Effect of Prophylactic Bronchodilator Treatment with Intravenous Colforsin Daropate, a Water-soluble Forskolin Derivative, on Airway Resistance after Tracheal Intubation

Background: After induction of anesthesia, lung resistance increases. The authors hypothesized that prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, before tracheal intubation would result in decreased lung resistance and increased lung compliance after tracheal intubation when compared with placebo medication.

Methods: Forty-six adult patients were randomized to placebo or colforsin daropate treatment. Patients in the control group received normal saline; patients in the colforsin group received 0.75 [mu]g [middle dot] kg-1 [middle dot] min-1 colforsin daropate intravenously until the study ended. Thirty minutes after the study began, the authors administered 5 mg/kg thiamylal and 5 [mu]g/kg fentanyl for induction of general anesthesia and 0.3 mg/kg vecuronium for muscle relaxation. A 15-mg [middle dot] kg-1 [middle dot] h-1 continuous infusion of thiamylal followed anesthetic induction. Four, 8, 12, and 16 min after tracheal intubation, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured.

Results: Patients in the colforsin group had significantly lower Rawm and Rawe and higher Cdyn after intubation than those in the control group. Differences in Rawm, Rawe, and Cdyn between the two groups persisted through the final measurement at 16 min. At 4 min after intubation, smokers had a higher Rawm and a lower Cdyn than nonsmokers in the control group. After treatment by intravenous colforsin daropate, Rawm, Rawe, and Cdyn values were similar for smokers and nonsmokers after tracheal intubation.     

Remodelling of cardiac gap junction connexin 43 and arrhythmogenesis

BACKGROUND: In cardiac muscle, the gap junction plays a pivotal role in electrical cell-to-cell coupling and impulse propagation between cells. The function of the gap junction depends on the regulation of connexin in the gap junction channel. A dysfunction of the gap junction is possibly caused by the downregulation of connexin or one of arrhythmogenic factors. The mechanisms of ventricular fibrillation, a lethal tachyarrhythmia, have been studied in relation to the remodelling of connexin. OBJECTIVES: To determine what type of connexin 43 (Cx43) remodelling contributes to the generation of ventricular fibrillation and what factors induce the modelling of Cx43. METHODS: Aconitine-induced ventricular fibrillation was induced in hearts isolated from adult rats. Alterations in the electrical activity, the phosphorylation of Cx43 and the expression of Cx43 were evaluated by both intracellular and extracellular recording of the action potentials, Western blotting and immunohistochemistry, respectively. Flutter activity after the application of aconitine shifted spontaneously to fibrillation, showing an electrical interaction between neighbouring cells in close proximity to one another. The facility of the shift from flutter to fibrillation was evaluated as a susceptibility of the heart to fibrillation in relation to gap junction function. The effects of phorbol 12-myristate 13-acetate, angiotensin II (AII) analogues, AII antagonists, the diabetic state, protein kinase A (PKA) activator, cyclic AMP analogues, d-sotalol (class III antiarrhythmic drug) and PKA inhibitors on the susceptibility of the heart to fibrillation were examined. RESULTS: Pathological hearts with heterogeneous expression of Cx43 at the gap junction, such as phorbol 12-myristate 13-acetate-and AII analogue-treated hearts, as well as diabetic hearts, showed a significantly higher susceptibility to fibrillation. On the other hand, hearts with augmentative expression of Cx43 at the gap junction, such as hearts pretreated with a PKA activator, a cyclic AMP analogue (8-bromo-cyclic AMP) or d-sotalol, showed a significantly lower susceptibility to fibrillation. At the beginning of fibrillation, an increase in the cardiac tissue AII level, an augmentation of the protein kinase C (PKC)-epsilon activity, the presence of PKC-mediated hyperphosphorylation, a suppression of the PKA-mediated phosphorylation of Cx43 and a reduction in the expression of Cx43 at the gap junction were observed. These alterations in Cx43 expression were also observed to increase as the fibrillation advanced. CONCLUSIONS: Augmentation of PKC-mediated phosphorylation and suppression of PKA-mediated phosphorylation induces the downward remodelling of Cx43. Such remodelling of Cx43 induces asynchronous electrical activities and makes the ventricular tissue susceptible to fibrillation. PKC is activated by AII. The fibrillation itself remodels Cx43, thereby causing a vicious cycle. As a result, PKC inhibitors, AII antagonists and PKA activators are considered to possibly have a protective effect against the initiation or advancement of ventricular fibrillation.     

