Epoxyalkanoyls as novel ACE inhibitors

The epoxyalkanoyl derivatives were designed and synthesized as ACE inhibitors. Coupling of unsaturated carboxylic acids with amino acids and following epoxidation with dimethyldioxirane gave the epoxyalkanoyls with high yield. The inhibitory activity of synthesized compounds on angiotensin converting enzyme was IC₅₀ values of 0.06≈5.5 μM.     

Post-transplantation diabetes is better controlled after conversion from prednisone to deflazacort: a prospective trial in renal transplants

It is well known that long-term use of steroids plays a decisive role in the development of glucose intolerance and diabetes mellitus (DM). Deflazacort, an oxazoline derivative of prednisolone, has been introduced as a potential substitute for conventional steroids in order to ameliorate glucose intolerance. We initiated a randomized study of conversion from prednisone to deflazacort in kidney transplantation (Tx) recipients presenting with pre-Tx or post-Tx DM to ascertain whether or not the switch to deflazacort would ameliorate the diabetic state. Forty-two recipients in the conversion group were compared with 40 patients on prednisone (the control group) in a prospective manner. The dose reduction of insulin or oral blood glucose-lowering agents, the adequacy of glucose control, and the development of side effects were the criteria for evaluating outcome. In the conversion group, patients were switched to deflazacort at a dose ratio of 6 mg deflazacort to 5 mg prednisone. During the mean follow-up period of 13.2 months, neither graft dysfunction nor acute rejection developed in the conversion group. Improvement in blood glucose control in the conversion group was noted. When the conversion group was stratified into pre- or post-Tx DM, promising effects were clearly evident in the post-Tx DM patients. More than 50 % dose reduction of blood glucose-lowering agents was possible in 42.3 % of post-Tx DM patients. In conclusion, it was readily possible to control blood glucose better in post-Tx DM recipients without seriously affecting the immunosuppressive activity after conversion to deflazacort. Received: 20 August 1996 Received after revision: 25 November 1996 Accepted: 6 December 1996     

Compositional sugar analysis of antitumor polysaccharides by high performance liquid chromatography and gas chromatography

Carbohydrate analysis is important in studying structure and activity of complex polysaccharides. New analytical method was applied to get an information on the composition of polysaccharides showing antitumor activity. Monosaccharides were labeled with 7-amino-1,3-naphthalenedisulfonic acid (7-AGA) by reductive amination and separated by HPLC. Five kinds of polysaccharides fromBasidiomycetes were hydrolyzed and analyzed in combination with electrophoresis and HPLC. At the same time, alditol acetate derivatives were prepared and analyzed by gas chromatography. Two different techniques using different derivatization methods showed very similiar results. The monosaccharides fromCoriolus versicolor andLentinus eodes were mainly composed of D-glucose, while those fromGanoderma lucidium andCordyceps militaris were glucose and galactose.Phellinus linteus composed of glucose, galactose, mannose, arabinose and fucose. The HPLC method with fluorescence detector was very sensitive compared to other methods.     

Isolation of isoguanosine fromCroton tiglium and its antitumor activity

This paper describes the isolation of isoguanosine from Croton tiglium L. and its cytotoxic effect against several tumor cell lines in culture and newly reports that isoguanosine has an antitumor activity against implanted S-180 ascitic tumor mice. Isoguanosine is effective at the dose of 24 mg/kg/day x 5, with T/C value of 168%. Isoguanosine inhibits the growth of S-180 and Ehrlich solid tumor in mice at the optimal doses of 96 mg/kg/day x 12 and 48 mg/kg/day x 12, with 1-T/C values of 65% and 60%, respectively.     

Isolation and identification of chondroitin sulfates from the mud snail

Chondroitin sulfates were isolated from the mud snail. For the quantitative analysis of enzymatic digestion products of isolated chondroitin sulfates, strong anion exchange-high performance liquid chromatography (SAX-HPLC) was performed. By the action of chondroitinase ABC, three unsaturated disaccharides 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-D-galactose (ΔDi-OS), 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (ΔDi-6S) and 2-acetamide-2-deoxy-3-O-(β-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (ΔDi-4S) were produced from the mud snail chondroitin sulfates. The analysis showed that relative proportion of ΔDi-OS/ΔDi-6S/ΔDi-4S was 58.7/3.1/38.2. The immunomodulating activity of chondroitin sulfate was examined by cell proliferation assay and these results suggest that it might be a immunosuppressant.     

Perioperative specific management of blood volume loss in craniosynostosis surgery

Accurate assessment and replacement of blood loss and fluid–electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg^–1 h^–1 except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis. Received: 16 February 1998     

Outcome after traumatic frontal intracerebral haemorrhage: a comparison of unilateral and bilateral haematomas

Frontal intracerebral haemorrhage (ICH) is a common result of cranial trauma. Outcome differences between bilateral and unilateral frontal ICH are not well studied but would be valuable to predict prognosis in clinical practice. Two aims are proposed in this study: first to compare the risk of developing delayed ICH after bilateral or unilateral frontal ICH, and second to determine the variables helpful to predict outcome according to the Glasgow Outcome Scale (GOS). Between January 1993 and December 1997, 694 consecutive patients with traumatic ICH were admitted to the Chang Gung Medical Center within 24 h of the trauma. Patients with ICH in sites other than the frontal lobes were excluded. A total of 161 cases (mean age 46.3+/-20.3 years), including 57 bilateral (mean age 52.5+/-18.7 years) and 104 unilateral (mean age 42.9+/-20.5 years) traumatic frontal ICH were studied. Twenty-eight of 57 patients (49%) with bifrontal ICH versus 17 of 104 patients (16%) with unilateral frontal ICH had a further, delayed ICH. In 42 of 45 patients (93%) with delayed ICH, this occurred within 5 days of the initial trauma. Multivariate logistic regression was used to select significant predictors of outcome. We found that delayed ICH (p<0.001), age (p=0.004) and mechanism of injury (p=0.001) explained the worse outcome in patients with bifrontal ICH. The best-fitting logistic regression model included three variables: delayed ICH (p=0.011), initial GCS (p=0.023), and a sum score of clinical and radiological variables (p=0.003). Bifrontal ICH tended to occur in older patients after a fall and was associated with a higher risk of developing delayed ICH or brain stem compression compared to unilateral ICH damage. Using these three variables - delayed ICH, initial GCS, and the sum score - in a logistical regression model is useful to predict outcome in patients with traumatic frontal ICH and may aid patient management.