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1.
Clin Exp Allergy ; 39(1): 138-46, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18778270

ABSTRACT

BACKGROUND: Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model. OBJECTIVE: To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR). METHODS: Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay. RESULTS: Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists. CONCLUSIONS: SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR.


Subject(s)
Allergens/immunology , Disease Models, Animal , Pollen/immunology , Rhinitis, Allergic, Seasonal/physiopathology , Tachykinins/metabolism , Animals , Guinea Pigs , Humans , Nasal Lavage Fluid/chemistry , Nasal Obstruction , Nasal Provocation Tests , Neurokinin A/metabolism , Nose , Receptors, Neurokinin-2/antagonists & inhibitors , Receptors, Neurokinin-2/therapeutic use , Receptors, Tachykinin/antagonists & inhibitors , Receptors, Tachykinin/therapeutic use , Rhinitis, Allergic, Seasonal/drug therapy , Rhinitis, Allergic, Seasonal/immunology , Rhinitis, Allergic, Seasonal/metabolism , Sneezing , Substance P/metabolism
2.
Inflamm Res ; 57(6): 247-51, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18516714

ABSTRACT

OBJECTIVE AND DESIGN: KP-496 is a novel dual antagonist for leukotriene (LT) D(4) and thromboxane (TX) A(2) receptors. We investigated effects of KP-496 on antigeninduced nasal blockage in 2 guinea pig models of allergic rhinitis. SUBJECTS: Male Hartley guinea pigs were used. TREATMENT: Animals were actively sensitized with ovalbumin (OVA) or Japanese cedar pollen, and were then repeatedly challenged with OVA or pollen, respectively. KP-496 (0.003 %-0.05 %) was intranasally administered 0.5 or 1 h before and 2 h after an antigen challenge. METHODS: As an indicator of nasal blockage, specific airway resistance was measured using a double-flow plethysmograph system. Statistical analyses were performed with Dunnett's test (OVA model) or t-test (pollen model). RESULTS: Although early phase response was not affected by even a high dose (0.03 %) of KP-496, late phase nasal blockage (1.68 +/- 0.26) was inhibited by 0.01 % (0.87 +/- 0.19; p <0.05) and 0.03 % (0.44 +/- 0.12; p <0.01) of KP-496 in the OVA model. On the other hand, both early (5.60 +/- 0.77) and late phase responses (7.90 +/- 1.70) were inhibited by 0.05 % KP-496 to 2.68 +/- 0.84 (p <0.05) and 2.71 +/- 0.83 (p <0.05), respectively, in the pollen model, in which nasal hyperresponsiveness had been acquired by multiple challenges. CONCLUSIONS: KP-496 may be clinically effective for nasal blockage in allergic rhinitis.


Subject(s)
Benzoates , Leukotriene Antagonists , Nasal Mucosa/drug effects , Receptors, Leukotriene/metabolism , Receptors, Thromboxane A2, Prostaglandin H2/antagonists & inhibitors , Rhinitis, Allergic, Perennial/drug therapy , Thiazoles , Airway Resistance/drug effects , Animals , Area Under Curve , Benzoates/pharmacology , Benzoates/therapeutic use , Disease Models, Animal , Guinea Pigs , Humans , Leukotriene Antagonists/pharmacology , Leukotriene Antagonists/therapeutic use , Male , Nasal Obstruction/immunology , Ovalbumin/immunology , Pollen/immunology , Rhinitis, Allergic, Perennial/immunology , Sneezing/drug effects , Thiazoles/pharmacology , Thiazoles/therapeutic use
3.
J Dent Res ; 86(1): 52-7, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17189463

ABSTRACT

Epidemiological studies have shown that post-menopausal women who do not use an estrogen supplement have fewer teeth than those who do. We hypothesized that changes in the dentition of post-menopausal women might be due to alveolar bone alterations by estrogen deficiency. To clarify this, we analyzed the microstructural alveolar bone changes in ovariectomized monkeys and compared these with their lumbar bone mineral density. The % of baseline bone mineral density showed a significant decrease in the ovariectomized group as compared with the controls. The second-molar interradicular septa in ovariectomized monkeys showed a significantly decreased nodes number, cortices number, and an increased structural model index value. More pores were seen in the ovariectomized group at the top of the septa. This study demonstrated that, in such monkeys, estrogen deficiency led to fragility of the trabecular structure of the molar alveolar bone, and such fragility was inversely correlated with lumbar bone mineral density.


