Recommendations of Polish Cardiac Society expert regarding the use of andexanet alpha in the Polish context. An interdisciplinary protocol

Andexanet alfa (AA) is a recombinant, inactive analog of human factor Xa (FXa), effectively reversing the effects of its inhibitors — rivaroxaban and apixaban, which are available in Poland. The drug was granted registration after the publication of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in a group of patients using the aforementioned anticoagulants was proven. Hence, AA is now recommended for patients receiving apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows to outrule the presence of clinically relevant plasma concentrations of the FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of hemostasis tests, as it depends solely on the time elapsed since the last dose of FXa inhibitor, and on the dose and type of long-term medication used. AA is administered as an intravenous (i.v.) bolus, followed by an i.v.infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be readministered

Stanowisko ekspertów Polskiego Towarzystwa Kardiologicznego dotyczące stosowania andeksanetu alfa w warunkach polskich — interdyscyplinarny protokół

Andeksanet alfa (AA) jest rekombinowanym, nieaktywnym analogiem ludzkiego czynnika Xa (FXa), skutecznie odwracającym działanie jego inhibitorów — dostępnych w Polsce rywaroksabanu i apiksabanu. Lek otrzymał rejestrację po opublikowaniu wyników badania ANNEXA-4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors 4), w którym udowodniono jego skuteczność w przywracaniu hemostazy w zagrażających życiu krwawieniach w grupie pacjentów stosujących te leki przeciwkrzepliwe. Dlatego AA jest obecnie zalecany u pacjentów stosujących terapię apiksabanem lub rywaroksabanem z masywnymi i niemożliwymi do opanowania krwotokami, w tym udarami krwotocznymi i krwawieniami z przewodu pokarmowego. Najodpowiedniejsze do oszacowania stężenia rywaroksabanu i apiksabanu w osoczu, poza jego bezpośrednią oceną, są chromogenne testy anty-Xa specyficzne dla leku. Brak aktywności anty-Xa stwierdzony przy użyciu tych oznaczeń wyklucza istotne klinicznie stężenie inhibitora FXa w osoczu. Dawka AA nie powinna być natomiast modyfikowana na podstawie wyników badań hemostazy. Zależy ona wyłącznie od czasu, jaki upłynął od przyjęcia ostatniej dawki inhibitora FXa, oraz od dawki i rodzaju stosowanego przewlekle leku. Andeksanet alfa podawany jest w postaci bolusa dożylnego a następnie włączony zostaje wlew dożylny leku. Maksymalne odwrócenie aktywności anty-Xa następuje w ciągu 2 minut od zakończenia podawania bolusa, a kontynuowanie ciągłej infuzji dożylnej umożliwia utrzymanie efektu aż do 2 godzin po jego zakończeniu. Ponieważ aktywność leku przeciwkrzepliwego może się pojawić ponownie po zakończeniu wlewu, obecnie nie jest jasne, w jakim momencie po podaniu AA można (ponownie) podać inhibitory FXa lub heparynę

Valuable energy of biochar from agricultural and forest waste streams

Wastes from forest and agricultural industry are still insufficiently used. One of the ways of their preprocessing is a pyrolysis process. Therefore, the aim of this study was to determine the energetic properties of biochar made of walnut shells, forest wood chips and willow chips. The studies were performed according to standards. The moisture contents of the material, the ash contents, the net and gross calorific values were determined. Low moisture and ash content were found in each of the biochar species. For all tested samples the ash contents were lower than 6% and for forest wood chips it was 1.5% only. The way of processing the biomass in the pyrolysis process significantly increased the calorific value of the raw materials. It was found that the net calorific values of the tested materials were high and reached the amount of 26.58 MJ‧ kg-1 for biochar made of walnut shells, 22.29 MJ‧ kg-1 for biochar made of forest wood chips and 24.59 MJ‧ kg-1 for biochar made of willow chips. Due to the good physical properties of biochar produced from waste and biological materials, it was found that these solid fuels can be used for energy purposes

The use of various species of fungi in biofiltration of air contaminated with odorous volatile organic compounds

Air pollution with odorous compounds is a significant social and environmental problem. This paper presents biological deodorization methods. The attention is focused on the application of biotrickling filters for air deodorization. Principles of their operation are discussed, indicating the key role of the selection of microorganisms responsible for the degradation of odorous compounds. A literature overview of the used fungal species is presented and the advantages of using fungi in comparison with bacteria are indicated. The results of experimental studies on the n-butanol removal in biotrickling filter are presented

Total knee replacement induces peripheral blood lymphocytes apoptosis and it is not prevented by regional anesthesia – a randomized study

