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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 -
Scientific Reports Nov 2019Accumulating evidence suggests that neuroinflammatory processes are implicated in the initiation and progression of amyotrophic lateral sclerosis (ALS). Previous reports...
Accumulating evidence suggests that neuroinflammatory processes are implicated in the initiation and progression of amyotrophic lateral sclerosis (ALS). Previous reports have demonstrated an increase in microgliosis and astrogliosis in the lumbar spinal cord of SOD1 transgenic mice before the onset of symptoms, a neuroinflammatory response which correlated with disease progression. Importantly, early stage homeostatic microglia enhanced motor neuron survival, while pro-inflammatory microglia were toxic to motor neurons in the SOD1 mice. Recent studies from our group have demonstrated that cromolyn sodium, an FDA approved compound, exerts neuroprotective effects in mouse models of Alzheimer's disease by altering microglial cell activation. Here, we tested the neuroprotective and anti-inflammatory effects of cromolyn sodium in the SOD1 mouse model of ALS. Our results indicate that cromolyn sodium treatment significantly delayed the onset of neurological symptoms, and improved deficits in PaGE performance in both male and female mice, however, there was only an effect on survival in female mice. Furthermore, there was a significant increase in motor neuron survival in the lumbar spinal cord as well as a significant decrease in the denervation of the neuromuscular junction of the tibialis anterior muscle in cromolyn treated transgenic SOD1 mice. Lastly, cromolyn treatment decreased the expression of pro-inflammatory cytokines/chemokines in the lumbar spinal cord and plasma and decreased mast cell degranulation in the tibialis anterior muscle of transgenic SOD1 mice. Together, these findings suggest that cromolyn sodium provides neuroprotection in the SOD1 mice by decreasing the inflammatory response.
Topics: Amyotrophic Lateral Sclerosis; Animals; Anti-Inflammatory Agents; Cromolyn Sodium; Cytokines; Female; Male; Mice; Mice, Inbred C57BL; Motor Neurons; Neuromuscular Junction; Neuroprotective Agents; Spinal Cord; Superoxide Dismutase-1
PubMed: 31776380
DOI: 10.1038/s41598-019-53982-w -
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 -
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 -
The Cochrane Database of Systematic... Jan 2017This is an update of a review last published by Cochrane in June 2012 entitled "Cromolyn sodium for the prevention of chronic lung disease in preterm infants", which... (Review)
Review
BACKGROUND
This is an update of a review last published by Cochrane in June 2012 entitled "Cromolyn sodium for the prevention of chronic lung disease in preterm infants", which included two studies. This 2016 update identified no further studies.Chronic lung disease (CLD) frequently occurs in preterm infants and has a multifactorial aetiology including inflammation. Cromolyn sodium is a mast cell stabiliser that inhibits neutrophil activation and neutrophil chemotaxis and therefore may have a role in the prevention of CLD.
OBJECTIVES
To determine the effect of prophylactic administration of cromolyn sodium on the incidence of CLD at 28 days or 36 weeks' postmenstrual age (PMA), mortality, or the combined outcome of mortality and CLD at 28 days or 36 weeks' PMA in preterm infants.
SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1966 to 12 May 2016), Embase (1980 to 12 May 2016), and CINAHL (1982 to 12 May 2016). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled clinical trials involving preterm infants. Initiation of cromolyn sodium administration was during the first two weeks of life. The intervention had to include administration of cromolyn sodium by nebuliser or metered dose inhaler with or without spacer device versus placebo or no intervention. Eligible studies had to include at least one of the following outcomes: overall mortality, CLD at 28 days, CLD at 36 weeks' PMA, or the combined outcome mortality and CLD at 28 days.
DATA COLLECTION AND ANALYSIS
We used the standard method for Cochrane as described in the Cochrane Handbook for Systematic Reviews of Interventions. We reported risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous data. The meta-analysis used a fixed-effect model. We examined heterogeneity using the I2 statistic. We assessed the quality of evidence for the main comparison at the outcome level using the GRADE approach.
