Aspergillus awamori-fermented mung bean seed coats enhance the antioxidant and immune responses of weaned pigs.

The potential benefits of Aspergillus-fermented mung bean seed coats (FMSC) for weaned pigs remain unexplored. Both in vitro and in vivo experiments were employed to evaluate the potential of FMSC supplement on the growth, antioxidant and immune responses of weaned pigs. The total polyphenols and DPPH scavenging capability of ethanol extract of FMSC exhibited a greater (p < 0.01) increase than those of pre-fermentation. With the addition of the polyphenol of FMSC extract, an increase in phagocytosis by neutrophils and proliferation of peripheral blood mononuclear cells (PBMC) were found. However, these observations were significantly inhibited (p < 0.05) in those activated cells. Next, 96 weaned pigs were allotted with a randomized complete block design into four dietary treatments, including 0 (control), 600, 1200 or 1800 mg/kg FMSC in a corn-soya bean meal basal diet for a 35-day trial. The pigs were injected with swine enzootic pneumonia (SEP) vaccines at day 3 and day 21 respectively. The results showed that dietary treatment failed to affect growth performance or serum SEP titre. The diet supplemented with 600-1800 mg/kg FMSC decreased faecal lactoferrin on day 21 and increased plasma trolox equivalent antioxidant capacity (TEAC) and erythrocytes catalase activity, as well as decreased (p < 0.01) plasma malondialdehyde (MDA) concentration on day 35. Diet supplementation of 1800 mg/kg FMSC increased phagocytosis by neutrophils and PBMC proliferation induced by pokeweed mitogen (PWM). However, the polymorphonuclear leucocytes (PMN)-positive respiratory burst cells were decreased in the supplementation of 1200 or 1800 mg/kg FMSC respectively. In addition, the serum haptoglobin concentration was decreased in the supplementation with 1200 mg/kg FMSC. Taken together, FMSC enriches polyphenols with antioxidative and immune modulated properties. After feeding FMSC, an improvement in antioxidative capability and immunocompetence was found, implying that FMSC could provide as a feed additive at optimal level 1200 mg/kg for weaned pigs.

Intra-arterial plus i.v. chemotherapy for advanced bulky squamous cell carcinoma of the buccal mucosa.

From July 1994 to December 1996, 41 patients with previously untreated, advanced bulky squamous cell carcinoma arising from the buccal mucosa (BSCC) were enrolled. All patients were males with a median age of 47 years (range 29-72). The tumor extent was stage III/IV: three of 38, T4: 85%, N2-3: 20%. Patients were initially scheduled to receive intra-arterial (i.a.) chemotherapy, followed by i.v. chemotherapy and regional therapy. The i.a. chemotherapy catheter was properly placed by external carotid artery angiography via the femoral artery. The i.a. chemotherapy consisted of cisplatin (P) 100 mg/m(2) day 1 plus 5-fluorouracil (F) 1000 mg/m(2) day 1-4, and the i.v. chemotherapy consisted of PF (10 patients) or PF plus methotrexate 200 mg/m(2) day 15 and 22 (31 patients). All chemotherapy regimens were administered at 4-week intervals. The response rate of i.a. plus i.v. chemotherapy for the primary site was 85% (35 of 41) with 29% complete remission (CR) (12 of 41). The response and CR rates of neck nodes were 82% (14 of 17) and 41% (seven of 17), respectively. The combined overall response rate was 80% (33 of 41) with a 29% CR (12 of 41). Major toxicity from i.a. chemotherapy of WHO grade > or = 3 included: mucositis of infusion area (76%), hemialopecia (56%) and leukopenia (5%). Three neurologic complications of i.a. chemotherapy including one hemiparesis occurred. The median follow-up time was 47 months (range 36-66 months), and the overall survival and disease-free survival were both 34% (14 of 41). Four patients were cured with chemotherapy alone and eight patients (19.5%) were cured without surgical intervention. Using i.a. chemotherapy as a cytoreductive therapy followed by subsequent i.v. chemotherapy produces a high response rate and an encouraging degree of complete response rate in advanced bulky BSCC. However, toxicity management and catheter placement will need to be improved in order to better define the role of this therapy in advanced BSCC.

