Efficacy of Clarithromycin against Experimentally Induced Pneumonia Caused by Clarithromycin-Resistant Haemophilus influenzae in Mice

ABSTRACT Clarithromycin is a 14-member lactone ring macrolide with potent activity against Haemophilus influenzae, including ampicillin-resistant strains. We evaluated the in vivo efficacy of clarithromycin at 40 mg/day and 100 mg/day for 3 days in the treatment of a murine model of pneumonia using a macrolide-resistant H. influenzae strain, which was also ampicillin resistant. The MIC of clarithromycin was 64 μg/ml. The viable bacterial counts in infected tissues after treatment with 100 mg clarithromycin/kg of body weight were lower than the counts obtained in control and 40-mg/kg clarithromycin-treated mice. The concentrations of macrophage inflammatory protein 2 (MIP-2) and interleukin 1β (IL-1β) in bronchoalveolar lavage fluid (BALF) samples from mice treated at both concentrations were lower than in the control group. Pathologically, following infection, clarithromycin-treated mice, particularly at a dose of 100 mg/kg, showed lower numbers of neutrophils in alveolar walls, and inflammatory changes had apparently improved, whereas large aggregates of inflammatory cells were observed within the alveoli of control mice. In addition, we demonstrated that clarithromycin has bacteriological effects against intracellular bacteria at levels below the MIC. Our results indicate that clarithromycin may be useful in vivo for macrolide-resistant H. influenzae, and this phenomenon may be related to the good penetration of clarithromycin into bronchoepithelial cells. We also believe that conventional drug susceptibility tests may not reflect the in vivo effects of clarithromycin.

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MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway

Open Medicine ◽

10.1515/med-2020-0198 ◽

2020 ◽

Vol 15 (1) ◽

pp. 1202-1212

Author(s):

Aichun Zhang ◽

Yangzi Jin

Keyword(s):

Allergic Rhinitis ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Specific Ige ◽

Inflammatory Factors ◽

Pcr Analysis ◽

Reverse Transcription Pcr ◽

Pathway Activation ◽

Nasal Lavage Fluid

AbstractAllergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.

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Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1994.266.6.l593 ◽

1994 ◽

Vol 266 (6) ◽

pp. L593-L611 ◽

Cited By ~ 13

Author(s):

M. D. Evans ◽

W. A. Pryor

Keyword(s):

Cigarette Smoke ◽

Proteinase Inhibitor ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Lung Lavage ◽

Tissue Destruction ◽

Phagocytic Cells ◽

Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

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3-Pentylcatechol, a Non-Allergenic Urushiol Derivative, Displays Anti-Helicobacter pylori Activity In Vivo

Pharmaceuticals ◽

10.3390/ph13110384 ◽

2020 ◽

Vol 13 (11) ◽

pp. 384

Author(s):

Hang Yeon Jeong ◽

Tae Ho Lee ◽

Ju Gyeong Kim ◽

Sueun Lee ◽

Changjong Moon ◽

...

Keyword(s):

Helicobacter Pylori ◽

Triple Therapy ◽

Inflammatory Cells ◽

Control Group ◽

Vitro Assay ◽

Low Concentrations ◽

H Pylori ◽

Stomach Mucous Membrane

We previously reported that 3-pentylcatechol (PC), a synthetic non-allergenic urushiol derivative, inhibited the growth of Helicobacter pylori in an in vitro assay using nutrient agar and broth. In this study, we aimed to investigate the in vivo antimicrobial activity of PC against H. pylori growing in the stomach mucous membrane. Four-week-old male C57BL/6 mice (n = 4) were orally inoculated with H. pylori Sydney Strain-1 (SS-1) for 8 weeks. Thereafter, the mice received PC (1, 5, and 15 mg/kg) and triple therapy (omeprazole, 0.7 mg/kg; metronidazole, 16.7 mg/kg; clarithromycin, 16.7 mg/kg, reference groups) once daily for 10 days. Infiltration of inflammatory cells in gastric tissue was greater in the H. pylori-infected group compared with the control group and lower in both the triple therapy- and PC-treated groups. In addition, upregulation of cytokine mRNA was reversed after infection, upon administration of triple therapy and PC. Interestingly, PC was more effective than triple therapy at all doses, even at 1/15th the dose of triple therapy. In addition, PC demonstrated synergism with triple therapy, even at low concentrations. The results suggest that PC may be more effective against H. pylori than established antibiotics.

