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Frontiers in Medicine 2021Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear. Bone marrow mononuclear cells from 10...
Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear. Bone marrow mononuclear cells from 10 patients newly diagnosed with aplastic anemia and 10 healthy volunteers were collected and cultured together with stanozolol, danazol, or blank control separately for marrow colony assays. K562 cell lines that had been incubated with stanozolol, danazol, or blank control were tested for erythroid or megakaryocytic differentiation. Meanwhile, CB6F1/Crl mice were injected with 1 × 10 C57BL/6 donor-originated lymphocytes after irradiation with 5 Gy total body irradiation to establish a model for immune-mediated bone marrow failure (aplastic anemia mouse model). Mice with aplastic anemia were treated with cyclosporin A monotherapy, cyclosporin A in combination with stanozolol, and cyclosporin A in combination with danazol for 30 days. Peripheral blood cell counts once a week and bone marrow colony assays at the end of 1 month were performed. The proportion of T cell subsets, level of inflammatory factors, erythropoietin, and thrombopoietin were detected before and after treatment. The levels of erythropoietin receptors on bone marrow mononuclear cells after treatment were tested using western blotting. In the experiments, the number of burst-forming units-erythroid; colony-forming units-granulocyte and macrophage; and colony-forming units-granulocyte, erythrocyte, monocyte, and megakaryocyte in the patients with aplastic anemia were significantly lower than that in the normal controls ( < 0.05). However, the number of colonies and mean fluorescence intensity of CD235a or CD41 expression in the harvested cultured cells were not significantly different among the different treatment groups in the patients with aplastic anemia, normal controls, and K562 cell lines. These results show that stanozolol and danazol produce no direct hematopoiesis-stimulating effects on progenitor cells. In the experiment, the mice with aplastic anemia treated with cyclosporin A and danazol exhibited the most rapid recovery of platelet; the platelet count returned to normal levels after 3 weeks of treatment, which was at least 1 week earlier than in the other groups. In contrast, mice treated with cyclosporin A and stanozolol exhibited the highest hemoglobin level at the end of treatment ( < 0.05). Bone marrow colony assays at 30 days showed that the number of burst-forming units-erythroid was the highest in mice treated with cyclosporin A and stanozolol, while the number of colony-forming units-granulocyte and macrophage was the highest in those treated with cyclosporin A and danazol. Compared to cyclosporin A monotherapy, additional stanozolol and danazol can both increase the level of regulatory T cells and upregulate interleukin-10, inhibiting the expression of tumor necrosis factor-α ( < 0.05). However, IL-2 was more effectively reduced by danazol than by stanozolol ( < 0.05). The cyclosporin A- and stanozolol-treated mice showed higher serum erythropoietin (corrected by hemoglobin level) and higher erythropoietin receptor levels in bone marrow mononuclear cells than the other groups ( < 0.05). Neither stanozolol nor danazol directly stimulated hematopoiesis . However, , stanozolol may exhibit an advantage in improving erythropoiesis, while danazol may induce stronger effects on platelets. Both danazol and stanozolol exhibited immunosuppressive roles. Stanozolol could enhance the secretion of erythropoietin and expression of erythropoietin receptor in bone marrow mononuclear cells.
PubMed: 34124083
DOI: 10.3389/fmed.2021.615195 -
Cureus Aug 2020Diamond-Blackfan anemia (DBA) is a congenital cause of bone marrow failure predominantly involving the erythroid cell line, with occasional impact on other cell lines.... (Review)
Review
Diamond-Blackfan anemia (DBA) is a congenital cause of bone marrow failure predominantly involving the erythroid cell line, with occasional impact on other cell lines. In the vast majority of cases, it is diagnosed by one year of age. We looked at the existing literature on the disease presentation along with established as well as upcoming treatment options. Numerous genes have been identified and extensively studied in the context of their part in the pathogenesis of DBA. Treatment revolves around the use of steroids and regular blood transfusions, with hematopoietic stem cell transplantation reserved for steroid-resistant cases. Newer modalities such as gene therapy, l-leucine, sotatercept, trifluoperazine, SMER28, and danazol are also concisely discussed. The purpose of this article is to review the previous literature on DBA and weigh the role of newer therapeutic agents.
