Catheter-based impedance measurements in the right atrium for continuously monitoring hematocrit and estimating blood viscosity changes; an in vivo feasibility study in swine

Hematocrit is the most important determinant of whole blood viscosity and it affects thrombosis. As hematocrit can be measured accurately in vitro by using an electrical impedance technique, aim of the present study is to investigate the diagnostic potential of using this technique in vivo to continuously monitor hematocrit.

Characteristics of a special catheter for in vivo measurement of electrical resistivity in blood in the right atrium are described. In five anesthetized swine hematocrit is monitored continuously with this catheter while different levels of hemoconcentration are induced. In addition, blood viscosity is increased by inducing ‘acute phase’ reaction the day before surgery, resulting in variable degree of elevated fibrinogen levels in the five swine. Good reproducibility of the resistivity measurements (S.D.<0.01) and excellent correlation between resistivity data in vivo and hematocrit levels in each swine are found (r²=0.95–0.99). Furthermore, stepwise regression analysis of data from all swine shows a highly significant contribution also of other important parameters of blood viscosity, such as fibrinogen, total protein and temperature (cumulative r²=0.97).

Determining hematocrit continuously in vivo by electrical resistivity measurements with a catheter in the right atrium is feasible and these measurements correlate significantly also with other important parameters of blood viscosity.     

A Kazal-Type Serine Protease Inhibitor from the Defense Gland Secretion of the Subterranean Termite Coptotermes formosanus Shiraki

Coptotermes formosanus is an imported, subterranean termite species with the largest economic impact in the United States. The frontal glands of the soldier caste termites comprising one third of the body mass, contain a secretion expelled through a foramen in defense. The small molecule composition of the frontal gland secretion is well-characterized, but the proteins remain to be identified. Herein is reported the structure and function of one of several proteins found in the termite defense gland secretion. TFP4 is a 6.9 kDa, non-classical group 1 Kazal-type serine protease inhibitor with activity towards chymotrypsin and elastase, but not trypsin. The 3-dimensional solution structure of TFP4 was solved with nuclear magnetic resonance spectroscopy, and represents the first structure from the taxonomic family, Rhinotermitidae. Based on the structure of TFP4, the protease inhibitor active loop (Cys⁸ to Cys¹⁶) was identified.     

Liposomal daunorubicin as treatment for Kaposi's sarcoma

Anthracycline compounds including daunorubicin are the foundation of many modem chemotherapeutic regimens. However, the side-effects of these compounds can be severe, leading to alopecia, nausea, immune deficiency, and cardiotoxicity. For immunocompromised patients with aggressive Kaposi's sarcoma (KS), these complications often preclude the completion of appropriate chemotherapeutic regimens. This review focuses on the development and efficacy of liposomal daunorubicin (DaunoXome; DNX) carriers for the treatment of KS. Encouragingly, DNX demonstrated increased in vivo stability and specificity. As a result, KS patients benefit from higher cumulative chemotherapeutic doses without significant cardiotoxicity. Tumor response to DNX treatment surpasses that of non-encapsulated daunorubicin and is similar to that observed with conventional multi-drug therapies such as ABV (doxorubicin, bleomycin, vincristine). Moreover, some reports indicate the patient quality of life during therapy may improve with DNX treatment. Although the development of DNX represents a significant advance in KS therapy, recent data suggest that additional modification of the liposomal carrier to include pegylation or target specific antibodies may further increase daunorubicin efficacy in the future.     

Auxin transport at cellular level: new insights supported by mathematical modelling

The molecular basis of cellular auxin transport is still not fully understood. Although a number of carriers have been identified and proved to be involved in auxin transport, their regulation and possible activity of as yet unknown transporters remain unclear. Nevertheless, using single-cell-based systems it is possible to track the course of auxin accumulation inside cells and to specify and quantify some auxin transport parameters. The synthetic auxins 2,4-dichlorophenoxyacetic acid (2,4-D) and naphthalene-1-acetic acid (NAA) are generally considered to be suitable tools for auxin transport studies because they are transported specifically via either auxin influx or efflux carriers, respectively. Our results indicate that NAA can be metabolized rapidly in tobacco BY-2 cells. The predominant metabolite has been identified as NAA glucosyl ester and it is shown that all NAA metabolites were retained inside the cells. This implies that the transport efficiency of auxin efflux transporters is higher than previously assumed. By contrast, the metabolism of 2,4-D remained fairly weak. Moreover, using data on the accumulation of 2,4-D measured in the presence of auxin transport inhibitors, it is shown that 2,4-D is also transported by efflux carriers. These results suggest that 2,4-D is a promising tool for determining both auxin influx and efflux activities. Based on the accumulation data, a mathematical model of 2,4-D transport at a single-cell level is proposed. Optimization of the model provides estimates of crucial transport parameters and, together with its validation by successfully predicting the course of 2,4-D accumulation, it confirms the consistency of the present concept of cellular auxin transport.     

