Synthesis and Study of Building Blocks with Dibenzo[b,f]oxepine: Potential Microtubule Inhibitors.

The synthesis of biphenylmethoxydibenzo[b,f]oxepine or photoswitchable fluorinated dibenzo[b,f]oxepine derivatives with one or three azo bonds, potential microtubule inhibitors, is described. Our studies provide a concise method for constructing derivatives containing the dibenzo[b,f]oxepine skeleton. An analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light.

Impact of SARS CoV-2 /COVID-19 infection on the course of advanced chronic liver disease and hepatocellular carcinoma.

BACKGROUND: About 20% of patients infected with SARS-CoV-2 develop COVID-19-the disease that has dominated health care in the last two years. The course of COVID-19 in patients with advanced liver disease tends to be severe, patients also suffer from a higher risk of complications and death. The primary object of this study was to assess the risk and causes of death in patients with cirrhosis and hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From a group of 4,314 patients hospitalized at Jerzy Gromkowski Regional Specialist Hospital in Wroclaw (Poland) due to SARS-CoV-2/COVID-19 infection between March 15, 2020, and January 31, 2022, we selected a cohort of 31 patients with liver cirrhosis (12 women and 19 men) and 7 patients with HCC developed on the cirrhotic liver (1 woman, 6 men). The control group included 123 patients without liver disease. In the entire cohort, we analyzed the course of COVID-19 infection, baseline oxygen demand, liver function (assessed using the CTP-Child-Turoctte-Pugh score and MELD-Model of End-Stage Liver Disease scales), length of hospitalization, development of acute-on-chronic liver failure, and deaths. RESULTS: The mean age of the patients was 56.6 years in the liver cirrhosis group, 63.3 years for patients with (HCC) hepatocellular carcinoma, and 64 years in the control group. Time of hospitalization averaged 15.52 days and 11.14 days for patients with liver cirrhosis and liver cancer, respectively. For the control group, the average duration of the hospital stay was 11.61 days. With respect to baseline liver function assessed using the CTP score, in the cirrhosis group 10 patients were CTP class A, 19 patients were class B and 9 patients were class C. The cancer group included 3 patients with class A, 2 patients with class B, and 2 patients with class C. In the studied cohort, 22 patients had a baseline MELD score < 12 points, and in 15 patients was > 12. In the HCC group, it was, respectively, CTP A:3, B: 2, C: 2, and MELD < 12: 3, ≥12: 4 people. Most of these patients presented with a progression of liver disease. Fifteen patients died, including 12 with cirrhosis and 3 with HCC, accounting for 39.47% in the entire cohort, 39% in the cirrhotic group and 43% in the HCC group, and 13 in the control group (10.6%), There was a clear statistical difference between the mortality rate in the group with liver disease and in the control group. CONCLUSIONS: Infection with SARS-CoV-2/COVID-19 in patients with cirrhosis and HCC tends to have a more severe course and leads to exacerbation of the liver disease. The most common cause of death in the analyzed cohort infected with SARS-CoV-2/COVID-19 was the progression of liver disease, complicated by liver failure.

Liver Injury in Patients with COVID-19 without Underlying Liver Disease.

SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and-where it is particularly challenging-on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19. MATERIAL AND METHODS: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury. RESULTS: Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death. CONCLUSIONS: (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values.

Hemophagocytic Lymphohistiocytosis Secondary to Peripheral T Cell Lymphoma with Rapid Onset and Fatal Progression in a Young Patient: A Case Report and Review of the Literature.

BACKGROUND Constant stimulation of lymphocytes and histiocytes can result in hemophagocytic lymphohistiocytosis (HLH), which can be primary or secondary (sHLH). The main causes of sHLH are infections and hematological malignancies, especially non-Hodgkin lymphoma. Despite new insights into the pathogenesis of HLH, the diagnosis and treatment of this immune disorder remain a great challenge. CASE REPORT We present a case of a young adult without comorbidities whose clinical course was nonspecific for several months and resulted in late diagnosis of HLH secondary to peripheral T cell lymphoma (PTCL). The etiological factor of recurring fever, hepatosplenomegaly, and deteriorating condition was unidentified for a long time before fatal sHLH was finally diagnosed. The patient was treated according to the HLH-2004 protocol; however, he did not achieve any response. Unfortunately, due to nonspecific symptoms, lack of lymphadenopathy for a long time, and negative positron emission tomography results, the diagnosis of PTCL was established only after the patient's death. CONCLUSIONS It should be emphasized that early diagnosis is crucial for better prognosis of patients with sHLH. Bone marrow biopsy is worth considering in patients with prolonged fever of unknown origin, hyperferritinemia, splenomegaly, and unexplained cytopenia of 2 or more lineages. Despite the existence of diagnostic and therapeutic protocols available in the literature, the prompt diagnosis and treatment of HLH remains a great challenge. More precise and specific diagnostic tools for HLH are needed.

