-5 years before other clinical manifestations of MS. Eight patients had seizures only during MS relapses (provoked seizures). In two of them, seizures were the only manifestations of relapse. In 12 patients, seizures occurred regardless of the phase of MS (chronic epilepsy). In the majority of patients, seizures were partial with secondary generalization. Five patients experienced episodes of status epilepticus, and they all had dementia. Abnormal EEG pattern was found in 11 patients. Brain MRI disclosed cortical-subcortical lesions in nine patients and focal cortical atrophy in one, whereas in the remaining patients, findings were inconclusive. Probable EEG-MRI-seizure type correlation existed in 10 patients. CONCLUSIONS: Our data suggest that epilepsy may represent an initial symptom of MS and a single clinical manifestation of a relapse, and further support the assumption of the existing correlation between the presence of cortical-subcortical lesions and epileptic seizures or epilepsy in patients with MS.

Adolescent↗
PubMed2001

Raised cerebrospinal fluid nitrite and nitrate levels in patients with multiple sclerosis: no correlation with disease activity.

A growing body of evidence implicates excessive generation of nitric oxide (NO) within the central nervous system (CNS) in multiple sclerosis (MS). The aim of our study is to analyse nitrite and nitrate as end products of NO in the cerebrospinal fluid (CSF) from MS patients and correlate the concentrations with clinicol characteristics of the disease. CSF nitrite and nitrate concentrations were measured after reduction of nitrate, by Griess reaction, in 105 MS potients, 27 patients with non-inflammatory neurological disorders (NIND) and 13 individuals without neurological disorder (Co). Mean CSF nitrite and nitrate concentrations were significantly higher in patients with MS and NIND compared with the Co patients (9.44 and 8.68, respectively, versus 6.85 microM; P=0.0001 and P=0.031, respectively). There was no significant correlation between CSF nitrite and nitrate concentrations and activity, phase, severity and duration of MS. Our data are in agreement with the results of previous studies which have demonstrated raised concentrations of CSF NO metabolites in MS patients, providing further evidence for NO involvement in MS. The lack of correlation between NO metabolites and disease activity speaks in favour of the possible dual role of NO, as both immunoregulatory and pro-inflammatory molecule, in the pathogenesis of MS.

Adolescent↗
PubMed1998

Serum interleukin-12 levels in patients with multiple sclerosis.

Increasing body of evidence which suggests a crucial role for interleukin (IL)-12 in modulating immune responses in multiple sclerosis (MS) prompted us to analyze IL-12 in serum from MS patients. We measured the sera concentrations of IL-12, tumor necrosis factor (TNF)-alpha and transforming growth factor-beta1, in 21 MS patients and 13 patients with non-inflammatory nervous diseases. In clinically active MS, serum levels of IL-12 were detectable in 53% and TNF-alpha in 40% of patients. None of the patients with clinically inactive MS had detectable IL-12 and TNF-alpha sera levels. Analysis of serum concentrations of all three cytokines revealed no significant differences between MS patients and controls. These findings provide further evidence that both IL-12 and TNF-alpha might have an active role in immunopathogenesis of MS.

Adult↗
PubMed1998

NO concentration in the periendothelial area of the femoral artery of the dog measured in vivo.

.NO concentration was measured in the periendothelial area of the femoral artery by Malinski's porphyrinic .NO sensor in seven anaesthetized dogs. The basal concentration was 154.2 +/- 5.6 nM and two-minute intraarterial infusions of acetylcholine (3-4 micrograms/ml/min) or bradykinin (30-40 ng/ml/min) increased this value significantly to 204.3 +/- 16.4 and 266.5 +/- 16.4 nM (P < 0.01), respectively. Inhibition of .NO synthase by L-NAME (50 mg/kg) declined the basal .NO concentration only to 137.2 +/- 3.3 nM (P < 0.01). Subsequent administration of acetylcholine and bradykinin attenuated significantly the increase in .NO concentration. Surprisingly, both agonists still induced a significant increase of .NO concentration by 125.3 +/- 8.3 and 156.6 +/- 26.9 nM, respectively (P < 0.01). One of the possible explanations may be that besides arginine-citrulline plus the .NO pathway other sources of .NO could be involved in the high level of .NO after .NO synthase blockade by L-NAME.

Acetylcholine↗
PubMed1997

Interleukin-12 and tumor necrosis factor-alpha levels in cerebrospinal fluid of multiple sclerosis patients.