Subject(s)
Alveolar Process/ultrastructure , Lumbar Vertebrae/ultrastructure , Osteoporosis/pathology , Absorptiometry, Photon , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/pathology , Alveolar Process/diagnostic imaging , Animals , Bone Density/physiology , Disease Models, Animal , Estradiol/blood , Female , Image Processing, Computer-Assisted , Lumbar Vertebrae/diagnostic imaging , Macaca fascicularis , Osteoporosis/diagnostic imaging , Ovariectomy , Random Allocation , Time Factors , Tomography, X-Ray Computed , Tooth Socket/diagnostic imaging , Tooth Socket/ultrastructure
4.
Inflamm Res ; 54(9): 370-4, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16273335

ABSTRACT

OBJECTIVE AND DESIGN: Because immediate allergic symptoms are aggravated by repetitive antigen challenges in a guinea pig model of Japanese cedar pollen-induced conjunctivitis, we determined whether conjunctival mast cells are different in number between the acute and chronic stages. METHODS: Sensitised guinea pigs were challenged by dropping a pollen suspension into their eyes once a week. Conjunctival tissue sections were stained with toluidine blue. Ophthalmic lavage was performed to assay for mast cell mediators. RESULTS: At the 20th and 40th challenges, the number of mast cells increased by 4- to 5-fold compared with the 1st challenge. Although mast cell degranulation was insignificant 10 min after the 1st challenge, the 20th and 40th challenges produced significant degranulation. After multiple challenges, the amount of histamine and tryptase-like activity in the lavage fluid was dramatically increased. CONCLUSION: Increased mast cells are associated with aggravated symptoms. Mast cell mediators may be involved in pathogenesis at the chronic stage.


Subject(s)
Cedrus/immunology , Conjunctivitis/immunology , Conjunctivitis/pathology , Immunization , Mast Cells/immunology , Mast Cells/pathology , Pollen/immunology , Acute Disease , Animals , Cell Count , Cell Degranulation , Chronic Disease , Conjunctivitis/metabolism , Guinea Pigs , Histamine/metabolism , Hyperplasia , Male , Serine Endopeptidases/metabolism , Therapeutic Irrigation , Tryptases
5.
Aliment Pharmacol Ther ; 18(1): 101-7, 2003 Jul 01.
Article in English | MEDLINE | ID: mdl-12848631

ABSTRACT

BACKGROUND: There is currently no optimal second-line treatment after failure of Helicobacter pylori triple therapy. AIM: To determine effective salvage therapy after failure of lansoprazole-amoxicillin-clarithromycin. METHODS: After failure of lansoprazole-amoxicillin-clarithromycin 123 out-patients were randomized to receive either 2-week rabeprazole (20 mg b.d.) + amoxicillin (1000 mg b.d.) (RA group) or 1-week rabeprazole (10 mg b.d.) + amoxicillin (750 mg twice b.d.) + metronidazole (250 mg b.d.) (RAM group). Eradication was assessed by the 13C-urea breath test. We also evaluated cytochrome p450 (CYP) 2C19 genotype status, determined by polymerase chain reaction - restriction fragment length polymorphism, and susceptibility to clarithromycin and metronidazole. RESULTS: On an intention-to-treat basis, H. pylori infection cure was achieved in 37 of 63 (59%) patients in the RA group and in 49 of 60 (82%) patients in the RAM group. Per protocol-based eradication rates in the RA and RAM groups were 66% (37/56) and 88% (49/56), respectively. In both analytic sets there were significant differences between the treatment groups (P < 0.01 in each). Mild adverse events were observed in eight and five patients from the RA and RAM groups, respectively. Genetic predisposition of CYP2C19 and antibiotic resistance did not influence the treatment outcome either regimen. CONCLUSIONS: The rabeprazole + amoxicillin + metronidazole therapy yielded satisfactory results. In contrast, the cure rate in high-dose rabeprazole + amoxicillin was below an acceptable level.


