Magnetic resonance imaging: absence of in vitro cytogenetic damage

Human lymphocytes and Chinese hamster ovary (CHO) cells in culture were exposed for 12 1/2 hours to a magnetic resonance imaging apparatus with a 2.35-Tesla magnet and 100-MHz radio frequency emission. The cells were examined for cytogenetic damage manifested either as chromosome aberrations or sister chromatid exchanges (SCEs), which constitute very sensitive measures of genetic and cellular damage. In either unstimulated or stimulated human lymphocytes, as well as in exponentially growing CHO cells, no increase in either chromosome aberrations or SCEs was found as a result of exposure to these MR conditions. The data indicate that long-term exposure to MR imaging conditions far exceeding those to be found in the clinical situation does not cause cytogenetic damage.     

The biological activity and activation of 15,16-dihydro-1,11-methanocyclopenta[a]phenanthren-17-one, a carcinogen with an obstructed bay region

The proposal that an unobstructed bay region is a prerequisite for tumorigenic activity in cyclopenta[a]phenanthrene-17-ones is not supported by the observation of the tumorigenicity of 15,16-dihydro-1,11-methanocyclopenta[a]phenanthrene-17-one towards the skin of T.O. mice. The title compound is oxidised in vitro by a mixed function oxidase to produce, inter alia, a trans-3,4-dihydrodiol, postulated as the proximate tumorigen. Unequivocal identification of a second metabolite as a trans-1,2-dihydrodiol derivative demonstrates the potential for enzymatic oxidation within the obstructed bay region and supports the proposal that the ultimate tumorigen is a trans-3,4-dihydrodiol-anti-1,2-oxide. This is further substantiated by the chromatographic behaviour of the major hydrocarbon-nucleoside adduct derived from mouse skin treated with the parent compound in vivo. The structures of certain others of the metabolites produced in vitro are also considered.     

Granulomatous angiitis of the nervous system: a case report of long-term survival

In 1977, a 61-year-old man developed an occipital hemorrhage, and a biopsy specimen revealed granulomatous angiitis of the nervous system. No concurrent infection or systemic vasculitis was present. After initial treatment with steroids and cyclophosphamide, the patient did well on chronic steroids alone for 4 years. He then independently stopped taking the steroids and suffered a second hemorrhage. Steroids were reinstated, and he did well for 3 more years before he experienced a third hemorrhage. Intravenous steroids were given acutely and tapered to a chronic maintenance dose. Although granulomatous angiitis of the nervous system usually causes death within weeks to months of the appearance of symptoms, the patient is still alive more than 12 years since the tissue-proven diagnosis. This unusually long survival is attributed to the continued use of steroids, even when the patient is asymptomatic.     

The pharmacology of epanolol (ICI 141292)--a new beta 1-selective adrenoceptor partial agonist

The clinical benefit of beta-adrenoceptor partial agonists is still debated. To clarify the situation, epanolol, ICI 141,292 [N-[-2-(3-o-cyanophenoxy-2-hydroxypropylamino)ethyl]-4- hydroxyphenylactamide], has been developed to assess the role of modest beta-adrenoceptor partial agonist activity in humans. Animal studies have shown that epanolol is a potent beta-adrenoceptor partial agonist with a greater affinity for beta 1- than beta 2-adrenoceptors. In vitro, the PA2 values obtained for espanolol at atrial and tracheal beta-adrenoceptors were 8.42 and 6.33, respectively (isoproterenol as agonist), giving a selectivity ratio of 123. The potency was studied in vivo in the dog, where it was also shown that as an antagonist at the cardiac beta 1-adrenoceptor, it was 18 and 40 times more potent than atenolol and practolol, respectively. Espanolol has less partial agonist activity in the rat than pindolol, but more than practolol. In this species, it is also a classical partial agonist, exhibiting agonist activity at all beta-adrenoceptor blocking doses. This is in contrast to pindolol, which caused predominantly beta-adrenoceptor blockade at low doses and partial agonist activity at higher doses. These differences were confirmed in haemodynamic studies in the dog. In contrast to many other partial agonists, the partition coefficient, log P, of epanolol in octanol and water is low (0.92).     

Coiled nucleocapsid configuration in subacute sclerosing panencephalitis (SSPE)

Summary In this case of documented subacute sclerosing panencephalitis (SSPE), electron microscopy of a brain biopsy revealed a previously unreported fingerprint configuration of tubular inclusions or nucleocapsids. The pattern resembled that of the whorled filamentous nuclear bodies which are so frequently encountered in ultrastructural studies of this disease. Furthermore, an apparent tubule was seen running parallel to filaments within the nucleus of still another affected cell. These findings lend support to the concept that nuclear bodies are converted into and/or synthesize nucleocapsids.     

咪苯嗪酮对TXA2和HHT生成的选择性抑制作用

咪苯嗪酮(CI-914)能抑制大鼠血小板环氧酶和TXA₂合成酶产物HHT的生成,而对脂氧酶产物12-HETE的生成仅高浓度药物才有弱的抑制作用,提示CI-914主要影响花生四烯酸(AA)环氧酶途径,而对脂氧酶途径影响较少。在大鼠血小板和中性白细胞CI-914能抑制TXA₂的生成,同时CI-914还可使白细胞6-keto-PGF_1a和血小板PGE₂的产生量显著增加,提示CI-914在这两种细胞引起了AA的转向合成。上述结果基本证实,CI-914在大鼠中性白细胞和血小板对TXA₂合成酶具有选择性抑制作用。     

Cerebrospinal fluid analyses in migraine patients and controls

To investigate the role of central neurotransmitters in the pathogenesis of migraine, we measured cerebrospinal fluid (CSF) levels of certain amino acids (glycine, taurine, glutamine) and metabolites of biogenic amines (5-hydroxyindoleacetic acid and homovanillic acid) in 38 migraine patients and compared them with the levels from 10 headache-free controls. The levels of taurine, glycine and glutamine were significantly higher in the migraine patients (p < 0.0001 for taurine and glycine; p < 0.0009 for glutamine); there were no significant differences among the three migraine subgroups (infrequent migraine, frequent migraine and transformed migraine). In seven patients subsequently treated with divalproex sodium, CSF taurine levels decreased significantly from pretreatment baseline values. These data support the concept that migraine is at least in part a disorder of central neurotransmission.