Inhibition of NADPH oxidase alleviates experimental diabetes-induced myocardial contractile dysfunction.

AIM: O(2) (-) production is implicated in cardiac dysfunction for a number of diseases including diabetes. Activation of the O(2) (-)-producing enzyme NADPH oxidase is seen in diabetes, although its role in diabetic cardiomyopathy is unclear. This study was designed to evaluate the effect of NADPH oxidase inhibition on cardiac function in diabetes. METHODS: Experimental diabetes was induced in adult C57 mice using streptozotocin (STZ, 150 mg/kg, i.p.) prior to the administration of the NADPH oxidase inhibitor apocynin (4 mg/kg/day) for 2 weeks. Left ventricular (LV) and myocyte contractile functions were evaluated using echocardiography and edge-detection, respectively. RESULTS: STZ elicited hyperglycaemia and reduced body weight gain, which was unaffected by apocynin. STZ significantly reduced fractional shortening, LV wall thickness, peak shortening, maximal velocity and duration of shortening or relengthening, the effects of which - with the exception of wall thickness - were significantly attenuated or ablated by apocynin. Western blot analysis revealed that the effects of comparable Akt phosphorylation, reduced AMPK phosphorylation, downregulation of sarco(endo)plasmic reticulum Ca(2+)-ATPase and lessened phosphorylation of phospholamban in diabetic myocardium were unaffected by apocynin. Both apocynin and the nitric oxide synthase (NOS) inhibitor l-arginine methyl ester (L-NAME) inhibited elevated O(2) (-) production in diabetes without any additive effect between the two, indicating the presence of endothelial nitric oxide synthase (eNOS) uncoupling. However, neither diabetes nor apocynin altered the expression of heat shock protein 90 and eNOS phosphorylation (Ser(1177)). In addition, apocynin mitigated elevated levels of nitrotyrosine and nitric oxide in diabetes. CONCLUSION: Taken together, these data indicate the beneficial role of NADPH oxidase inhibition in diabetes-induced myocardial contractile dysfunction.

Monitoring system for isolated limb perfusion based on a portable gamma camera.

BACKGROUND: The treatment of malignant melanoma or sarcomas on a limb using extremity perfusion with tumour necrosis factor (TNF-alpha) and melphalan can result in a high degree of systemic toxicity if there is any leakage from the isolated blood territory of the limb into the systemic vascular territory. Leakage is currently controlled by using radiotracers and heavy external probes in a procedure that requires continuous manual calculations. The aim of this work was to develop a light, easily transportable system to monitor limb perfusion leakage by controlling systemic blood pool radioactivity with a portable gamma camera adapted for intraoperative use as an external probe, and to initiate its application in the treatment of MM patients. METHODS: A special collimator was built for maximal sensitivity. Software for acquisition and data processing in real time was developed. After testing the adequacy of the system, it was used to monitor limb perfusion leakage in 16 patients with malignant melanoma to be treated with perfusion of TNF-alpha and melphalan. RESULTS: The field of view of the detector system was 13.8 cm, which is appropriate for the monitoring, since the area to be controlled was the precordial zone. The sensitivity of the system was 257 cps/MBq. When the percentage of leakage reaches 10% the associated absolute error is +/-1%. After a mean follow-up period of 12 months, no patients have shown any significant or lasting side-effects. Partial or complete remission of lesions was seen in 9 out of 16 patients (56%) after HILP with TNF-alpha and melphalan. CONCLUSION: The detector system together with specially developed software provides a suitable automatic continuous monitoring system of any leakage that may occur during limb perfusion. This technique has been successfully implemented in patients for whom perfusion with TNF-alpha and melphalan has been indicated.

Search for the rare decay B-->pil+ l-.

We have performed a search for the flavor-changing neutral-current decays B-->pil+ l-, where l+ l- is either e+ e- or mu+ mu-, using a sample of 230 x 10(6) Upsilon(4S)-->BB decays collected with the BABAR detector. We observe no evidence of a signal and measure the upper limit on the isospin-averaged branching fraction to be B(B-->pil+ l-)<9.1 x 10(-8) at 90% confidence level. We also search for the lepton-flavor-violating decays B-->pie+/- mu-/+ and measure an upper limit on the isospin-averaged branching fraction of B(B-->pie+/- mu-/+)<9.2 x 10(-8) at 90% confidence level.