Subject(s)
Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Ulcer Agents/administration & dosage , Benzimidazoles/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori , Metronidazole/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Aged , Drug Resistance, Bacterial , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Omeprazole/analogs & derivatives , Penicillins/administration & dosage , Prospective Studies , Rabeprazole , Treatment Outcome
6.
J Endocrinol ; 175(2): 289-96, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12429027

ABSTRACT

Some plant compounds or herb mixtures are popular alternatives to conventional therapies and contain organic compounds that bind to some nuclear receptors, such as the estrogen receptor (ER), to exert various biological effects. We studied the effect of various herbal extracts on ERalpha and ERbeta isoforms. One herbal extract, Rhei rhizoma (rhubarb), acts as an agonist to both ERalpha and ERbeta. The phytochemical lindleyin, a major component of rhubarb, might contribute to this estrogenic activity through ERalpha and ERbeta. 4-Hydroxytamoxifen, an ER antagonist, completely reversed the estrogenic activity of lindleyin. Lindleyin binds to ERalpha in vitro, as demonstrated using a fluorescent polarization assay. The in vivo effect of rhubarb extract was studied using a vitellogenin assay system in the freshwater fish, Japanese medaka (Oryzias latipes). There were marked increases in serum vitellogenin levels in male medaka exposed to rhubarb extract. We conclude that lindleyin, a component of some herbal medicines, is a novel phytoestrogen and might trigger many of the biological responses evoked by the physiological estrogens.


Subject(s)
Glucosides/metabolism , Receptors, Estrogen/metabolism , Rheum/metabolism , Cells, Cultured , Estrogen Receptor alpha , Estrogen Receptor beta , Fluorescence Polarization/methods , Humans , Plant Extracts/metabolism , Transfection/methods , Vitellogenins/metabolism
7.
Clin Microbiol Infect ; 8 Suppl 2: 12-42, 2002.
Article in English | MEDLINE | ID: mdl-12427206

ABSTRACT

Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serious problem and is increasing in prevalence world-wide at an alarming rate. Streptococcus pneumoniae, one of the main organisms implicated in respiratory tract infections, has developed multiple resistance mechanisms to combat the effects of most commonly used classes of antibiotics, particularly the beta-lactams (penicillin, aminopenicillins and cephalosporins) and macrolides. Furthermore, multidrug-resistant strains of S. pneumoniae have spread to all regions of the world, often via resistant genetic clones. A similar spread of resistance has been reported for other major respiratory tract pathogens, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. To develop and support resistance control strategies it is imperative to obtain accurate data on the prevalence, geographic distribution and antibiotic susceptibility of respiratory tract pathogens and how this relates to antibiotic prescribing patterns. In recent years, significant progress has been made in developing longitudinal national and international surveillance programs to monitor antibiotic resistance, such that the prevalence of resistance and underlying trends over time are now well documented for most parts of Europe, and many parts of Asia and the Americas. However, resistance surveillance data from parts of the developing world (regions of Central America, Africa, Asia and Central/Eastern Europe) remain poor. The quantity and quality of surveillance data is very heterogeneous; thus there is a clear need to standardize or validate the data collection, analysis and interpretative criteria used across studies. If disseminated effectively these data can be used to guide empiric antibiotic therapy, and to support-and monitor the impact of-interventions on antibiotic resistance.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/drug therapy , Drug Resistance, Bacterial , Respiratory Tract Infections/drug therapy , Sentinel Surveillance , Africa/epidemiology , Americas/epidemiology , Asia/epidemiology , Community-Acquired Infections/epidemiology , Europe/epidemiology , Haemophilus influenzae/drug effects , Haemophilus influenzae/growth & development , Humans , Microbial Sensitivity Tests , Moraxella catarrhalis/drug effects , Moraxella catarrhalis/growth & development , Respiratory Tract Infections/epidemiology , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/growth & development , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/growth & development
8.
Inflamm Res ; 51(4): 206-12, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12058959

