Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 2.

A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation.     

Surgical repair of discrete subaortic stenosis complicated with prosthetic valve endocarditis--a case report]

A 46-year-old man was referred to our hospital because of prosthetic valve regurgitation. Eight years previously he had undergone aortic valve replacement because of aortic regurgitation due to infective endocarditis. At reoperation, we found prosthetic valve endocarditis and discrete subaortic stenosis. The obstructing fibrous tissue was resected and the aortic valve was replaced. Because discrete subaortic stenosis is usually located just below the aortic valve, the aortic valve cusps are liable to become thickened by the jet through the discrete stenosis and thus are vulnerable to infective endocarditis. It is pointed out that care must be taken not to overlook discrete subaortic stenosis in the presence of other associated cardiac disorders.     

Dispersion of Pressure to the Head in Brain/NeuroSurgery

Skin and soft tissue defects are sometimes problematic especially when the defects large, contaminated, irradiated, or poor blood supplied. The human mesenchymal stem cells (hMSCs) are proliferated upon basic fibroblast growth factor (bFGF) stimuli in vitro and in vivo. In this experiment, the skin and soft tissue defects are investigated if the wounds are able to be reepithelialized or accelerated by hMSCs, bFGF and porcine‐derived bilayered skin template.
1.5 × 1.5 cm² nude rat skin and soft tissue defects including panniculus carnosus are excised and 1 × 10⁶ hMSCs and various doses of bFGF (1–100 μg) applied. Before and after normal reepithelialization, the tissues are tested for protein expressions by immunohistochemistry and Western blotting.
The wound sizes are significantly decreased at day 7 with hMSCs with 1, 10, or 100 μg bFGF compared to hMSCs‐alone or medium‐only. All the wounds healed by day 42. 42 Kda and 38 Kda human‐derived pancytokeratin expressions, which do not cross‐react with murine antigens, by Western blotting significantly augmented by 10 μg bFGF compared to hMSCs‐alone. The epidermal immunolocalizations such as integrin α3 and SKALP (Skin‐derived Anti Leukoproteinase) are greatly elevated in time and dose‐dependent manner. Human pan‐cytokeratin expressions are immunoreactive even at day 42.
These data suggest the skin and soft tissue wound healing is accelerated by hMSCs together with bFGF, partly by means of differentiation of hMSCs toward epidermal components.     

Effect of denopamine on residual left ventricular dysfunction after complete revascularization]

Denopamine (15 mg/day) was administered to 20 patients with residual left ventricular dysfunction after successful percutaneous transluminal coronary angioplasty (75% or more diameter stenosis). Echocardiography was performed before and 6 months after denopamine administration to analyze the left ventricular function. There were significant decreases in both end-diastolic and end-systolic dimensions from 58 +/- 8.3 to 54 +/- 8.4 mm (p = 0.001), and from 44 +/- 10.1 to 40 +/- 10.3 mm (p = 0.005)), respectively, while % fractional shortening remained nearly constant (from 25 +/- 8.3 to 27 +/- 9.6%). Thus, denopamine improved the left ventricular function by decreasing left ventricular size while maintaining wall contractility.     

A case report of deficiency in an inhibitor of calcium-dependent association of protein S with C4B-binding protein suggested by a modified crossed immunoelectrophoresis

We have experienced a coagulation factor VIII-deficient patient whose plasma has normal protein S (PS) activity and masses of free PS and its bound form in complex with C4b-binding protein (C4BP). Although the patient's plasma showed a normal ratio of free PS to PS-C4BP complex in the presence of 5 mM EDTA, the plasma gave an abnormally retarding major C4BP peak together with a major PS peak in the crossed immunoelectrophoresis (CIE) in the presence of 2 mM CaCl₂. It was revealed that the major peak was formed by a mixture of PS-C4BP complex and free form. The addition of normal human plasma (NHP) to the patient's plasma inhibited the retardation of the major PS-C4BP complex. These suggest that the patient's plasma lacks some component(s) to inhibit Ca²⁺-dependent association of PS with C4BP.     

Computerized tomography observation of a calcifying cystic odontogenic tumor with an odontoma: case report.

The calcifying cystic odontogenic tumor is a rare benign odontogenic lesion. This report documents a case of this lesion associated with odontoma arising from the anterior maxilla in a 14-year-old boy. The diagnosis was confirmed based on computerized tomography findings, which clearly depicted the internal structures obscured in conventional images.     

