Determination of the Primary Molecular Target of 1,2,4-Triazole-Ciprofloxacin Hybrids

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.This research was supported by the Ministry of Science and Higher Education under Iuventus Plus grant No. IP2014 037473. Tomasz Plech is a recipient of the Fellowship for Young Researchers with Outstanding Scientific Achievements from the Medical University of Lublin (Lublin, Poland)

Effectiveness of domestic rural wastewater treatment in soil-plant system

The characteristics of Polish rural agglomerations indicate that only 32% of these areas are villages typified by compact buildings where the use of a collective sewage system is economically justified. In other areas, it is necessary to apply solutions that allow for the sewage utilization in place of their creation and safe discharge into the environment, e.g. in the form of home systems based on biological processes, e.g. in soil-plant systems. The purpose of the work was to determine the soil-plant efficiency of wastewater treatment with the use of so-called energy plants. The experiment was conducted in 2012–2014 in lysimeters at a depth of 130 cm and 100 cm in diameter. These were submerged in the ground, filled with sand clay and equipped with installations enabling the drainage of gravity water in the form of lysimeter effluents. Two species of plants were used: Miscanthu giganteus and Sida hermaphrodita (L.) Rusby. They were irrigated with pre-treated domestic sewage (variant I – 1200 mm • year−1 and variant II – 1600 mm • year−1). For irrigation, sewage from a group of buildings inhabited by six families was used. Raw domestic sewage was discharged into the tank, consisting of four chambers, which constituted a relatively good level of pre-cleaning. For the irrigation of plants in the experiment, pre-treated sewage was used. In order to determine the effectiveness of wastewater treatment in the soil-plant environment, the concentrations of the following components were determined in the effluents: TSS, BOD5, COD, Ntot. The quantities of pollutants contained in the sewage were characterized by considerable variability, especially in relation to COD (390.6– 1583.0 mg O2 • dm−3) and Ntot (47.0–250.2 mg N • dm−3)

Nadużywanie sterydów anabolicznych prowadzące do rozwoju guza insulinowego trzustki

Background. Anabolic steroid abuse is very common among bodybuilders and is related with a number of medical complications including tumorgenesis.Case report. A 29-year-old male bodybuilder with one year history of abusing large doses of anabolic steroids presented with several episodes of neuroglycopenia with concomitant loss of consciousness. Results of imaging studies (USG, MRI, EUS) showed smooth-demarcated, focal solid lesion of 2cm in diameter in the body of the pancreas. The patient was characterized by Whipple's triad (hyperinsulinemia accompanied by hypoglycemia and signs of symptoms resolving upon glucose administration).  No other disturbances were observed. The patient was qualified for the surgical treatment. Intraoperatively, tumor enucleation was performed. Postoperative time was complicated by pancreatic fistula that required reoperation involving Roux pancreaticojejunostomy.  The pathological examination revealed encapsulated benign neuroendocrine tumor. The patient has been followed up for 3 years and remained disease free.Conclusion. Given the widespread use anabolic steroids among bodybuilder, another potentially life-threatening tumor is highlighted. Insulinoma has not been previously reported in athletes. Bodybuilders should be aware of the serious medical risks including neuroendocrine tumors.Wprowadzenie. Nadużywanie steroidów anabolicznych jest częste wśród kulturystów. Powiązane jest to z wieloma negatywnymi skutkami zdrowotnymi – w tym z rozwojem nowotworów.Opis przypadku. 29-letni kulturysta z rocznym przyjmowaniem dużych dawek steroidów anabolicznych w wywiadzie zaprezentował kilka epizodów neuroglikopenii z towarzyszącymi utratami przytomności. Wyniki badań obrazowych (USG, MRI, EUS) ujawniły lite ognisko o dość wyraźnych granicach i średnicy 2cm w trzonie trzustki. Objawy pacjenta układały się w obraz triady Whipple’a (hiperinsulinemia z towarzyszącą hipoglikemią oraz ustępowanie objawów po podaniu glukozy). Innych odchyleń od normy nie zaobserwowano. Pacjent został zakwalifiko-wany do leczenia chirurgicznego – przeprowadzono zabieg wyłuszczenia guza trzustki. Przebieg pooperacyjny był powikłany wystąpieniem przetoki trzustkowej, wymagającej reoperacji z zespoleniem trzustkowo-jelitowym sposobem Roux. Badanie histopatologiczne wykazało obecność oto-rebkowanego łagodnego guza neuroendokrynnego. Pacjent był poddany obserwacji przez 3 lata, w tym czasie nie zaobserwowano nawrotu choroby.Wnioski. Biorąc pod uwagę częste zjawisko zażywania sterydów anabolicznych przez kulturystów, niniejsza praca zwraca uwagę na możliwość wtórnego rozwoju kolejnego, potencjalnie zagrażającego życiu nowotworu. Guz insulinowy nie był poprzednio opisywany u sportowców. Kulturyści powinni być świadomi pewnych następstw zdro-wotnych w związku z zażywaniem steroidów anabolicznych