ABSTRACT

OBJECTIVE AND DESIGN: We evaluated the effectiveness of oral treatment with Japanese cedar pollen on experimental allergic rhinitis in guinea pigs. SUBJECTS: Male Hartley guinea pigs. TREATMENT: From 16 days before the first sensitisation, 1 and 100 mg/time/animal pollen suspension was orally administered twice weekly. Animals were then sensitised and repeatedly challenged with the pollen. METHOD: Guinea pigs were sensitised by intranasal instillation of cedar pollen extracts adsorbed onto Al(OH)3 at a dose of 0.3 microg pollen protein/0.3 mg Al(OH)3/3 microl/nostril twice a day for 7 days. Then the animal was challenged by inhalation with cedar pollen (1.8 mg/nostril) once every week. We evaluated the effects of the oral treatment with antigen on: 1) sneezing frequency, 2) nasal blockage after antigen challenge, 3) nasal hyperresponsiveness to histamine and leukotriene D4, and 4) titres of anaphylactic antibodies. RESULTS: During the course of the high dose administration, several animals died from a possible cytotoxicity, whereas the low dose caused no discernible change. The oral administration of the pollen at both the doses significantly inhibited nasal blockage, and the hyperresponsiveness to the stimuli was also strongly suppressed by the oral treatment. Inhibitory effectiveness did not differ substantially between the 1 and 100 mg/animal-treated groups. In contrast, neither sneezing frequency nor the increasing level of anaphylactic antibodies was influenced by the oral administration. CONCLUSIONS: In this study, we found that the pollen-induced nasal blockage and hyperresponsiveness were suppressed by the oral administration of the pollen in the sensitised guinea pig.


Subject(s)
Antigens/pharmacology , Nasal Obstruction/physiopathology , Rhinitis, Allergic, Seasonal/physiopathology , Administration, Oral , Airway Resistance/drug effects , Animals , Antigens/administration & dosage , Cedrus , Guinea Pigs , Histamine/pharmacology , Hypersensitivity/immunology , Immunoglobulin E/biosynthesis , Leukotriene D4/pharmacology , Male , Nasal Obstruction/etiology , Passive Cutaneous Anaphylaxis , Pollen/immunology , Rhinitis, Allergic, Seasonal/complications , Sneezing/physiology
9.
Jpn J Pharmacol ; 86(2): 170-82, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11459119

ABSTRACT

We examined whether nasal hyperresponsiveness to leukotriene (LT) D4 is seen in our allergic rhinitis model, which showed sneezing and biphasic nasal blockage by repeated antigen inhalation challenge, and whether a dilatation of mucosal blood vessels contributes to this hyperresponsiveness. Nasal blockage [increase of specific airway resistance (sRaw)] was indexed as nasal (hyper)responsiveness. The sensitized-challenged guinea pig showed a remarkable dose-dependent increase in sRaw by intranasal instillation of LTD4 (10 microl/nostril) at 10(-10) to 10(-6) M 10 h and 2 days but not 7 days after the challenge. The increase in sRaw induced by LTD4 was largely blocked by pranlukast or naphazoline, and this was dose-dependently suppressed by N(omega)-nitro-L-arginine methyl ester. Sodium nitroprusside induced an elevation of sRaw in the sensitized-challenged animal in the hyperresponsiveness state, but the degree did not differ from that in the non-sensitized-non-challenged group. The amount of NO2- and NO3- in nasal cavity lavage fluid after LTD4 instillation in the sensitized-challenged animal in the hyperresponsiveness state was significantly greater than that before the instillation. These results demonstrate that the hyperresponsiveness to LTD4 acquired by repeated antigen challenge is mainly due to dilatation of nasal blood vessels, which can be related to hyperproduction of nitric oxide through cysteinyl LT1-receptor activation.


