Synthesis and vasorelaxant activity of 4-(cyclic amido)-2H-naphtho[1,2-b]pyrans

A series of 4-(cyclic amido)-2H-naphtho[1,2-b]pyrans related to cromakalim (1) has been prepared and their vasorelaxant activities on isolated rat thoracic aorta precontracted with phenylephrine have been evaluated. The relaxant mechanism of 3a was found not through ATP-sensitive K(+) channels as cromakalim, but through opening voltage-sensitive K(+) channels.     

Comparison of three-dimensional anthropometric body surface scanning to waist-hip ratio and body mass index in correlation with metabolic risk factors

In this study, we used a three-dimensional (3D) body scanner to evaluate subjects with central obesity. These measurements were correlated with blood pressure, blood glucose, lipid, and uric acid levels. We randomly selected 1,204 subjects who visited the Department of Health Management at Chang Gung Medical Center in Linkou. The health index (HI) was calculated as HI = (body weight x 2 x waist profile area)/[body height(2) x (breast profile area + hip profile area)]. Among the 1,204 subjects, body mass index (BMI) equal to or greater than 30 kg/m(2) was found in 8.3% of the subjects. Pearson correlation coefficient studies revealed that HI was a better index for correlating metabolic parameters than BMI and waist-to-hips girth ratio. Of the 1,204 subjects, 9.5% (114) had diabetes mellitus, according to American Diabetes Association criteria. The percentages of men and women with total cholesterol greater than or equal to 245 mg/dL were almost the same (11.0% vs. 11.1%). Elevated low-density lipoprotein (> or =130 mg/dL) was found in 36.9% (444) of subjects. In conclusion, HI as determined by 3D scanning, is another method to predict these metabolic abnormalities. Further prospective long-term follow-up study is needed to determine the relationships of 3D body scanning data and HI to blood pressure, blood glucose, lipid, and uric acid levels.     

The concentration of serum transforming growth factor beta-1 (TGF-beta1) is decreased in cervical carcinoma patients

Transforming growth factor beta-1 (TGF-beta1) is a multifunctional growth factor and known to inhibit the proliferation of epithelial cell. The relationship between serum TGF-beta1 level and the presence of cervical cancer was investigated in this study. The patients with cervical squamous cell carcinoma (SCC) had significantly lower level of serum TGF-beta1 (39.14 +/- 9.03 ng/mL; mean +/- SD) than those with myoma (49.17 +/- 9.38 ng/mL) and normal subjects (49.13 +/- 8.81 ng/mL), (p < 0.007 and p < 0.001, respectively). TGF-beta1 level was also lower in the patients with cervical intraepithelial neoplasia (CIN3) (42.07 +/- 9.38 ng/mL) than in normal controls (49.13 +/- 8.81 ng/mL) (p < 0.04). It suggested that diminution of the production of TGF-beta1 has close association with the neoplastic transformation of cervical epithelium.     

A new device for measuring density of jaw bones

OBJECTIVES: The purpose of this project was to develop a lightweight, simple device to evaluate alveolar process bone density using normal intraoral and extraoral imaging procedures. METHODS: A simple lightweight device was constructed using barium sulfate as the major radiopaque component. The 5 x 32 x 12 mm(3) resin block has eight segments with known densities ranging from 1.304 (g/cm(3)) to 1.982 (g/cm(3)). The device was integrated into an XCP unit for standard intraoral radiographs and placed between the jaws for computer aided tomographic imaging. The relationship between the device segment densities and the optical densities of the exposed film was plotted. RESULTS: A linear inverse relationship was found between the device segment densities and optical densities when segment densities were between 1.304 (g/cm(3)) to 1.882 (g/cm(3)). However, the relationship was non-linear for segment densities above 1.882 (g/cm(3)). CONCLUSIONS: Normal human bone density is 1.85 (g/cm(3)), and this densitometer is useful for determination of material densities from 1.304 (g/cm(3)) to 1.882 (g/cm(3)). The device may be useful for precise bone density assessment.     

