Detection of hepatocellular carcinoma by tissue resonance interaction method (TRIM)

Introduction: Diagnosis of hepatocellular carcinoma (HCC) is considerably delayed, being frequently done in the non-curative stage of disease. The reason for delayed diagnosis is indolent course in early stages and/or unspecific symptoms indistinguishable from underlying cirrhosis. Hitherto methods used for screening of HCC have important limitations. TRIMprob is a non-invasive method, which showed utility in detection of cancers located in prostate, breast, or urinary bladder. Aim: To determine the diagnostic accuracy of TRIMprob in detecting HCC in cirrhotic liver. Material and methods: Forty-five patients were prospectively enrolled according to final clinical diagnosis into a group of cirrhosis and HCC or a group of cirrhosis without HCC. A control group consisted of 33 healthy subjects. Hepatocellular carcinoma was diagnosed by computed tomography (CT) or magnetic resonance (MR) and guided biopsy. The TRIMprob examination was performed in each patient. Three wave frequencies were used: 465, 930, and 1395 MHz. Results: In patients with HCC the intensity of return signal using wave a frequency of 465 MHz was significantly reduced in patients with HCC in comparison to healthy subjects (p < 0.0005), but not to cirrhotic patients without HCC. Moreover, cirrhosis was associated with significantly decreased TRIMprob signal in comparison to healthy liver (p < 0.002). In ROC analysis an optimal cut-off value for detection of HCC was 106 units, which yielded 80% sensitivity. Conclusions: TRIMprob identifies HCC with good sensitivity; however, the accuracy of this method to identify HCC in screening circumstances may be hindered by attenuation of the resonance interaction signal by cirrhosis itself

Hyperbolic-like manifolds, geometrical properties and holomorphic mappings

The authors are dealing with the Dirichlet integral-type biholomorphic-invariant pseudodistance $ρ_{X}^{α}(z_0,z)[]$ introduced by Dolbeault and Ławrynowicz (1989) in connection with bordered holomorphic chains of dimension one. Several properties of the related hyperbolic-like manifolds are considered remarking the analogies with and differences from the familiar hyperbolic and Stein manifolds. Likewise several examples are treated in detail

Betulin Acid Ester Derivatives Inhibit Cancer Cell Growth by Inducing Apoptosis through Caspase Cascade Activation: A Comprehensive In Vitro and In Silico Study

Betulin, or naturally occurring triterpene, possesses promising antiproliferative activity. To further explore this potential, thirty-eight betulin acid ester derivatives modified at the C-28 position were tested for antitumor activities. Four human cancer cell lines, MV4-11 (leukemia), A549 (lung), PC-3 (prostate), MCF-7 (breast) as well as the normal BALB/3T3 (mouse fibroblasts) cell line were examined using MTT and SRB assays. A few derivatives exhibited strong antiproliferative activity with IC50 values between 2 and 5 &micro;M. Subsequent mechanistic studies revealed that some derivatives induced apoptosis by inducing caspase-3/7 activity. A strong structure&ndash;activity correlation of tested compounds has been proposed along with experimental and in silico pharmacokinetic properties

Can laboratory parameters be predictive factors for treatment effectiveness of patients suffering from viral hepatitis C?

