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Journal of Computer-aided Molecular... Feb 2023Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease caused by the protozoa Trypanosoma cruzi, affecting nearly 7 million people only...
Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease caused by the protozoa Trypanosoma cruzi, affecting nearly 7 million people only in the Americas. Polyamines are essential compounds for parasite growth, survival, and differentiation. However, because trypanosomatids are auxotrophic for polyamines, they must be obtained from the host by specific transporters. In this investigation, an ensemble of QSAR classifiers able to identify polyamine analogs with trypanocidal activity was developed. Then, a multi-template homology model of the dimeric polyamine transporter of T. cruzi, TcPAT12, was created with Rosetta, and then refined by enhanced sampling molecular dynamics simulations. Using representative snapshots extracted from the trajectory, a docking model able to discriminate between active and inactive compounds was developed and validated. Both models were applied in a parallel virtual screening campaign to repurpose known drugs as anti-trypanosomal compounds inhibiting polyamine transport in T. cruzi. Montelukast, Quinestrol, Danazol, and Dutasteride were selected for in vitro testing, and all of them inhibited putrescine uptake in biochemical assays, confirming the predictive ability of the computational models. Furthermore, all the confirmed hits proved to inhibit epimastigote proliferation, and Quinestrol and Danazol were able to inhibit, in the low micromolar range, the viability of trypomastigotes and the intracellular growth of amastigotes.
Topics: Humans; Putrescine; Ligands; Danazol; Quinestrol; Polyamines; Trypanosoma cruzi; Chagas Disease; Membrane Transport Proteins; Trypanocidal Agents
PubMed: 36494599
DOI: 10.1007/s10822-022-00491-0 -
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 -
Archives of Gynecology and Obstetrics Jan 2023Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective antiestrogen that induces endometrial atrophy and/or amenorrhea. The purpose of this systematic review is to provide an evaluation of safety and effectiveness of gestrinone for the treatment of endometriosis.
METHODS
We performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science and Scopus. Our selected primary outcomes were the changes in dysmenorrhea, pain relief including pelvic pain and dyspareunia. The secondary outcomes embrace hormones parameters, pregnancy rate and adverse events.
RESULTS
Of 3269 references screened, 16 studies were included involving 1286 women. All studies compared gestrinone with other drugs treatments (placebo, Danazol, Mifepristone tablets, Leuprolide acetate, Quyu Jiedu Recipe) during 6 months. When compared with other drugs treatments, gestrinone relieved dysmenorrhea, pelvic pain, and morphologic response in the ovary. There was an increase on the pregnancy rate. Regarding the side effects observed, gestrinone showed the same adverse events and increased the risk of acne and seborrhea when compared to other treatments. Even if there was any difference in efficacy between gestrinone, danazol, leuprolide acetate, or Quyu Jiedu Recipe Chinese Medicine, it remains unclear due to insufficient data.
CONCLUSION
Based limited evidence available suggests that gestrinone appeared to be safe and may have some efficacy advantages over danazol, as well as other therapeutic interventions for treating endometriosis. However, this conclusion should be interpreted with caution, due the quality of the evidence provided is generally very low or unclear.
TRIAL REGISTRATION
CRD42021284148.
Topics: Pregnancy; Female; Humans; Endometriosis; Gestrinone; Danazol; Leuprolide; Dysmenorrhea; Pelvic Pain
PubMed: 36434439
DOI: 10.1007/s00404-022-06846-0 -
International Journal of Transgender... 2024Pelvic pain is a common complaint among individuals assigned female at birth. However, few studies have explored pelvic pain among transmasculine patients on...
