Late Effects of Ionizing Radiation on the Ultrastructure of Hepatocytes and Activity of Lysosomal Enzymes in Mouse Liver Irradiated In Vivo.

The study aimed to investigate late radiation-induced changes in the histology, ultrastructure, and activity of lysosomal enzymes in mouse liver exposed to ionizing radiation. The experiment was conducted on C57BL/6J male mice whose distal part of the liver was exposed occasionally to single doses of radiation (6 MV photons) during targeted heart irradiation; estimated doses delivered to analyzed tissue were 0.025 Gy, 0.25 Gy, 1 Gy, and 2 Gy. Tissues were collected 40 weeks after irradiation. We have observed that late effects of radiation have an adaptive nature and their intensity was dose-dependent. Morphological changes in hepatocytes included an increased number of primary lysosomes and autophagic vacuoles, which were visible in tissues irradiated with 0.25 Gy and higher doses. On the other hand, a significant increase in the activity of lysosomal hydrolases was observed only in tissues exposed to 2 Gy. The etiology of these changes may be multifactorial and result, among others, from unintentional irradiation of the distal part of the liver and/or functional interaction of the liver with an irradiated heart. In conclusion, we confirmed the presence of late dose-dependent ultrastructural and biochemical changes in mouse hepatocytes after liver irradiation in vivo.

Molecular mechanisms of tigecycline-resistance among Enterobacterales.

The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to acquire mobile genetic elements such as plasmids, represent one of the most hazardous microorganisms. This phenomenon poses a serious threat to public health. Notably, the significance of tigecycline, a member of the antibiotic group glycylcyclines and derivative of tetracyclines has increased. Tigecycline is one of the last-resort antimicrobial drugs used to treat complicated infections caused by multidrug-resistant (MDR) bacteria, extensively drug-resistant (XDR) bacteria or even pan-drug-resistant (PDR) bacteria. The primary mechanisms of tigecycline resistance include efflux pumps' overexpression, tet genes and outer membrane porins. Efflux pumps are crucial in conferring multi-drug resistance by expelling antibiotics (such as tigecycline by direct expelling) and decreasing their concentration to sub-toxic levels. This review discusses the problem of tigecycline resistance, and provides important information for understanding the existing molecular mechanisms of tigecycline resistance in Enterobacterales. The emergence and spread of pathogens resistant to last-resort therapeutic options stands as a major global healthcare concern, especially when microorganisms are already resistant to carbapenems and/or colistin.

Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure.

Cells exposed to densely ionising high and scattered low linear energy transfer (LET) radiation (50 % dose of each) react more strongly than to the same dose of each separately. The relationship between DNA double strand break location inside the nucleus and chromatin structure was evaluated, using high-resolution transmission electron microscopy (TEM) in breast cancer MDA-MB-231 cells at 30 min post 5 Gy. Additionally, response to high and/or low LET radiation was assessed using single (1 ×1.5 Gy) versus fractionated dose delivery (5 ×0.3 Gy). By TEM analysis, the highest total number of γH2AX nanobeads were found in cells irradiated with alpha radiation just prior to gamma radiation (called mixed beam), followed by alpha, then gamma radiation. γH2AX foci induced by mixed beam radiation tended to be surrounded by open chromatin (lighter TEM regions), yet foci containing the highest number of beads, i.e. larger foci representing complex damage, remained in the heterochromatic areas. The γH2AX large focus area was also greater in mixed beam-treated cells when analysed by immunofluorescence. Fractionated mixed beams given daily induced the strongest reduction in cell viability and colony formation in MDA-MB-231 and osteosarcoma U2OS cells compared to the other radiation qualities, as well as versus acute exposure. This may partially be explained by recurring low LET oxidative DNA damage by every fraction together with a delay in recompaction of chromatin after high LET, demonstrated by low levels of heterochromatin marker H3K9me3 at 2 h after the last mixed beam fraction in MDA-MB-231. In conclusion, early differences in response to complex DNA damage may lead to a stronger cell kill induced by fractionated exposure, which suggest a therapeutic potential of combined high and low LET irradiation.

The impact of limited access of photodynamic therapy during COVID-19 pandemic on patients with vulvar lichen sclerosus.

