Arrhythmogenic mechanisms in the isolated perfused hypokalaemic murine heart

AIM: Hypokalaemia is associated with a lethal form of ventricular tachycardia (VT), torsade de pointes, through pathophysiological mechanisms requiring clarification. METHODS: Left ventricular endocardial and epicardial monophasic action potentials were compared in isolated mouse hearts paced from the right ventricular epicardium perfused with hypokalaemic (3 and 4 mm [K(+)](o)) solutions. Corresponding K(+) currents were compared in whole-cell patch-clamped epicardial and endocardial myocytes. RESULTS: Hypokalaemia prolonged epicardial action potential durations (APD) from mean APD(90)s of 37.2 ± 1.7 ms (n = 7) to 58.4 ± 4.1 ms (n =7) and 66.7 ± 2.1 ms (n = 11) at 5.2, 4 and 3 mm [K(+)](o) respectively. Endocardial APD(90)s correspondingly increased from 51.6 ± 1.9 ms (n = 7) to 62.8 ± 2.8 ms (n = 7) and 62.9 ± 5.9 ms (n = 11) giving reductions in endocardial–epicardial differences, ΔAPD(90), from 14.4 ± 2.6 to 4.4 ± 5.0 and −3.4 ± 6.0 ms respectively. Early afterdepolarizations (EADs) occurred in epicardia in three of seven spontaneously beating hearts at 4 mm [K(+)](o) with triggered beats followed by episodes of non-sustained VT in nine of 11 preparations at 3 mm. Programmed electrical stimulation never induced arrhythmic events in preparations perfused with normokalemic solutions yet induced VT in two of seven and nine of 11 preparations at 4 and 3 mm [K(+)](o) respectively. Early outward K(+) current correspondingly fell from 73.46 ± 8.45 to 61.16±6.14 pA/pF in isolated epicardial but not endocardial myocytes (n = 9) (3 mm [K(+)](o)). CONCLUSIONS: Hypokalaemic mouse hearts recapitulate the clinical arrhythmogenic phenotype, demonstrating EADs and triggered beats that might initiate VT on the one hand and reduced transmural dispersion of repolarization reflected in ΔAPD(90) suggesting arrhythmogenic substrate on the other

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Ocena uszkodzeń typowej prefabrykowanej hali magazynowej

This article presents a case of a damaged warehouse building built in the typical reinforced concrete precast technology. Damage and irregularities identified during an inspection were described and their causes were analyzed. Identification of the type and extent of the damage led to the conclusion that the most important are the concrete cracks and losses along the edges of the load-bearing structure column heads at the level of the roof girders support, and not the cracks and displacements of the curtain wall fragments, which the user was most concerned with. The described example is a confirmation of a need to carry out regular evaluations of the technical condition of buildings, so that users can rationally plan renovation works for the further safe use of the structure.W artykule przedstawiono przypadek uszkodzonej hali magazynowej wzniesionej w typowej żelbetowej technologii prefabrykowanej. Opisano stwierdzone podczas inwentaryzacji uszkodzenia i nieprawidłowości oraz przeanalizowano przyczyny ich powstania. Rozpoznanie zakresu uszkodzeń doprowadziło do sformułowania wniosku, że najistotniejsze są pęknięcia i ubytki betonu wzdłuż krawędzi głowic słupów konstrukcji nośnej na poziomie oparcia dźwigarów dachowych, a nie pęknięcia i przemieszczenia fragmentów ścian osłonowych, które wzbudzały niepokój użytkownika. Przedstawiony przykład potwierdza potrzebę wykonywania okresowych ocen stanu technicznego budynków, dzięki którym użytkownicy mogą racjonalnie planować prace remontowe niezbędne do dalszej bezpiecznej eksploatacji obiektu

Wpływ zabezpieczeń profilaktycznych na stan techniczny budynku sakralnego usytuowanego na terenie górniczym

The article presents the case study of a historical religious building located in the area of “Bogdanka” S.A. Coal Mine. As the building lacked adequate resistance to the expected effects of mining, the Mine undertook efforts so that it was fully protected against mining impacts before the commencement of mining operations. A preventive conservation system was used, consisting of an external stiffening reinforced concrete plate at the ground level and a system of steel tie rods established at the level of vault supports. The article assesses the effect of undertaken preventive conservation measures on the current technical condition of the building. The basis for the assessment was the extent of damage to the building confirmed after the occurrence of impacts from the performed mining operations combined with the analysis of ground deformation.W artykule przedstawiono przypadek zabytkowego budynku sakralnego, usytuowanego na terenie górniczym Kopalni LW „Bogdanka” S.A. Z powodu braku odpowiedniej odporności na prognozowane wpływy górnicze, staraniem Kopalni budynek ten został kompleksowo zabezpieczony profilaktycznie przeciw wpływom górniczym jeszcze przed rozpoczęciem eksploatacji. Zastosowano system zabezpieczeń profilaktycznych złożony z zewnętrznej żelbetowej tarczy usztywniającej w poziomie terenu oraz układu stalowych ściągów, założonych w poziomie oparcia sklepień. W artykule dokonano oceny wpływu podjętych działań profilaktycznych na aktualny stan techniczny budynku. Podstawą oceny był zakres uszkodzeń budynku stwierdzony po ujawnieniu się wpływów od dokonanej eksploatacji górniczej, w powiązaniu z analizą deformacji terenu

Point mutation analysis of the Xenopus laevis RNA polymerase I core promoter.

The core region of the Xenopus laevis pre-ribosomal RNA promoter was subjected to point mutation analysis. A total of 27 point mutants within a 78 base pair region from -64 to +14, (relative to the start of transcription at +1), were assayed by oocyte microinjection. The results locate the 3' boundary of the core promoter at +4 and the 5' boundary at between -33 and -39 and suggest that this region of the Xenopus promoter is generally similar in organisation to mammalian core promoters. In particular, the conserved guanidine nucleotides at -7 and -16 are clearly essential for promoter function. The data suggest that interactions between the transcription machinery and the promoter occur in four distinct regions around +2 to +4, -7, -17 to -20 and -28 to -33. This particular periodicity of functionally important nucleotides is consistent with a model in which all protein-DNA interactions take place from predominantly one side of the DNA helix

St. John's Daily Star, 1920-12-31

The St. John's Daily Star was published daily except Sunday between 17 April 1915 - 23 July 1921

Gametophyte-specific transposition of the maize Ds element in transgenic tobacco

To assess the potential advantages of a transposon-tagging system based on gametophyte-specific transposition a fusion between the anther-specific Arabidopsis thaliana apg promoter and the maize Ac transposase gene was constructed and introduced into tobacco. The ability of this transposase source to activate Ds transposition in a developmentally controlled manner was monitored by crossing to plants harbouring the cell autonomous excision marker gene construct, Ds—SPT. A number of fully green, streptomycin-resistant seedlings resulting from germinal transposition events were observed in the progeny of apg-TPase x Ds—SPT F1 plants. Streptomycin-resistant sectors were not observed in either F1 seedlings or F2 progeny, indicating a complete lack of somatic excision. Further crosses of apg—TPase sources to plants containing Ds—bar herbicide selection excision marker constructs gave reproducible gametophytic excision frequencies of up to 0.3%. Sequencing of Ds excision sites from F2 seedlings derived from single F1 plants revealed various sequence alterations in the original Ds insertion ‘footprint’ indicative of independent Ds excision events. Independent re-insertion was confirmed by Southern analysis of F2 siblings. It is concluded that apg-controlled Ac transposase expression activates male gametophyte-specific Ds transposition