A nonerythropoietic derivative of erythropoietin inhibits tubulointerstitial fibrosis in remnant kidney

Background

The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO.

Methods

To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8?weeks.

Results

CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak ??SMA staining. Furthermore, PCR analysis demonstrated that TGF-?? and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis.

Conclusion

We established a long-term therapeutic approach to protect tubulointerstitial injury with CEPO, and thus, the therapeutic value of this approach warrants further attention and preclinical studies.     

Ischemic events due to intraoperative microemboli developing in the cerebral hemisphere contralateral to carotid endarterectomy in a patient with preoperative cerebral hemodynamic impairment

A 74-year-old man with a history of asymptomatic right internal carotid artery (ICA) occlusion experienced amaurosis fugax in the left eye. Angiography showed left cervical ICA stenosis in addition to right cervical ICA occlusion. The right anterior and middle cerebral artery (MCA) territories were perfused from the left ICA via the anterior communicating artery. Brain perfusion single-photon emission computed tomography revealed reduced cerebral blood flow and reduced cerebrovascular reactivity to acetazolamide only in the right cerebral hemisphere. The patient underwent left carotid endarterectomy (CEA). Transcranial Doppler monitoring showed microembolic signals in the left MCA during dissection of the left ICA, but intraoperative monitoring suggested absence of global hypoperfusion or ischemia in the bilateral cerebral hemispheres during left ICA clamping. Transient and slight motor weakness of the left upper extremity was noted on recovery from anesthesia. Diffusion-weighted magnetic resonance imaging demonstrated the development of new spotty ischemic lesions only in the right cerebral hemisphere. The present case suggests that intraoperative cerebral embolism causing postoperative neurological deficits can develop exclusively in the cerebral hemisphere contralateral to CEA if the hemisphere has preoperative hemodynamic impairment and collateral circulation via the anterior communicating artery from the ICA ipsilateral to CEA.     

The neuroprotective effect of lactate is not due to improved glutamate uptake after controlled cortical impact in rats

Abstract For many years lactate was considered to be a waste product of glycolysis. Data are accumulating that suggest that lactate is an important energy substrate for neurons during activation. In severe traumatic brain injury (TBI) glutamate release and ischemic cerebral blood flow (CBF) are major factors for a mismatch between energy demand and supply and for neuronal cell death. Although ATP and behavior could be improved by lactate treatment after TBI, no histological correlate nor any linkage to better astrocytic glutamate uptake or CBF as possible mechanisms have been described. We subjected male rats to a controlled cortical impact (CCI; 5?m/sec, 2.5?mm). To study the effects of lactate treatment on lesion volume, glutamate release, and CBF, animals were infused with either NaCl or 100?mM lactate for up to 3?h. The role of endogenous lactate was investigated by inhibiting transport with α-cyano-4-hydroxy-cinnamic acid (4-CIN; 90?mg/kg). Lactate treatment 15?min post-CCI reduced lesion volume from 21.1±2.8?mm(3) to 12.1±1.9?mm(3) at day 2 after CCI. Contusion produced a significant three- to fourfold increase of glutamate in microdialysates, but there was no significant difference between treatments that began 30?min before CCI. In this experiment lesion volume was significantly reduced by lactate at day 7 post-CCI (23.7±4 to 9.3±1-2?mm(3)). CBF increased immediately after CCI and dropped thereafter below baseline in all animals. Lactate infusion 15?min post-CCI elevated CBF for 20?min in 7 of 10 animals, whereas 7 of 8 NaCl-treated animals showed a further CBF decline. Neuroprotection was achieved by lactate treatment following contusion injury, whereas blocking of endogenous lactate transport exerted no adverse effects. Neuroprotection was not achieved by improved glutamate uptake into astrocytes, but was supported by augmented CBF following CCI. Due to its neuroprotective property, lactate might be a beneficial pharmacological treatment for TBI patients.     

A combination of aortic arch debranching and off-pump coronary artery bypass

The prevalence of coronary artery disease in patients with aortic aneurysm is high. As an antecedent percutaneous coronary intervention with antiplatelet therapy may cause a rupture of aortic aneurysm, concomitant treatment for aortic arch aneurysm and coronary artery disease is recommended. We report a technique of a combined procedure of antegrade endovascular repair with aortic arch debranching and off-pump coronary artery bypass grafting.     

