Carcinoma, a fibrolamellar variant--immunohistochemical analysis of 4 cases

BACKGROUND/AIMS: To analyze, by means of immunocytochemistry, the cases of fibrolamellar variant of hepatocellular carcinoma (FLC), diagnosed in our Department. METHODOLOGY: The material comprised 4 FLC cases of tumors resected surgically. Besides the routine morphological assessment, we used a panel of immunohistochemical stainings including: hepatocellular cytokeratin, CK7, CK19, Ki67, PCNA, chromogranin A, synaptophysin, NSE, insulin, calcitonin, parathormon, CD34, EBV (LMP), Bcl2, cyclin D1. RESULTS: In 3 out of 4 cases, we observed co-expression of CK7 with hepatocellular CK. In addition, there was positive staining with some endocrine markers in the majority of patients. In one case, we found strong cyclin D1 immunoreactivity which correlated with EBV (LMP) immunoreactivity, in the same patient. The score of PCNA positivity varied between 15 and 90%. In all cases Ki67 was negative. CONCLUSIONS: The incidence of FLC, among all hepatocellular carcinomas diagnosed in our Department was 5.1%. In accordance with other reports, all our FLC cases were young patients without underlying liver disease. We were unable to find a correlation between FLC cellular immunophenotype, and histological and clinical markers of malignancy. In addition, it appears that PCNA is a better marker of cell-proliferation in FLC than Ki67. The significance of EBV infection in FLC requires further study.     

Towards potent but less toxic nanopharmaceuticals – lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units.     

New synthetic pathway leading to oxospirochlorins

In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on the use of an imino-keto intermediate formed in situ from 2-amino-5,10,15,20-tetraphenylporphyrins and inverse electron demand Diels–Alder (iEDDA) cycloaddition with 3,6-di-2-pyridyl-1,2,4,5-tetrazine. The mechanism of reaction was analyzed employing theoretical methods by comparing the difference in energy of Frontier Molecular Orbitals (FMO) for appropriate reagents. Ground-state molecular electrostatic (ESP) potential maps were employed as additional tools allowing explanation of the reactivity of substrates. The new class of spirochlorin compounds was fully characterized by means of mass spectrometry, IR, liquid and solid state NMR and X-ray crystallography. Correlation between molecular structure and optical properties for the obtained title compounds is discussed.

Oxospirochlorins – novel analogs of porphyrinoids were synthesized and characterized by various methods including X-ray, NMR spectroscopy and mass spectrometry.     

Terapia celowana i transplantacja komórek krwiotwórczych szansą na wyleczenie chorych z ostrą białaczką szpikową

Acute myeloid leukemia (AML) is a heterogeneous disorder with a diverse prognosis. About 70% of AML patients may achieve complete remission after conventional chemotherapy, but long-term outcome remains unsatisfactory. The development of molecular biology resulted in a better understanding of AML pathogenesis as well as it allowed us the introduction of targeted therapy. However, most AML patients still require the allogeneic hematopoietic stem cell transplantation (alloHSCT) to be cured. The long-term results of alloHSCT for AML depend on a variety of factors including the age at transplant, the presence of well-defined risk factors and disease status at transplant. It seems that the combination of targeted therapy with conventional chemotherapy and subsequent alloHSCT may be a chance for curing a significant proportion of AML patients.     

Progressive-toric IOL design reduces residual astigmatism with increasing pupil size: a ray-tracing simulation based on corneal topography data

Population studies indicate that astigmatism decreases from the corneal center toward the periphery. A standard toric intraocular lens (IOL) with a constant cylinder power cannot correct uniformly across this gradient. We built an astigmatic eye model based on corneal topography data. A progressive-toric lens with gradually decreasing cylinder power was compared with an identically designed lens but featuring conventional astigmatism correction. Residual astigmatism did not differ significantly (P=0.06) at 3 mm, and the Strehl ratio was identical for both lenses (0.51 ±0.15, P=0.88). At 5 mm, the progressive IOL yielded significantly lower residual astigmatism by 0.10 D (P<0.001). The Strehl ratio was 0.30 ±0.08 with the progressive and 0.29 ±0.08 with the standard lens (P<0.001). At 3 mm, the optical performance was comparable for both IOLs. However, at 5 mm, the progressive-toric was more effective in correcting astigmatism, and it yielded reduced residual astigmatism compared to a standard toric lens.     