Titania-Containing Bone Cement Shows Excellent Osteoconductivity in A Synovial Fluid Environment and Bone-Bonding Strength in Osteoporosis

Titania bone cement (TBC) reportedly has excellent in vivo bioactivity, yet its osteoconductivity in synovial fluid environments and bone-bonding ability in osteoporosis have not previously been investigated. We aimed to compare the osteoconductivity of two types of cement in a synovial fluid environment and determine their bone-bonding ability in osteoporosis. We implanted TBC and commercial polymethylmethacrylate bone cement (PBC) into rabbit femoral condyles and exposed them to synovial fluid pressure. Rabbits were then euthanized at 6, 12, and 26 weeks, and affinity indices were measured to evaluate osteoconductivity. We generated a rabbit model of osteoporosis through bilateral ovariectomy (OVX) and an 8-week treatment with methylprednisolone sodium succinate (PSL). Pre-hardened TBC and PBC were implanted into the femoral diaphysis of the rabbits in the sham control and OVX + PSL groups. Affinity indices were significantly higher for TBC than for PBC at 12 weeks (40.9 ± 16.8% versus 24.5 ± 9.02%) and 26 weeks (40.2 ± 12.7% versus 21.2 ± 14.2%). The interfacial shear strength was significantly higher for TBC than for PBC at 6 weeks (3.69 ± 1.89 N/mm² versus 1.71 ± 1.23 N/mm²) in the OVX + PSL group. These results indicate that TBC is a promising bioactive bone cement for prosthesis fixation in total knee arthroplasty, especially for osteoporosis patients.     

A case of Pneumocystis carinii pneumonia with pulmonary cysts and increased level of serum KL-6]

In August, 1999, a 46-year-old man with fever, cough, and dyspnea was admitted to a hospital. On the basis of the clinical and radiographic findings, bacterial pneumonia was suspected. Antibiotics were not effective, because of atypical lymphocytes in the peripheral blood and positive anti-human T-cell leukemia virus antibody, and he was transferred to our hospital. A chest radiograph and a CT scan revealed bilateral ground-glass opacities with huge multiple cysts. Intensive treatment of Pneumocystis carinii pneumonia associated with human T-cell leukemia was unsuccessful. Pneumocystis carinii was found in the bronchoalveolar lavage fluid. Human T-cell leukemia and Pneumocystis carinii pneumonia were diagnosed. In this case, numerous pulmonary cysts were progressing rapidly, the largest cyst being 8.7 cm in diameter, and the largest cyst in our experience either in clinical practice or in reading of the literature in Pneumocystis carinii pneumonia. The maximum serum KL-6 was markedly increased to 15,200 U/ml, which is the highest level reported for Pneumocystis carinii pneumonia.     

A case of MPO-ANCA positive vasculitis associated with diffuse alveolar hemorrhage and various cardiac conducting system abnormalities following propylthiouracil treatment]

A 50-year-old woman had been treated with propylthiouracil (PTU) for hyperthyroidism. She was admitted to our hospital because of hemosputum, and severe hypoxemia developed. The CT scan showed diffuse infiltration in both lung fields, bronchoalveolar lavage fluid revealed diffuse alveolar hemorrhage, and the level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was high; and therefore diffuse alveolar hemorrhage associated with MPO-ANCA positive vasculitis induced by PTU was diagnosed. Following corticosteroid therapy initiated after the termination of PTU, the pulmonary infiltration rapidly improved and the patient's MPO-ANCA level returned to normal. Recrudescence of diffuse alveolar hemorrhage occurred following a reduction in steroids, but no recurrence was found after cyclophosphamide therapy was combined with steroid therapy. During the course of therapy, various cardiac conducting system abnormalities which correlate with the course of steroid therapy were found, indicating that cardiac conducting system abnormalities may be associated with MPO-ANCA-positive vasculitis.     

A case of lymphangioleiomyomatosis with carcinomatous lymphangiosis]

A 66-year-old woman had a history of partial gastrectomy and resection of the residual stomach because of early gastric cancer and its recurrence. She had been suffering from dyspnea on effort, hemosputum, and cough since the age of 52 years. Chronic pulmonary emphysema and bronchial asthma were diagnosed when she was 59. On January 31, 1996, she was admitted to UOEH hospital with a complaint of increased dyspnea. In spite of treatment with oxygen, steroid, and inhaled anti-cholinergic agent, her condition deteriorated. Subsequently, she had DIC, respiratory failure and reticulolinear opacities were seen on chest radiographs, and she died 2 weeks after admission. At autopsy, the lung specimen revealed numerous cystic spaces surrounded by a proliferation of smooth muscle cells. Immunohistological examination showed these cells to be positive for HMB-45. Signet cells were seen in the lymphatics and vessels, and hemosiderin-laden macrophages were found in the alveolar spaces. This was a rare case of lymphangioleiomyomatosis with carcinomatous lymphangiosis.     