Pelvic pain is a common complaint among individuals assigned female at birth. However, few studies have explored pelvic pain among transmasculine patients on gender-affirming testosterone treatment, and most of these were performed in adult populations. The aim of our study was to investigate the prevalence, risk factors, nature and treatment of pelvic pain among trans adolescents on testosterone. A retrospective cohort study was performed on all trans adolescents started on gender-affirming testosterone treatment at our institution between 2007 and 2020. Among 158 trans adolescents who were started on testosterone therapy and followed-up for at least six months, 37 (23.4%) reported pelvic pain, with a median interval between testosterone initiation and reported onset of pain of 1.6 months (range 0.3-6.4). The prevalence of pelvic pain was higher in patients who were receiving menstrual suppression (n = 36, 26.3%) compared to those who were not (n = 1, 4.8%), giving a risk difference of 21.5% (95% CI 9.8% to 33.2%, p = 0.028). The most common descriptive terms were "cramps" (n = 17, 45.9%) and "similar to previous period pain" (n = 8, 21.6%). A range of different pharmacological strategies were employed, including paracetamol, NSAIDs, danazol, norethisterone, medroxyprogesterone, etonogestrel implant, intra-uterine device, goserelin and pelvic floor physiotherapy, with variable outcomes. In conclusion, we report here - in what is to our knowledge the first time - the prevalence rate of pelvic pain in trans adolescents on gender-affirming testosterone treatment, and observe that a quarter of them described pelvic pain. Limitations of our study include its retrospective nature, which is likely to be associated with under-reporting of pelvic pain, and the limited documentation of the nature and likely causes of this pain within the medical records. Prospective longitudinal studies to better understand the nature, etiology and optimal management of testosterone-associated pelvic pain are therefore warranted.
PubMed: 38323021
DOI: 10.1080/26895269.2022.2147118 -
Pharmaceuticals (Basel, Switzerland) Nov 2022Danazol is a treatment option for autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Three patients with AIHA and eight patients with ITP between 2008...
Danazol is a treatment option for autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Three patients with AIHA and eight patients with ITP between 2008 and 2022 were enrolled in the Rheumatology Outpatient Clinic of Chang Gung Memorial Hospital, Kaohsiung. Those patients were refractory or intolerant to conventional therapy and were treated with danazol. All the patients received an initial dose of danazol (200-400 mg). The observation period was 6 months. Three patients (100%) with AIHA and six (75%) with ITP achieved treatment response after 6 months of danazol therapy. The dose of glucocorticoid for responders could be reduced to ≤5 mg/day of prednisolone, and the immunosuppressants, except hydroxychloroquine and azathioprine for systemic lupus erythematosus, could be discontinued. Adverse events were acne in two (18.2%) patients and transient dose-related liver function impairment in one (9.1%) patient in the current series. Danazol therapy appears to be a favorable alternative for refractory AIHA and ITP by altering the erythrocyte membrane to resist osmotic lysis and protecting platelets against complement-mediated lysis. In this report, we also performed a literature review and searched the PubMed/Cochrane Library for articles published from 1984 to January 2022 on danazol therapy for patients with AIHA and ITP.
PubMed: 36355549
DOI: 10.3390/ph15111377 -
The Surgical Clinics of North America Dec 2022Breast pain is a common symptom in most women during their lifetime, and many times is self-limited. Mastalgia is categorized into 3 main groups: cyclic, noncyclic and... (Review)
Review
Breast pain is a common symptom in most women during their lifetime, and many times is self-limited. Mastalgia is categorized into 3 main groups: cyclic, noncyclic and extramammary. A good history, examination and targeted imaging can help to delineate the underlying cause of mastalgia and therefore guide treatment options. Diet, medications, stress, hormonal fluctuations, and an ill-fitting bra can be contributing factors for physiologic causes of mastalgia. Breast cancer is rarely a cause but should be excluded. Reassurance, support, dietary changes, nonsteroidal anti-inflammatory drugs and occasionally hormonal medications are options to help with improving breast pain.
Topics: Female; Humans; Mastodynia; Breast Neoplasms; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 36335929
DOI: 10.1016/j.suc.2022.06.001 -
The Cochrane Database of Systematic... Nov 2022Hereditary angioedema (HAE) is a serious and potentially life-threatening condition that causes acute attacks of swelling, pain and reduced quality of life. People with... (Review)
Review
BACKGROUND
Hereditary angioedema (HAE) is a serious and potentially life-threatening condition that causes acute attacks of swelling, pain and reduced quality of life. People with Type I HAE (approximately 80% of all HAE cases) have insufficient amounts of C1 esterase inhibitor (C1-INH) protein; people with Type II HAE (approximately 20% of all cases) may have normal C1-INH concentrations, but, due to genetic mutations, these do not function properly. A few people, predominantly females, experience HAE despite having normal C1-INH levels and C1-INH function (rare Type III HAE). Several new drugs have been developed to treat acute attacks and prevent recurrence of attacks. There is currently no systematic review and meta-analysis that included all preventive medications for HAE.
OBJECTIVES
To assess the benefits and harms of interventions for the long-term prevention of HAE attacks in people with Type I, Type II or Type III HAE.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 3 August 2021.