Subject(s)
Leukotriene D4/adverse effects , Nasal Mucosa/drug effects , Nasal Obstruction/chemically induced , Rhinitis, Allergic, Perennial/chemically induced , Vasodilation/drug effects , Airway Resistance/drug effects , Airway Resistance/immunology , Allergens/adverse effects , Animals , Disease Models, Animal , Guinea Pigs , Male , Nasal Mucosa/blood supply , Nasal Obstruction/immunology , Pollen/adverse effects , Rhinitis, Allergic, Perennial/immunology , Vasodilation/immunology
10.
Eur J Pharmacol ; 423(1): 63-70, 2001 Jun 29.
Article in English | MEDLINE | ID: mdl-11438308

ABSTRACT

We have developed a reproducible allergic rhinitis model showing biphasic nasal blockage on repetitive inhalation challenge with Japanese cedar pollen in sensitised guinea pigs. The role of nitric oxide (NO) in inducing nasal blockage was evaluated with this model. N(omega)-nitro-L-arginine methyl ester (L-NAME), a non-selective NO synthase (NOS) inhibitor, intravenously administered before the challenge, significantly inhibited both early and late nasal blockage by approximately 80% and 50%, respectively. When L-NAME treatment was performed after the challenge, the late response was inhibited by approximately 70%. This inhibition was completely reversed by co-administration of L-arginine. However, aminoguanidine and L-N(6)-(1-iminoethyl)lysine, selective inhibitors of inducible NOS, negligibly influenced the degree of nasal blockage. Meanwhile, the alpha-adrenergic agonist, naphazoline, strongly suppressed both early and late nasal blockage. These results indicate that NO, likely produced by constitutive rather than inducible NOS, plays a major role in the occurrence of biphasic nasal blockage, primarily by inducing vasodilatation.


Subject(s)
Nasal Obstruction/immunology , Nitric Oxide/physiology , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , Administration, Intranasal , Adrenergic alpha-Agonists/pharmacology , Allergens/immunology , Animals , Arginine/pharmacology , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Guinea Pigs , Injections, Intravenous , Lysine/analogs & derivatives , Lysine/pharmacology , Male , NG-Nitroarginine Methyl Ester/pharmacology , Naphazoline/pharmacology , Nasal Obstruction/prevention & control , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Rhinitis, Allergic, Seasonal/prevention & control , Sneezing/drug effects , Time Factors
11.
J Int Med Res ; 29(3): 181-8, 2001.
Article in English | MEDLINE | ID: mdl-11471855

ABSTRACT

Deficiency of micronutrients, especially selenium, is common in critically ill patients. We investigated the micronutrient status (selenium, zinc, copper and manganese) and glutathione peroxidase (GSH-Px) activity in 30 tube-fed patients and 21 hospitalized non-tube-fed control patients. Serum levels of selenium, copper and manganese in tube-fed patients were significantly lower than in control patients (selenium: 4.85+/-1.38 microg/dl versus 8.67+/-1.45 pg/dl; copper: 44.7+/-36.9 microg/dl versus 92.1+/-21.2 microg/dl; manganese 0.59+/-0.41 microg/dl versus 1.52+/-0.59 microg/dl). However, zinc and log GSH-Px in the serum were similar in the two groups. Serum selenium concentration correlated with the daily intake of selenium in tube-fed patients, but zinc, copper and manganese concentrations did not correlate with the daily intake of the respective trace elements in tube-fed patients. Blood GSH-Px activity correlated positively with serum selenium concentrations in the control patients, but not in tube-fed patients. These results demonstrate that selenium content of enteral feed appears to be insufficient to maintain normal serum levels in elderly bedridden patients. Our findings emphasize the importance of monitoring micronutrient status in patients on enteral feeding to avoid trace element deficiencies.