Propofol-induced anesthesia in mice is mediated by gamma-aminobutyric acid-A and excitatory amino acid receptors

To elucidate the role of gamma-aminobutyric acid (GABA)(A) receptor complex and excitatory amino acid receptors (N-methyl-D-aspartate [NMDA] and non-NMDA receptors) in propofol-induced anesthesia, we examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol anesthesia in mice. All drugs were administered intraperitoneally. General anesthetic potencies were evaluated using a righting reflex assay. The GABA(A) receptor agonist muscimol potentiated propofol (140 mg/kg; 50% effective dose for loss of righting reflex) induced anesthesia. Similarly, the benzodiazepine receptor agonist diazepam and the NMDA receptor antagonist MK-801 augmented propofol anesthesia, but the non-NMDA receptor antagonist CNQX did not. In contrast, the GABA(A) receptor antagonist bicuculline antagonized propofol (200 mg/kg; 95% effective dose for loss of righting reflex) induced anesthesia. However, neither the benzodiazepine receptor antagonist flumazenil, the GABA synthesis inhibitor L-allylglycine, nor the NMDA receptor agonist NMDA reversed propofol anesthesia. Conversely, the non-NMDA receptor agonist kainate enhanced propofol anesthesia. These results suggest that propofol-induced anesthesia is mediated, at least in part, by both GABA(A) and excitatory amino acid receptors. IMPLICATIONS: We examined behaviorally the effects of GABAergic and glutamatergic drugs on propofol-induced anesthesia in mice. The results suggest that propofol anesthesia is mediated, at least in part, by both GABA(A) and excitatory amino acid receptors.     

Diffusion tensor imaging of the brain: effects of distortion correction with correspondence to numbers of encoding directions

Purpose  The aim of the study was to estimate the effect of distortion correction with correspondence to numbers of encoding directions to acquire diffusion tensor imaging (DTI) of improved quality. Materials and methods  Ten volunteers underwent DTI of the head using echo planar imaging with 6, 13, 27, and 55 encoding directions. Fractional anisotropy (FA) maps and apparent diffusion coefficient (ADC) maps were created before and after distortion correction. Regions of interest were placed in the corpus callosum on each map, and standard deviations of FA and ADC were calculated. FA maps were also evaluated visually by experienced neuroradiologists. Results  Dispersion of standard deviations tended to be reduced after distortion correction, with significant differences found in FA maps with 6 encoding directions, ADC maps with 6 directions, and ADC maps with 13 directions (P < 0.001, P < 0.005, and P < 0.05, respectively). Visual image quality was improved after distortion correction (P < 0.01 for all of the visual comparisons). Conclusion  Distortion correction is effective in providing DTI of enhanced quality, notwithstanding the number of encoding directions. This article was presented at a Japan Radiological Society meeting in 2002     

Prophylaxis of nausea and vomiting after laparoscopic cholecystectomy with ramosetron: randomised controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of ramosetron (a 5-hydroxytryptamine type 3 receptor antagonist) for the prevention of nausea and vomiting after laparoscopic cholecystectomy. DESIGN: Prospective, randomised, double-blind, placebo-controlled study. SETTING: University and university-affiliated hospitals, Japan. SUBJECTS: 100 patients, 65 women and 35 men, who had laparoscopic cholecystectomy. INTERVENTIONS: Patients were given either placebo or ramosetron at 3 different doses (0.15 mg, 0.3 mg, 0.6 mg) intravenously at the completion of operation. The general anaesthetic technique and postoperative analgesia were standard. MAIN OUTCOME MEASURES: Vomiting and safety were assessed for 0 to 24 hours and 24 to 48 hours after anaesthesia. RESULTS: The number of patients who had a complete response (no nausea, no retching, no vomiting) during 0 to 24 hours after anaesthesia was 15/25 with placebo, 17/25 with ramosetron 0.15 mg, 23/25 with ramosetron 0.3 mg, and 23/25 with ramosetron 0.6 mg; The corresponding numbers from 24 to 48 hours were 16, 17, 23, and 23. No serious adverse events were observed in any of the groups. CONCLUSIONS: Ramosetron 0.3 mg was the minimum effective dose for preventing postoperative nausea and vomiting during 0 to 48 hours after anaesthesia in patients undergoing laparoscopic cholecystectomy.     

Acute early failure of a bioprosthesis after mitral valve replacement with completely preserved annuloventricular continuity

We report a case of acute early bioprosthetic failure after mitral valve replacement with completely preserved annuloventricular continuity. A 77-year-old man with left ventricular dysfunction underwent double valve replacement with Carpentier-Edwards pericardial bioprostheses. Routine postoperative echocardiography revealed 1.4 cm² of estimated mitral valve area, and computed tomography revealed a large thrombus in the left atrium. Transesophageal echocardiography showed a restricted opening of the bioprosthetic leaflets. After a month of strict anticoagulation therapy, cusp mobility improved, with a calculated mitral valve area of 3.5 cm²; and the left atrial thrombus had almost disappeared 2 months after initiation of therapeutic anticoagulation. Surgeons should be watchful for bioprosthetic thrombosis in patients with left ventricular dysfunction who undergo mitral valve replacement with a preserved mitral subvalvular apparatus.