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H Kume

Publications and source records attributed to H Kume.

At least 19 recordsLinked to original sources
PubMed2001

Protection by tetracyclines against ion transport disruption caused by nystatin in human airway epithelial cells.

Polyene antifungal antibiotics like nystatin form monovalent cation pores on the plasma membrane that perturb the intracellular electrolyte milieu, resulting in cell damage. In the present study, we investigated the effects of tetracyclines (minocycline and tetracycline) on ion transporters disrupted by nystatin in cultured human airway Calu-3 cells. Apical application of nystatin (50 microM) on a monolayer of the cells stimulated Na(+)-K(+) pump activity as estimated by ouabain (1 mM)-sensitive short-circuit current (I(sc)). The nystatin-potentiated I(sc) was inhibited by minocycline (IC(50) = 25 microM) or tetracycline (IC(50) = 150 microM) applied only from the apical (nystatin-treated) side. Nystatin increased monolayer conductance that was reversed by the application of tetracyclines. In contrast, ouabain potentiated the nystatin-induced change in the conductance. Further, Na(+)-glucose transport affected by nystatin was also normalized by tetracyclines from the nystatin-treated side of the membrane. These data suggest that tetracyclines may lower the cell permeability potentiated by nystatin, protecting cells against damage.

Cell Line↗
PubMed2001

Novel effects of minocycline on Ca(2+)-dependent Cl(-) secretion in human airway epithelial Calu-3 cells.

The present study concerns previously unreported effects of the antibiotic minocycline on the transepithelial Cl(-) transport in Calu-3 cells, which display electrophysiological properties consistent with human airway serous cells. Basolateral 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 200 microM) augmented Cl(-) secretion, which was detected as a 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB, 100 microM, a Cl(-) channel blocker)-sensitive short-circuit current (I(sc)). The DIDS-induced I(sc) was composed of Ca(2+)-activated K(+) (K(Ca)) channel-dependent and -independent components. The former was selectively inhibited by 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl)ester (BAPTA/AM, 10 microM), charybdotoxin (ChTx, 100 nM), clotrimazole (10 microM), basolateral Ca(2+) removal, and basolateral minocycline (IC(50) = 20 microM). The latter was attenuated by basolateral BaCl (5 mM). In contrast, forskolin (10 microM)-induced I(sc), which is insensitive to BAPTA/AM and ChTx, was unaffected by minocycline (100 microM). ATP-induced I(sc) was partially inhibited by basolateral but not by apical minocycline. I(sc) due to basolateral application of ionomycin (1 microM) was markedly suppressed by NPPB and basolateral Ca(2+) removal. These inhibitory effects were mimicked by minocycline applied only from the basolateral side of the monolayer. In the basolateral absence of Ca(2+), 1-ethyl-2-benzimdazolinone (500 microM), a K(Ca) channel opener, generated a sustained I(sc) sensitive to ChTx. Minocycline had no significant effect on the ChTx-sensitive component of the I(sc). It is concluded that minocycline inhibits K(Ca) channel-dependent Cl(-) secretion via a blockade of Ca(2+) influx across the basolateral membrane from the extracellular side.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2001

Adrenomedullin and proadrenomedullin N-terminal 20 peptide induce histamine release from rat peritoneal mast cell.

Adrenomedullin (ADM)-induced histamine release from rat peritoneal mast cells was investigated. We compared the ability of full-length ADM to induce histamine release to the fragments ADM-(1-25) and ADM-(22-52), as well as proadrenomedullin N-terminal 20 peptide (PAMP). ADM (10(-8) to 10(-5) M) and PAMP (10(-8) to 10(-5) M) dose-dependently increased histamine release from peritoneal mast cell preparations. The effect of ADM-(1-25) was similar to ADM, whereas ADM-(22-52) did not show any effects. These data suggest the relative importance of the ADM C-terminal fragment, which contains a six-membered ring structure. Histamine release, induced by ADM, was significantly and dose-dependently inhibited by the addition of ADM-(22-52) (10(-5) M), Ca(2+) (0.5 to 2.0 mM), and benzalkonium chloride (3 to 7 microM), a selective inhibitor of Gi type G proteins. In contrast, PAMP (10(-5) M)-induced histamine release was not inhibited by Ca(2+). These results suggest that ADM induce histamine release via a putative ADM receptor in a manner sensitive to Gi-protein function and extracellular Ca(2+) concentration, and that PAMP might produce its effect by a different mechanism than ADM.

