Prevalence of Intersex/Differences in Sex Development and Primary Gonadal Insufficiency in a Pediatric Transgender Population.

Purpose: This study aims to assess the prevalence of intersex variations/differences in sex development (I/DSDs), associated adrenal conditions, and primary gonadal insufficiency in children with gender dysphoria.

Methods: We performed a comprehensive review of the medical records for individuals who carried the diagnostic codes for gender dysphoria in addition to intersex and/or other conditions associated with sex steroid variations among patients evaluated by pediatric endocrinologists from 2013 to 2022.

Results: We found that 9 of 612 (1.

Mast cell-mediated immune regulation in health and disease.

Mast cells are important components of the immune system, and they perform pro-inflammatory as well as anti-inflammatory roles in the complex process of immune regulation in health and disease. Because of their strategic perivascular localization, sensitivity and adaptability to the microenvironment, and ability to release a variety of preformed and newly synthesized effector molecules, mast cells perform unique functions in almost all organs. Additionally, Mast cells express a wide range of surface and cytoplasmic receptors which enable them to respond to a variety of cytokines, chemicals, and pathogens.

Hyperinsulinemic Hypoglycemia and Growth Hormone Deficiency Secondary to 20p11 Deletion.

Hypoglycemia is concerning for neurological complications in infants and children. Determining the cause of hypoglycemia is essential in providing appropriate treatment. Hyperinsulinism and growth hormone deficiency are known causes of hypoglycemia but are not commonly found together.

Variations in Morning Serum Cortisol Levels Based on Sex and Pubertal Status.

Introduction: Patients with suspected adrenal insufficiency undergo screening with a serum morning cortisol level and confirmatory testing with an adrenocorticotropic hormone (ACTH) stimulation test. However, much of the data collected to determine appropriate values for morning cortisol levels are derived from adult populations and may not accurately represent pediatric physiology. The purpose of this study was to evaluate the mean morning cortisol level in the pediatric population based on pubertal status and sex in order to better understand such influences on laboratory evaluation of adrenal insufficiency.

Mast Cell Degranulation Decreases Lipopolysaccharide-Induced Aortic Gene Expression and Systemic Levels of Interleukin-6 .

Mast cells play an important role in immunomodulation and in the maintenance of vascular integrity. Interleukin-6 (IL-6) is one of the key biomarkers and therapeutic target in systemic vasculitis. The objective of the current study is to describe the role of mast cells in arterial IL-6 homeostasis.

A New Paediatric Diabetes Knowledge Test - M-WIKAD Development and Factor Analysis.

The purpose of this study was to develop a measure of type 1 diabetes mellitus (T1DM) knowledge that is aimed at youth and is based on contemporary management standards. An 88-item test was derived from the American Association of Diabetes Educators 7 Self-Care Behaviors. A multidisciplinary team selected the best 49 items which were piloted in a sample of 119 youths (59 males, aged 12-18, having a mean ± standard deviation glycated haemoglobin (A1C) of 9.

Employing a results-based algorithm to reduce laboratory utilization in ACTH stimulation testing.

Background: The High Dose Adrenocorticotropic Hormone (ACTH) Stimulation Test is the gold standard to diagnose adrenal insufficiency. Normal adrenal function is defined as a peak cortisol response to pharmacologic stimulation with cosyntropin of ≥18 μg/dL. Our practice was to obtain cortisol levels at 0, 30 and 60 min after cosyntropin administration.

Intravenous Cocaine Results in an Acute Decrease in Levels of Biomarkers of Vascular Inflammation in Humans.

Cocaine use causes significant cardiovascular morbidity from its hemodynamic effects. It is less clear whether cocaine promotes atherosclerosis. Vascular inflammation is one of the earliest steps in the pathophysiology of atherosclerosis.

Protective Role of Mast Cells in Primary Systemic Vasculitis: A Perspective.

Mast cells are important cells of the immune system. Although traditionally considered as key players in allergic and hypersensitivity reactions, emerging evidence suggests that mast cells have many complex roles in vascular disease. These include regulation of vasodilation, angiogenesis, activation of matrix metalloproteinases, apoptosis of smooth muscle cells, and activation of the renin angiotensin system.

A novel AVPR2 splice site mutation leads to partial X-linked nephrogenic diabetes insipidus in two brothers.

Unlabelled: X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed.