ESR studies on reaction of saccharide with the free radicals generated from the xanthine oxidase/hypoxanthine system containing iron.

The free radicals generated from the iron containing system of xanthine oxidase and hypoxanthine (Fe-XO/HX) were directly detected by using spin trapping. It was found that not only superoxide anion (O(2)*-) and hydroxyl radical (OH*), but also alkyl or alkoxyl radicals (R*) were formed when saccharides such as glucose, fructose and sucrose were added into the Fe-XO/HX system. The generated amount of R* was dependent on the kind and concentration of saccharides added into the Fe-XO/HX system and no R* were detected in the absence of saccharides, indicating that there is an interaction between the saccharide molecules and the free radicals generated from the Fe-XO/HX system and saccharide molecules are essential for generating R* in the Fe-XO/HX system. It is expected that the toxicity of R* would be greater than of hydrophilic O(2)*- and OH* because they are liposoluble and their lives are longer and the active sites of biomolecules are closely related with lipophilic phase, thus they can damage cells more seriously than O(2)*- and OH*. The R* generated from the saccharide containing Fe-XO/HX can be effectively scavenged by selenium containing abzyme (Se-abzyme), indicating Se-abzyme is a promising antioxidant.

Weekly high-dose 5-fluorouracil (5-FU), leucovorin (LV) and bimonthly cisplatin in patients with advanced gastric cancer.

BACKGROUND: A phase II clinical trial was performed to evaluate the activity and toxicity of bimonthly cisplatin and weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer. PATIENTS AND METHODS: From September 1997 to March 1998, 23 chemo-naive patients of advanced gastric cancer were enrolled in this study. The regimen consisted of weekly 24-h infusion of 5-FU (2,600 mg/m2) and LV 150 mg and bimonthly cisplatin (25-50 mg/m2) bolus for 12 weeks followed by a 2-week break. RESULTS: There were 10 male and 13 female patients with a median age of 52 years. A total of 428 chemotherapy treatments were given with a mean of 11. Seventeen patients were evaluable for response. There were 41% (7/17) partial response, 18% (3/17) stable disease and 41% (7/17) progressive disease. The grade III or IV toxicity included anorexia 35% (8/23), fatigue 26% (6/23), vomiting 17% (4/23) and mucositis 9% (2/23). One patient developed perforated duodenal stump after chemotherapy. One patient died of hyperammonemia-related coma. The median times to disease progression and overall survival were 3.5 and 7 months, respectively. CONCLUSIONS: This regimen showed modest activity against gastric cancer. However, there was no survival advantage and there was greater toxicity than with weekly high-dose 5-FU-LV alone.

Colon carcinoma with synchronous ovarian metastasis--report and discussion of five cases.

Ovarian metastasis may present at the time of initial diagnosis of colon carcinoma or as a later recurrence. Little meaningful information is available regarding the treatment and outcome of synchronous ovarian metastasis of colon carcinoma. This report describes the clinical course of five patients with synchronous ovarian metastasis of colon carcinoma who were treated with aggressive surgery and chemotherapy. The treatment consisted of maximal surgical debulking followed by systemic chemotherapy with weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin. All of the five patients had subsequent disease-free periods ranging from 6 to 43+ months following operation. Two of the patients who had no or minimal peritoneal involvement were still alive without disease at 33 and 43 months. The data from these cases suggest that aggressive surgery and systemic chemotherapy may be highly efficacious in the treatment of colon carcinoma with synchronous ovarian metastasis. Maximal debulking followed by chemotherapy may be particularly effective in those patients with minimal peritoneal involvement.

Weekly 24-h infusion of high-dose 5-flurouracil and leucovorin in patients with advanced gastric cancer.

