Anti-inflammatory activity of lipoic acid in mice peritonitis model

This work aimed to investigate the effect of lipoic acid (LA) on sulfane sulfur (S*) level, infiltration of neutrophils and vascular permeability in a model of zymosan-induced peritonitis. The study showed that lipoic acid increased the sulfane sulfur level. Also, it decreased count of neutrophils and inhibition of intensity of early vascular permeability compared to the control group. These studies indicated that LA exhibits antiinflammatory activity. LA serves as a sulfane sulfur acceptor and releases sulfane sulfur in the form of hydrogen sulfide (H2S), which is probably responsible for its anti-inflammatory activity

Hypotensive effect of alpha-lipoic acid after a single administration in rats

Objective: The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful. Methods: The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alphalipoic acid and/or glibenclamide) and 80 min thereafter. Results: Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA. Conclusion: This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alphalipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension. (Anatol Cardiol 2016; 16: 306-9

Noninvasive assessment of liver status in adult patients after the Fontan procedure

A hemodynamic derangement in Fontan circulation causes liver pathology known as Fontan‑associated liver disease. Although liver biopsy is a standard for diagnosis of liver fibrosis, noninvasive methods are being developed, including shear wave elastography (SWE). We aimed to evaluate the degree of liver stiffness (LS) using SWE in patients with Fontan circulation in a long‑term follow‑up and to investigate a relationship between patient characteristics and LS. The study included 59 patients after the Fontan procedure. Clinical examinations and laboratory tests were performed. According to the stage of LS, patients were divided into 2 subgroups: group 1 (METAVIR stages F1 and F2) and group 2 (METAVIR stages F3 and F4). The ratio of aspartate transaminase to alanine transaminase, aspartate transaminase‑to‑platelet ratio index (APRI), fibrosis‑4 (FIB‑4) score, and Forns index were assessed. The median LS was 9.1 kPa (interquartile range, 3.9–18.5 kPa). Five patients (9%) demonstrated LS in stage F1; 14 (26%), F2; 28 (52%), F3; and 7 (13%), F4. Group 2 had significantly higher aspartate transaminase and γ‑glutamyltranspeptidase levels, APRI, FIB‑4, and Forns index, and lower platelet count than group 1. A canonical correlation analysis indicated that LS and thrombocytopenia were related to time from the Fontan procedure, age at procedure, and single ventricular ejection fraction. We showed that adult patients after the Fontan procedure develop liver dysfunction. Time from surgery, age at procedure, and single ventricular ejection fraction are related to the degree of LS assessed by SWE. Finally, SWE, APRI, Forns index, and FIB‑4 score may help assess the degree of liver fibrosis

In Vivo Anti-inflammatory Activity of Lipoic Acid Derivatives in Mice

Background: In mammals lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) function as cofactors for multienzymatic complexes catalyzing the decarboxylation of α-ketoacids. Moreover, LA is used as a drug in a variety of diseases including inflammatory diseases. The aim of the study was to examine anti-inflammatory properties of LA metabolites.Material/methods:The present paper reports the chemical synthesis of 2,4-bismethylthio-butanoic acid (BMTBA) and tetranor-dihydrolipoic acid (tetranor-DHLA). BMTBA is one of the biotransformation products of LA, while tetranor-DHLA is an analogue of DHLA. Structural identity of these compounds was confirmed by 1H NMR. These compounds were assessed for their anti-inflammatory activity in mice. For this purpose, the zymosan-induced peritonitis and the carrageenan-induced hind paw edema animal models were applied.Results/conclusions: The obtained results indicated that the early vascular permeability measured at 30 min of zymosan-induced peritonitis was significantly inhibited in groups receiving BMTBA (10, 30, 50 mg/kg). The early infiltration of neutrophils measured at 4 hours of zymosan-induced peritonitis was inhibited in the group receiving BMTBA (50 mg/kg) and tetranor-DHLA (50 mg/kg). The results indicated that the increase in paw edema was significantly inhibited in the groups receiving BMTBA (50, 100 mg/kg) and tetranor-DHLA (30, 50 mg/kg). In summary, the present studies clearly demonstrated that both BMTBA and tetranor-DHLA were able to act as anti-inflammatory agents. This is the first study examining in vivo the anti-inflammatory properties of LA metabolites

Relationship of urinary isoprostanes to prostate cancer occurence

To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation–isoprostanes (8-isoPGF2) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer’s instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2–2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.This study was supported by the Grant 506/810(KBO) from University of Lodz, Polan