Development of a variable-radius pinhole SPECT system with a portable gamma camera.

OBJECTIVE: To develop a small-animal SPECT system using a low cost commercial portable gamma camera equipped with a pinhole collimator, a continuous scintillation crystal and a position-sensitive photomultiplier tube. MATERIAL AND METHODS: The gamma camera was attached to a variable radius system, which enabled us to optimize sensitivity and resolution by adjusting the radius of rotation to the size of the object. To investigate the capability of the SPECT system for small animal imaging, the dependence of resolution and calibration parameters on radius was assessed and acquisitions of small phantoms and mice were carried out. RESULTS: Resolution values, ranging from 1.0mm for a radius of 21.4mm and 1.4mm for a radius of 37.2mm were obtained, thereby justifying the interest of a variable radius SPECT system. CONCLUSIONS: The image quality of phantoms and animals were satisfactory, thus confirming the usefulness of the system for small animal SPECT imaging.

Radioguided occult lesion localisation in breast cancer using an intraoperative portable gamma camera: first results.

PURPOSE: The role of the radioguided occult lesion localisation (ROLL) technique in breast cancer has been increasing in recent years. One of the important drawbacks of such a technique is radiotracer spillage within the mammary gland that makes the precise lesion resection difficult, and this requires the use of a hook-wire collocation to reach the lesion. The possibility of obtaining an intraoperative image of the specimen could help to confirm whether the lesion is correctly removed. Some types of portable gamma cameras have been designed, but up to now, intraoperative use has been confined to surgery of parathyroid adenomas and sentinel lymph node location. The aim of the study was to value the usefulness of an intraoperative gamma camera to assess the resection of non-palpable breast lesions. MATERIALS AND METHODS: The study involved 42 women diagnosed with non-palpable early breast cancer. Lymphoscintigraphy was performed on the day before surgery by injection of (99m)Tc-labelled nanocolloid. During surgery a gamma probe was used to guide the surgeon, and afterwards images of the surgical bed and the tumoral specimen were acquired by means of a portable gamma camera, fitted with a pinhole collimator. A (99m)Tc pointer was used to draw an outline image around the specimen. RESULTS: On lymphoscintigraphy, radiotracer was concentrated in 31 cases. During surgery, all lesions were removed. In the images acquired by the portable gamma camera, the lesion was centred inside the surgical specimen in 23 of 42 cases, non-centred in 15 and in contact in 4 cases. Congruence of 60% was found between the intraoperative images and the histopathological results. The posterior margin was the most frequently involved. The whole acquisition time for the tumoral specimen with its margins was 5 min at most. CONCLUSION: The use of portable gamma cameras in theatre is in an early phase. The short period of time required during the surgical procedure will allow the surgical team to improve this technique until it can replace hand-held probes. The intraoperative acquisition of such images can predict the involvement of surgical margins, avoiding future surgical procedures.

Exclusive branching-fraction measurements of semileptonic tau decays into three charged hadrons, into phipi(-)nu tau, and into phi K(-)nu tau.

Using a data sample corresponding to an integrated luminosity of 342 fb(-1) collected with the BABAR detector at the SLAC PEP-II electron-positron storage ring operating at a center-of-mass energy near 10.58 GeV, we measure B(tau(-)--> pi(-)pi(-)pi+nu(tau)(ex.K(S0))=(8.83+/-0.01+/-0.13)%, B(tau(-) -->K(-)pi(-)pi+nu tau(ex.K(S0))=(0.273+/-0.002+/-0.009)%, B(tau(-) -->K(-)pi(-)K+nu tau)=(0.1346+/-0.0010+/-0.0036)%, and B(tau(-) -->K(-)K(-)K+nu tau)=(1.58+/-0.13+/-0.12)x10;{-5}, where the uncertainties are statistical and systematic, respectively. These include significant improvements over previous measurements and a first measurement of B(tau(-) -->K(-)K(-)K+nu tau) in which no resonance structure is assumed. We also report a first measurement of B(tau(-) -->var phi(-)nu tau)=(3.42+/-0.55+/-0.25)x10(-5), a new measurement of B(tau(-) -->var phi K(-)nu tau)=(3.39+/-0.20+/-0.28)x10(-5) and a first upper limit on B(tau(-) -->K(-)K(-)K+nu tau(ex.var phi)).

