Suppression of circadian clock protein cryptochrome 2 promotes osteoarthritis.

OBJECTIVES: Abnormal chondrocyte gene expression promotes osteoarthritis (OA) pathogenesis. A previous RNA-sequencing study revealed that circadian rhythm pathway and expression of core clock gene cryptochrome 2 (CRY2) are dysregulated in human OA cartilage. Here we determined expression patterns and function CRY1 and CRY2. METHODS: CRY mRNA and protein expression was analyzed in normal and OA human and mouse cartilage. Mice with deletion of Cry1 or Cry2 were analyzed for severity of experimental OA and to determine genes and pathways that are regulated by Cry. RESULTS: In human OA cartilage, CRY2 but not CRY1 staining and mRNA expression was significantly decreased. Cry2 was also suppressed in mice with aging-related OA. Cry2 knock out (KO) but not Cry1 KO mice with experimental OA showed significantly increased severity of histopathological changes in cartilage, subchondral bone and synovium. In OA chondrocytes, the levels of CRY1 and CRY2 and the amplitude of circadian fluctuation were significantly lower. RNA-seq on knee articular cartilage of wild-type and Cry2 KO mice identified 53 differentially expressed genes, including known Cry2 target circadian genes Nr1d1, Nr1d2, Dbp and Tef. Pathway analysis that circadian rhythm and extracellular matrix remodeling were dysregulated in Cry2 KO mice. CONCLUSIONS: These results show an active role of the circadian clock in general, and of CRY2 in particular, in maintaining extracellular matrix (ECM) homeostasis in cartilage. This cell autonomous network of circadian rhythm genes is disrupted in OA chondrocytes. Targeting CRY2 has potential to correct abnormal gene expression patterns and reduce the severity of OA.

Matrix-material dependence on the elongation of embedded gold nanoparticles induced by 4 MeV C60 and 200 MeV Xe ion irradiation.

We report the elongation of embedded Au nanoparticles (NPs) in three different matrices, i.e. amorphous carbon (a-C), crystalline indium tin oxide (InxSn1-xOz; ITO) and crystalline calcium fluoride (CaF2), under irradiations of 4 MeV C60 + cluster ions and 200 MeV Xe14+ ions. Under 4 MeV C60 cluster irradiation, strong sputtering is induced in CaF2 layer so that the whole the layer was completely lost at a fluence of 5 × 1013 ions cm-2. Au NPs were partly observed in the SiO2, probably due to the recoil implantation. Amorphous carbon (a-C) layer exhibits low sputtering loss even under 4 MeV C60 irradiation. However, the elongation in a-C layer was low. While the ITO layer showed a certain decrease in thickness under 4 MeV C60 irradiation, large elongation of Au NPs was observed under both 4 MeV C60 and 200 MeV Xe irradiation. The ITO layer preserved the crystallinity even after large elongation was induced. This is the first report of the elongation of metal NPs in a crystalline matrix.

Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1.

Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP-CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan.

Hillocks created for amorphizable and non-amorphizable ceramics irradiated with swift heavy ions: TEM study.

In a previous study, we found that hillocks (i.e. surface ion tracks) can be imaged using transmission electron microscopy (TEM) by irradiating thin CeO2 samples with swift heavy ions (SHI) at oblique incidence. In the present study, the same TEM method is applied to Y3Fe5O12 (YIG) and three fluorides (CaF2, SrF2 and BaF2) for observing hillocks. For YIG, which is one of the amorphizable materials, hillocks are found to have amorphous features consistent with amorphous features of ion tracks. For the fluorides, it is found that the hillocks do not exhibit amorphous features, and they are composed of nanocrystallites. Although hillocks for YIG and CaF2 exhibit different crystallographic features, hillock diameter agrees with the molten region diameter predicted by the thermal spike model for both materials. It is found that for YIG the hillock diameter is comparable to the ion track diameter, whereas for the fluorides it is always larger than the ion track diameter. The present result shows the existence of the velocity effect for ion track diameter in CaF2. It is also found that for fluorides both hillock and ion track diameters vary in the order of cation mass (i.e. CaF2 < SrF2 < BaF2). The above results of hillocks and ion tracks for SHI-irradiated fluorides can be consistently interpreted within the framework of the thermal spike model, if melting and successive recrystallization are assumed.

Effect of periodontal surgery on oral health-related quality of life in patients who have completed initial periodontal therapy.

