Adding salmeterol to an inhaled corticosteroid reduces allergen-induced serum IL-5 and peripheral blood eosinophils

BACKGROUND: Adding a long-acting beta(2)-agonist to inhaled corticosteroids results in better symptomatic asthma control than increasing the dose of inhaled corticosteroids. OBJECTIVE: Investigating whether adding the long-acting beta(2)-agonist salmeterol to the inhaled corticosteroid fluticasone propionate has an effect on allergen-induced allergic inflammation in asthma. METHODS: Bronchial allergen challenges were performed in 26 patients with allergic asthma, pretreating them with a single dose of either fluticasone/salmeterol (100/50 microg) or fluticasone alone (100 microg), in a double-blind, randomized, cross-over design. Sputum and serum markers of bronchial inflammation were measured after allergen challenge, as well as lung function parameters. Primary outcomes were sputum eosinophil numbers and eosinophil cationic protein. RESULTS: Asthmatic responses after allergen challenge were significantly reduced after pretreatment with fluticasone/salmeterol relative to fluticasone alone. Sputum inflammatory markers after allergen challenge were not significantly affected by fluticasone/salmeterol pretreatment. By contrast, serum IL-5 was significantly reduced (geometric mean serum IL-5 [SEM]: 0.5 [0.3] vs 1.1 [0.3] pg/mL 1 hour and 0.6 [0.3] vs 1.1 [0.3] pg/mL 6 hours after challenge with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P values < .05). Also, peripheral blood eosinophils were significantly reduced (geometric mean number x 10(6)/L [SEM]: 172 [0.1] vs 237 [0.1] at 6 hours and 271 [0.1] vs 351 [0.1] at 24 hours with fluticasone/salmeterol vs fluticasone alone pretreatment, respectively; P < .05). CONCLUSION: Adding salmeterol to fluticasone reduces allergen-induced serum IL-5 and peripheral blood eosinophils. This phenomenon may contribute to the improved clinical outcomes that result from adding a long-acting beta(2)-agonist to inhaled corticosteroids.     

Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity

Heat shock proteins (HSP) are widely distributed and highly immunogenic molecules. A novel property reported here is that stimulation with HSP70 of CD8-enriched T cells derived from naive non-human primates caused a dose-dependent increase in concentrations of the beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha or MIP-1beta. However, the concentrations of these beta-chemokines were greatly increased when the CD8 T cells derived from HSP70-immunized non-human primates were stimulated with HSP70. HSP linked to peptides or proteins combined generation of beta-chemokines with an adjuvant function by enhancing specific T cell proliferative responses and IgG and IgA antibodies. The beta-chemokine and adjuvant functions were also elicited by topical mucosal administration of HSP linked to an antigen. We postulate that microbial HSP can stimulate beta-chemokine production which may be responsible for innate adjuvanticity, as was found in cells eluted from normal rectal mucosal tissue, and constitutes a significant component of the mucosal-associated lymphoid system. Furthermore, stimulation of innate immunity may drive adaptive immunity and account for the protective effects of HSP against tumors and viruses.     

Mesenteric neovascularization during spring-mediated intestinal lengthening

BackgroundShort gut syndrome, a condition characterized by inadequate absorption of nutrients owing to decreased bowel length, has minimal avenues for treatment. We have proposed spring-mediated distraction enterogenesis to lengthen bowel in porcine jejunum as a treatment for short gut. We aim to evaluate the extent of mesenteric neovascularization in segments of lengthened bowel via spring-mediated enterogenesis.MethodsFemale juvenile Yucatan pigs underwent laparotomy and insertion of gelatin-encapsulated compressed nitinol springs, held in place with plication sutures, into the jejunum. At surgery and sacrifice, macroscopic mesenteric blood vessels were counted between the plication sites. Histologic samples of the mesentery were obtained to evaluate microscopic vasculature.ResultsA statistically significant increase in macroscopic mesenteric blood vessels was seen after intestinal lengthening (before: 1.9 ± 0.7 vessels, after: 4.7 ± 1.2 vessels, p = 0.001). A statistical significance is also seen in the density of arterioles (control: 3.0 ± 3.0 vessels/mm, spring: 7.0 ± 9.0 vessels/mm, p = 0.01) and venules (control: 4.0 ± 3.0 vessels/mm, spring: 8.0 ± 8.0 vessels/mm, p = 0.003).ConclusionIntestinal segments lengthened by intraluminal springs demonstrated total greater number of macroscopic vessels and microscopic blood vessels per length of mesentery as compared to control. This suggests local changes within the mesentery to recruit blood supply to growing intestine.Level of evidenceN/AType of studyTreatment study.     

