Hydrolysis of phenyl esters in cyclodextrin-polymer systems

The catalytic hydrolysis of phenyl esters in systems containing ß-cyclodextrin (ß-CD) and polyelectrolytes was investigated. Poly(methacrylic acid) was found to exhibit an inhibition effect on the hydrolysis, while poly(sodium styrenesulfonate) (NaPSS) shows a pronounced acceleration effect on the hydrolysis: the larger the molecular weight and the lower the degree of substitution, the greater is the acceleration effect. On the other hand, sodium ethylbenzenesulfonate and sodium dodecylbenzenesulfonate inhibit the reaction. The acceleration of the reaction in presence of NaPSS is attributed to the concentration of ß-CD and the substrate esters near to the chain of the macromolecule, through inclusion effects and hydrophobic interactions.     

Case of dermatomyositis complicated with massive pleural effusion that preceded the myopathy]

A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.     

Genetic alteration in carcinoid tumors of the lung.

Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis.     

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.     

Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).

CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.     

Angiotensin I-converting enzyme inhibitor improves reactive hyperemia in elderly hypertensives with arteriosclerosis obliterans.

Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. Blood flows of the forearms and legs were measured by strain-gauge plethysmography. The vasodilatory response to the release of compression of the forearms and thighs at 200 mmHg or 20 mmHg more than systolic blood pressure for 5 min and to sublingual administration of nitroglycerin (0.3 mg) was assessed. The maximum reactive hyperemic flow in 35 legs with arteriosclerosis obliterans was significantly (p < 0.001) decreased compared to the value in legs in the control hypertensive subjects. Moreover, maximum reactive hyperemic flow in the forearms of patients with arteriosclerosis obliterans was significantly (p = 0.002) decreased compared to that in the control subjects. Blood pressure was similarly decreased by treatment with temocapril or amlodipine. Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.     

NEW METHOD OF STENTING TREATMENT FOR MALIGNANT DUODENAL STENOSIS: USING DOUBLE‐BALLOON ENTEROSCOPY

Recently, a self‐expandable metallic stent has been recognized for treatment of malignant duodenal stenosis. But the complications by stenting are important problems even now. In the present study, we report our new method of duodenal stenting by using of double‐balloon enteroscopy considered safe and effective.     

Small extra-adrenal pheochromocytoma causing severe hypertension in an elderly patient.

We report the case of a 67-year-old woman with severe hypertension caused by an extra-adrenal pheochromocytoma. The tumor was detected by 131I metaiodobenzylguanidine scintigraphy and it was found to be small (2 cm ?) by enhanced CT. After the extirpation of the tumor, the blood pressure of the patient immediately normalized. It should be taken into account that a small extra-adrenal pheochromocytoma can be one of the causes of secondary hypertension in elderly patients. Since small extra-adrenal pheochromocytomas are difficult to detect, it is also important to perform suitable examinations to establish the diagnosis. Furthermore, we emphasize the importance of an accurate diagnosis in elderly patients with pheochromocytoma, for they often have less symptomatology and more severe cardiovascular complications due to refractory hypertension than younger patients.