Essential oils from the Herba and fruits of Peucedanum luxurians and their antituberculosis activity

The Apiaceae family has been accompanying people for thousands of years, being present in the kitchen, as well as in the pharmacy. Plants belonging to this family are well known as sources of coumarins and essential oils.                Essential oils from the Herba, as well as fruits, of Peucedanum luxurians Tamamsch. (an endemic umbelliferous plant taxon from Armenia) were obtained by hydrodistillation in a Deryng apparatus for the first time. The GC-MS analyses showed the presence of trans-β-farnesene (16%) and germacrene D (13%) as the most abundant components of the essential oils.                One of the most valuable properties of essential oils is their antimicrobial activity. It is a very desirable feature, especially in the case of some bacteria, which cause huge health problems. A good example is Mycobacterium tuberculosis, one of the leading causes of human morbidity and mortality.                The activity of essential oils from different parts of P. luxurians was tested for antituberculosis activity. Minimal Inhibitory Concentrations (MIC) values for the essential oils were determined by a 96-well microplate method with alamarBlue (Invitrogen). The inoculum of the reference strain of Mycobacterium tuberculosis H37Ra in Middlebrook 7H9 broth (Difco) was 5 x 105 cfu/mL per well, according to CLSI standards. Serial twofold dilutions of essential oils ranged from 8 to 256 µg/mL. As the internal control of the method, serial twofold dilutions of four first-line antibiotics dedicated to tuberculosis treatment: isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and streptomycin (SM) were used [1,2]

Volatile compounds from different species of Lycopodium with anti-tuberculosis activity

Different species belonging to the genus Lycopodium L. (Lycopodiaceae) were used in folk medicine due to their antibacterial, healing effects on wounds, and properties used in the treatment of mental diseases, like amnesia, schizophrenia and different types of dementia.                Extracts containing volatiles obtained from different Lycopodium species: L. clavatum, L. annotinum, and Huperzia serrata (syn. Lycopodium serratum Thunb.), were tested against Mycobacterium tuberculosis. Dichloromethane and petroleum ether extracts of the mentioned species collected in different geographical sites (in Poland and Ukraine) have shown interesting activities.                Minimal Inhibitory Concentrations (MIC) values for the extracts were determined by a 96-well microplate method with alamarBlue (Invitrogen). The inoculum of the reference strain of Mycobacterium tuberculosis H37Ra in Middlebrook 7H9 broth (Difco) was 5 x 105 cfu/mL per well, according to CLSI standards. Serial twofold dilutions of the extracts ranged from 8 to 256 µg/mL. As the internal control of the method, serial twofold dilutions of four first-line antibiotics dedicated to tuberculosis treatment: isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and streptomycin (SM) were used [1,2]

Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants

Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis

Wyniki leczenia wemurafenibem chorych na zaawansowanego czerniaka w ramach programu lekowego w Polsce