BACKGROUND AND OBJECTIVE: Patient-centered assessments are particularly important in periodontal treatment in which their concerns may differ from the traditional clinical endpoints. However, information is limited regarding the influence of periodontal surgery on patients' quality of life (QoL). The aim of the present study was to investigate the impact of surgical periodontal therapy on the oral health-related QoL of patients who have received initial periodontal therapy. METHODS: A three-center prospective clinical study design was used, with the study participants comprising patients with moderate to severe periodontitis. Following initial periodontal therapy, the participants received either surgical or non-surgical periodontal treatment. The Oral Health-related Quality of Life Model for Dental Hygiene (OHRQL instrument), was used to assess participants' oral health-related QoL at each periodontal assessment interval: baseline (phase I), after initial therapy (phase II) and after surgery or during supportive periodontal therapy (phase III). RESULTS: Seventy-six patients (26 non-surgery, 50 surgery) completed the third phase of OHRQL assessment and were subjected to data analysis. From phase II to III, an improvement was achieved in all clinical parameters (p < 0.05-0.001) in the surgery group, whereas no such improvement was observed in the non-surgery group. In both groups, a significant difference in total OHRQL score was noted between phases I and III (p < 0.001 for surgery and p < 0.05 for non-surgery). The OHRQL domain scores for pain and eating/chewing function showed a significant improvement between these time points. However, no further significant improvement in OHRQL scores was achieved from phase II to III. CONCLUSION: A significant improvement in oral health-related QoL was noted between phases I and III in the surgery and non-surgery groups. Such improvement was less pronounced in the non-surgery vs. the surgery group. From phase II to III, neither surgery nor non-surgical treatment yielded significant improvement in oral health-related QoL.

Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT).

SUMMARY: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. INTRODUCTION: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. METHODS: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. RESULTS: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. CONCLUSIONS: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile.

Experimental evidence of crystalline hillocks created by irradiation of CeO2 with swift heavy ions: TEM study.

In this study, CeO2 was irradiated with 200 MeV Au ions at oblique incidence. Observation of as-irradiated samples by transmission electron microscopy (TEM) shows that hillocks are created not only at the wide surfaces, but also at the crack faces of the thin samples. Since the hillocks created at the crack faces can be imaged by TEM, their shape and crystallographic features can be revealed. From the images of hillocks created at the crack faces, many of the hillocks are found to be spherical. We present the first experimental evidence that hillocks created for CeO2 irradiated with swift heavy ions have a crystal structure whose lattice spacing and orientation coincide with those of the matrix. The mechanism of spherical crystalline hillock formation is discussed based on the present results.

Optical birefringence of Zn nanoparticles embedded in silica induced by swift heavy-ion irradiation.

Zn nanoparticles (NPs) embedded in a silica matrix subjected to irradiation with swift heavy ions of 200 MeV Xe¹4⁺ have been found to undergo shape elongation from spheres to prolate-spheroids while maintaining the major axes of the NPs in parallel alignment. The directionally-aligned Zn spheroids enable acquisition of optical properties, such as linear dichroism and birefringence. In this paper, the birefringence of the Zn spheroids was evaluated by the crossed-Nicols (XN) transmittance, where a sample was inserted between a pair of optical polarizers that were set in an orthogonal configuration. Linearly-polarized light aligned by the first polarizer was transformed to an elliptic polarization by the birefringence of the Zn spheroids. The existence of the birefringence was confirmed by the non-zero transmittance of the second polarizer in the orthogonal configuration. The sample irradiated with a fluence of 5.0 × 10¹³ ions/cm² exhibited a maximum XN transmittance of 2.1% at a photon energy of ~4 eV. The XN transmission was observed down to a fluence of 1.0 × 10¹² ions/cm², but reduced below the detection limit at a fluence of 1.0 × 10¹¹ ions/cm². The possible application of the elongated Zn NPs as a polarizer with nanometric thickness working in the near- and mid-ultraviolet region is discussed.

Shape elongation of Zn nanoparticles in silica irradiated with swift heavy ions of different species and energies: scaling law and some insights on the elongation mechanism.

