Oxidized Low-density Lipoproteins and Lipopolysaccharides Augment Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine.

Atherosclerosis is a chronic inflammatory disease and hypercholesterolemia is a risk factor. This study aims to compare the potency of lipopolysaccharide (LPS) and oxidized low-density lipoproteins (oxLDL) to induce plaque formation and increase plaque vulnerability in the carotid artery of hypercholesterolemic Yucatan microswine. Atherosclerotic lesions at the common carotid artery junction and ascending pharyngeal artery were induced in hypercholesterolemic Yucatan microswine at 5-6 months of age with balloon angioplasty. LPS or oxLDL were administered intraluminally at the site of injury after occluding the arterial flow temporarily. Pre-intervention ultrasound (US), angiography, and optical coherence tomography (OCT) were done at baseline and just before euthanasia to assess post-op parameters. The images from the US, OCT, and angiography in the LPS and the oxLDL-treated group showed increased plaque formation with features suggestive of unstable plaque, including necrotic core, thin fibrous caps, and a signal poor region more with oxLDL compared to LPS. Histomorphology of the carotid artery tissue near the injury corroborated the presence of severe lesions in both LPS and oxLDL-treated pigs but more in the oxLDL group. Vascular smooth muscle and endothelial cells treated with LPS and oxLDL showed increased folds changes in mRNA transcripts of the biomarkers of inflammation and plaque vulnerability compared to untreated cells. Collectively, the results suggest that angioplasty-mediated intimal injury of the carotid arteries in atherosclerotic swine with local administration of LPS or ox-LDL induces vulnerable plaques compared to angioplasty alone and oxLDL is relatively more potent than LPS in inducing vulnerable plaque.

Traumatic pulmonary pseudocyst: An underreported entity.

BACKGROUND: Traumatic pulmonary pseudocysts (TPP) are underreported cavitary lesions of the pulmonary parenchyma that can develop following blunt chest trauma. Although the occurrence of traumatic pulmonary pseudocyst is rare, this condition should be considered in the differential diagnosis of any cavitary lesion. Awareness of this injury and its clinical significance is important for successful management in order to avoid medical errors in the course of treatment. METHODS: A literature search was conducted through Medline using the key phrases "traumatic pulmonary pseudocyst" and "traumatic pneumatocele." Relevant articles, especially those with focus on diagnosis and management of traumatic pneumatocele in adults, were selected. Due to the scarcity of literature and lack of Level I evidence on this subject, studies published in any year were considered. RESULTS: A search of "traumatic pulmonary pseudocyst" and "traumatic pneumatocele" yielded 114 studies. Most of these were excluded based on inclusion and exclusion criteria. Thirty-five articles were reviewed. The majority of these were individual case studies; only eight articles were considered large case studies (greater than eight patients). CONCLUSION: Traumatic pulmonary pseudocysts are lesions that occur secondary to blunt chest trauma. Diagnosis is based on a history of trauma and appearance of a cystic lesion on CT. Accurate diagnosis of traumatic pulmonary pseudocyst is imperative to achieve successful outcomes. Failure to do so may lead to unnecessary procedures and complications.

Numerical Verification of an Analytical Model for Phase Noise in MEMS Oscillators.

A new analytical formulation for phase noise in MEMS oscillators was recently presented encompassing the role of essential nonlinearities in the electrical and mechanical domains. In this paper, we validate the effectiveness of the proposed analytical formulation with respect to the unified theory developed by Demir et al. describing phase noise in oscillators. In particular, it is shown that, over a range of the second-order mechanical nonlinear stiffness of the MEMS resonator, both models exhibit an excellent match in the phase diffusion coefficient calculation for a square-wave MEMS oscillator.

Bismuth Titanate Fabricated by Spray-on Deposition and Microwave Sintering For High-Temperature Ultrasonic Transducers.

Thick films of ferroelectric bismuth titanate (Bi4Ti3O12) have been fabricated by spray-on deposition in conjunction with microwave sintering for use as high-temperature ultrasonic transducers. The elastic modulus, density, permittivity, and conductivity of the films were characterized. Electro-mechanical properties of the films were estimated with a commercial d33 meter which gave 16 pC/N. This value is higher than typically reported for bulk bismuth titanate; however, these films withstand higher field strengths during poling which is correlated with higher d33 values. Films were capable of operating at 650 °C for roughly 5 min before depoling and can operate at 600 °C for at least 7 days.

A highly efficient and compact long pulse Nd:YAG rod laser with 540 J of pulse energy for welding application.