Measurement of the absolute branching fraction of D0-->K-pi+.

We measure the absolute branching fraction for D(0)-->K(-)pi(+) using partial reconstruction of B(0)-->D(*+)Xl(-)nu(l) decays, in which only the charged lepton and the pion from the decay D(*+)-->D(0)pi(+) are used. Based on a data sample of 230 x 10(6) BB pairs collected at the Upsilon(4S) resonance with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC, we obtain B(D(0)-->K(-)pi(+)) = (4.007+/-0.037+/-0.072)%, where the first uncertainty is statistical and the second is systematic.

Measurement of branching fractions and mass spectra of B-->Kpipigamma.

We present a measurement of the partial branching fractions and mass spectra of the exclusive radiative penguin processes B-->Kpipigamma in the range m(Kpipi)<1.8 GeV/c(2). We reconstruct four final states: K(+)pi(-)pi(+)gamma, K(+)pi(-)pi(0)gamma, K(S)(0)pi(-)pi(+)gamma, and K(S)(0)pi(+)pi(0)gamma, where K(S)(0)-->pi(+)pi(-). Using 232 x 10(6) e(+)e(-)-->BB events recorded by the BABAR experiment at the SLAC PEP-II asymmetric-energy storage ring, we measure the branching fractions B(B(+)-->K(+)pi(-)pi(+)gamma)=[2.95+/-0.13(stat)+/-0.20(syst)] x 10(-5), B(B(0)-->K(+)pi(-)pi(0)gamma)=[4.07+/-0.22(stat)+/-0.31(syst)] x 10(-5), B(B(0)-->K(0)pi(+)pi(-)gamma)=[1.85+/-0.21(stat)+/-0.12(syst)] x 10(-5), and B(B(+)-->K(0)pi(+)pi(0)gamma)=[4.56+/-0.42(stat)+/-0.31(syst)] x 10(-5).

Evidence of a broad structure at an invariant mass of 4.32 GeV/c2 in the reaction e+e- --> pi+pi-psi(2S) measured at BABAR.

We present a measurement of the cross section of the process e(+)e(-)-->pi(+)pi(-)psi(2S) from threshold up to 8 GeV center-of-mass energy using events containing initial-state radiation, produced at the SLAC PEP-II e(+)e(-) storage rings. The study is based on 298 fb(-1) of data recorded with the BABAR detector. A structure is observed in the cross section not far above threshold, near 4.32 GeV. We also investigate the compatibility of this structure with the Y(4260) previously reported by this experiment.

Observation of CP violation in B(0) --> K(+)pi(-) and B(0) --> pi(+)pi(-).

We report observations of CP violation in the decays B(0) --> K(+)pi(-) and B(0) --> pi(+)pi(-) in a sample of 383 x 10(6) Upsilon(4S) --> BB[over] events. We find 4372+/-82 B(0) --> K(+)pi(-) decays and measure the direct CP-violating charge asymmetry A(Kpi) = -0.107+/-0.018(stat)(-0.004)(+0.007)(syst), which excludes the CP-conserving hypothesis with a significance of 5.5 standard deviations. In the same sample, we find 1139+/-49 B(0) --> pi(+)pi(-) decays and measure the CP-violating asymmetries S(pipi) = -0.60+/-0.11(stat)+/-0.03(syst) and C(pipi) = -0.21+/-0.09(stat)+/-0.02(syst). CP conservation in B(0) --> pi(+)pi(-) (S(pipi) = C(pipi) = 0) is excluded at a confidence level 1-C.L. = 8 x 10(-8), corresponding to 5.4 standard deviations.

Observation of a Charmed Baryon Decaying to D;{0}p at a Mass Near 2.94 GeV/c;{2}.