Zinc nanoparticles (NPs) embedded in silica were irradiated with swift heavy ions (SHIs) of seven different combinations of species and energies. The shape elongation induced by the irradiations was evaluated by optical linear dichroism (OLD) spectroscopy, which is a sensitive tool for determining the change in the mean aspect ratio (AR) of NPs. Although the mean AR change indicated a linear fluence dependence in the low- and medium-fluence regions, it indicated a nonlinear dependence in the high-fluence region. The data reveal that the elongation efficiency of Zn is correlated with the electronic stopping power 'Se in silica' and is not correlated with either the 'Se in Zn' or the nuclear stopping power. The elongation efficiency plotted as a function of the 'Se in silica' revealed a linear relationship, with a threshold value of ∼2 keV nm(-1), which is the same dependence exhibited by the ion-track formation in silica. The log-log plot showed that the elongation efficiency increased linearly with Se above a critical value of ∼3 keV nm(-1) and steeply decreased with Se to the power of 5 below the critical Se. The steep decrease can be ascribed to the discontinuous nature of the ion tracks, which is expected at Se ∼ 2-4 keV nm(-1) in silica. The fluence Φ dependences of AR - 1 under various irradiations are well-normalized with the electronic energy deposition of SHIs, i.e., the product of Se and Φ, with a Se greater than the same critical value of ∼3 keV nm(-1). The normalized data above the critical value fell on a linear relation, AR(Φ) - 1 ∝ SeΦ, for SeΦ < 2 keV nm(-3) and a sublinear relation, AR(Φ) - 1 ∝ (SeΦ)(1/2) for SeΦ > 2 keV nm(-3). On the basis of these experimental results, we discuss some insights into the elongation mechanism.

Latent ion tracks were finally observed in diamond.

Injecting high-energy heavy ions in the electronic stopping regime into solids can create cylindrical damage zones called latent ion tracks. Although these tracks form in many materials, none have ever been observed in diamond, even when irradiated with high-energy GeV uranium ions. Here we report the first observation of ion track formation in diamond irradiated with 2-9 MeV C60 fullerene ions. Depending on the ion energy, the mean track length (diameter) changed from 17 (3.2) nm to 52 (7.1) nm. High resolution scanning transmission electron microscopy (HR-STEM) indicated the amorphization in the tracks, in which π-bonding signal from graphite was detected by the electron energy loss spectroscopy (EELS). Since the melting transition is not induced in diamond at atmospheric pressure, conventional inelastic thermal spike calculations cannot be applied. Two-temperature molecular dynamics simulations succeeded in the reproduction of both the track formation under MeV C60 irradiations and the no-track formation under GeV monoatomic ion irradiations.

Ion tracks in silicon formed by much lower energy deposition than the track formation threshold.

Damaged regions of cylindrical shapes called ion tracks, typically in nano-meters wide and tens micro-meters long, are formed along the ion trajectories in many insulators, when high energy ions in the electronic stopping regime are injected. In most cases, the ion tracks were assumed as consequences of dense electronic energy deposition from the high energy ions, except some cases where the synergy effect with the nuclear energy deposition plays an important role. In crystalline Si (c-Si), no tracks have been observed with any monomer ions up to GeV. Tracks are formed in c-Si under 40 MeV fullerene (C60) cluster ion irradiation, which provides much higher energy deposition than monomer ions. The track diameter decreases with decreasing the ion energy until they disappear at an extrapolated value of ~ 17 MeV. However, here we report the track formation of 10 nm in diameter under C60 ion irradiation of 6 MeV, i.e., much lower than the extrapolated threshold. The diameters of 10 nm were comparable to those under 40 MeV C60 irradiation. Furthermore, the tracks formed by 6 MeV C60 irradiation consisted of damaged crystalline, while those formed by 40 MeV C60 irradiation were amorphous. The track formation was observed down to 1 MeV and probably lower with decreasing the track diameters. The track lengths were much shorter than those expected from the drop of Se below the threshold. These track formations at such low energies cannot be explained by the conventional purely electronic energy deposition mechanism, indicating another origin, e.g., the synergy effect between the electronic and nuclear energy depositions, or dual transitions of transient melting and boiling.

C60 ions of 1 MeV are slow but elongate nanoparticles like swift heavy ions of hundreds MeV.

This study reports that high fluence fullerene ion (C60+) irradiation of 1-6 MeV, which was made possible by a new-type of high-flux ion source, elongates metal nanoparticles (NPs) in amorphous SiO2 as efficiently as swift heavy ions (SHIs) of 200 MeV Xe14+, i.e., two orders of the magnitude higher energy ions. Comparing the irradiation effects induced by both the beams, the stopping processes of C60 ions in SiO2 are discussed in this paper. Despite of having almost the same elongation efficiency, the C60+ irradiation induced ~10 times more efficient sputtering due to the clustering enhancement and/or the synergy effect. Ion tracks of ~10.4 nm in diameter and 60-80 nm in length were observed in crystalline SiO2 under 4 MeV C60 irradiation. While the track diameter was comparable to those by SHIs of the same electronic stopping, much shorter track lengths than those predicted by a rigid C60 molecule model indicates that the fragmentation occurred due to nuclear collisions. The elongation of the metal NPs was induced only down to the depth where the tracks were observed but not beyond.

