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Acta Gastro-enterologica Belgica 2016Eosinophilic gastroenteritis (EGE) is a rare disease which belongs to primary eosinophilic gastrointestinal disorders (primary EGIDs), characterized by an accumulation... (Review)
Review
Eosinophilic gastroenteritis (EGE) is a rare disease which belongs to primary eosinophilic gastrointestinal disorders (primary EGIDs), characterized by an accumulation of eosinophils in the gastrointestinal (GI) tract and is strongly associated with atopy and allergy. The clinical presentations vary depending on the site and depth of eosinophilic intestinal infiltration. Radiology pictures may show irregular thickening of the folds, but these findings can also be present in other conditions like inflammatory bowel disease and lymphoma. The endoscopic appearance is also nonspecific. The definite diagnosis requires biopsy for histological evidence of GI eosinophilic infiltration and clinicians make the diagnosis in correlation with and by exclusion of other possible causes of eosinophilic infiltration. Because EGE is a rare disease, the treatment is based on limited case reports and clinicians' experience. Corticosteroids are the mainstay of therapy. The prognosis of EGE is relatively good when patients receive timely and proper treatment.
Topics: Acetates; Adrenal Cortex Hormones; Biopsy; Cromolyn Sodium; Cyclopropanes; Endoscopy, Digestive System; Enteritis; Eosinophilia; Gastritis; Histamine H1 Antagonists; Humans; Immunologic Factors; Immunosuppressive Agents; Infliximab; Intestine, Small; Ketotifen; Leukotriene Antagonists; Mercaptopurine; Quinolines; Stomach; Sulfides; Tomography, X-Ray Computed
PubMed: 27382945
DOI: No ID Found -
American Family Physician Jun 2010Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should... (Review)
Review
Allergic rhinitis is a common chronic respiratory illness that affects quality of life, productivity, and other comorbid conditions, including asthma. Treatment should be based on the patient's age and severity of symptoms. Patients should be advised to avoid known allergens and be educated about their condition. Intranasal corticosteroids are the most effective treatment and should be first-line therapy for mild to moderate disease. Moderate to severe disease not responsive to intranasal corticosteroids should be treated with second-line therapies, including antihistamines, decongestants, cromolyn, leukotriene receptor antagonists, and nonpharmacologic therapies (e.g., nasal irrigation). With the exception of cetirizine, second-generation antihistamines are less likely to cause sedation and impair performance. Immunotherapy should be considered in patients with a less than adequate response to usual treatments. Evidence does not support the use of mite-proof impermeable covers, air filtration systems, or delayed exposure to solid foods in infancy.
Topics: Administration, Intranasal; Administration, Oral; Adrenal Cortex Hormones; Cromolyn Sodium; Histamine Antagonists; Humans; Nasal Decongestants; Rhinitis, Allergic, Perennial
PubMed: 20540482
DOI: No ID Found -
Clinical Drug Investigation Nov 2017BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated...
UNLABELLED
BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers.
METHODS
In this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was performed for 6 h after co-administration in all subjects; cerebrospinal fluid (CSF) was collected in three to four subjects per cohort for 4 h following co-administration. Safety parameters, including adverse events (AEs), were monitored throughout the study.
RESULTS
For cromolyn, the mean (±SD) maximum observed concentration (C ) in plasma was 46.69 ± 32.97 and 96.75 ± 46.22 ng/ml after single- and double-dose inhalation, respectively [time to C (t ) ~22 min for each; terminal elimination half-life (t ) ~1.8 h for each]. For ibuprofen, the plasma C was 1090.98 ± 474.64 ng/ml and 2062.96 ± 655.13 ng/ml after single- and double-dose oral administration, respectively (t ~1.6-1.8 h; t ~1.9 h for each). For cromolyn, the CSF C was 0.24 ± 0.08 ng/ml at 3.72 ± 0.70 h after single-dose administration and 0.34 ± 0.17 ng/ml at 3.45 ± 0.95 h after double-dose administration, and for ibuprofen, the CSF C was 3.94 ± 1.29 ng/ml at 2.55 ± 0.96 h after single-dose administration and 8.93 ± 3.29 ng/ml at 3.15 ± 1.05 h after double-dose administration. Three (12%) subjects reported mild or moderate AEs which were unlikely to be related to study drug.
CONCLUSIONS
The combination of cromolyn and ibuprofen was safe and well tolerated. The concentrations of cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate the estimated daily amyloid production and the associated inflammatory response in patients with AD.