Subject(s)
Deficiency Diseases/blood , Enteral Nutrition , Glutathione Peroxidase/blood , Nutritional Status , Aged , Aged, 80 and over , Copper/blood , Copper/deficiency , Deficiency Diseases/enzymology , Female , Humans , Male , Manganese/blood , Manganese/deficiency , Middle Aged , Selenium/blood , Selenium/deficiency , Zinc/blood , Zinc/deficiency
12.
Jpn J Pharmacol ; 85(4): 409-15, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11388645

ABSTRACT

We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.


Subject(s)
Immunization, Passive/methods , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , Vaccination/methods , Airway Resistance/drug effects , Airway Resistance/immunology , Animals , Guinea Pigs , Histamine/metabolism , Histamine H1 Antagonists/pharmacology , Histamine H1 Antagonists/therapeutic use , Leukotriene D4/pharmacology , Male , Nasal Provocation Tests/methods , Pyrilamine , Rhinitis, Allergic, Seasonal/drug therapy , Rhinitis, Allergic, Seasonal/physiopathology , Sneezing/drug effects , Sneezing/immunology , Trees/immunology
14.
Inflamm Res ; 49(8): 398-403, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11028756

ABSTRACT

OBJECTIVE AND DESIGN: Whether Mao-Bushi-Saishin-To (MBST), one of the formulas of classical Chinese medicine, is effective on 48-h passive cutaneous anaphylaxis (PCA) in rats and which substance in the formula is responsible for its inhibitory action were examined. TREATMENT: In the studies on PCA, MBST (hot water extract of the whole herbal formula), extracts of Ephedra herb (Mao), l-ephedrine and other reference drugs were orally administered immediately or at various times before or 5 min after the antigen challenge. In the experiments on anaphylactic histamine release from rat peritoneal mast cells, l-ephedrine and d-pseudoephedrine were added at 10(-4)-10(-7) g/ml at 30, 10, 3 or 0 min before antigen provocation. RESULTS: The time course study indicated that MBST produced a prompt and long lasting inhibition of PCA. Among the constituents of Mao, l-ephedrine exerted this prompt inhibitory activity, but d-pseudoephedrine did not. Neither pseudoephedrine nor l-ephedrine prevented the anaphylactic histamine release from isolated peritoneal mast cells. CONCLUSIONS: It is strongly emphasised that the rapid suppression of PCA by orally administered l-ephedrine must be exerted by a mechanism distinct from that of suppression produced following gastrointestinal absorption of the drug, because the time required for the inhibition was extraordinarily short. However, direct inhibition of anaphylactic histamine release from isolated mast cells was excluded in this inhibition of PCA.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Ephedrine/pharmacology , Passive Cutaneous Anaphylaxis/drug effects , Animals , Anti-Inflammatory Agents/analysis , Drugs, Chinese Herbal/analysis , Ephedrine/analysis , Histamine Release/drug effects , Male , Mast Cells/physiology , Rats , Rats, Wistar
15.
J Int Med Res ; 28(1): 28-35, 2000.
Article in English | MEDLINE | ID: mdl-10815645

ABSTRACT

Prostaglandins exert a protective effect on colonic mucosa in experimentally induced colitis. This study investigated the effect of enprostil, a prostaglandin E2 (PGE2) analogue, on trinitrobenzenesulphonic acid (TNBS)-induced colitis in rats. Each rat received a rectal enema containing TNBS (30 mg), followed 24 h later by intrarectal once-daily enprostil (200 microg). Enprostil-treated and control rats were killed on day 3 (enprostil group, n = 5; control, n = 6) or day 10 (enprostil group, n = 5; control, n = 5) after TNBS treatment. The area of damaged mucosa of the colon was measured relative to the total colonic area. We also determined the macroscopic score of mucosal damage, and measured PGE2, 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2) concentration in portal vein blood samples. Enprostil significantly reduced both the area of damaged mucosa (including the ulcer area) and the macroscopic score after 3 days' treatment compared with control. Similarly, enprostil significantly reduced plasma concentration of PGE2, 6-keto-PGF1alpha and TXB2 during the acute phase at day 3 of treatment compared with control, but not at day 10. These results suggest that PGE2 enema may have therapeutic potential for treating patients with proctitis or left-sided colitis.


