Protective effect of anisodamine against Shiga toxin-1: inhibition of cytokine production and increase in the survival of mice.

The purpose of this study was to investigate whether anisodamine could inhibit Shiga toxin-1 (Stx1)-induced cytokine production and increase the survival of Stx1-treated mice. Human monocytic cells were stimulated by Stx1 (1 to 100 ng/mL) with or without anisodamine addition (1 to 400 microg/mL). For in vivo evaluations, C57BL/6 mice were given a single intraperitoneal injection of anisodamine (1 mg) or saline solution after intraperitoneal injection of Stx1 (2.75 microg/kg). The results showed that anisodamine significantly suppressed Stx1-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-8 production. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that anisodamine suppressed Stx1-mediated TNF-alpha mRNA expression. Further study showed that this TNF-alpha inhibitory effect was via a prostaglandin E2-dependent mechanism. Anisodamine treatment prolonged the survival time of mice and decreased the lethality of Stx1 (94.5% to 44%). Because cytokines, in particular TNF-alpha, contribute to the pathologic process in Stx-producing Escherichia coli (STEC) infection, this study suggested that anisodamine could be a potential drug for treatment of STEC infection.

Saponins isolated from Allium chinense G. Don and antitumor-promoting activities of isoliquiritigenin and laxogenin from the same drug.

Investigation of the Chinese crude drug "Xiebai," the bulbs of Allium chinense G. Don (Liliaceae), led to the isolation of 2 saponins, xiebai-saponin I (laxogenin 3-O-beta-xylopyranosyl (1-->4)-[alpha-arabinopyranosyl (1-->6)-beta-glucopyranoside) (1) and laxogenin 3-O-alpha-arabinopyranosyl (1-->6)-beta-glucopyranoside (2), and the aglycone, laxogenin (3), together with 2 chalcones, isoliquiritigenin (4) and isoliquiritigenin-4-O-glucoside (5), and beta-sitosterol glucoside (6). Compounds 1-5 were tested in vitro for their inhibitory effect on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32Pi-incorporation into phospholipids of HeLa cells. In addition to this, laxogenin (3) was proven to have an antitumor-promoting activity in a two-stage lung carcinogenesis experiment.

Double ventricular response by a single ventricular extrastimulus to the inner loop of reentry in a patient without apparent heart disease.

In a patient without apparent heart disease, a ventricular extrastimulus delivered from the left ventricular apex where the electrogram was recorded 30 ms after the onset of the QRS complex during VT advanced the second QRS complex, but not the first QRS complex. The morphology of the second QRS complex was the same as that of VT. The postpacing interval was the same as the cycle length of the VT. These findings indicated that the site of stimulation was at the inner loop of the reentry circuit of the VT. A ventricular extrastimulus with a shorter coupling interval advanced the first and second QRS complexes, indicating that the ventricle was activated by antidromic and orthodromic activation from the extrastimulus. Radiofrequency ablation at that site of stimulation terminated the VT and no further VT could be induced.

Selective effects of genistein, a soybean isoflavone, on B-lymphopoiesis and bone loss caused by estrogen deficiency.

Genistein, an isoflavone abundantly present in soybeans, has structural similarity to estrogen, suggesting that genistein may act as a phytoestrogen. To examine the possible role of genistein in hemopoiesis and bone metabolism, female mice were either sham-operated or ovariectomized (OVX), and selected OVX mice were administered genistein for 2-4 weeks (0.1-0.7 mg/day) or 17beta-estradiol (E2; 0.01-0.1 microg/day) s.c., using a miniosmotic pump (Alza Corp., Palo Alto, CA). In OVX mice, uterine weight declined but was completely restored by E2 administration. In contrast, genistein did not demonstrate a reversal of the OVX-induced uterine atrophy. The number of bone marrow cells markedly increased, 2-4 weeks after OVX, and most of these were B220-weakly positive pre-B cells. The increased B-lymphopoiesis was completely restored, not only by E2 but also by genistein administration. In OVX mice, the trabecular bone volume of the femoral distal metaphysis, measured by microcomputed tomography scanning and dual-energy x-ray absorptiometry, was markedly reduced; and genistein restored this, as did E2. These results indicate that genistein exhibits estrogenic action in bone and bone marrow, to regulate B-lymphopoiesis and prevent bone loss, without exhibiting estrogenic action in the uterus. Phytoestrogens may be useful for preventing bone loss caused by estrogen deficiency in females.

Does potassium induce the release of nitric oxide in the rabbit corpus cavernosum?

