Extreme ultraviolet time-resolved photoelectron spectroscopy of adenine, adenosine and adenosine monophosphate in a liquid flat jet.

Time-resolved photoelectron spectroscopy using an extreme-ultraviolet (XUV) probe pulse was used to investigate the UV photoinduced dynamics of adenine (Ade), adenosine (Ado), and adenosine-5-monophosphate (AMP) in a liquid water jet. In contrast to previous studies using UV probe pulses, the XUV pulse at 21.7 eV can photoionize all excited states of a molecule, allowing for full relaxation pathways to be addressed after excitation at 4.66 eV. This work was carried out using a gas-dynamic flat liquid jet, resulting in considerably enhanced signal compared to a cylindrical jet. All three species decay on multiple time scales that are assigned based on their decay associated spectra; the fastest decay of ∼100 fs is assigned to ππ* decay to the ground state, while a smaller component with a lifetime of ∼500 fs is attributed to the nπ* state. An additional slower channel in Ade is assigned to the 7H Ade conformer, as seen previously. This work demonstrates the capability of XUV-TRPES to disentangle non-adiabatic dynamics in an aqueous solution in a state-specific manner and represents the first identification of the nπ* state in the relaxation dynamics of adenine and its derivatives.

Time-resolved photoelectron spectroscopy of iodide-4-thiouracil cluster: The ππ* state as a doorway for electron attachment.

The photophysics of thiobases-nucleobases in which one or more oxygen atoms are replaced with sulfur atoms- vary greatly depending on the location of sulfonation. Not only are direct dynamics of a neutral thiobase impacted, but also the dynamics of excess electron accommodation. In this work, time-resolved photoelectron spectroscopy is used to measure binary anionic clusters of iodide and 4-thiouracil, I- · 4TU. We investigate charge transfer dynamics driven by excitation at 3.88 eV, corresponding to the lowest ππ* transition of the thiouracil, and at 4.16 eV, near the cluster vertical detachment energy. The photoexcited state dynamics are probed by photodetachment with 1.55 and 3.14 eV pulses. Excitation at 3.88 eV leads to a signal from a valence-bound ion only, indicating a charge accommodation mechanism that does not involve a dipole-bound anion as an intermediate. Excitation at 4.16 eV rapidly gives rise to dipole-bound and valence-bound ion signals, with a second rise in the valence-bound signal corresponding to the decay of the dipole-bound signal. The dynamics associated with the low energy ππ* excitation of 4-thiouracil provide a clear experimental proof for the importance of localized excitation and electron backfilling in halide-nucleobase clusters.

Analysis of five cases showing false-high Hemoglobin A1c due to reduced catalase activity.

We encountered five cases that exhibited false-high Hemoglobin A1c (HbA1c) levels when samples were examined using the enzyme-based NORUDIA N HbA1c kit. HbA1c levels were higher than those obtained using other methods, such as HPLC, immune-based methods, and other enzyme-based kits. This kit produced inaccurate results for HbA1c when residual peroxides were present in samples. The addition of peroxidase solution restored false-high HbA1c levels in the five cases, indicating that reduced catalase activity was responsible for these values because catalase eliminates peroxide. Catalase activity and gene mutations were examined in the five cases and an immunohistological analysis was performed to assess the expression of catalase. Cases #1 and 2 were diagnosed as acatalasemia and cases #3, 4, and 5 as hypocatalasemia based on compound heterozygous SNP and heterozygous splicing mutations in the catalase gene. Therefore, impaired catalase activity was responsible for false-high HbA1c levels measured by the NORUDIA N HbA1c kit.

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Case 1 presented with severe anemia and received an intrauterine blood cell transfusion at 33 weeks of gestation. The anemia spontaneously improved in early infancy. Case 2, the father of Case 1, had an uneventful birth with no evidence of anemia, though microcytic anemia was observed during childhood. The genetic analysis of the ß-globin gene cluster identified a novel heterozygous deletion of DNA extending from the Gγ-globin gene downstream to the ß-globin gene, confirming a diagnosis of (G γA γδß)0 -thalassemia. In cases where thalassemia is suspected based on blood tests, a genetic diagnosis should be performed for the sake of the offspring.

