Interleukin-1 is known to repress a number of hepatic drug-metabolizing enzymes in rats and humans. The effect of interleukin-1 beta on lauric acid 12-hydroxylase (CYP4A family) was studied in cultured fetal rat hepatocytes after clofibric acid induction. Dexamethasone was used as an agent promoting differentiation and long-term maintenance of active hepatocytes. Dexamethasone and clofibric acid in combination allowed maximal (13.5-fold) induction of CYP4A1. Lauric acid 12-hydroxylase activity was found to increase with time in culture. Interleukin-1 beta adversely affected P4504A clofibric acid-induced activity, totally eliminating the effect of induction at doses exceeding 5 ng/ml. This repression/inhibition was dose-dependent. The mechanism by which interleukin-1 beta prevents the development of cytochrome P4504A activity is unclear.

Animals↗

PubMedDate not supplied

In vitro metabolism of GV150013X by using liver microsomes and liver tissue slices from different species.

The metabolism of GV150013X was studied in vitro using washed liver microsomes and liver tissue slices from different species. This work was carried out in order to compare the metabolite profiles resulting from incubation of GV150013X with human, rat, dog and rabbit liver microsomes and those from rat, rabbit and human liver tissue slices. This compound was found to be converted to at least 8 metabolites by rat and human liver microsomes. In rabbit liver microsomes, the three metabolites M4, M7 and M8, and in dog liver microsomes metabolite M1, were not detected. The main metabolites, M2, M5 and M6, were present in human, rat and rabbit liver tissue slices, while the three metabolites M3, M4 and M8 and metabolite M1 were not detected in rabbit and rat liver tissue slices, respectively. In rat liver tissue slices, the major metabolites plus five minor metabolites, one sulphate conjugate of a monohydroxylated, three trihydroxylated and one dihydroxylated were identified based on HPLC retention time and thermospray-mass spectrometry data. Quantitative species differences among rat, dog, rabbit and human were observed, while qualitative differences only between rabbit and other species were detected.

Adamantane↗

PubMedDate not supplied

The propagation of Gaussian modulated pulses in dissipative and/or dispersive media such as tissue.

The interrogating pulse used in most conventional medical ultrasonic imaging systems can be approximated as a band-limited Gaussian modulated pulse. In this paper we analyze the propagation of such a pulse in an attenuating media such as tissue. We show that an initially Gaussian pulse retains its Gaussian shape during propagation provided that the medium has attenuation with a power-law dependence on frequency of between zero and two. That is, if the attenuation factor is e- alpha x, where alpha is the attenuation coefficient and x is the distance over which the pulse has traveled, then the pulse will remain Gaussian provided alpha = afp, where a is a constant, f is the frequency, and 0 less than p less than or equal to 2. This condition is certainly valid for soft tissue (p approximately 1) as well as for all other attenuating materials with which we are familiar. Although a Gaussian pulse retains its Gaussian shape in an attenuating media, it does suffer a shift in its mean frequency as well as a broadening in its shape. Here we also obtain analytical expressions relating the mean frequency shift and the pulse broadening to the attenuating properties of the medium. In contrast to other studies recently published in the literature, we consider propagation in a medium which has velocity dispersion as well as frequency dependent loss.

Animals↗

PubMedDate not supplied

The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels.

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.

Aged↗

PubMedDate not supplied

Lactose malabsorption and recurrent abdominal pain in Italian children.

The role of lactose malabsorption (LM) was investigated in 32 children (mean age 8.13 +/- 2.46 years) with recurrent abdominal pain (RAP). LM was detected in 75% of them by a lactose breath hydrogen test (LBHT) after a 2-g/kg (max 50-g) load. Of the 18 malabsorbers who participated in a 3-month lactose-free diet (LFD), 14 were judged "improved" and reported lower pain frequency (p less than 0.001). The malabsorbers who improved versus the not improved had comparable past lactose ingestion but were distinguishable on the basis of their lactose absorption capacity (0.36 vs. 0.81 g/kg; p less than 0.01), as subsequently determined by multiple LBHTs with 25-, 12.5-, and 6-g loads. The ratio between past lactose ingestion and lactose absorption was 1.89 in the improved and 0.55 in the not improved groups (p less than 0.01), retrospectively indicating lactose as a possible cause of the symptoms in the improved group. The reintroduction of lactose in amounts not exceeding the absorption capacity into the diet of each malabsorber who had improved with LFD caused relapse in none of the 14 subjects monitored for 2-6 months. In conclusion, LM seems an important cause of symptoms in Italian children with RAP. Assessment of the lactose absorption threshold of each subject of LBHTs provides a basis for reintroduction of "calibrated" amounts of lactose-containing foods (e.g., milk) into the diet.

Administration, Oral↗

PubMedDate not supplied

A feasibility study using polychemotherapy (cisplatin + vindesine + dacarbazine) plus interferon-alpha or monochemotherapy with dacarbazine plus interferon-alpha in metastatic melanoma.

