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Translational Psychiatry Mar 2023In the revised diagnostic classification systems ICD-11 and DSM-5, secondary, organic forms of obsessive-compulsive disorder (OCD) are implemented as specific...
In the revised diagnostic classification systems ICD-11 and DSM-5, secondary, organic forms of obsessive-compulsive disorder (OCD) are implemented as specific nosological entities. Therefore, the aim of this study was to clarify whether a comprehensive screening approach, such as the Freiburg-Diagnostic-Protocol for patients with OCD (FDP-OCD), is beneficial for detecting organic OCD forms. The FDP-OCD includes advanced laboratory tests, an expanded magnetic resonance imaging (MRI) protocol, and electroencephalography (EEG) investigations as well as automated MRI and EEG analyses. Cerebrospinal fluid (CSF), [F]fluorodeoxyglucose positron emission tomography, and genetic analysis were added for patients with suspected organic OCD. The diagnostic findings of the first 61 consecutive OCD inpatients (32 female and 29 male; mean age: 32.7 ± 12.05 years) analyzed using our protocol were investigated. A probable organic cause was assumed in five patients (8%), which included three patients with autoimmune OCD (one patient with neurolupus and two with specific novel neuronal antibodies in CSF) and two patients with newly diagnosed genetic syndromes (both with matching MRI alterations). In another five patients (8%), possible organic OCD was detected (three autoimmune cases and two genetic cases). Immunological serum abnormalities were identified in the entire patient group, particularly with high rates of decreased "neurovitamin" levels (suboptimal vitamin D in 75% and folic acid in 21%) and increased streptococcal (in 46%) and antinuclear antibodies (ANAs; in 36%). In summary, the FDP-OCD screening led to the detection of probable or possible organic OCD forms in 16% of the patients with mostly autoimmune forms of OCD. The frequent presence of systemic autoantibodies such as ANAs further support the possible influence of autoimmune processes in subgroups of patients with OCD. Further research is needed to identify the prevalence of organic OCD forms and its treatment options.
Topics: Humans; Female; Male; Young Adult; Adult; Inpatients; Anastrozole; Autoantibodies; Diagnostic and Statistical Manual of Mental Disorders; Electroencephalography
PubMed: 36882422
DOI: 10.1038/s41398-023-02368-8 -
Breast Cancer Research and Treatment May 2023The development of oestrogen resistance is a major challenge in managing hormone-sensitive metastatic breast cancer. Saracatinib (AZD0530), an oral Src kinase inhibitor,... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The development of oestrogen resistance is a major challenge in managing hormone-sensitive metastatic breast cancer. Saracatinib (AZD0530), an oral Src kinase inhibitor, prevents oestrogen resistance in animal models and reduces osteoclast activity. We aimed to evaluate the efficacy of saracatinib addition to aromatase inhibitors (AI) in patients with hormone receptor-positive metastatic breast cancer.
METHODS
This phase II multicentre double-blinded randomised trial allocated post-menopausal women to AI with either saracatinib or placebo (1:1 ratio). Patients were stratified into an "AI-sensitive/naïve" group who received anastrozole and "prior-AI" group who received exemestane. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and toxicity.
RESULTS
140 patients were randomised from 20 UK centres to saracatinib/AI (n = 69) or placebo/AI (n = 71). Saracatinib was not associated with an improved PFS (3.7 months v. 5.6 months placebo/AI) and did not reduce likelihood of bony progression. There was no benefit in OS or ORR. Effects were consistent in "AI-sensitive/naive" and "prior-AI" sub-groups. Saracatinib was well tolerated with dose reductions in 16% and the main side effects were gastrointestinal, hypophosphatemia and rash.
CONCLUSION
Saracatinib did not improve outcomes in post-menopausal women with metastatic breast cancer. There was no observed beneficial effect on bone metastases. CRUKE/11/023, ISRCTN23804370.
Topics: Female; Humans; Breast Neoplasms; Aromatase Inhibitors; Aromatase; Estrogens; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36859649
DOI: 10.1007/s10549-023-06873-8 -
Life (Basel, Switzerland) Feb 2023Male infertility is significantly influenced by the plasma-protein sex hormone-binding globulin (SHBG). Male infertility, erectile dysfunction, prostate cancer, and...