Identification of catchment areas with phosphorus pollution risk for lowland river water quality

The study aimed to analyse the seasonal variability of phosphorus concentrations and phosphorus content and the impact of catchment development of the Panew Mała River. The study presents the findings of a two-year experimental investigation (comprising 17 measurement series across 12 measurement cross-sections) into the concentration of phosphorus (P) and its soluble form, orthophosphates (PO42−). The mean phosphate concentrations were found to be low, with a range of 0.03 to 0.08 PO42− mg∙dm−3. In contrast, the total phosphorus concentrations were relatively high, with a range of 0.11 to 0.43 mg∙dm−3 The seasonal variability was analysed based on quarterly means and half-yearly periods covering quarters II and III (spring–summer) and quarters I and IV (autumn–winter), respectively. The analysis of spatial variability was conducted using cluster analysis according to Ward’s method, with the Euclidean distance employed as a measure of distance and the results related to the utilisation of different catchment area. Due to the slight differences in the phosphate concentration, the total phosphorus concentration was analysed in detail. The analysis of variance showed no significant differences between phosphorus concentrations in certain quarters, while greater variations were obtained for half-yearly periods. The applied method of grouping the sampling sites made it possible to distinguish several groups of sampling sites, which indicate relations between the values of phosphorus concentration in the waters of Mała Panew and the type of use of the catchment area

Test hamowania oktreotydem w diagnostyce i prognozowaniu skuteczności terapii u chorych z guzami neuroendokrynnymi. Doniesienie wstępne

Introduction: Chromogranin A (CgA) is a non-specific marker of neuroendocrine tumors (NET) and is important in monitoring the disease course and NET treatment. Aim of the study: Usefulness of suppression test of CgA secretion with octreotide in diagnosis and predicting the therapy outcome in NET patients. Material and methods: The study included 32 patients with NET of gastrointestinal tract, lung and of unknown origin. CgA level in blood plasma on fasting, before and 30, 60, 90 and 120 minutes after subcutaneous administration of 100 μg octreotide, was determined in all patients. The subjects were divided into two subgroups with relation to CgA level and to the results of somatostatin receptor scintigraphy (SRS). Results: Statistically significant CgA decrease after octreotide administration in all study time points and positive results of SRS were found in the patients with the elevated CgA level. No statistically significant decrease of CgA level after octreotide was found in the group with normal CgA levels. In this group, 13 patients had a negative result of SRS, and somatostatin receptors expression was found in one patient. Tolerance of somatostatin analogs (SSA) therapy was very good. Conclusions: Octreotide suppression test with CgA level assessment in NET patients is a simple, straightforward examination, providing information on the predicted response to the applied SSA and the data on initial clinical tolerance of those agents. This examination can also be a screening test useful in planning the treatment with SSA in patients with NET.Wstęp: Chromogranina A (CgA) jest niespecyficznym markerem guzów neuroendokrynnych (NET). Jest ona przydatna w monitorowaniu przebiegu choroby i leczenia chorych z NET. Cel pracy: Użyteczność testu hamowania wydzielania CgA z użyciem oktreotydu w diagnostyce i prognozowaniu skuteczności terapii chorych z guzami neuroendokrynnymi. Materiał i metody: Do badania włączono 32 chorych z guzami neuroendokrynnymi układu pokarmowego, płuc i o nieznanym miejscu pochodzenia. U wszystkich badanych oznaczano stężenie CgA w osoczu krwi na czczo, przed oraz 30, 60, 90 i 120 minut po podaniu podskórnym 100 µg oktreotydu. Badane osoby podzielono na dwie podgrupy w zależności od stężenia CgA oraz wyniku scyntygrafii receptorów somatostatynowych. Wyniki: U chorych z podwyższonymi stężeniami CgA wykazano znamienne statystycznie obniżenie stężenia CgA po podskórnym podaniu oktreotydu w badanych punktach czasowych oraz dodatni wynik scyntygrafii receptorów somatostatynowych (SRS). W grupie chorych z prawidłowymi stężeniami CgA nie wykazano statystycznie znamiennego obniżenia stężenia CgA po podaniu oktreotydu. W tej grupie 13 chorych miało ujemny wynik SRS, u jednego chorego stwierdzono ekspresję receptorów somatostatynowych. Tolerancja leczenia analogami somatostatyny (SSA) była bardzo dobra. Wnioski: Wykonywanie testu z oktreotydem z oznaczaniem stężeń CgA u chorych z guzami neuroendokrynnymi jest prostym, łatwym do wykonania badaniem dającym informacje o przewidywanej odpowiedzi na zastosowanie analogów somatostatyny, jak również dostarczającym danych na temat wstępnej tolerancji klinicznej tych preparatów. Badanie to może być przesiewowym, przydatnym testem w planowaniu leczenia analogami somatostatyny u chorych z NET

