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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 -
Integrative Medicine Research Sep 2021This study aimed at determining the effect of the herbal mixture estrogen inhibition formula (EIF) and its possible mechanisms by precocious puberty animal models and...
BACKGROUND
This study aimed at determining the effect of the herbal mixture estrogen inhibition formula (EIF) and its possible mechanisms by precocious puberty animal models and network pharmacology-based analysis.
METHODS
Precocious puberty animal models were established by a single injection of 300 μg danazol, then female rats were administered EIF, vaginal openings were monitored, uterus and pituitary indices were determined. The levels of ALP, E2, LH, and FSH were measured using ELISA kits. Real-time PCR was performed to evaluate the mRNA expression of GnRH, UNC5C, and netrin-1 in hypothalamic tissues. We applied network pharmacological analysis to predict potential targets and pathways of EIF.
RESULTS
EIF delayed danazol-induced early vaginal opening. In the onset model, EIF reduced the increased levels of serum ALP, E2, LH, and FSH; as well as mRNA expressions of GnRH, Netrin-1, and UNC5C. Moreover, long-term administration of EIF not only diminished all impaired factors but also had no effect on the normal development of the animals. The gene set enrichment analysis showed that the targets of EIF are mainly associated with the GnRH signaling and ovarian steroidogenesis pathways.
CONCLUSION
EIF could be used in preclinical research for the treatment of precocious puberty by the inhibition of HPGA pre-maturation.
PubMed: 33665096
DOI: 10.1016/j.imr.2020.100708 -
Journal of the Formosan Medical... Aug 2021Hereditary angioedema (HAE) is an autosomal dominant disease characterized clinically by recurrent episodes of swelling in the tissues of the extremities, face, abdomen,...
Hereditary angioedema (HAE) is an autosomal dominant disease characterized clinically by recurrent episodes of swelling in the tissues of the extremities, face, abdomen, and respiratory tract. It is most often caused by C1 esterase inhibitor (C1 INH) gene mutation. This swelling may lead to bradykinin release, resulting in recurrent, paroxysmal, painful angioedema. Blister formation is an uncommon cutaneous manifestation of HAE. Herein, we report a case of a patient with HAE who developed linear wrist blisters on her skin, with swelling, as a rare complication of HAE. She was treated with attenuated androgens (Danazol) for two weeks at our clinic, after which the blisters showed dramatic improvement. To date, only a few HAE cases have been reported across the world. Therefore, it is important to focus on and recognize the development of edema blisters as a flare of HAE, which could consequently avoid unnecessary dermatological diagnostic workup and treatment.
Topics: Angioedemas, Hereditary; Blister; Chest Pain; Complement C1 Inhibitor Protein; Female; Humans; Taiwan; Wrist
PubMed: 33640192
DOI: 10.1016/j.jfma.2021.02.006 -
Journal of Investigational Allergology... Feb 2021Hereditary angioedema due to C1-esterase inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease. In the last decade, new drugs and new indications for... (Review)
Review
Hereditary angioedema due to C1-esterase inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease. In the last decade, new drugs and new indications for old drugs have played a role in the management of C1-INH-HAE. This review examines current therapy for C1-INH-HAE and provides a brief summary of drugs that are under development. Increased knowledge of the pathophysiology of C1-INH-HAE has been crucial for advances in the field, with inhibition of the kallikrein-kinin system (plasma kallikrein, activated factor XII) as a key area in the discovery of new drugs, some of which are already marketed for treatment of C1-INH-HAE. Pharmacological treatment is based on 3 pillars: treatment of acute angioedema attacks (on-demand treatment), short-term (preprocedure) prophylaxis, and long-term prophylaxis. The 4 drugs that are currently available for the treatment of acute angioedema attacks (purified plasma-derived human C1 esterase inhibitor concentrate, icatibant acetate, ecallantide, recombinant human C1 esterase inhibitor) are all authorized for self-administration, except ecallantide. Purified plasma-derived human C1 esterase inhibitor concentrate is the treatment of choice for short-term prophylaxis. Tranexamic acid, danazol, intravenous and subcutaneous nanofiltered purified plasma-derived human C1 esterase inhibitor concentrate, and lanadelumab can be used for long-term prophylaxis. New drugs are being investigated, mainly as long-term prophylaxis, and are aimed at blocking the kallikrein-kinin system by means of antiprekallikrein, antikallikrein, and anti-activated FXII action.