Male infertility is significantly influenced by the plasma-protein sex hormone-binding globulin (SHBG). Male infertility, erectile dysfunction, prostate cancer, and several other male reproductive system diseases are all caused by reduced testosterone bioavailability due to its binding to SHBG. In this study, we have identified 345 phytochemicals from 200 literature reviews that potentially inhibit severe acute respiratory syndrome coronavirus 2. Only a few studies have been done using the SARS-CoV-2 inhibitors to identify the SHBG inhibitor, which is thought to be the main protein responsible for male infertility. In virtual-screening and molecular-docking experiments, cryptomisrine, dorsilurin E, and isoiguesterin were identified as potential SHBG inhibitors with binding affinities of -9.2, -9.0, and -8.8 kcal/mol, respectively. They were also found to have higher binding affinities than the control drug anastrozole (-7.0 kcal/mol). In addition to favorable pharmacological properties, these top three phytochemicals showed no adverse effects in pharmacokinetic evaluations. Several molecular dynamics simulation profiles' root-mean-square deviation, radius of gyration, root-mean-square fluctuation, hydrogen bonds, and solvent-accessible surface area supported the top three protein-ligand complexes' better firmness and stability than the control drug throughout the 100 ns simulation period. These combinatorial drug-design approaches indicate that these three phytochemicals could be developed as potential drugs to treat male infertility.
PubMed: 36836833
DOI: 10.3390/life13020476 -
Journal of Clinical Medicine Feb 2023dopamine agonists are the recommended treatment for male prolactinomas, but some patients may develop dopamine-agonist-resistant hyperprolactinemia, leading to... (Review)
Review
BACKGROUND
dopamine agonists are the recommended treatment for male prolactinomas, but some patients may develop dopamine-agonist-resistant hyperprolactinemia, leading to persistent hypogonadism that requires treatment with testosterone. However, testosterone replacement therapy may be associated with a decrease in the efficacy of dopamine agonists due to the aromatization of testosterone to estradiol, which can stimulate the proliferation and hyperplasia of lactotroph cells in the pituitary, inducing resistance to dopamine agonists.
OBJECTIVE
this paper systematically reviewed the role of aromatase inhibitors for men with prolactinoma and dopamine-agonist-resistant or persistent hypogonadism following treatment.
METHOD
we performed a systematic review of all studies (according to PRISMA guidelines), assessing the role of aromatase inhibitors, including anastrozole and letrozole, for male prolactinoma. An English-language search for relevant studies was conducted on PubMed from its inception to 1 December 2022. The reference lists of the relevant studies were also reviewed.
RESULTS
our systematic review identified six articles (nine patients), including five case reports and a single case series, on the use of aromatase inhibitors for male prolactinomas. Reducing estrogen levels with an aromatase inhibitor improved sensitivity to dopamine agonists, as the addition of anastrozole or letrozole improves the control of prolactin levels and may lead to the shrinkage of tumors.
CONCLUSION
aromatase inhibitors are of potential value to patients with dopamine-agonist-resistant prolactinoma, or when hypogonadism persists while using high-dose dopamine agonists.
PubMed: 36835974
DOI: 10.3390/jcm12041437 -
The American Journal of Case Reports Feb 2023BACKGROUND Vision loss secondary to optic neuritis is an uncommon adverse effect of nonsteroidal aromatase inhibitors. There have been few reports in the literature on...
BACKGROUND Vision loss secondary to optic neuritis is an uncommon adverse effect of nonsteroidal aromatase inhibitors. There have been few reports in the literature on visual disturbance in patients on long-term treatment with Anastrozole for breast cancer prevention; but none had symptoms worse than blurry vision and/or xerostomia. The present patient had acute onset of right-sided vision loss without other neurologic deficits while using the aromatase inhibitor Anastrozole for breast cancer treatment. CASE REPORT A 69-year-old woman presented to the Emergency Department with approximately 1 month of worsening right eye vision loss that was not associated with any other neurologic deficits or any acute symptoms. The symptom was constant and without alleviating or aggravating factors. After extensive workup with ophthalmologic evaluation, Infectious Disease evaluation, autoimmune tests, brain imaging, lumbar puncture with CSF analysis, and temporal artery biopsy reporting unremarkable results, it was determined that the patient was in an inflammatory state induced by long-term use of Anastrozole, an aromatase inhibitor. CONCLUSIONS The patient's long-term use of Anastrozole likely played a large part in developing right visual disturbance secondary to optic neuritis, as a patient of this age has little risk of developing conditions such as optic neuritis, unilateral loss of vision, and/or autoimmune conditions.
Topics: Female; Humans; Aged; Anastrozole; Aromatase Inhibitors; Optic Neuritis; Vision Disorders; Breast Neoplasms
PubMed: 36823967
DOI: 10.12659/AJCR.939026 -
Frontiers in Pharmacology 2023Breast cancer is the most common cancer, except for non-melanoma skin cancer, among women in Brazil and worldwide. Breast cancer treatment involves surgery,...