Establishment of a reference interval for glycated albumin based on medical check-up data from multiple medical institutions.

Objectives: Data were collected to establish a reference interval for glycated albumin (GA), as well as to calculate a cutoff value for diagnosing diabetes mellitus and the GA level corresponding to a 75-g oral glucose tolerance test (OGTT) 2 h plasma glucose (2h-PG) level of 200 mg/dL.Methods: This study involved 1,843 subjects who were undergoing medical check-ups at several medical institutions and whose HbA1c and GA levels had been measured by OGTT.Results: The GA reference interval that was calculated based on the data obtained from study subjects with normal glucose tolerance was 12.1-17.1%. Using standardized major axis regression, the levels that corresponded to an OGTT 2h-PG level of 11.1 mmol/L were a GA level of 17.5% and an HbA1c level of 47.5 mmol/mol. A receiver-operating characteristic curve analysis was used to calculate the points at which sensitivity and specificity matched as the cutoff values, and the results yielded a GA level of 15.0% (sensitivity 69.3%).Conclusions: The GA reference interval was calculated to be 12.1-17.1%. We propose a GA level of 17.4% as a cutoff value to diagnose diabetes mellitus and a GA level of 15.0% as a screening cutoff value for diabetes mellitus, taking previous reports into account.

Estimation of mean erythrocyte age using HbA1c or HbA1c/glycated albumin for evaluation of anemia severity.

BACKGROUND: Hemoglobin A1c (HbA1c) levels are low in patients with hemolytic anemia, as HbA1c reflects mean erythrocyte age (MRBC ). Erythrocyte creatine (EC) is a hemolytic indicator that also reflects MRBC . We previously reported an equation for estimating MRBC using EC (EC-MRBC ). AIMS: In this study, EC-MRBC was compared to the HbA1c level expressed in the International Federation of Clinical Chemistry and Laboratory Medicine units (iA1c) and to the iA1c/glycated albumin (GA) ratio to estimate MRBC . METHODS: This study included 238 subjects, including patients with hemolytic anemia and/or type 2 diabetes mellitus (T2DM). RESULTS: In non-diabetic individuals, both iA1c and iA1c/GA showed a strong positive correlation with EC-MRBC (p < 0.0001). The equations to estimate iA1c-MRBC and iA1c/GA-MRBC derived from the regression equations between EC-MRBC and iA1c, and EC-MRBC and iA1c/GA in nondiabetic individuals were 1.45 × iA1c and 20.0 × iA1c/GA, respectively. iA1c-MRBC and iA1c/GA-MRBC in non-diabetic individuals without hemolytic anemia were 57.6 ± 4.0 and 57.1 ± 6.4 days, respectively, and iA1c/GA-MRBC in T2DM patients without hemolytic anemia was 56.0 ± 8.8 days.; no significant difference was seen in the comparisons. CONCLUSIONS: The MRBC can be estimated using iA1c or iA1c/GA in non-diabetic individuals, and iA1c/GA in T2DM patients.

Femtosecond dynamics of stepwise two-photon ionization in solutions as revealed by pump-repump-probe detection with a burst mode of photoexcitation.

Pump-repump-probe spectroscopy with a burst mode of photoexcitation was applied to the direct observation of the photoionization dynamics of perylene in the solution phase. Irradiation of a pump pulse train generated with birefringent crystals effectively accumulated an intermediate S1 state and a repump pulse triggered photoionization in the higher excited state, ensuring sufficiently large signal intensity to probe. Two-photon excitation to the energy level, which is 0.7 eV lower than the ionization potential in the gas phase, results in instantaneous formation of the radical cation of perylene in acetonitrile, unlike aromatic amines in previous reports. In addition, subsequent recombination dynamics between the radical cation and ejected electron was monitored in polar and nonpolar solvents. The ultrafast recombination in nonpolar solvents suggests that the distribution of the distance in the cation-ejected electron pair largely evolves even in acetonitrile in the femtosecond timescale, in which the solvation is not completed and the dielectric constant is still low. The recombination process in acetonitrile was well reproduced with simulations based on the Smoluchowski equation taking account of the transient change in the dielectric constant by solvation.