Subject(s)
Colitis/pathology , Colon/drug effects , Enprostil/therapeutic use , Animals , Colitis/chemically induced , Colitis/drug therapy , Colon/metabolism , Colon/pathology , Eicosanoids/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Rats , Rats, Sprague-Dawley , Trinitrobenzenesulfonic Acid/administration & dosage , Trinitrobenzenesulfonic Acid/adverse effects
16.
J Antimicrob Chemother ; 44(6): 827-9, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10590286

ABSTRACT

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.


Subject(s)
Antifungal Agents/therapeutic use , Cryptococcosis/drug therapy , Cryptococcus neoformans/drug effects , Triazoles/therapeutic use , Animals , Antifungal Agents/pharmacokinetics , Antifungal Agents/pharmacology , Brain/microbiology , Colony Count, Microbial , Cryptococcosis/microbiology , Cryptococcus neoformans/isolation & purification , Humans , Lung/microbiology , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/microbiology , Mice , Microbial Sensitivity Tests , Triazoles/pharmacokinetics , Triazoles/pharmacology
17.
Ann Allergy Asthma Immunol ; 83(4): 305-10, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10541422

ABSTRACT

BACKGROUND: The pathogenic mechanisms of airway hyperresponsiveness (AHR) in asthma are unknown and only a few studies have examined the importance of sensitivity to antigens in AHR in young adults. OBJECTIVE: We investigated the correlation between AHR and sensitivity to specific antigens, atopy, history of childhood asthma and spirometry in a young adult population. METHODS: Based on the results of interviews with 447 students at our university, 308 non-smoker students were classified into six groups. Group 1 comprised subjects with intermittent mild bronchial asthma; group 2, subjects with history of childhood asthma; group 3, subjects with atopic disease, and a RAST score for Dermatophagoides farinae (Def) of > or = 2; group 4, normal subjects with a RAST score for Def of > or = 2; group 5, subjects with cedar pollinosis; and group 6, normal subjects. We measured AHR to methacholine (MCh), spirometry, immunoglobulin E-radioimmunosorbent test (IgE-RIST), IgE-radioallergosorbent test to six common antigens, eosinophil cationic protein (ECP), and eosinophil count in peripheral blood in each subject. RESULTS: Airway hyperresponsiveness to MCh did not correlate with IgE-RIST, eosinophil count, or ECP. The highest AHR to MCh was present in groups 1 and 2 and lowest in groups 5 and 6. Multiple regression analysis showed that sensitivity to Def was the only factor that significantly influenced AHR to MCh. Airway hyperresponsiveness to MCh of groups with a RAST score for Def of 0/1 was lower than groups with a RAST score of 2 to 6. Airway hyperresponsiveness to MCh did not correlate with the degree of positivity to Def antigen among positive sensitized groups (RAST score 2 to 6). CONCLUSIONS: Sensitivity to mite antigen may be important in the pathogenesis of AHR and Def is a major contributing antigen in young adults in Japan. Once asthma occurs, AHR remains positive for a long time even after the disappearance of asthma-related symptoms.