OBJECTIVES: Stressful situations have an impact on progression of lichen sclerosus. The aim of the study was to investigate fears and complaints of patients with vulvar lichen sclerosus and progression of disease at the beginning of the COVID-19 pandemic. MATERIAL AND METHODS: The analysis was based on 103 women with mean age was 64.81 ± 11.36 years divided into two groups. The first one comprised of patients with stabilization of disease during the pandemic with mean age 66.02 ± 10.01 (32-87), while the second one with progression of vulvar symptoms with mean age 63.49 ± 12.66 (25-87). RESULTS: Delay of diagnosis was reported to be a problem for respectively 25.93% of women from both groups. Fear about COVID-19 was described respectively by 57.4% and 55.1%. Stabilization of disease was more frequent in patients after photodynamic therapy before pandemic. Progression of vulvar symptoms and features were observed more in patients who did not conduct PDT previously. All patients from the second group who underwent photodynamic therapy reported disappointment because of no access for continuation of treatment. On the other hand, 81.4% (43 women) regret that have no chance for trying photodynamic therapy. CONCLUSIONS: Photodynamic therapy seems to be a method of treatment with longer survival without progression of lichen sclerosus in times of pandemics. There has been no investigation until now about concerns of patients with vulvar lichen sclerosus. Better understanding of problems connected with the pandemic can help medical personnel in taking care of patients with vulvar lichen sclerosus.

Nano-Sized Selenium Maintains Performance and Improves Health Status and Antioxidant Potential While Not Compromising Ultrastructure of Breast Muscle and Liver in Chickens.

The poultry industry is looking for the most effective sources of selenium (Se) for commercial use. Over the past five years, nano-Se has attracted a great deal of attention in terms of its production, characterisation and possible application in poultry production. The objective of this study was to evaluate the effects of dietary levels of inorganic and organic Se, selenised yeast and nano forms of selenium on breast meat quality, liver and blood markers of antioxidants, the ultrastructure of tissue and the health status of chickens. A total of 300 one-day-old chicks Ross 308 were divided into 4 experimental groups, in 5 replications, with 15 birds per replication. Birds were fed the following treatments: a standard commercial diet containing inorganic Se in the form of inorganic Se at the level of 0.3 mg/kg diet and an experimental diet with an increased level of Se (0.5 mg/kg diet). The use of other forms of Se (nano-Se) versus sodium selenate significantly influences (p ≤ 0.05) a higher collagen content and does not impair physico-chemical properties in the breast muscle or the growth performance of the chickens. In addition, the use of other forms of selenium at an increased dose versus sodium selenate affected (p ≤ 0.01) the elongation of sarcomeres in the pectoral muscle while reducing (p ≤ 0.01) mitochondrial damage in hepatocytes and improving (p ≤ 0.05) oxidative indices. The use of nano-Se at a dose of 0.5 mg/kg feed has high bioavailability and low toxicity without negatively affecting the growth performance and while improving breast muscle quality parameters and the health status of the chickens.

The Levels of Anti-SARS-CoV-2 Spike Protein IgG Antibodies Before and After the Third Dose of Vaccination Against COVID-19.

Purpose: The COVID-19 pandemic has been going on for almost three years, and so far, many preventive and therapeutic strategies have been developed. The issue of subsequent booster vaccinations is currently being discussed. We aimed to analyze how the third dose of vaccination against COVID-19 correlates with the dynamics of IgG anti-SARS-CoV-2 spike protein antibody levels in a group of healthy people. Patients and Methods: The prospective study included 93 participants before and after a second booster of COVID-19 vaccination, from whom 4 blood samples were collected at intervals. The levels of IgG anti-SARS-CoV-2 in serum were identified using the chemiluminescent immunoassay specific for the receptor-binding domain (RBD) of the S1 protein. The analysis of the results was performed using appropriate statistical methods, considering p <0.05 as a statistically significant value. Results: The IgG levels were significantly higher and less diverse after the same follow-up time from the second booster vaccination compared to the first booster. The antibody levels were positively correlated with female, healthcare workers, the elderly and participants with a negative COVID-19 history. Furthermore, the increase in IgG antibodies after the second booster vaccination correlated inversely with the baseline level of antibodies before the vaccination. The latest results showed that antibody levels dropped 1.5-fold after approx. 10 months from the second booster vaccination but still remained at a protective level. Conclusion: Booster vaccinations seem to better stimulate immune memory, and in the case of borderline IgG level induces the greatest increase in antibodies. It is worth considering the individual parameters of patients and measuring antibodies before vaccination.