Electron attachment dynamics following UV excitation of iodide-2-thiouracil complexes.

The dynamics of low energy electron attachment to the thio-substituted uracil analog 2-thiouracil are investigated using time-resolved photoelectron spectroscopy (TRPES) of iodide-2-thiouracil (I-·2TU) binary clusters. In these experiments, the anions are excited at pump energies of 4.16 and 4.73 eV, and the ensuing dynamics are probed by photodetachment at 1.59 and 3.18 eV. Upon excitation near the vertical detachment energy (4.16 eV), dipole bound (DB) and valence bound (VB) anion signals appear almost instantaneously, and the DB state of the 2TU anion undergoes an ultrafast decay (∼50 fs). At 4.73 eV, there is no evidence for a DB state, but features attributed to two VB states are seen. The transient negative ions formed by photoexcitation decay by autodetachment and I- fragmentation. The I- dissociation rates and their dependence on excitation energy agree reasonably well with the Rice-Ramsperger-Kassel-Marcus calculations. Notable differences with respect to TRPES of the related iodide-uracil anion are observed and discussed.

Direct determination of molar absorption coefficients of several molecules in the lowest excited singlet states.

Molar absorption coefficient of the lowest excited state is an indispensable information for the quantitative investigation of photochemical reactions by means of transient absorption spectroscopy. In the present work, we quantitatively estimated the molar absorption coefficients of the S1 state of the solute in three solution systems, Rhodamine B in ethanol, ZnTPP in DMF and N,N'-bis(2,6-diisopropylphenyl)terrylene-3,4,11,12-tetracarboxydiimide (TDI) in chloroform, by perfectly bleaching the ground state molecules using the picosecond 532-nm laser pulse with a large number of photons. These solution systems were selected because no obvious photodegradation was detected in the present range of the excitation intensity. The molar absorption coefficient obtained by this method was verified by the numerical analysis of the excitation intensity dependence of the transient absorbance by taking into account the inner filter effect (absorption of the excitation light by the S1 state produced by the leading part of the pump pulse) and the decrease of the ground state molecules by the pump process (depletion). In addition, these molar absorption coefficients were confirmed by the comparison of relations between the excitation intensity and the transient absorbance of the S1 state under the condition where the fraction of the excited solute is ≪ 10% by the femtosecond pulsed laser excitation. From these results, the error of the molar absorption coefficients was estimated to be < 5%. These values can be used as reference ones for the estimation of molar absorption coefficients of other systems leading to the quantitative elucidation of the photochemical reactions detected by the transient absorption spectroscopy.

Slow photoionization via higher excited states of N,N-dimethylaniline in ethanol solution probed by femtosecond transient absorption spectroscopy under two-pulse two-photon excitation.

Photoionization dynamics of N,N-dimethylaniline (DMA) from highly electronically excited states in ethanol solution was investigated by means of femtosecond two-pulse two-photon excitation transient absorption (2PE-TA) spectroscopy. The first pump pulse prepares the lowest singlet excited state (S1 state) of DMA, and the second one excites the S1 state into higher excited states. In the case with the second pulse at 500 nm, the ionization took place via a rapid channel (<100 fs) and a slow one with the time constant of ∼10 ps. The excitation wavelength effect of the second pulse indicated that a specific electronic state produced directly from higher excited states was responsible for the slow ionization. By integrating these results with the time evolution of the transient absorption spectra of the solvated electron in neat ethanol detected by the simultaneous two-photon excitation, it was revealed that the slow ionization of DMA in ethanol was regulated by the formation of the anionic species just before the completion of the solvation of the electron, leading to the solvated electron in the relaxed state. From these results, it was strongly suggested that the capture of the electron of the Rydberg-like state by the solvent or solvent cluster regulates the appearance of the cation radical.

Ultrafast capture of electrons ejected by photoionization leading to the formation of a charge-separated state at a high energy level.