Adrenomedullin↗
PubMed2001

[(Dihydroindenyl)oxy]alkonic acid inhibits the cystic fibrosis transmembrane conductance regulator.

We investigated the effects of [(dihydroindenyl)oxy]alkaonic acid (DIOA) on the Cl(-) secretion in Calu-3 human airway epithelial cells that exclusively express the cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl(-) channel. The 5'-nitro-2-(3-phenylpropylamino) benzoate (NPPB)-sensitive short-circuit current (I(sc)) and apical conductance were markedly reduced by DIOA (100 microM) in the presence and absence of isoproterenol (10 nM). Replacement of the butyl group in DIOA with a methyl group attenuated the inhibitory effects. The ED(50) of DIOA (17.0+/-1.0 microM) was almost equivalent to that of NPPB (15.6+/-2.1 microM). In conclusion, DIOA inhibits CFTR as strongly as NPPB does.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Usefulness of lanoconazole (Astat) cream in the treatment of hyperkeratotic type tinea pedis. Comparative study of monotherapy and combination therapy with 10% urea ointment (Pastaron).

Hyperkeratotic type tinea pedis is a refractory type of superficial dermatomycosis. Treatment for hyperkeratotic type tinea pedis is mainly with oral antimycotics, such as griseofulvin, and healing is generally considered to be difficult with only topical antimycotics. In this randomized comparative study, the usefulness of a topical application of 1% lanoconazole cream (Astat) monotherapy (group I) was compared with that of combination therapy with 1% lanoconazole cream and 10% urea ointment (Pastaron) (group II) in a series of patients with hyperkeratotic type tinea pedis. The clinical improvement rates (percentage of 'marked improvement' plus 'moderate improvement') was 70.0% in group I and 95.7% in group II. The fungal eradication rate was 5.0% in group I and 43.5% in group II after 4 weeks of treatment, and was 70.0% and 95.7% after 12 weeks of treatment, respectively. The usefulness rate (percentage of 'very useful' plus 'useful') was 70% in group I and 95.7% in group II. Both lanoconazole monotherapy and the combination therapy with 10% urea ointment were highly effective and safe. Both treatments should be recommended for patients with hyperkeratotic type tinea pedis for whom an oral treatment is not appropriate or for whom a sufficient improvement with oral medications cannot be expected.

Administration, Topical↗
PubMed2001

Butenafine hydrochloride (Mentax) cream for the treatment of hyperkeratotic type tinea pedis and its transfer into the horny layer, with or without concomitant application of 20% urea ointment (Keratinamin).

Forty-five patients were divided into two groups: group I, 23 patients, treated with butenafine hydrochloride (Mentax) cream alone, and group II, 22 patients, treated with butenafine hydrochloride and 20% urea ointment (Keratinamin) to evaluate the usefulness of the treatments. We also measured the transfer of these drugs to the horny layer in some patients. The clinical improvement rate of dermatological symptoms (marked improvement + improvement) was 91.3% in group I, 100% in group II, with therapeutic effects evident earlier in group II than in group I. The mycological eradication rate was found to be 47.4% in group I, 50.0% in group II after 4 weeks of treatment, and 81.8 and 87.5% at 12 weeks thereaftcr. respectively, with no adverse reactions found. The clinical utility rate (markedly useful + useful) was 91.3% in group I and 86.4% in group II. These results demonstrate that application of butenafine hydrochloride alone was extremely effective for the treatment of hyperkeratotic-type tinea pedis and that combination application with urea ointment resulted in an earlier improvement of dermatological symptoms. The concentration of butenafine in the horny layer from healthy volunteers reached a steady state in both groups I and II at 2 weeks after the application, with a lower concentration found in group II (about 70 ng mg(-1)) than in group I (about 100 ng,mg(-1)). Although some variations in concentration were found in case by case, patients in whom the treatment was determined to be 'markedly effective and effective' showed the increase in concentration of the drug in the lesional horny layer to be directly proportional to the number of days of treatment, with a lower concentration found in group II than in group I. This trend was also seen in healthy volunteers.

Administration, Topical↗
PubMed2001

Differential effect of phosphodiesterase inhibitors on IL-13 release from peripheral blood mononuclear cells.