PubMed: 32983714
DOI: 10.7759/cureus.10019 -
Revista Brasileira de Ginecologia E... Oct 2022Different drugs are used to treat mastalgia, such as danazol and bromocriptine, and both are associated with side effects, due to which most of women and healthcare... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Different drugs are used to treat mastalgia, such as danazol and bromocriptine, and both are associated with side effects, due to which most of women and healthcare providers are interested in herbal medicines. Therefore we aim to study the effectiveness of phytoestrogens on the severity of cyclic mastalgia.
METHODS
To carry out the present study, English electronic resources such as the Cochrane Library, ISI Web of Science, Scopus, and PubMed were used systematically and with no time limitation up to February 10, 2020.
RESULTS
In total, 20 studies were included in the present meta-analysis. The results of the meta-analysis showed that herbal medicines versus the control group (standard mean difference [SMD] = - 0.585; 95% confidence interval [CI]: - 0.728-- 0.44; heterogeneity; = 0.02; I2 = 42%), herbal medicines versus the B group (SMD = - 0.59; 95%CI: - 0.75-- 0.44; heterogeneity; = 0.03; I2 = 42%), and its subgroups, such as phytoestrogen (SMD = - 0.691; 95%CI: - 0.82-- 0.55; heterogeneity; = 0.669; I2 = 0%), Vitex-agnus-castus (SMD = - 0.642; 95%CI: - 0.84-- 0.44; < 0.001; = 203; I2 = 32%), flaxseed (SMD = - 0.63; 95%CI: - 0.901-- 0.367; = 0.871; I2 = 0%), and evening primrose (SMD= - 0.485; 95%CI:- 0.84-- 0.12; = 0.008; heterogeneity; = 0.06; I2 = 56%] may have effective and helpful effects on improving cyclic breast mastalgia. Also, chamomile, isoflavone, cinnamon, and nigella sativa significantly reduced mastalgia symptoms.
CONCLUSION
Herbal medicines and their subgroups may have effective and helpful effects on improving cyclic breast mastalgia. The findings of our meta-analysis must be done cautiously because low methodological quality in some evaluated studies of this systematic review.
Topics: Female; Humans; Mastodynia; Plants, Medicinal; Breast; Plant Extracts
PubMed: 36446563
DOI: 10.1055/s-0042-1755456 -
International Journal of Environmental... Jun 2021Mastalgia, or breast pain, is common among women which can lead to significant impairment in daily living. Hence, finding an effective treatment that can alleviate the... (Meta-Analysis)
Meta-Analysis Review
Mastalgia, or breast pain, is common among women which can lead to significant impairment in daily living. Hence, finding an effective treatment that can alleviate the symptom is very important. Thus, we carry out this study to determine the efficacy of evening primrose oil (EPO) for mastalgia treatment in women. The review included published randomised clinical trials that evaluated EPO used for treating mastalgia against a placebo or other treatments, irrespective of the blinding procedure, publication status, or sample size. Two independent authors screened the titles and abstracts of the identified trials; full texts of relevant trials were evaluated for eligibility. Two reviewers independently extracted data on the methods, interventions, outcomes, and risk of bias. The random-effects model was used for estimating the risk ratios and mean differences with 95% confidence intervals. Thirteen trials with 1752 randomised patients were included. The results showed that EPO has no difference to reduce breast pain compared to topical NSAIDS, danazol, or vitamin E. The number of patients who achieved pain relief was no different compared to the placebo or other treatments. The EPO does not increase adverse events, such as nausea, abdominal bloating, headache or giddiness, increase weight gain, and altered taste compared to a placebo or other treatments. EPO is a safe medication with similar efficacy for pain control in women with mastalgia compared to a placebo, topical NSAIDS, danazol, or vitamin E.
Topics: Female; Humans; Linoleic Acids; Mastodynia; Oenothera biennis; Plant Oils; Randomized Controlled Trials as Topic; gamma-Linolenic Acid
PubMed: 34200727
DOI: 10.3390/ijerph18126295 -
Annals of Allergy, Asthma & Immunology... Mar 2021Physician surveys on hereditary angioedema (HAE) management in 2010 and 2013 revealed important trends in HAE care.
BACKGROUND
Physician surveys on hereditary angioedema (HAE) management in 2010 and 2013 revealed important trends in HAE care.
OBJECTIVE
To evaluate current HAE management and the impact of new treatment options on physician practice patterns over time.