Subject(s)
Bronchial Hyperreactivity/etiology , Dust/adverse effects , Mites/immunology , Ribonucleases , Adult , Allergens/immunology , Animals , Antigens, Dermatophagoides , Aspergillus fumigatus/immunology , Asthma/epidemiology , Asthma/etiology , Blood Proteins/immunology , Bronchial Hyperreactivity/epidemiology , Bronchial Provocation Tests , Cats , Dogs , Eosinophil Granule Proteins , Eosinophilia/epidemiology , Eosinophilia/etiology , Female , Forced Expiratory Volume , Glycoproteins/immunology , Hair/immunology , Humans , Hypersensitivity, Immediate/epidemiology , Immunoglobulin E/blood , Immunoglobulin E/immunology , Japan/epidemiology , Male , Methacholine Chloride , Pollen/immunology , Radioallergosorbent Test , Spirometry
18.
Inflamm Res ; 48(6): 325-36, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10442485

ABSTRACT

OBJECTIVE AND DESIGN: To develop a model of experimental allergic conjunctivitis, guinea pigs were given repetitive and topical applications of Japanese cedar pollen as an antigen, and the resulting allergic reaction was characterised. SUBJECTS: Male Hartley guinea pigs. TREATMENT: Guinea pigs were sensitised by insertion of small gelatin sponge pieces (3 pieces/eye, both eyes) containing the pollen extracts + Al(OH)3 into the palpebra superior/inferior sulci of both eyes for 8 h/day for 6 days. Then the animals were challenged by dropping pollen suspension in each eye once every week. METHODS: Time-course changes of conjunctivitis intensity score (CIS), which represents oedema and redness, and scratching frequency, and gamma1 and IgE levels in sera were assessed following the respective 1st-17th challenges. Ophthalmic lavage was performed to assay for albumin leakage and migrated leukocytes at each of the odd-numbered challenges. RESULTS: At relatively early stages of the repeated challenge, only a gradual increase of CIS was observed. However, thereafter, considerably higher CIS with the maximum at 30 min after the challenge was provoked at the 12th-17th challenges. Quite interestingly, there were differences in the CIS between the right and left eyes, depending on the individuals. Scratching, and albumin leakage and neutrophil influx into the lavage fluid were also developed during the challenges. Although the anaphylactic antibodies against the antigen were detected in the sera from half of the animals, the levels were not correlated to severity of the symptoms. CONCLUSIONS: The present sensitisation/challenge procedures are unique in terms of topical application of antigen. The lack of any correlation between the levels of the anaphylactic antibodies and severity of anaphylactic symptoms, and the difference of CIS between the left and right eyes of an individual strongly suggest that the anaphylactic antibodies are formed in locally limited tissue surrounding an eye. The present method should be useful for analysing the mechanisms of allergic conjunctivitis.


Subject(s)
Allergens/immunology , Conjunctivitis/immunology , Disease Models, Animal , Plant Proteins/immunology , Pollen/immunology , Administration, Topical , Albumins/analysis , Algorithms , Allergens/administration & dosage , Allergens/analysis , Animals , Conjunctivitis/etiology , Guinea Pigs , Immunoglobulin E/blood , Leukocyte Count , Male , Plant Proteins/administration & dosage , Plant Proteins/analysis , Time Factors , Trees
19.
Intern Med ; 38(3): 276-8, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10337941

ABSTRACT

The tracheal tumor of a 74-year-old female was detected on bronchoscopy and histologically diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma. We successfully treated the tumor with endoscopic neodyminum-yttruim-aluminium-garnet (Nd-YAG) laser photoresection followed by local ethanol injection. This is the first case in which tracheal MALT lymphoma was successfully treated with bronchoscopy. Bronchoscopic therapy seems to be one of the most valuable strategies for treatment of MALT lymphomas of the central airway.


Subject(s)
Bronchoscopy , Endoscopy/methods , Ethanol/administration & dosage , Laser Therapy/methods , Lymphoma, B-Cell, Marginal Zone/therapy , Solvents/administration & dosage , Tracheal Neoplasms/therapy , Aged , Ethanol/therapeutic use , Female , Fiber Optic Technology , Follow-Up Studies , Humans , Injections, Intralesional , Lymphoma, B-Cell, Marginal Zone/diagnosis , Radiography, Thoracic , Solvents/therapeutic use , Tomography, X-Ray Computed , Tracheal Neoplasms/diagnosis
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