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Role of Mouse Cytochrome P450 Enzymes of the Cyp2abfgs Subfamilies in the Induction of Lung Inflammation by Cigarette Smoke Exposure

Toxicological Sciences ◽

10.1093/toxsci/kfz171 ◽

2019 ◽

Vol 172 (1) ◽

pp. 123-131

Author(s):

Matthew Hartog ◽

Qing-Yu Zhang ◽

Xinxin Ding

Keyword(s):

Cytochrome P450 ◽

Tobacco Smoke ◽

Lung Inflammation ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Cigarette Smoke Exposure ◽

Histopathological Analysis ◽

Cytochrome P450 Enzymes

Abstract Many constituents of tobacco smoke (TS) require bioactivation to exert toxic effects; however, few studies have examined the role of bioactivation enzymes in the adverse effects of TS exposure. This knowledge gap is a major source of uncertainty for risk assessment and chemoprevention efforts. Our aim is to test the hypothesis that cytochrome P450 (P450) enzyme-mediated bioactivation is essential to the development of TS exposure-induced lung toxicity, by determining the contributions of P450 enzymes in the mouse Cyp2abfgs gene subfamilies to environmental tobacco smoke (ETS)-induced lung inflammation. Adult female wildtype (WT) and Cyp2abfgs-null mice (both on C57BL/6J background) were exposed to filtered air or ETS, intermittently, for 1 or 2 weeks. Lung inflammation was assessed by quantification of inflammatory cells, cytokines, chemokines, and proteins in bronchoalveolar lavage fluid (BALF) and histopathological analysis. Glutathione (GSH) conjugates of 2 ETS constituents, naphthalene (NA), and 3-methylindole (3MI), were measured in mice exposed to ETS for 4 h. Persistent macrophagic and neutrophilic lung inflammation was observed in ETS-exposed WT mice; the extent of which was significantly reduced in ETS-exposed Cyp2abfgs-null mice. Levels of proinflammatory cytokines and chemokines, along with the total protein concentration, were increased in cell-free BALF from ETS-exposed WT mice, but not Cyp2abfgs-null mice. Additionally, GSH conjugates of NA and 3MI were detected in the lungs of WT, but not Cyp2abfgs-null, mice following ETS exposure. These results provide the first in vivo evidence that the mouse Cyp2abfgs gene cluster plays an important role in ETS-induced lung inflammation.

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Vinpocetine alleviates lung inflammation via macrophage inflammatory protein-1β inhibition in an ovalbumin-induced allergic asthma model

PLoS ONE ◽

10.1371/journal.pone.0251012 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0251012

Author(s):

Won Seok Choi ◽

Hyun Sik Kang ◽

Hong Jo Kim ◽

Wang Tae Lee ◽

Uy Dong Sohn ◽

...

Keyword(s):

Lung Inflammation ◽

Allergic Inflammation ◽

Inflammatory Cells ◽

Specific Ige ◽

Control Group ◽

Bronchial Disease ◽

Inflammatory Protein ◽

Bronchial Inflammation ◽

Bronchial Mucus ◽

Macrophage Inflammatory Protein

Asthma is a well-known bronchial disease that causes bronchial inflammation, narrowing of the bronchial tubes, and bronchial mucus secretion, leading to bronchial blockade. In this study, we investigated the association between phosphodiesterase (PDE), specifically PDE1, and asthma using 3-isobutyl-1-methylxanthine (IBMX; a non-specific PDE inhibitor) and vinpocetine (Vinp; a PDE1 inhibitor). Balb/c mice were randomized to five treatment groups: control, ovalbumin (OVA), OVA + IBMX, OVA + Vinp, and OVA + dexamethasone (Dex). All mice were sensitized and challenged with OVA, except for the control group. IBMX, Vinp, or Dex was intraperitoneally administered 1 h before the challenge. Vinp treatment significantly inhibited the increase in airway hyper-responsiveness (P<0.001) and reduced the number of inflammatory cells, particularly eosinophils, in the lungs (P<0.01). It also ameliorated the damage to the bronchi and alveoli and decreased the OVA-specific IgE levels in serum, an indicator of allergic inflammation increased by OVA (P<0.05). Furthermore, the increase in interleukin-13, a known Th2 cytokine, was significantly decreased by Vinp (P<0.05), and Vinp regulated the release and mRNA expression of macrophage inflammatory protein-1β (MIP-1β) increased by OVA (P<0.05). Taken together, these results suggest that PDE1 is associated with allergic lung inflammation induced by OVA. Thus, PDE1 inhibitors can be a promising therapeutic target for the treatment of asthma.