New trends in application of the fumigation method in medical and non-medical fields.

INTRODUCTION: In the twentieth century, fumigation became a very popular method of disinfection, although in the same century many agents used as fumigants were withdrawn for ecological reasons. Fogging (fumigation) is a relatively new disinfection technology using dry fog, which behaves more like a gas and easily fills the sanitized space, reaching all surfaces in the room. The undoubted advantage of fumigation is the possibility of disinfecting difficult to clean areas. Fumigation has become particularly important in the twenty-first century due to procedures related to combating and preventing the spread of the coronavirus that causes COVID-19. OBJECTIVE: The aim of this review article is to summarize the current state of knowledge in the field of fumigation on the basis of past results of original research, taking into account new trends and possibilities of its application. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Due to the fact that fumigation is safe for apparatus, equipment, and electronics, while simultaneously enabling the highest possible bactericidal and virucidal levels, this method is widely used in various areas, both medical and non-medical. Fogging technology is used in the medical, pharmaceutical, and food industries, as well as in transportation, for air fumigation or surface disinfection in closed spaces, such as hospital and laboratory rooms, incubators, refrigerators, ships, trucks, railway containers, and aircraft, to name only a few. The most common fumigants are hydrogen peroxide and peracetic acid, and their mechanism of action is related to their oxidizing properties. SUMMARY: Hydrogen peroxide and peracetic acid are highly effective and non-toxic fumigants that can be safely used for fogging laboratory and medical equipment, pharmaceutical facilities, hospital rooms, and animal breeding rooms.

Air Disinfection-From Medical Areas to Vehicle.

Cars with air conditioning systems have become the norm, but these systems can be dangerous for human health as a result of the accumulation of different microorganisms, including pathogenic ones, causing severe allergy or inflammation problems. The novel purpose of this study is 2-fold: on the one hand, to test different disinfection agents on a new area, that is, automobile cabins, and on the other, to compare activity in the gas phase of these agents for disinfection of car air conditioning and cabin surfaces. This study shown that tested disinfectant agents dedicated for decontamination medical areas (agent based on peracetic acid and an agent containing didecyldimethylammonium chloride, 2-phenoxyethanol with cinnamaldehyde) can be successfully used for disinfection car air conditioning and cabin surfaces. Both disinfectants were examined in comparison to a commercial "ready-to-use" spray from a local supermarket dedicated to car air conditioning disinfection. Our research found that very effective agents in this regard were acid stabilized by hydrogen peroxide applied by fumigator, and a combination of didecyldimethylammonium chloride, 2-phenoxyethanol, and cinnamaldehyde applied by atomizer. Tested disinfection procedures of car air conditioning significantly influence the quality of cabin air and surfaces by reducing the amount of microorganisms. The comparison of disinfection properties studied agents in the gas phase reveal statistically significant differences between it effect for disinfection car air conditioning and cabin surfaces. Our research found that very effective agents in this regard were acid stabilized by hydrogen peroxide applied by fumigator, and a combination of didecyldimethylammonium chloride, 2-phenoxyethanol, and cinnamaldehyde applied by atomizer. Tested disinfection procedures of car air conditioning significantly influence the quality of cabin air and surfaces by reducing the amount of microorganisms.

Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A.

Manumycin A (MA) is a well-tolerated natural antibiotic showing pleiotropic anticancer effects in various preclinical in vitro and in vivo models. Anticancer drugs may themselves act as stressors to induce the cellular adaptive mechanism that can minimize their cytotoxicity. Heat shock proteins (HSPs) as cytoprotective factors can counteract the deleterious effects of various stressful stimuli. In this study, we examined whether the anticancer effects of MA can be counteracted by the mechanism related to HSPs belonging to the HSPA (HSP70) family. We found that MA caused cell type-specific alterations in the levels of HSPAs. These changes included concomitant upregulation of the stress-inducible (HSPA1 and HSPA6) and downregulation of the non-stress-inducible (HSPA2) paralogs. However, neither HSPA1 nor HSPA2 were necessary to provide protection against MA in lung cancer cells. Conversely, the simultaneous repression of several HSPA paralogs using pan-HSPA inhibitors (VER-155008 or JG-98) sensitized cancer cells to MA. We also observed that genetic ablation of the heat shock factor 1 (HSF1) transcription factor, a main transactivator of HSPAs expression, sensitized MCF7 cells to MA treatment. Our study reveals that inhibition of HSF1-mediated heat shock response (HSR) can improve the anticancer effect of MA. These observations suggest that targeting the HSR- or HSPA-mediated adaptive mechanisms may be a promising strategy for further preclinical developments.