Pharmacological study on kefir--a fermented milk product in Caucasus. I. On antitumor activity (1)]

The antitumor activity of kefir (YK-1), a fermented milk product in Caucasus, was investigated. YK-1 at oral doses of 100 or 500 mg/kg inhibited the proliferation of solid tumor of Ehrlich ascites carcinoma transplanted subcutaneously in mice. YK-1 did not show an inhibitory effect on the ear swelling induced contact dermatitis caused by picryl chloride (PC-CD). However, YK-1 inhibited the immunosuppression in Ehrlich carcinoma-bearing mice and with the frozen and dried ascites of the tumor-bearing mice containing immunosuppressive substances (EC-sup) in PC-CD-induced mice. And also, YK-1 activated the immunosuppressive activity of spleen cells of mouse treated with EC-sup. These results suggest that YK-1 may have antitumor activity against Ehrlich carcinoma and activate the immunosuppression with it.     

Pulmonary hemodynamics and home oxygen therapy in patients with chronic respiratory failure]

The authors examined pulmonary hemodynamics with respect to underlying diseases, severity and type of chronic respiratory failure, and the incidence and effect of home oxygen therapy (HOT) in 155 patients with chronic lung diseases (old pulmonary tuberculosis (OTB) 45, chronic pulmonary emphysema (CPE) 54, chronic bronchitis (CBR) 42 and fibrosing lung disease (FLD) 14). They underwent right heart catheterization during a stable period, while breathing room air. The arterial PO2 ranged from 64.3 +/- 9.7 Torr (CBR) to 69.9 +/- 10.0 Torr (CPE), and the mean pulmonary arterial pressure ranged from 17.3 +/- 4.6 mmHg (CPE) to 20.6 +/- 5.4 mmHg (OTB). The incidence of pulmonary hypertension (PH, PA mean greater than or equal to 20 mmHg) was 53.3% in OTB, 40% in CBR, 35.7% in FLD, 23.8% in CPE, 69% in respiratory failure, 40% in quasi-respiratory failure, and 2.1% in non-respiratory failure. The percentage of patients who received HOT was 84.5% in respiratory failure and 54.1% in quasi-respiratory failure. Comparing Type I with Type II chronic respiratory failure, the incidence of PH was lower in the former than the latter (38.3% vs 80.6%), whereas HOT was applied to an equal percentage of patients (67.4%) in both groups. The effect of HOT was evaluated in 11 patients with chronic respiratory failure. The mean pulmonary arterial pressure was 22.7 +/- 4.7 mmHg before HOT, and decreased to 20.7 +/- 5.6 mmHg after 24.5 +/- 10.1 months of HOT. Although this difference was not significant statistically, this result suggests the desirable effect of HOT on pulmonary hemodynamics.     

Effect of natural panting frequency and cheek support on the plethysmographic determination of thoracic gas volume in patients with chronic obstructive pulmonary disease]

The authors studied the effects of natural panting frequency (NF) and the cheek support on the plethysmographic measurement of thoracic gas volume (TGV) in 8 normal subjects (non-smokers) and 46 patients with chronic obstructive pulmonary disease (COPD). The patients were divided into 2 groups according to the degree of airway obstruction (group I; specific airway conductance (SGaw) greater than 0.1 (n = 18), group II; SGaw less than 0.1 (n = 28)). TGV was measured with a pressure-type body plethysmograph (BP). NF was 2.00 +/- 0.43 Hz (mean +/- SD) in control subjects, 1.92 +/- 0.78 Hz in group I, and 1.39 +/- 0.59 Hz in group II, respectively, indicating lower NF in the patients with severe airway obstruction. In control subjects and group I, the differences between TGV at NF and at 0.5-1.0 Hz (TGVNF-TGV1.0) were -0.01 +/- 0.07L, and -0.06 +/- 0.16L, respectively, and cheek support did not alter the difference. On the other hand, in group II, the difference was slightly larger than other groups in spite of the lower NF, and this overestimation was abolished by cheek support (0.13 +/- 0.25L-----0.06 +/- 0.27L, p less than 0.05). These results suggest that, in patients with severe airway obstruction, TGVNF may be overestimated even if NF is relatively low. This overestimation may be mainly due to the extrathoracic airway compliance including the cheek.