Inhibition of HIV-1 integrase by galloyl glucoses from Terminalia chebula and flavonol glycoside gallates from Euphorbia pekinensis

The bioassay-directed isolation of Terminalia chebula fruits afforded four human immunodeficiency virus type 1 (HIV-1) integrase inhibitors, gallic acid ( 1) and three galloyl glucoses ( 2 - 4). In addition, four flavonol glycoside gallates ( 5 - 8) from Euphorbia pekinensis containing the galloyl moiety also showed the inhibitory activity at a level comparable to those of 2 - 4. By comparison with the activities of the compounds not bearing this moiety, it is proposed that the galloyl moiety plays a major role for inhibition against the 3'-processing of HIV-1 integrase of these compounds.     

Tumors of the Central Nervous System in Korea A Multicenter Study of 3221 Cases.

The Neuropathology Study Group of the Korean Society of Pathologists conducted a nationwide collection of central nervous system (CNS) tumors to evaluate the relative frequency in Korea of CNS tumors belonging to the revised World Health Organization (WHO) classification categories. A total of 3221 histologically proven cases of CNS tumors were collected from 13 institutes between 1997 and 1998. All the cases were classified according to the revised WHO histological types and analyzed for the relative frequency, the distribution of age and sex, and location of tumors. The most frequent type of CNS tumors in Korea was meningiomas, followed by pituitary adenoma, glioblastoma, astrocytoma, and schwannoma. Among the pediatric CNS tumors, pilocytic astrocytoma, medulloblastoma, craniopharyngioma, germ cell tumors, and ependymomas were common types of tumors. Compared with a previous nationwide study, the rates for neuronal/glial tumors, glioblastoma, malignant lymphoma, and cystic lesion were increased, and the rate of embryonal tumors was decreased. The overall male to female ratio was 0.9:1, which may be attributed to the greater number of female-predominate meningiomas and pituitary adenoma. Compared with Western countries, Koreans had higher rates of pituitary adenoma and meningiomas and lower rate of gliomas. The relative frequency of CNS tumors among Koreans is very similar to that reported in Taiwan. The occurrence rates for various subtypes of CNS tumors in Korea are distinct from those in the United States and Europe and similar in many ways to those in Asian and Mexican population.     

Medullary nephrocalcinosis associated with long-term furosemide abuse in adults.

BACKGROUND: The use of furosemide is well recognized as a predisposing factor of nephrocalcinosis in infants. Although furosemide is widely used for various medical conditions in adults, its association with nephrocalcinosis in adults is not well established. METHODS: We studied 18 consecutive adult patients (male:female ratio 1:17, age range 21-59 years) who habitually took furosemide to control weight or oedema for long periods of time (range 3-25 years). The daily dose of continuous intake of furosemide ranged from 40 to 2800 mg. Nephrocalcinosis was evaluated using renal ultrasonography (US), computed tomography (CT), or kidney biopsies. RESULTS: Renal US and CT revealed bilateral nephrocalcinosis of the medullary pyramids in 15 (83.3%) out of 18 patients. The duration of furosemide abuse was similar between nephrocalcinosis positive (NC(+)) and nephrocalcinosis negative (NC(-)) groups. The daily dose of furosemide was nearly 10 times higher in the NC(+) group (range 120-2800 mg, mean 538 mg) than the NC(-) group (range 40-80 mg, mean 67 mg). All patients showed variable degrees of renal insufficiency and there was no difference in creatinine clearance between the NC(+) and NC(-) groups (P>0.05). Kidney biopsies performed in three patients showed focal tubulo-interstitial fibrosis and atrophy and calcifications were observed in outer medullary tubulo-interstitium. CONCLUSIONS: Long-term furosemide abuse can cause medullary nephrocalcinosis in adults, and the risk of developing of nephrocalcinosis seems to be correlated with the daily dose of furosemide. We suggest that long-term furosemide abuse should be suspected in adult patients when medullary nephrocalcinosis is incidentally detected by US or CT.     