Children with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension Treated with Pulmonary Vasodilators-The Pediatric Cardiologist Point of View.

Pulmonary hypertension in children with bronchopulmonary dysplasia (BPD-PH) significantly worsens the prognosis. Pulmonary vasodilators are often used in BPD-PH but the short-term outcome of treatment is not well described. The aim of this study was to evaluate BPD-PH children diagnosed beyond 36 weeks postmenstrual age treated with pulmonary vasodilators (sildenafil, bosentan, or both) and to assess the short and long-term effect of oral pulmonary vasodilators treatment. Twenty patients were included in the study. Cardiology evaluation (WHO-FC, NTproBNP, oxygen saturation, pulmonary to systemic pressure ratio PAP/SAP) was performed at diagnosis and after treatment initiation. In the majority of patients improvement in all evaluated factors was observed. No side effects of vasodilators were observed. PH resolved in 10 patients after a mean of 21.4 months of treatment. Six patients died. The number of poor prognostic factors commonly used to assess patients with pulmonary arterial hypertension (PAH) decreased significantly during BPD-PH treatment. The influence of BPD-PH perinatal risk factors on prognosis was considered but was not confirmed. In conclusion, the treatment of BPD-PH with pulmonary vasodilators was well tolerated and led to a clinical improvement with the possibility of discontinuation without recurrence of PH. Prognostic factors used in pediatric PAH risk stratification also seem to be useful in assessing treatment efficacy and prognosis in patients with BPD-PH.

Aging-Related Changes in the Ultrastructure of Hepatocytes and Cardiomyocytes of Elderly Mice Are Enhanced in ApoE-Deficient Animals.

Biological aging is associated with various morphological and functional changes, yet the mechanisms of these phenomena remain unclear in many tissues and organs. Hyperlipidemia is among the factors putatively involved in the aging of the liver and heart. Here, we analyzed morphological, ultrastructural, and biochemical features in adult (7-month-old) and elderly (17-month-old) mice, and then compared age-related features between wild type (C57Bl/6 strain) and ApoE-deficient (transgenic ApoE-/-) animals. Increased numbers of damaged mitochondria, lysosomes, and lipid depositions were observed in the hepatocytes of elderly animals. Importantly, these aging-related changes were significantly stronger in hepatocytes from ApoE-deficient animals. An increased number of damaged mitochondria was observed in the cardiomyocytes of elderly animals. However, the difference between wild type and ApoE-deficient mice was expressed in the larger size of mitochondria detected in the transgenic animals. Moreover, a few aging-related differences were noted between wild type and ApoE-deficient mice at the level of plasma biochemical markers. Levels of cholesterol and HDL increased in the plasma of elderly ApoE-/- mice and were markedly higher than in the plasma of elderly wild type animals. On the other hand, the activity of alanine transaminase (ALT) decreased in the plasma of elderly ApoE-/- mice and was markedly lower than in the plasma of elderly wild type animals.

Dynamic academic networking concept and its links with English language skills and research productivity-non-Anglophone context.

Although the Science of Team Science or SciTS has already provided substantial evidence for research collaboration positive links to scientific productivity, much less is known about such links with broadly defined academic networking, especially with regard to the dilemma about forms of academic networking that may help individual scholars in handling risks and dynamics inherent in academic connections. This study uses cross-disciplinary theoretical insights to conceptualize "dynamic academic networking" as a distinct collaboration-related phenomenon that is theoretically linked with research productivity on the one hand, and with English language skills on the other, especially in the context of non-Anglophone academic systems. The study combines survey-based data and Scopus-based data to test two main hypothesized connections while controlling for the potential effects of other factors, e.g. home faculty research connections and faculty-industry professional connections. The research results provide support for the structural model which is also interpreted in terms of dynamic networking being valid concept in relation to further development of SciTS.

Biochemical and morphological changes in mouse liver induced by mistletoe toxins.