INTRODUCTION: The combined therapy of pegylated alpha interferon and rybavirin is a gold standard of chronic viral hepatitis C (cvhC) treatment. AIM: The aim of the study is to evaluate the laboratory test differences between the group of cvhC patients which achieved and did not achieve sustained virologic response (SVR). MATERIALS AND METHODS: 51 patients (25 women, 26 men, age 48.7 ± 12.8 years) were divided into two groups depending on SVR achievement. SVR was achieved in 41.2% of patients [(SVR(+)]. The concentration of hemoglo-bin, hematocrite, the number of erythrocytes, leucocytes, platelets, glucose, bilirubin, creatinin, uric acid, fT3, fT4, TSH, C-reactive protein (CRP), the activity of asparaginian and alaninian transaminases, alkaline phosphatase, gammaglutamylotranspeptidase, were estimated before the start of treatment and after 12, 24, 48 and 72 weeks after beginning it. Statistic analysis was performed by ANOVA of Friedmann, U Mann-Withney and t-Student tests. RESULTS: The activity of AspAT, AlAT in the SVR(+) group was lower from the 12th week until the 72nd week of observation. GGTP activity was statistically significant lower in the SVR(+)group. The decrease in TSH concentration in the 12th week and the increase in fT4 concentration in week 24 was clearer in the SVR(+) group. The hematocrite was lower in the SVR(+) group in the 48th week from the beginning of therapy and 24 weeks after the end of it. CONCLUSIONS: Patients treated with pegylated interferon 2a and rybavirine due to cvhC rarely achieve SVR if the GGTP activity is higher before the treatment and if the aminotranferases activity is higher during therapy. Latent hyperthyreosis can be a good predictive factor.WSTĘP: Złotym standardem terapii przewlekłego wirusowego zapalenia wątroby typu C (PWZW-C) w naszym kraju jest terapia skojarzona pegylowanym interferonem alfa (PEG-If-) i rybawiryną. Celem pracy była ocena różnic w wartościach poszczególnych parametrów morfologii krwi obwodowej oraz wyników badań biochemicznych w toku leczenia chorych z PWZW-C, u których osiągnięto i nie osiągnięto trwałej odpowiedzi wirusologicznej (sustained virologic response – SVR). MATERIAŁ I METODY: 51 chorych (25 kobiet i 26 mężczyzn, średnia wieku 48,7 ± 12,8 roku) zakażonych genotypem 1b wirusa HCV podzielono na dwie grupy: pierwszą stanowili chorzy (41,2%) których terapia zakończyła się osiągnięciem SVR [SVR(+)], drugą stanowili pozostali chorzy [SVR(-)]. Przed rozpoczęciem terapii oraz po 12, 24, 48 tygodniach od rozpoczęcia, a następnie po 24 tygodniach od zakończeniu leczenia oceniano: stężenie hemoglobiny, hematokryt, liczbę erytrocytów, leukocytów oraz płytek krwi, aktywność aminotransferazy asparaginianowej (AspAT), aminotransferazy alaninowej (AlAT), fosfatazy alkalicznej (ALP) oraz gamma-glutamylotranspeptydazy (GGTP), stężenie glukozy, bilirubiny, kreatyniny, kwasu moczowego, fT3, fT4, TSH, białka C-reaktywnego (CRP). Analizę statystyczną przeprowadzono przy użyciu testów: ANOVA Friedmana, U Manna-Withneya oraz t-Studenta. WYNIKI: Aktywność AspAT, AlAT w grupie była niższa w grupie SVR(+) od 12 tygodnia aż do 72 tygodnia. Aktywność GGTP była znamiennie niższa w grupie SVR(+). Spadek stężenia TSH w 12 tygodniu oraz wzrost stężenia fT4 w 24 tygodniu leczenia był wyraźniejszy u osób SVR(+). Hematokryt osiągnął niższe wartości w grupie SVR(+) w 48 tygodni od włączenia i 24 tygodnie po zakończeniu terapii. WNIOSKI: Chorzy leczeni z powodu PWZW-C rzadziej osiągają SVR w przypadku podwyższonej aktywności GGTP przed rozpoczęciem leczenia i utrzymywania się zwiększonej aktywności aminotransferaz w trakcie terapii. Korzystny wpływ może mieć utajona nadczynność tarczycy

Can laboratory parameters be predictive factors for treatment effectiveness of patients suffering from viral hepatitis C?

