The effect of prednisolone on substance P-induced vascular permeability in mice

The effect of prednisolone on the substance P (SP)-induced vascular permeability increase in male ddY, WBB6 F₁–+/+ (control) and WBB6 F₁-W/W^v (no mast cell in skin or internal organs) mice was investigated. 1) SP (1–10 000 pg/site) increased vascular permeability in ddY, WBB6 F₁–+/+ and WBB6 F₁-W/W^v mice ears. 2) SP (100 pg/site)-induced vascular permeability was inhibited by prednisolone (10 mg/kg) administered intraperitoneally 3 to 12 hours prior to the elicitation of the reaction in ddY mice. When dexamethasone at a dose of 1 mg/kg was administered intraperitoneally 2 to 24 hours prior to the elicitation of the reaction, significant inhibition was observed. When prednisolone was administered intraperitoneally 8 hours prior to the elicitation of the reaction, the SP-induced capillary permeability increase in both ddY and WBB6 F₁-W/W^v mice was clearly inhibited by the drug at doses of 5 and 10 mg/kg. 3) Diphenhydramine (1 and 10 mg/kg) inhibited SP-induced vascular reaction in ddY mice but not in WBB6 F₁-W/W^v mice. 4) Atropine (10 mg/kg) inhibited SP-induced vascular reaction in both ddY and WBB6 F₁-W/W^v mice. But acetylcholine did not cause an increase of vascular permeability in ddY and WBB6 F₁-W/W^v mice ears. 5) Prednisolone (5 mg/kg) inhibited histamine- and serotonin-induced vascular permeability in ddY and WBB6 F₁-W/W^v mice ears. 6) Prednisolone (5 and 10 mg/kg) inhibited the SP-induced histamine release from ddY mice peritoneal mast cells. These results suggest that the vascular effect of SP is mediated by both mast cell dependent (release of histamine from mast cells) and mast cell independent mechanisms. Prednisolone inhibits the SP-induced vascular permeability mediated by both mechanisms in mice.     

Concentration quenching of photoluminescent Ru(bpy) dispersed in a polysiloxane film containing 2,2′-bipyridine pendant groups in dependence of molecular distribution

The photoluminescent Ru(bpy) complex was dispersed in a polysiloxane film containing 2,2′-bipyridine (bpy) pendant groups. The unusually long photoluminescence lifetime of the Ru(bpy) (1,94 μs at 25°C) and the blue-shifted photoluminescent wavelength suggest a rigid polymer matrix. The fluorescence yield becomes lower with higher probe concentration, indicating concentration quenching. According to the analysis based on Stern-Volmer plots, the quenching obeys a mechanism composed of both static and dynamic processes. A statistical intermolecular distance distribution between the probes was used to interpret the results in terms of static and dynamic quenching. It is shown that in the present system the dispersed complexes diffuse slightly during the excited state.     

SARCOIDOSIS OF THE SPINAL CORD

The authors report a female elderly patient with quadriplegia, hypesthesia below the neck, and rectourinary dysfunction, which were found at autopsy to have been caused by involvement of the lower cervical and upper thoracic segments of the spinal cord in systemic sarcoidosis. Sixty cases of spinal cord sarcoidosis reported in the literature are also reviewed. Most patients had clinical signs which mimicked those of a spinal cord tumor or meningomyelitis. Only in less than one-third of the cases had sarcoidosis been diagnosed before neurological symptoms occurred. Macroscopically, most intramedullary lesions formed a mass, whereas extramedullary lesions usually manifested as meningitis. Histologically, perivascular distribution of sarcoid granulomas was noted in our patient as well as in many cases reported in the literature. The clinical course of the patients with spinal sarcoidosis was usually poor when early diagnosis was not made. ACTA PATHOL. JPN. 35: 1007–1022, 1985.     

Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules.

To elucidate the mechanism(s) of myocardial reperfusion injury, we investigated the roles of cell adhesion molecules on both leukocytes and vascular endothelial cells in the reperfused myocardia. We found that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia and clarified, for the first time, that the expression of intercellular adhesion molecule-1 was enhanced on the capillary and venous endothelial cells from 8 to 96 hours after the start of reperfusion. Furthermore, pretreatment with individual monoclonal antibodies against cell adhesion molecules (CD11a, CD11bc, CD18, and intercellular adhesion molecule-1) reduced not only the infiltration of leukocytes but also the area of infarction in the reperfused hearts. These observations suggest that cell adhesion molecules play a critical role in the pathogenesis of myocardial reperfusion injury.     