Electron transfer reactions driven by two-photon ionization in the higher excited state were investigated via transient absorption spectroscopy, with the aim to develop a method for creating the charge-separated (CS) state with a large formation rate, high energy level, and long lifetime. In the proof-in-principle experiments using pyrene and biphenyl as a model system, femtosecond transient absorption spectroscopy revealed that intense irradiation of an ultraviolet laser pulse at 355 nm efficiently pumps up pyrene into a higher excited state via a stepwise two-photon absorption, and then an ionization process takes place. An electron ejected from pyrene is directly captured by biphenyl with a time constant of 200 fs without the diffusion process of the electron in solution. The energy level of the CS state (Py+-Bp-) thus formed was estimated to be higher than that of the S1 state of pyrene by 0.53 eV. In addition, the subsequent ionic dissociation without a remarkable geminate recombination in the sub-nanosecond to nanosecond time region effectively avoids the quantity loss of the CS state. By applying the two-photon excitation method, we experimentally achieved ultrafast formation of the long-lived CS state at a high energy beyond the traditional framework of electron transfer reactions.

Usefulness of the index calculated as the product of levels of fasting plasma glucose and hemoglobin A1c for insulinoma screening.

Hypoglycemia is the major symptom of insulinoma. Chronic and recurrent hypoglycemia leads to the disappearance of autonomic symptoms and persistence of non-specific symptoms alone, possibly contributing to the delayed diagnosis of insulinoma and accounting for several undiagnosed cases. We previously reported the usefulness of hemoglobin A1c (HbA1c) and glycated albumin as markers for early insulinoma screening; however, their diagnostic prediction performance and diagnostic performance were not satisfactory. We hypothesized that the product of fasting plasma glucose (FPG) and HbA1c levels (FPG × HbA1c index) is low in insulinoma, and this index may be a useful marker for screening. This cross-sectional multicenter study compared 82 insulinoma patients with 100 age-, sex-, and body mass index-matched controls with normal glucose tolerance based on 75-g oral glucose tolerance test. The FPG × HbA1c index was significantly lower in the insulinoma group than in the control group. Receiver operating curve analysis showed that the optimal cutoff point of the FPG × HbA1c index to diagnose insulinoma was 447.1, and the area under the curves (AUCs) of the FPG × HbA1c index and HbA1c were 0.998 and 0.966, respectively. The AUC of the index was significantly higher than that of HbA1c (p = 0.010). Conversely, no significant difference existed between the AUC of the FPG × HbA1c index and that of the FPG/fasting immunoreactive insulin index. Thus, in apparently healthy population, the product of FPG and HbA1c yields a useful index for insulinoma screening in terms of accuracy and versatility.

Usefulness of hemoglobin A1c and glycated albumin measurements for insulinoma screening: an observational case-control study.

BACKGROUND: Insulinoma represents hypoglycemia as a predominant symptom; the autonomic symptoms may be resolved by chronically recurrent hypoglycemia resulting in the persistence of non-specific symptoms alone. Therefore, it has been estimated that there are many patients in whom the disease takes longer to diagnose and has remained undiagnosed. Although some parameters exist for the definitive diagnosis of the disease, there are currently no indices for early screening. Indices of glycemic control, hemoglobin A1c (HbA1c), and glycated albumin (GA) may be useful for the screening of patients with insulinoma having chronic hypoglycemia because the values become low in such a condition. Because there are no articles that have reported the point, we examine the effective cutoff values of HbA1c and GA for the diagnosis of insulinoma in the present study. METHODS: In a multicenter cross-sectional study, 31 patients with insulinoma were included for comparison with 120 control subjects with normal glucose tolerance based on 75 g oral glucose tolerance tests whose characteristics were matched to the patients. The primary outcomes were optimal cutoff values of HbA1c and GA for the screening of insulinoma. RESULTS: HbA1c was significantly lower in the insulinoma group at 4.7 ± 0.4% compared to the healthy control group at 5.7 ± 0.3% (p < 0.001), and GA was significantly lower in the insulinoma group at 11.6 ± 1.8% compared to the healthy control group at 14.5 ± 1.0% (p < 0.001). According to a receiver operating characteristic (ROC) analysis, optimal cutoff values of HbA1c and GA for the diagnosis of insulinoma were 5.0 and 12.4%, respectively. Area under the curve values of HbA1c and GA were 0.970 and 0.929, respectively, showing no significant difference (p = 0.399). CONCLUSIONS: In the present study, HbA1c and GA values in patients with insulinoma were significantly lower compared to the healthy controls, and effective cutoff values for screening were shown in the diagnosis of insulinoma for the first time. HbA1c and GA can be useful indices for insulinoma screening. Because malignant insulinoma have a similar diagnostic process to that of benign insulinoma, these could be useful for malignant insulinoma.

