Cytotoxic effect of the biotechnologically-derived justicidin B on human lymphoma cells.

Purpose of work: The study was aimed to assess the antineoplastic activity of justicidin B in vitro and to search for its general toxicological profile in vivo. The anti-neoplastic activity of the arylnaphthalene lignin, justicidin B, was assessed in a panel of human lymphoma cell lines and compared with etoposide as a reference compound. A screening of the cytotoxicity after 24, 48 and 72 h exposure was performed by the MTT-dye reduction assay. Dose- and time-dependent cytotoxic effect was observed and the IC50 values ranged from 0.17 µM (RPMI-8226, 72 h) to 183 µM (U-266, 24 h) and more than 200 µM (HD-MY-Z, 24 and 48 h). Activation of caspase 3 and 8 was involved in the induction of programmed cell death in DOHH-2 cell line. NF-κB modulation occurred in DOHH-2 and HH cells. The general toxicity in mice after i.p. injection was also tested. The highest applied dose (50 mg/kg = 137.25 µM) did not show any toxicity. Justicidin B possesses definite and potent selective antineoplastic activity, related to its ability to induce programmed cell death in NHL-derived human cell lines at concentrations that can be reached in mice without toxicity.

Real life clinical study design supporting the effectiveness of extra-fine inhaled beclomethasone/formoterol at the level of small airways of asthmatics.

BACKGROUND: In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol (I-EF-BDP/F) formulation differs from other combinations of inhaled corticosteroid (ICS) and long acting beta-agonist (LABA), we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it. METHODS: We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F (Foster(®), Chiesi Farmaceutici S.p.A., Italy). The effects of 8-weeks of treatment were documented by means of visual analog scale (VAS), quality of life by Asthma Quality of Life Questionnaire (AQLQ), spirometry and markers of airway or systemic inflammation: exhaled breath temperature (EBT), blood eosinophils (Eos), and high sensitivity C-reactive protein (CRP). Before/after treatment differences between forced vital capacity percent of predicted (%FVC), a simple indicator of small airways involvement, were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response. Subjects above the 75th percentile (n = 15), "top responders", were then compared with those below the 25th percentile (n = 15) "poor responders". RESULTS: On average, the 59 patients completing the study (mean age ± SD 51 ± 12 years, 38 women) had significant improvement in VAS and QLQ scores at the end of the treatment period (49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively, P < 0.001), but not in the inflammatory indicators (EBT, CRP and Eos). However, when comparing the "top responders" with the "poor responders", significant improvement in these inflammatory indicators was observed: EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[°C] to 33.57 ± 0.33, P = 0.003, Eos in blood fell from 381.7 ± 91.2 [cells/µL] to 244.2 ± 43.2, P = 0.02. Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders (Mann-Whitney test, P = 0.04). CONCLUSION: Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation. These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping. Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment. However, improved compliance due to the "promise of a new drug" effect should also be considered as contributing to the treatment results.

Hard two-body photodisintegration of 3He.

We have measured cross sections for the γ(3)He → pd reaction at photon energies of 0.4-1.4 GeV and a center-of-mass angle of 90°. We observe dimensional scaling above 0.7 GeV at this center-of-mass angle. This is the first observation of dimensional scaling in the photodisintegration of a nucleus heavier than the deuteron.

Precise extraction of the induced polarization in the 4He(e,e'p)3H reaction.

We measured with unprecedented precision the induced polarization P(y) in (4)He(e,e'p)(3)H at Q(2)=0.8 and 1.3 (GeV/c)(2). The induced polarization is indicative of reaction-mechanism effects beyond the impulse approximation. Our results are in agreement with a relativistic distorted-wave impulse approximation calculation but are overestimated by a calculation with strong charge-exchange effects. Our data are used to constrain the strength of the spin-independent charge-exchange term in the latter calculation.

Diagnostics of liver echinococcosis.

We analyze the clinical data and the possible methods for diagnostics of liver echinococcosis. The most common clinical manifestations are: burden, dull or colic pain in right hypochondrium, hepatomegaly plus. Against this clinical picture available eosinophilia is indicative sign in the diagnostic process; echography is binding method in the study. Establish the possibilities of each diagnostic method individually and in combination. It is recommended that the application of ultrasound in combination with the immunological method, which combined in 9/10 of the patients decided to avoid diagnosis and diagnostic polipragmatic approach. The other, considerably more expensive and radiological overdosing methods must be applied in exceptional cases. In every manifestation of allergy must be investigation to exclude the echinococcosis. We highly recommended the introduction in Bulgaria of screening methods for early detection of disease and timely treatment.

Polarization transfer in the 4He(e,e'p)3H reaction at Q2=0.8 and 1.3 (GeV/c)2.

Proton recoil polarization was measured in the quasielastic 4He(e,e'p)3H reaction at Q{2}=0.8 and 1.3 (GeV/c){2} with unprecedented precision. The polarization-transfer coefficients are found to differ from those of the 1H(e,e'p) reaction, contradicting a relativistic distorted-wave approximation and favoring either the inclusion of medium-modified proton form factors predicted by the quark-meson coupling model or a spin-dependent charge-exchange final-state interaction. For the first time, the polarization-transfer ratio is studied as a function of the virtuality of the proton.

[Immunodiagnostic of liver echinococcosis].

Four immunological reactions of the liver echinococcosis are examined - Complement fixation test (CF), Latex agglutination test (LA), Bentonite agglutination test (BA) and Indirect haemagglutination test (IHA). The diagnostic "potentialities" of every sample are specified separately. IHA has given the best results, followed by LA. BA and CF in last place. The great significance of the immunodiagnostic with regard to diagnose of the disease is demonstrated and its place in the postoperative observation for clarifying of the prediction and for proving of the recidivation. It's obligatory to use several immunological samples, which complement one another. The immunological titers can stay at high rate in every stage of the illness, including during suppuration or partial calcification of the cyst.

Measurements of the proton elastic-form-factor ratio mu pG p E/G p M at low momentum transfer.

High-precision measurements of the proton elastic form-factor ratio, mu pG p E/G p M, have been made at four-momentum transfer, Q2, values between 0.2 and 0.5 GeV2. The new data, while consistent with previous results, clearly show a ratio less than unity and significant differences from the central values of several recent phenomenological fits. By combining the new form-factor ratio data with an existing cross-section measurement, one finds that in this Q2 range the deviation from unity is primarily due to G p E being smaller than expected.