Here, we describe the production and characterization of a novel p65/LysMCre mouse model, which lacks canonical nuclear factor-kappaB member RelA/p65 (indicated as p65 hereafter) in bone marrow-derived macrophages. Cultured bone marrow-derived macrophages that lack p65 protein reveal NF-κB signaling deficiencies, a reduction in phagocytic ability, and reduced ability to produce nitrites. Despite abnormal bone marrow-derived macrophage function, p65/LysMCre mice do not exhibit differences in naïve systemic immune profiles or colony forming units and time to death following infection as compared to controls.
View Article and Find Full Text PDFInsulin infusion therapy is commonly utilized for treatment of severe hypertriglyceridemia, however, data supporting a standardized dosing approach is lacking. This study aimed to determine the average initial insulin dose utilized for treatment of hypertriglyceridemia and the associated reduction in serum triglycerides. This single-center, retrospective, descriptive analysis conducted at an academic medical center included adult hospitalized patients with serum triglyceride levels greater than 1000 mg/dL receiving treatment with an intravenous insulin infusion between November 2017 and August 2020.
View Article and Find Full Text PDFMicroglia, the tissue-resident macrophage of the central nervous system (CNS), play a paramount role in brain health and disease status. Here, we describe a novel method for enriching and isolating primary microglia from mouse brain tissue. This isolation method yields a high number of cells from either young or adult mice, and importantly, maintains the health and function of the cells for subsequent cell culture.
View Article and Find Full Text PDFInt J Womens Dermatol
December 2021
Lower urinary tract symptomatology is often difficult to categorize if history and investigation focus only on the urinary tract. Disease and dysfunction in organs more posteriorly can often cause or influence such bladder and urethral symptoms. Vulvovaginal skin diseases are an important but often missed influence on lower urinary tract symptomatology.
View Article and Find Full Text PDFBackground/objectives: Vulval lichen sclerosus (VLS) is a chronic inflammatory skin condition predominantly affecting the anogenital region in women and children. To date, there is lack of agreement amongst experts on a severity scale to aid assessment, research and treatment stratification on VLS. Furthermore, literature on best practice for long-term management of VLS is lacking.
View Article and Find Full Text PDFThis cohort study uses data from a medical record review of a dermatogynecology practice to describe the association between reduced recurrence of vulvar squamous cell carcinoma and use of topical corticosteroids in the treatment of vulvar lichen sclerosus.
View Article and Find Full Text PDFVulval lichen sclerosus (VLS) is a chronic inflammatory skin condition affecting the anogenital area in women. Serious long-term consequences of VLS include the risk of developing squamous cell carcinoma of the vulva as well as of scarring and alteration of vulval architecture. The treatment of choice for genital lichen sclerosus in females is potent to very potent topical corticosteroids.
View Article and Find Full Text PDFTumor development and therapeutic resistance are linked with tumor-associated macrophage (TAM) and myeloid-derived suppressor cell (MDSC) infiltration in tumors via chemokine axis. Chemokine expression, which determines the pro or anti-inflammatory status of myeloid cells, are partly regulated by the nuclear factor-kappa B (NF-κB) pathway. Here, we identified that conditional deletion of canonical NF-κB signaling (p65) in myeloid cells inhibited syngeneic glioblastoma (GBM) through decreased CD45 infiltration in tumors, as characterized by decreased TAMs (CD206+) and MDSCs (Gr1+ CD11b+), increased dendritic cells (CD86+) and cytotoxic T cells (CD8+) in the p65 knockout (KO) mice.
View Article and Find Full Text PDFMyeloid-derived suppressor cells (MDSC) are a major obstacle to promising forms of cancer immunotherapy, but tools to broadly limit their immunoregulatory effects remain lacking. In this study, we assessed the therapeutic effect of the humanized anti-Jagged1/2-blocking antibody CTX014 on MDSC-mediated T-cell suppression in tumor-bearing mice. CTX014 decreased tumor growth, affected the accumulation and tolerogenic activity of MDSCs in tumors, and inhibited the expression of immunosuppressive factors arginase I and iNOS.
View Article and Find Full Text PDFAustralas J Dermatol
February 2018
Oestrogen hypersensitivity vulvovaginitis is a rare chronic cyclical vulvovaginitis responsive to oestrogen suppression or antagonism. We present a case series of 16 patients with refractory cyclical vulvovaginitis, all of whom responded to oestrogen suppression with cyproterone acetate.