Natural compounds are often characterized by high biological activity and sometimes toxicity. This also applies to compounds contained in the herb mistletoe. The objective of this study was to investigate short-term effects (up to 48 h) of mistletoe toxins on mouse hepatocytes. Standardized mistletoe extract Iscador P was given to female mice as a single injection (0.1 mg/kg b.w., 1 mg/kg b.w., or 2 mg/kg b.w). Activities of lysosomal hydrolases: acid phosphatase, cathepsins D and L, N-acetyl-ß-D-hexosaminidase, ß-D-glucuronidase, ß-D-glucosidase and cytosolic proteases: arginine and leucine aminopeptidases were analyzed in the liver fractions 24 and 48 h after the injection. The morphology of hepatocytes was examined by light and transmission electron microscopy. Iscador P caused a decrease in the activity of all lysosomal hydrolases (except cathepsins) in the lysosomal pellet, and an increase in the activity of both aminopeptidases and ß-D-glucuronidase in the cytosol. However, despite membranotropic properties of the viscotoxins, we did not find a significant labilising effect on the lysosomal membranes. Only ß-D-glucuronidase activity was relocated to the supernatant of lysosomal fraction. Microscopic examinations revealed that hepatocyte mitochondria were enlarged and increased in number, whereas the surface of the rough endoplasmic reticulum was decreased significantly.

Changes in activity and structure of lysosomes from liver of mouse irradiated in vivo.

PURPOSE: Lysosomes may have an important role in response to ionizing radiation. Moreover, radiation could affect autophagy, which process involves the activity of lysosomal enzymes. In the present study, the effect of ionizing radiation on the lysosomal compartment of mouse liver was investigated after in vivo exposure. MATERIALS AND METHODS: Morphology and ultrastructure of hepatocytes were assessed by light and electron microscopy, and activities of selected lysosomal enzymes were assessed in 12, 36 and 120 h after exposure to the mean dose of 1 Gy. The levels of autophagy-related proteins LC3-II and p62 were compared by Western blotting between untreated and irradiated animals (120 h after exposure). RESULTS: Increased number of autophagic vacuoles in hepatocytes from exposed animals was documented in the ultrastructural study; destroyed mitochondria were the dominant component of such vacuoles. Moreover, an increased activity of lysosomal hydrolases was observed after exposure. However, levels of autophagy substrates LC3-II and p62 were barely affected in exposed animals 120 h after irradiation when the accumulation of autophagic vacuoles was observed. CONCLUSION: Effects of irradiation included an increased number of autophagic vacuoles, especially of autophagosomes, and increased activity of lysosomal enzymes. However, putative markers of autophagic flux were not observed, which suggested suppression of the completion of the radiation-mediated autophagy pathway.

Long-term effects of low-dose mouse liver irradiation involve ultrastructural and biochemical changes in hepatocytes that depend on lipid metabolism.

The aim of the study was to investigate long-term effects of radiation on the (ultra)structure and function of the liver in mice. The experiments were conducted on wild-type C57BL/6J and apolipoprotein E knock-out (ApoE-/-) male mice which received a single dose (2 or 8 Gy) of X-rays to the heart with simultaneous exposure of liver to low doses (no more than 30 and 120 mGy, respectively). Livers were collected for analysis 60 weeks after irradiation and used for morphological, ultrastructural, and biochemical studies. The results show increased damage to mitochondrial ultrastructure and lipid deposition in hepatocytes of irradiated animals as compared to non-irradiated controls. Stronger radiation-related effects were noted in ApoE-/- mice than wild-type animals. In contrast, radiation-related changes in the activity of lysosomal hydrolases, including acid phosphatase, ß-glucuronidase, N-acetyl-ß-D-hexosaminidase, ß-galactosidase, and α-glucosidase, were observed in wild type but not in ApoE-deficient mice, which together with ultrastructural picture suggests a higher activity of autophagy in ApoE-proficient animals. Irradiation caused a reduction of plasma markers of liver damage in wild-type mice, while an increased level of hepatic lipase was observed in plasma of ApoE-deficient mice, which collectively indicates a higher resistance of hepatocytes from ApoE-proficient animals to radiation-mediated damage. In conclusion, liver dysfunctions were observed as late effects of irradiation with an apparent association with malfunction of lipid metabolism.

Correction: Colchicine metallocenyl bioconjugates showing high antiproliferative activities against cancer cell lines.

Correction for 'Colchicine metallocenyl bioconjugates showing high antiproliferative activities against cancer cell lines' by Karolina Kowalczyk et al., Dalton Trans., 2017, 46, 17041-17052.