Topics: Angioedemas, Hereditary; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Complement C1 Inhibitor Protein; Humans; Kallikrein-Kinin System; Peptides; Recombinant Proteins
PubMed: 33602658
DOI: 10.18176/jiaci.0653 -
International Journal of Environmental... Jan 2021The aim of this review is to clarify the relative association between adenomyosis and infertility and the possible treatment for an infertile patient. Although... (Review)
Review
The aim of this review is to clarify the relative association between adenomyosis and infertility and the possible treatment for an infertile patient. Although adenomyosis is detected more often in women of late reproductive age, its influence on pregnancy rates is important, especially considering the tendency to delay pregnancy among women in developed countries. In this article, we present a critical analysis of the literature data concerning the impact of adenomyosis on fertility. The possible effects of treatment on the pregnancy rate will also be discussed. We conducted a literature search; publications from Pubmed, Embase and Cochrane databases published from 1982 to 2019 were retrieved using terms 'adenomyosis and infertility' and 'adenomyosis and pregnancy outcomes', extensively studied in the aspects of diagnosis, pathogenesis of infertility and possible treatment methods. Molecular studies have given deep insight into the pathogenesis of adenomyosis in the recent few years, but there is a huge discrepancy between in vitro studies and praxis. Oral contraceptive pills, anti-prostaglandins, oral or parenteral progestins, danazol and gonadotrophin-releasing hormone (GnRH) analogues have all been used to control menstrual pain and menorrhagia in women with adenomyosis, but they temporarily suppress the menstrual cycle. Additionally, endometrial ablation and hysterectomy used to alleviate pain caused by adenomyosis exclude pregnancy planning. The development of imaging techniques-ultrasound and MRI-enables the diagnosis of adenomyosis with very high accuracy nowadays, but the methods of treatment mentioned above have not given satisfactory results in women planning pregnancy. For these patients, the high-intensity-focused ultrasound method (HIFU) and combined treatment before assisted reproductive techniques can prove beneficial in adenomyosis patients.
Topics: Adenomyosis; Dysmenorrhea; Female; Humans; Infertility; Menorrhagia; Pregnancy; Pregnancy Rate
PubMed: 33573117
DOI: 10.3390/ijerph18031235 -
Frontiers in Pharmacology 2020The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in...
The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To confirm the effect of the Fy formula on PP through the GPR54/GnRH signaling pathway, we first treated GT1-7 cells with the Fy formula and observed changes in the expression of related genes and proteins and in GnRH secretion. Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15. The time of vaginal opening, the wet weights of the ovary and uterus, serum hormone levels and the expression of hypothalamic-related genes were observed. We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway.
PubMed: 33551803
DOI: 10.3389/fphar.2020.596525 -
Anesthesia and Pain Medicine Jan 2021Hereditary angioedema (HAE) is a rare disease caused by the deficiency of C1 esterase inhibitor. HAE has a risk of life-threatening complications such as capillary leak...
BACKGROUND
Hereditary angioedema (HAE) is a rare disease caused by the deficiency of C1 esterase inhibitor. HAE has a risk of life-threatening complications such as capillary leak syndrome (CLS) and disseminated intravascular coagulation (DIC).
CASE
A 42-year-old male patient with HAE presented for deceased-donor kidney transplantation. Prophylactic fresh frozen plasma (FFP) was given before surgery because of the risk of edema development. With careful management during anesthesia, there were no problems during surgery. However, generalized edema, hypotension, hypoalbuminemia, massive drainage of serosanguineous fluids from the intraabdominal space, and DIC occurred on the day after surgery. CLS was suspected and sustained hypotension with generalized edema became worse despite treatment with albumin, danazol, FFP, and vasoactive drugs. The patient's condition worsened despite intensive care and he died due to shock.
CONCLUSIONS
The anesthesiologist should prepare for the critical complications of HAE and prepare the appropriate treatment options.
PubMed: 33530679
DOI: 10.17085/apm.20098 -
Scientific Reports Dec 2020Cytochrome P450 2J2 (CYP2J2) is responsible for the epoxidation of endogenous arachidonic acid, and is involved in the metabolism of exogenous drugs. To date, no crystal...
Cytochrome P450 2J2 (CYP2J2) is responsible for the epoxidation of endogenous arachidonic acid, and is involved in the metabolism of exogenous drugs. To date, no crystal structure of CYP2J2 is available, and the proposed structural basis for the substrate recognition and specificity in CYP2J2 varies with the structural models developed using different computational protocols. In this study, we developed a new structural model of CYP2J2, and explored its sensitivity to substrate binding by molecular dynamics simulations of the interactions with chemically similar fluorescent probes. Our results showed that the induced-fit binding of these probes led to the preferred active poses ready for the catalysis by CYP2J2. Divergent conformational dynamics of CYP2J2 due to the binding of each probe were observed. However, a stable hydrophobic clamp composed of residues I127, F310, A311, V380, and I487 was identified to restrict any substrate access to the active site of CYP2J2. Molecular docking of a series of compounds including amiodarone, astemizole, danazol, ebastine, ketoconazole, terfenadine, terfenadone, and arachidonic acid to CYP2J2 confirmed the role of those residues in determining substrate binding and specificity of CYP2J2. In addition to the flexibility of CYP2J2, the present work also identified other factors such as electrostatic potential in the vicinity of the active site, and substrate strain energy and property that have implications for the interpretation of CYP2J2 metabolism.