INTRODUCTION: The combined therapy of pegylated alpha interferon and rybavirin is a gold standard of chronic viral hepatitis C (cvhC) treatment. AIM: The aim of the study is to evaluate the laboratory test differences between the group of cvhC patients which achieved and did not achieve sustained virologic response (SVR). MATERIALS AND METHODS: 51 patients (25 women, 26 men, age 48.7 ± 12.8 years) were divided into two groups depending on SVR achievement. SVR was achieved in 41.2% of patients [(SVR(+)]. The concentration of hemoglo-bin, hematocrite, the number of erythrocytes, leucocytes, platelets, glucose, bilirubin, creatinin, uric acid, fT3, fT4, TSH, C-reactive protein (CRP), the activity of asparaginian and alaninian transaminases, alkaline phosphatase, gammaglutamylotranspeptidase, were estimated before the start of treatment and after 12, 24, 48 and 72 weeks after beginning it. Statistic analysis was performed by ANOVA of Friedmann, U Mann-Withney and t-Student tests. RESULTS: The activity of AspAT, AlAT in the SVR(+) group was lower from the 12th week until the 72nd week of observation. GGTP activity was statistically significant lower in the SVR(+)group. The decrease in TSH concentration in the 12th week and the increase in fT4 concentration in week 24 was clearer in the SVR(+) group. The hematocrite was lower in the SVR(+) group in the 48th week from the beginning of therapy and 24 weeks after the end of it. CONCLUSIONS: Patients treated with pegylated interferon 2a and rybavirine due to cvhC rarely achieve SVR if the GGTP activity is higher before the treatment and if the aminotranferases activity is higher during therapy. Latent hyperthyreosis can be a good predictive factor.WSTĘP: Złotym standardem terapii przewlekłego wirusowego zapalenia wątroby typu C (PWZW-C) w naszym kraju jest terapia skojarzona pegylowanym interferonem alfa (PEG-If-) i rybawiryną. Celem pracy była ocena różnic w wartościach poszczególnych parametrów morfologii krwi obwodowej oraz wyników badań biochemicznych w toku leczenia chorych z PWZW-C, u których osiągnięto i nie osiągnięto trwałej odpowiedzi wirusologicznej (sustained virologic response – SVR). MATERIAŁ I METODY: 51 chorych (25 kobiet i 26 mężczyzn, średnia wieku 48,7 ± 12,8 roku) zakażonych genotypem 1b wirusa HCV podzielono na dwie grupy: pierwszą stanowili chorzy (41,2%) których terapia zakończyła się osiągnięciem SVR [SVR(+)], drugą stanowili pozostali chorzy [SVR(-)]. Przed rozpoczęciem terapii oraz po 12, 24, 48 tygodniach od rozpoczęcia, a następnie po 24 tygodniach od zakończeniu leczenia oceniano: stężenie hemoglobiny, hematokryt, liczbę erytrocytów, leukocytów oraz płytek krwi, aktywność aminotransferazy asparaginianowej (AspAT), aminotransferazy alaninowej (AlAT), fosfatazy alkalicznej (ALP) oraz gamma-glutamylotranspeptydazy (GGTP), stężenie glukozy, bilirubiny, kreatyniny, kwasu moczowego, fT3, fT4, TSH, białka C-reaktywnego (CRP). Analizę statystyczną przeprowadzono przy użyciu testów: ANOVA Friedmana, U Manna-Withneya oraz t-Studenta. WYNIKI: Aktywność AspAT, AlAT w grupie była niższa w grupie SVR(+) od 12 tygodnia aż do 72 tygodnia. Aktywność GGTP była znamiennie niższa w grupie SVR(+). Spadek stężenia TSH w 12 tygodniu oraz wzrost stężenia fT4 w 24 tygodniu leczenia był wyraźniejszy u osób SVR(+). Hematokryt osiągnął niższe wartości w grupie SVR(+) w 48 tygodni od włączenia i 24 tygodnie po zakończeniu terapii. WNIOSKI: Chorzy leczeni z powodu PWZW-C rzadziej osiągają SVR w przypadku podwyższonej aktywności GGTP przed rozpoczęciem leczenia i utrzymywania się zwiększonej aktywności aminotransferaz w trakcie terapii. Korzystny wpływ może mieć utajona nadczynność tarczycy

A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients

Abstract Background Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population. Methods Subjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays. Results Nineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance ( P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously ..