Summary Thrombospondin-1 (TSP-1), a multifunctional matricellular glycoprotein, can activate transforming growth factor-β, an important profibrotic cytokine involved in various fibrotic diseases. ...TSP-1 is expressed in the lung tissue of animal models of bleomycin-induced pulmonary fibrosis and in patients with some interstitial lung diseases. The present study investigated the serum and bronchoalveolar lavage fluid (BALF) levels of TSP-1 in the idiopathic interstitial pneumonias (IIPs) and the relationship between these levels and other clinical factors. The TSP-1 in the serum and BALF were measured in 45 patients with pathologically diagnosed IIPs 22 with usual interstitial pneumonia (UIP), 23 patients with non-specific interstitial pneumonia (NSIP), as well as in 28 patients with pulmonary sarcoidosis and 15 healthy volunteers using a competitive enzyme immunoassay. The expression and localization of TSP-1 in the lungs were analyzed by immunohistochemical staining. The serum TSP-1 levels were significantly higher in patients with IIPs than in either those with sarcoidosis or the controls. These levels correlated well with those of an angiogenic cytokine vascular endothelial growth factor while correlating inversely with the %VC. Positive immunostaining of TSP-1 was predominantly observed in the regenerated alveolar epithelium and alveolar macrophages in the lung. Our findings suggest that the circulating TSP-1 levels are associated with the presence of interstitial pneumonia, but further studies are required before we can definitively conclude that TSP-1 plays a role in the pathogenesis of these diseases.
The physiological importance of muscarinic M
3 and M
2 receptors for bladder function was investigated in vivo using mice lacking M
3 or M
2 receptors and littermate WT controls.
Unanesthetized mice ...of each sex underwent continuous cystometry before and after administration of atropine (1 mg/kg
−1).
Male M
3 knockout (KO) mice had longer voiding intervals, and larger micturition volumes and bladder capacity than M
2 KO or WT males. There was no significant difference in any cystometric parameters between male M
2 KO and WT mice. In females M
3 KO and M
2 KO mice had longer voiding intervals and larger micturition volumes than WT animals. Atropine had marked inhibitory effects on voiding efficacy in WT and M
2 KO mice but it had no effect on any cystometric parameters in M
3 KO mice.
The current results confirm that M
3 receptor is the principal muscarinic receptor subtype responsible for bladder contraction and the role of M
2 receptors is of minor importance. Functional impairments found in M
3 KO mice were milder than those elicited by acute blockade of muscarinic receptors by atropine in WT mice, suggesting that noncholinergic mechanisms can compensate for a chronic loss of M
3 receptors.
A new therapeutic drug of cerebrovascular disorders, (E)-1-(3-fluoro-6, 11-dihydrodibenz b,eoxepin-11-yl)-4-(3-phenyl-2-propenyl) piperazine dimaleate (AJ-3941), is practically insoluble in water and ...unstable in acidic media. The solid dispersions with an enteric polymer, such as hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMC-AS), and Eudragit L100 (Eud), carboxymethylethylcellulose (CMEC), and a water soluble polymer, such as hydroxypropylcellulose (HPC-L), hydroxypropylmethylcellulose (HPMC), and polyvinylpyrrolidon (PVP) with enteric membrane were prepared. It was observed by a powder X-ray diffractometry and a differential scanning calorimetry that AJ-3941 was present in the amorphous form. These preparations showed good dissolution properties and good bioavailability after oral administrations to dogs. AJ-3941 in these preparations, using an enteric polymer was unstable in an aluminum package at 40°C and 75% relative humidity, but in these preparations the use of a water soluble polymer was stable in the aluminum package. These preparations may be a useful means to improve the bioavailability and stability of AJ-3941. Furthermore, we tried to prepare the solid dispersion by the spray-drying method without dichloromethane. The preparation using PVP had the same characteristics as the one prepared by using dichloromethane. It was therefore suggested that this method could be useful for the preparation of solid dispersions of AJ-3941 without the use of poisonous dichloromethane.
Oral 6-mercaptopurine (6-MP) is an integral component of maintenance chemotherapy for children with acute lymphoblastic leukemia (ALL). A clinical comparative study of 6-MP given at 175 mg/m2/day vs. ...250 mg/m2/day for 5 days was carried out. Ten patients on a CCLSG ALL 874 and 911 study received 6-MP at 175 mg/m2/day and 9 patients on a CCLSG ALL 941 study received 6-MP at 250 mg/m2/day. There was no significant difference in the value of WBC, Hb, and platelet counts between these two groups. The mean value of GPT level was significantly increased in a higher dosage group with no delay of 6-MP administration. The mean value of GPT peak level was decreased gradually following repeated cycles of 6-MP administration. Five days of 6-MP at 250 mg/m2/day was well tolerated and safe for the maintenance chemotherapy of childhood ALL.
The physiological importance of muscarinic M3 and M2 receptors for bladder function was investigated in vivo using mice lacking M3 or M2 receptors and littermate WT controls.
Unanesthetized mice of ...each sex underwent continuous cystometry before and after administration of atropine (1 mg/kg).
Male M3 knockout (KO) mice had longer voiding intervals, and larger micturition volumes and bladder capacity than M2 KO or WT males. There was no significant difference in any cystometric parameters between male M2 KO and WT mice. In females M3 KO and M2 KO mice had longer voiding intervals and larger micturition volumes than WT animals. Atropine had marked inhibitory effects on voiding efficacy in WT and M2 KO mice but it had no effect on any cystometric parameters in M3 KO mice.
The current results confirm that M3 receptor is the principal muscarinic receptor subtype responsible for bladder contraction and the role of M2 receptors is of minor importance. Functional impairments found in M3 KO mice were milder than those elicited by acute blockade of muscarinic receptors by atropine in WT mice, suggesting that noncholinergic mechanisms can compensate for a chronic loss of M3 receptors.
A 37-year-old woman admitted elsewhere for a high fever, dry cough, stridor, and dyspnea was found in chest radiography and computed tomography on admission to have a thickened bronchial wall with ...centrilobular nodules in both lower lobes and skipped consolidations in the lower and middle lobe of the right lung. She had been diagnosed with mycoplasmal pneumonia because of high Mycoplasma pneumoniae antibody titer, so clarithromycin (CAM) was administrated. She was referred to us due to hypoxia with obstructive impairment in the pulmonary function test. Ventilation/perfusion radioisotope in the lung scan indicated heterogeneous distribution without mismatch, suggesting bronchiolitis obliterans due to M. pneumoniae pneumonia, so steroids were started. Five weeks of steroid administration ameliorated clinical symptoms, hypoxia, and abnormal shadows, but obstructive impairment diod not disappear completely. Early administration of steroid with antibiotics is required for bronchiolitis obliterans caused by M. pneumoniae. We review cases of mycoplasmal bronchiolitis reported in Japan.
Background. Whole lung lavage is commonly performed for pulmonary alveolar proteinosis (PAP), however, segmental bronchoalveolar lavage is thought to be less useful. Patients and Method. We ...retrospectively evaluated the clinical features of 8 patients, who had been given a diagnosis of idiopathic PAP between 1995 and 2008. Results. All cases showed improvement during observation periods of from 1 to 13 years. One case improved naturally. Five cases, which had been treated with segmental bronchoalveolar lavage therapy, showed improvements in many aspects, such as symptoms, serum markers, and/or chest imaging findings. Conclusion. Our results suggest that not only whole lung lavage therapy, but also segmental bronchoalveolar lavage therapy may be a useful therapeutic method for idiopathic PAP, and it is important to determine the therapeutic approach, depending on the disease severity.
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