Genetic basis of enzymatic resistance of E. coli to aminoglycosides.

PURPOSE: Over the past years, an increase in resistance to aminoglycosides has been observed among Enterobacteriaceae rods. This resistance development reduces therapeutic options for infections caused by multidrug-resistance organisms. Because of the changing epidemiology of extended-spectrum ß-lactamases (ESBLs) and resistance to aminoglycosides, we investigated the prevalence of the aac(3)-Ia, aac(6')-Ib, ant(4')-IIa, ant(2")-Ia, and aph(3")-Ib genes encoding aminoglycoside-modifying enzymes (AMEs) in ESBL-producing Escherichia coli as well as ESBL-non-producing isolates. To understand bacterial resistance to aminoglycoside antibiotics, we estimated resistance phenotypes and the presence of genes responsible for this resistance. MATERIALS AND METHODS: The study was conducted on 44 E.coli strains originated from patients hospitalized at University Hospital of Bialystok. MIC values were obtained for gentamicin, amikacin, netilmicin, and tobramycin. Isolates were tested for the presence of the aac(3)-Ia, aac(6')-Ib, ant(4')-IIa, ant(2")-Ia, and aph(3")-Ib genes with the use of the PCR technique. RESULTS: Resistance to aminoglycosides was found in 79.5% of the isolates. The highest percentages of resistance were observed for tobramycin (70,5%) and gentamicin (59%), followed by netilmicin (43.2%) and amikacin (11.4%). PCR assays revealed the presence of aac(6')-Ib among 26 (59.2%) strains, aph(3")-Ib among 16 (36.2%), aac(3)-Ia among 7 (15.9%), and ant(2")-Ia among 2 (4.6%) strains. CONCLUSIONS: The enzymatic resistance against aminoglycosides in northeastern Poland among clinical isolates of E. coli is predominantly caused by aac(6')-Ib and aph(3")-Ib. Amikacin may be used for therapy of infections caused by ESBL-producing E. coli, because of the low rates of resistance.

Novel scintillating material 2-(4-styrylphenyl)benzoxazole for the fully digital and MRI compatible J-PET tomograph based on plastic scintillators.

A novel plastic scintillator is developed for the application in the digital positron emission tomography (PET). The novelty of the concept lies in application of the 2-(4-styrylphenyl)benzoxazole as a wavelength shifter. The substance has not been used as scintillator dopant before. A dopant shifts the scintillation spectrum towards longer wavelengths making it more suitable for applications in scintillators of long strips geometry and light detection with digital silicon photomultipliers. These features open perspectives for the construction of the cost-effective and MRI-compatible PET scanner with the large field of view. In this article we present the synthesis method and characterize performance of the elaborated scintillator by determining its light emission spectrum, light emission efficiency, rising and decay time of the scintillation pulses and resulting timing resolution when applied in the positron emission tomography. The optimal concentration of the novel wavelength shifter was established by maximizing the light output and it was found to be 0.05 ‰ for cuboidal scintillator with dimensions of 14 mm x 14 mm x 20 mm.

Colchicine metallocenyl bioconjugates showing high antiproliferative activities against cancer cell lines.

A series of ferrocenyl and ruthenocenyl conjugates with colchicine bearing a 1,2,3-triazole moiety were synthesized and their anticancer properties were evaluated. We found that the most potent metallocenyl derivatives Rc4 and Rc5 are 6-7 times more cytotoxic toward HepG2 cells, while Fc4 and Fc5 are two times more cytotoxic toward HCT116 cells as colchicine. We also found that compounds Fc4, Fc5, Rc1 and Rc3-Rc5 are able to induce apoptosis, while compound Fc2 arrests mitosis.

Megamitochondria formation in hepatocytes of patient with chronic hepatitis C - a case report.

Although chronic hepatitis C virus (HCV) infection affect 185 million people world-wide, pathomechanism of liver damage is still unclear. Electron microscopy can reveal liver injury in very early stage and help understanding the mechanisms that is crucial in the pathogenesis of chronic hepatitis C. We present the morphological changes in the liver of HCV infected 24-year-old female patient, using light and transmission electron microscopy. Examination by TEM revealed wide range of specific subcellular abnormalities in hepatocellular ultrastructure. The most common observed changes were ring-shaped nuclei with intranuclear inclusion, megamitochondria, and "membranous web" structures - the hallmark of RNA-viruses infection.