We have developed an efficient and high average power flash lamp pumped long pulse Nd:YAG laser capable of generating 1 kW of average output power with maximum 540 J of single pulse energy and 20 kW of peak power. The laser pulse duration can be varied from 1 to 40 ms and repetition rate from 1 to 100 Hz. A compact and robust laser pump chamber and resonator was designed to achieve this high average and peak power. It was found that this laser system provides highest single pulse energy as compared to other long pulsed Nd:YAG laser systems of similar rating. A slope efficiency of 5.4% has been achieved, which is on higher side for typical lamp pumped solid-state lasers. This system will be highly useful in laser welding of materials such as aluminium and titanium. We have achieved 4 mm deep penetration welding of these metals under optimized conditions of output power, pulse energy, and pulse duration. The laser resonator was optimized to provide stable operation from single shot to 100 Hz of repetition rate. The beam quality factor was measured to be M(2) ~ 91 and pulse-to-pulse stability of ±3% for the multimode operation. The laser beam was efficiently coupled through an optical fiber of 600 µm core diameter and 0.22 numerical aperture with power transmission of 90%.

Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model.

BACKGROUND: Asthma is a chronic disease associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodelling. NF-κB is a transcriptional factor that regulates and co-ordinates the expression of various inflammatory genes. The NF-κB subunits, p50 and Rel-A, are translocated to the nucleus by importin α3 and importin α4. There is growing evidence that vitamin D is a potent immunomodulator. However, the evidence for beneficial or adverse effects of vitamin D in asthma is still unclear. OBJECTIVE: In this study, we examined the effect of vitamin D status on AHR, airway inflammation and cytokines in the bronchoalveolar lavage fluid (BALF) in a murine model of allergic asthma. METHODS: Female BALB/c mice were fed with special vitamin D-deficient or vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet for 13 weeks. Mice were sensitized and challenged with ovalbumin (OVA). The effect of vitamin D on lung histology, AHR, T regulatory cells (Tregs) and BALF cytokines was examined. The expression of importin-α3 and Rel-A in the lung of OVA-sensitized mice was analysed using immunofluorescence. RESULTS: Vitamin D deficiency was associated with higher AHR in OVA-sensitized and challenged mice than those in vitamin D-sufficient mice. This was accompanied with marked signs of airway remodelling, high BALF eosinophilia, increased BALF pro-inflammatory cytokines, reduced BALF IL-10 levels, reduced blood Tregs, increased expression of importin-α3 and Rel-A in the lung tissue. Vitamin D supplementation attenuated the pro-inflammatory effects, but did not completely reverse the features of allergic airway inflammation. CONCLUSION AND CLINICAL RELEVANCE: Vitamin D could be beneficial as an adjunct therapy in the treatment of allergic asthma.

A cephalometric evaluation of tongue from the rest position to centric occlusion in the subjects with class II division 1 malocclusion and class I normal occlusion.

BACKGROUND: One of the common types of oro-dental morphopathologic relationship is the Class II Division 1 malocclusion. Therefore, the study of tongue position in Class II Division 1 may reveal a role of the tongue in the etiology or diagnosis of malocclusion. AIMS: Present study was done with the aim to evaluate the tongue position radiographically in centric occlusion and rest position in the subjects with Angle's Class 1 normal occlusion and subjects with Angle's Class II Division 1 malocclusion and to find out any differences in tongue position between Angle's Class 1 normal occlusion and Angle's Class II Division 1 malocclusion group. MATERIALS AND METHODS: The present study was conducted on lateral cephalogram of 40 subjects between the age ranges of 16 to 22 years. The samples were divided into the Angle's Class 1 normal occlusion group (Group I) and the Angle's Class II Division 1 malocclusion group (Group II) with the 20 in each groups. The study involved the evaluation of tongue position at rest position and centric occlusion on the lateral head cephalogram. RESULTS: This study for the evaluation of the tongue position from the rest position to the centric occlusion showed no statistically significant changes in both groups. However, there were greater changes in various parameters (From the rest position to the centric occlusion) in the subjects with Angle's Class II Division 1 malocclusion as compared to the subjects with the Angle's Class I normal occlusion group. CONCLUSION: FROM THE PRESENT STUDY FOLLOWING CONCLUSION CAN BE DRAWN: with the closure of mandible from the rest position to centric occlusion the tongue moved antero-superiorly in the tip region, superiorly in the dorsum region, and antero-superiorly in the posterior region in normal occlusion and postero-superiorly in Class II Division 1 malocclusion.