Selected predictors of maternal-fetal attachment in pregnancies with congenital disorders, other complications, and in healthy pregnancies.

BACKGROUND: The mother-infant attachment begins to form during pregnancy and is important for the future development of the child. Pregnancy complications can affect this relationship. The purpose of the study was to identify predictors of maternal-fetal attachment in physiological and high-risk pregnancies. PARTICIPANTS AND PROCEDURE: The study group included women in pregnancies with congenital disorders (n = 65) or with other pregnancy complications (n = 65). A third group included women in healthy pregnancies (n = 65). Data were collected by: the Maternal-Fetal Attachment Scale, the Questionnaire of Attachment Styles, the Rosenberg Self-Esteem Scale, the State-Trait Anxiety Inventory, the Social Support Scale, a standardized interview, the Dependency on Intimate Partner Scale, and the Pregnancy Experiences Scale. RESULTS: No significant differences in maternal-fetal attachment (MFA) were found between the groups. No predictors of MFA were observed for the women with a pregnancy with a congenital disorder. In the group of pregnancies with other complications, the only predictor of attachment intensity was pregnancy experience: a more negative attitude toward pregnancy was associated with lower MFA. In physiological pregnancies, MFA was found to be determined by pregnancy experience, gestational age, maternal age and dependency on one's intimate partner. MFA increased as pregnancy progressed. Younger mothers in physiological pregnancies, who have more positive pregnancy experiences and are less dependent on a partner, achieve higher levels of MFA. CONCLUSIONS: The presence of high-risk pregnancy, or its absence, does not differentiate the intensity of the emotional bond between mother and fetus. However, women with healthy pregnancies demonstrate different predictors of MFA than those with high-risk pregnancies.

Allelopathic effects of Chara species (C. aspera, C. baltica, and C. canescens) on the bloom-forming picocyanobacterium Synechococcus sp.

The role of macroalgal allelopathy in aquatic systems has received increasing attention as a potential means of controlling cyanobacterial blooms. However, the allelopathic activity of Chara sp. on coexisting and bloom-forming picocyanobacteria is still largely unknown. Therefore, the laboratory experiments were conducted to investigate the allelopathic activity of extracts of Chara aspera, C. baltica, and C. canescens on the growth, the fluorescence parameters: maximum and effective quantum yield of photosystem II (PSII) photochemistry (Fv/Fm and ΦPSII, respectively) and photosynthesis parameters such as the initial slope of photosynthesis-irradiance (P-E) curves (alpha) and photosynthetic capacity (Pm) of the picocyanobacterium Synechococcus sp. Batch cultures of picocyanobacterium were exposed to three concentrations of extracts originating from three charophyte cultures and the effect was followed at three sampling times. Dried specimens of C. aspera, C. baltica, and C. canescens were extracted in the water-based matrix and the initial Synechococcus sp. inoculum, derived from unialgal culture media, was used. We found both negative and positive allelopathic effects of all tested Chara extracts on Synechococcus sp. The strongest adverse impact of picocyanobacterium growth was caused by C. baltica. This study clearly demonstrated that the allelopathic effect depends on the Chara species identity. Our results also suggested that some allelopathic Chara sp. have the potential to mitigate harmful cyanobacterial blooms in systems dominated by Synechococcus sp.

Stage of liver fibrosis in patients with congenital bleeding disorders and infected with hepatitis C virus.

