Flecainide overdose – support using an intra-aortic balloon pump

BACKGROUND: Flecainide is an antiarrhythmic agent which is being used increasingly for the management of super-ventricular arrhythmias. Overdose with flecainide is frequently fatal with mortality reported as high as 22% due to arrhythmias, myocardial depression and conduction defects leading to electro-mechanical dissociation and asytole. Supportive measures are often required during the case and previously have included inotropes, extracorporeal membrane oxygenation and cardiopulmonary bypass. CASE PRESENTATION: A 47 year old lady presented to the emergency department with a four hour history of severe central chest pain. Her ECG showed atrial fibrillation and broad QRS complexes with a sine wave appearance. She had a past history of paroxysmal atrial fibrillation and significant psychiatric history. Following thrombolysis for a presumed myocardial infarction she developed cardiogenic shock with severely impaired left ventricular function. An intra-aortic balloon pump was inserted and coronary angiography demonstrated normal coronary arteries. With inotropic support she improved over 48 hours, with both her QRS duration and left ventricular function returning to normal. Biochemical testing following her discharge demonstrated significantly elevated levels of flecainide. CONCLUSION: The use of an intra-aortic balloon pump is a useful supportive measure during the acute phase of flecainide overdose associated with severe myocardial depression

Activation of the B cell receptor leads to increased membrane proximity of the Igα cytoplasmic domain.

Binding of antigen to the B cell receptor (BCR) induces conformational changes in BCR's cytoplasmic domains that are concomitant with phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs). Recently, reversible folding of the CD3ε and ξ chain ITAMs into the plasma membrane has been suggested to regulate T cell receptor signaling. Here we show that the Igα and Igβ cytoplasmic domains of the BCR do not associate with plasma membrane in resting B cells. However, antigen binding and ITAM phosphorylation specifically increased membrane proximity of Igα, but not Igβ. Thus, BCR activation is accompanied by asymmetric conformational changes, possibly promoting the binding of Igα and Igβ to differently localized signaling complexes

Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression

<p>Abstract</p> <p>Background</p> <p>Cimetidine, a histamine type-2 receptor antagonist, has been reported to inhibit the growth of glandular tumors such as colorectal cancer, however the mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma is well known as a malignant salivary gland tumor which preferentially invades neural tissues. We demonstrated previously that human salivary gland tumor (HSG) cells spontaneously express neural cell adhesion molecule (NCAM), that HSG cell proliferation may be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. We further demonstrated that cimetidine inhibited NCAM expression and induced apoptosis in HSG cells. Here, we investigated the effects of cimetidine on growth and perineural/neural invasion of salivary gland tumor cells.</p> <p>Methods</p> <p>In this study, we have examined the effect of cimetidine on cancer cell adhesion to neural cells <it>in vitro</it>, one of the critical steps of cancer invasion and metastasis. We have also used an <it>in vivo </it>carcinogenesis model to confirm the effect of cimetidine.</p> <p>Results</p> <p>We have demonstrated for the first time that cimetidine can block the adhesion of HSG cells to neural cell monolayers and that it can also induce significant apoptosis in the tumor mass in a nude mouse model. We also demonstrated that these apoptotic effects of cimetidine might occur through down-regulation of the cell surface expression of NCAM on HSG cells. Cimetidine-mediated down-regulation of NCAM involved suppression of the nuclear translocation of NF-κB, a transcriptional activator of NCAM gene expression.</p> <p>Conclusion</p> <p>These findings suggest that growth and perineural/neural invasion of salivary gland tumors can be blocked by administration of cimetidine via induction of apoptosis and in which NCAM plays a role.</p

Garlic's ability to prevent in vitro Cu(2+)-induced lipoprotein oxidation in human serum is preserved in heated garlic: effect unrelated to Cu(2+)-chelation

BACKGROUND: It has been shown that several extracts and compounds derived from garlic are able to inhibit Cu(2+)-induced low density lipoprotein oxidation. In this work we explored if the ability of aqueous garlic extract to prevent in vitro Cu(2+)-induced lipoprotein oxidation in human serum is affected by heating (a) aqueous garlic extracts or (b) garlic cloves. In the first case, aqueous extract of raw garlic and garlic powder were studied. In the second case, aqueous extract of boiled garlic cloves, microwave-treated garlic cloves, and pickled garlic were studied. It was also studied if the above mentioned preparations were able to chelate Cu(2+). METHODS: Cu(2+)-induced lipoprotein oxidation in human serum was followed by the formation of conjugated dienes at 234 nm and 37°C by 240 min in a phosphate buffer 20 mM, pH 7.4. Blood serum and CuSO(4 )were added to a final concentration of 0.67% and 0.0125 mM, respectively. The lag time and the area under the curve from the oxidation curves were obtained. The Cu(2+)-chelating properties of garlic extracts were assessed using an approach based upon restoring the activity of xanthine oxidase inhibited in the presence of 0.050 mM Cu(2+). The activity of xanthine oxidase was assessed by monitoring the production of superoxide anion at 560 nm and the formation of uric acid at 295 nm. Data were compared by parametric or non-parametric analysis of variance followed by a post hoc test. RESULTS: Extracts from garlic powder and raw garlic inhibited in a dose-dependent way Cu(2+)-induced lipoprotein oxidation. The heating of garlic extracts or garlic cloves was unable to alter significantly the increase in lag time and the decrease in the area under the curve observed with the unheated garlic extracts or raw garlic. In addition, it was found that the garlic extracts were unable to chelate Cu(2+). CONCLUSIONS: (a) the heating of aqueous extracts of raw garlic or garlic powder or the heating of garlic cloves by boiling, microwave or pickling do not affect garlic's ability to inhibit Cu(2+)-induced lipoprotein oxidation in human serum, and (b) this ability is not secondary to Cu(2+)-chelation

TCR signal strength controls thymic differentiation of discrete proinflammatory gamma delta T cell subsets

The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g+/− Cd3d+/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gd T cell subsets and their impact on pathophysiology

Chronic Myeloid Leukemia Patients in Prolonged Remission following Interferon-alpha Monotherapy Have Distinct Cytokine and Oligoclonal Lymphocyte Profile

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