Preparation and evaluation of transdermal plasters containing norfloxacin: a novel treatment for burn wound healing.

OBJECTIVE: In an attempt for better treatment of bacterial infections and burn wounds, plaster formulations containing different concentrations of norfloxacin were prepared using polymers like polyvinylpyrrolidone and polyvinyl alcohol and evaluated for physicochemical parameters, in vitro drug release, antimicrobial activity, and burn wound healing properties. The prepared formulations were compared with silver sulfadiazine cream 1%, USP. METHODS: Plaster formulations containing different concentrations of norfloxacin were prepared by solvent casting method using combination of polymers like polyvinylpyrrolidone and polyvinyl alcohol. These plasters were characterized for drug content, thickness, percentage elongation, tensile strength, in vitro drug release properties, and antimicrobial activity against various strains of aerobic and anaerobic microorganisms. The wound healing property was evaluated by histopathological examination and by measuring the wound contraction. RESULTS: The in vitro release and in vitro skin permeation followed the first-order kinetics followed by diffusion as dominant release mechanism. In spite of the significant antimicrobial and wound healing effects produced by plasters, the observed values were less than the values obtained with silver sulfadiazine 1% cream (P < .05). Various histopathological changes observed during the study period (days 1, 4, 8, and 12) also supported the wound healing process. CONCLUSION: Based on the observed in vitro performances along with antimicrobial and wound healing effects, the 5% norfloxacin transdermal plasters could be employed as an alternative to commercial silver sulfadiazine 1% cream.

Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease.

Angiopoietin-1 (Ang-1) is the primary agonist for Tie2 tyrosine kinase receptor (Tie2), and the effect of Ang-1-Tie2 signalling is context-dependent. Deficiency in either Ang-1 or Tie2 protein leads to severe microvascular defects and subsequent embryonic lethality in murine model. Tie2 receptors are expressed in several cell types, including endothelial cells, smooth muscle cells, fibroblasts, epithelial cells, monocytes, neutrophils, eosinophils and glial cells. Ang-1-Tie2 signalling induces a chemotactic effect in smooth muscle cells, neutrophils and eosinophils, and induces differentiation of mesenchymal cells to smooth muscle cells. Additionally, this signalling pathway induces the secretion of serotonin, matrix metalloproteinases (MMPs) and plasmin. Ang-1 inhibits the secretion of tissue inhibitor of matrix metalloproteinase (TIMPs). Aberrant expression and activity of Tie2 in vascular and non-vascular cells may result in the development of rheumatoid arthritis, cancer, hypertension and psoriasis. Ang-1 has an anti-inflammatory effect, when co-localized with vascular endothelial growth factor (VEGF) in the vasculature. Thus, Ang-1 could be potentially important in the therapy of various pathological conditions such as pulmonary hypertension, arteriosclerosis and diabetic retinopathy. In this article, we have summarized and critically reviewed the pathophysiological role of Ang-1-Tie2 signalling pathway.

Interaction of suplatast tosilate (IPD) with chloride channels in human blood eosinophils: a potential mechanism underlying its anti-allergic and anti-asthmatic effects.

INTRODUCTION: Alterations in chloride ion channels have been implicated in the induction of changes in cell shape and volume. Because blood and tissue eosinophilia are hallmarks of bronchial asthma, in this study we examined the role of chloride channels in the underlying effects of suplatast tosilate (IPD), an anti-allergic drug, in human blood eosinophils. METHODS: Eosinophils were isolated and purified from the blood of allergic asthmatic donors. Chloride ion currents were recorded using the whole-cell patch-clamp technique in freshly isolated eosinophils. The current-voltage relationship of whole-cell currents in human blood eosinophils was calculated and recorded. The effect of chloride channel blockers was examined on superoxide release, eosinophil chemotaxis as measured by the Boyden chamber, and eosinophil adhesion to endothelial cells. Radioligand binding studies with [3H]IPD and competition curves with chloride channel blockers were performed. RESULTS: IPD increased both inward and outward chloride currents in human blood eosinophils. IPD in 1 ng/mL did not have significant effect on chloride current. However, at 5 ng/mL IPD activated both outward and inward currents in human blood eosinophils. Chloride channel blockers inhibited IPD-induced respiratory burst in eosinophils, eosinophil chemotaxis, and eosinophil adhesion to endothelial cells. All these effects of IPD on chloride current and the resultant functional responses in human blood eosinophils were not due to its basic salt, p-toluenesulphonic acid monohydrate. Human blood eosinophils contained specific binding sites for [3H]IPD with K(D) and B(max) values of 187.7+/-105.8 nm and 58.7+/-18.7 fmol/10(6) cells, respectively. Both NPPB and DIDS competed, in a dose-dependent manner, for the specific binding of [3H]IPD in human blood eosinophils. CONCLUSION: These data suggest that the anti-allergic and anti-asthmatic effects of IPD could be due to its interaction with chloride channels in human blood eosinophils.