Residual left ventricular pump function after acute myocardial infarction in NIDDM patients.

OBJECTIVE: Left ventricular remodeling occurs immediately after MI, involving structural changes in noninfarcted segment. However, the residual left ventricular pump function in NIDDM patients after acute MI has not been clarified. The purpose of this study was to evaluate the difference in the process of left ventricular remodeling between NIDDM and nondiabetic patients. RESEARCH DESIGN AND METHODS: Left ventricular regional EF images obtained by radionuclide angiography were investigated in 20 NIDDM and 29 nondiabetic patients the 3rd wk after acute MI. RESULTS: Regional EF of the noninfarcted area and P/V had a significant hyperbolic relation with left ventricular EDV in both groups of patients. Despite no difference in the extent of myocardial necrosis and the number of coronary vessels diseased between NIDDM and nondiabetic patients, regional EF of the noninfarcted area and P/V were significantly lower when left ventricular EDV increased in NIDDM patients compared with nondiabetic patients. CONCLUSIONS: Pathogenetic changes of the residual myocardium associated with NIDDM may adversely influence the process of left ventricular remodeling after MI, especially in patients with increased left ventricular EDV.

Translational regulation of angiotensin II type 1A receptor. Role of upstream AUG triplets.

The cDNA sequence of rat angiotensin II type 1A receptor (AT1AR) shows that AT1AR transcripts have AUG triplets in the 5'-leader region that may begin a short open reading frame encoding an 11-amino acid peptide. In this study, the mutational inactivation of the start codon of the short open reading frame in AT1AR-chloramphenicol acetyltransferase (CAT) reporter gene constructs resulted in a 2.6-fold increase in CAT activity, whereas CAT transcript levels were not affected. Furthermore, experiments with rat AT1AR cDNA-transfected Cos-7 cells revealed that mutagenesis of the upstream AUG increased the AT1AR protein up to 2.5-fold, although AT1AR transcript levels showed no changes. The synthetic peptide corresponding to the sequence of the short open reading frame significantly suppressed the amount of AT1AR product in the in vitro translation system. The inhibiting effect of the short open reading frame appears to operate at least in part at the level of translation initiation, because polysome analysis with transfected Cos-7 cells showed that mutagenesis of the upstream AUG resulted in a shift of AT1AR mRNA distribution from a smaller to larger fraction of polysomes. Taken together, these results show that the upstream AUG inhibits translational regulation, suggesting that the short open reading frame in the 5'-leader region of AT1AR transcripts has a certain role in the translation of AT1AR protein.

Arteriovenous differences of blood alcohol concentrations after celiac plexus block.

After a celiac plexus block with ethyl alcohol, patients sometimes complain of symptoms of alcohol intoxication. We studied the consecutive changes of arterial and venous blood alcohol concentrations in 11 patients and investigated whether an arteriovenous difference exists. We performed a celiac plexus block with 10 ml absolute ethyl alcohol. The sampling sites were radial artery and internal jugular vein. Blood samples were collected at 0, 5, 10, 15, 30, 60, 120, 240 and 480 minutes after the block. The maximum level was reached 15 minutes after injection in both arterial and venous blood, 29.9 +/- 19.4 and 27.7 +/- 21.8 mg/dl (means +/- SD), respectively. Arteriovenous differences were observed 5 and 10 minutes after ethyl alcohol injection (p less than 0.01). There was a significant negative correlation between the ratio of arteriovenous differences to venous sampling and the time elapsed after the block (r = 0.41, p less than 0.01).

Left ventricular function in myocardial infarction. Predictive value during negative low-level exercise three weeks postinfarction.

To evaluate whether the response of left ventricular pump function during low-level exercise in the early postinfarction period can anticipate its change during the first year after acute myocardial infarction (MI), global and regional ejection fractions (EF) were investigated using radionuclide angiography in 52 consecutive patients with negative predischarge exercise test. The changes in left ventricular EF and regional EF of the noninfarcted area during the early exercise test had a good linear relation with the changes during the first year after MI (r = 0.86, p less than 0.001 and r = 0.81, p less than 0.001, respectively). Our results indicate that the mobilization of the Frank-Starling mechanism and myocardial contractility were the important factors related to the change of left ventricular EF, and that the changes of left ventricular EF during exercise in the patient with a negative predischarge exercise test can predict the direction of change (concordant rise or fall) during the first year after MI.

