Inhibition of Ca2+ channel current by μ- and κ-opioid receptors coexpressed in Xenopus oocytes: desensitization dependence on Ca2+ channel α1 subunits

1. Desensitization of μ- and κ-opioid receptor-mediated inhibition of voltage-dependent Ca²⁺ channels was studied in a Xenopus oocyte translation system.
2. In the oocytes coexpressing κ-opioid receptors with N- or Q-type Ca²⁺ channel α₁ and β subunits, the κ-agonist, U50488H, inhibited both neuronal Ca²⁺ channel current responses in a pertussis toxin-sensitive manner and the inhibition was reduced by prolonged agonist exposure.
3. More than 10 min was required to halve the inhibition of Q-type channels by the κ-agonist. However, the half-life for the inhibition of N-type channels was only 6±1 min. In addition, in the oocytes coexpressing μ-opioid receptors with N-type or Q-type channels, the uncoupling rate of the μ-receptor-mediated inhibition of N-channels was also faster than that of Q-type channels.
4. In the oocytes coexpressing both μ- and κ-receptors with N-type channels, stimulation of either receptor resulted in a cross-desensitization of the subsequent response to the other agonist. Treatment of oocytes with either H-8 (100 μM), staurosporine (400 nM), okadaic acid (200 nM), phorbol myristate acetate (5 nM) or forskolin (50 μM) plus phosphodiesterase inhibitor did not affect either the desensitization or the agonist-evoked inhibition of Ca²⁺ channels.
5. These results suggest that the rate of rapid desensitization is dependent on the α₁ subtype of the neuronal Ca²⁺ channel, and that a common phosphorylation-independent mechanism underlies the heterologous desensitization between opioid receptor subtypes.

     

Simple scintigraphic parameters with Tc-99m galactosyl human serum albumin for clinical staging of chronic hepatocellular dysfunction

Technetium-99m labeled diethylenetriaminepentaacetic acid (DTPA)-galactosyl human serum albumin (GSA) has been used for hepatocellular functional evaluation. This study proposed new and simple parameters to overcome the limitations of conventional parameters, and they were applied to the clinical staging of chronic liver dysfunction. The study group consisted of 93 patients including 81 with liver dysfunction and 12 control patients. In addition to the two conventional parameters, namely, receptor index (LHL15 = liver count divided by the sum of liver and heart counts at 15 minutes) and clearance index (HH15 = heart count at 15 minutes divided by the heart count at 3 minutes), 6 new parameters for Tc-99m GSA uptake and clearance were generated. The conventional receptor index of LHL15 showed a large variation depending on the size of region of interest (ROI) over the heart. The LHL15 normalized by the ROI size (nLHL15) showed more stable data and a better separation of mild liver dysfunction. A hyperbolic relationship between the LHL15 and HH 15 changed to a linear relationship by using the nLHL15 index. The combination of the liver to heart average count ratio at 15 minutes (LH 15) and T-half (minute) of the heart count also could differentiate each stage well. In conclusion, the use of the ROI-area normalized nLHL is recommended instead of the conventional LHL15. The indices of LH15 and T-half could be alternatively used as practical parameters for clinical staging in liver function.     

Oligodendroglioma-like cells (clear cells) in ependymoma

A brain tumor of a 22-year-old man was composed mostly of round cells with perinuclear halos (clear cells), forming clusters intersected by small blood vessels. In some areas, the tumor cells showed perivascular arrangement and epithelial pattern. Phosphotungstic-acid hematoxylin stain and immunoperoxidase stain for glial fibrillary acidic protein (GFAP) technique failed to stain the clear cells. Electron microscopy of the clear cells revealed them to be classical ependymoma cells with well developed intercellular junctions, microvilli and cilia. As no reporters in the past showed the evidence to clarify the nature of the clear cells, this case is considered a good example to support the viewpoint that the clear cells (oligodendroglioma-like cells) commonly observed in ependymomas are in reality ependymoma cells. It is stressed that the diagnosis of "mixed glioma" or "oligoependymoma" should be made with sufficient caution despite the recent advances of GFAP technique.     