Concentrations of interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) were measured in patients with multiple sclerosis (MS) and control patients with non-inflammatory neurological diseases (NIND) by an enzyme-linked immunosorbent assay. TNF-alpha was detectable in the CSF of 60% of the patients with active MS, none of those with inactive MS and 29% of patients with NIND. CSF concentrations of TNF-alpha correlated with the degree of disability in MS patients (P < 0.05). Detectable levels of IL-12 were found in 10% of the MS CSF samples and 18% of NIND CSF samples. There was a significant relationship between CSF concentrations of IL-12 and those of TNF-alpha in MS patients (P < 0.05); no relationship was observed between the presence of IL-12 and disease activity or severity. These findings further stress the involvement of T helper 1 type-response within the central nervous system in MS.

Adult↗
PubMed1997

Comparison of two laser Doppler systems on the measurement of blood flow of premolar teeth under different pulpal conditions.

An in vivo investigation was conducted to assess the ability of two laser Doppler flowmeters (DRT4, Moor Instruments Ltd; Laserflo BPM2, Vasamedics) to differentiate between vital pulp, ischaemically necrosed pulp, and an empty pulp chamber in premolar teeth in children. Sixteen intact, vital teeth in need of extraction for orthodontic purposes were identified. Laser Doppler blood flow readings were taken prior to (T1) and after the administration of adrenaline-free local anaesthetic (T2), after extraction and replantation of the teeth (T3), and after broaching the pulp tissue and replanting the teeth (T4). The data collected (flux values) for both instruments were analysed using a repeated measures ANOVA. Significant differences were found for vital pulp (T1, T2) versus ischaemically necrosed pulp (T3), and for vital pulp (T1, T2) versus an empty pulp chamber (T4), with the Moor DRT4 instrument. This instrument also detected a significant difference in pulpal blood flow to the vital pulp, before and after the administration of local anaesthetic. No other significant differences were found.

Analysis of Variance↗
PubMed1997

Periodontal healing of extracted dogs' teeth air-dried for extended periods and soaked in various media.

The aim of this study was to determine the periodontal healing of replanted dogs' teeth which, after extended extra-oral dry times, had been soaked in various media before replantation. Incisors and premolars of beagle dogs were root canal treated, extracted and bench dried. The teeth were grouped according to dry times of 30, 45 and 60 minutes. Each group of teeth was soaked in one of three media, Hank's balanced salt solution, ViaSpan (Belzer UW-CSS, Dupont Pharmaceuticals), or Conditioned Medium (supernatant of confluent culture of human gingival fibroblasts) for 30 minutes before replantation. Controls consisted of teeth extracted and replanted without drying on soaking (negative control), and bench-dried teeth replanted without soaking in the media (positive control). The dogs were killed 6 months after replantation of the teeth, which were prepared for histologic evaluation. Five microns cross-sections (every 70 microns) of the root and surrounding tissue were evaluated for healing/resorption according to Andreasen's criteria. The best healing occurred for the roots which had been immediately replanted. Healing in the positive control groups decreased with increased dry time. For the 30-minute dry time groups, soaking in media had no beneficial effect on periodontal healing compared with the controls. Soaking in ViaSpan resulted in an increased healing incidence for both the 45- and 60-minute bench-dried groups while soaking in the other media had no consistent beneficial effect. It appears from this study that an avulsed tooth that has been left dry for 30 minutes should be replanted immediately without soaking. However, teeth that have been dry for 45 or 60 minutes would benefit from soaking for 30 minutes in ViaSpan.

Adenosine↗
PubMed1997

Beta-adrenergic regulation of constitutive nitric oxide synthase in cardiac myocytes.

Nitric oxide (NO) has been implicated in endogenous control of myocardial contractility. However, NO release has not yet been demonstrated in cardiac myocytes. Accordingly, endogenous NO production was measured with a porphyrinic microsensor positioned on the surface of individual neonatal or adult rat ventricular myocytes (n > 6 neonatal and adult cells per experiment). In beating neonatal myocytes, there was no detectable spontaneous NO release with each contraction. However, norepinephrine (NE; 0.25-1 microM) elicited transient NO release from beating neonatal (149 +/- 11 to 767 +/- 83 nM NO) and noncontracting adult (157 +/- 13 to 791 +/- 89 nM NO) cells. NO was released by adrenergic agonists with the following rank order of potency: isoproterenol (beta1beta2) > NE (alpha/beta1) > dobutamine (beta1) approximately epinephrine (alpha/beta1beta2) > tertbutylene (beta2); NO was not released by phenylephrine (alpha). NE-evoked NO release was reversibly blocked by N(G)-monomethyl-L-arginine, trifluoperazine, guanosine 5'-O-(2-thiodiphosphate), and nifedipine but was enhanced by 3-isobutyl-1-methylxanthine (0.5 mM = 14.5 +/- 1.6%) and BAY K 8644 (10 microM = 11.9 +/- 1%). NO was also released by A-23187 (10 microM = 884 +/- 88 nM NO), guanosine 5'-O-(3-thiotriphosphate) (1 microM = 334 +/- 56 nM NO), and dibutyryl adenosine 3',5'-cyclic monophosphate (10-100 microM = 35 +/- 9 to 284 +/- 49 nM NO) but not by ATP, bradykinin, carbachol, 8-bromoguanosine 3',5'-cyclic monophosphate, or shear stress. This first functional demonstration of a constitutive NO synthase in cardiac myocytes suggests its regulation by a beta-adrenergic signaling pathway and may provide a novel mechanism for the coronary artery vasodilatation and enhanced diastolic relaxation observed with adrenergic stimulation.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Mechanical transduction of nitric oxide synthesis in the beating heart.

