The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review.

Oxidative stress is an important factor in many pathological conditions such as inflammation, cancer, ageing and organ response to ischemia-reperfusion. Humans have developed a complex antioxidant system to eliminate or attenuate oxidative stress. Liver ischemia-reperfusion injury occurs in a number of clinical settings, including liver surgery, transplantation, and hemorrhagic shock with subsequent fluid resuscitation, leading to significant morbidity and mortality. It is characterized by significant oxidative stress but accompanied with depletion of endogenous antioxidants. This review has 2 aims: firstly, to highlight the clinical significance of liver ischemia-reperfusion injury, the underlying mechanisms and the main pathways by which the antioxidants function, and secondly, to describe the new developments that are ongoing in antioxidant therapy and to present the experimental and clinical evidence about the role of antioxidants in modulating hepatic ischemia-reperfusion injury.     

Evidence that reduction of immunogenicity of T-depleted bone marrow depends on additional depletion of accessory cells. Implications for prevention of graft rejection

An effective prophylaxis of graft-versus-host reaction in clinical bone marrow transplantation can be achieved by T depletion of the graft. However, this kind of graft manipulation is accompanied by a strongly increased incidence of graft rejection. In order to eliminate this hazardous complication we studied the possibility of preventing rejection of a BM graft by reducing its immunogenicity. In this report we demonstrate that the capacity of human BM cells to induce proliferation of allogeneic T cells is strongly reduced after treatment with the antilymphocyte/antimonocyte monoclonal antibody K31+ rabbit complement (C), indicating a reduced immunogenicity of the BM cells. On the other hand, the allostimulatory capacity of BM treated with clinically established T-depleting MoAbs, including the more broadly reactive CAMPATH-1, was not or only slightly reduced. MHC class II induction on BM cells with human recombinant gamma-interferon did not restore the allostimulatory capacity reduced by K31+C. Exogenous IL-1 partially inhibited the K31-mediated reduction of allostimulatory capacity. Reduction of the allostimulatory capacity of BM cells with K31+C correlated with a reduction of their capacity to support mitogen-induced proliferation of purified autologous T cells, indicating the absence of accessory functions. Addition of autologous peripheral adherent cells to K31+C treated BM restored its accessory function as well as its allostimulatory capacity. Labeling studies confirmed that accessory cells are critical for the described K31-mediated effects. We conclude that depletion of accessory cells in addition to lymphocytes with K31+C strongly reduces the immunogenicity of a BM graft, may help prevent graft rejection, and may serve as a model for preconditioning other organ grafts.     

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.     

Age-specific cerebral perfusion in 4- to 15-year-old children: a high-resolution brain SPET study using 99mTc-ECD

This study addresses the question of whether the normal range for distribution of local cerebral blood flow (lCBF) in adults can be transferred to the 4- to 15-year-old age group. Twenty-three children (age: 4–15 years; mean 11±3 years, group I) and 10 adults (age: 27–56 years; mean 45±10 years, group II) without evidence of cerebrovascular disease or other brain diseases underwent technetium-99m ethyl cysteinate dimer single-photon emission tomography. Counts in cortical and subcortical regions of interest (ROIs) were related to those in cerebellar ROIs (= 100%). Relative cortical activity in group I exceeded that in group II, particularly in left parietal (107.6%±9.8% vs 84.1%±12.4%), left frontal (97.7%±6.7% vs 79.4%±8.9%) and left temporal areas (99.7%±7.4% vs 84.9%±10.1%) and in the cingulate cortex (112.1%±9.1% vs 95.9%±10.1%, P<0.05). Cerebral activity uptake per injected dose was inversely correlated with age in 19 children of group I (r = –0.77, P<0.001). In group I, there was also an inverse correlation between age and the relative local count density in the parietal (r = –0.42 to –0.57), frontal (r = –0.48), temporal (r = –0.42 to –0.58) and occipital cortex (r = –0.44). In these cortical regions relative counts differed when subgroups of children aged 4–10 and 11–15 years were analysed. It is concluded that there are systematic differences between 4- to 15-year-old children and adults with regard to normal lCBF. Diagnostic use of perfusion agents has to consider age-adjusted normal flow maps; normal ranges should be determined separately for the age groups 4–10 and 11–15 years. Received 23 March and in revised form 11 July 1997     

Surgical therapy in patients with active infective endocarditis: seven-year single centre experience in a subgroup of 255 patients treated with the Shelhigh stentless bioprosthesis