A search for charmed baryons decaying to D(0)p reveals two states: the Lambdac(2880)+ baryon and a previously unobserved state at a mass of [2939.8+/-1.3(stat)+/-1.0(syst)] MeV/c2 and with an intrinsic width of [17.5+/-5.2(stat)+/-5.9(syst)] MeV. Consistent and significant signals are observed for the K(-)pi(+) and K(-)pi(+)pi(-)pi(+) decay modes of the D0 in 287 fb(-1) annihilation data recorded by the BABAR detector at a center-of-mass energy of 10.58 GeV. There is no evidence in the D+p spectrum of doubly charged partners. The mass and intrinsic width of the Lambdac(2880)+ baryon and relative yield of the two baryons are also measured.

Observation of CP violation in B --> eta'K0 decays.

We present measurements of the time-dependent CP-violation parameters S and C in B(0) --> eta(')K(0) decays. The data sample corresponds to 384 x 10(6) BB pairs produced by e(+)e(-) annihilation at the Upsilon(4S). The results are S=0.58+/-0.10+/-0.03 and C=-0.16+/-0.07+/-0.03. We observe mixing-induced CP violation with a significance of 5.5 standard deviations in this b --> s penguin dominated mode.

Vector-tensor and vector-vector decay amplitude analysis of B0-->phiK*0.

We perform an amplitude analysis of the decays B(0)-->phiK*(2)(1430)(0), phiK*(892)(0), and phi(Kpi)(0)(S-wave) with a sample of about 384x10(6) BB[over ] pairs recorded with the BABAR detector. The fractions of longitudinal polarization f(L) of the vector-tensor and vector-vector decay modes are measured to be 0.853(-0.069+0.061)+/-0.036 and 0.506+/-0.040+/-0.015, respectively. Overall, twelve parameters are measured for the vector-vector decay and seven parameters for the vector-tensor decay, including the branching fractions and parameters sensitive to CP violation.

Observation of B-->eta'K* and evidence for B+-->eta'rho+.

We present an observation of B-->eta'K*. The data sample corresponds to 232x10(6) BB[over ] pairs collected with the BABAR detector at the PEP-II asymmetric-energy B factory at the Stanford Linear Accelerator Center. We measure the branching fractions (in units of 10(-6)) B(B(0)-->eta'K*0)=3.8+/-1.1+/-0.5 and B(B+-->eta'K*+)=4.9(1.7)(+1.9)+/-0.8, where the first error is statistical and the second systematic. A simultaneous fit results in the observation of B-->eta'K* with B(B-->eta'K*)=4.1(-0.9)(+1.0)+/-0.5. We also search for B-->eta'rho and eta'f(0)(980)(f(0)-->pi+pi-) with results and 90% confidence level upper limits B(B+-->eta'rho+)=8.7(-2.8-1.3)(+3.1+2.3) (<14), B(B(0)-->eta'rho0)<3.7, and B(B(0)-->eta'f(0)(980)(f(0)-->pi+pi-))<1.5. Charge asymmetries in the channels with significant yields are consistent with zero.

Measurement of the CP asymmetry and branching fraction of B0-->rho0K0.

We present a measurement of the branching fraction and time-dependent CP asymmetry of B(0)-->rho0K0. The results are obtained from a data sample of 227x10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at Stanford Linear Accelerator Center. From a time-dependent maximum likelihood fit yielding 111+/-19 signal events, we find B(B(0)-->rho0K0)=(4.9+/-0.8+/-0.9)x10(-6), where the first error is statistical and the second systematic. We report the measurement of the CP parameters S(rho)(0)K(0)S=0.20+/-0.52+/-0.24 and C(rho)(0)K(0)S=0.64+/-0.41+/-0.20.

Search for lepton flavor violating decays tau(+/-) --> l(+/-)pi0, l(+/-)eta, l(+/-)eta'.

A search for lepton flavor violating decays of the tau lepton to a lighter mass lepton and a pseudoscalar meson has been performed using 339 fb;{-1} of e;{+}e;{-} annihilation data collected at a center-of-mass energy near 10.58 GeV by the BABAR detector at the SLAC PEP-II storage ring. No evidence of a signal has been found, and upper limits on the branching fractions are set at the 10;{-7} level.

Observation of decays B0-->Ds(*)+ pi- and B0-->Ds(*)- K+.