METHODS
During June and July 2019, 5382 physicians were contacted by means of postal mail to complete a 47-question survey; 177 responded (3%).
RESULTS
Across the 3 surveys, the home replaced the emergency department as the most typically reported setting for HAE attack treatment (54.3% vs 11.6% in 2010 and 32.5% in 2013; P < .001). Physicians reported C1 esterase inhibitor (C1-INH) as the most typically prescribed long-term prophylactic treatment (LTP) (60.0% vs 20.4% in 2010 and 56.7% in 2013; P < .001). Subcutaneous LTP medications were most typically prescribed over intravenous (C1-INH, 41.4%; subcutaneous lanadelumab, 21%; intravenous C1-INH, 18.6%). Danazol, the most frequently prescribed LTP treatment, dropped to 6.4% (55.8% in 2010 and 23.4% in 2013; P < .001). The strongest nonefficacy factor influencing clinician treatment choice changed over time, with cost and (or) insurance coverage increasing to 43.7% (from 24.4% in 2010 and 40.5% in 2013; P = .001), whereas the concern over adverse effects dropped to 16.2% (from 55.8% in 2010 and 29.5% in 2013; P < .001). Physician-reported patient satisfaction remains high, with only 1.5% of physicians indicating patients are not satisfied with treatment.
CONCLUSION
The US physician survey data reflect improvements in the HAE management in recent years. Therapeutic advances in HAE have led to reported higher rates of home treatment of HAE attacks, reduced concern for adverse treatment effects, and high levels of patient satisfaction.
Topics: Angioedemas, Hereditary; Complement C1 Inhibitor Protein; Danazol; Emergency Service, Hospital; Health Care Surveys; Hospitalization; Humans; Patient Satisfaction; Physicians; Practice Patterns, Physicians'; United States
PubMed: 33122123
DOI: 10.1016/j.anai.2020.10.009 -
European Review For Medical and... Jun 2023The aim of this study is to investigate the temporal relationship between the first occurrence of thromboembolic events (TEE) and the timing of myeloproliferative...
OBJECTIVE
The aim of this study is to investigate the temporal relationship between the first occurrence of thromboembolic events (TEE) and the timing of myeloproliferative neoplasm (MPN) diagnosis and to determine risk factors for TEE-related mortality in MPN.
PATIENTS AND METHODS
A total of 138 BCR-ABL-negative MPN patients with TEE, diagnosed from January 2010 to December 2019, were included in this retrospective cohort. Patients were compared according to mortality and subjects were classified into three groups with respect to having suffered index TEE before, during, or after MPN diagnosis.
RESULTS
The mean age of surviving patients was 57.5±13.8, while those who had died had a mean age of 72.0±9.0 (p<0.001). Males represented 56.5% of patients with mortality and 60.9% of those without mortality (p=0.876). TEE was detected in 26.0% of MPN patients, and TEE-related mortality rate was 16.7%. There was no relationship between mortality and the classification of patients according to index TEE (p =0.884). High age (p<0.001) and danazol use (p=0.014) were independently associated with TEE-related mortality.
CONCLUSIONS
The temporal relationship between TEE and MPN diagnosis was not found to influence mortality. Older patients and danazol recipients should be considered to have a higher risk of TEE-related mortality.
Topics: Male; Humans; Middle Aged; Aged; Aged, 80 and over; Retrospective Studies; Danazol; Neoplasms; Myeloproliferative Disorders; Thromboembolism
PubMed: 37318468
DOI: 10.26355/eurrev_202306_32611 -
ADMET & DMPK 2020An established pharmaceutical strategy to increase oral drug absorption of low solubility-high permeability drugs is to create nanoparticles of them. Reducing the size... (Review)
Review
An established pharmaceutical strategy to increase oral drug absorption of low solubility-high permeability drugs is to create nanoparticles of them. Reducing the size of the solid-state particles increases their dissolution and transport rate across the mucus barrier and the aqueous boundary layer. Suspensions of nanoparticles also sometimes behave differently than those of larger particles in the fed state. This review compares the absorption mechanisms of nano- and larger particles in the lumen at different prandial states, with an emphasis on data derived from in vivo models. Four BSC class II drugs-aprepitant, cyclosporine, danazol and fenofibrate-are discussed in detail based on information from preclinical intestinal perfusion models.