Lithostratigraphy of Zechstein evaporites of the central and north-western parts of the Mogilno Salt Diapir, based on boreholes Z-9 and Z-17 Litostratygrafia ewaporatów cechsztyńskich w centralnej i północno-zachodniej części wysadu solnego Mogilno, na podstawie danych z otworów Z-9 i Z-17 /

Tyt. z nagłówka.Bibliogr. s. 147-148.W artykule przedstawiono wyniki kompleksowych badań mineralogiczno-petrograficznych, przeprowadzonych na skałach ewaporatowych wieku cechsztyńskiego (górny perm) napotkanych w badawczych otworach wiertniczych w wysadzie solnym Mogilno. Na podstawie otrzymanych wyników stwierdzono w badanych otworach sole kamienne, sole potasowo-magnezowe (sylwinity kizerytowe), sole ilaste, zubry i anhydrytowce. Powyższe utwory przydzielono do cyklotemów PZ-3 i PZ-2. Nie stwierdzono obecności ewaporatów cyklotemów PZ-1 i PZ-4. Rozpoznane skały zbudowane są głównie z halitu, sylwinu, kizerytu, anhydrytu. W mniejszych ilościach występują polihalit, kainit, węglany i minerały ilaste. Zidentyfikowano wiele minerałów akcesorycznych, których zawartość w skałach solnych jest rzędu ppm.This paper presents the results of comprehensive mineralogical and petrographic studies conducted on evaporite rocks of the Zechstein (Upper Permian) period, extracted from boreholes drilled in the Mogilno diapir. Based on the research results, the occurrence of rock salts, potash-magnesium salts (kieseritic sylvinites), clayey salts, zubers, and anhydrites was identified. Those formations were assigned to cyclothems PZ-3 and PZ-2. No presence of evaporites belonging to cyclothems PZ-1 and PZ-4 were discovered. The recognized rocks were mainly composed of halite, sylvine, kieserite and anhydrite. Smaller quantities of polyhalite, kainite, carbonates and clayey minerals were also found. A number of accessory minerals were identified, with their salt rock contents from several to about several tens of ppm.Dostępny również w formie drukowanej.SŁOWA KLUCZOWE: górny perm, ewaporaty cechsztyńskie, litostratygrafia cechsztynu, sól kamienna, sole potasowo-magnezowe, minerały solne, wysad solny Mogilno. KEYWORDS: Upper Permian in Poland, Zechstein evaporites, Zechstein lithostratigraphy, rock salt, potash-magnesium salts salt minerals, Mogilno Salt Diapir

O-GlcNAcylacja, receptory dla steroidów i nowotwory

The addition of a single residue of O-linked N-acetylglucosamine (O-GlcNAc) to serine or threonine is a post-translational modification (O-GlcNAcylation) of proteins found in the cytoplasm or the nucleus. This dynamic modification is dependent on the environmental glucose concentration. O-GlcNAc modification is catalysed by a glycosyltransferase named O-linked N-acetylglucosaminyltransferase (OGT), and O-GlcNAc residue is removed by the antagonistic enzyme β-N-acetylglucosaminidase (O-GlcNAcase; OGA). Cytosolic O-GlcNAcylation is important for the proper transduction of signalling cascades, whereas nuclear O-GlcNAc is crucial for the transcriptional regulation. O-GlcNAcylation is also important in the regulation of the transcriptional activity of steroid hormone receptors. Both O-GlcNAc transferase and O-GlcNAcase are found in all tissues and have been shown to be essential for development in vertebrates, which underscores their fundamental roles in vital processes as well as in pathological conditions such as neoplastic transformation.Glikozylacja polegająca na przyłączeniu pojedynczych reszt β-N-acetylo- D-glukozaminy do reszt seryny lub treoniny polipeptydu wiązaniem O-glikozydowym (O-GlcNAc), jest powszechną modyfikacją białek jądrowych i cytoplazmatycznych. Modyfikacja ta pozostaje w ścisłym związku z dostępnością glukozy. β-N-acetyloglukozaminylotransferaza (O-GlcNAc transferaza, OGT) jest enzymem odpowiedzialnym za katalityczne przyłączenie reszt O-GlcNAc, natomiast β-N-acetylo-D-glukozaminidaza (OGA) reszty te odłącza. Proces O-GlcNAcylacji zachodzący w cytozolu jest istotny z punktu widzenia transmisji sygnału komórkowego, natomiast przyłączanie reszt O-GlcNAc na terenie jądra wpływa na proces transkrypcji. Wykazano, że proces O-GlcNAcylacji moduluje regulację aktywności transkrypcyjnej receptorów hormonów steroidowych. Oba enzymy, O-GlcNAc transferaza i β-N-acetylo- D-glukozaminidaza wykrywane są we wszystkich tkankach i jak wykazano, niezbędne są dla prawidłowego rozwoju organizmu, jak również mogą uczestniczyć w procesie transformacji nowotworowej