We report the observation of decays B{0}-->D{s}{(*)+}pi- and B{0}-->D{s}{(*)-}K+ in a sample of 230 x 10(6) Upsilon(4S)-->BB[over] events recorded with the BABAR detector at the SLAC PEP-II asymmetric-energy e+ e- storage ring. We measure the branching fractions B(B{0}-->D{s}{+}pi-)=(1.3+/-0.3(stat)+/-0.2(syst))x10(-5), B(B{0}-->D{s}{-} K+)=(2.5+/-0.4(stat)+/-0.4(syst))x10(-5), B(B{0}-->D{s}{*+}pi-)=(2.8+/-0.6(stat)+/-0.5(syst))x10(-5), and B(B{0}-->D{s}{*-}K+)=(2.0+/-0.5(stat)+/-0.4(syst))x10(-5). The significances of the measurements to differ from zero are 5, 9, 6, and 5 standard deviations, respectively. This is the first observation of B{0}-->D{s}{+}pi-, B{0}-->D{s}{*+}pi-, and B{0}-->D{s}{*-}K+ decays.

Measurement of the B0-->pi(-l)(+nu) form-factor shape and branching fraction, and determination of /Vub/ with a loose neutrino reconstruction technique.

We report the results of a study of the exclusive charmless semileptonic decay, B0-->pi(-l)(+nu), undertaken with approximately 227 x 10(6) BB pairs collected at the Upsilon(4S) resonance with the BABAR detector. The analysis uses events in which the signal B decays are reconstructed with an innovative loose neutrino reconstruction technique. We obtain partial branching fractions in 12 bins of q2, the momentum transfer squared, from which we extract the f + (q2) form-factor shape and the total branching fraction B(B0-->pi(-l)(+nu))=(1.46+/-0.07stat+/-0.08syst) x 10(-4). Based on a recent unquenched lattice QCD calculation of the form factor in the range q2>16 GeV2, we find the magnitude of the Cabibbo-Kobayashi-Maskawa matrix element /Vub/ to be (4.1+/-0.2stat +/- 0.2syst(+0.6)-0.4_{FF}) x 10(-3), where the last uncertainty is due to the normalization of the form factor.

Measurement of CP violation parameters with a Dalitz plot analysis of B{+/-}-->D{pi{+}pi{-}pi{0}}K{+/-}.

We report the results of a CP violation analysis of the decay B{+/-}-->D{pi{+}pi{-}pi;{0}}K{+/-}, where D{pi{+}pi{-}pi{0}} indicates a neutral D meson detected in the final state pi{+}pi{-}pi{0}, excluding K{S}{0}pi{0}. The analysis makes use of 324 x 10{6}e{+}e{-}-->BB[over ] events recorded by the BABAR experiment at the PEP-II e;{+}e;{-} storage ring. Analyzing the pi;{+}pi;{-}pi;{0} Dalitz plot distribution and the B{+/-}-->D{pi{+}pi{-}pi{0}}K{+/-} branching fraction and decay rate asymmetry, we find the following one-standard-deviation constraints on the amplitude ratio and on the weak and strong phases: 0.06pi{+}pi{-}pi{0} decay amplitude.

Evidence for B(0) --> rho(0)rho(0) decays and implications for the Cabibbo-Kobayashi-Maskawa angle alpha.

We search for the decays B(0) --> rho(0)rho(0), B(0) --> rho(0)f(0)(980), and B(0) --> f(0)(980)f(0)(980) in a sample of about 384 x 10(6) Upsilon(4S) --> BB[over] decays collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) collider at Stanford Linear Accelerator Center. We find evidence for B(0) --> rho(0)rho(0) with 3.5 sigma significance and measure the branching fraction B = (1.07 +/- 0.33 +/- 0.19) x 10(-6) and longitudinal polarization fraction f(L) = 0.87 +/- 0.13 +/- 0.04, where the first uncertainty is statistical, and the second is systematic. The uncertainty on the Cabibbo-Kobayashi-Maskawa quark-mixing matrix unitarity angle alpha due to penguin contributions in B --> rho rho decays is 18 degrees at the 1 sigma level. We also set upper limits on the B(0) --> rho(0)f(0)(980) and B(0) --> f(0)(980)f(0)(980) decay rates.