Effects of Gadolinium Chloride on the Rat Lung Following Intratracheal Instillation

The metabolic behavior, clearance, and pulmonary effects ofgadolinium (Gd), one of the rare earth elements, were investigatedafter single intratracheal instillation of gadolinium chloride(GdCl₃) in male Wistar rats. There was a dose-related increasein Gd content of lung tissue. Gd content in the supernatantof bronchoalveolar lavage fluid (BALF) did not exceed 5 µgGd/ BALF even at a dose of 100 µg Gd/rat. Gd in the lungtissue decreased very slowly with a biological half-life of136 days at a dose of 50 µg Gd/rat. On the other hand,Gd content in the super natant of BALF was not detectable after31 days. These results suggest that intratracheally instilledGd can be retained in epithelial lining fluid only to a limitedextent as soluble forms and is deposited in the lung tissueprobably in insoluble forms which are metabolized very slowly.Calcium (Ca) content in BALF increased more rapidly than othertoxicological indices such as lactate dehydrogenase activity,protein concentration, and inflammatory cell counts. In thelung tissue, levels of Ca in Gd-instilled groups did not differfrom the control value. Although these data suggest that theorigin of Ca may be blood plasma, biological and/or toxicologicalsignificance of increased Ca is not known. The number of neutrophilsreached the maximum at 12 hr after instillation, indicatingthat Gd has the potency to cause acute lung toxicity. Summarizingthe observation, Gd instilled intratracheally into rats wasdeposited in the lung tissue in nonsoluble forms with an extremelylong half-life, while the metal caused a rapid and selectiveinfiltration of serum Ca before acute lung toxicity.     

Long-term effect of α-glucosidase inhibitor on late dumping syndrome

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. α-Glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of α-glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long-term effect of α-glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of α-glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered α-glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the α-glucosidase inhibitor treatment. All patients had late dumping-related symptoms, such as weakness, palpitation and dizziness before the induction of α-glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping-related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the α-glucosidase inhibitor treatment. These data suggest a long-term therapeutic efficacy of α-glucosidase inhibitor for late dumping patients.     

Heterogeneity of Epstein-Barr virus infection in angioimmunoblastic lymphadenopathy type T-cell lymphoma

To investigate the relationship of Epstein-Barr virus (EBV) and angioimmunoblastic lymphadenopathy with dysproteinemia, we performed DNA analysis using the polymerase chain reaction (PCR), Southern blot, in situ hybridization, and immunohistochemical analysis of lymph nodes in five patients who were followed up and biopsied more than once. In the course of the disease, nodal architecture diminished, cellular atypia worsened, and clear cells increased in number. In the DNA analysis of the receptor genes, the clonal population increased in number. EBV nucleic acid sequences were found by either PCR or in situ hybridization in all examined nodes. The number of EBV-positive cells varied widely among the cases and throughout the course of the disease in the same patients. The analysis of EBV terminal repeats or lymphocyte-determined membrane antigen genes showed polyclonal populations of EB-infected cells. EBV-positive cells possessed intermediate- to large-sized nuclei, and the cells with large nuclei, especially, expressed latent membrane protein of EBV. These large cells varied in number among the cases. Double-labelling immunohistochemistry/in situ hybridization studies demonstrated that most of the EBV-positive cells expressed B-cell antigen (CD20). The presence of EBV seems to be associated with the selective defects of the immune system, rather than with the direct pathogenesis of angioimmunoblastic lymphadenopathy.     

Influence of Twinline,an Elemental Diet,on the Generation of Nitric Oxide and Reactive-oxygen Intermediates from Mouse Peritoneal Macrophages and Polymorphonuclear Leukocytes

