A New Single Chamber Implantable Defibrillator with Atrial Sensing: A Practical Demonstration of Sensing and Ease of Implantation

Implantable cardioverter-defibrillators (ICDs) terminate ventricular tachycardia (VT) and ventricular fibrillation (VF) with high efficacy and can protect patients from sudden cardiac death (SCD). However, inappropriate shocks may occur if tachycardias are misdiagnosed. Inappropriate shocks are harmful and impair patient quality of life. The risk of inappropriate therapy increases with lower detection rates programmed in the ICD. Single-chamber detection poses greater risks for misdiagnosis when compared with dual-chamber devices that have the benefit of additional atrial information. However, using a dual-chamber device merely for the sake of detection is generally not accepted, since the risks associated with the second electrode may outweigh the benefits of detection. Therefore, BIOTRONIK developed a ventricular lead called the Linox^SMART S DX, which allows for the detection of atrial signals from two electrodes positioned at the atrial part of the ventricular electrode. This device contains two ring electrodes; one that contacts the atrial wall at the junction of the superior vena cava (SVC) and one positioned at the free floating part of the electrode in the atrium. The excellent signal quality can only be achieved by a special filter setting in the ICD (Lumax 540 and 740 VR-T DX, BIOTRONIK). Here, the ease of implantation of the system will be demonstrated.     

Ochratoxin A in human blood serum – retrospective long-term data

In a long-term study (1990–1997) on ochratoxin A (OTA) in human blood serum, 102 serum samples from 36 persons of the Munich Institute for Hygiene and Technology of Food of Animal Origin were analysed by enzyme immunoassay (EIA), and by high performance liquid chromatography (HPLC) for control. Detection limits were at 50 pg/ml (EIA) and 50–70 pg/ml (HPLC), recoveries were 80–120% (EIA) and 30–60% (LC). OTA was detected in 98% (EIA, 368 ± 217 pg/ml) and 93% (HPLC, 271 ± 170 pg/ml) of samples (maximum 1,290 pg/ml). Using published conversion factors for serum/intake estimates (1.34 or 1.97), the mean daily OTA intake of these 36 persons was 493–725 pg/kg bw. Long-term individual mean OTA levels of nine persons ranged from 162 ± 80 pg/ml to 549 ± 172 pg/ml. Our data were compared with published OTA serum levels (1985–2008) for apparently healthy persons from a total of 30 countries. On a worldwide basis, the mean of means for OTA in human serum was estimated to be 700 pg/ml, corresponding to a mean daily OTA intake of 940–1380 pg/kg bw. This level, which was relatively stable over the last decades, is well below published tolerable daily intake values (14,000–18,000 pg/kg bw).     

Pharmacokinetics of chlorogenic acid and rutin in larvae of Heliothis zea

Studies using [³H]chlorogenic acid and [³H]rutin demonstrated that the kinetics of uptake of these plant phenolics into the haemolymph of 5th-instar Heliothis zea (Boddie) following actue oral administration is a first-order process. The total quantity of either phenolic present in the haemolymph within 1 hr amounts to 5% or less of the total ingested dose. Based on TLC analyses, 80% or more of the radioactivity in the haemolymph occurs as the parent phenolic. Retention of [³H]-chlorogenic acid or [³H]-rutin in H. zea following chronic feeding from 1st to 3rd-instar larvae is also linearly related to dietary dose. Chlorogenic acid and rutin are both equitoxic and equivalent in bioavailability to H. zea.Loss of [³H]-rutin from the haemolymph of 5th-instar larvae following injection is biphasic. One half of the injected dose is excreted in the frass in the first 6 hr after injection; the other half is thereafter eliminated at 1/20th of the initial rate. Analyses of extracts of frass by thin-layer chromatography indicate that after either chronic or acute feeding 90% of the ingested phenolic is excreted unchanged. Possible sites and modes of action of phenolics in insects are discussed in light of these findings.     

Involvement of transmembrane domain interactions in signal transduction by alpha/beta integrins

The alpha and beta subunits of alpha/beta heterodimeric integrins function together to bind ligands in the extracellular region and transduce signals across cellular membranes. A possible function for the transmembrane regions in integrin signaling has been proposed from structural and computational data. We have analyzed the capacity of the integrin alpha(2), alpha(IIb), alpha(4), beta(1), beta(3), and beta(7) transmembrane domains to form homodimers and/or heterodimers. Our data suggest that the integrin transmembrane helices can help to stabilize heterodimeric integrins but that the interactions do not specifically associate particular pairs of alpha and beta subunits; rather, the alpha/beta subunit interaction constrains the extramembranous domains, facilitating signal transduction by a promiscuous transmembrane helix-helix association.     

Synthetic guinea pig insulin B-chain C-terminal decapeptide: a novel immunogen for generating immunocytochemical-grade antisera

Antisera to guinea pig insulin are not commonly available, largely because of the short supply and limited immunogenicity of the intact hormone. To overcome these problems we have employed a novel reagent, synthetic guinea pig insulin B-chain C-terminal decapeptide, as a hapten for raising antibodies that react with intact guinea pig insulin. The decapeptide, coupled to bovine serum albumin, was successfully used as an immunogen in rabbits. The resulting anti-serum was employed for immunocytochemical staining of guinea pig insulin in pancreatic sections. The specificity of the staining was verified by both pre-absorption and pre-immune serum controls. The utility of this new antiserum for investigations of guinea pig insulin physiology is discussed.     

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis

A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.     

On the Role of CD8?T Cells in the Control of Persistent Infections

The control of pathogen density during infections is typically assumed to be the result of a combination of resource limitation (loss of target cells that the pathogen can infect), innate immunity, and specific immunity. The contributions of these factors have been considered in acute infections, which are characterized by having a short duration. What controls the pathogen during persistent infections is less clear, and is complicated by two factors. First, specific immune responses become exhausted if they are subject to chronic stimulation. Exhaustion has been best characterized for CD8 T cell responses, and occurs through a combination of cell death and loss of functionality of surviving cells. Second, new nonexhausted T cells can immigrate from the thymus during the infection, and may play a role in the control of the infection. In this article, we formulate a partial-differential-equation model to describe the interaction between these processes, and use this model to explore how thymic influx and exhaustion might affect the ability of CD8 T cell responses to control persistent infections. We find that although thymic influx can play a critical role in the maintenance of a limited CD8 T cell response during persistent infections, this response is not sufficiently large to play a significant role in controlling the infection. In doing so, our results highlight the importance of resource limitation and innate immunity in the control of persistent infections.