Benzo[a]pyrene degradation using simultaneously combined chemical oxidation,biotreatment with Fusarium solani and cyclodextrins

The interest of simultaneously combining chemical (Fenton’s reaction) and biological treatments for the degradation of a high molecular weight polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) has been studied in laboratory tests. An optimal concentration of 1.5 × 10⁻³ M H₂O₂ as Fenton’s reagent was firstly determined as being compatible with the growth of Fusarium solani, the Deuteromycete fungus used in the biodegradation process. For the enhancement of BaP solubilisation, cyclodextrins were also used in the performed tests. The best degradation performance was achieved through the use of 5 × 10⁻³ M hydroxypropyl-β-cyclodextrin (HPBCD) in comparison with randomly methylated-β-cyclodextrin (RAMEB). When Fenton’s treatment was combined with biodegradation, a beneficial effect on BaP degradation (25%) was obtained in comparison with biodegradation alone (8%) or with chemical oxidation alone (16%) in the presence of HPBCD for 12 days of incubation.     

Gamma-glutamyltransferase,possible novel biomarker in colon diverticulosis: a case-control study

The gamma-glutamyltransferase (GGT) is recognized in medical practice as a useful indicator for the detection of liver lesions, especially those induced by the excessive consumption of alcoholic or cholesterol-associated drinks. The present study, although it includes a very small number of cases diagnosed with colon diverticulosis-diverticulitis associated with polyposis at the same intestinal level, identifies the presence of increased circulating concentrations of this enzyme in the serum. Its serum levels are tracked “dynamically” throughout a year after the diagnosis and start of the therapy. The study calls into question the release of the enzyme from the edge of the enterocytes’ brush-like edge, leading to the pathogenic disturbance of regional redox homeostasis. The hypothesis gives the circulating values of GGT predictive value for cellular oxidative stress, as well as for indirectly expressing the glutathione level in cytosol.     

Reduction of surgical site infection using a novel intervention (ROSSINI): study protocol for a randomised controlled trial

Background

Surgical site infection (SSI) is a common complication following abdominal surgery. It is associated with considerable morbidity and mortality, and its management results in significant cost to health services within both primary and secondary care. Some surgeons believe that the use of a wound-edge protection device may reduce the incidence of SSI. Whilst there is some encouraging evidence showing that such devices may lead to a reduction in SSI, there are no controlled trials of sufficient size or quality to support their routine use.

Methods/Design

750 patients will be recruited from around 20 surgical units within the United Kingdom. Patients undergoing laparotomy through any major abdominal incision for any indication, elective or emergency, are eligible. Patients under the age of 18, those undergoing a laparoscopic assisted procedure or who have undergone laparotomy within the previous 3 months, and those who are unable to give informed consent will be excluded. Patients will be randomised (1:1 ratio) to the use of a wound-edge protection device or no wound-edge protection device during surgery.Follow up will consist of blinded clinical wound reviews at 5-7 days and 30-33 days postoperatively with a self-completed questionnaire covering the intervening period. Quality of life questionnaires will be completed prior to surgery and at the subsequent wound review points and information on resource usage will also be captured.The primary outcome measure is SSI within 30 days of surgery. Secondary outcomes include the impact of the degree of wound contamination, patient comorbidity, and operative characteristics on the efficacy of a wound-edge protection device in reducing SSI and whether the use of a wound-edge protection device has an effect on health-related quality of life or length of hospital stay and is cost-effective.

Discussion

Rossini is the first multicentre observer-blinded randomised controlled trial of sufficient size and quality to establish whether the use of a wound-edge protection device in adult patients undergoing abdominal surgery leads to a lower rate of SSI. The results of this study will be used to inform current surgical practice and may potentially benefit patients undergoing surgery in the future.

Trial registration number

Current Controlled Trials ISRCTN: ISRCTN40402832

     

Mixtures of wild-type and a pathogenic (E22G) form of Abeta40 in vitro accumulate protofibrils,including amyloid pores

Although APP mutations associated with inherited forms of Alzheimer's disease (AD) are relatively rare, detailed studies of these mutations may prove critical for gaining important insights into the mechanism(s) and etiology of AD. Here, we present a detailed biophysical characterization of the structural properties of protofibrils formed by the Arctic variant (E22G) of amyloid-beta protein (Abeta40(ARC)) as well as the effect of Abeta40(WT) on the distribution of the protofibrillar species formed by Abeta40(ARC) by characterizing biologically relevant mixtures of both proteins that may mimic the situation in the heterozygous patients. These studies revealed that the Arctic mutation accelerates both Abeta oligomerization and fibrillogenesis in vitro. In addition, Abeta40(ARC) was observed to affect both the morphology and the size distribution of Abeta protofibrils. Electron microscopy examination of the protofibrils formed by Abeta40(ARC) revealed several morphologies, including: (1) relatively compact spherical particles roughly 4-5 nm in diameter; (2) annular pore-like protofibrils; (3) large spherical particles 18-25 nm in diameter; and (4) short filaments with chain-like morphology. Conversion of Abeta40(ARC) protofibrils to fibrils occurred more rapidly than protofibrils formed in mixed solutions of Abeta40(WT)/Abeta40(ARC), suggesting that co-incubation of Abeta40(ARC) with Abeta40(WT) leads to kinetic stabilization of Abeta40(ARC) protofibrils. An increase in the ratio of Abeta(WT)/Abeta(MUT(Arctic)), therefore, may result in the accumulation of potential neurotoxic protofibrils and acceleration of disease progression in familial Alzheimer's disease mutation carriers.