Increased cyclic AMP (cAMP)-phosphodiesterase (PDE) activity in peripheral blood leucocytes is associated with the immunological inflammation that characterizes allergic diseases, such as atopic dermatitis and allergic rhinitis. Recently, it has been found that IL-13 has similar biological functions to IL-4. The aim of this study was to investigate the possible involvement of cAMP-PDE activity on IL-13 release from peripheral blood mononuclears cells (PBMC) from atopic asthma patients. Phytohaemagglutinin (PHA)-induced IL-13 release from PBMC was concentration-dependently inhibited by rolipram, a type 4 PDE inhibitor, as well as by dibutyryl cAMP, a membrane-permeant cAMP analogue. However, theophylline, a non-specific PDE inhibitor, and cilostazol, a type 3 PDE inhibitor, failed to inhibit IL-13 release. The inhibitory effect of rolipram was enhanced by the addition of forskolin (10(-4) m), an adenylyl cyclase stimulator. PHA itself did not alter the intracellular cAMP level. Rolipram concentration-dependently increased cAMP level in PHA-stimulated PBMC, and this increase was synergistically facilitated by the addition of forskolin (10(-4) m). These results suggest that type 4 PDE inhibitors, alone or synergistically in combination with forskolin, inhibit PHA-induced IL-13 release from PBMC of atopic asthma patients by elevating intracellular cAMP concentrations. These inhibitors have the potential to exert an anti-inflammatory effect by inhibiting IL-13 production in allergic diseases such as atopic asthma.

Adult↗
PubMed2001

Possible involvement of Rho kinase in Ca2+ sensitization and mobilization by MCh in tracheal smooth muscle.

We examined the effects of Rho kinase on contraction and intracellular Ca2+ concentration ([Ca2+](i)) in guinea pig trachealis by measuring isometric force and the fura 2 signal [340- to 380-nm fluorescence ratio (F340/F380)]. A Rho kinase inhibitor, Y-27632 (1-1,000 microM), inhibited methacholine (MCh)-induced contraction, with a reduction in F340/F380 in a concentration-dependent manner. The values of EC(50) for contraction and F340/F380 induced by 1 microM MCh with Y-27632 were 27.3 +/- 5.1 and 524.1 +/- 31.0 microM, respectively. With 0.1 microM MCh, the values for these parameters were decreased to 1.0 +/- 0.1 and 98.2 +/- 6.2 microM, respectively. Tension-F340/F380 curves for MCh indicated that Y-27632 caused an ~50% inhibition of MCh-induced contraction, without a reduction in F340/F380. These effects of Y-27632 were not inhibited by a protein kinase C inhibitor, GF-109203X. Our results indicate that inhibition of Rho kinase attenuates both Ca2+ sensitization and [Ca2+](i).

Amides↗
PubMed2001

Role of lysophosphatidylcholine in the desensitization of beta-adrenergic receptors by Ca(2+) sensitization in tracheal smooth muscle.

Lysophosphatidylcholine (Lyso-PC) is generally considered to promote tissue inflammation. To determine the involvement of exogenous Lyso-PC in the beta-adrenergic desensitization by phospholipase A2, we examined the inhibitory effects of isoproterenol (ISO) on tension and intracellular Ca(2+) concentration by methacholine (MCh) after continuous exposure to Lyso-PC in guinea-pig tracheal smooth muscle, using isometric tension recordings and fura-2 signal (F340/F380 ratio). Pre- exposure to 10 microM Lyso-PC markedly reduced subsequent inhibition by 0.3 microM ISO against 1 microM MCh-induced contraction in a time-dependent manner. In contrast, values of percent F340/F380 ratio for MCh with ISO were not affected after exposure to Lyso-PC. In the presence of Y-27632, a selective rho-kinase inhibitor, a reduction in subsequent relaxation by ISO after exposure to Lyso-PC was inhibited in a concentration-dependent manner. Preincubation with cholera toxin also inhibited reduced responsiveness to ISO by Lyso-PC. Pre-exposure to Lyso-PC did not attenuate subsequent relaxation by agents that bypass beta-adrenergic receptors. These results indicate that continuous exposure to Lyso-PC may cause homologous desensitization of beta-adrenergic receptors via an augmentation in sensitivity to Ca(2+) by rho, a small G protein, in airway smooth muscle, and that activation of the stimulatory G protein of adenylyl cyclase, G(s), may prevent this phenomenon.

Adenylate Cyclase Toxin↗