Further characterization of trimethylamine N-oxide reductase from Escherichia coli, a molybdoprotein.

Escherichia coli trimethylamine N-oxide (TMAO) reductase I, the major enzyme among inducible TMAO reductases, was purified to homogeneity by an improved method including heat treatment, ammonium sulfate precipitation, and chromatographies on Bio-Gel A-1.5m, DEAE-cellulose, and Reactive blue-agarose. The molecular weight was estimated by gel filtration to be approximately 200,000. A single subunit peptide with a molecular weight of 95,000 was found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This enzyme contained 1.96 atoms of molybdenum, 0.96 atoms of iron, 1.52 atoms of zinc, and less than 0.4 atoms of acid-labile sulfur per molecular weight of 200,000. The absorption spectrum of the enzyme showed a peak at 278 nm and a shoulder at 288 nm, but no characteristic absorption was found from 350 to 700 nm. A fluorescent derivative of molybdenum cofactor was found when the enzyme was boiled with iodine in acidic solution; its fluorescence spectra were almost the same as those of the form A derivative of molybdopterin found in sulfite oxidase. The molybdenum cofactor released from heated TMAO reductase I reconstituted nitrate reductase in the extracts of Neurospora crassa mutant strain nit-1 lacking molybdenum cofactor. Thus, TMAO reductase I contains molybdopterin, which is a common constituent of some molybdenum-containing enzymes. Some kinetic properties were also determined.

End-tidal CO2 and plasma lactate level: a comparison of their use as parameters for evaluating successful CPR.

Serial changes of end-tidal CO2 (ETCO2) and plasma lactate levels during CPR have been described as useful to investigate or evaluate the results of CPR. However, there have been no reports comparing these parameters in the same model. By inducing cardiopulmonary arrest (2-7 min) in 28 Wistar rats, ETCO2 and serum lactate levels were studied after and just before CPR, respectively. In the survived group (N = 16), ETCO2 was maintained in high levels (20.1-16.3 mmHg), however in the non-survived group (N = 12), ETCO2 showed an abrupt decline (6.0-2.0 mmHg). The lactate levels before CPR in two groups were significantly higher than those of control levels, however there was no significant difference just before the CPR between the two groups. ETCO2 during CPR is a useful indicator for determining the successful application of CPR. However, serum lactate levels sampled just before the onset of CPR did not prove to be a useful indicator of successful CPR in rats.

Arteriovenous differences in PCO2 and cardiac output during CPR in the dog.

Using 14 mongrel dogs, we investigated the correlation between arteriovenous differences of PCO2 (AVD-CO2) and cardiac output (CO) during CPR. Ventricular fibrillation was induced by an electrical current and the respirator was stopped for 5 min. Cardiopulmonary resuscitation (CPR) was performed during the next 10 min and CO was measured with simultaneous arterial and venous blood gas analysis. CO was measured 26 times during CPR. The animals were divided into two groups according to the values of CO during CPR: low-CO group (CO < 0.3 l/min) and high-CO group (CO > or = 0.3 l/min). AVD-CO2 in the low CO group was 39.8 +/- 5.7 mmHg and that of the high group was 27.4 +/- 14.8 mmHg (mean +/- S.D., P < 0.05). In conclusion, AVD-CO2 showed an inverse result with the degree of CO during CPR.

Plasma lidocaine, monoethylglycinexylidide, and glycinexylidide concentrations after epidural administration in geriatric patients.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the effect of age on the pharmacokinetics of lidocaine after epidural administration. METHODS: Two percent lidocaine with epinephrine (5 microg/mL) was administered in two different age groups: an adult group (age 42 +/- 6 years, n = 10) and an elderly group (age 77 +/- 4 years, n = 10). Concentrations of lidocaine and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in plasma samples obtained after 15, 30, 45, 60, 90, 120, 150, and 180 minutes of administration using high-performance liquid chromatography with ultraviolet detection. RESULTS: No significant differences in plasma concentrations of lidocaine and its metabolites were observed between the two groups during the 3 hours of study. However, the elderly group showed significantly longer mean residence times (MRTs) and lower plasma clearance of lidocaine during the period compared with the adult group (P < .05). Plasma concentration ratios of MEGX/lidocaine were significantly lower in the elderly group after 2 hours of lidocaine administration (P < .05). CONCLUSIONS: The increase in plasma lidocaine concentration after epidural anesthesia in elderly patients was not as high as anticipated. However, the elderly patients showed longer MRTs, lower clearance, and lower ratios of MEGX/lidocaine than did the adult (middle-age) patients.