PubMed: 35300192
DOI: 10.5599/admet.881 -
Genetics in Medicine : Official Journal... Jul 2019The acquisition of pathogenic variants in the TERT promoter (TERTp) region is a mechanism of tumorigenesis. In nonmalignant diseases, TERTp variants have been reported...
PURPOSE
The acquisition of pathogenic variants in the TERT promoter (TERTp) region is a mechanism of tumorigenesis. In nonmalignant diseases, TERTp variants have been reported only in patients with idiopathic pulmonary fibrosis (IPF) due to germline variants in telomere biology genes.
METHODS
We screened patients with a broad spectrum of telomeropathies (n = 136), their relatives (n = 52), and controls (n = 195) for TERTp variants using a customized massively parallel amplicon-based sequencing assay.
RESULTS
Pathogenic -124 and -146 TERTp variants were identified in nine (7%) unrelated patients diagnosed with IPF (28%) or moderate aplastic anemia (4.6%); five of them also presented cirrhosis. Five (10%) relatives were also found with these variants, all harboring a pathogenic germline variant in telomere biology genes. TERTp clone selection did not associate with peripheral blood counts, telomere length, and response to danazol treatment. However, it was specific for patients with telomeropathies, more frequently co-occurring with TERT germline variants and associated with aging.
CONCLUSION
We extend the spectrum of nonmalignant diseases associated with pathogenic TERTp variants to marrow failure and liver disease due to inherited telomerase deficiency. Specificity of pathogenic TERTp variants for telomerase dysfunction may help to assess the pathogenicity of unclear constitutional variants in the telomere diseases.
Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Blood Cell Count; Bone Marrow Diseases; Child; Child, Preschool; Cohort Studies; Female; Humans; Idiopathic Pulmonary Fibrosis; Liver Diseases; Male; Middle Aged; Promoter Regions, Genetic; Retrospective Studies; Telomerase; Telomere; Young Adult
PubMed: 30523342
DOI: 10.1038/s41436-018-0385-x -
Chinese Medical Journal Nov 2022
Topics: Humans; Danazol; Angioedemas, Hereditary
PubMed: 36583927
DOI: 10.1097/CM9.0000000000002144 -
Allergy and Asthma Proceedings Mar 2021Hereditary angioedema (HAE) is a rare disease that often leads to misdiagnosis. The delay of diagnosis is > 10 years in China. Recurrent and acute abdominal pain is one...
Hereditary angioedema (HAE) is a rare disease that often leads to misdiagnosis. The delay of diagnosis is > 10 years in China. Recurrent and acute abdominal pain is one of the common symptoms of HAE. Because of the high misdiagnosis rate, it usually results in unnecessary surgical procedures. This study focused on the clinical symptoms and management of HAE-related abdominal attacks in Chinese patients to provide some new insight for the emergency department (ED) physicians and gastroenterologists. A Web-based survey was conducted among 107 patients with HAE from 94 unrelated families. Detailed questions with respect to the abdominal attacks were asked, including the frequency, symptoms, and duration before and after confirmed diagnosis. The demographic characteristics, diagnosis process, and treatment outcomes were also included. Approximately 70% of the patients with HAE presented with abdominal symptoms during the onset of edema, mostly characterized by pain (94.8%), nausea (83.1%), vomiting (83.1%), diarrhea (59.7%), and constipation (23.4%). The patients were easily misdiagnosed as having gastroenteritis (35.1%) and appendicitis (10.4%), and 24.7% of them received unnecessary appendectomy or laparotomy. Danazol, a widely used drug for long-term prophylaxis of HAE in China, can reduce the attack frequency and alleviate the abdominal symptoms, but the adverse effects are also significant and more severe in women. Abdominal symptoms are common and important clinical features of HAE but are easily confused with other gastrointestinal diseases. ED physicians and gastroenterologists should consider HAE when patients experience recurrent and unexplained abdominal pain. Proper medical treatment should be administered in a timely manner if an HAE diagnosis is confirmed and efforts are required to increase access in China to medications both for on-demand treatment and long-term prophylaxis.
Topics: Abdominal Pain; Acute Pain; Adolescent; Adult; Aged; Angioedemas, Hereditary; Child; China; Danazol; Delayed Diagnosis; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pain Measurement; Predictive Value of Tests; Recurrence; Treatment Outcome; Unnecessary Procedures; Young Adult
PubMed: 33685557
DOI: 10.2500/aap.2021.42.210001