We investigated the effects of increases in the extracellular potassium concentration on the function of the rabbit corpus cavernosum. The resting tissue tension increased as the potassium concentration was increased from 4.7 mM to 20 mM or 30 mM. The maximum contraction induced by 200 microM phenylephrine was significantly decreased in the presence of 30 mM potassium compared with 4.7 mM potassium. After precontraction was induced with 200 microM phenylephrine, the magnitude of field-stimulated relaxation increased significantly as the potassium concentration was increased from 4.7 mM to 10 or 20 mM, but was almost completely abolished at 30 mM potassium. There was no difference in the suppressive effect of L-NAME on field-stimulated relaxation between specimens treated with 4.7 mM or 20 mM potassium. ATP- and bethanechol-induced relaxation was not affected by increases in the extracellular potassium concentration. A high-dose potassium solution (124 mM) induced contraction of the corpus cavernosum. In tissue precontracted with phenylephrine, a high-dose potassium solution that contained phenylephrine induced relaxation of corpus cavernosum; this relaxation was completely suppressed by L-NAME. These findings suggest that small increases in the extracellular potassium concentration increase field-stimulated relaxation of the corpus cavernosum and that this relaxation is not related to the effects of nitric oxide. Relaxation induced by high-dose potassium in tissue precontracted with phenylephrine is probably the result of release of nitric oxide.

Effects of alterations in potassium and calcium concentrations on the pressure generated in rat whole bladder in vitro.

BACKGROUND: Various physiologic systems maintain the ionic equilibrium essential for normal neuron and smooth muscle function. These systems are impaired by nonphysiologic concentrations of extracellular cations. This study investigated the effects of altered extracellular concentrations of potassium and calcium on the in vitro pressure generation in the whole bladder of rats. METHODS: Pressure increases in response to field stimulation, as well as low and high doses of bethanechol, were determined in a Krebs solution containing a normal amount of potassium, and in excess of 10 mmol/L and 20 mmol/L of potassium. Each of these solutions had calcium concentrations, that were low (0.8 mmol/L), normal (2.5 mmol/L), or high (7.5 mmol/L). RESULTS: The response to field stimulation was significantly decreased at the 20-mmol/L concentration of potassium in the presence of the different concentrations of calcium. The response to field stimulation increased as the extracellular concentration of calcium increased. The pressure increase caused by a low dose of bethanechol was significantly enhanced by elevations in the concentrations of both potassium and calcium. There was no difference in the response to a high dose of bethanechol in the presence of the various concentrations of potassium and calcium. CONCLUSION: These findings indicated that changes in the cationic equilibrium that result in blocking of the neuronal sodium channels, as well as increasing the level of intracellular bound calcium in smooth muscle, alter bladder function in vitro.

[Clinical trials of TAE using micro-coil coated with n-butyl 2-cyanoacrylate and lipiodol].

Clinical trials of TAE using microcoils (Target, USA) coated with n-butyl 2-cyanoacrylate and lipiodol were performed. The procedures were as follows. First, a small amount of lipiodol was injected into a Tracker 18 catheter. Secondly, a microcoil coated with n-butyl 2-cyanoacrylate and lipiodol was inserted into the microcatheter. Thirdly, a small amount of lipiodol was again administered into the catheter just behind the coil. Finally, the coil was pushed safely out from the catheter with a special guidewire. With this method, excellent occlusion of small arteries was obtained. There were no complications.

Amino acid-induced responses in CNS neurons of normal mouse and Wriggle Mouse Sagami.

Amino acid-induced responses and their regional heterogeneities in the motor cortical and hippocampal (CA1) neurons of normal mouse and Wriggle Mouse Sagami (WMS) were studied by conventional patch-clamp techniques. There were no differences in the current densities and EC50s of glutamate-, gamma-amino butyric acid (GABA)-, and glycine-induced responses between the two groups of mice. In both types of mice, the GABA-induced current density of cortical neurones was higher and EC50 was lower than in hippocampal neurones, whereas the responses induced by glycine and glutamate did not show any differences.

[The clinical application of oxygen saturation pulse oximeter in otolaryngological field].

Recently, we had opportunity to use an oxygen saturation pulse oximeter (minolta pulsox-7) which is a compact, light-weight device and allows continuous, percutaneous easy determination of arterial blood oxygen saturation. We obtained the following results from clinical application of this device in the field of otorhinolaryngology. 1. There was a high coefficient of correlation (0.899) between the values of oxygen saturation determined with a Minolta Pulsox-7 and an arterial blood gas analyzer. 2. This instrument was simple to handle and was clinically applicable, and seems to be highly useful for a) timing of tracheostomy, b) objective evaluation of dyspnea, c) monitor of nasal surgery under local anesthesia.