The effect of biochemical modulation of weekly high-dose 5-fluorouracil (5-FU) 24 h infusion by leucovorin (LV) in the treatment of 39 consecutive patients with advanced gastric cancer without prior chemotherapy from October 1996 to August 1997 was examined. There were 21 male and 18 female patients with a median age of 56 years. The regimen consisted of 5-FU 2600 mg/m2 and LV 150 mg administered by 24 h infusion weekly for 6 weeks followed by a 2 week break. The treatment was repeated every 8 weeks until disease progression, patient refusal or unacceptable toxicity. Placement of a central vascular device and a portable external infusion pump was required in all patients and was used for outpatient treatment. The response to treatment was evaluated every 8 weeks. A total of 395 chemotherapy treatments were given with a mean of 10 (2-24). This response rate was: 33% (12 of 36) partial response (PR) rate, 33% (12 of 36) stable disease (SD) and 33% (12 of 36) progressive disease (PD). In general, the toxicity was mild but two toxic deaths occurred, one due to neutropenic sepsis and the other due to hyperammonemia. The median time to progression was 4 months. The overall median survival was 7 months. The survivals of the PR, SD and PD were 12, 8 and 5 months, respectively. This regimen showed a modest activity against gastric cancer with acceptable toxicity. Weekly 24 h infusion of high-dose 5-FU with LV in an outpatient setting for patients with gastric cancer is feasible and deserves further study as a basis for combination therapy.

A simplified regimen of weekly high dose 5-fluorouracil and leucovorin as a 24-hour infusion in patients with advanced colorectal carcinoma.

BACKGROUND: Reports of in vitro experiments in colorectal carcinoma cells suggest that prolonged cellular exposure to 5-fluorouracil (5-FU) combined with relatively low concentrations of leucovorin (LV) provides optimal enhancement of 5-FU efficacy. In this study, a simplified regimen of weekly 24-hour infusion of high dose 5-FU combined with a relatively low dose of LV was used to treat patients with advanced colorectal carcinoma. METHODS: Thirty-six patients with advanced colorectal carcinoma received 5-FU, 2600 mg/m2, admixed with LV, 100 mg/m2, in a portable infusion pump administered intravenously over a 24-hour period. High dose 5-FU/LV was delivered once a week for 5 consecutive weeks followed by a 1-week recovery period. All patients were assessable for toxicity and response. RESULTS: Two complete responses and 15 partial responses were observed (response rate of 47.2%; 95% confidence interval, 30.1-64.4%). The median response duration was 9.6 months. The median survival and time to progression were 11.9 months and 7.1 months, respectively. The toxicity was mild and acceptable. The major dose-limiting factors were hand-foot syndrome and fatigue. CONCLUSIONS: This simplified regimen of weekly 24-hour continuous infusion of high dose 5-FU/LV is an effective regimen in the treatment of patients with advanced colorectal carcinoma. Further study of the pharmacokinetics of combination therapy with 5-FU and LV as used in this regimen and its correlation with response and toxicity is warranted.

Clinical benefit and response in patients with gastric cancer to weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV).

BACKGROUND: A prospective study evaluated the efficacy and correlation of different outcome measurements, including the WHO response criteria and clinical benefit (CB), to weekly high-dose 5-FU and LV for patients with advanced gastric cancer. PATIENTS AND METHODS: Thirty-nine chemotherapy-naive patients were enrolled from Sep. 1996 to Oct. 1997. The treatment consisted of a 24-hour continuous infusion of 5-FU 2600 mg/m2 & LV 150 mg weekly for 6 weeks with a subsequent 2-week break. The responses were evaluated by CB and WHO criteria at the end of the 8th week, then at 8-week intervals. RESULTS: There were 21 male and 18 female patients with a median age of 56 years. The median Karnofsky performance score was 70%. Thirty-six patients were evaluable for WHO criteria, and 12 (33.3%) had partial response, 12 (33.3%) had stable disease and 12 (33.3%) had progressive disease. Twenty-one of the 35 (60%) evaluable patients for CB were found to have a positive response. There was a significant correlation between WHO response and CB. The median survival was 10.5 months for CB responders, while the median survival among the CB non-responders was 5 months only. CONCLUSIONS: This study found that this regimen yielded a 60% CB, despite a 33% WHO response rate. Improvement in CB resulted in an improvement in survival as well as the correlation between CB and WHO response, and suggested the value of CB as an alternative indicator for clinical response.

Protection of myocardial mitochondria against oxidative damage by selenium-containing abzyme m4G3.