Cytotoxic constituents ofPilea mongolica

Bioassay-guided fractionation of the aerial parts ofPilea mongolica (Urticaceae) afforded two cytotoxic triterpenoids, epi-oleanolic acid (I) and oxo-oleanolic acid (II). The structures of the compounds were confirmed by spectral and synthetic evidences. CompoundI and compoundII exhibited cytotoxicity against cultured human tumor cell lines, A549 (non small cell lung adenocarcinoma), SK-OV-3 (ovarian), SK-MEL-2 (skin melanoma), XF498 (CNS) and HCT15 (colon) with ED(50) values of 3.2 approximately 8.1 mug/ml and 0.7 approximately 6.8 mug/ml, respectively.     

Flavonoids fromCirsium rhinoceros

Six flavonoids were isolated from the aerial parts ofCirsium rhinoceros. The flavonoids were identified as apigenin, luteolin, pectolinarigenin-7-O-β-D-glucopyranoside, linarin, pectolinarin and hispidulin-7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside on the basis of chemical and spectral evidence.     

Cytokines modulate contraction of periosteal explants from rabbit calvariae

Periosteal explants obtained from rabbit calvariae are introduced as a model system to study contraction of soft connective tissue. Culturing of these explants resulted in a substantial time-dependent decrease of the surface area which coincided with a similar decrease in volume. A 75% reduction of the initial explant surface area was observed after a culture period of 72h in the presence of 10% serum. Also in the absence of serum contraction of explants was found, indicating that serum components were not essential. Following devitalization of the explants no contraction did occur. A strong inhibition of contraction was found following interference with the formation of microfilaments, microtubules or intracellular cyclic-AMP levels by using cytochalasin B, colchicine or dibutyryl-cAMP, respectively. These data indicated that viable cells and an intact cytoskeleton were a prerequisite for contraction to occur. A number of cytokines (EGF, aFGF, bFGF, IGF-1, PDGF, TGF-beta and IL-1alpha) was tested for their ability to influence contraction. IL-1alpha was shown to inhibit contraction from the 48h culture period on. Anti-IL-1alpha-serum completely abolished this effect. The IL-1alpha-inducible inhibition of contraction was also partially blocked by indomethacin. TGF-beta enhanced contraction dose-dependently during the 24-48h culture period, whereas TGF-1 and IL-1alpha, added to the cultures in combination, proved to antagonize each other. The other growth factors did neither influence contraction not the IL-1alpha-induced inhibition of contraction.     

Early one-stage orthotopic jejunal pedicle-graft interposition in long-gap esophageal atresia

Since 1988, four children with long-gap esophageal atresia have undergone one-stage orthotopic jejunal pedicle-graft interposition at the age of 2 to 3 months. Obtaining enough jejunal length was no problem and major early complications did not occur. In one patient stenosis of the distal anastomosis was problematic and required corrective surgery. None of the patients demonstrated jejunitis as a result of gastroesophageal reflux. With follow-up periods of 12, 27, 46, and 60 months, all patients are doing well. It is concluded that the jejunum is a better esophageal substitute than is generally appreciated.     

Hyperthermia in combination with chemotherapy in gynecological cancers

Hyperthermia in combination with chemotherapy has a strong biological rationale based on thermal enhancement of cytotoxicity and partial circumvention of resistance. Weekly locoregional hyperthermia in combination with cisplatin is an effective treatment (response rate: 52%) for patients with a recurrence of a previously irradiated carcinoma of the uterine cervix. A comparative trial versus cisplatin alone was recently started. Hyperthermic intraperitoneal chemotherapy is aimed at situations after optimal cytoreductive surgery in patients with carcinomatous peritonitis. The warmth enhances the penetration of the oncolytic agent. Whole-body hyperthermia using the Aquatherm apparatus in combination with chemotherapy is feasible: results in patients with metastatic sarcomas are promising. Trials with whole-body hyperthermia are in progress in patients with platinum refractory ovarian cancer and in patients with a metastatic carcinoma of the uterine cervix.     

Demonstration of Bartonella grahamii DNA in ocular fluids of a patient with neuroretinitis

We describe the clinical and laboratory features of a 55-year-old human immunodeficiency virus-negative female patient who presented with bilateral intraocular inflammatory disease (neuroretinitis type) and behavioral changes caused by a Bartonella grahamii infection. Diagnosis was based on the PCR analysis of DNA extracted from the intraocular fluids. DNA analysis of the PCR product revealed a 100% identity with the 16S rRNA gene sequence of B. grahamii. The patient was successfully treated with doxycycline (200 mg/day) and rifampin (600 mg/day) for 4 weeks. This is the first report that demonstrates the presence of a Bartonella species in the intraocular fluids of a nonimmunocompromised patient and that indicates that B. grahamii is pathogenic for humans.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.