Topics: Administration, Oral; Aged; Alzheimer Disease; Cromolyn Sodium; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Half-Life; Healthy Volunteers; Humans; Ibuprofen; Male; Middle Aged
PubMed: 28856569
DOI: 10.1007/s40261-017-0549-5 -
British Medical Journal Feb 1980
Topics: Adult; Asthma; Asthma, Exercise-Induced; Body Temperature Regulation; Child; Cromolyn Sodium; Humans; Pulmonary Ventilation
PubMed: 6766773
DOI: No ID Found -
Scientific Reports Apr 2021Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder...
Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer's Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line. The direct effect of cromolyn on HMC3 microglia is on cytokines and chemokines production following their activation by the inflammatory cytokine TNF-α. Cromolyn and a new fluorinated analog dramatically reduced the secretion of a wide spectrum of inflammatory mediators, which included cytokines such as IL-1β, IL-6, IL-8 and IFN-γ, and chemokines such as CXCL10, CCL2, CCL3 and CCL4. These results bolster our understanding of how our cromolyn platform modulates toxic microglia behavior as a dynamic future treatment option for neurodegenerative disorders.
Topics: Alzheimer Disease; Cromolyn Sodium; Cytokines; Inflammation; Microglia
PubMed: 33850164
DOI: 10.1038/s41598-021-85702-8 -
Journal of Neuroinflammation Oct 2023Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely...
Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and improve stroke outcomes. We used the transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18 mo) male mice to investigate the role of MC in neuroinflammation post-stroke. After MCAO we treated mice with 25 mg/kg body weight of cromolyn (MC stabilizer) by oral gavage. Cromolyn was administered at 3 h, 10 h, 24 h and every 24 h for 3 days post-stroke. Three control groups were used. One group underwent a sham surgery and was treated with cromolyn, one received sham surgery with PBS vehicle and the third underwent MCAO with PBS vehicle. Mice were euthanized at 24 h and 3 days post-stroke. Cromolyn administration significantly reduced MC numbers in the brain at both 24 h and 3 days post-stroke. Infarct volume was not significantly different between groups, however improved functional outcomes were seen at 3 days post-stroke in mice that received cromolyn. Treatment with cromolyn reduced plasma histamine and IL-6 levels in both the 24-h and 3-day cohorts. Gut MCs numbers were significantly reduced after cromolyn treatment at 24 h and 3 days after stroke. To determine if MC trafficking from the gut to the brain occurred after injury, GFPMCs were adoptively transferred to c-kit MC knock-out animals prior to MCAO. 24 h after stroke, elevated MC recruitment was seen in the ischemic brain. Preventing MC histamine release by cromolyn improved gut barrier integrity and an improvement in stroke-induced dysbiosis was seen with treatment. Our results show that preventing MC histamine release possesses prevents post-stroke neuroinflammation and improves neurological and functional outcomes.
Topics: Humans; Mice; Male; Animals; Histamine Release; Mast Cells; Cromolyn Sodium; Histamine; Neuroinflammatory Diseases; Stroke; Inflammation; Infarction, Middle Cerebral Artery; Ischemia
PubMed: 37805585
DOI: 10.1186/s12974-023-02887-7 -
La Clinica Terapeutica 2023Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been...
BACKGROUND
Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema.
OBJECTIVE
Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema.
METHODS
Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks.
RESULTS
Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity.
CONCLUSION
Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.
Topics: Humans; Female; Lipedema; Cromolyn Sodium; Mast Cells; Histamine; Pilot Projects
PubMed: 37994773
DOI: 10.7417/CT.2023.2496 -
BioMed Research International 2021Nonpharmacological therapies with a good tolerability and safety profile are of interest to many patients with allergic rhinitis, as a relevant proportion of them have... (Review)
Review
Nonpharmacological therapies with a good tolerability and safety profile are of interest to many patients with allergic rhinitis, as a relevant proportion of them have reservations about guideline-concordant pharmacological therapies due to their local irritations and side effects. Ectoine is a bacterial-derived extremolyte with an ability to protect proteins and biological membranes against damage caused by extreme conditions of salinity, drought, irradiation, pH, and temperature. Evidence from preclinical and clinical studies attests its effectiveness in the treatment of several inflammatory diseases, including allergic rhinitis. In this review, we analyzed 14 recent clinical trials investigating ectoine nasal spray in patients with allergic rhinitis and/or conjunctivitis, including sensitive patient groups like children or pregnant women. Some studies investigated monotherapy with ectoine; others investigated combination therapy of ectoine and an antihistamine or a corticosteroid. Analysis of the study results demonstrated that patients with mild-to-moderate symptoms of allergic rhinitis can be successfully treated with ectoine-containing nasal spray. When applied as monotherapy, ectoine exerted noninferior effects compared to first-line therapies such as antihistamines and cromoglicic acid. Using ectoine as an add-on therapy to antihistamines or intranasal glucocorticosteroids accelerated symptom relief by days and improved the level of symptom relief. Importantly, concomitant treatment with ectoine was proven beneficial in a group of difficult-to-treat patients suffering from moderate-to-severe rhinitis symptoms. Taken together, the natural substance ectoine represents a viable alternative for allergic rhinitis and conjunctivitis patients who wish to avoid local reactions and side effects associated with pharmacological therapies.