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The extract of black cumin, licorice, anise, and black tea alleviates OVA-induced allergic rhinitis in mouse via balancing activity of helper T cells in lung

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00587-6 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Chengsong Liao ◽

Yangyang Han ◽

Zhijing Chen ◽

Huricha Baigude

Keyword(s):

Allergic Rhinitis ◽

Nasal Mucosa ◽

Aqueous Extract ◽

Nigella Sativa ◽

Inflammatory Cells ◽

Serum Levels ◽

Lavage Fluid ◽

Ar Model ◽

Control Group ◽

Black Cumin

Abstract Background A formulation of black cumin (Nigella sativa L.), licorice (Glycyrrhiza glabra L.), anise (Pimpinella anisum L.) and tea (Camellia sinensis (L.) Kuntze) (denoted BLAB tea) is traditionally used to relief allergy reaction including allergic rhinitis. However, little is known about its underlining mechanism of anti-allergic effects. Methods To investigate the anti-allergenic mechanism of BLAB tea, we treated ovalbumin (OVA)-induced allergic rhinitis (AR) model of mice with BLAB tea, and elucidated its possible mechanism of action. Mice in the control group were treated with phosphate-buffered saline only. Subsequently, the infiltration of different inflammatory cells was measured. In addition, histopathological changes in the nasal mucosa, and the levels of allergen-specific cytokines and OVA-specific immunoglobulins were measured. Results The aqueous extract of BLAB significantly alleviated the nasal symptoms and reduced the accumulation of inflammatory cells in the nasal mucosa and nasal lavage fluid of AR model of mice. Conclusion The aqueous extract of BLAB induced the production of Th1 and Treg cytokines and inhibited the release of Th2 cytokines and histamine in nasal mucosa and serum of mice while decreasing the serum levels of OVA-specific IgE, IgG1, and IgG2a. These results suggest the potential of the aqueous extract of BLAB as a treatment option for allergic diseases.

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Efficacy of adjuvant intrastromal and combination of intrastromal and intracameral voriconazole in Aspergillus fumigatus-induced moderate fungal keratitis in rabbits

Medical Journal of Indonesia ◽

10.13181/mji.oa.203726 ◽

2021 ◽

Vol 30 (1) ◽

pp. 13-9

Author(s):

Dyah Tjintya Sarika ◽

Melva Louisa ◽

Anna Rozaliyani ◽

Evelina ◽

Made Susiyanti

Keyword(s):