Effects of growth hormone treatment on thyroid function in pediatric patients with Prader–Willi syndrome

It is unclear whether hypothyroidism is present in patients with Prader–Willi syndrome (PWS). This study aimed to clarify the state of the hypothalamic–pituitary–thyroid axis and the effects of growth hormone (GH) treatment on thyroid function in pediatric patients with PWS. We retrospectively evaluated thyroid function in 51 patients with PWS before GH treatment using a thyroid‐releasing hormone (TRH) stimulation test (29 males and 22 females; median age, 22 months). We also evaluated the effect of GH therapy on thyroid function by comparing serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels at baseline, 1 year, and 2 years after GH therapy. TSH, fT4, and fT3 levels were 2.28 μU/ml (interquartile range [IQR]; 1.19–3.61), 1.18 ng/dl (IQR; 1.02–1.24), and 4.02 pg/dl (IQR; 3.54–4.40) at baseline, respectively. In 49 of 51 patients, the TSH response to TRH administration showed a physiologically normal pattern; in two patients (4.0%), the pattern suggested hypothalamic hypothyroidism (delayed and prolonged TSH peak after TRH administration). TSH, fT4, and fT3 levels did not change significantly during 1 or 2 years after GH treatment. The TSH response to TRH showed a normal pattern in most patients, and thyroid function did not change significantly during the 2 years after initiating GH treatment.     

Reciprocal changes in gluconeogenic enzyme activity in liver and kidney by VMH lesion

The effects of bilateral lesions of the ventromedial hypothalamus (VMH) on daily rhythms of the activity of a gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), in the liver and kidney of rats were examined. PEPCK activity in the liver was considerably lowered by VMH lesions, but its rhythm remained similar to that of control liver. In contrast, PEPCK activity in the kidney was markedly elevated by the lesions. From these findings, it is suggested that the VMH is not the site of the master biological clock of the rhythm of PEPCK activity. Although these results do not exclude the possibility that hyperphagia and hyperinsulinemia associated with VMH lesions induce changes in the levels of PEPCK activities, they support the hypothesis that suppression of the sympathetic nervous system causes the changes in PEPCK activity through direct or indirect mechanisms. These findings also suggest that the reciprocal change in PEPCK activities in the liver and kidney after VMH lesions is related to complementary functions of the two organs in maintenance of homeostasis of blood glucose.     

Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila

Polyglutamine (polyQ) diseases are a growing class of inherited neurodegenerative diseases including Huntington's disease, which are caused by abnormal expansions of the polyQ stretch in each unrelated disease protein. The expanded polyQ stretch is thought to confer toxic properties on the disease proteins through alteration of their conformation leading to pathogenic protein-protein interactions including oligomerization and/or aggregation. Hypothesizing that molecules with selective binding affinity to the expanded polyQ stretch may interfere with the pathogenic properties, we previously identified Polyglutamine Binding Peptide 1 (QBP1) from combinatorial peptide phage display libraries. We show here that a tandem repeat of the inhibitor peptide QBP1, (QBP1)(2), significantly suppresses polyQ aggregation and polyQ-induced neurodegeneration in the compound eye of Drosophila polyQ disease models, which express the expanded polyQ protein under the eye specific promoter. Most importantly, (QBP1)(2) expression dramatically rescues premature death of flies expressing the expanded polyQ protein in the nervous system, resulting in the dramatic increase of the median life span from 5.5 to 52 days. These results suggest that QBP1 can prevent polyQ-induced neurodegeneration in vivo. We propose that QBP1 prevents polyQ oligomerization and/or aggregation either by altering the toxic conformation of the expanded polyQ stretch, or by simply competing with the expanded polyQ stretches for binding to other expanded polyQ proteins. The peptide inhibitor QBP1 is a promising candidate with great potential as a therapeutic molecule against the currently untreatable polyQ diseases.