OBJECTIVE: We investigated outcomes after surgical therapy in patients with active infective endocarditis (AIE) with regard to survival in relation to surgical urgency, valve position, number of valves implanted and abscess formation. We aimed to identify independent risk factors for early mortality. METHODS AND RESULTS: Two hundred and fifty-five patients received Shelhigh bioprostheses between February 2000 and March 2007. A total of 74.1% had native and 25.9% prosthetic AIE. Surgery was regarded as urgent in 57.3% and as an emergency procedure in 38.4%. There was a highly significant difference in survival rate between patients who were operated on urgently versus in an emergency (p<0.0001), between single and double valve replacement (p=0.0206) and between patients with and without abscess formation (p=0.0245). There were two cases of early reinfection (0.78%) and six of late reinfection (2.35%) leading to re-operation. CONCLUSIONS: The survival of patients differs significantly in dependence on their surgical urgency. Better outcome could have been achieved if patients had been referred earlier for surgery and operated upon before heart failure or septic shock developed. Long-term survival was better in patients without abscess formation. The low reinfection rate of Shelhigh bioprostheses in AIE is promising and the early and mid-term results achieved need to be verified in the long-term course.     

Coronary atherosclerosis of the donor heart--impact on early graft failure.

OBJECTIVE: Due to the shortage of donor hearts, the criteria for organ acceptability have been considerably extended and donor grafts with coronary atherosclerosis are among those offered. This study evaluated whether and to what degree pre-existing coronary atherosclerosis may be acceptable. METHODS: A total of 1253 consecutive HTx recipients were investigated retrospectively for donor-transmitted coronary atherosclerosis (DCAS). Donor-transmitted coronary atherosclerosis was defined as focal atherosclerosis with stenosis of at least 50%. Inclusion criteria were absence of pre-HTx angiogram but performance of angiogram or autopsy within 6 months after heart transplantation. Kaplan-Meier analysis and log-rank test were used. RESULTS: Eighty-five out of 1253 (6.8%) cases were excluded, since coronary evaluation was not performed within 6 months (n=45) or hearts had undergone pre-transplant angiography (n=40). In 1086 patients no donor-transmitted coronary atherosclerosis was found (NDCAS group) and in 82 patients (7%) donor-transmitted coronary atherosclerosis was diagnosed by angiography (n=49) or autopsy (n=33). Single-vessel donor-transmitted coronary atherosclerosis was found in 53/82 patients (DCAS1 group) and double- or triple-vessel donor-transmitted coronary atherosclerosis in 26/82 patients (DCAS2/3 group). Three of the 82 patients with donor-transmitted coronary atherosclerosis were excluded since the autopsy report was unclear regarding degree of atherosclerosis. Early after heart transplantation the 30-day mortality in the NDCAS and DCAS1 groups was 12.2% versus 13.2% whereas in the DCAS2/3 group it was 61.5%. Beyond the first year the annual decrease with and without donor-transmitted coronary atherosclerosis (single-vessel disease) is comparable. CONCLUSIONS: Donor screening without coronary angiogram overlooks significant atherosclerotic lesions in a considerable number of cases (7.0%). Therefore, angiographic donor screening should be performed. Donor grafts with single-vessel coronary atherosclerosis may be accepted as marginal hearts; however, in our opinion, revascularisation (CABG, PTCA) should be considered. Grafts with two- or even three-vessel coronary atherosclerosis seem to have a serious risk for early graft failure. Beyond the first year the outcome of healthy grafts and grafts with donor-transmitted coronary atherosclerosis seems to be comparable.     

Near fatal infection of a patient with a left ventricular assist device due to unrecognized fetal death.

We report on an unusual case of a young female patient who received an implantable LVAD after unsuccessful emergency coronary bypass surgery following acute myocardial infarction. After LVAD placement, it became evident that the patient had been pregnant. She had to undergo gynaecological surgery during mechanical support to remove the deceased fetus.     

Linear birefringence measurements of the in vitro human cornea

This paper presents results of an in vitro investigation of the optical anisotropy of the human cornea. Computer controlled imaging polarimetry and the Jones formalism were used to investigate the distribution of the birefringence and the azimuth angle across the surface of 12 corneas taken from the corneal bank. Each map of the birefringence and the azimuth angle has no rotational symmetry and is different for each cornea. The minimal value of the birefringence always appears in the corneal centre and varies from 9 to 43 degrees for different corneas. Birefringence of the cornea increases monotonically more than one order in the direction of the corneal periphery. Close to the centre of the cornea the azimuth angle is almost constant and varies significantly away from the optical part of the cornea.     

Effect of tissue fixatives on telomere length determination by quantitative PCR

Telomere length is a well established marker of cellular senescence and thus biological age. Quantitative PCR allows the determination even from very low amounts of tissue by using telomere specific and single copy gene primers. Comparing a directly processed tissue sample to a 4% formaldehyde fixed one showed a significantly reduced efficiency of PCR reactions (mainly in single copy gene experiments) in a storage time-dependent manner resulting in an artificial increase in reported relative telomere length. This effect was not seen when the tissue was stored in RNA later solution. In summary, telomere length determination from formaldehyde fixed material by quantitative PCR is not a reliable method. Unfortunately therefore, many easily accessible tissue samples from pathology laboratories are unsuitable for this technique.