Introduction. Melanoma is a heterogeneous group of tumours with poor prognosis if the disease is metastatic. More than half of patients with melanoma of the skin have detectable mutations in the BRAF gene. Vemurafenib is the BRAF kinase inhibitor used in the treatment of patients with advanced melanoma with the BRAF mutation. This improves time to progression-free survival and overall survival in patients with this diagnosis. The aim of the study was to analyse the results of treatment and safety of vemurafenib in patients treated during the Polish drug programme. Materials and methods .Between October 2013 and April 2015 a total of 189 patients were treated, 90 women and 99 men, who had previously been diagnosed with unresectable/metastatic melanoma with BRAF V600 mutation. Patients received vemurafenib in 960 mg dose twice per day. The estimated progression-free survival, overall survival and adverse events were assessed. For the survival analysis the Kaplan-Meier method and log-rank test (log-rank) for multi-factor analysis were used. Results. In the first evaluation of the effectiveness of treatment, 8 patients (4.3%) had a complete response, 75 patients (39.7%) partial response, 62 patients (32.8%) had stable disease, and 44 patients (23.2%) had progression of the disease. The disease was controlled in 76.7% of patients. After progression during the therapy with vemurafenib 27% of the patients received subsequent lines of systemic therapy. Twenty-eight patients received chemotherapy and 22 patients immunotherapy with ipilimumab. During the last analysis dated 5 September 2015, the median observation time for still living patients was 8 months (range 3–26). Median progression-free survival was 6.7 months. The median overall survival was 12 months. 146 patients (77%) had adverse events, mostly in the form of dermal toxicity of Grades 1 and 2. Thirty-two patients (17%) presented with side effects of the 3rd and 4th grades of toxicity. Two patients had to stop the treatment due to the toxicity. There were no deaths reported due to the toxicity of treatment. Conclusions. The multicentre analysis confirmed the efficacy and safety of vemurafenib in routine clinical practice in a heterogeneous group of advanced melanomas with BRAF mutation. We confirmed the importance of the known prognostic factors for overall survival in this group of patients, such as lactate dehydogenaze activity (LDH) and ECOG performance status. The current survival of patients with the metastatic melanomas with BRAF mutations are longer than those observed in historical groups.  Wstęp. Czerniak należy do heterogennej grupy nowotworów o bardzo złym rokowaniu w przypadku rozsiewu choroby. U ponad połowy chorych na czerniaka skóry stwierdza się obecność mutacji w obrębie genu BRAF. Wemurafenib jest inhibitorem kinazy BRAF stosowanym w leczeniu chorych na zaawansowanego czerniaka z mutacją BRAF, który poprawia u nich czas przeżycia wolny od progresji choroby oraz przeżycia całkowitego. Celem pracy jest analiza wyników leczenia oraz bezpieczeństwa terapii wemurafenibem u chorych leczonych w ramach programu lekowego w Polsce. Materiały i metody. W okresie od października 2013 do kwietnia 2015 roku leczonych było 189 chorych (90 kobiet i 99 mężczyzn) z rozpoznaniem nieresekcyjnego/przerzutowego czerniaka z mutacją BRAF V600. Chorzy otrzymywali wemurafenib w dawce wyjściowej 960 mg dwa razy na dobę. Oceniano czas wolny od progresji choroby, czas przeżycia całkowitego oraz monitorowano działania niepożądane. Do analizy przeżycia użyto metody Kaplana-Meiera oraz testu logarytmicznego rang (log-rank) dla analiz dwuczynnikowych. Wyniki. W pierwszej ocenie skuteczności leczenia u 8 chorych (4,3%) stwierdzono całkowitą odpowiedź, u 75 chorych (39,7%) częściową odpowiedź, u 62 chorych (32,8%) stabilizację choroby, a u 44 chorych (23,2%) progresję choroby. Kontrolę choroby wykazano u 76,7% chorych. Po progresji w trakcie terapii wemurafenibem 27% chorych otrzymało kolejne linie leczenia systemowego — 28 chorych chemioterapię, 22 chorych ipilimumab. Podczas ostatniej analizy z dnia 5 września 2015 mediana czasu obserwacji dla żyjących chorych wyniosła 8 miesięcy (zakres 3–26). Mediana przeżycia wolnego od progresji wyniosła 6,7 miesiąca. Mediana czasu całkowitego przeżycia wyniosła 12 miesięcy. U 146 chorych (77%) stwierdzono działania niepożądane, głównie pod postacią toksyczności skórnej w stopniu 1. i 2., u 32 chorych (17%) objawy uboczne w 3.–4. stopniu toksyczności. U dwóch chorych zakończono leczenie z powodu toksyczności. Nie było zgonów spowodowanych toksycznością leczenia. Wnioski. Przeprowadzona analiza wieloośrodkowa potwierdziła skuteczność i bezpieczeństwo leczenia wemurafenibem w rutynowej praktyce klinicznej w heterogennej grupie zaawansowanych czerniaków z obecnością mutacji BRAF. Potwierdzono wagę znanych czynników prognostycznych dla całkowitego przeżycia w tej grupie chorych, takich jak aktywność dehydrogenazy mleczanowej (LDH) i wyjściowy stan sprawności wg ECOG. Obecne przeżycia chorych w grupie przerzutowych czerniaków z mutacją BRAF są dłuższe niż obserwowane w próbach historycznych.