In stent restenosis: bane of the stent era.

The long term outcome of stent implantation is affected by a process called in stent restenosis (ISR). Multiple contributory factors have been identified, but clear understanding of the overall underlying mechanism remains an enigma. ISR progresses through several different phases and involves numerous cellular and molecular constituents. Platelets and macrophages play a central role via vascular smooth muscle cell migration and proliferation in the intima to produce neointimal hyperplasia, which is pathognomic of ISR. Increased extracellular matrix formation appears to form the bulk of the neointimal hyperplasia tissue. Emerging evidence of the role of inflammatory cytokines and suppressors of cytokine signalling make this an exciting and novel field of antirestenosis research. Activation of Akt pathway triggered by mechanical stretch may also be a contributory factor to ISR formation. Prevention of ISR appears to be a multipronged attack as no therapeutic "magic bullet" exists to block all the processes in one go.

A comparison of stent-induced stenosis in coronary and peripheral arteries.

BACKGROUND AND OBJECTIVES: Restenosis is a complication of interventional procedures such as angioplasty and stenting, often limiting the success of these procedures. Knowledge regarding the relative behaviour of different arteries after these procedures is limited, despite the extensive use of different vascular models. Although the results from studies using different vessels are analysed to predict the behaviour of coronary arteries and other vasculature, direct controlled comparisons between different arteries are necessary for a better understanding of the differential response to restenosis. METHODS: This study examines the response to stenting in coronary and internal iliac arteries as characterised by intimal hyperplasia and restenosis. In a swine model of in-stent stenosis, coronary arteries exhibited higher levels of intimal hyperplasia and per cent stenosis than internal iliac arteries. RESULTS: After normalisation for injury score, coronary arteries were found to undergo 47% more intimal hyperplasia (p<0.05), whereas per cent stenosis normalised for injury score tended to be higher (p = 0.01). Other measurements reflecting post-stenting intimal hyperplasia (maximal intimal thickness, medial area) did not exhibit significant differences between the artery groups. CONCLUSIONS: These results show that coronary vessels are more prone to develop significant intimal hyperplasia and subsequent restenosis than internal iliac vessels. A better insight into how different arteries and arterial components behave is important in understanding and developing newer and better therapeutic measures for restenosis.

Sustained Akt/PKB activation and transient attenuation of c-jun N-terminal kinase in the inhibition of apoptosis by IGF-1 in vascular smooth muscle cells.

Characteristics of hVSMC apoptosis and its inhibition by insulin-like growth factor-1 (IGF-1) remain unclear. Also unclear is whether a balance in hVSMCs exists whereby c-Jun N-terminal stress kinases (JNK) promote apoptosis while extracellular signal-regulated (ERK1/2) MAP kinases inhibit cell death. In this study, we examined the involvement of Akt/PKB and its upstream kinase, PDK1 and whether JNK activation correlated with human and rat VSMC apoptosis induced by staurosporine and by c-myc, respectively. We observed a strong, sustained JNK activation (and c-Jun phosphorylation), which correlated with VSMC apoptosis. IGF-1 (13.3 nM), during apoptosis inhibition, transiently inhibited JNK activity at 1 h in a phosphatidylinositol 3-kinase (PI3-K)- and MEK-ERK-dependent manner, as wortmannin (100 nM) or PD98059 (30 muM) partially attenuated the IGF-1 effect. PKC down-regulation had no effect on JNK inhibition by IGF-1. While IGF-1 alone produced a strong phosphorylation of Akt/PKB in hVSMCs up to 6 h, it was notably stronger and more sustained during ratmyc and hVSMCs apoptosis inhibition. Further, whereas transient expression of phosphorylated Akt protected VSMCs from apoptosis by nearly 50%, expression of dominant interfering alleles of Akt or PDK1 strongly inhibited IGF-1-mediated VSMC survival. These results demonstrate for the first time that transient inhibition of a pro-apoptotic stimulus in VSMCs may be sufficient to inhibit a programmed cell death and that sustained anti-apoptotic signals (Akt) elicited by IGF-1 are augmented during a death stimulus. Furthermore, PI3-K and ERK-MAPK pathways may cooperate to protect VSMCs from cell death.