Plasma concentration of atrial natriuretic peptide is related to the duration of atrial fibrillation in patients with advanced heart failure

BACKGROUND: Plasma concentration of atrial natriuretic peptide (ANP) is elevated in patients with atrial fibrillation (AF) and in patients with chronic heart failure (CHF).Aim. To assess ANP level in patients with permanent AF and advanced CHF. METHODS: The study group consisted of 41 patients (27 males, mean age 62+/-8 years) with AF of a mean duration of 8.8 months. Twenty six (63%) patients were in NYHA class II, and 15 (37%) - in NYHA class III or IV. All patients underwent clinical and echocardiographic evaluation as well as ANP plasma concentration assessment. Multiple regression analysis was used to identify factors which determine ANP plasma concentration. RESULTS: Mean ANP plasma concentration was 52.4+/-22.7 pg/ml in the whole study group; 38.6+/-10.8 pg/ml in NYHA class II patients and 74.9+/-18.7 pg/ml in NYHA class III-IV subjects (p<0.0001). Among echocardiographic parameters, patients with NYHA class III or IV had significantly lower left ventricular ejection fraction and greater left atrial volume than patients with NYHA class II (32% versus 56%, p<0.0001 and 101.0+/-23.8 cm(3) versus 83.4+/-16.1 cm(3), p<0.006, respectively). Multiple regression analysis revealed a significant negative correlation between AF duration and ANP level (p=0.0013) in a group of patients with NYHA class III or IV and identified AF duration as an independent predictor of ANP plasma concentration in this group of patients. CONCLUSIONS: ANP plasma concentration in patients with persistent AF and advanced CHF is determined by AF duration - the longer the AF duration the lower the ANP level.     

Shaping Physiological Indices,Swimming Technique,and Their Influence on 200m Breaststroke Race in Young Swimmers

The aim of this study was to investigate somatic properties and physiological capacity, and analyze kinematic parameters in the 200 m breaststroke swimming race. Twenty-seven male swimmers participated in the study. They were 15.7±1.98 years old. Their average height was 1.80 ± 0.02 m and lean body mass (LBM) was 62.45 ± 8.29 kg. Physiological exercise capacity was measured in two separate 90 sec. all-out tests, one for the arms and second for legs. During the tests total work of arm cranking (TWAR) and cycling (TWLG) as well as peak of VO₂ for arm (VO_2peakAR) and leg (VO_2peakLG) were measured. The underwater swimmers body movements were recorded during the all-out swimming 200m breaststroke speed test using an underwater camera installed on a portable trolley. The swimming kinematic parameters and propulsive or non-propulsive movement phases of the arms and legs as well as average speed (V200), surface speed (V200surface) and swimming speed in turn zones (V200turns) were extracted. V200surface was significantly related to the percentage of leg propulsion and was shown to have large effect on VO_2peakLG in the Cohen analysis. V200turns depended significantly on the indicators of physiological performance and body structure: TWAR, VO_2peak LG and LBM, LBM, which in turn strongly determined the measured results of TWAR, TWLG, VO_2peakAR and VO_2peakLG. The V200turns and V200surface were strongly associated with V200, 0.92, p < 0.001 and 0.91, p < 0.001 respectively. In each lap of the 200m swimming there was an increased percentage of propulsion of limb movement observed simultaneously with a reduction in the gliding phase in the breaststroke cycles.

Key points

• This study investigated the influence of the selected indicators of somatic properties and physiological capacity as well kinematic and coordination parameters on breaststroke swimming.
• In this observations the body’s functional capacity have an important impact on achieving good breaststroke swimming results, the V₂₀₀ was moderately associated on VO₂peakLG, moreover, separate V₂₀₀turns depended with VO₂peakLG and on LBM and TWAR.
• The speed of surface breaststroke swimming - V₂₀₀surface similarly as V₂₀₀turns had a very strong influence on the end result of V_{200 ,} 0.91, p<0.001 and 0.92, p<0.001 respectively.
• The ability to swim fast on the surface (V₂₀₀surface) was positively and significantly associated with the percentage time of propulsion generation -LP in the breaststroke cycle.

Key words: Breaststroke swimming, physiological indices, lean body mass, kinematic indices