Ionization dynamics of a phenylenediamine derivative in solutions as revealed by femtosecond simultaneous and stepwise two-photon excitation.

Femtosecond transient absorption spectroscopy with off-resonant simultaneous and resonant stepwise two-photon excitation methods were applied to the direct observation of photoionization dynamics of a phenylenediamine derivative in n-hexane, ethanol and acetonitrile solutions. Upon the selective excitation of the solute via the off-resonant two-photon excitation to the energy level almost equivalent with the ionization potential in the gas phase, rapid appearance of the radical cation (within ca. 100-200 fs) was observed in polar and nonpolar solutions. On the other hand, in the case where the excited energy level from the ground state is 0.8 eV lower than the ionization potential in the gas phase, the radical cation appears only in polar solutions in sub-ps to ps time scales, indicating that the photoionization does not occur directly from the highly electronically excited state even in the polar solution. Comparison of the dynamics between ethanol and acetonitrile solutions strongly suggested that the solvation process of the precursor species leading to the ionization took a crucial role in the electron ejection process with lower energy in polar solutions.

Hemolysis causes a decrease in HbA1c level but not in glycated albumin or 1,5-anhydroglucitol level.

HbA1c has been widely used as a glycemic control indicator or as a diagnostic indicator for diabetes mellitus. However, HbA1c is affected by the erythrocyte life span and, therefore, shows falsely low values in hemolytic patients. Erythrocyte creatine (EC) is a sensitive hemolytic marker that reflects the mean erythrocyte age. In the present study, the relationships of HbA1c, glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG) with different hemolytic markers, including EC, were investigated in non-diabetic individuals. A total of 43 non-diabetic individuals whose complete blood count and reticulocytes were measured via medical examinations were included in this study (28 individuals with hemolysis and 15 individuals without hemolysis). Those with suspected diabetes mellitus based on medical history, low 1,5-AG values, or had comorbid liver and renal diseases were excluded from this study. HbA1c, GA, 1,5-AG, and various hemolytic markers were measured to examine the correlation of the glycemic control indicators with the various hemolytic markers. A significant correlation was observed between GA and 1,5-AG but not between HbA1c and GA or 1,5-AG. Significant correlations were observed between HbA1c values and various hemolytic markers (reticulocytes, haptoglobin, and EC) but not between GA or 1,5-AG values and those hemolytic markers. HbA1c, but not with GA and 1,5-AG, showed significant correlations with the hemolytic markers. These results suggested that HbA1c does not reflect the glycemic control accurately in hemolytic patients, while GA and 1,5-AG values are not affected by mean erythrocyte age and, therefore, accurately reflect the glycemic control.

Shortened mean erythrocyte age in female patients with type 2 diabetes mellitus.

BACKGROUND: The hyperglycemic state is known to shorten the erythrocyte life span. Erythrocyte creatine (EC) reflects the mean erythrocyte age and is useful as an indicator of hemolysis. Here, we studied the relationship between EC and glycemic control indicators [HbA1c or glycated albumin (GA)] in non-diabetic subjects and diabetic patients. METHODS: This study included 119 patients with type 2 diabetes mellitus (T2DM) and 76 non-diabetic subjects matched by sex and age. We studied the relationships between EC and HbA1c or GA in patients with T2DM and non-diabetic subjects. RESULTS: Erythrocyte creatine in T2DM patients was significantly higher than that in non-diabetic subjects, and the ratio of high EC levels (>1.8 µmol/g Hb) in T2DM patients was significantly higher as well. Furthermore, female EC was significantly higher than male EC, and the ratio of high EC levels in females was significantly higher than in the males as well. While male EC had no significant correlation with HbA1c or GA, female EC had significant positive correlations with both. Male EC had no significant difference between T2DM patients and non-diabetic subjects, while the EC in female patients with T2DM was significantly higher than in female non-diabetic subjects. CONCLUSIONS: The significant positive correlations of EC with HbA1c and GA in female patients with T2DM suggested that the mean erythrocyte age decreased in female diabetic patients with poor glycemic control.