Topics: Adrenal Cortex Hormones; Amino Acids, Diamino; Bacteria; Clinical Trials as Topic; Cromolyn Sodium; Drug Therapy, Combination; Glucocorticoids; Histamine Antagonists; Humans; Hydrogen-Ion Concentration; Nasal Sprays; Ophthalmic Solutions; Rhinitis, Allergic; Temperature
PubMed: 34159193
DOI: 10.1155/2021/5562623 -
Journal of Cystic Fibrosis : Official... Dec 2006Therapy of chronic respiratory diseases often involves inhalation therapy with nebulizers. Patients often attempt to shorten the time consuming administration procedure... (Review)
Review
Therapy of chronic respiratory diseases often involves inhalation therapy with nebulizers. Patients often attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. This article considers the issue of physico-chemical compatibility of admixtures of drug solutions/suspensions in nebulizers. A search of databases, prescribing information and primary literature was conducted to locate literature concerning the physico-chemical compatibility of inhalation solutions/suspensions. This was supplemented by telephone interviews. Admixtures of albuterol with ipratropium and/or cromolyn, of albuterol and budesonide, or tobramycin, or colistin are physico-chemically compatible. Physico-chemical compatibility has been demonstrated for admixtures of cromolyn with albuterol and/or ipratropium and for admixtures of cromolyn and budesonide. Admixtures of budesonide with ipratropium and/or fenoterol, and admixtures of budesonide and albuterol, or cromolyn are physico-chemically compatible. Both cromolyn and colistin are incompatible with benzalkonium chloride. Admixtures should be prepared from inhalation solutions/suspensions formulated without preservatives. Besides studies of the physico-chemical compatibility, the aerodynamic behaviour of physico-chemical mixtures needs to be studied before a final recommendation of simultaneous nebulization of compatible admixtures can be made.
Topics: Acetylcysteine; Administration, Inhalation; Albuterol; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Bronchodilator Agents; Budesonide; Colistin; Cromolyn Sodium; Cystic Fibrosis; Deoxyribonuclease I; Drug Therapy, Combination; Expectorants; Humans; Ipratropium; Nebulizers and Vaporizers; Respiratory Therapy; Tobramycin
PubMed: 16678502
DOI: 10.1016/j.jcf.2006.03.007 -
Molecular Cancer Therapeutics May 2013We have previously shown that the antiallergic drug cromolyn blocks S100P interaction with its receptor receptor for advanced glycation end product (RAGE) and improves...
We have previously shown that the antiallergic drug cromolyn blocks S100P interaction with its receptor receptor for advanced glycation end product (RAGE) and improves gemcitabine effectiveness in pancreatic ductal adenocarcinoma (PDAC). However, the concentration required to achieve its effectiveness was high (100 μmol/L). In this study, we designed and synthesized analogs of cromolyn and analyzed their effectiveness compared with the parent molecule. An ELISA was used to confirm the binding of S100P with RAGE and to test the effectiveness of the different analogs. Analog 5-methyl cromolyn (C5OH) blocked S100P binding as well as the increases in NF-κB activity, cell growth, and apoptosis normally caused by S100P. In vivo C5OH systemic delivery reduced NF-κB activity to a greater extent than cromolyn and at 10 times lesser dose (50 mg vs. 5 mg). Treatment of mice-bearing syngeneic PDAC tumors showed that C5OH treatment reduced both tumor growth and metastasis. C5OH treatment of nude mice bearing orthotopic highly aggressive pancreatic Mpanc96 cells increased the overall animal survival. Therefore, the cromolyn analog, C5OH, was found to be more efficient and potent than cromolyn as a therapeutic for PDAC.
Topics: Animals; Antineoplastic Agents; Apoptosis; Calcium-Binding Proteins; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cell Proliferation; Cromolyn Sodium; Drug Design; Drug Evaluation, Preclinical; Humans; Male; Mice; Mice, Nude; NF-kappa B; Neoplasm Proteins; Pancreatic Neoplasms; Protein Binding; Receptor for Advanced Glycation End Products; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 23303403
DOI: 10.1158/1535-7163.MCT-12-0771