Electrical field stimulation promotes anastomotic healing in poorly perfused rat colon.

Introduction: Hypoperfusion of the bowel is a risk factor for anastomotic failure. Electrical field stimulation has been shown to improve repair in ischemic tissue, but its influence in hypoperfused colon has not been investigated. The hypothesis of this experimental animal study was that electrical field stimulation improves anastomotic healing in ischemic bowel.

Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics.

Type 1 diabetics have a well-recognised risk of accelerated cardiovascular disease. Even in the absence of clinical signs there are detectable abnormalities of conduit vessel function. Our group has previously reported reversal of endothelial dysfunction in diabetics with pravastatin.

Contrast-induced nephrotoxicity: possible synergistic effect of stress hyperglycemia.

Objective: Oxidative stress on the renal tubules has been implicated as a mechanism of injury in both stress hyperglycemia and contrast-induced nephrotoxicity. The purpose of this study was to determine whether the combination of these effects has a synergistic effect on accentuating renal tubular apoptosis and therefore increasing the risk of contrast-induced nephrotoxicity.

Materials And Methods: Dog kidney cells were incubated with 5- and 30-mmol/L glucose solutions and no glucose and then exposed for 2 hours to three types of contrast media-high osmolar (370 mg I/mL), low osmolar (300 mg I/mL), and isoosmolar (320 mg I/mL)-and a mannitol control solution.

Iodinated contrast media alter immune responses in pro-inflammatory states.

Background: Hypertonic saline causes a transient elevation of blood osmolality and has been shown to alter cellular inflammatory responses in pro-inflammatory states. Intravascular administration of iodine contrast media also causes a transient elevation of blood osmolarity.

Purpose: To investigate the effect of iodine contrast media on leukocyte-endothelial interaction in vivo using intravital microscopy.

The antiendotoxin agent taurolidine potentially reduces ischemia/reperfusion injury through its metabolite taurine.

Background: Cardiopulmonary bypass results in ischemia/reperfusion (I/R)-induced endotoxemia. We conducted a prospective randomized trial to investigate the effect of taurolidine, an antiendotoxin agent with antioxidant and membrane-stabilizing properties, on patients undergoing coronary artery bypass grafting (CABG).

Methods: A total of 60 patients undergoing CABG were randomized into 4 groups.

The evolving role of taurolidine in cancer therapy.

Background And Design: Taurolidine consists of two taurinamide rings derived from the naturally occurring amino acid taurine. It has been utilized to prevent adhesions, as an antimicrobial, and as an anti-inflammatory agent. More recently, it has been found to exert antineoplastic activity.

Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI.

Should incidental asymptomatic angiographic stenoses and occlusions be treated in patients with peripheral arterial disease?

Purpose: The clinical importance of angiographically detected asymptomatic lower-limb stenoses and occlusions is unknown. This study aims to (i) assess the clinical outcome of asymptomatic lesions in the lower limb, (ii) identify predictors of clinical deterioration, and (iii) determine which asymptomatic lower-limb lesions should be treated at presentation.

Materials And Methods: All 918 patients undergoing peripheral angiography with or without angioplasty over a period of 7.

Attenuation of lipopolysaccharide-mediated left ventricular dysfunction by glutamine preconditioning.

Objective: Myocardial dysfunction is often seen during the inflammatory response to major surgery at 4 to 6h postoperatively. The aim of this study was to investigate the effect of glutamine pretreatment, as a means of preconditioning, on lipopolysaccharide-induced myocardial dysfunction.

Methods: C57BL/6 mice were randomized into four groups: Control; lipopolysaccharide; glutamine plus lipopolysaccharide; and Quercetin, an inhibitor of heat shock protein synthesis plus glutamine and lipopolysaccharide.

GLUT-1 expression and response to chemoradiotherapy in rectal cancer.

Preoperative chemoradiotherapy is used in locally advanced rectal cancer to reduce local recurrence and improve operability, however a proportion of tumors do not undergo significant regression. Identification of predictive markers of response to chemoradiotherapy would improve patient selection and may allow response modification by targeting of specific pathways. The aim of this study was to determine whether expression of glucose transporter-1 (GLUT-1) and p53 in pretreatment rectal cancer biopsies was predictive of tumor response to chemoradiotherapy.

The Tromped: a solution for flight-related deep vein thrombosis?

Flight-related deep vein thrombosis (DVT) is well recognized. Reduced venous return occurs during immobility. This alteration in venous hemodynamics may contribute to DVT development.

Vascular endothelial growth factor is an autocrine survival factor for breast tumour cells under hypoxia.

Vascular endothelial growth factor (VEGF) is produced by most tumour types and stimulates the growth of new blood vessels in the tumour. The expansion of a solid tumour ultimately leads to the development of hypoxic regions, which increases VEGF production and further angiogenesis. In this study, we examined the role of VEGF in the survival of breast tumour cells under hypoxia.

Glutamine preconditioning protects against tourniquet-induced local and distant organ injury in a rodent ischemia-reperfusion model.

Introduction: Ischemia-reperfusion (IR) injury is a common surgical event, with tourniquet use being a recognized cause in orthopedic surgery. Preconditioning is a highly evolutionarily conserved endogenous protective mechanism, but finding a clinically safe, acceptable method of induction has proven difficult. Glutamine, a known inducer of the heat shock protein response, offers pharmacological modulation of injury through clinically acceptable preconditioning.

Two-week treatment with pravastatin improves ventriculo-vascular haemodynamic interactions in young men with type 1 diabetes.