INTRODUCTION: Hepatitis C virus (HCV) is the major cause of chronic liver disease in patients with hemophilia. However, since liver biopsy should not be routinely used in these patients, the accurate assessment of the stage of fibrosis has been limited so far. OBJECTIVES: The aim of this study was to determine the stage of liver fibrosis in HCV­infected patients with hemophilia by using noninvasive methods of fibrosis assessment, and to analyze the influence of risk factors on liver fibrosis. PATIENTS AND METHODS: The study included 71 HCV­infected patients with hemophilia and other congenital bleeding disorders. Patients were divided into 3 groups: HCV-RNA negative after successful treatment, HCV-RNA negative after spontaneous elimination of infection, and HCV­RNA positive. Liver fibrosis was measured with shear wave elastography and FibroTest. The risk factors for liver fibrosis were analyzed, including demographic factors, HCV genotype, coinfections, and comorbidities. RESULTS: Cirrhosis or significant fibrosis (METAVIR score >F2) was observed in 26.8% of the patients. The stage of fibrosis was associated with age and estimated duration of infection (P <0.001). Active and past HBV infection did not affect fibrosis. The stage of liver fibrosis was lower in patients with spontaneous clearance of HCV (P = 0.007). CONCLUSIONS: Patients in our study had a similar stage of liver fibrosis to that reported by other studies on hemophilia. The older age and long duration of infection are the main risk factors for advanced fibrosis. Noninvasive methods such as shear wave elastography and FibroTest may allow a proper assessment of the fibrosis stage in hemophilia patients, particularly when used together and in correlation with other clinical parameters. They may also be useful in other groups of HCV­infected patients.

Co-Infection of the Hepatitis C Virus With Other Blood-Borne and Hepatotropic Viruses Among Hemophilia Patients in Poland.

BACKGROUND: The prevalence of HCV infection in people with hemophilia is substantially higher than that in the general population (63% - 98%). Multiple transfusions and substitutive therapy have also been linked to a high risk of HBV and HIV transmission. However, the prevalence of other blood-borne viral infections in this population is less well known. OBJECTIVES: This study aimed to assess the prevalence of co-infection with HBV and other blood-borne viruses in Polish HCV-infected hemophiliacs. METHODS: Seventy-one individuals, the majority of whom were male (94.36%), who had congenital bleeding disorders (60 had hemophilia A, five had hemophilia B, and six had other factor deficiencies) and HCV infection, which was defined as the presence of positive anti-HCV antibodies, were included in this study. The study group was divided into two subgroups according to the year in which blood donors were first tested for HBsAg in Poland. The serological markers were screened using commercially available enzyme immunoassays according to the manufacturer's instructions. The molecular tests were performed using real-time PCR technology with commercial assays according to the manufacturer's instructions. RESULTS: The spontaneous elimination rate of HCV RNA was 29.6%. The HCV genotype 1 was detected in 28 patients (65.1%), genotype 2 in one patient (2.3%), genotype 3 in 11 patients (25.6%), genotype 4 in two patients (4.7%), and a mixed infection with genotypes 1 and 4 was detected in one person (2.3%). Fifty-three patients (74.6%) were anti-HBc positive. Among the seven HBsAg(+) patients, three individuals were HBV-DNA positive. No occult hepatitis B was detected. In six HBsAg positive patients, the HCV RNA was positive, while one patient was also infected with HIV. The prevalence rate of past infection with HAV in the study group was 30.9%, with a tendency for a higher prevalence in older patients. The prevalence of CMV and EBV infection was high and similar to that seen in the general population. All the patients were HGV and HTLV-1 negative. CONCLUSIONS: The diagnostics and management of infections with hepatotropic viruses, particularly HBV, are neglected in hemophilic patients. All patients with coagulation disorders and a history of exposure to non-inactivated blood products should be screened for blood-borne infections. The prevalence of other potentially blood-borne viral infections exhibited a pattern similar to that observed in the general population.

Current Possibilities to Assess the Degree of Liver Fibrosis in Patients with Haemophilia Infected with HCV--Review.

Haemophilia is an entity, wherein the HCV infection rate is greater than in the general population and ranges between 70-90%. The majority of HCV infections were acquired by hemophiliacs in the 1980s, by the use of infected cryoprecipitate or fresh frozen plasma preparations. It is therefore highly likely that many of them, more than twenty years after the infection, have developed advanced liver disease. Until recently, in order to assess its severity, it was necessary to perform a liver biopsy. Currently, we observe rapid developments of non-invasive methods that are particularly useful in patients with bleeding disorders. The most popular include elastography (Fibroscan, SWE) and the algorithms based on measurements of the relevant blood parameters (e.g. FibroTest, Fibrometer, APRI index). Ease of implementation of these studies, no need for hospitalization of the patient or specific preparation for surgery, allow for quick and minimally invasive assessment of liver disease progression and classification of the patient to the appropriate antiviral therapy.

