Lecithinized superoxide dismutase treatment improves steroid-refractory interstitial pneumonia

Pulmonary fibrosis associated with amyopathic dermatomyositis is known to have a generally aggressive course and is ultimately fatal. We report the case of a 50-year-old patient with amyopathic dermatomyositis, who developed progressive interstitial pneumonia that was unresponsive to corticosteroids and multiple immunosuppressive agents, including cyclosporine and tacrolimus hydrate. Five courses of lecithinized superoxide dismutase were administered without adverse effects. Improvements in physiological parameters, such as pulmonary function and exercise tolerance, as well as the serum Krebs von den Lungen 6 level, were observed. This is the first report of a case of steroid-refractory interstitial pneumonia treated with lecithinized superoxide dismutase.     

Usefulness of computed tomography in the diagnosis of an overdose

Computed tomography (CT) is superior for the detection of substances with low radiolucency in comparison with abdominal roentgenograms. In the present study, medical chart review was retrospectively performed for patients who were admitted and underwent plain CT including the stomach on arrival to investigate whether CT is useful for diagnosing overdose (OD). The subjects were divided into patients with OD who did not undergo gastric lavage (OD group) and those without OD (Control group). The presence of a radiopaque area (Hounsfield number over 100 on a range of interest of 3 mm2) in the stomach on CT was defined as a positive finding. The average Glasgow Coma Scale in the OD group (n=11) was significantly lower than that in the Control group (n=137). Positive findings on CT were found more frequently in the OD group than in the Control group (100 vs. 19.7%, p＜0.0001). Based on the finding of a high-density deposition in the bottom of the stomach, the CT predicted OD with 98.5% specificity. Accordingly, CT findings of a high-density deposition in the stomach of a patient with a diminished consciousness may suggest the presence of a recent overdose.     

Comparisons of insulin related parameters in commercial-type chicks: Evidence for insulin resistance in broiler chicks

The aim of this study is to elucidate whether insulin acts differentially within the central nervous system (CNS) of two types of commercial chicks to control ingestive behavior. Male layer and broiler chicks (4-day-old) were intracerebroventricularly (ICV) injected with saline or insulin under satiated and starved conditions. Feed intake was measured at 30, 60 and 120 min after treatment. Secondly, blood and hypothalamus were collected from both chick types under ad libitum feeding and fasting for 24 h. Plasma insulin concentration was measured by time-resolved fluoro-immunoassay. Hypothalamic insulin receptor mRNA expression levels were measured by quantitative RT-PCR. The ICV injection of insulin significantly inhibited feed consumption in layer chicks when compared with saline (P < 0.05), but not broiler chicks (P > 0.1). Plasma insulin concentration of both chick types significantly decreased following 24 h of fasting, while insulin concentrations in the broiler chicks were significantly higher compared to the layers fed under ad libitum conditions. Hypothalamic insulin receptor mRNA expression levels were significantly lower (P < 0.05) in broiler chicks than in layer ones under ad libitum feeding. Feed deprivation significantly decreased insulin receptor mRNA levels in layer chicks (P < 0.01), but not in broiler chicks (P > 0.1). Moreover, plasma insulin concentrations correlated negatively with hypothalamic insulin receptor protein expression in the two types of chicks fed ad libitum (P < 0.05). These results suggest that insulin resistance exists in the CNS of broiler chicks, possibly due to persistent hyperinsulinemia, which results in a down-regulation of CNS insulin receptor expression compared to that in layer chicks.     

Antibody to receptor activator of NF-κB ligand ameliorates T cell-mediated periodontal bone resorption

Activated T and B lymphocytes in periodontal disease lesions express receptor activator of NF-κB ligand (RANKL), which induces osteoclastic bone resorption. The objective of this study was to evaluate the effects of anti-RANKL antibody on periodontal bone resorption in vitro and in vivo. Aggregatibacter actinomycetemcomitans outer membrane protein 29 (Omp29) and A. actinomycetemcomitans lipopolysaccharide (LPS) were injected into 3 palatal gingival sites, and Omp29-specific T clone cells were transferred into the tail veins of rats. Rabbit anti-RANKL IgG antibody or F(ab′)₂ antibody fragments thereof were injected into the palatal sites in each rat (days −1, 1, and 3). Anti-RANKL IgG antibody significantly inhibited soluble RANKL (sRANKL)-induced osteoclastogenesis in vitro, in a dose-dependent manner, but also gave rise to a rat antibody response to rabbit IgG in vivo, with no significant inhibition of periodontal bone resorption detected. Lower doses (1.5 and 0.15 μg/3 sites) of F(ab′)₂ antibody were not immunogenic in the context of the experimental model. Periodontal bone resorption was inhibited significantly by injection of the anti-RANKL F(ab′)₂ antibody into gingivae. The sRANKL concentrations for the antibody-treated groups were decreased significantly compared to those for the untreated group. Osteoclasts on the alveolar bone surface were also diminished significantly after antibody injection. Gingival sRANKL concentration and bone loss showed a significant correlation with one another in animals receiving anti-RANKL F(ab′)₂ antibody. These results suggest that antibody to RANKL can inhibit A. actinomycetemcomitans-specific T cell-induced periodontal bone resorption by blockade and reduction of tissue sRANKL, providing an immunological approach to ameliorate immune cell-mediated periodontal bone resorption.Host immune responses play a key role in periodontal diseases (11, 29). Compelling evidence now indicates that periodontitis is not a conventional infectious disease but is an inflammatory disease triggered by the host immune response to the microorganism(s) associated with periodontal biofilm (22, 26, 28, 30, 34). Recently, a close relationship between the immune and skeletal systems within the interdisciplinary field called “osteoimmunology” has attracted much attention due to accumulating evidence that bone destruction can be caused by an inflammatory activation of the immune system in rheumatoid arthritis and in periodontitis (31). Many studies have demonstrated that host immune responses play a key role in stimulating osteoclastogenesis and in promoting bone resorption in periodontal disease (9, 27). T and B lymphocytes found in periodontal lesions express abundant receptor activator of NF-κB ligand (RANKL). Stimulation of RANKL expression by these lymphocytes is inhibited (in vitro and in vivo) by a decoy receptor for RANKL, osteoprotegerin (OPG), which suggests that bone resorption is RANKL dependent. These findings provide a fundamentally new understanding of the mechanism of periodontal disease and support the hypothesis that tissue destruction in periodontal disease can be ameliorated by inhibition of RANKL activity in immune effector cells. If this hypothesis is correct, then therapeutic strategies based on immune modulation may be effective in preventing bone resorption and tooth loss in people with periodontitis. The hypothesis has been tested in osteoporotic individuals with immunological blockade of RANKL-RANK interaction by use of antibody to RANKL. Such an antibody (denosumab; formerly known as AMG 162) has been shown to effectively increase bone mineral density in postmenopausal women and to decrease bone resorption (20, 21). Preliminary data from clinical trials suggest that denosumab might be an effective treatment for osteoporosis. However, much remains to be determined before such a strategy (capable of modulating the RANKL-RANK interaction) could be administered safely for the management of bone-resorptive diseases other than osteoporosis.In this study, anti-RANKL antibody treatments were assessed in an in vitro osteoclastogenesis model and in a validated rat model of periodontal disease (12, 31). We evaluated a method of reducing periodontal bone resorption by direct inhibition of RANKL with anti-RANKL neutralizing antibody. This study provides an understanding of the mechanisms by which the host immune response mediates bone resorption and may lead to future clinical translational studies of strategies for preventing tooth loss in periodontitis.     