NO alters contractile and relaxant properties of the heart. However, it is not known whether changes in ventricular loading conditions affect cardiac NO synthesis. To understand this potential contractile-relaxant autoregulatory mechanism, production of cardiac NO in response to mechanical stimuli was measured in vivo using a porphyrinic sensor placed in the left ventricular myocardium. The beating rabbit heart exhibited cyclic changes in [NO], peaking at 2.7+/-0.1 micromol/L near the endocardium and 0.93+/-0.20 micromol/L in the midventricular myocardium (concentrations were 15+/-4% lower in the rat heart). In the present study, we demonstrate for the first time that increasing or decreasing ventricular preload in vivo is followed by parallel changes in [NO], which may represent a novel autoregulatory mechanism to adjust cardiac performance or perfusion on a beat-to-beat basis. To quantify the relationship between applied force and NO synthesis, intermittent compressive or distending forces applied to ex vivo nonbeating hearts were shown to cause bursts of NO synthesis, with peak [NO] linearly related to ventricular transmural pressure. Experiments in which denuding cardiac endothelial and endocardial cells abrogated the NO signal indicate that these cells transduce mechanical stimulation into NO production in the heart. Taken together, these studies may help explain load-dependent relaxation, cardiac memory for mechanical events of preceding beats, diseases associated with myocardial distension, autoregulation of myocardial perfusion, and protection from thrombosis in the turbulent flow environment within the beating heart.

Animals↗
PubMed1996

Direct in situ measurement of nitric oxide in mesenteric resistance arteries. Increased decomposition by superoxide in hypertension.

The endothelium plays a critical role in maintaining vascular tone by releasing vasoconstrictor and vasodilator substances. Endothelium-derived nitric oxide is a vasodilator that can be rapidly inactivated by superoxide (reaction rate constant, K = 3.6 x 10(9) L/mol per second). The measurement of nitric oxide concentration in biological systems is a challenging analytic problem because nitric oxide is also rapidly inactivated by Fe(II), Fe(III), and O2, all of which are found in great abundance in biological systems. To date, no currently used instrumental technique has been suitable for direct in situ measurement of NO in isolated resistance arteries. We designed the present study to perform for the first time direct in situ measurements of NO in rat mesenteric resistance arteries and to delineate the effects of hypertension on the release of NO and/or its interaction with superoxide. We describe here an adaptation of the recently published design of a porphyrinic sensor for direct in vitro measurement of NO in a single cell. The most significant advantage of this modified porphyrinic microsensor is that its small size makes it ideal for NO measurement in resistance arteries with an internal diameter of 200 microns or less. Small segments of the third-order branch of the mesenteric artery were isolated from normotensive Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats and placed in an organ chamber filled with Hanks' balanced salt solution buffer (2 mL, 37 degrees C). The tip of the porphyrinic microsensor was inserted into the lumen of an isolated vascular ring, and NO release was monitored in situ after maximal stimulation of NO synthase with the receptor-independent agonist calcium ionophore A23187 (10 mumol/L). Maximal surface concentration of NO measured after A23187 administration was significantly smaller in 15-week-old hypertensive rats (0.28 +/- 0.03 mumol/L, n = 10) than in age-matched normotensive rats (0.38 +/- 0.03 mumol/L, n = 10, P < .03). However, in the presence of the superoxide scavenger superoxide dismutase (100 U/mL), the peak NO level from the hypertensive rats was 0.37 +/- 0.04 mumol/L (n = 10), which was comparable to that observed for the normotensive rats in the absence and presence of superoxide dismutase. In summary, our results demonstrate that in rat mesenteric resistance arteries hypertension is associated with increased NO decomposition by superoxide, whereas NO release remains unaffected. This may be important in the pathogenesis of hypertension and its cardiovascular complications.

Animals↗
PubMed1995

Role of superoxide in the depressed nitric oxide production by the endothelium of genetically hypertensive rats.