Aspergillus Fumigatus ◽

Clinical Response ◽

Histopathological Examination ◽

Inflammatory Cells ◽

Fungal Keratitis ◽

Control Group ◽

Corneal Tissue ◽

Epithelial Defect ◽

Treatment Groups

BACKGROUND There is no in vivo evidence for the effectiveness of adjuvant intrastromal and combination of intrastromal and intracameral voriconazole (VCZ) for treating Aspergillus fumigatus keratitis. This study aimed to compare the efficacy of both agents against it. METHODS A randomized, masked, controlled experimental study was conducted on 11 albino New Zealand white rabbits in which moderate fungal keratitis was induced by inoculating spores of A. fumigatus to the cornea. The rabbits were allocated into 3 groups: 50 μg/0.1 ml intrastromal VCZ injection, 50 μg/0.1 ml intrastromal VCZ and intracameral VCZ injections, and topical VCZ (control). The treatment was given 5 days after inoculation. Epithelial defect, infiltrate size, corneal ulcer depth, and hypopyon were evaluated clinically. Histopathological and mycological examinations were also done 14 days after treatment. RESULTS All rabbits in the adjuvant treatment groups demonstrated a tendency of a better clinical response with decreasing size of epithelial defect (p = 0.679) and infiltrate (p = 0.755) than in the control group. Direct microscopy, corneal culture, and chop corneal tissue culture were still positive in most of the rabbits from all groups. Histopathological examination showed an increase of inflammatory cells after treatment in all groups, especially in rabbits which were inoculated with A. fumigatus spores in both eyes. CONCLUSIONS An adjuvant combination of intrastromal and intracameral VCZ showed a tendency of better clinical response for A. fumigatus-induced moderate fungal keratitis in rabbits.

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Experimental induced wound cicatrisation after highly diluted products treatment

International Journal of High Dilution Research - ISSN 1982-6206 ◽

10.51910/ijhdr.v11i40.601 ◽

2021 ◽

Vol 11 (40) ◽

pp. 211-212

Author(s):

Fernando Fortunato Jeronimo ◽

Jenifer Pendiuk GonÃƒÆ’Ã‚Â§alves ◽

Katia Fialho Do Nascimento ◽

Simone Martins De Oliveira ◽

Carolina Camargo De Oliveira ◽

...

Keyword(s):

Connective Tissue ◽

Inflammatory Cells ◽

Control Group ◽

Type I ◽

Chelidonium Majus ◽

Conium Maculatum ◽

The Matrix ◽

Aconitum Napellus

Introduction: Skin is an attractive target to study extracellular matrix, due to abundance in Connective tissue. In cases of injuries the first step is an inflammatory reaction and subsequent the healing that involves several changes in the matrix. These changes are fundamental to inflammatory cells activities allowing healing. Highly diluted products were shown to facilitate inflammatory mediators and to activate immune cells in vivo and in vitro, thus it can be effective to wound healing. Aims: This study aims to evaluate highly diluted products effects on inflammation and cicatrization process. Methodology: Three compounds (M8 (Aconitum napellus 20dH, Arsenicum album 18dH, Asa foetida 20dH, Calcarea carbonica 16dH, Conium maculatum 17dH, Ipecacuanha 13dH, Phosphorus 20dH, Rhus toxicodendron 17dH, Silicea 20dH, Sulphur 24dH, Thuja occidentalis 19dH), M1 (Chelidonium majus 20dH, Cinnamon 20dH, Echinaceae purpurea 20dH, Gelsemium sempervirens 20dH plus all M8 compounds) and Curcuma cH30 ÃƒÂ¢Ã¢â€šÂ¬Ã¢â‚¬Å“ simple product), were manipulated as a gel and applied on mice dorsal flank after incision and suture (approximately 1 cm and three points), for 3 consecutive days. After the treatments the scars were evaluated macroscopically, the animals were killed, the skin samples collected, fixed and processed for Hematoxilin-Eosin (HE) and Masson Tricromic (to observe the collagen fibers type I). The slices were analyzed and images collected by a light microscope Olympus BX51 with camera attached Olympus DP72. Results: It was observed a higher and faster rate of tissue epithelization in the treated groups after three days of gel-product application. This could be observed in lower rates in the control group (no treatment) - Figure 1 and 2). Regeneration and organization of connective tissue were proportional to epithelization the treated groups. We also observed evidences of changes in amount of neutrophils and fibroblasts, resulting in changes in the healing period. Analyses for these confirmations are in progress.

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Salidroside Mitigates Airway Inflammation in Asthmatic Mice via the AMPK/Akt/GSK3β Signaling Pathway

International Archives of Allergy and Immunology ◽

10.1159/000519295 ◽

2021 ◽

pp. 1-11

Author(s):

Xue Luan ◽

Chunai Cui ◽

Jingzhi Jiang ◽

Chongyang Wang ◽

Li Li ◽

...