The immune complex p53 protein/anti-p53 autoantibodies in the pathogenesis of ovarian serous carcinoma

Objectives: The tests conducted were intended to analyze the concentration of p53 protein and anti-p53 autoantibodies in serum of women with ovarian tumours. Material and methods: The study included patients with diagnosed ovarian cancer: Cystadenoma serosum or Cystadenocarcinoma papillare serosum at IIIc stage (including 10 women who had G1, 14 women who had G2 and 30 women who had G3 staging). Concentrations of parameters were measured by ELISA. Results: The analysis of the obtained results showed statistical significance between the concentration of p53 protein depending on the degree of differentiation of G1 and G3 (p < 0.001) and anti-p53 autoantibodies depending on the degree of differentiation of G1 and G2 (p < 0.05) as well as G2 and G3 (p < 0.01). In addition, the determined p53/anti-p53 autoantibodies ratio was only significant between G1 and G2 (p < 0.05), as was the assessment of the percentage of the tested parameters in the immune complex. Conclusions: Immune system disorders involving the p53 protein and anti-p53 autoantibodies may be one of the immune mechanisms involved in the pathogenesis of ovarian serous cancer

Palliative surgery in cases of unresectable pancreatic head cancer

Wstęp. W niniejszej pracy omówiono postępowanie paliatywne u chorych z nieresekcyjnym rakiem głowy trzustki. Celem pracy było porównanie różnych rodzajów operacji, wykonywanych przy braku możliwości leczenia radykalnego. Materiał i metody. Analizie poddano 108 chorych z rakiem głowy trzustki, których operowano w Klinice Chirurgii Ogólnej i Transplantacyjnej w latach 1995-2004. U 94 chorych śródoperacyjnie stwierdzono nieresekcyjność zmiany bez naciekania dwunastnicy. Chorych tych podzielono na 2 grupy: w pierwszej (60 chorych) wykonano zespolenie odbarczające drogi żółciowe, a w drugiej (34 chorych) - zespolenie odbarczające drogi żółciowe i dodatkowo zabieg drenujący żołądek. W obu grupach operowanych chorych porównano średni czas pobytu w szpitalu, częstość występowania powikłań chirurgicznych i śmiertelność. Wyniki. Obydwie grupy chorych były porównywalne pod względem wieku i płci. Chorzy po operacji zespolenia żółciowego przebywali w szpitalu średnio 19,2 ± 7,9 dnia, a po zabiegu uzupełnionym o profilaktyczne zespolenie żołądkowo-jelitowe - 18,1 ± 9,1 dnia. Porównując częstość powikłań pooperacyjnych i śmiertelność w grupach, nie stwierdzono pomiędzy nimi różnic istotnych statystycznie. Wnioski. Tradycyjnie stosowany w zabiegach paliatywnych przy zaawansowanym raku trzustki drenaż dróg żółciowych można rozszerzyć o zespolenie żołądkowo-jelitowe bez ryzyka zwiększenia częstości powikłań pooperacyjnych.Background. The authors discuss surgical palliative procedures in patients with unresectable pancreatic head cancer. Aim of the study is to compare diffrent surgical procedures in respect of postoperative complication and mortality rate in cases, when the radical treatment was not possible. Material and methods. We analysed 108 patients who underwent surgery for the pancreatic head cancer in Department of General and Transplant Surgery of the Medical University in Łódź between years 1995 and 2004. Of those in 94 cases unresectable lesion without duodenal involvement was detected during surgery. The patients were divided into two groups - in the first group of 60 - biliary by-pass procedure has been done and in the second group of 34 - similiar procedure with gastroenterostomy. We compared the frequency of postoperative complications and mortality rate in mentioned above groups. Results. Patients, who underwent combined biliary and gastric by-pass remained in hospital for 18.1 ± 9.1 and following biliary by-pass alone - 19.2 ± 7.9 days. There were no statistically significant differences between these groups while the complication frequency and mortality rate were found similar. Conclusions. In advanced pancreatic cancer, traditionally executed biliary drainage can be extended by a gastro-jejunostomy without the increased risk of post-operative complications or mortality

