Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen

Exposure of ZR-75-1 human breast cancer cells for 48 h to human recombinant interferon alpha (IFN alpha) resulted in increased expression of oestrogen receptors as measured in a whole cell binding assay. This effect was inversely proportional to dose being significant following treatment with 10-100 IU IFN ml-1 and was only observed at a low initial cell plating density. The extent of the increase in oestrogen receptor levels ranged from 1.2- to 7.2-fold following treatment with 10 IU IFN ml-1. No increase in progesterone receptor expression was observed under the same experimental conditions. Concentrations of IFN which increased oestrogen receptor levels had no effect on cell proliferation. IFN (500 IU ml-1) inhibited cell proliferation and the combination of this treatment with tamoxifen (2 microM) had a greater anti-proliferative effect than either drug alone although there was no evidence of synergism. However, a 5-day pretreatment of cells with IFN (10 IU ml-1) markedly sensitised them to the growth-inhibiting effect of a subsequent 6-day exposure to tamoxifen.     

Corpus callosotomy: a palliative therapeutic technique may help identify resectable epileptogenic foci.

Corpus callosotomy has a long history as a palliative treatment for intractable epilepsy. Identification of a single epileptogenic zone is critical to performing successful resective surgery. We describe three patients in which corpus callosotomy allowed recognition of unapparent seizure foci, leading to subsequent successful resection. We retrospectively reviewed our epilepsy surgery database from 2003 to 2005 for children who had a prior callosotomy and were candidates for focal resection. All underwent magnetic resonance imaging and scalp video electroencephalograph monitoring, and two had magnetoencephalography, electrocorticography and/or intracranial video electroencephalograph monitoring. The children were 8 and 9 years old, and seizure onset varied from early infancy to early childhood. One child had a history of head trauma preceding seizure onset, one had a large intracerebral infarct and dysplastic cortex in the contralateral frontal lobe, and the other had an anterior temporal lobe resection without improvement in seizure frequency. After medical management failed, callosotomy was performed with the expectation of decreasing the seizure types affecting both hemispheres. Following transection of the callosal fibers, a single focus was recognized and resected, with resultant dramatic improvement in seizure control. In medically refractory epilepsy, where rapid secondary bisynchrony is suspected but the electroencephalograph is non-localizing, callosotomy should be considered as a means of treating generalized seizure types, but may also assist in identifying potentially operable seizure foci. Study limitations include its retrospective nature and cohort size. The findings, however, suggest the need for prospective, systematic, well-controlled studies of the use of corpus callostomy in this intractable patient population.     

Osteoinductive ability of confluent Saos-2 cells correlates with enhanced expression of bone morphogenetic proteins

Implants of defatted, freeze-dried Saos-2 human osteosarcoma cells grown to confluency induce de novo bone formation in athymic mice. These cells are also richly endowed with bone morphogenetic proteins and express mRNA for bone morphogenetic proteins 1, 2, 3, 4, and 6, as well as for transforming growth factor-β1. Our aim was to study whether the ability to induce bone formation is related to the level of expression of bone morphogenetic protein. We studied the osteoinductive abilities and levels of expression of bone morphogenetic protein of Saos-2 cells both during the growth phase and after confluency was reached. Subconfluent cells were at least 70% less effective in their osteoinductive ability than confluent cells. Comparison of bone morphogenetic protein mRNA expression in confluent and subconfluent cells revealed that the latter had lower expression of all the mRNAs studied. The expression of bone morphogenetic protein-1, bone morphogenetic protein-2, and bone morphogenetic protein-6 mRNAs was 2, 3, and 6 to 10-fold lower, respectively, in subconfluent cells. These results suggest that the ability of Saos-2 cells to induce de novo bone formation may be correlated with the relative expression of these proteins; the expression of bone morpho-genetic proteins in Saos-2 cells also may be dependent on the cell cycle.     

The Results of Water Fluoridation in Ireland

The visit of Dr. Trendley Dean to Dublin in the mid-1950s helped accelerate the decision to introduce water fluoridation as a public health measure in the prevention of caries in the Republic of Ireland. A challenge to the constitutional validity of the Health (Fluoridation of Water Supplies) Act 1960 failed and in 1964 the water supplies of Dublin city were fluoridated. Over the next seven to eight years all the major urban communities in the Republic of Ireland were fluoridated. Currently, 67 percent of the 3.5 million people in the country reside in fluoridated communities. Studies conducted over the last 20 years show that residents of fluoridated communities have better dental health than those in nonfluoridated communities—the mean dmft is lower in children and the number of natural teeth present in adults is higher.     

Detection of antidrug IgG antibodies in patients with adverse drug reactions to amodiaquine

Antidrug IgG antibodies have been detected in some patients receiving amodiaquine (AQ). Antidrug antibodies were detected in 6/7 patients who experienced serious well-defined adverse drug reactions during malaria prophylaxis and in 7/22 patients who received comparable doses of the drug (at least 400 mg weekly x 6) but did not present with clinical adverse drug reactions. In contrast antidrug antibodies were not detected in 7 patients who received the drug for treatment (1.0-1.2 g total over 3 days). The specificity of the IgG response was defined by hapten inhibition experiments (IC50 value for AQ ranged between 0.050 and 0.282 microM) which suggest that the antibody recognised the drug linked to cysteine residues in protein via the 4-hydroxyanilino side chain. The data show that AQ is immunogenic in man and are consistent with the hypothesis that idiosyncratic adverse reactions to the drug have an immunological aetiology.     

Ovariectomy in the rat induces a rapid increase in the urinary excretion of hydroxylysine glycosides and non-reducible crosslink residues

The ovariectomized rat is the most commonly used animal model of human postmenopausal osteoporosis, exhibiting a high rate of bone turnover with resorption exceeding formation. At present, bone turnover is quantified directly by dynamic histomorphometry. The aim of the present study was to determine whether the measurement of the urinary output of some specific bone collagen catabolites — pyridinolines and hydroxylysine glycosides — could be used to indirectly monitor the initial phase of bone turnover increase in ovariectomized 90-day-old rats. Ninety-day-old female rats were randomly divided into three groups (n=6): ovariectomized, sham-operated and non-treated controls. Urine samples (24 h) were collected 6 days before surgery and twice weekly for the 4 weeks following ovariectomy. Urinary excretion of pyridinoline (PYD), deoxypyridinoline (DPD), glucosyl-galactosyl-hydroxylysine (GGHYL) and galactosyl-hydroxylysine (GHYL) were measured. As expected, ovariectomy was associated with a significant decrease in bone mineral density in both the proximal tibial and distal femoral metaphysis. Compared with both sham-operated and control animals, ovariectomized rats showed significant increases in PYD, GGHYL and GHYL urinary output 8 days after surgery and in DPD output after 15 days. These changes were maintained throughout the study. The results confirm that measurement of the urinary excretion of pyridinolines and hydroxylysine glycosides represents a powerful tool for detecting the onset of bone turnover in ovariectomized 90-day-old rats.