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.      

Langerhans' cell histiocytosis with thyroid involvement masquerading as thyroid carcinoma

A 28-year-old woman was admitted to our Hospital with a chief complaint of progressive gingival swelling and loosening of teeth over about a year. According to past history, she had received total thyroidectomy 2 years previously due to thyromegaly. The thyroidectomy specimen was at first interpreted as 'poorly differentiated carcinoma of the thyroid'. One year ago, she began to be aware of gingival swelling and loosening of teeth. A gum biopsy was taken and the pathologic features were similar to her 'thyroid carcinoma'. Subsequent investigations, including immunohistochemical stain, showed the gum was heavily infiltrated with histiocyte-like Langerhans' cells which were positive for S-100 protein. Ultrastructural examination of the cells under electron microscope revealed many typical intra-cytoplasmic Birbeck granules. Langerhans' cell histiocytosis was diagnosed. Langerhans' cell histiocytosis with thyroid involvement is extremely rare and may run a relatively indolent course. Even on a retrospective examination, it may easily be confused with poorly differentiated carcinoma of the thyroid. We suspect that this error may have been made on other occasions and that the occurrence of this condition may be underreported.      

Enalapril in RAPIDISC (wafer formulation): pharmacokinetic evaluation of a novel, convenient formulation

BACKGROUND: Enalapril in RAPIDISC* (wafer), a new easy-to-administer formulation of enalapril, may improve the convenience of enalapril therapy, thereby helping patients adhere to antihypertensive treatment. SUBJECTS AND METHODS: To determine whether 20 mg enalapril wafer is bioequivalent to the conventional 20 mg enalapril tablet, an open-label, two-period crossover study was performed in 16 healthy male volunteers. Cumulative urinary recovery of free enalaprilat (active metabolite of enalapril) and the serum maximum concentration of free enalaprilat (Cmax) were the primary pharmacokinetic parameters used to determine bioequivalence in this study. Bioequivalence was defined as the geometric mean ratio (wafer: tablet) falling within the equivalence limits of 0.80 to 1.25 for both parameters. RESULTS: Cumulative urinary recovery of free enalaprilat (0 - 72 hours) was similar between the wafer and conventional tablet formulations (arithmetic mean 5.13 vs. 5.03 mg, about 36% of dose). The geometric mean ratio of the urinary recovery of free enalaprilat (wafer: tablet) was 1.03 (90% CI: 0.93, 1.15). Cmax of serum enalaprilat was also similar between the wafer and conventional tablet formulations (arithmetic mean 85.7 vs. 76.3 ng/ml). The geometric mean Cmax ratio (wafer: tablet) was 1. 10 (90% CI: 1.00, 1.22). Both enalapril formulations were well tolerated. CONCLUSION: This study demonstrates that 20 mg enalapril in RAPIDISC is bioequivalent to 20 mg enalapril conventional tablet.     

EBV DNA polymerase inhibition of tannins from Eugenia uniflora

Nasopharyngeal carcinoma (NPC) is one of the high population malignant tumors among Chinese in southern China and southeast Asia. Epstein-Barr virus (EBV) is a human B lymphotropic herpes virus which is known to be closely associated with NPC. EBV DNA polymerase is a key enzyme during EBV replication and is measured by its radioactivity. The addition of phorbol 12-myristate 13-acetate to Raji cell cultures led to a large increase in EBV DNA polymerase, which was purified by sequential DEAE-cellulose, phosphocellulose and DNA-cellulose column chromatography. Four tannins were isolated from the active fractions of Eugenia uniflora L., which were tested for the inhibition of EBV DNA polymerase. The results showed the 50% inhibitory concentration (IC(50)) values of gallocatechin, oenothein B, eugeniflorins D(1) and D(2) were 26.5 62.3, 3.0 and 3.5 microM, respectively. Furthermore, when compared with the positive control (phosphonoacetic acid), an inhibitor of EBV replication, the IC(50) value was 16.4 microM. In view of the results, eugeniflorins D(1) and D(2) are the potency principles in the inhibition of EBV DNA polymerase from E. uniflora.     