In vivo and in vitro evidence for the glycoxidation of low density lipoprotein in human atherosclerotic plaques

Although there have been suggestions that the glycation and oxidation of low density lipoprotein (LDL) might increase its atherogenic potential, little is known about the presence of glycoxidative LDL in human atherosclerotic lesions. We developed specific antibodies against different immunological epitopes of AGE structures, including N(epsilon)-(carboxymethyl)lysine-protein adduct (CML), a glycoxidation product, and structure(s) other than CML (nonCML), and a monoclonal antibody against oxidized phosphatidylcholine (oxPC), as an epitope of oxidized LDL. Immunohistochemical analysis demonstrated that the CML- and oxPC-epitopes were accumulated mainly in macrophage-derived foam cells in atherosclerotic lesions, including fatty streaks and atherosclerotic plaques. On the other hand, the nonCML-epitope and apolipoprotein B were localized mainly in extracellular matrices of atherosclerotic lesions. The CML- and oxPC-epitopes were characterized by a model antigen-generating system using the copper ion-induced peroxidation and/or glucose-induced glycation of LDL. The glycoxidation of LDL caused the formation of CML-epitope with increasing concentrations of copper ion and glucose. It was also formed to some extent in LDL incubated with high concentrations (500 mM) of glucose. However, no CML-epitope was observed in oxidized LDL induced by copper ion alone. On the other hand, the formation of oxPC-epitope in LDL was dependent on copper ion-induced peroxidation, but independent of glucose-induced glycation. The addition of chelators, ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, reduced the increase in electrophoretic mobility and TBARS caused by the peroxidation and glycoxidation of LDL, but had no effects on the formation of fructosamine caused by the glycation and glycoxidation of LDL. Chelators as well as aminoguanidine protected the formation of CML-epitope in glycated or glycoxidative LDL. Although the formation of oxPC-epitope was completely inhibited by the addition of chelators, it was partially protected by aminoguanidine. These in vitro results suggest that the glycoxidative modification of LDL may occur in the arterial intima, and may contribute to the development of human atherosclerotic lesions.     

Intravenous verapamil blunts hyperdynamic responses during electroconvulsive therapy without altering seizure activity

IMPLICATIONS: A dose of 0.1 mg/kg of verapamil, administered immediately before anesthesia, significantly reduces the increase in peak heart rate and mean arterial blood pressure after electroconvulsive therapy. Furthermore, the administration of verapamil does not reduce the duration of the seizure.     

Carboxymethyllysine in dermal tissues of diabetic and nondiabetic patients with chronic renal failure: relevance to glycoxidation damage

Carboxymethyllysine (CML) is currently recognized as a major advanced glycation end product and a marker for glycoxidation. Plasma CML levels are increased in patients with chronic renal failure (CRF). However, significance and mechanism of CML accumulation in these patients are poorly understood. The objective of the present study was to analyze CML in soluble and collagen-binding fractions of the dermis to investigate CML deposition and formation and collagen damage related to CML accumulation in patients with CRF. Skin samples (among them autopsy samples) were obtained from 33 subjects: 8 nondiabetic CRF patients, 7 diabetic predialysis patients with CRF (CRF-DM), 7 hemodialysis patients, and 11 control subjects without either CRF or DM. The dermal samples were extracted sequentially by phosphate-buffered normal saline, pepsin, and collagenase. The extracts were referred to as the soluble fraction and the proteinase-extracted fraction (including pepsin-extracted and collagenase-extracted fractions). Our ELISA assay for CML in dermal collagen from predialysis patients with CRF (CRF and CRF-DM groups) demonstrated that the levels of CML in both the soluble fraction (containing soluble CML which was mainly determined by serum clearance) and the structural collagen-binding proteinase-extracted fraction (in which high CML levels could be a strong indication of in situ formation) were increased and could not be completely reduced after hemodialysis in CRF-DM and CRF groups. These results suggest that accumulation of CML may be due to both a low serum clearance and/or increased in situ CML formation in CRF. CML contents in the proteinase extracted fraction inversely correlated with the susceptibility of collagen to extraction by proteinases (n = 33, r = -0.59, p < 0.001). Our results provide the first biochemical evidence that CML level is increased in both the soluble and collagen-binding fractions and that increased CML level resulted in increased fractions of proteinase-resistant collagen in dermal extracts of patients with CRF.