Mast Cell: A Multi-Functional Master Cell.

Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells are known to regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification.

Cigarette Smoke Amplifies Inflammatory Response and Atherosclerosis Progression Through Activation of the H1R-TLR2/4-COX2 Axis.

Emerging evidence suggests that infection and persistent inflammation are key players in the pathogenesis of atherosclerotic cardiovascular disease (CVD). Although it is well established that cigarette smoke (CS) promotes atherosclerotic CVD, very little is known about the potential impact of the collective effects of CS and intermittent or chronic subclinical infection on atherosclerosis. Our previous studies demonstrated that mast cell-derived histamine and lipopolysaccharide (LPS) synergistically enhance endothelial cell inflammatory response.

Chronic ingestion of H1-antihistamines increase progression of atherosclerosis in apolipoprotein E-/- mice.

Although increased serum histamine levels and H1R expression in the plaque are seen in atherosclerosis, it is not known whether H1R activation is a causative factor in the development of the disease, or is a host defense response to atherogenic signals. In order to elucidate how pharmacological inhibition of histamine receptor 1 (H1R) signaling affects atherogenesis, we administered either cetirizine (1 and 4 mg/kg. b.

H1-antihistamines exacerbate high-fat diet-induced hepatic steatosis in wild-type but not in apolipoprotein E knockout mice.

We examined the effects of two over-the-counter H1-antihistamines on the progression of fatty liver disease in male C57Bl/6 wild-type and apolipoprotein E (ApoE)-/- mice. Mice were fed a high-fat diet (HFD) for 3 mo, together with administration of either cetirizine (4 mg/kg body wt) or fexofenadine (40 mg/kg body wt) in drinking water. Antihistamine treatments increased body weight gain, gonadal fat deposition, liver weight, and hepatic steatosis in wild-type mice but not in ApoE-/- mice.

Type 2 diabetes mellitus in children and adolescents.

On the basis of strong research evidence and consensus, type 1 diabetes mellitus (DM) remains the most common form of DM in children and adolescents. The incidence of type 2 DM in the pediatric population is rapidly increasing because of the obesity epidemic, and minority groups are disproportionately affected. (2) (10) (19) On the basis of some research evidence and consensus, it can be challenging to initially differentiate between type 2 DM and type 1 DM clinically because of the increased prevalence of obesity, the complex interplay of autoimmunity and obesity, and common symptoms at presentation.

Mast cell deficiency attenuates progression of atherosclerosis and hepatic steatosis in apolipoprotein E-null mice.

Mast cells are important cells of the immune system and are recognized as participants in the pathogenesis of atherosclerosis. In this study, we evaluated the role of mast cells on the progression of atherosclerosis and hepatic steatosis using the apolipoprotein E-deficient (ApoE(-/-)) and ApoE(-/-)/mast cell-deficient (Kit(W-sh/W-sh)) mouse models maintained on a high-fat diet. The en face analyses of aortas showed a marked reduction in plaque coverage in ApoE(-/-)/Kit(W-sh/W-sh) compared with ApoE(-/-) after a 6-mo regimen with no significant change noted after 3 mo.

Human mast cells (HMC-1 5C6) enhance interleukin-6 production by quiescent and lipopolysaccharide-stimulated human coronary artery endothelial cells.

We examined the effect of intact human mast cells (HMC-1 5C6) and their selected mediators on interleukin-6 (IL-6) production and bone morphogenetic protein-2 (BMP-2) expression in human coronary artery endothelial cells (HCAEC) in the presence and absence of lipopolysaccharide (LPS). Scanning electron microscopy showed that HMC-1 5C6 cells adhere to HCAEC in cocultures. Addition of HMC-1 5C6 cells markedly enhanced the IL-6 production by quiescent and LPS-activated HCAEC even at the maximal concentration of LPS.

Regulation of the expression of cyclooxygenases and production of prostaglandin I₂ and E₂ in human coronary artery endothelial cells by curcumin.

Curcumin regulates prostaglandin (PG) synthesis in a variety of cells. PGE₂ and PGI₂ are generated from arachidonic acid (AA) by cyclooxygenases 1 and 2 (COX-1 and COX-2) and the synthase (PGES and PGI₂S) pathways. This study evaluates the in vitro effect of curcumin on the expression of COX-1, COX-2, PGI₂S and microsomal PGES-1 (mPGES-1), and the production of PGE₂ and PGI₂ in human coronary artery endothelial cells (HCAEC).