Subcutaneous Peroneus Longus Tendon Rupture Associated with OS Peroneum Fracture

We report a rare case of subcutaneous peroneus longus tendon rupture associated with os peroneum fracture. Three dimensional computed tomographic scan was useful to understand this disorder. We treated the patient with excision of fractured os peroneum and tenodesis of the proximal stump of the ruptured peroneus longus tendon to the lateral aspect of the calcaneus.

Key points

• In order to understand a rare case of subcutaneous peroneus longus tendon rupture associated with os peroneum fracture, three dimensional computed tomographic scan was useful.
• The patient was treated with excision of fractured os peroneum and tenodesis of the proximal stump of the ruptured peroneus longus tendon to the lateral aspect of the calcaneus.

Key words: Os peroneum, fracture, rupture, peroneus longus tendon.     

Ghrelin differentially modulates glucose-induced insulin secretion according to feeding status in sheep

The present study was conducted to investigate roles of ghrelin in glucose-induced insulin secretion in fasting- and meal-fed state in sheep. Castrated Suffolk rams were fed a maintenance diet of alfalfa hay cubes once a day. Hyperglycemic clamp (HGC) was carried out to examine glucose-induced insulin response from 48 to 53 h (fasting state) and from 3 to 8 h (meal-fed state) after feeding in Experiment 1 and 2 respectively. Total dose of 70 nmol/kg body weight of D-Lys3-GHRP6, a GH secretagogue receptor 1a (GHS-R1a) antagonist, was intravenously administered at 0, 60, and 120 min after the commencement of HGC. In the fasting state, the ghrelin antagonist significantly (P < 0.01) enhanced glucose-induced insulin secretion. In the meal-fed state, i.v. administration of synthetic ovine ghrelin (0.04 microg/kg body weight per min during HGC) significantly (P < 0.05) enhanced glucose-induced insulin secretion. d-Lys3-GHRP6 treatment suppressed ghrelin-induced enhancement of the insulin secretion. In conclusion, ghrelin has an inhibitory and stimulatory role in glucose-induced insulin secretion via GHS-R1a in fasting- and meal-fed state respectively.     

Coronary malperfusion due to acute type A aortic dissection; surgical strategy and results

Coronary malperfusion due to acute type A aortic dissection (DAA) is a lethal complication. It is especially difficult to rescue the patients with left coronary malperfusion because of acute global myocardial infarction (AMI), even with successful surgical treatments, including the replacement of the ascending aorta and coronary artery bypass grafting (CABG). We review our experience and illustrate our approach to these critically ill patients. In addition, we classify the mechanism of malperfusion into 4 types based upon perioperative findings and discuss surgical management indivisually. From January 1990 to April 2005, a total of 260 patients were operated for DAA in our institution. Twenty (7.7%) patients, 11 men and 9 women were suffering from coronary malperfusion due to DAA. The mean age was 55 (range 28-72) years. The right coronary artery was involved in 9 patients, and the left in 11. All procedures such as graft replacement and CABG were done on an emergent or urgent basis. Hospital mortality rate of right coronary malperfusion was 22% (2/9 patients), and that related to left coronary malperfusion was 5/11 (45%). Assisting device was required in 9 cases, veno-arterial bypass (VAB) in 6 cases, left ventricular assist system (LVAS) in 1, left heart bypass (LHB) in 1, LHB+right heart bypass (RHB) in 1. We lost all patients using VAB. Only 3 patients supported with strong assist device survived. Aggressive myocardial resuscitation and early operation are the key factors in the management of these critically ill patients. But once severe myocardial infarction occurs, V-A bypass (percutaneous cardiopulmonary support) is useless in treating patients with DAA who develop severe heart failure. We recommend to implant stronger assist device including LVAS immediately before exacerbation of multiple organ failure. In conclusion, surgical management is not easy for emergency patients with DAA in association with myocardial ischemia. However, reasonable surgical results can be obtained with supplemental CABG and strong mechanical support of the left ventricle.