PROPRANOLOL FOR MIGRAINE PROPHYLAXIS

SYNOPSIS
The preventive effect of propranolol on migraine attacks was compared to placebo in a double-blind cross-over trial. Thirty-two patients with serious and prolonged migraine participated in the 12-week study. The effect of propranolol was significantly better than that of placebo. The number of migraine attacks during the propranolol period was reduced in 22 patients (69%), and in 11 of these (34%) a reduction of more than 50% was seen. The intensity of headache was significantly reduced during the propranolol period. The intake of analgesics and preparations containing ergotamine was significantly reduced during the propranolol period also. No serious side effects were noted.     

Menstrual bleeding with copper-covered ihtrauterine contraceptive devices

The menstrual blood loss before and during three menstruations after insertion of two copper-covered intrauterine devices (TCu 200 and Cu 7 200) was studied in 82 women.

Of 66 women with normal menstruations, 50 were fitted with a TCu 200 and 16 with a Cu 7 200 device. Sixteen women with profuse menstrual bleeding were fitted with a TCu 200 device.

The menstrual blood loss was increased during the first two periods, but by only half of that reported after insertion of other intrauterine contraceptive devices (IUDs), and it was followed by an improvement in the third period. Women with menorrhagia before insertion of the devices had no significant increase in bleeding. The use of copper IUDs reduces the need of medication and control tests.     

The β-adrenoceptors of the lung mediating inhibition of antigen-induced histamine release

The β-adrenoceptor stimulants, isoprenaline (IPR), orciprenaline (OPR), terbutaline (TRB), and ITP^** were studied for effects on antigen-induced release of histamine from guinea-pig lung tissue and for effects on guinea-pig isolated trachea and heart. The order of potency for the agents in the four functions studied were: (a) inhibition of histamine release, IPR > OPR ≈ TRB ITP = 0; (b) heart stimulation, chronotropic effect, IPR > OPR > ITP ≈ TRB; (c) heart stimulation, inotropic effect, IPR > OPR > ITP > TRB; (d) trachea relaxation: IPR > TRB > OPR ITP. These findings suggest that the β-adrenoceptors mediating inhibition of antigen-induced release of histamine are more related to those mediating trachea relaxation (β₂) than those mediating cardiac stimulation (β₁).     

Cytochrome c stimulated oxidation of ethanol by liver mitochondria

The addition of ethanol, NAD, alcohol dehydrogenase and cytochrome c to liver mitochondria gives rise to an oxygen consumption which is proportional to the amount of ethanol oxidized. The system is insensitive to rotenone and antimycin and not coupled to phosphorylation and is in these respects identical with the well-known NADH-cytochrome c reductase present in the outer membrane of liver mitochondria. The respiration is directly proportional to the added cytochrome c in the range of 1.6–16.3 μmoles/1. and follows the Michaelis-Menten equation for different ethanol concentrations (K_m = 6.2 μmoles/1). As cytochrome c is easily washed out of mitochondria during fractionation, the externally added cytochrome c probably replaces it in vitro. It is therefore suggested that cytochrome c may alternate between the outer and inner membrane and may be available in vivo for the oxidation of extramitochondrial NADH by means of the NADH-cytochrome c reductase in the outer membrane.     

Scintigraphic molecular imaging

Modern medicine is currently focusing its basic and clinical research towards "molecular medicine". This trend, together with the decoding of the human genome and the resulting design and use of transgenic mouse models of human diseases, demands that innovative imaging approaches are developed for man and mice. Non-invasive imaging modalities capable of quantifying molecular processes in vivo (collectively defined as "molecular imaging" techniques) are extremely interesting in this respect. This review focuses on the clinical and experimental scintigraphic molecular-imaging modalities SPECT and PET, and summarizes their actual and future impact in medicine.     

An aminoacridine derivative for radionuclide therapy: DNA binding properties studied in a novel cell-free in vitro assay

Radiolabelled DNA-binding compounds can be used to increase the efficiency of radionuclide cancer therapy of disseminated disease. In this work, the aminoacridine compound N-[3-(acridine-9-ylamino)-propyl]-3-iodobenzamide (A3) labelled with the Auger-emitting nuclide 125I using Chloramine-T was studied. Optimal labelling conditions of 125I-A3 were investigated and the interaction with DNA was studied using a novel cell-free in vitro assay with naked human genomic DNA in agarose plugs. This novel assay showed to be simple and reliable. The results verify that 125I-A3 specifically binds DNA with low dissociation and is potent in causing double-strand breaks, yielding 1.0-1.4 breaks per decay. In conclusion, 125I-A3 is a most suitable DNA-binding compound for future therapeutic studies of Auger-electron emitters like 125I.     

Prognostic and predictive value of changes in tumour cell proliferation in locally advanced breast cancer primarily treated with doxorubicin

We previously reported that high tumour cell proliferation evaluated by Ki-67 expression, high mitotic frequency and high histological grade were associated with resistance to primary doxorubicin monotherapy in locally advanced breast cancer harbouring wild-type (wt) TP53. The aim of our present study was to evaluate the predictive and prognostic impact of proliferation parameters assessed in tumour tissue obtained after chemotherapy, and alterations induced in tumour cell proliferation. While we found a significant reduction in Ki-67 expression and mitotic frequency in tumours with wtTP53 (p=0.001 and p=0.008, respectively), no significant change was recorded in tumours expressing mutant TP53. For histological grade there was no significant change in either group. There was a direct correlation between pre- and post-treatment values for Ki-67 and mitotic frequency in tumours harbouring wtTP53 (p=0.0001 for both), but no correlation in tumours harbouring mutated TP53. High post-treatment Ki-67 expression and mitotic frequency were found to predict doxorubicin resistance only in patients with wtTP53 (p=0.04 and p=0.03, respectively). The prognostic importance of proliferation markers and histological grade was found to be similar whether they were determined in the pre- or post-treatment samples (Ki-67; pre: p=0.02; post: p=0.03; mitotic frequency; p=0.002 and p=0.01, respectively; histological grade; p=0.0001 and p=0.002, respectively). While the reduction in mitotic frequency was associated with improved survival (p=0.03), no significant associations between changes in other parameters and outcome were recorded.