Identification and Analysis of Problems in Selected European Historic Gardens during the COVID-19 Pandemic

The paper is based on a survey and investigates the functioning of historic gardens during the pandemic. The authors collected and analysed information on the impact of the pandemic on the behaviour of visitors, maintenance, and condition of cultural heritage assets, European historic gardens. Four aspects were considered particularly carefully: the situation of gardens during the COVID-19 pandemic, maintenance and care in gardens, virtual activity and communication, and financial consequences. The authors determined the conditions of the gardens and the problems they faced based on a survey completed by 23 managers of 31 historic gardens from June to August 2020 and then proposed a diagnosis. The paper presents the survey results. In general, visitor volumes tended to drop in 2020, which significantly affected gardens’ financial standing and contributed to workforce reductions. The garden condition and treatments were affected, as well. Reduced visitor volumes resulted in positive environmental changes. Among them were ecological succession, the stability of landscaped plants, increase in vegetation, improved biodiversity in the ground cover, and enhanced animal presence. Additional safety measures were implemented after the gardens were reopened to the public during the pandemic, mostly social distancing, and obligatory face masks. Less than half of the gardens had contingency plans, and 25% of the respondents were working to develop one. The analyses provided foundations to start working on a universal emergency strategy similar to procedures used for years for permanent collections at museums. Note that, being open public spaces and live museums, historic gardens were the first places reopened after the lockdown. Recommendations based on the study can contribute to the future safe functioning of historic gardens in other similar crises. The guidelines offer instructions, advice, and recommendations that form foundations of the development of a universal management model facilitating the preservation of historic gardens in good condition while exploiting their ecological potential

Comparison of the Results of Therapy for cT1 Renal Carcinoma with Nephron-Sparing Surgery (NSS) vs. Percutaneous Thermal Ablation (TA)

Implementation of ultrasonography (USG), computed tomography (CT) and magnetic resonance imaging (MRI) into abdominal cavity diagnostics enabled early detection of cT1 graded renal cancers. According to European Association of Urology (EAU) and Polish urological Association (PUA) recommended method of treatment is sparing resection of renal parenchyma with tumour—nephron-sparing surgery (NSS). In selected cases other methods such as thermal ablation (TA) or cryoablation can be introduced /1/. Objectives: To evaluate the results of treatment of cT1 renal tumours with the use of NSS and TA methods. Material and methods: 140 patients with cT1 renal carcinoma were treated in 2nd Department of Urology of Medical University of Lodz between 2014 and 2017. Neuron-sparing surgery was performed in 56 cases (40%), while percutane-ous thermal ablation (TA) in 84 cases (60%). Demographic data, clinical data (lab results, Charlson index), nephrometry data (tumour size, location, R.E.N.A.L. score) post-operative data (Clavien-Dindo classifica-tion) were investigated. Histopathology results, Fuhrman malignancy grading, as total three-year survival of patients were evaluated. The following methods were used for statistical evaluation: Chi2, Fisher, W Shapiro-Wilk, U Mann-Whitney tests, Kaplan-Meier’s curve and Cox model. The results were displayed in a form of median and upper and lower quartile values (25–75%). Results: No statistical differences in gender nor left/right kidney location were observed. Patients, who underwent TA were at average 10 years older and had multiple comorbidities (median age for TA was 79, for NSS 68; median Charlson index for TA was 5 and for NSS was 3). TA patients had lesser haematological values (Hb, Ht). R.E.N.A.L. scoring demonstrated comparable nephrometry in both groups. NSS procedure was open laparotomy without temporary clamping of renal vessels. Surgical margins of resected tumours were negative. TA was performed with Cool-Tip Covidienequipment with the use of Cluster electrode and was ultraso-nography-guided. Post-treatment complications evaluated with the use of Clavien-Dindo classification were slightly more frequent for NSS method. Patients after NSS were discharged at average after 8.5 days and after TA after 3 days. Histopathological type and Fuhrman malignancy grading were comparable in both groups. TA treated patients’ death risk was 9-fold of that observed in NSS treated patients. There was 1 death for each group in perioperative period. Conclusion: 1. NSS was associated with slightly higher side effect rate but resulted in prolonged survival. 2. TA was applied to elderly patients with comorbidities. Despite less invasive treatment this group had poorer/reduced survival. 3. Charlson Comorbidity Index (CCI) and the treatment method were relevant survival factors in patients treated due to cT1 renal cancer tumours