Thallium-201 SPECT with triple-headed gamma camera for differential diagnosis of small pulmonary nodular lesion 20 mm in diameter or smaller

AIM: Although thallium-201 (201Tl) has been used for the diagnosis of lung cancer, its detectability of small pulmonary nodules is not known. The aim of this study was to evaluate the ability of 201Tl SPECT for the differential diagnosis for the pulmonary nodules 20 mm in diameter or smaller. METHODS: 201Tl SPECT was performed in 31 patients suspected of having primary lung cancer. The final diagnosis was established by histology, and tumor size was 10 to 20 mm in diameter. Twenty of 31 patients had malignant tumors, including squamous cell lung cancer (n = 5), adenocarcinoma (n = 14) and small cell lung cancer (n = 1), but in none of them was there mediastinal lymphnode involvement. RESULTS: Ten of 20 malignant tumors and 1 of 11 benign lesions demonstrated significant 201Tl uptake, so that the positive predictive value, negative predictive value, sensitivity and specificity for the diagnosis of lung cancer were 90.9% (10/11), 50.0% (10/20), 50.0% (10/20) and 90.9% (10/11), respectively. CONCLUSION: These data suggest that sensitivity for detecting lung cancer 20 mm or less in diameter may be insufficient, but even in patients with small pulmonary nodules, a positive 201Tl result is highly predictive of lung cancer.     

Methamphetamine induces cytosolic Ca2+ oscillations in the VTA dopamine neurons

Methamphetamine (METH) induces a schizophrenia-like psychosis. The dopamine neurons in the ventral tegmental area (VTA) have been implicated in schizophrenia and drug abuse. The present study investigated direct effects of METH on VTA dopamine neurons. We treated adult SD rats with METH (5 mg/kg/day) or saline for 7 days, isolated single VTA neurons, and monitored neuronal activities by measuring cytosolic Ca2+ concentration ([Ca2+]i) in immunocytochemically identified dopamine neurons. Acutely administered METH increased [Ca2+]i in dopamine neurons from METH- and saline-treated rats and induced oscillations of [Ca2+]i in dopamine neurons only from METH-treated rats. The METH-induced [Ca2+]i oscillations were inhibited by Ca(2+)-free conditions and Ca2+ channel blockers. The results indicate that acute METH increases [Ca2+]i in VTA dopamine neurons and that subchronic METH treatment sensitizes them to this drug, resulting in induction of [Ca2+]i oscillations. The activation of VTA dopamine neurons may be related to psycho-stimulant effects of METH.     

Surgical repair of extracardiac unruptured acquired Valsalva aneurysms

Two cases of extracardiac unruptured Valsalva aneurysms due to rare causes are reported. One patient had been suffering from hyper eosinophilic syndrome. Operative corrections consisted of total replacement of the aortic root. The other patient had an aneurysm of just noncoronary sinus of Valsalva and a dilated ascending aorta due to cystic mucoid degeneration. Replacement of the ascending aorta with patch closure for the aneurysm was successfully performed.     

Biocompatibility of silicone-coated oxygenator in cardiopulmonary bypass

BACKGROUND: This study was designed to analyze the biocompatibility of silicone-coated oxygenators using inflammatory response as the outcome measure, and to investigate whether the silicone-coated oxygenators perform better in terms of postoperative organ dysfunction. METHODS: The 32 patients who underwent cardiopulmonary bypass (CPB) were divided into 3 groups: group A (n = 10), heparin-coated circuit with silicone-coated oxygenator; group B (n = 11), whole heparin-coated circuit; and group C (n = 11), whole untreated circuit. The plasma concentrations of the proinflammatory markers, made of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8), terminal complement complex (C5b-9), and polymorphonuclear elastase (PMN-E), were measured by enzyme-linked immunosorbant assay. RESULTS: All proinflammatory markers were significantly lower in groups A and B than in group C, especially C5b-9 and PMN-E concentrations, which were significantly lower in group A than in group B. The alveolar-arterial oxygen gradients (A-aDO2) and the respiratory index were significantly better in group A than in group C. In group B, however, only the A-aDO2 was significantly better than in group C. The duration of intubation and the length of stay in the intensive care unit stay were significantly shorter in groups A and B than in group C. CONCLUSIONS: Silicone-coated oxygenators are biocompatible and prevent postoperative organ dysfunction.     

Extracorporeal lung support for advanced lung failure: a new era in thoracic surgery and translational science

For the patients with progressively decompensating acute or acute-on-chronic respiratory failure, the first-choice treatment remains as mechanical ventilation. Despite the consistent value of mechanical ventilation, the majority of lung specialists are aware of its limitations, in particular for the patients with advanced lung failure, and inherent drawbacks that augment disease progression. More recently, the concept of allowing the lungs to ‘rest and recover’ has been supported by quite a few clinical studies. The pressure and volume of gas delivered to the lungs are reduced compared with mechanical ventilation. Based on recent remarkable evidence and experiences using extracorporeal lung support (ECLS) before, during and after lung transplant, there is growing interest in and expectations for the use of ECLS beyond lung transplant to encompass the entire field of pulmonary medicine. The purpose of this review article is to provide an update on evolving ECLS technologies and their effectiveness and discuss the future of ECLS for advanced lung failure as a new subspecialty in cardiothoracic surgery.