Cold ischemia contributes to the development of chronic rejection and mitochondrial injury after cardiac transplantation

Chronic rejection (CR) remains an unsolved hurdle for long-term heart transplant survival. The effect of cold ischemia (CI) on progression of CR and the mechanisms resulting in functional deficit were investigated by studying gene expression, mitochondrial function, and enzymatic activity. Allogeneic (Lew F344) and syngeneic (Lew Lew) heart transplantations were performed with or without 10 h of CI. After evaluation of myocardial contraction, hearts were excised at 2, 10, 40, and 60 days for investigation of vasculopathy, gene expression, enzymatic activities, and mitochondrial respiration. Gene expression studies identified a gene cluster coding for subunits of the mitochondrial electron transport chain regulated in response to CI and CR. Myocardial performance, mitochondrial function, and mitochondrial marker enzyme activities declined in all allografts with time after transplantation. These declines were more rapid and severe in CI allografts (CR-CI) and correlated well with progression of vasculopathy and fibrosis. Mitochondria related gene expression and mitochondrial function are substantially compromised with the progression of CR and show that CI impacts on progression, gene profile, and mitochondrial function of CR. Monitoring mitochondrial function and enzyme activity might allow for earlier detection of CR and cardiac allograft dysfunction.

Conjunctival Proliferation After a Mild Pepper Spray Injury in a Young Child

PURPOSE To report a case of conjunctival proliferation in a 2.5-year-old boy after initial evidence of a mild chemical injury after ocular exposure to pepper spray (oleoresin capsicum). METHODS Case report with ophthalmologic and histologic findings. RESULTS A child presented with mild conjunctival injection and chemosis without any corneal erosion after direct exposure to pepper spray. Three weeks later, a significant conjunctival proliferation was found at the limbus, which was refractory to treatment with topical corticosteroids. Finally, proliferative tissue was surgically excised without clinical recurrence during 2 months of follow-up. CONCLUSIONS We hypothesize that the young age of the patient may have been an important factor for the severe conjunctival proliferation in comparison to a mainly uncomplicated course of pepper spray injuries in most adults. We recommend the use of topical antiinflammatory treatment even in apparently mild pepper spray injuries, especially in young children.

Level of G protein-coupled receptor kinase-2 determines myocardial ischemia/reperfusion injury via pro- and anti-apoptotic mechanisms

Activation of prosurvival kinases and subsequent nitric oxide (NO) production by certain G protein-coupled receptors (GPCRs) protects myocardium in ischemia/reperfusion injury (I/R) models. GPCR signaling pathways are regulated by GPCR kinases (GRKs), and GRK2 has been shown to be a critical molecule in normal and pathological cardiac function.

Co2-dependent vasomotor reactivity of cerebral arteries in patients with severe traumatic brain injury: time course and effect of augmentation of cardiac output with dobutamine

Failing cerebral blood flow (CBF) autoregulation may contribute to cerebral damage after traumatic brain injury (TBI). The purpose of this study was to describe the time course of CO(2)-dependent vasoreactivity, measured as CBF velocity in response to hyperventilation (vasomotor reactivity [VMR] index). We included 13 patients who had had severe TBI, 8 of whom received norepinephrine (NE) based on clinical indication. In these patients, measurements were also performed after dobutamine administration, with a goal of increasing cardiac output by 30%. Blood flow velocity was measured with transcranial Doppler ultrasound in both hemispheres. All patients except one had an abnormal VMR index in at least one hemisphere within the first 24 h after TBI. In those patients who did not receive catecholamines, mean VMR index recovered within the first 48 to 72 h. In contrast, in patients who received NE within the first 48 h period, VMR index did not recover on the second day. Cardiac output and mean CBF velocity increased significantly during dobutamine administration, but VMR index did not change significantly. In conclusion, CO(2) vasomotor reactivity was abnormal in the first 24 h after TBI in most of the patients, but recovered within 48 h in those patients who did not receive NE, in contrast to those eventually receiving the drug. Addition of dobutamine to NE had variable but overall insignificant effects on CO(2) vasomotor reactivity.

Interdisciplinary rehabilitation after whiplash injury: an observational prospective outcome study

To examine the state of, and change in, biopsycho-social health and quality of life of patients after whiplash injury, before and after an inpatient interdisciplinary pain management programme.

Tailored protection against plasmalemmal injury by annexins with different Ca2+ sensitivities

The annexins, a family of Ca(2+)- and lipid-binding proteins, are involved in a range of intracellular processes. Recent findings have implicated annexin A1 in the resealing of plasmalemmal injuries. Here, we demonstrate that another member of the annexin protein family, annexin A6, is also involved in the repair of plasmalemmal lesions induced by a bacterial pore-forming toxin, streptolysin O. An injury-induced elevation in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) triggers plasmalemmal repair. The highly Ca(2+)-sensitive annexin A6 responds faster than annexin A1 to [Ca(2+)](i) elevation. Correspondingly, a limited plasmalemmal injury can be promptly countered by annexin A6 even without the participation of annexin A1. However, its high Ca(2+) sensitivity makes annexin A6 highly amenable to an unproductive binding to the uninjured plasmalemma; during an extensive injury accompanied by a massive elevation in [Ca(2+)](i), its active pool is severely depleted. In contrast, annexin A1 with a much lower Ca(2+) sensitivity is ineffective at the early stages of injury; however, it remains available for the repair even at high [Ca(2+)](i). Our findings highlight the role of the annexins in the process of plasmalemmal repair; a number of annexins with different Ca(2+)-sensitivities provide a cell with the means to react promptly to a limited injury in its early stages and, at the same time, to withstand a sustained injury accompanied by the continuous formation of plasmalemmal lesions.

Serotonin-producing enterochromaffin cell tumors of the pancreas: clinicopathologic study of 15 cases and comparison with intestinal enterochromaffin cell tumors

Serotonin-producing tumors of the pancreas are rare endocrine neoplasms composed of enterochromaffin (EC) cells that have been mainly described in the literature as case reports. This study analyzes the clinicopathologic features of a series of pancreatic EC cell neoplasms and their similarities to and differences from intestinal EC cell tumors.

Toward optimal early management after whiplash injury to lessen the rate of transition to chronicity: discussion paper 5

Expert debate and synthesis of research to inform future management approaches for acute whiplash disorders.