Breast cancer is the most common cancer, except for non-melanoma skin cancer, among women in Brazil and worldwide. Breast cancer treatment involves surgery, radiotherapy and chemotherapy, which is used in 70% of patients. This study analyzes the utilization of antineoplastic agents among women undergoing their first round of chemotherapy in Brazil's public health system (SUS) in the state of Rio de Janeiro. Data from the SUS Outpatient Information System's authorizations for high-complexity outpatient procedures (APACs) billed between January 2013 and December 2019 were extracted, and three datasets were created: all type 1 and type 2 APACs (including all chemotherapy procedures performed); all type 1 APACs; and first type 1 APACs (containing data only for the first round of breast cancer chemotherapy). Names of antineoplastic agents were standardized to enable the subsequent classification of therapy regimens, mitigating limitations related to data quality. Absolute and relative frequencies were used to describe sociodemographic, clinical and treatment characteristics, therapy regimen and supportive drugs. We analyzed 23,232 records of women undergoing their first round of chemotherapy. There was a progressive increase in the number of procedures over time. Women were predominantly white, lived in the capital and close to the treatment center. Most had stage 3 cancer at diagnosis (50.51%) and a significant proportion had regional lymph node invasion (37.9%). The most commonly used chemotherapy regimens were TAC (docetaxel, doxorubicine, cyclophosphamide) (21.05%) and and cyclophosphamide (17.71%), followed by tamoxifen (15.65%) and anastrozole (12.94%). Supportive drugs were prescribed to 386 women and zoledronic acid was predominant (59.58%). The findings point to important bottlenecks and possible inequities in access to treatment and medicine utilization for breast cancer patients in Brazil. Efforts to improve breast cancer treatment and prevention should not only focus on interventions at the individual level but address the disease as a public health problem. The study focused on women undergoing their first round of treatment, providing valuable insight into patient and treatment characteristics to inform policy decisions.
PubMed: 36814497
DOI: 10.3389/fphar.2023.1069505 -
Scientific Reports Feb 2023In the current work, a new type of micelle is designed that has active connectivity in respond to exterior stimulus and the desired water solubility. Two end-ornamented...
In the current work, a new type of micelle is designed that has active connectivity in respond to exterior stimulus and the desired water solubility. Two end-ornamented homopolymers, polystyrene-beta-cyclodextrin (PS-β-CD) and polyethylene oxide-ferrocene (PE-FE), can aggregate as a supramolecular micelle (PS-β-CD/PE-FE) by the guest-host interactions. Our results showed that the Lennard-Jones and hydrophobic interactions are the main powerful forces for the micelle formation process. It was found that the electrical field plays a role as a driving force in the reversible assembly-disassembly of the micellar system. Moreover, for the first time, we examined the PS-β-CD/PE-FE micelle interaction as a drug delivery system with anastrozole (ANS) and mitomycin C (MIC) anti-cancer drugs. The investigation of the total energy between PS-β-CD/PE-FE micelle and drugs predicts the drug adsorption process as favorable (E = - 638.67 and - 259.80 kJ/mol for the Micelle@ANS and Micelle@MIC complexes, respectively). Our results offer a deep understanding of the micelle formation process, the electrical field-respond, and drug adsorption behaviors of the micelle. This simulation study has been accomplished by employing classical molecular dynamics calculation.
Topics: Micelles; Drug Delivery Systems; Polyethylene Glycols; Molecular Dynamics Simulation; Polystyrenes
PubMed: 36792790
DOI: 10.1038/s41598-023-29835-y -
Journal of Medical Cases Jan 2023Breast cancer is widely known as the most common cancer in women in the United States. If left untreated, it can have detrimental effects. If the breast cancer is...
Breast cancer is widely known as the most common cancer in women in the United States. If left untreated, it can have detrimental effects. If the breast cancer is aggressive in nature, it can metastasize to the lymph nodes, bones, liver, lungs, and brain. A rare location of metastasis is the leptomeninges, specifically the pia and arachnoid matter. This term is coined as leptomeningeal carcinomatosis. Its diagnosis can be challenging to make as patients can present with non-specific symptoms. We present the case of an elderly female with a prior history of breast cancer that was treated with 12 cycles of chemotherapy with paclitaxel, radiation to her left axilla, and daily anastrozole for 3 years who came into the emergency department for worsening confusion, urinary incontinence, and difficulty ambulating. Cerebral spinal fluid obtained from a lumbar puncture supported a diagnosis of leptomeningeal carcinomatosis.
PubMed: 36756000
DOI: 10.14740/jmc4024 -
Asian Journal of Surgery Jul 2023
Topics: Humans; Female; Anastrozole; Arthralgia; Bone and Bones; Exercise Therapy; Breast Neoplasms
PubMed: 36737325
DOI: 10.1016/j.asjsur.2023.01.036