Ocena stężenia produków zaawansowanej glikacji białek i przeciwciał anty-CEL i anty-CML w surowicy pacjentów chorujących na orbitopatię Gravesa przed i po leczeniu metyloprednizolonem

  Introduction: The glycation process is a non-enzymatic modification of proteins occurring due to the reactions of reductive carbohydrates. The glycated residues lose their biological functions, and their removal process is ineffective. They accumulate, and as a result they cause an immunological response. The aim of this study was a determination of the concentrations of advanced glycation end-products and antibodies against carboxymethyl lysine (anti-CML) and carboxyethyl lysine (anti-CEL) in the sera of Graves’ orbitopathy patients. Material and methods: The study group were patients from the Division of Endocrinology of the Medical University of Silesia (n = 25) suffering from Graves’ orbitopathy. The concentration of AGE-peptides using flow spectrofluorimetry method, and anti-CML and anti-CEL IgG antibodies using immunoenzymatic technique (ELISA), were measured in patients sera before and after methylprednisolone treatment. Results: In sera of the study group the concentrations of AGE-peptides and anti-CML were significantly lower before and after treatment in comparison to the control group (p < 0.05). Mean values of anti-CEL concentrations were comparable (at both phases of treatment) with the value observed in the control group. After treatment the concentrations of AGE-peptides and anti-CEL significantly decreased (p < 0.05); however, the concentration of anti-CML was also lower but the observed change was not significant (p > 0.05). Conclusions: In the course of Graves’ orbitopathy the glycation process is disturbed. The treatment modifies significantly the process by lowering the concentration of advanced glycation end-products and suppressing the immune response to them. (Endokrynol Pol 2016; 67 (4): 383–389)    Wstęp: Glikacja jest nieenzymatyczną modyfikacją białek zachodzącą z udziałem cukrów redukujących. Produkty glikacji białek tracą swoje biologiczne funkcje, przez co ich usuwanie staje się nieefektywne. Kumulują się one, a jako neoepitopy wywołują odpowiedź immunologiczną. Celem pracy była ocena stężeń końcowych produktów zaawansowanej glikacji białek (AGE-peptydów) i przeciwciał przeciwko karboksymetylolizynie (anty-CML) i karboksyetylolizynie (anty-CEL) w surowicy chorych na orbitopatię Gravesa. Materiał i metody: Badaną grupę stanowili pacjenci Kliniki Endokrynologii Śląskiego Uniwersytetu Medycznego (n = 25) cierpiący na orbitopatię Gravesa. W surowicy krwi żylnej oznaczono zawartość AGE-peptydów przy użyciu metody spektrofluorymetrii przepływowej oraz przeciwciał anty-CML i anty-CEL w klasie IgG przy użyciu techniki immunoenzymatycznej (ELISA), przed i po leczeniu preparatem metyloprednizolonu. Wyniki: W próbkach surowicy grupy badanej wykazano istotne statystycznie niższe stężenia AGE-peptydów i anty-CML zarówno przed, jak i po leczeniu w porównaniu z grupą kontrolną (p < 0,05). Średnie stężenia anty-CEL były porównywalne (w obu etapach leczenia) do obserwowanych w grupie kontrolnej. Po zastosowanym leczeniu stężenie AGE-peptydów oraz anty-CEL uległo znaczącemu obniżeniu (p < 0,05); stężenie anty-CML również było niższe, lecz zaobserwowana różnica nie była znamienna statystycznie (p > 0,05). Wnioski: W przebiegu orbitiopatii Gravesa procesy glikacji białek ulegają zaburzeniu. Na podstawie wyników wstępnych badań można stwierdzić, że leczenie istotnie modyfikuje ten proces, zmniejszając stężenie końcowych produktów zaawansowanej glikacji oraz hamując odpowiedź immunologiczną przeciwko nim. (Endokrynol Pol 2016; 67 (4): 383–389)