Lipopolysaccharide induces H1 receptor expression and enhances histamine responsiveness in human coronary artery endothelial cells.

Summary Histamine is a well-recognized modulator of vascular inflammation. We have shown that histamine, acting via H1 receptors (H1R), synergizes lipopolysaccharide (LPS)-induced production of prostaglandin I(2) (PGI(2)), PGE(2) and interleukin-6 (IL-6) by endothelial cells. The synergy between histamine and LPS was partly attributed to histamine -induced expression of Toll-like receptor 4 (TLR4).

Increased aortic atherosclerotic plaque development in female apolipoprotein E-null mice is associated with elevated thromboxane A2 and decreased prostacyclin production.

The production of thromboxane A(2) (TXA(2)) and prostacyclin (prostaglandin I(2), PGI(2)) is known to be increased in patients with atherosclerosis. In this study, we evaluated the influence of gender on TXA(2) and PGI(2) production, and their association with the progression of atherosclerosis in apolipoprotein E-null (ApoE(-/-)) mice maintained on a high fat diet for 3 months. En face analyses of aortas showed marked increases in plaque formation in female ApoE(-/-) mice.

Histamine directly and synergistically with lipopolysaccharide stimulates cyclooxygenase-2 expression and prostaglandin I(2) and E(2) production in human coronary artery endothelial cells.

Although histamine plays an essential role in inflammation, its influence on cyclooxygenases (COX) and prostanoid homeostasis is not well understood. In this study, we investigated the effects of histamine on the expression of COX-1 and COX-2 and determined their contribution to the production of PGE(2), prostacyclin (PGI(2)), and thromboxane A(2) in human coronary artery endothelial cells (HCAEC). Incubation of HCAEC monolayers with histamine resulted in marked increases in the expression of COX-2 and production of PGI(2) and PGE(2) with no significant change in the expression of COX-1.

Chymase increases glomerular albumin permeability via protease-activated receptor-2.

Increased infiltration of the kidney by mast cells is associated with proteinuria, and interstitial fibrosis in various renal diseases. Mast cells produce serine proteases including tryptase and chymase (MCC) that act via protease-activated receptors (PARs) to induce synthesis of fibrogenic cytokines by renal cells. In the present study, we investigated direct effect of MCC and role of PARs on glomerular albumin permeability (P(alb)).

Human conjunctival epithelial cells lack lipopolysaccharide responsiveness due to deficient expression of MD2 but respond after interferon-gamma priming or soluble MD2 supplementation.

Inflammatory responses to Gram-positive and Gram-negative bacterial cell wall components are initiated by Toll-like receptor 2 (TLR2) and TLR4, respectively. Therefore, the existence of functionally active TLR2 and TLR4 in human conjunctival epithelial cells (HCEC) are critical for the effective host defense against bacterial infections in the eye. We examined the ability of HCEC to respond to TLR4 ligand, lipopolysaccharide (LPS), or TLR2 ligands, lipoteichoic acid (LTA) and peptidoglycan (PGN) using the Chang conjunctival epithelial cell line and the primary conjunctival epithelial cell line (IOBA-NHC) as in vitro models.

Constitutive expression of functionally active protease-activated receptors 1 and 2 in human conjunctival epithelial cells.

Protease-activated receptors (PARs) are G-protein-coupled receptors which initiate inflammatory responses when activated by specific serine proteases. This study was conducted to examine whether human conjunctival epithelial cells (HCECs) express functionally active PAR1 and PAR2 using Chang conjunctival epithelial cells as in vitro model. We performed RT-PCR and immunofluorescence analyses to determine the expression of PAR1 and PAR2, and monitored the production of IL-6 after activating HCECs with PAR1 activating agents (thrombin or TFLLRN) or PAR2 activating agents (tryptase, trypsin, or SLIGKV).

Endothelial cell activation by mast cell mediators.

Mast cells are important cells of the immune system, and their secretory products regulate many vascular functions. Although considerable interest is focused on the role of mast cells and infectious agents in atherosclerosis, whether or not mast cell mediators act in concert with bacterial agents to regulate endothelial activation is not known. Here, we have described experimental techniques and presented related results to demonstrate how mast cell granule (MCG) mediators and bacterial products synergize endothelial cell inflammatory responses.