MAIN RESULTS
We identified two eligible studies with small numbers of infants enrolled (64 infants). Prophylaxis with cromolyn sodium did not result in a statistically significant effect on the combined outcome of mortality and CLD at 28 days (typical RR 1.05, 95% CI 0.73 to 1.52; typical RD 0.03, 95% CI -0.20 to 0.27; 2 trials, 64 infants; I2 = 0% for both RR and RD); mortality at 28 days (typical RR 1.31, 95% CI 0.52 to 3.29; I2 = 73% typical RD 0.06, 95% CI -0.13 to 0.26; I2 = 87%; 2 trials, 64 infants) (very low quality evidence); CLD at 28 days (typical RR 0.93, 95% CI 0.53 to 1.64; I2 = 40%; typical RD -0.03, 95% CI -0.27 to 0.20; I2 = 38%; 2 trials, 64 infants) or at 36 weeks' PMA (RR 1.25, 95% CI 0.43 to 3.63; RD 0.08, 95% CI -0.29 to 0.44; 1 trial, 26 infants). There was no significant difference in CLD in survivors at 28 days (typical RR 0.97, 95% CI 0.58 to 1.63; typical RD -0.02, 95% CI -0.29 to 0.26; I2 = 0% for both RR and RD; 2 trials, 50 infants) or at 36 weeks' PMA (RR 1.04, 95% CI 0.38 to 2.87; RD 0.02, 95% CI -0.40 to 0.43; 1 trial, 22 infants). Prophylaxis with cromolyn sodium did not show a statistically significant difference in overall neonatal mortality, incidence of air leaks, necrotising enterocolitis, intraventricular haemorrhage, sepsis, and days of mechanical ventilation. There were no adverse effects noted. The quality of evidence according to GRADE was very low for one outcome (mortality to 28 days) and low for all other outcomes. The reasons for downgrading the evidence was due to design (risk of bias in one study), inconsistency between the two studies (high I2 values for mortality at 28 days for both RR and RD), and lack of precision of estimates (small sample sizes). Further research does not seem to be justified.
AUTHORS' CONCLUSIONS
There is currently no evidence from randomised trials that cromolyn sodium has a role in the prevention of CLD. Cromolyn sodium cannot be recommended for the prevention of CLD in preterm infants.
Topics: Chronic Disease; Clinical Trials as Topic; Cromolyn Sodium; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Meta-Analysis as Topic; Respiratory System Agents
PubMed: 28114736
DOI: 10.1002/14651858.CD003059.pub3 -
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 -
Molecules (Basel, Switzerland) Dec 2020Advanced and sensitive spectrophotometric and chemometric analytical methods were successfully established for the stability-indicating assay of cromolyn sodium (CS) and...
Advanced and sensitive spectrophotometric and chemometric analytical methods were successfully established for the stability-indicating assay of cromolyn sodium (CS) and its alkaline degradation products (Deg1 and Deg2). Spectrophotometric mean centering ratio spectra method (MCR) and chemometric methods, including principal component regression (PCR) and partial least square (PLS-2) methods, were applied. Peak amplitudes after MCR at 367.8 nm, 373.8 nm and 310.6 nm were used within linear concentration ranges of 2-40 µg mL, 5-40 µg mL and 10-100 µg mL for CS, Deg1 and Deg2, respectively. For PCR and PLS-2 models, a calibration set of eighteen mixtures and a validation set of seven mixtures were built for the simultaneous determination of CS, Deg1 and Deg2 in the ranges of 5-13 µg mL, 8-16 µg mL, and 10-30 µg mL, respectively. The authors emphasize the importance of a stability-indicating strategy for the investigation of pharmaceutical products.
Topics: Cromolyn Sodium; Hydroxides; Least-Squares Analysis; Potassium Compounds; Principal Component Analysis; Sodium Hydroxide; Spectrophotometry
PubMed: 33339114
DOI: 10.3390/molecules25245953 -
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 -
The Turkish Journal of Gastroenterology... Jan 2023Relevant studies have indicated that hepatic mast cells may have potential roles in the progression of cholestasis and cholestasis-induced itch. We aimed to compare the...
BACKGROUND
Relevant studies have indicated that hepatic mast cells may have potential roles in the progression of cholestasis and cholestasis-induced itch. We aimed to compare the effects of cromolyn sodium and other medications on cholestatic pruritus, serum biochemistry, histamine, total bile acids, autotaxin, liver histopathology, and mast cell distribution in tissues in an experimental cholestasis model conducted by bile duct ligation.
METHODS
Rats received the determined treatment consecutively for 10 days in addition to bile duct ligation. On the 5th and 10th days of the experiment, the rats' itching behaviors were observed for 5 minutes. After 10 days, blood and tissue samples were taken.
RESULTS
Significant decreases in serum histamine and autotaxin levels, plasma total bile acids, total bilirubin, and biliary enzymes were reported only in cromolyn sodium-treated rats compared to the control group. In immunohistochemistry of the liver samples, the peribiliary mast cells stained positive for autotaxin. Except for bile duct infarctus, all histopathological findings of cholestasis significantly improved only in cromolyn sodium-treated and sertraline-treated rats. The liver and peritoneal mast cells significantly decreased only in cromolyn sodium-treated rats compared to the control group. On the 10th day of the experiment, the mean duration of itching was significantly lower in all groups, except for naloxone- and ondansetron-treated rats.
CONCLUSION
Cromolyn sodium has promising antipruritic efficacy and provides biochemical and histopathological recovery of the relevant parameters of cholestasis induced by bile duct ligation. For the first time in the literature, we showed that peribiliary mast cells can produce autotaxin, which is a very important pruritogenic signal in the setting of cholestasis.
Topics: Rats; Animals; Cromolyn Sodium; Mast Cell Stabilizers; Histamine; Cholestasis; Liver; Pruritus; Ligation
PubMed: 36098363
DOI: 10.5152/tjg.2022.21744 -
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