Young patients with diabetes but without established vascular disease have altered conduit and resistance artery reactivity. Early endothelial dysfunction is an initial step in atherogenesis: reductions in nitric oxide (NO) production in these vascular beds are implicated. The study aim was two-fold: first, to detect baseline abnormalities in cardiac function, conduit vessels and the microcirculation using applanation tonometry, brachial artery ultrasound and laser Doppler fluximetry, respectively; and second, to investigate any modification in these parameters with the use of pravastatin.

Taurine attenuates acute hyperglycaemia-induced endothelial cell apoptosis, leucocyte-endothelial cell interactions and cardiac dysfunction.

Objectives: Hyperglycaemia is implicated in microvascular inflammatory injury and subsequent cardiac injury/dysfunction. Leucocyte adhesion to the endothelium, migration into tissue and toxic metabolite release are early critical steps. Taurine is a semi-essential amino acid that is endothelial protective and restrains excess leucocyte activity by the formation of less toxic inflammatory mediators.

Tourniquet injuries: pathogenesis and modalities for attenuation.

Although it is widespread in orthopaedic surgery, tourniquet use is associated with appreciable morbidity and even mortality. We review the use of tourniquets, highlighting how an understanding of their design and application can reduce the complications and injuries associated with their use. We also review the attempts being made to modulate these injuries through physical and pharmacological advances, in particular looking at the phenomenon of preconditioning.

Comparison of catecholamine hormone release in patients undergoing carotid artery stenting or carotid endarterectomy.

Purpose: To investigate the pattern of catecholamine response in patients undergoing carotid endarterectomy (CEA) or carotid artery stenting (CAS).

Methods: Adrenaline, noradrenaline, and renin levels were measured at 5 time points in 12 patients undergoing 13 CEAs (1 bilateral) and 13 patients undergoing unilateral CAS. Arterial blood samples were taken at the following time points: (1) after induction in CEA patients or 5 minutes following first contrast injection in CAS patients, (2) 5 minutes following ICA clamp release in surgical patients or deflation of the balloon in the CAS cohort, (3) 60 minutes following ICA clamp release in surgical patients or deflation of the balloon in the CAS cohort, and (4) 24 hours following the procedure.

Taurine protects against PMN dysfunction and death in urine.

The polymorphonuclear neutrophil (PMN) is the primary pro-inflammatory cell in the host response to bacterial infection and, as the first line of defence, is the principal cell responsible for the recognition, phagocytosis and killing of bacteria. PMN function is known to be defective in the urine. High osmolarity is physiologic in the urine and this hypertonic environment has been shown to compromise neutrophil function.

A novel gene delivery system for mammalian cells.

Although gene therapy holds great promise for the treatment of both acquired and genetic diseases, its development has been limited by practical considerations. Non-viral efficacy of delivery remains quite poor. We are investigating the feasibility of a novel lipid-based delivery system, cochleates, to deliver transgenes to mammalian cells.

Long-term protective effects of hypothermia on reperfusion injury post-testicular torsion.

Objective: As many as two-thirds of salvaged testes post-torsion will atrophy within 2 years. Subsequent testicular damage is due at least in part to an ischaemia/reperfusion injury. Thus we analysed the long-term protective effects of subjecting the ischaemic testis to hypothermia in an attempt to prevent or attenuate subsequent testicular damage.

Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies.

Tissue hypoxia occurs where there is an imbalance between oxygen supply and consumption. Hypoxia occurs in solid tumours as a result of an inadequate supply of oxygen, due to exponential cellular proliferation and an inefficient vascular supply. It is an adverse prognostic indicator in cancer as it is associated with tumour progression and resistance to therapy.

Clinically applicable thermal preconditioning attenuates leukocyte-endothelial interactions.

Background: We have previously demonstrated that clinically applicable thermal preconditioning induces heat shock protein 72 (HSP72) and protects against a subsequent ischemia-reperfusion (I/R) injury in an animal model. A core component of I/R injuries is the interaction between activated leukocytes and endothelial cells. We hypothesized that the effects of clinically applicable thermal preconditioning are mediated through attenuation of this leukocyte-endothelial (L-E) interaction.

Neoadjuvant antiangiogenic therapy with tamoxifen does not impair gastrointestinal anastomotic repair in the rat.

Introduction: Antiangiogenic therapy has the potential to moderate tumour and micrometastatic growth. Its use in the perioperative period is attractive but its potential to compromise wound and anastomotic healing is a cause for concern. Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound healing.

Taurolidine attenuates the hemodynamic and respiratory changes associated with endotoxemia.

The purpose of this study was to determine if prereatment with taurolidine, a known anti-endotoxin agent, would attenuate the hemodynamic and respiratory responses associated with endotoxin induced lung injury in a large animal model in a randomized controlled study under license from the Department of Health. All animals underwent a general anesthetic. Vascular catheters were placed in the femoral artery and in the femoral vein.

Cyclooxygenase isozyme expression and intimal hyperplasia in a rat model of balloon angioplasty.

Prostaglandin formation is enhanced in vascular disease, in part through induction of cyclooxygenase (COX-2) in vascular smooth muscle cells. Because COX regulates cell growth and migration, we examined whether the COX expression plays a role in the development of intimal hyperplasia after vascular injury. Rats undergoing balloon angioplasty of the carotid artery were randomized to receive a selective COX-2 inhibitor (SC-236), a selective COX-1 inhibitor (SC-560) or a combination of the two.