Topics: Arachidonic Acid; Astemizole; Butyrophenones; Catalytic Domain; Cytochrome P-450 CYP2J2; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Humans; Hydrophobic and Hydrophilic Interactions; Kinetics; Molecular Docking Simulation; Oxidation-Reduction; Piperidines; Protein Binding; Substrate Specificity
PubMed: 33335233
DOI: 10.1038/s41598-020-79284-0 -
Blood Jan 2021Cyclic thrombocytopenia (CTP) is a rare disease, which is characterized by periodic fluctuation of the platelet count. The pathogenesis of CTP is unknown and most likely...
Cyclic thrombocytopenia (CTP) is a rare disease, which is characterized by periodic fluctuation of the platelet count. The pathogenesis of CTP is unknown and most likely heterogeneous. Patients with CTP are almost always misdiagnosed as having primary immune thrombocytopenia (ITP). The interval between ITP and CTP diagnosis can be many years. CTP patients often receive ITP-specific therapies including corticosteroids, thrombopoietin receptor agonists, rituximab, and splenectomy, which are followed by a transient increase in platelet count that is wrongly attributed to treatment effect with inevitable "relapse." CTP can be diagnosed by frequent platelet count monitoring, which reveals a typical pattern of periodic platelet cycling. An early diagnosis of CTP will prevent these patients from being exposed to possibly harmful therapies. The bleeding phenotype is usually mild and consists of mucocutaneous bleeding at the time when the platelet count is at its nadir. Severe bleeding from other sites can occur but is rare. Some patients respond to cyclosporine A or to danazol, but most patients do not respond to any therapy. CTP can be associated with hematological malignancies or disorders of the thyroid gland. Nevertheless, spontaneous remissions can occur, even after many years.
Topics: Blood Platelets; Humans; Platelet Count; Thrombocytopenia
PubMed: 33197928
DOI: 10.1182/blood.2020008218 -
American Journal of Hematology Jan 2021Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied... (Review)
Review
DISEASE OVERVIEW
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations. Additional disease features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.
DIAGNOSIS
Bone marrow morphology is the primary basis for diagnosis. Presence of JAK2, CALR, or MPL mutation, expected in around 90% of the patients, is supportive but not essential for diagnosis; these mutations are also prevalent in the closely related MPNs, namely polycythemia vera (PV) and essential thrombocythemia (ET). The 2016 World Health Organization classification system distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic ET in its presentation. Furthermore, approximately 15% of patients with ET or PV might progress into a PMF-like phenotype (post-ET/PV MF) during their clinical course.
ADVERSE MUTATIONS
SRSF2, ASXL1, and U2AF1-Q157 mutations predict inferior survival in PMF, independent of each other and other risk factors. RAS/CBL mutations predicted resistance to ruxolitinib therapy.
ADVERSE KARYOTYPE
Very high risk abnormalities include -7, inv (3), i(17q), +21, +19, 12p-, and 11q-.
RISK STRATIFICATION
Two new prognostic systems for PMF have recently been introduced: GIPSS (genetically-inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation- and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSSv2 includes, in addition, clinical risk factors. GIPSS features four and MIPSSv2 five risk categories.
RISK-ADAPTED THERAPY
Observation alone is advised for MIPSSv2 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment for "very high" and "high" risk disease (estimated 10-year survival 0%-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. In non-transplant candidates, conventional treatment for anemia includes androgens, prednisone, thalidomide, and danazol; for symptomatic splenomegaly, hydroxyurea and ruxolitinib; and for constitutional symptoms, ruxolitinib. Fedratinib, another JAK2 inhibitor, has now been FDA-approved for use in ruxolitinib failures. Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for non-hepatosplenic EMH and extremity bone pain.
NEW DIRECTIONS
A number of new agents, alone or in combination with ruxolitinib, are currently under investigation for MF treatment (ClinicalTrials.gov); preliminary results from some of these clinical trials were presented at the 2020 ASH annual meeting and highlighted in the current document.
Topics: Disease-Free Survival; Humans; Mutation; Primary Myelofibrosis; Risk Assessment; Survival Rate
PubMed: 33197049
DOI: 10.1002/ajh.26050