Excited state dynamics for visible-light sensitization of a photochromic benzil-subsituted phenoxyl-imidazolyl radical.

Visible-light sensitized photoswitches have been paid particular attention in the fields of life sciences and materials science because long-wavelength light reduces photodegradation, transmits deep inside of matters, and achieves the selective excitation in condensed systems. Among various photoswitch molecules, the phenoxyl-imidazolyl radical complex (PIC) is a recently developed thermally reversible photochromic molecule whose thermal back reaction can be tuned from tens of nanoseconds to tens of seconds by rational design of the molecular structure. While the wide range of tunability of the switching speed of PIC opened up various potential applications, no photosensitivity to visible light limits its applications. In this study, we synthesized a visible-light sensitized PIC derivative conjugated with a benzil unit. Femtosecond transient absorption spectroscopy revealed that the benzil unit acts as a singlet photosensitizer for PIC by the Dexter-type energy transfer. Visible-light sensitized photochromic reactions of PIC are important for expanding the versatility of potential applications to life sciences and materials science.

Multiphoton-gated cycloreversion reaction of a fluorescent diarylethene derivative as revealed by transient absorption spectroscopy.

The one- and two-photon cycloreversion reactions of a fluorescent diarylethene derivative with oxidized benzothiophene moieties were investigated by means of ultrafast laser spectroscopy. Femtosecond transient absorption spectroscopy under the one-photon excitation condition revealed that the excited closed-ring isomer is simply deactivated into the initial ground state with a time constant of 2.6 ns without remarkable cycloreversion, the results of which are consistent with the very low cycloreversion reaction yield (<10-5) under steady-state light irradiation. On the other hand, an efficient cycloreversion reaction was observed under irradiation with a picosecond laser pulse at 532 nm. The excitation intensity dependence of the cycloreversion reaction indicates that a highly excited state attained by the stepwise two-photon absorption is responsible for the marked increase of the cycloreversion reaction, and the quantum yield at the highly excited state was estimated to be 0.018 from quantitative analysis, indicating that the reaction is enhanced by a factor of >1800.

Glycemic control indicator levels at diagnosis of neonatal diabetes mellitus: Comparison with other types of insulin-dependent diabetes mellitus.

BACKGROUND: Neonatal diabetes mellitus (NDM) is a monogenic insulin-dependent diabetes that develops within 6 months of age. The progression of hyperglycemia until diagnosis is unknown. Glycemic control indicators at diagnosis are useful to estimate the extent and duration of hyperglycemia. We recently established that age-adjusted glycated albumin (GA) is a useful indicator of glycemic control, regardless of age. OBJECTIVE: To compare the levels of various glycemic control indicators at diagnosis between NDM and other types of insulin-dependent diabetes mellitus. PATIENTS AND METHODS: We included 8 patients with NDM, 8 with fulminant type 1 diabetes (FT1D), and 24 with acute-onset autoimmune type 1 diabetes (T1AD). Plasma glucose, glycated hemoglobin (HbA1c), GA, and age-adjusted GA (calculated as previously reported) were measured and compared. RESULTS: There were no significant differences in the plasma glucose levels of the group of patients with NDM and those with FT1D or T1AD. HbA1c and GA levels in the NDM group were not significantly different from those in the FT1D group, and both indicators were lower than those in the T1AD group. Age-adjusted GA levels in the NDM group did not differ significantly from those in the T1AD group, but were higher than those in the FT1D group. CONCLUSIONS: These findings suggest that the time-course of plasma glucose elevation in NDM until diagnosis is similar to that in T1AD. In addition, the high age-adjusted GA value at diagnosis of NDM indicates that this test is useful for assessing chronic hyperglycemia in NDM.