Keyword(s):

Airway Inflammation ◽

Dose Group ◽

Bronchial Hyperresponsiveness ◽

Lavage Fluid ◽

Inflammatory Factors ◽

Control Group ◽

High Dose ◽

Inflammatory Infiltration ◽

Ifn Γ

Introduction: This study aimed to explore the effects and mechanisms of salidroside (SAL) in airway inflammation in asthmatic mice. Methods: Mice were sensitized with ovalbumin (OVA) to establish an asthma model. They were divided into the control group, OVA group, SAL low-dose group (SAL-L), SAL high-dose group (SAL-H), and dexamethasone (DXM) group. The airway reactivity of the mice was measured, and the total cells, neutrophils, eosinophils, and lymphocytes were counted, respectively. The levels of IL-4, IL-5, IL-13, and IFN-γ in bronchoalveolar lavage fluid (BALF) were detected by ELISA. Immunohistochemistry was used to detect the expression levels of p-AMPK, p-Akt, and p-GSK3β. Western blot was used to detect cytokine levels in lung tissue and p-AMPK, p-Akt, and p-GSK3β levels in LPS-induced 16HBE cells. Results: The airway hyperresponsiveness of asthmatic mice in the SAL-H group decreased (p < 0.05), and the total number of cells, neutrophils, eosinophils, and lymphocytes decreased significantly (p < 0.05). In addition, the airways of mice showed airway inflammatory infiltration and goblet cell proliferation, and the corresponding cellular inflammatory factors IL-4, IL-5, and IL-13 were significantly decreased. However, the expression of IFN-γ in BALF and lung tissues was increased (p < 0.05). Moreover, after the mice were treated with SAL, the phosphorylation level of AMPK was significantly increased, which further reduced the phosphorylation levels of Akt and GSK3β (p < 0.05). Both SAL and AMPK inhibitors exerted effects on LPS-induced 16HBE cells, consistent with in vivo results. Conclusion: SAL can inhibit bronchial hyperresponsiveness and reduce tracheal inflammation by increasing AMPK phosphorylation and inhibiting Akt and GSK3β signaling pathways.

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Amelioration of ovalbumin induced allergic symptoms in Balb/c mice by potentially probiotic strains of lactobacilli

Beneficial Microbes ◽

10.3920/bm2014.0141 ◽

2015 ◽

Vol 6 (5) ◽

pp. 669-678 ◽

Cited By ~ 5

Author(s):

M. Nawaz ◽

C. Ma ◽

M.A.R Basra ◽

J. Wang ◽

J. Xu

Keyword(s):

Mrna Expression ◽

Transforming Growth Factor ◽

Immunoglobulin E ◽

Lactobacillus Rhamnosus ◽

Inflammatory Cells ◽

Transforming Growth Factor Β ◽

Lavage Fluid ◽

Specific Ige ◽

Control Group ◽

Probiotic Strains

To evaluate the antiallergic effect of newly characterised probiotic strains, Lactobacillus fermentum NWS29, Lactobacillus casei NWP08 and Lactobacillus rhamnosus NWP13, mice were divided into six experimental groups: control, ovalbumin (OVA), NWS29, NWP08, NWP13 and L. rhamnosus GG (LGG). Mice were immunised and probiotics were administered via oral gavage followed by challenge with OVA. After last challenge with OVA, inflammatory cells in bronchoalveolar lavage fluid (BALF), recruitment of inflammatory cells in airways and OVA-specific immunoglobulin E (IgE) in serum were determined by Giemsa, haematoxylin and eosin (HE) staining, and ELISA, respectively. Relative mRNA expression of interleukins (IL-4, IL-5, IL-10, IL-13 and IL-17), transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ) in lung and spleen tissue was determined by real time RT-PCR. OVA-specific IgE levels, recruitment of eosinophils and mRNA expressions of inflammatory cytokines were remarkably increased in OVA-exposed mice compared with the control group. Administration of NWS29 and NWP13 suppressed inflammatory cell infiltration in airways and BALF, and level of OVA-specific IgE in serum of OVA-exposed mice. Furthermore, NWS29 and NWP13 also abrogated the mRNA expression of 1L-4, IL-5, IL-13 and TGF-β in mice immunised and exposed to OVA. Our findings suggest that NWS29 and NWP13 might be good candidates for the prevention of allergic airway inflammation.

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