Browse

You are looking at 21 - 30 of 742 items for

Open access

Monika Karczewska-Kupczewska, Agnieszka Nikołajuk, Magdalena Stefanowicz, Natalia Matulewicz, Irina Kowalska and Marek Strączkowski

Objective

The aim of the study was to assess serum chemerin concentration and s.c. adipose tissue (SAT) chemerin expression in relation to insulin sensitivity and obesity in young healthy subjects.

Design

We performed a cross-sectional study including 128 subjects, 44 with normal weight, 44 with overweight and 40 with obesity.

Methods

Hyperinsulinemic-euglycemic clamp and SAT biopsy were performed. Next, 30 subjects with obesity underwent 12-week weight-reducing dietary intervention.

Results

Serum chemerin was higher and SAT chemerin expression was lower in subjects with obesity in comparison with other groups. The relationship of serum chemerin with SAT expression and insulin sensitivity were positive in normal weight and overweight individuals, and negative in individuals with obesity. In the entire study population, serum chemerin was also positively related to hsCRP, serum fetuin A and alanine aminotransferase. SAT chemerin was positively related to insulin sensitivity, SAT insulin signaling and adipogenic genes. Weight loss decreased serum chemerin, whereas SAT chemerin increased in subjects with the highest increase in insulin sensitivity.

Conclusions

Serum and SAT chemerin is differentially associated with insulin sensitivity and the relationship between serum chemerin and insulin sensitivity depends on adiposity. SAT chemerin is positively associated with insulin sensitivity across a wide range of BMIs and may be proposed as a biomarker of metabolically healthy SAT. Our results suggest that SAT is not the main source of serum chemerin in obesity.

Open access

Rolf Jorde and Guri Grimnes

Objective

In addition to its skeletal effects, vitamin D may also be important for health in general. It is uncertain what level of serum 25-hydroxyvitamin D (25(OH)D), marker of vitamin D status, is sufficient for these effects. With decreasing serum 25(OH)D levels there is an increase in serum PTH. The point at which this occurs has been considered as a threshold for vitamin D sufficiency. The thresholds found have varied widely and have mainly been based on observational studies. However, to truly establish a threshold for vitamin D effects, this has to be based on randomized controlled trials (RCTs).

Methods

The study included 2803 subjects from a general health survey, the Tromsø study, and pooled individual person data from five vitamin D intervention studies (n = 1544). Serum parathyroid hormone (PTH) and change in PTH after vitamin D supplementation were related to serum 25(OH)D levels in steps of 25 nmol/L (<24, 25–49, 50–74, 75–99, and >99 nmol/L).

Results

In the Tromsø study, in the females there was a gradual decrease in serum PTH with increasing serum 25(OH)D with no apparent plateau, whereas in the males the decrease in PTH in subjects with serum 25(OH)D >74 nmol/l was marginal. In pooled RCTs, there was a significant reduction in serum PTH by vitamin D supplementation regardless of baseline serum 25(OH)D level.

Conclusions

The use of the serum PTH–25(OH)D relation from observational studies to determine a threshold for vitamin D sufficiency is highly questionable.

Open access

Britt J van Keulen, Conor V Dolan, Bibian van der Voorn, Ruth Andrew, Brian R Walker, Hilleke Hulshoff Poll, Dorret I. Boomsma, Joost Rotteveel and Martijn J.j. Finken

Objective: Sex differences in disease susceptibility might be explained by sexual dimorphism in hypothalamic-pituitary-adrenal axis activity, which has been postulated to emerge during puberty. However, studies conducted thus far lacked an assessment of Tanner pubertal stage. This study aimed to assess the contribution of pubertal development to sexual dimorphism in cortisol production and metabolism.

Methods: Participants (n=218), were enrolled from a population-based Netherlands Twin Register. At the ages of 9, 12 and 17 years Tanner pubertal stage was assessed, and early-morning urine samples were collected. Cortisol metabolites were measured with GC-MS/MS, and ratios were calculated, representing cortisol metabolism enzyme activities, such as A-ring reductases, 11β-HSDs and CYP3A4. Cortisol production and metabolism parameters were compared between sexes for pre-pubertal (Tanner stage 1), early-pubertal (Tanner stage 2-3) and late-pubertal (Tanner stage 4-5) stages.

Results: Cortisol metabolite excretion rate decreased with pubertal maturation in both sexes, but did not significantly differ between sexes at any pubertal stage, although in girls a considerable decrease was observed between early- and late-pubertal stage (P<0.001). A-ring reductase activity was similar between sexes at pre- and early-pubertal stages, and was lower in girls than in boys at late-pubertal stage. Activities of 11β-HSDs were similar between sexes at pre-pubertal stage, and favored cortisone in girls at early- and late-pubertal stages. Cytochrome P450 3A4 activity did not differ between sexes.

Conclusions: Prepubertally, sexes were similar in cortisol parameters. During puberty, as compared to boys, in girls the activities of A-ring reductases declined and the balance between 11β-HSDs progressively favored cortisone. Our findings suggest that the sexual dimorphism in cortisol may either be explained by rising concentrations of sex steroids or by puberty-induced changes in body composition.

Open access

Thabiso R P Mofokeng, Salem A Beshyah, Fazleh Mahomed, Kwazi C Z Ndlovu and Ian L Ross

Background

The burden and management of primary adrenal insufficiency (PAI) in Africa have not been well documented. We aimed to identify specific disease characteristics, patient demographics, and patterns of clinical management in established PAI in Africa.

Methods

An online survey of physicians’ experience relating to PAI.

Results

There were 1334 responses received, 589 were complete, and 332 respondents reported managing patients with hypoadrenalism. The described responses were related to a calculated pool of 5787 patients with hypoadrenalism (2746 females, 3041 males), of whom 2302 had PAI. The likely causes of PAI in Sub-Saharan Africa (SSA) vs the Middle East and North Africa (MENA) regions included autoimmune disease (20% vs 60.3%; P < 0.001), tuberculosis (34% vs 4.1%; P < 0.001), AIDS (29.8% vs 1%; P < 0.001), malignancy, and genetic conditions. Sixteen percent of AD patients (376/2302) presented in an adrenal crisis. Medical emergency identification was not used by 1233 (83.6%) SSA vs 330 (40.4%) MENA patients (P < 0.001), respectively. Relative non-availability of diagnostic tests across both regions included adrenal antibodies 63% vs 69.6% (P = 0.328), s-cortisol 49.4 % vs 26.7% (P = 0.004), s-ACTH 55.7% vs 53.3% (P = 0.217), and adrenal CT scans 52.4% vs 31.8% (P = 0.017) in the SSA and MENA region, respectively. Across the entire cohort, the overall hydrocortisone use and extrapolated proportion of synacthen use were 59.4% and 50.7%, respectively.

Conclusions

Through the perception and practice of healthcare professionals, we identified significant challenges in the diagnosis and management of PAI which may herald high mortality. Differences between regions may reflect the allocation of healthcare resources.

Open access

Rocío del Carmen Bravo-Miana, Ana Belén Della Vedova, Ana Lucía De Paul, María Mónica Remedi, María Laura Guantay, Mónica Beatriz Gilardoni, Claudia Gabriela Pellizas and Ana Carolina Donadio

Tumor-stroma crosstalk leads to a tumor-promoting microenvironment. In this milieu, extracellular vesicles (EVs) are protagonists in cell-cell communication. Despite thyroid cancer being the most common endocrine malignancy, the contribution of the tumor microenvironment to thyroid cancer progression is still largely underexplored. We focused on the role of thyroid tumor cell-fibroblast interaction and EVs as mediators of tumor-stroma interplay, in the promotion of thyroid tumor aggressiveness. Thyroid tumor (TPC-1, 8505c) or non-tumor thyroid cells (NThyOri) were co-cultured with human fibroblasts (Fb). Thyroid cell migration was investigated by the wound-healing assay and actin-network staining. Cell-CD147 expression was characterized by flow cytometry. EVs, obtained by ultracentrifugation of conditioned media (CMs), were characterized by transmission electron-microscopy and CD81 and CD147 expression. Metalloproteinases (MMPs) were evaluated by zymography in CMs. A migratory phenotype was triggered in thyroid tumor cells treated with CMs from Fb or from Fb-thyroid tumor cell co-cultures. Fb-thyroid cell co-cultures induced the secretion of proMMP9 and proMMP2, and led to a significant MMP2 activation in CMs. Fb, thyroid cells and Fb-thyroid cell co-cultures released EVs, and remarkably, EVs released by Fb-thyroid tumor cell co-cultures induced the secretion of proMMP2 and the expression of MMP2 from normal Fb. A significant CD147 expression was demonstrated in Fb-thyroid tumor cell derived EVs. These findings reveal the role of Fb and thyroid tumor cell-Fb interaction in the promotion of a microenvironment suitable for thyroid tumor progression. Moreover, they highlight for the first time the role of thyroid tumor cell-Fb interaction in the production of specialized EVs.

Open access

Aleksandra Gilis-Januszewska, Łukasz Kluczyński and Alicja Hubalewska-Dydejczyk

Traumatic brain injury affects many people each year, resulting in a serious burden of devastating health consequences. Motor-vehicle and work-related accidents, falls, assaults, as well as sport activities are the most common causes of traumatic brain injuries. Consequently, they may lead to permanent or transient pituitary insufficiency that causes adverse changes in body composition, worrisome metabolic function, reduced bone density, and a significant decrease in one’s quality of life. The prevalence of post-traumatic hypopituitarism is difficult to determine, and the exact mechanisms lying behind it remain unclear. Several probable hypotheses have been suggested. The diagnosis of pituitary dysfunction is very challenging both due to the common occurrence of brain injuries, the subtle character of clinical manifestations, the variable course of the disease, as well as the lack of proper diagnostic algorithms. Insufficiency of somatotropic axis is the most common abnormality, followed by presence of hypogonadism, hypothyroidism, hypocortisolism, and diabetes insipidus. The purpose of this review is to summarize the current state of knowledge about post-traumatic hypopituitarism. Moreover, based on available data and on our own clinical experience, we suggest an algorithm for the evaluation of post-traumatic hypopituitarism. In addition, well-designed studies are needed to further investigate the pathophysiology, epidemiology, and timing of pituitary dysfunction after a traumatic brain injury with the purpose of establishing appropriate standards of care.

Open access

Willem de Ronde and Diederik L Smit

This review summarizes 10 years experience with male abusers of anabolic androgenic steroids (AAS). The typical user of AAS is male, aged between 20 and 40 and lifting weights. Illegal AAS are cheap and easily obtained via internet or local suppliers. AAS are mostly used in cycles with a duration between 6 and 18 weeks. Most AAS cycles contain multiple agents, used simultaneously in a dose vastly exceeding a substitution dose. A variety of other performance and image-enhancing drugs are commonly used, including human growth hormone, thyroid hormone, tamoxifen, clomiphene citrate and human chorionic gonadotrophin. Short-term clinical and biochemical side effects are well established. Long-term side effects are uncertain, but may include heart failure, mood-and anxiety disorders, hypogonadism and subfertility. We share our views on the management of common health problems associated with AAS abuse.

Open access

Martine Cohen-Solal, Thomas Funck-Brentano and Pablo Ureña Torres

Mineral and bone diseases (MBD) are predominant in patients with chronic kidney disease (CKD) and lead to several bone manifestations, from pain to skeletal fractures. Cumulative traditional clinical risk factors, such as age and gender, in addition to those related to CKD, enhance the risk of comorbidity and mortality related to fractures. Despite great advances in understanding MBD in CKD, clinical and biological targets are lacking, which leads to under-management of fractures. Optimal PTH control results in a net improvement in defining the levels of bone remodeling. In addition, circulating biomarkers such as bone-specific alkaline phosphatase and cross-linked collagen type I peptide will also provide additional information about remodeling rate, bone mineralization and the evaluation of fracture risk. Imaging techniques identify patients at risk by measurement of bone mineral density by DEXA or by high peripheral QCT, which allow the discrimination of trabecular and cortical bone. Here, we have reviewed the literature related to epidemiology and the pathophysiological role of mineral and biochemical factors involved in CKD-MBD with a special focus on fracture risk. We also provide an algorithm that could be used for the management of bone diseases and to guide treatment decisions. Finally, the combined expertise of clinicians from various disciplines is crucial for the best prevention of fractures.

Open access

N K Stepto, D Hiam, M Gibson-Helm, S Cassar, C L Harrison, S K Hutchison, A E Joham, B J Canny, A Moreno-Asso, B J Strauss, N Hatzirodos, R J Rodgers and H J Teede

Objective

Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways.

Methods

A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training.

Results

We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3.

Conclusions

We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.

Open access

Angelica Lindén Hirschberg

Emerging evidence indicates that testosterone, which can increase muscle mass and strength, stimulates erythropoiesis, promotes competitive behaviour, and enhances the physical performance of women. Indeed, the levels of testosterone within the normal female range are related to muscle mass and athletic performance in female athletes. Furthermore, among these athletes, the prevalence of hyperandrogenic conditions, including both polycystic ovary syndrome and rare differences/disorders of sex development (DSD), which may greatly increase testosterone production, are elevated. Thus, if the androgen receptors of an individual with XY DSD are functional, her muscle mass will develop like that of a man. These findings have led to the proposal that essential hyperandrogenism is beneficial for athletic performance and plays a role in the choice by women to compete in athletic activities. Moreover, a recent randomized controlled trial demonstrated a significant increase in the lean mass and aerobic performance by young exercising women when their testosterone levels were enhanced moderately. Circulating testosterone is considered the strongest factor to explain the male advantage in sport performance, ranging between 10 and 20%. It appears to be unfair to allow female athletes with endogenous testosterone levels in the male range (i.e. 10–20 times higher than normal) to compete against those with normal female androgen levels. In 2012, this consideration led international organizations to establish eligibility regulations for the female classification in order to ensure fair and meaningful competition, but the regulations are controversial and have been challenged in court.