beta-Cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus

BACKGROUND: Our study was undertaken to investigate the pathogenesis and possible risk factors for postrenal transplantation diabetes mellitus (PTDM). METHODS: We recruited 114 patients with normal glucose tolerance (NGT) and performed both 75-g oral glucose tolerance tests (OGTT) and short insulin tolerance tests 1 week before and 9-12 months after transplantation. RESULTS: The subjects were classified into three groups by World Health Organization criteria on the basis of OGTT after transplantation: (a) 36 (31.6%) subjects with normal glucose tolerance; (b) 51 (45.7%) subjects with impaired glucose tolerance (IGT); and (c) 27 (23.7%) subjects with postrenal transplantation diabetes mellitus. Dosages of steroid and cyclosporine were equivalent among the three groups. Before transplantation, the fasting and 2-hr plasma glucose and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but the insulin sensitivity index (ISI) was not significantly different among the three groups. In addition, the area under the curve-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, the ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSIONS: These results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of PTDM. Furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of PTDM.     

A Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer.

PURPOSE: The purpose of this study was to determine the feasibility and maximum tolerated dose of (90)Yttrium-CC49 ((90)Y-CC49) as the radioimmunotherapy (RIT) component of an i.p. combined modality treatment for recurrent ovarian cancer. EXPERIMENTAL DESIGN: A Phase I trial of (90)Y-CC49 RIT was conducted in ovarian cancer patients who had persistent or recurrent intra-abdominal disease, had failed one or two prior chemotherapy regimens, and demonstrated TAG-72 expression. Patients were treated with a previously established combined modality treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages of i.p. (90)Y-CC49. Patients were monitored for toxicity, generation of human antimouse antibody response, and clinical efficacy. RESULTS: Twenty eligible patients were treated per study specifications. All patients had been treated with debulking and paclitaxel/carboplatin-based chemotherapy at initial diagnosis. The patients included 11 patients with persistent disease at the time of second look laparotomy and 9 patients with delayed recurrence. Patients were treated with i.p. (90)Y-CC49 given in combination with s.c. IFN alpha2b (dose of 3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100 mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The maximum tolerated dose of i.p. (90)Y-CC49 was established at 24.2 mCi/m(2) in this combined regimen. Of nine patients with measurable disease, two had partial responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease, median time to progression was 6 months in 7 patients who recurred; 4 of these patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months. CONCLUSIONS: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p. paclitaxel is feasible and well tolerated at a dose of < or =24.2 mCi/m(2).     

Adverse effects of perioperative transfusion on patients with stage III and IV gastric cancer

BACKGROUND: The degree of immunomodulation by perioperative blood transfusion and its resultant effects on cancer surgery are a subject of controversy. We evaluated the prognostic effects of perioperative blood transfusion on gastric cancer surgery. METHODS: A total of 1710 patients who underwent curative gastrectomy for gastric cancer from 1991 to 1995 were retrospectively reviewed. Uni- and multivariate analyses of the incidence, amount, and timing of perioperative blood transfusions and a comparison of the clinicopathological features were performed. RESULTS: A higher incidence of blood transfusions was associated with female sex, large tumors, upper-body location, Borrmann type III or IV lesions, longer operations, total gastrectomies, splenectomies, and D3 or more extended lymphadenectomy. The tumors in the transfused group were more advanced in depth of invasion and nodal classification. More frequent tumor recurrences were found in the transfused group. A dose-response relationship between the amount of transfused blood and prognosis was evident. Subgroup analyses of prognosis according to stage showed significant differences in stages III and IV between the transfused and nontransfused groups. On multivariate analysis, transfusion was shown to be an independent risk factor for recurrence and poor prognosis. CONCLUSIONS: These results suggest that perioperative transfusion is an unfavorable prognostic factor. It is thus better to refrain from unnecessary blood transfusion and to give the least amount of blood to patients with gastric cancer when transfusion is inevitable, especially for those with stage III and IV gastric cancers.     