We undertook these studies to determine whether a deficient nitric oxide production in genetically hypertensive rats could result from its being scavenged by an excess production of superoxide. In one study we used a porphyrinic microsensor to measure nitric oxide concentrations released by cultured endothelial cells from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). SHRSP cells released only about one third the concentration of nitric oxide as did WKY cells. Treatment of cells with superoxide dismutase increased nitric oxide release, demonstrating that normally nitric oxide is scavenged by endogenous superoxide. The increase in nitric oxide release in response to superoxide dismutase treatment was more than twice as great from SHRSP as from WKY cells, demonstrating the greater amount of superoxide in the hypertensive rats. A direct measure of superoxide with the use of lucigenin demonstrated the presence of 68.1 +/- 7.1 and 27.4 +/- 3.5 nmol/L of this anion in SHRSP and WKY endothelial cells, respectively. The presence of superoxide in the rat aorta was also estimated by quantification of its effect on carbachol relaxation. This relaxation was diminished when endogenous superoxide dismutase was blocked by diethyldithiocarbamic acid. This blockade reduced the relaxation by 51.2 +/- 5.2% in SHRSP aortas and by only 22.0 +/- 8.2% (P = .015) in WKY aortas. Data from these diverse systems are in agreement that superoxide production is excessive in SHRSP tissues. This excess superoxide, by scavenging endothelial nitric oxide, could contribute to the increased vascular smooth muscle contraction and hence to the elevated total peripheral resistance of these rats.

Animals↗
PubMed1995

Simultaneous measurements of Ca2+ and nitric oxide in bradykinin-stimulated vascular endothelial cells.

The production of endothelium-derived relaxing factor (EDRF), known to be nitric oxide (NO), is triggered by a rise in the cytoplasmic calcium concentration ([Ca2+]i) subsequent to receptor binding of vasoactive agonists. In vascular endothelial cells, NO is synthesized from L-arginine by the Ca2+/calmodulin-dependent NO synthase. In this study, we report the first simultaneous measurements of [Ca2+]i and [NO] at the level of single endothelial cells. In cultured bovine aortic endothelial cells, extracellular application of bradykinin (BK, 10 to 20 mumol/L) caused transient (sometimes oscillatory) increase in [Ca2+]i, which was measured with the fluorescent Ca2+ indicator fura 2 and fluorescence imaging microscopy. BK caused an increase in [Ca2+]i, primarily through release from intracellular stores. Under identical experimental conditions, BK caused a transient increase in [NO], which was measured by application of a porphyrinic NO microsensor. [NO] peaked at approximately 0.5 mumol/L. Simultaneous measurements of [Ca2+]i and [NO] in BK-stimulated endothelial cells revealed that a transient increase in [Ca2+]i was rapidly followed by an increase in [NO] that outlasted the [Ca2+]i transient.

Animals↗
PubMed1995

Osteoclast radical interactions: NADPH causes pulsatile release of NO and stimulates superoxide production.

Osteoclasts have been shown to destroy calcified tissue by complex developmental steps involving cell recruitment, cell attachment and deployment of multiple enzymes. They also appear to regulate resorption by several mechanisms. In particular, earlier investigations have indicated that oxygen radical metabolites may be produce by osteoclasts. These labile reactants could accelerate destruction of calcified tissue. In addition, recent studies have suggested that nitric oxide may have an inhibitory role in bone resorption. Previous studies of these radical substituents have predicted that interactions of nitric oxide and oxygen radicals could explain the conflicting roles of these radicals in the control of bone resorption. In view of the requirement of both of the enzymes, NADPH-oxidase and NO synthase (NOS), for NADPH(beta-nicotinamide adenine dinucleotide phosphate), one level of interaction could be related to competition for this necessary cofactor. To test this hypothesis, we have investigated the ability of the osteoclast to generate nitric oxide and oxygen radicals after stimulation by NADPH. Consistent with earlier diaphorase histochemistry, we have shown that resorbing osteoclasts produce NO. Addition of NADPH (10 microM) resulted in a transient burst of NO production (measured by porphyrin coated microsensor) with an amplitude of 152 +/- 43 nM and a duration of 4 seconds. Repetitive stimulation resulted in a decremental response with a partial recovery after 30 minutes. Addition of L-NAME (N omega-nitro-L-arginine methyl ester, 100 microM) to the cells resulted in at least 50% inhibition of the amplitude of NO peak and produced an extended peak duration. To compare the effect of the added NADPH on superoxide production by osteoclast NADPH-oxidase, osteoclast oxygen radicals were detected by EPR(electron paramagnetic resonance) spectrometer with the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The production of a spin adduct with a quadruplet signal was inhibited by SOD (superoxide dismutase). We were not able to demonstrate an increase in superoxide production after addition of L-NAME, another possible interaction of NOS and NADPH-oxidase. These results demonstrate that although osteoclasts produce both NO and superoxide, NOS competition for NADPH is not a major site of interaction with NADPH-oxidase under these conditions. Additionally, these initial findings set the stage for the further investigation of interactions of osteoclast radicals in modulating bone resorption.

Animals↗