Effect of NZ-107, a newly synthesized pyridazinone derivative, on antigen-induced contraction of human bronchial strips and histamine release from human lung fragments or leukocytes.

The effects of a newly synthesized pyridazinone derivative, NZ-107, 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone, and two well-known antiasthmatic drugs, amlexanox (orally active disodium cromoglycate-like drug) and disodium cromoglycate (DSCG) on antigen-, histamine- and leukotriene C4 (LTC4)-induced constriction of isolated human tracheal muscle, and histamine release from human lung tissues and leukocytes were investigated in vitro. In some experiments, salbutamol was used as a reference drug. NZ-107 inhibited antigen-, histamine- and LTC4-induced contraction of tracheal muscle. Amlexanox and DSCG did not affect the contractile response of tracheal muscle caused by each stimulant. Salbutamol inhibited antigen-induced contraction of tracheal muscle. NZ-107, amlexanox, DSCG and salbutamol clearly inhibited the antigen-induced release of histamine and LTC4 from human lung tissue. The antigen-induced histamine release from atopic human leukocytes was inhibited by NZ-107 and amlexanox, but not by DSCG. Pretreatment with IL-3 did not alter antigen-induced contraction of tracheal muscle and histamine release from lung tissue, but antigen- or calcium ionophore A 23187-induced histamine release from leukocytes was clearly enhanced. Amlexanox inhibited the IL-3-induced enhancement of histamine release from leukocytes in the case of both stimuli, but NZ-107 and DSCG had no effect. These data suggest that NZ-107 has potent anti-allergic actions based on the inhibition of antigen-induced contraction of human tracheal muscle and mediator release from human lung tissue and leukocytes.     

Regional cerebral blood flow (rCBF) in patients with ruptured cerebral aneurysm: site of aneurysm and rCBF

To investigate the relationship between the site of ruptured cerebral aneurysm and rCBF, 92 measurements of rCBF were conducted in 57 patients with ruptured cerebral aneurysm. Excluded from this study were patients with multiple aneurysms, intracerebral hematoma, and/or hydrocephalus. Twenty-four patients had the anterior communicating aneurysm (A-com), 20 patients had the internal carotid aneurysm (ICA), and 13 patients had the middle cerebral aneurysm (MCA). All patients underwent unilateral fronto-temporal craniotomy for clipping of the aneurysm and their rCBF measurements, using the xenon-133 inhalation method, were performed in the first three weeks after surgery. In each rCBF measurement, the hemispheric mean value of initial slope index (meanISI) was calculated in both cerebral hemispheres, that is, in the cerebral hemispheres ipsilateral and contralateral to craniotomy. The authors defined the "symmetry index of the meanISI (%): symmetry index" as the ratio of the meanISI in the cerebral hemisphere ipsilateral to craniotomy compared to the meanISI in the cerebral hemisphere contralateral to craniotomy. There was no significant relationship between the site of aneurysm and the meanISI in both hemispheres, and this result suggests that the site of aneurysm makes no difference in the incidence of vasospasm. In the postoperative first week, the "symmetry index" was 91.2 +/- 7.4% in MCA, 95.3 +/- 4.1% in ICA, and 97.9 +/- 8.2% in A-com; that is, MCA had significant asymmetry of meanCBF compared with A-com (p less than 0.05). In the second and third postoperative weeks, there was no significant relationship between the site of aneurysm and the asymmetry of meanCBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Novel organosilicon-containing polymers for an oxygen permselective membrane

Synthesis and gas permeation measurements of several types of polymers from methylstyrene derivatives containing mono-and bis(trialkylsilyl) group(s) were carried out. Upon radical homo-and co-polymerization of silicon-containing monomers high-molecular-weight polymers were obtained. Results from gas permeation measurements showed that these types of silicon-containing polymers exhibit fairly high oxygen permselectivity (ratio of oxygen and nitrogen permeation coefficients P/P = 3,1 ? 4,6), keeping the oxygen permeation coefficients (P) in the range of between 1,4 · 10^?9 and 4,5·10^?9 cm³ (STP) · cm · cm^?2 · s^?1 · cmHg^?1. From time lag measurements, it was found that permeation coefficients are dependent on the solubility of gases in the membranes rather than on diffusivity. Actually, the oxygen solubility coefficients increase with increasing silicon content in the polymers. Permselectivity of oxygen against nitrogen is governed by polymer constitution rather than by silicon content.     

Functional evaluation of the hypothalamic-pituitary-adrenal axis

The regulation of hypothalamic pituitary-adrenal (HPA) axis is controlled by three major factors: stress, circadian rhythm and negative feedback. Hypothalamic CRF binds to CRF receptor on ACTH cells and stimulates synthesis and secretion of ACTH. However, vasopressin binds to V1b receptor and enhances CRF induced ACTH secretion. ACTH stimulate secretion of cortisol and DHEA-S. Cortisol inhibits secretion of CRF and ACTH with negative feedback mechanism. To evaluate the ability of the hypothalamus to secrete CRF, insulin-induced hypoglycemia and metyrapone tests are used. For evaluation of the secretion of pituitary ACTH and adrenal cortisol, a CRF test is useful. Autonomic secretion of ACTH and/or cortisol is evaluated with a dexamethasone suppression test.     

Degradation of methyl and ethyl mercury into inorganic mercury by oxygen free radical-producing systems: Involvement of hydroxyl radical

Degradation of methyl mercury (MeHg) and ethyl Hg (EtHg) with oxygen free radicals was studied in vitro by using three well-known hydroxyl radical (OH)-producing systems, namely Cu²⁺-ascorbate, xanthine oxidase (XOD)-hypoxanthine (HPX)-Fe(III)EDTA and hydrogen peroxide (H₂O₂)-ultraviolet light B. For this purpose, the direct determination method for inorganic Hg was employed. MeHg and EtHg were readily degraded by these three systems, though the amounts of inorganic Hg generated from MeHg were one half to one third those from EtHg. Degradation activity of XOD-HPX-Fe(III)EDTA system was inhibited by Superoxide dismutase, catalase and the OH scavengers and stimulated by H₂O₂. Deletion of the OH formation promoter Fe(III)EDTA from XOD-HPX-Fe(III)EDTA system resulted in the decreased degradation of MeHg and EtHg, which was enhanced by further addition of the iron chelator diethylenetriamine pentaacetic acid. In all these cases, a good correlation was observed between alkyl Hg degradation and deoxyribose oxidation determining OH. By contrast, their degradation appeared to be unrelated to either Superoxide anion production or H₂O₂ production alone. We further confirmed that H₂O₂ (below 2 mM) itself did not cause significant degradation of MeHg and EtHg. These results suggested that OH, but not and H₂O₂, might be the oxygen free radical mainly responsible for the degradation of MeHg and EtHg.     

Treatment failures secondary to drug interactions with divalent cations and fluoroquinolone

We observed four cases of therapeutic failures while patients were simultaneously taking medications that contained divalent cations and oral fluoroquinolones. Patients improved after conversion to the intravenous formulation of the same antibiotics, proper spacing of the divalent cation, or conversion to a different antibiotic class. Patients prescribed oral fluoroquinolones should receive instructions on proper separations of these antibiotics with divalent cations. Health care professionals should be cognizant of these interactions and educated on their potential deleterious effect.