Survivin expression at the mRNA level in tumors and the protein concentration in the serum and peritoneal fluid in patients with serous ovarian tumors

Objectives: Ovarian cancer is one of the gynecological cancers that have the worst prognosis. The expression of the proteins from the IAP family (inhibitor of apoptosis protein), including survivin, is observed in many types of cancer. The aim of the study was to evaluate survivin at the mRNA level in tumors and the protein concentration in the serum and peritoneal fluid of patients with serous ovarian cancer in order to assess the relationship between the concentration of survivin and the histological subtypes of cancer. Material and methods: The study group consisted of 55 women, including patients with serous ovarian cancer (n = 30, nine low-grade serous carcinoma LGSC, 21 high-grade serous carcinoma HGSC), serous cysts (n = 10) and the control group (n = 15). The concentration of protein in the peritoneal fluid and serum was assessed using ELISA tests. The expression of survivin gene BIRC5 in the tumors was assessed using the RT-qPCR method. Results: The data that was obtained indicated that the concentration of survivin was higher in the serum of the women with serous ovarian cancer compared those that had benign tumors (p < 0.05) and the control group (p < 0.001). The survivin concentration was also higher in both the serum and peritoneal fluid in the HGSC group compared to the LGSC group (p < 0.001). The mRNA level was highest in the HGSC group, and there was a statistically significant difference compared to those in the benign tumor group and HGSC group ( p < 0.05). Conclusions: The observed changes prove that the expression level increases significantly in HGSC in both the protein and mRNA levels. Based on these findings, it can be assumed that assessing this parameter could be a useful additional indicator of the progression and differentiation of this type of cancer. However, this requires further research in a larger group of patients and possibly in other types of ovarian cancer

The impact of the COVID-19 Pandemic on hypertension phenotypes (ESH ABPM COVID-19 study)

Objective: The COVID-19 pandemic had a major impact on medical care. This study evaluated the influence of the pandemic on blood pressure (BP) control and hypertension phenotypes as assessed by office and 24-hour ambulatory BP monitoring (ABPM). Design and methods: Data were collected from 33 centers including Excellence Centers of the European Society of Hypertension. Two groups of patients with treated hypertension were compared. Pandemic group: including participants who had ABPM twice - at visit 2 during the COVID-19 pandemic and visit 1 performed 9-15 months prior to visit 2. Pre-pandemic group: had ABPM at two visits, performed before the pandemic within 9-15 months interval. We determined the following hypertension phenotypes: masked hypertension, white coat hypertension, sustained controlled hypertension (SCH) and sustained uncontrolled hypertension (SUCH). We analyzed the prevalence of phenotypes and their changes between visits. Results: Data of 1419 patients, 616 (43 %) in the pandemic group and 803 (57 %) in the pre-pandemic group, were analyzed. At baseline (visit 1), the prevalence of hypertension phenotypes did not differ between groups. In the pandemic group, the change in hypertension phenotypes between two visits was not significant (p = 0.08). In contrast, in the pre-pandemic group, the prevalence of SCH increased during follow-up (28.8 % vs 38.4 %, p < 0.01) while the prevalence of SUCH decreased (34.2 % vs 27.8 %, p < 0.01). In multivariable adjusted analysis, the only factor influencing negative changes of hypertension phenotypes was the COVID-19 pandemic period. Conclusion: These results indicate a negative impact of the COVID-19 pandemic on BP control assessed by hypertension phenotypes