Cl- channels are expressed in human normal monocytes: a functional role in migration, adhesion and volume change.

Increased adhesion and diapedesis of monocytes appear to be primary initiating factors in the pathophysiology of occlusive vascular diseases, including atherosclerosis and restenosis. However, the underlying mechanisms of transendothelial migration and invasion of monocytes into the blood vessels are not known. Alterations in ion channels on the cell membrane are generally involved in induced changes in shape and volume. In the present study, we investigated the expression and functional role of chloride channels in freshly isolated human blood monocytes. The Cl- currents in whole-cells were measured by the patch-clamp technique. We observed whole cell Cl- currents, which were time-independent and outwardly rectifying. The chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and R(+)-[(6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5yl)-oxy]acetic acid 94 (IAA94) attenuated the Cl- currents. NPPB and IAA94 also inhibited chemotaxis of monocytes, as measured in Boyden chemotactic chambers, with the same sensitivity. NPPB but not IAA94, increased the cell volume as measured by shape change, and decreased tumour necrosis factor (TNF)-alpha-induced monocyte adhesion to endothelial cells. These results suggest that monocytes contain Cl- channels which regulate transendothelial migration of monocytes, due presumably to an alteration in cell volume.

Anti-inflammatory properties of desloratadine.

BACKGROUND: Allergic rhinitis (AR) is associated with robust infiltration of immune cells and mediators that may contribute to clinical manifestations of the disease. OBJECTIVE: To review the complex immune effector mechanisms involved in the allergic response and discuss their effects on the pathophysiological and clinical manifestations of AR. Desloratadine, a novel antihistamine, was used as a probe with the goal of attaining a better understanding of the inflammatory processes underlying the allergic response. METHODS: Data were obtained from abstracts and peer-reviewed journals. The pathophysiology of the allergic response has been extensively studied. This paper presents only data from studies that used desloratadine at physiologically relevant concentrations. RESULTS: Key mediators involved in the allergic response and in pathophysiological and clinical manifestations of the immune response were reviewed. Desloratadine was used as a probe to further elucidate the mechanisms involved during an allergic response. CONCLUSIONS: Some have proposed a link between the pathophysiology of AR and the clinical manifestation of symptoms. Desloratadine, a new-generation antihistamine, has demonstrated anti-inflammatory effects in vitro; indeed, desloratadine is capable of intervening at various points in the immune cascade. Although in vitro results do not necessarily correlate with clinical efficacy, the anti-inflammatory properties of desloratadine may contribute to its efficacy in patients with AR, allergy-induced asthma, and other related allergic conditions. Antihistamines that modulate in the immune system at various stages may optimize treatment of allergic disease.

Flt3 ligand: a novel cytokine prevents allergic asthma in a mouse model.

Flt-3 ligand (FL), a recently described growth factor affecting early hematopoietic progenitor cells, can also support the expansion of dendritic cells secreting IL-12. Since type 2 T cells predominate in asthma and IL-12 prevents the differentiation of naive T lymphocytes to a type 2 phenotype, we hypothesized that FL could prevent the development of asthma-like conditions in the ovalbumin mouse model. We found that co-administration of FL during ovalbumin sensitization abrogated late allergic responses, but had no effect on early allergic responses. Airway hyperresponsiveness to methacholine was also blocked by FL treatment. Analysis of bronchoalveolar lavage (BAL) fluid demonstrated a significant reduction in eosinophils, with concomitant decreases in IL-5 and increases in IFN-gamma levels. However, there was no change in BAL fluid IL-4 and serum IgE levels. These data suggest that FL treatment prevents ovalbumin-induced asthma in the mouse and may provide a useful adjuvant in the treatment of human asthma.

Modification of eosinophil function by suplatast tosilate (IPD), a novel anti-allergic drug.

