Heme oxygenase-1 and transplantation tolerance.

Tolerance is the ultimate goal of transplantation: the lack of any need for immunosuppression with long-term survival of the transplanted tissue and a full immunological response to all antigens other than those on the transplant. In honor of my dear friend and colleague, Prof. Dr.

Carbon monoxide orchestrates a protective response through PPARgamma.

Carbon monoxide (CO) suppresses proinflammatory responses in macrophages reacting to LPS. We hypothesize that CO acts by inducing a molecule(s) that suppresses the inflammatory response to subsequent stress. Exposure of macrophages to CO alone in vitro produced a brief burst of mitochondrial-derived ROS, which led to expression of PPARgamma.

Patterns of experimentally induced pain in pericranial muscles.

Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.

Differential effect of ketamine and lidocaine on spontaneous and mechanical evoked pain in patients with nerve injury pain.

Background: The mechanisms underlying neuropathic pain are incompletely understood. Targeting specific molecular mechanisms in the pain signaling system may assist in understanding key features in neuropathic pains such as allodynia. This study examined the effect of systemically administered ketamine, an N-methyl-D-aspartate receptor antagonist and lidocaine, a sodium channel blocker, on spontaneous pain, brush-evoked pain, and pinprick-evoked pain in patients with nerve injury pain.

Direct arthrography of the pisotriquetral joint.

Objective: The purpose of this study was to describe and evaluate a simple and safe procedure for direct arthrography of and steroid injection into the pisotriquetral joint.

Conclusion: Direct pisotriquetral arthrography using a medial approach is an effective and easy-to-perform technique for injection of steroids.

Heme oxygenase-1 is essential for and promotes tolerance to transplanted organs.

This investigation focused on obtaining a further understanding of the role of heme oxygenase-1 (HO-1) in tolerance induction. Hearts from C57BL/6 (H-2b) mice survived long-term when transplanted into BALB/c (H-2d) recipients treated with the tolerance-inducing regimen of anti-CD40L antibody (MR-1) plus donor-specific transfusion (DST). Grafts did not, however, survive long-term in (HO-1-/-) recipients given the same treatment.

Bilirubin can induce tolerance to islet allografts.

Induction of heme oxygenase-1 (HO-1) expression in recipients of allogeneic islets can lead to long-term survival (>100 d) of those islets. We tested whether administration of bilirubin would substitute for the beneficial effects of HO-1 expression in islet transplantation. Administering bilirubin to the recipient (B6AF1) or incubating islets in a bilirubin-containing solution ex vivo led to long-term survival of allogeneic islets in a significant percentage of cases.

Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs.

Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide (CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO (one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs.

Reduced cold pressor pain tolerance in non-recovered whiplash patients: a 1-year prospective study.

Unlabelled: Whiplash injury and chronic whiplash syndrome represent major health problems in certain western communities, pain being the main symptom. Sensitization of the nociceptive system may play a role for non-recovery after whiplash injury.

Aims: This study examined if tolerance to endure pain stimuli may predict outcome in whiplash injury.

Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation.

Background: Bilirubin, a natural product of heme catabolism by heme oxygenases, was considered a toxic waste product until 1987, when its antioxidant potential was recognized. On the basis of observations that oxidative stress is a potent trigger in vascular proliferative responses, that heme oxygenase-1 is antiatherogenic, and that several studies now show that individuals with high-normal or supranormal levels of plasma bilirubin have a lesser incidence of atherosclerosis-related diseases, we hypothesized that bilirubin would have salutary effects on preventing intimal hyperplasia after balloon injury.

Methods And Results: We found less balloon injury-induced neointima formation in hyperbilirubinemic Gunn rats and in wild-type rats treated with biliverdin, the precursor of bilirubin, than in controls.

[Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis--secondary publication].

Cannabinoids reduce allodynia/hyperalgesia in animal pain models, but few clinical studies evaluated the analgesic action in humans. We aimed to evaluate the effect of delta-9-tetrahydrocannabinol (dronabinol) on central pain in MS patients. Twenty-four MS patients participated in a double-blind placebo-controlled crossover trial.

Donor treatment with carbon monoxide can yield islet allograft survival and tolerance.

Treatment of animals or certain cells with carbon monoxide (CO), a product of heme degradation by heme oxygenase-1 (HO-1), has potent anti-inflammatory and antiapoptotic effects that contribute to the survival of transplanted organs. We report here that inducing HO-1 in, or administering CO to, only the donor can be used in a therapeutic manner to sustain the survival of transplanted allogeneic islets. Similar treatments of only the islets or only the recipient are also salutary.

Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial.

Background: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine.

Methods: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min.

Heme oxygenase-1-generated biliverdin ameliorates experimental murine colitis.

Background: Heme oxygenase-1 (HO-1) seems to have an important protective role in acute and chronic inflammation. The products of heme catalysis, biliverdin/bilirubin, carbon monoxide (CO), and iron (that induces apoferritin) mediate the beneficial effects of HO-1. Blockade of HO-1 activity results in exacerbation of experimental colitis.

Sensory function and quality of life in patients with multiple sclerosis and pain.

Central neuropathic pain is well known in multiple sclerosis (MS), but the underlying mechanisms are unclear. In the present study we studied sensory function in MS patients with pain, MS patients without pain and healthy subjects in order to clarify the role of sensory abnormalities in pain. Fifty MS patients with pain were randomly recruited from a previous epidemiological MS study in Aarhus County, Denmark.

Breakthrough pain in malignant and non-malignant diseases: a review of prevalence, characteristics and mechanisms.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non-malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non-malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP.

Protection against ischemia/reperfusion injury in cardiac and renal transplantation with carbon monoxide, biliverdin and both.

Both carbon monoxide (CO) and biliverdin, products of heme degradation by heme oxygenase, have been shown to attenuate ischemia/reperfusion (I/R) injury. We hypothesized in this study that dual-treatment with CO and biliverdin would induce enhanced protective effects against cold I/R injury. Heterotopic heart and orthotopic kidney transplantation were performed in syngeneic Lewis rats after 24-h cold preservation in UW solution.