Apoptotic signals induce specific degradation of ribosomal RNA in yeast

Organisms exposed to reactive oxygen species, generated endogenously during respiration or by environmental conditions, undergo oxidative stress. Stress response can either repair the damage or activate one of the programmed cell death (PCD) mechanisms, for example apoptosis, and finally end in cell death. One striking characteristic, which accompanies apoptosis in both vertebrates and yeast, is a fragmentation of cellular DNA and mammalian apoptosis is often associated with degradation of different RNAs. We show that in yeast exposed to stimuli known to induce apoptosis, such as hydrogen peroxide, acetic acid, hyperosmotic stress and ageing, two large subunit ribosomal RNAs, 25S and 5.8S, became extensively degraded with accumulation of specific intermediates that differ slightly depending on cell death conditions. This process is most likely endonucleolytic, is correlated with stress response, and depends on the mitochondrial respiratory status: rRNA is less susceptible to degradation in respiring cells with functional defence against oxidative stress. In addition, RNA fragmentation is independent of two yeast apoptotic factors, metacaspase Yca1 and apoptosis-inducing factor Aif1, but it relies on the apoptotic chromatin condensation induced by histone H2B modifications. These data describe a novel phenotype for certain stress- and ageing-related PCD pathways in yeast

Wykorzystanie środków fizjoterapeutycznych w leczeniu astmy oskrzelowej

The bronchial asthma is a chronic inflammation of a respiratory system, involving many cells and substances released by them. A chronic inflammation causes a hyperactivity of the bronchi, leading subsequently to recurrent attacks of dyspnoea, wheezing breath, coughing and tightness in breast, appearing especially at night or at dawn. Such attacks are usually accompanied by a flooding bronchial obturation with a diversified intensity, often subsiding spontaneously or because of a treatment. The aim of the present paper is introducing of mechanisms causing bronchial asthma and current trends of rehabilitation proceedings. Conclusions: The rehabilitation methods in patients suffering from bronchial asthma should be individually selected, considering the advance of an illness, occurring of co-existing diseases and complications. In order to obtaining the maximum level of recovery, a complete rehabilitation program should be worked up and applied. Full rehabilitation proceedings cause a significant improvement of the patients` life comfort.Astma oskrzelowa jest przewlekłą chorobą zapalną dróg oddechowych, w której uczestniczy wiele komórek i substancji przez nie uwalnianych. Przewlekłe zapalenie jest przyczyną nadreaktywności oskrzeli, prowadzącej do nawracających epizodów świszczącego oddechu, duszności, ściskania w klatce piersiowej i kaszlu, występujących szczególnie w nocy lub nad ranem. Epizodom tym zwykle towarzyszy rozlana obturacja oskrzeli o zmiennym nasileniu, często ustępująca samoistnie lub pod wpływem leczenia. Celem pracy jest przedstawienie mechanizmów powstania astmy oskrzelowej oraz aktualnych trendów postępowania rehabilitacyjnego. Wnioski: Podejście rehabilitacyjne u chorych na astmę oskrzelową powinno być dobrane indywidualnie. Powinno ono uwzględniać stopień zaawansowania choroby, występowanie chorób współistniejących oraz występowanie powikłań. W celu osiągnięcia maksymalnej poprawy stanu zdrowia pacjenta należy opracować i zastosować kompleksowy program rehabilitacji. Pełne postępowanie rehabilitacyjne daje znaczną poprawę jakości życia chorych