SELECTION CRITERIA
We included randomised controlled trials in children or adults with HAE that used medications to prevent HAE attacks. The comparators could be placebo or active comparator, or both; approved and experimental drug trials were eligible for inclusion. There were no restrictions on dose, frequency or intensity of treatment. The minimum length of four weeks of treatment was required for inclusion; this criterion excluded the acute treatment of HAE attacks.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. HAE attacks (number of attacks per person, per population) and change in number of HAE attacks; 2. mortality and 3. serious adverse events (e.g. hepatic dysfunction, hepatic toxicity and deleterious changes in blood tests). Our secondary outcomes were 4. quality of life; 5. severity of breakthrough attacks; 6. disability and 7. adverse events (e.g. weight gain, mild psychological changes and body hair). We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified 15 studies (912 participants) that met the inclusion criteria. The studies included people with Type I and II HAE. The studies investigated avoralstat, berotralstat, subcutaneous C1-INH, plasma-derived C1-INH, nanofiltered C1-INH, recombinant human C1-INH, danazol, and lanadelumab for the prevention of HAE attacks. We did not find any studies on the use of tranexamic acid for prevention of HAE attacks. All drugs except avoralstat reduced the number of HAE attacks compared with placebo. For breakthrough attacks that occurred despite prophylactic treatment, intravenous and subcutaneous forms of C1-INH and lanadelumab reduced attack severity. It is not known whether other drugs have a similar effect, as the severity of breakthrough attacks in people taking drugs other than C1-INH and lanadelumab was not reported. For quality of life, avoralstat, berotralstat, C1-INH (all forms) and lanadelumab increased quality of life compared with placebo; there were no data for danazol. Four studies reported on changes in disability during treatment with C1-INH, berotralstat and lanadelumab; all three drugs decreased disability compared with placebo. Adverse events, including serious adverse events, did not occur at a rate higher than placebo. However, serious adverse event data and other adverse event data were not available for danazol, which prevented us from drawing conclusions about the absolute or relative safety of this drug. No deaths were reported in the included studies. The analysis was limited by the small number of studies, the small number of participants in each study and the lack of data on older drugs, therefore the certainty of the evidence is low. Given the rarity of HAE, it is not surprising that drugs were rarely directly compared, which does not allow conclusions on the comparative efficacy of the various drugs for people with HAE. Finally, we did not identify any studies that included people with Type III HAE. Therefore, we cannot draw any conclusions about the efficacy or safety of any drug in people with this form of HAE.
AUTHORS' CONCLUSIONS
The available data suggest that berotralstat, C1-INH (subcutaneous, plasma-derived, nanofiltered and recombinant), danazol and lanadelumab are effective in lowering the risk or incidence (or both) of HAE attacks. In addition, C1-INH and lanadelumab decrease the severity of breakthrough attacks (data for other drugs were not available). Avoralstat, berotralstat, C1-INH (all forms) and lanadelumab increase quality of life and do not increase the risk of adverse events, including serious adverse events. It is possible that danazol, subcutaneous C1-INH and recombinant human C1-INH are more effective than berotralstat and lanadelumab in reducing the risk of breakthrough attacks, but the small number of studies and the small size of the studies means that the certainty of the evidence is low. This and the lack of head-to-head trials prevented us from drawing firm conclusions on the relative efficacy of the drugs.
Topics: Adult; Child; Female; Humans; Male; Angioedemas, Hereditary; Quality of Life; Danazol; Complement C1 Inhibitor Protein; Administration, Intravenous; Treatment Outcome
PubMed: 36326435
DOI: 10.1002/14651858.CD013403.pub2 -
Water Science and Technology : a... Oct 2022This study is devoted to the scale-up potential of TiO/UV photocatalyst for real wastewater treatment including its durability tests. The activity of the prepared TiO...