The influence of Twinline (SNN-6010), an elemental diet containing medium-chain triglycerides, on the generation of nitric oxide (NO) and superoxide (O₂^?) has been examined in mouse peritoneal macrophages and polymorphonuclear leukocytes (PMN). When PMN and peritoneal macrophages obtained from untreated mice were cultured in medium containing 0·1% and 1% (v/v) Twinline for 48h and stimulated with phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine, their chemiluminescence and O₂^? generation were strongly suppressed, as was NO generation from peritoneal macrophages. PMN and peritoneal macrophages obtained from mice fed Twinline for 30 days generated much smaller amounts of O₂^? and NO compared with PMN and peritoneal macrophages from control mice. In conjunction with this suppressed NO generation, inducible NO synthase and its mRNA expression in peritoneal macrophages were suppressed by Twinline both in-vivo and ex-vivo. Although phagocytosis of PMN and peritoneal macrophages was not suppressed by Twinline; their candida-killing activity was markedly suppressed. These results indicate that Twinline suppresses the host-defence function of PMN and peritoneal macrophages by down-regulating their generation of reactive-oxygen intermediates and NO.     

Concentration gradient of oxalate from cortex to papilla in rat kidney

BACKGROUND: The kidney eliminates the major fraction of plasma oxalate. It is well known that oxalate is freely filtered by glomeruli and secreted by the proximal tubules. However, the renal handling of oxalate in distal nephrons, which is considered as playing an important role in stone formation, remains obscure. METHODS: At 15-180 min after intravenous injection of 14C-oxalate to rats, the intrarenal localization of radioactivity was quantitatively measured by the radioluminographic method using a bioimaging analyzer. Tissue radioactivity was compared with plasma, and urinary radioactivities were measured by a liquid scintillation counter. The control study was conducted with 14C-inulin. RESULTS: The radioactivity of 14C-oxalate in the papilla was 10 times greater than in the cortex and eight times greater than in the medulla 180 min after injection when almost no radioactivity was present in the urine. In contrast, the radioactivity of 14C-inulin was nine times less in the papilla than in the cortex at the same time. CONCLUSION: Oxalate remains in the renal papilla for an extended period. This accumulation of oxalate may be attributed to calcium oxalate crystal fixation along the deep nephron which is considered to be the first step of stone formation.     

Turcot's Syndrome: Report of an Adult Case

Abstract: This study reports on a non familial case of Turcot's syndrome in a 40-year-old man with an astrocytoma (grade II) in the pineal region, colonic polyposis and four adenomas in the gastric antrum. In previous reports, most patients with Turcot's syndrome revealed symptoms until early in the fourth decade of their lives. In most cases, a complete resection of the brain tumors were impossible, and/or colonic polyps had already developed malignant transformation at the time of diagnosis, which led to a poor prognosis. In our case, however, the brain tumor was completely resected and a detailed histological analysis of the polyps in the colectomy specimen revealed no malignant transformation. A good prognosis, therefore, could be expected with a careful follow-up. In this paper, we compare our case with 50 previous cases of Turcot's syndrome histopathologically confirmed and reported in the literature, with special reference to their gastrointestinal manifestations.     

Effect of atracurium, vecuronium, pancuronium and tubocurarine on renal sympathetic nerve activity in baroreceptor denervated dogs

The mechanism of arterial hypotension induced by non-depolarizingneuromuscular blocking agents may be multifactorial and differbetween drugs. The purpose of this study was to evaluate theeffect of high-dose atracurium and equivalent doses of othernon-depolarizing neuromuscular blocking agents on haemodynamicstate and sympathetic nervous activity. In studies on 24 mongreldogs anaesthetized with alpha-chloralose, the left kidney wasexposed retroperitoneally and renal sympathetic nerve activitywas recorded continuously after bilateral sino-aortic denervationand cervical vagi section. The dogs were allocated to four groups;atracurium 1.5 mg kg^–1, tubocurarine 0.3 mg kg^–1pancuronium 0.3 mg kg^–1 or vecuronium 0.3 mg kg^–1was administered to six dogs in each group. Histamine 1 µgkg^–1 was given to two dogs in each group, 1 h before administrationof neuromuscular blocking agents. We observed that atracuriumand tubocurarine significantly decreased arterial pressure,heart rate and renal sympathetic nerve activity (P <0.05),but pancuronium and vecuronium did not. Histamine-induced arterialhypotension but did not affect heart rate or renal sympatheticnerve activity. As both arterial and cardiopulmonary baroreflexpathways were inactivated in these animals, we conclude thatatracurium decreased arterial pressure by suppressing efferentsympathetic nerve activity in a manner similar to that of tubocurarine.