Suplatast tosilate (IPD), a new dimethylsulfonium agent, is used therapeutically in allergic diseases. Suplatast has been reported to attenuate airway hyperresponsiveness in guinea pigs, human IgE synthesis, and murine peritoneal eosinophilia. However, the effect of suplatast on human eosinophils is not known. In this study, we examined the effects of suplatast in human eosinophils on platelet activating factor (PAF, 1 microM)-induced chemotaxis by the blind well chamber technique, eosinophil adhesion to TNF-alpha (10 ng/ml) or IL-4 (10 ng/ml)-stimulated human umbilical vein endothelial cells (HUVECs), and expression of very late antigen-4 (VLA-4) on eosinophils and vascular cell adhesion molecule-1 (VCAM-1) on HUVECs by flow cytometry. Suplatast suppressed IL-4-induced eosinophil adhesion to HUVECs in a dose-dependent manner. Eosinophils from the normal subjects did not express VLA-4. However, there was a significant increase (P < 0.01) in the basal expression of VLA-4 in allergic patients. PAF or IL-4 did not enhance VLA-4 expression on eosinophils, and there was no significant effect of suplatast on VLA-4 expression in allergic patients. Suplatast did not affect TNF-alpha-induced VCAM-1 expression. Interestingly, suplatast significantly suppressed IL-4 induced VCAM-1 expression on HUVECs and PAF-induced eosinophil chemotaxis. These data suggest that suplatast may modify eosinophil participation in airway inflammation by attenuating inflammatory mediators-induced chemotaxis and adhesion to endothelial cells, and thus might be useful in the treatment of bronchial asthma.

Mycobacterial antigens attenuate late phase response, airway hyperresponsiveness, and bronchoalveolar lavage eosinophilia in a mouse model of bronchial asthma.

Allergens, in combination with genetic predisposition, drive undifferentiated T cells towards the type 2 T cells. Some childhood infections may activate the production of a type 1 T cell profile. It is reasonable to speculate that a decrease in childhood infections may increase the incidence of allergy by allowing the immune balance to shift towards the type 2 T cells. We hypothesized that pre-exposure of mycobacterial antigens in sensitized mice would prevent the development of asthma-like conditions. Specifically, we examined the effect of mycobacterial antigens, Bacillus Calmette-Guerin (BCG) vaccine and Mycobacterium vaccae, on antigen-induced bronchoconstriction, airway hyperresponsiveness to methacholine, bronchoalveolar lavage eosinophilia, and plasma IL-4 and IL-12 levels in ovalbumin (OVA)-sensitized and challenged Balb/c mice. Challenge with OVA produced a 2-3-fold increase in bronchoconstriction within 3-5 min, followed by a delayed response after 60 min, the latter of which was significantly attenuated by both BCG and M. vaccae. Airway hyperresponsiveness to methacholine 24 h after OVA challenge was prevented by BCG and M. vaccae. Airway eosinophilia was also prevented by BCG and M. vaccae. The plasma IL-12 levels were significantly increased and plasma IL-4 levels were significantly decreased following BCG or M. vaccae administration in OVA-sensitized and challenged mice. Interestingly, a significant increase in plasma IL-12 was observed with BCG as compared to M. vaccae administration, suggesting a stronger type 1 response to BCG. These data support our hypothesis and suggest that BCG and M. vaccae may prevent the underlying pathophysiological changes in asthma.

Pharmacology and clinical efficacy of desloratadine as an anti-allergic and anti-inflammatory drug.

Desloratadine is a biologically active metabolite of the second-generation antihistamine loratadine. Desloratadine is a highly selective peripheral H1 receptor antagonist that is significantly more potent than loratadine. Results of in vitro and in vivo studies have suggested that desloratadine has anti-allergic effects that are unrelated to its ability to antagonise the effects of histamine. Desloratadine inhibits the expression of cell adhesion molecules, inhibits the generation and release of inflammatory mediators and cytokines, attenuates eosinophil chemotaxis, adhesion and superoxide generation. Studies in animals indicate that desloratadine does not cross the blood-brain barrier and therefore does not cause sedation and does not impair cognition or psychomotor performance. Desloratadine has an excellent overall safety profile. It has no effect on QRS and QTc intervals and does not cause arrhythmias. Desloratadine is not associated with any significant changes in gastrointestinal function. In clinical studies, oral desloratadine is rapidly absorbed and bioavailability is not affected by ingestion with food or grapefruit juice. The half-life of desloratadine in humans is 27 h; the linear kinetic profile is unaltered by race or gender. Desloratadine is not a substrate for P-glycoprotein or organic anion transport polypeptide and the drug does not appear to be metabolised to a significant extent by the cytochrome P450 CYP3A4 pathway. It therefore may be safely administered with ketoconazole, erythromycin, fluoxetine, or azithromycin. Clinically, desloratadine effectively controls both nasal and non-nasal symptoms of seasonal allergic rhinitis (SAR), including nasal congestion. Desloratadine also provides significant relief of SAR symptoms in patients with co-existing asthma and is effective in the treatment of chronic idiopathic urticaria. Desloratadine improves quality of life and is well-tolerated.