Background: Among the many changes caused by a surgical insult one of the least studied is postoperative immunosuppression. This phenomenon is an important cause of infectious complications of surgery such as surgical site infection or hospital acquired pneumonia. One of the mechanisms leading to postoperative immunosuppression is the apoptosis of immunological cells. Anesthesia during surgery is intended to minimize harmful changes and maintain perioperative homeostasis. The aim of the study was evaluation of the effect of the anesthetic technique used for total knee replacement on postoperative peripheral blood lymphocyte apoptosis. Methods: 34 patients undergoing primary total knee replacement were randomly assigned to two regional anesthetic protocols: spinal anesthesia and combined spinal–epidural anesthesia. 11 patients undergoing total knee replacement under general anesthesia served as control group. Before surgery, immediately after surgery, during first postoperative day and seven days after the surgery venous blood samples were taken and the immunological status of the patient was assessed with the use of flow cytometry, along with lymphocyte apoptosis using fluorescent microscopy. Results: Peripheral blood lymphocyte apoptosis was seen immediately in the postoperative period and was accompanied by a decrease of the number of T cells and B cells. There were no significant differences in the number of apoptotic lymphocytes according to the anesthetic protocol. Changes in the number of T CD3/8 cells and the number of apoptotic lymphocytes were seen on the seventh day after surgery. Conclusion: Peripheral blood lymphocyte apoptosis is an early event in the postoperative period that lasts up to seven days and is not affected by the choice of the anesthetic technique. Resumo: Justificativa e objetivo: Dentre as muitas alterações causadas por uma ferida cirúrgica, uma das menos estudadas é a imunossupressão pós-operatória. Esse fenômeno é uma causa importante das complicações infecciosas relacionadas á cirurgia, como infecção do sítio cirúrgico ou pneumonia nosocomial. Um dos mecanismos que levam à imunossupressão pós-operatória é a apoptose de células imunológicas. Durante a cirurgia, a anestesia se destina a minimizar as alterações prejudiciais e manter a homeostase perioperatória. O objetivo deste estudo foi avaliar o efeito da técnica anestésica usada para artroplastia total de joelho sobre a apoptose em linfócitos de sangue periférico no pós-operatório. Métodos: 34 pacientes submetidos à artroplastia total primária de joelho foram randomicamente designados para dois protocolos de anestesia regional: raquianestesia e bloqueio combinado raqui-peridural. Onze pacientes submetidos à artroplastia total do joelho sob anestesia geral formaram o grupo controle. Antes da cirurgia, logo após a cirurgia, durante o primeiro dia de pós-operatório e sete dias após a cirurgia, amostras de sangue venoso foram colhidas e o estado imunológico do paciente foi avaliado com o uso de citometria de fluxo, juntamente com apoptose de linfócitos usando microscopia de fluorescência. Resultados: Apoptose em linfócitos de sangue periférico foi observada imediatamente no pós-operatório e acompanhada por uma redução do número de células T e B. Não houve diferença significativa no número de linfócitos apoptóticos de acordo com o protocolo anestésico. Alterações no número de células T CD3/8 e no número de linfócitos apoptóticos foram observadas no sétimo dia após a cirurgia. Conclusão: Apoptose em linfócitos de sangue periférico é um evento precoce no período pós-operatório que dura até sete dias e não é afetado pela escolha da técnica anestésica. Keywords: Total knee replacement, Regional anesthesia, General anesthesia, Lymphocytes, Apoptosis, Palavras-chave: Artroplastia total do joelho, Anestesia regional, Anestesia geral, Linfócitos, Apoptos

Regular paper PCR and real-time PCR assays to detect fungi of Alternaria alternata species*

Fungi of the Alternaria genus are mostly associated with allergic diseases. However, with a growing number of immunocompromised patients, these fungi, with A. alternata being the most prevalent one, are increasingly recognized as etiological agents of infections (phaeohyphomycoses) in humans. Nowadays, identification of Alternaria spp. requires their pure culture and is solely based on morphological criteria. Clinically, Alternaria infections may be indistinguishable from other fungal diseases. Therefore, a diagnostic result is often delayed or even not achieved at all. In this paper we present easy to perform and interpret PCR and real-time PCR assays enabling detection of A. alternata species. On the basis of alignment of β-tubulin gene sequences, A. alternata-specific primers were designed. DNA from fungal isolates, extracted in a two-step procedure, were used in PCR and real-time PCR assays followed by electrophoresis or melting temperature analysis, respectively. The assays specificity was confirmed, since positive results were obtained for all A. alternata isolates, and no positive results were obtained neither for other molds, dermatophytes, yeast-like fungi, nor human DNA. The assays developed here enable fast and unambiguous identification of A. alternata pathogens

Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin - new carriers of alkylating elements.