This study is devoted to the scale-up potential of TiO/UV photocatalyst for real wastewater treatment including its durability tests. The activity of the prepared TiO layers was first tested in a laboratory reactor on key representative pollutants diclofenac, chloramphenicol and triclosan. A special pilot plant reactor of a two-tube system with 21 stainless steel annulets covered by TiO thin layers and the inner volume of 3.5 L was constructed. Pilot tests were performed with wastewater from the pharmaceutical industry containing danazol and norethisterone with the concentration varying between 4 and 7 mg L at the flow 18 L h and municipal wastewater at the output sewage plant for 67,000 inhabitants containing bisphenol A, 4-nonyphenol, estron, ethinylestradiol and triclosan in the concentrations of the individual contaminants varying between 50 and 600 ng L at the flow 200 L h. After the treatment during the pilot photocatalytic test, the concentration of individual contaminants decreased by 82-100%, while no decrease in the efficiency of the photocatalytic process was recorded during the long-term tests lasting for 3-6 months.
Topics: Wastewater; Triclosan; Water Pollutants, Chemical; Catalysis; Water Purification; Titanium
PubMed: 36315090
DOI: 10.2166/wst.2022.313 -
Tropical Medicine and Infectious Disease Sep 2022Background: Aplastic anemia is a rare and life-threatening condition, seldomly witnessed concomitantly with Chagas disease. We aim to discuss the management of these...
Background: Aplastic anemia is a rare and life-threatening condition, seldomly witnessed concomitantly with Chagas disease. We aim to discuss the management of these patients under risk of chronic Chagas disease reactivation (CDR), a severe condition with a high morbimortality that occurs in chronic Chagas disease patients under immunosuppression. Case reports: Trypanosoma cruzi (T. cruzi) parasitemia was monitored in three patients for 4−58 months by conventional PCR (cPCR), quantitative PCR (qPCR), microhematocrit/buffy coat, blood culture, and/or xenodiagnosis. One patient received antiparasitic treatment (benznidazole) and the other received allopurinol. Although parasitemia was controlled during and after benznidazole treatment at 300 mg/d for 51 days, in one patient, hematologic parameters worsened continuously before, during, and after treatment. Allopurinol led only to the temporary suppression of T. cruzi parasitemia in the second patient, but after danazol and hematological improvement, parasitemia became undetectable until the end of monitoring. Discussion and Conclusion: Unexpected undetectable or low parasitemia by cPCR/qPCR was reported. We show that the monitoring of parasitemia by qPCR and the use of preemptive therapy when the parasitemia was positive proved to be beneficial to our patients. As a result of the toxicity of more effective antiparasitics, shorter regimens of benznidazole or less toxic drugs in preemptive therapy are options that deserve future studies.
PubMed: 36288009
DOI: 10.3390/tropicalmed7100268 -
American Family Physician Oct 2022Endometriosis is an inflammatory condition caused by the presence of endometrial tissue in extra-uterine locations and can involve bowel, bladder, and all peritoneal... (Review)
Review
Endometriosis is an inflammatory condition caused by the presence of endometrial tissue in extra-uterine locations and can involve bowel, bladder, and all peritoneal structures. It is one of the most common gynecologic disorders, affecting up to 10% of people of reproductive age. Presentation of endometriosis can vary widely, from infertility in asymptomatic people to debilitating pelvic pain, dysmenorrhea, and period-related gastrointestinal or urinary symptoms. Diagnosis of endometriosis in the primary care setting is clinical and often challenging, frequently resulting in delayed diagnosis and treatment. Although transvaginal ultrasonography is used to evaluate endometriosis of deep pelvic sites to rule out other causes of pelvic pain, magnetic resonance imaging is preferred if deep infiltrating endometriosis is suspected. Laparoscopy with biopsy remains the definitive method for diagnosis, although several gynecologic organizations recommend empiric therapy without immediate surgical diagnosis. Combined hormonal contraceptives with or without nonsteroidal anti-inflammatory drugs are first-line options in managing symptoms and have a tolerable adverse effect profile. Second-line treatments include gonadotropin-releasing hormone (GnRH) receptor agonists with add-back therapy, GnRH receptor antagonists, and danazol. Aromatase inhibitors are reserved for severe disease. All of these treatments are effective but may cause additional adverse effects. Referral to gynecology for surgical management is indicated if empiric therapy is ineffective, immediate diagnosis and treatment are necessary, or patients desire pregnancy. Alternative treatments have limited benefit in alleviating pain symptoms but may warrant further investigation.
Topics: Female; Humans; Pregnancy; Anti-Inflammatory Agents, Non-Steroidal; Aromatase Inhibitors; Contraceptive Agents; Danazol; Endometriosis; Gonadotropin-Releasing Hormone; Pelvic Pain; Receptors, LHRH
PubMed: 36260896
DOI: No ID Found