AIMS AND BACKGROUND: This trial evaluated the feasibility and tolerability of an immunochemotherapeutic approach that uses cisplatin, vindesine, and dacarbazine (DTIC), or only DTIC, in combination with interferon alpha-2a (IFN-alpha), in patients with metastatic melanoma, considering the significant toxicity of several different regimens used up to now. METHODS: Between May 1995 and September 1997, 51 melanoma patients (50 of whom were assessable) entered a multicentric trial and were randomized to receive cisplatin (30 mg/m2 daily for 3 days) + vindesine (2.5 mg/m2 only day 1) + DTIC (250 mg/m2 daily for 3 consecutive days) + IFN-alpha (3 MIU i.m. 3x/wk continuously) (CVD arm) versus DTIC (800 mg/m2 day 1) + IFN-alpha (3 MIU i.m. 3x/wk continuously) (DTIC arm). The chemotherapy was recycled every 21 days. Patient reevaluation was performed every two cycles, and the treatment was continued in case of objective response or stabilization of disease. RESULTS: We observed 3 complete responses, 2 partial responses and 5 stable diseases in the CVD arm, and 2 partial responses and 4 stabilizations of disease in the DTIC arm. CONCLUSIONS: We conclude that these chemotherapeutic regimens are well tolerated regimens with modest toxicity. Future trials will be conducted associating the CVD regimen with biological response modifiers (IFN, IL-2) in order to improve the results.

Adult↗

PubMedDate not supplied

Capecitabine: indications and future perspectives in the treatment of metastatic colorectal and breast cancer.

Fluoropyrimidines remain the most important drugs in the treatment of breast and colorectal carcinoma, but response rates and survival time have been disappointing. Optimal administration is by continuous intravenous infusion, which makes it cumbersome to use and compromises patient independence. Recently, a number of new agents, including fluorouracil prodrugs and selective dihydropyrimidine dehydrogenase inhibitors, have been studied, with promising results. Capecitabine is the first in a new class of fluoropyrimidines. It is an oral, tumor-activated anticancer drug whose activity mimics that of continuously infused 5-fluorouracil. Capecitabine circumvents dihydropyrimidine dehydrogenase catabolism and appears to be at least as active against metastatic colorectal and breast cancer as conventionally administered intravenous 5-fluorouracil, with significantly less toxicity, an improved quality of life, and lesser cost. Capecitabine may ultimately provide enhanced antitumor activity to fluorouracil-containing regimes for advanced colorectal and breast cancer.

Animals↗

PubMedDate not supplied

Mucinous markers in breast cancer.

Explore the source record for details and available documents.

Biomarkers, Tumor↗

PubMedDate not supplied

Serum levels of tartrate-resistant acid phosphatase-5b in breast cancer patients treated with pamidronate.

A novel immunoassay specific for the osteoclast-produced TRAP isoform 5b has been developed recently. By means of this assay we studied the usefulness of serum TRAP-5b in monitoring the response to palliative treatment with pamidronate in breast cancer patients with bone metastases. We correlated serum TRAP-5b levels with pain intensity and intake of analgesics to assess the possible utility of the marker in identifying patients who could benefit from pamidronate treatment. Twenty-eight advanced breast cancer patients with bone metastases entered the study. Patients were treated according to the following schedule: two two-week cycles of 60 mg/week pamidronate IV, with a three-week interval in between (six infusions over seven weeks), followed by one infusion every three weeks for a total of 24 infusions over a treatment period of 61 weeks. Blood samples were taken before the start of treatment and before each infusion during two treatment cycles. To measure serum TRAP levels we employed the new immunoassay kit BoneTRAP produced by Suomen Bioanalytiikka Oy (SBA), Oulu, Finland. In order to assess the usefulness of this marker in evaluating the response to pamidronate treatment we divided patients into two groups (group A, worsened; group B, improved) with respect to pain trend and analgesic intake. Our results did not show any statistically significant difference in baseline serum TRAP levels in the two groups. However, one week after the first pamidronate infusion TRAP-5b serum levels decreased by 39% and 18% in groups A and B, respectively (p=0.01); these levels persisted throughout the treatment period. In conclusion, a decrease in TRAP-5b serum levels may reflect the pharmacological activity of pamidronate and seems to predict pain relief and a reduction in analgesic consumption.

Acid Phosphatase↗

PubMedDate not supplied

Anti-malignin antibody evaluation: a possible challenge for cancer management.

The major problem in the management of cancer is the difficulty of an early diagnosis. Clinical signs and symptoms generally appear late in the course of the disease. The availability of a non-invasive test which detects a blood molecule closely associated with the malignant transformation of the cells could be of help in the early detection of cancer. Malignin is a 10 kDa polypeptide located in the cytoplasmic and outer membranes of all malignant cells. Anti-malignin antibodies (AMAs) are IgM immunoglobulins spontaneously produced by the host against the oncoprotein malignin when neoplastic transformation occurs; since AMAs are IgM, they can represent an "early" transformation indicator useful for the early detection of cancer. Elevated AMA serum concentrations, measured by means of TARGET@ reagent, have been demonstrated in patients with a wide spectrum of non-terminal active cancers, regardless of the anatomical site and histotype of the tumor. The AMA test showed a sensitivity and specificity of 95% on first determination and > 99% on repeated determinations, and has been reported to be a promising diagnostic tool for the early detection of cancer, as well as for monitoring of the response to treatment and possibly for screening of an asymptomatic population.

Adult↗