[SWE elastography in assessment of liver fibrosis]. / Elastografia SWE w ocenie wlóknienia watroby

Liver fibrosis is a relatively common consequence of chronic liver diseases, especially chronic viral hepatitis B and C. Biopsy still remains the gold standard in the assessment of liver fibrosis. However, due to its invasiveness and possible complications, less or even non-invasive methods are being developed, e.g. using biochemical parameters (Fibrotest) or elastography. Elastography is a new diagnostic tool that aims to evaluate stiffness of the tissues. Elastography techniques that are used in the assessment of liver fibrosis are transient elastography (TE), acoustic radiation force impulse (ARFI) and shear-wave elastography (SWE). SWE is a novel real-time two-dimensional elastography technique, which allows one to estimate stiffness quantitatively in kilopascals (kPa). Moreover, lapping elastography over regular B-mode allows precise choice of the region of interest. Therefore SWE creates the opportunity for accurate assessment of liver fibrosis. In this paper we describe processes leading to liver fibrosis as well as methods of liver fibrosis assessment, e.g. liver biopsy, biochemical tests or elastography. The main goal of this paper is to present the SWE technique, its role in liver fibrosis assessment and a short review of the most important clinical studies on SWE. We also present several examples of SWE examinations performed on patients with different stages of liver fibrosis - F0 to F4 on the METAVIR scale.

Nucleotide receptors as targets in the pharmacological enhancement of dermal wound healing.

With a growing interest of the involvement of extracellular nucleotides in both normal physiology and pathology, it has become evident that P2 receptor agonists and antagonists may have therapeutic potential. The P2Y2 receptor agonists (diquafosol tetrasodium and denufosol tetrasodium) are in the phase 3 of clinical trials for dry eye and cystic fibrosis, respectively. The thienopyridine derivatives clopidogrel and ticlopidine (antagonists of the platelet P2Y12 receptor) have been used in cardiovascular medicine for nearly a decade. Purines and pyrimidines may be of therapeutic potential also in wound healing since ATP and UTP have been shown to have many hallmarks of wound healing factors. Recent studies have demonstrated that extracellular nucleotides take part in all phases of wound repair: hemostasis, inflammation, tissue formation, and tissue remodeling. This review is focused on the potent purines and pyrimidines which regulate many physiological processes important for wound healing.

A review of chromatographic methods for determination of synthetic food dyes.

The purpose of this work was to present a chromatographic methods to analyse synthetic food dyes. The following techniques has been described: thin-layer liquid chromatography (TLC), high performance thin-layer chromatography (HPTLC), traditional column chromatography, high performance liquid chromatography (HPLC), include: ion-pair chromatography (HPLC IP), reversed phase chromatography (RP HPLC) and high performance ion chromatography.

Rilmenidine--its antihypertensive efficacy, safety and impact on quality of life in perimenopausal women with mild to moderate essential hypertension.

OBJECTIVES: A prospective, open-labeled study to assess the antihypertensive effect of monotherapy with rilmenidine and its impact on quality of life (QoL), as well as on biochemical parameters in perimenopausal women with essential hypertension. DESIGN AND METHODS: Fifty-five perimenopausal women with mild to moderate essential hypertension (mean age 51.4+/-2.4 years) were enrolled. At baseline and after 12-week monotherapy with rilmenidine, we assessed: systolic (SBP) and diastolic (DBP) blood pressure (BP), heart rate (HR), fasting glucose, serum creatinine and total cholesterol levels. QoL was also assessed at baseline and at 12 weeks by two standardized questionnaires: the Short Form - 36 (SF-36) and the Subjective Symptoms Assessment Profile (SSAP). Statistical analysis was performed using Student's t-test to compare changes in BP, QoL and biochemical parameters during therapy with rilmenidine. RESULTS: After 12 weeks of therapy, there was a significant decrease in BP and HR. Normalization of BP was observed in 46 (84%) women. Rilmenidine did not influence serum creatinine, fasting glucose and lipid profile. Treatment was very well tolerated by the patients and no side-effects were noted. Both the SF-36 and the SSAP demonstrated improvement in general QoL. We observed a significant improvement in all SF-36 subscales. In the SSAP, a similar significant improvement was found, except dizziness subscale. Improvement in QoL was not related to reduction of BP. CONCLUSIONS: Monotherapy with rilmenidine is safe and effective in BP treatment and significantly improves QoL in perimenopausal women with essential hypertension.