1 Leukotrienes have potent biological effects in vitro and in vivo and are found in tissue and in biological fluids in various pathological conditions including allergic diseases. Leukotriene B4 (LTB4) is a potent stimulus for eosinophil accumulation and activation and there is much interest in determining its importance in mediating the accumulation of eosinophils at sites of allergic inflamma...

1. Ligated intestinal segments from rats treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at the daily dose of 16 mumol (identical to 1 mg of phosphorus)/kg subcutaneously for 7 days show an increased rate of calcium absorption. 2. This dose of EHDP enhances the intestinal accumulation of a vitamin D3 metabolite with the chromatographic characteristics of 1,25-dihydroxycholecalci...

BACKGROUND Tetrandrine, a bisbenzylisoquinoline alkaloid, has cancer cell cytotoxicity. The effects of combined tetrandrine and radiation, alone or combined, on human SH-SY5Y neuroblastoma cells were examined. MATERIALS AND METHODS A combination treatment, using either concomitant irradiation at the beginning or end of the tetrandrine treatment (designated as the RT-Tet and Tet-RT protocols, ...

In order to identify the specific molecular mechanisms involved in neurosecretion, we investigated the mechanism of action of tetanus toxin, a potent presynaptic neurotoxin, in the rat adrenal pheochromocytoma PC12 cell line. It has recently been reported that tetanus toxin is a potent inhibitor of the release of depolarization-evoked 3H-acetylcholine (ACh) from nerve growth factor-differentiat...

Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show 'relevant' drug accumulation at steady state (SS). This new requireme...

The plasma and tissue disposition of CGP 69846A (ISIS 5132) was characterized in male CD-1 mice following iv bolus injections administered every other day for 28 days (total of 15 doses). The doses ranged from 0.8 mg/kg to 100 mg/kg. Urinary excretion of oligonucleotide was also monitored over a 24-hr period following single dose administration over the same dose range. Pharmacokinetic plasma p...

A greater persistence of unbound (exchangeable) drug in tumor cells versus drug-limiting normal tissue (proliferating epithelium of small intestine) correlates with the therapeutic effects of various antifolates against a group of murine tumors. After approsimate equimolar doses (3 mg/kg i.p.) of methotrexate (MTX) methasquin (MQ), aminopterin, and N-([2,4-diamino-5-chloro-6-quinazolinyl) methy...

Insulin-like growth factor (IGF-I) stimulates thyroid cell proliferation. Using primary cultured porcine thyroid cells, we studied the intracellular pathways that mediate the action of IGF-I on thyroid cell proliferation. IGF-I stimulates inositol phosphate accumulation, a rise in cytoplasmic free calcium [( Ca2+]i), and cell proliferation. Exposure to IGF-I results in a time- and dose-dependen...

Hypo-fractionated stereotactic body radiation therapy (SBRT) employs precisely-conforming high-level radiation dose delivery to improve tumor control probabilities and sparing of healthy tissue. However, the delivery precision and conformity of SBRT renders dose accumulation particularly susceptible to organ motion, and respiratory-induced motion in the abdomen may result in significant displac...