Selenium-containing abzyme (m4G3) was prepared and its protection of myocardial mitochondria against oxidative damage was studied using the swelling of mitochondria, quantity of lipid peroxidation products, and change in cytochrome-c oxidase activity as a measure of mitochondrial damage. The results showed that m4G3 could inhibit mitochondrial damage caused by the hypoxanthine-xanthine oxidase system in vitro. Electronic spin resonance (ESR) studies demonstrated that m4G3 could decrease the amount of free radicals generated in the damage system.

Efficacy and safety of estriol replacement therapy for climacteric women.

BACKGROUND: As an estrogen derivative, estriol is rather effective in the relief of climacteric symptoms due to estrogen deficiency. When given one dose a day, it will not provoke endometrial proliferation and shedding. Thus, it is suitable for postmenopausal women who no longer want to have uterine bleeding and for those with comparatively higher risk of endometrial hyperplasia. In the aspect of postmenopausal osteoporosis, the prevention of further bone loss due to estrogen deficiency is also important and to be evaluated. METHODS: We collected 20 patients, aged 44-62 years, who had undergone either natural or surgical menopause and were treated with estriol succinate (Synapause; Organon; Holland 2 mg/tab) 2 mg/day for 2 years, with relief of climacteric symptoms evaluated after the first 3 months of treatment. Bone mineral density (BMD) of lumbar spine was measured using quantitative computed tomography (QCT) after one and two years of treatment, respectively. RESULTS: Estriol was very effective in the improvement of major subjective climacteric complaints in 86% of patients, especially hot flush and insomnia within 3 months. The atrophic genital changes caused by estrogen deficiency were also improved satisfactorily. No subjective symptoms induced by the therapy were seen. The rate of uterine bleeding was low, complained by only one patient. However, our study did not show the preventive effect of estriol against osteoporosis. CONCLUSIONS: Estriol can be a safe and effective alternative in the relief of climacteric symptoms for postmenopausal women, but it cannot prevent the bone loss.

Some physicochemical and enzymic properties of selenium-containing abzyme.

We successfully prepared the Se-containing abzyme (Se-abzyme) with glutathione peroxidase (GPX) activity and further studied its physicochemical and enzymic properties and stabilities. Data showed that the isoelectric point of the abzyme was 6.95-7.08, and its molecular weight was 158 KD. The ranges of optimum pH and temperature of the Se-abzyme were wider than the native GPX. The store stability of the abzyme was higher than the native GPX. The Se content in the abzyme was found to be 5 mol Se/mol abzyme by X-ray photoelectron spectrum, and binding constant 1.11 x 10(7)M-1 by using ELISA method. The Se-abzyme was inhibited competitively by dithiobis(2-nitrobenzoic acid) (DTNB), and inhibition constant was determined to be 1.25 x 10(-3)M-1.

Transient neurological disturbances induced by the chemotherapy of high-dose methotrexate for osteogenic sarcoma.

Temporary neurologic abnormalities were observed in one out of 23 patients undergoing chemotherapy with high-dose methotrexate (HD-MTX) for osteogenic sarcoma. This patient developed sequential symptoms including alternative hemiparesis, dysarthria and altered consciousness 5 days after the second course of HD-MTX (8 gm/m2 by 6 h continuous infusion) with leucovorin rescue. Laboratory evaluations disclosed normal electrolytes, hemograms and non-toxic serum MTX levels at the onset of the symptoms. Computed tomography of the brain was normal but electroencephalography showed focal theta and delta slow waves over the right temporal-parietal-occipital area. The neurological symptoms resolved completely within 72 h.

Generation of selenium-containing abzyme by using chemical mutation.

A new strategy for generating abzyme was developed. Glutathione peroxidase (GPX, EC 1.11.1.9) is one of the important members of antioxidation enzyme system; it catalyzes the reductions of a variety of hydroperoxides in presence of glutathione(GSH). We have first prepared the monoclonal antibody (McAb) with GSH binding sites, then incorporated GPX catalytic group selenocystein (SeCys) into the antibody combining sites by using chemical mutation. Thus the mutated antibody displays high GPX activity, which approaches the magnitude level of native GPX, exhibits the kinetic behavior similar to native GPX, and has some advantages over native GPX.