View Article and Find Full Text PDFAust N Z J Obstet Gynaecol
August 2017
Background: There are few published data about the incidence of diagnoses or treatment outcomes, for chronic vulval pain.
Aims: To document diagnoses and treatment outcomes in a cohort of chronic vulval pain presentations.
Materials And Methods: A retrospective case review of the patient database of a private vulval clinic between January 2011 and March 2015.
Background: Conception using assisted reproduction treatments (ART) has been associated with an increased risk of pregnancy complications. It is uncertain if this is caused by ART directly, or is an association of the underlying factors causing infertility.
Aims: We assessed the relationship between assisted conception (AC) and maternal or fetal complications in a large retrospective cohort study.
Four hundred and twenty-one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross-sectional study to assess sexual dysfunction and infertility post-transplant. Survey instruments included the Sydney Post-Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) - BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft-versus-Host Disease (cGVHD) Activity Assessment- Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post-Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females).
View Article and Find Full Text PDFImportance: Adult vulvar lichen sclerosis (VLS) may be complicated by loss of vulvar structure and vulvar carcinoma. There is a lack of evidence as to the ideal method to maintain long-term remission and prevent complications.
Objectives: To determine whether long-term preventive topical corticosteroid (TCS) treatment of VLS, with a target outcome of induction and maintenance of normal skin texture and color, reduces the risk of vulvar carcinoma, relieves symptoms, improves function, and preserves vulvar architecture, and to evaluate the adverse effects of treatment.
The IKK/nuclear factor-kappaB pathway (NF-κB) is critical in proper immune function, cell survival, apoptosis, cellular proliferation, synaptic plasticity, and even memory. While NF-κB is crucial for both innate and adaptive immunity, defective regulation of this master transcriptional regulator is seen in a variety of diseases including autoimmune disease, neurodegenerative disease, and, important to this review, cancer. While NF-κB functions in cancer to promote a number of critical oncogenic functions, here we discuss the importance of the NF-κB signaling pathway in contributing to cancer through promotion of the tumor microenvironment and through maintenance/expansion of tumor-initiating cells, processes that appear to be functionally interrelated.
View Article and Find Full Text PDFJ Low Genit Tract Dis
January 2014
Objective: Although recurrent vulvovaginal candidiasis is defined as 4 or more discrete attacks of vulvovaginal candidiasis per year, there is no diagnostic nomenclature or definition for the many women who are chronically symptomatic. This study aims to establish and propose a definition and a set of diagnostic criteria, which would enable clinicians to promptly identify and treat women with chronic vulvovaginal candidiasis (CVVC).
Design: Prospective cohort study.
Objective: This study aimed to report on a novel approach to therapy in a large private dermatogynecology practice using multimodal therapies with adjunctive use of systemic agents where necessary.
Materials And Methods: This was a retrospective audit of the presentation and management of 131 patients with a clinical diagnosis of vulvovaginal lichen planus.
Results: The most frequently presenting symptoms were genital soreness, itch, and burning.
Background: Data regarding the treatment of nonsexually acquired genital ulceration (NSAGU) are limited.
Objective: We sought to provide evidence for the safety and efficacy of topical and systemic corticosteroids followed by doxycycline prophylaxis for acute and recurrent NSAGU.
Methods: A retrospective chart review was conducted of patients with NSAGU treated in a private dermogynecology practice.
J Low Genit Tract Dis
October 2012
Objective: There are limited data on psoriasis as it affects the vulva in the medical literature. This observational study aimed to describe the symptoms, signs, and management of vulvar psoriasis in adults and children in a private vulvar disease referral practice.
Materials And Methods: A review of the existing literature on vulvar psoriasis was used to generate inclusion criteria of a chronic noninfective erythematous vulvitis without vaginal involvement.
J Low Genit Tract Dis
January 2013
Objective: Vulvar lichen sclerosus (LS) and lichen planus (LP) may cause persistent symptomatic labial adhesions. In the scant literature on this topic, there is no agreement about which operation is suitable, or the role of suppressive medical therapy. We report on simple perineotomy in the context of careful preoperative and postoperative medical suppressions.
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