Acute outcome of treating patients admitted with electrical storm in a tertiary care centre

Background

Electrical storm (ES) is a life threatening emergency. There is little data available regarding acute outcome of ES.

Aims

The study aimed to analyze the acute outcome of ES, various treatment modalities used, and the factors associated with mortality.

Methods

This is a retrospective observational study involving patients admitted with ES at our centre between 1/1/2007 and 31/12/2013.

Results

41 patients (mean age 54.61 ± 12.41 years; 86.7% males; mean ejection fraction (EF) 44.51 ± 16.48%) underwent treatment for ES. Hypokalemia (14.63%) and acute coronary syndrome (ACS) (14.63%) were the commonest identifiable triggers. Only 9 (21.95%) patients already had an ICD implanted. Apart from antiarrhythmic drugs (100%), deep sedation (87.8%), mechanical ventilation (24.39%) and neuraxial modulation using left sympathetic cardiac denervation (21.95%) were the common treatment modalities used. Thirty-three (80.49%) patients could be discharged after a mean duration of 14.2 ± 2.31 days. Eight (19.5%) patients died in hospital. The mortality was significantly higher in those with EF < 35% compared to those with a higher EF (8 (42.11% vs 0 (0%), p = 0.03)). There was no significant difference in mortality between those with versus without a structural heart disease (8 (21.1% vs 0 (0%), p = 0.32)). Comparison of mortality an ACS with ES versus ES of other aetiologies (3 (50%) vs 5 (14.29) %, p = 0.076)) showed a trend towards significance.

Conclusion

With comprehensive treatment, there is reasonable acute survival rate of ES. Hypokalemia and ACS are the commonest triggers of ES. Patients with low EF and ACS have higher mortality.     

Nutritional and antinutritional attributes of faba bean (Vicia faba L.) germplasms growing in Bihar,India

Eleven germplasms of faba bean seeds from four agroclimatic regions of Bihar, India, have been investigated to estimate their nutritional (soluble protein, free amino acids, starch, reducing and non reducing sugar, total soluble sugar) and antinutritional (total extractable phenol and condensed tannin/proanthocyanidin) parameters. These parameters were found in varying concentration in all genotypes studied. The highest concentration of total extractable phenol and proanthocyanidin (condensed tannin) (2.56 and 1.59 % leucocyanidin equivalents respectively on dry matter basis) were found in Samastipur while the lowest from Patna (0.95 and 0.426 % leucocyanidin equivalent on dry matter basis). The different nutritional parameters were also found to be in variable concentration among different germplasms viz. total soluble protein ≈ 20–32 %, free amino acids ≈ 188–348 mg/100 g, starch ≈ 27–33 %, reducing sugars ≈ 85–188 mg/100 g, non reducing sugars ≈ 0.7–1.7 % and total soluble sugars ≈ 0.8–1.9 %.     

Vibrio cholerae Porin OmpU Induces Caspase-independent Programmed Cell Death upon Translocation to the Host Cell Mitochondria

Porins, a major class of outer membrane proteins in Gram-negative bacteria, primarily act as transport channels. OmpU is one of the major porins of human pathogen, Vibrio cholerae. In the present study, we show that V. cholerae OmpU has the ability to induce target cell death. Although OmpU-mediated cell death shows some characteristics of apoptosis, such as flipping of phosphatidylserine in the membrane as well as cell size shrinkage and increased cell granularity, it does not show the caspase-3 activation and DNA laddering pattern typical of apoptotic cells. Increased release of lactate dehydrogenase in OmpU-treated cells indicates that the OmpU-mediated cell death also has characteristics of necrosis. Further, we show that the mechanism of OmpU-mediated cell death involves major mitochondrial changes in the target cells. We observe that OmpU treatment leads to the disruption of mitochondrial membrane potential, resulting in the release of cytochrome c and apoptosis-inducing factor (AIF). AIF translocates to the host cell nucleus, implying that it has a crucial role in OmpU-mediated cell death. Finally, we observe that OmpU translocates to the target cell mitochondria, where it directly initiates mitochondrial changes leading to mitochondrial membrane permeability transition and AIF release. Partial blocking of AIF release by cyclosporine A in OmpU-treated cells further suggests that OmpU may be inducing the opening of the mitochondrial permeability transition pore. All of these results lead us to the conclusion that OmpU induces cell death in target cells in a programmed manner in which mitochondria play a central role.     

A Mechanism of Global Shape-dependent Recognition and Phosphorylation of Filamin by Protein Kinase A

Protein phosphorylation mediates essentially all aspects of cellular life. In humans, this is achieved by ∼500 kinases, each recognizing a specific consensus motif (CM) in the substrates. The majority of CMs are surface-exposed and are thought to be accessible to kinases for phosphorylation. Here we investigated the archetypical protein kinase A (PKA)-mediated phosphorylation of filamin, a major cytoskeletal protein that can adopt an autoinhibited conformation. Surprisingly, autoinhibited filamin is refractory to phosphorylation by PKA on a known Ser²¹⁵² site despite its CM being exposed and the corresponding isolated peptide being readily phosphorylated. Structural analysis revealed that although the CM fits into the PKA active site its surrounding regions sterically clash with the kinase. However, upon ligand binding, filamin undergoes a conformational adjustment, allowing rapid phosphorylation on Ser²¹⁵². These data uncover a novel ligand-induced conformational switch to trigger filamin phosphorylation. They further suggest a substrate shape-dependent filtering mechanism that channels specific exposed CM/kinase recognition in diverse signaling responses.     

Novel Route for Agmatine Catabolism in Aspergillus niger Involves 4-Guanidinobutyrase

Agmatine, a significant polyamine in bacteria and plants, mostly arises from the decarboxylation of arginine. The functional importance of agmatine in fungi is poorly understood. The metabolism of agmatine and related guanidinium group-containing compounds in Aspergillus niger was explored through growth, metabolite, and enzyme studies. The fungus was able to metabolize and grow on l-arginine, agmatine, or 4-guanidinobutyrate as the sole nitrogen source. Whereas arginase defined the only route for arginine catabolism, biochemical and bioinformatics approaches suggested the absence of arginine decarboxylase in A. niger. Efficient utilization by the parent strain and also by its arginase knockout implied an arginase-independent catabolic route for agmatine. Urea and 4-guanidinobutyrate were detected in the spent medium during growth on agmatine. The agmatine-grown A. niger mycelia contained significant levels of amine oxidase, 4-guanidinobutyraldehyde dehydrogenase, 4-guanidinobutyrase (GBase), and succinic semialdehyde dehydrogenase, but no agmatinase activity was detected. Taken together, the results support a novel route for agmatine utilization in A. niger. The catabolism of agmatine by way of 4-guanidinobutyrate to 4-aminobutyrate into the Krebs cycle is the first report of such a pathway in any organism. A. niger GBase peptide fragments were identified by tandem mass spectrometry analysis. The corresponding open reading frame from the A. niger NCIM 565 genome was located and cloned. Subsequent expression of GBase in both Escherichia coli and A. niger along with its disruption in A. niger functionally defined the GBase locus (gbu) in the A. niger genome.