Preoperative carcinoembryonic antigen level as an independent prognostic factor in colorectal cancer: Taiwan experience

BACKGROUND: Preoperative carcinoembryonic antigen (CEA) level is considered as a factor predictive of survival in colorectal cancer patients. Patients with normal (<5 ng/ml) or lower preoperative CEA levels were reported to have significantly longer survival. This study was carried out in an effort to evaluate the prognostic significance of preoperative CEA levels of patients with colorectal cancer in Taiwan. METHODS: Between 1990 and 1994, 218 patients with histologically confirmed colorectal cancers were evaluated retrospectively at the Veterans General Hospital-Taipei. All the patients had undergone potentially curative surgery. Patients with metastatic diseases were not included. 5-Fluorouracil-based adjuvant chemotherapy was administered if the patients had Dukes' C disease. Reference to the Dukes' classification was according to the classical criteria described in 1932 for carcinoma of the rectum and adapted for use in colonic tumors. Data on gender, age, degree of tumor differentiation, location of the tumor, tumor size, lymph node metastasis, penetration of the bowel wall and preoperative CEA levels were analyzed to determine their association with survival. Blood samples for CEA measurement were taken a few days before operation and were analyzed using the radioimmunoassay method. Multivariate analysis by Cox's proportional hazards regression model was performed to determine the most important predictors of survival among all of the possible variables. RESULTS: By univariate analysis, the size of the tumor (p = 0.012), lymph node metastases (p = 0.007), penetration of the bowel wall (p < 0.001) and preoperative CEA levels (p < 0.001) were found to be significant prognostic factors, while gender, age, degree of tumor differentiation and location of the tumor were not significant. By multivariate Cox analysis, lymph node metastases (p = 0.003), penetration of the bowel wall (p = 0.0001) and preoperative CEA levels (p = 0.0001) were found to be independent prognostic factors in colorectal cancer patients. CONCLUSIONS: The data from our study indicate that in addition to lymph node metastases and penetration of the bowel wall, the preoperative CEA levels are also an independent prognostic factor in non-metastatic colorectal cancer patients after curative surgery. This could serve as an appropriate modification to the initial Dukes' scheme in colorectal cancer.     

Studies on the mechanism of action of a new Ca-2+ antagonist, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride in smooth and skeletal muscles.

1. The rabbit aortic strip, guinea-pig ileum and rabbit skeletal muscle sarcoplasmic reticulum preparations were used to determine at which sites and in what manner 8-(N,N-diethylamino)-octyl 3,4,5,-trimethoxybenzoate (TMB-8) interferes with Ca2+ availability in smooth and skeletal muscles. 2. TMB-8 (50 muM) significantly inhibited equivalent responses of the rabbit aortic strip to KCl and noradrenaline. 3. TMB-8 (65 muM) produced no significant alteration in the extracellular space of the guinea-pig ileum as measured with [3H]-sorbitol. 4. The resting cellular Ca2+ influx as well as the resting 45Ca2+ efflux in the guinea-pig ileum preparation were significantly inhibited by TMB-8 (65 muM). 5. TMB-8 (5 muM and 50 muM) had no significant effect on the uptake of 45Ca2+ by the sarcoplasmic reticulum preparation of skeletal muscle; however, TMB-8 (5 muM) did significantly inhibit the caffeine (20 mM)-induced release of 45Ca2+ from this preparation. 6. It is concluded that TMB-8 reduces Ca2+ availability in smooth and skeletal muscles by stabilizing Ca2+ binding to cellular Ca2+ stores and thereby inhibits the release of this Ca2+ by contractile stimuli.