A series of netropsin and distamycin analogues was synthesised and investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7

PCR and real-time PCR assays to detect fungi of Alternaria alternata species

Fungi of the Alternaria genus are mostly associated with allergic diseases. However, with a growing number of immunocompromised patients, these fungi, with A. alternata being the most prevalent one, are increasingly recognized as etiological agents of infections (phaeohyphomycoses) in humans. Nowadays, identification of Alternaria spp. requires their pure culture and is solely based on morphological criteria. Clinically, Alternaria infections may be indistinguishable from other fungal diseases. Therefore, a diagnostic result is often delayed or even not achieved at all. In this paper we present easy to perform and interpret PCR and real-time PCR assays enabling detection of A. alternata species. On the basis of alignment of β-tubulin gene sequences, A. alternata-specific primers were designed. DNA from fungal isolates, extracted in a two-step procedure, were used in PCR and real-time PCR assays followed by electrophoresis or melting temperature analysis, respectively. The assays specificity was confirmed, since positive results were obtained for all A. alternata isolates, and no positive results were obtained neither for other molds, dermatophytes, yeast-like fungi, nor human DNA. The assays developed here enable fast and unambiguous identification of A. alternata pathogens

Artroplastia total do joelho induz apoptose em linfócitos de sangue periférico e não é evitada por anestesia regional – estudo randomizado

ResumoJustificativa e objetivoDentre as muitas alterações causadas por uma ferida cirúrgica, uma das menos estudadas é a imunossupressão pós‐operatória. Esse fenômeno é uma causa importante das complicações infecciosas relacionadas à cirurgia, como infecção do sítio cirúrgico ou pneumonia nosocomial. Um dos mecanismos que levam à imunossupressão pós‐operatória é a apoptose de células imunológicas. Durante a cirurgia, a anestesia se destina a minimizar as alterações prejudiciais e manter a homeostase perioperatória. O objetivo deste estudo foi avaliar o efeito da técnica anestésica usada para artroplastia total de joelho sobre a apoptose em linfócitos de sangue periférico no pós‐operatório.MétodosTrinta e quatro pacientes submetidos à artroplastia total primária de joelho foram randomicamente designados para dois protocolos de anestesia regional: raquianestesia e bloqueio combinado raqui‐peridural. Onze pacientes submetidos à artroplastia total do joelho sob anestesia geral formaram o grupo controle. Antes da cirurgia, logo após a cirurgia, durante o primeiro dia de pós‐operatório e sete dias após a cirurgia, amostras de sangue venoso foram colhidas e o estado imunológico do paciente foi avaliado com o uso de flow cysts 87 m, juntamente com apoptose de linfócitos com o uso de microscopia de fluorescência.ResultadosApoptose em linfócitos de sangue periférico foi observada imediatamente no pós‐operatório e acompanhada por uma redução do número de células T e B. Não houve diferença significativa no número de linfócitos apoptóticos de acordo com o protocolo anestésico. Alterações no número de células T CD3/8 e no número de linfócitos apoptóticos foram observadas no sétimo dia após a cirurgia.ConclusãoApoptose em linfócitos de sangue periférico é um evento precoce no período pós‐operatório que dura até sete dias e não é afetado pela escolha da técnica anestésica.AbstractBackgroundAmong the many changes caused by a surgical insult one of the least studied is postoperative immunosuppression. This phenomenon is an important cause of infectious complications of surgery such as surgical site infection or hospital acquired pneumonia. One of the mechanisms leading to postoperative immunosuppression is the apoptosis of immunological cells. Anesthesia during surgery is intended to minimize harmful changes and maintain perioperative homeostasis. The aim of the study was evaluation the effect of the anesthetic technique used for total knee replacement on postoperative peripheral blood lymphocyte apoptosis.Methods34 patients undergoing primary total knee replacement were randomly assigned to two regional anesthetic protocols: spinal anesthesia and combined spinal‐epidural anesthesia. 11 patients undergoing total knee replacement under general anesthesia served as control group. Before surgery, immediately after surgery, during first postoperative day and seven days after the surgery venous blood samples were taken and the immunological status of the patient was assessed with the use of flow cysts 87 m, along with lymphocyte apoptosis using fluorescent microscopy.ResultsPeripheral blood lymphocyte apoptosis was seen immediately in the postoperative period and was accompanied by a decrease of the number of T cells and B cells. There were no significant differences in the number of apoptotic lymphocytes according to the anesthetic protocol. Changes in the number of T CD3/8 cells and the number of apoptotic lymphocytes were seen on the seventh day after surgery.ConclusionPeripheral blood lymphocyte apoptosis is an early event in the postoperative period lasts up to seven days and is not affected by the choice of the anesthetic technique