Inherited disorders of 3-methylcrotonyl CoA carboxylation

The clinical course of 4 patients who had reduced activities of 3-methylcrotonyl CoA carboxylase (also called 3-methylcrotonylglycinuria) is described. Two children presented with a metabolic acidosis, one in the neonatal period and the other with episodes of acidosis that started in the second year of life. In the other 2 children neurological symptoms were prominent, one having infantile spasms and the other developmental regression with a skin rash and alopecia. Three of the children responded well to oral biotin and dietary protein restriction but the fourth, despite a biochemical response to biotin, has a severe neurological handicap. The clinical presentation of inborn errors of 3-methylcrotonyl CoA carboxylase is variable. Metabolic acidosis may not be conspicuous and instead neurological features may predominate.     

Secondary Cardiac Tumor in Children

We describe our clinical experience of eight cases of secondary cardiac tumor. The pathology of the tumors were lymphoma (three), Wilms' tumor (two), malignant teratoma (one), neuroblastoma (one), and pleuropulmonary blastoma (one). Metastatic sites were the right atrium in Wilms' tumor and neuroblastoma, the left atrium in pleuropulmonary blastoma and malignant teratoma, and multiple sites in lymphoma. Primary masses in the mediastinum extended directly to the heart (three lymphoma, malignant teratoma, pleuropulmonary blastoma). Wilms' tumor and neuroblastoma showed cardiac metastases through the inferior vena cava. Many cases revealed vague abnormal cardiovascular findings (symptoms in six; physical signs in five). In five cases surgery was performed to relieve the possible obstruction to flow and to identify the pathology (lymphoma in three, Wilms' tumor in one, and malignant teratoma in one). Chemotherapy prior to operation resulted in the disappearance of the intracardiac masses in each case of Wilms' tumor and pleuropulmonary blastoma. All three patients with lymphoma died immediately after operation. Four died of multiple metastases or Pneumocystis pneumonia several months after operation. This study indicates that suspicion of a secondary cardiac tumor is crucial to early diagnosis. Because of the poor postoperative outcome, surgery for secondary cardiac tumors should be done cautiously only in cases with definite hemodynamic decompensation.     

Comparison of IY81149 with omeprazole in rat reflux oesophagitis

1. This study was aimed at evaluating the effects of IY81149[2-[[(4methoxy-3-methyl)-2-pyridinyl]methylsulfinyl]-5-(1H-pyrrol-1-yl)-1H-benzimidazole], a new proton pump inhibitor, on the development of the surgically induced reflux oesophagitis, on gastric secretion and on lipid peroxidation which is a marker of oxidative stress. Omeprazole was used as a reference drug. We furthermore investigated the influence of quercetin and desferrioxamine (DFO) on the development of the surgically induced reflux oesophagitis in rats on gastric secretion and on lipid peroxidation. 2. IY81149 and omeprazole significantly prevented the development of reflux oesophagitis and gastric secretion in a dose-dependent manner. The ED50 values of IY81149 for inhibition of oesophagitis and volume of gastric secretion were lower than of omeprazole (5.7 vs. 14.2 micromol, 15.3 vs. 24.0 micromol, respectively). IY81149 was also more potent in the acid output inhibition with an ED50 of 6.8 micromol compared with 20.8 micromol of omeprazole. 3. Malonyldialdehyde (MDA) content, the end product of lipid peroxidation, increased significantly in the oesophageal mucosa after the induction of reflux oesophagitis. IY81149 and omeprazole significantly and dose-dependently prevented lipid peroxidation. Quercetin (200 mg kg-1, p.o.) and DFO (800 mg kg-1, i.d.) significantly prevented the development of reflux oesophagitis and inhibited the lipid peroxidation independent of their actions on gastric secretion. 4. This result suggests that IY81149 is comparable with omeprazole in the treatment of reflux oesophagitis.