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Limbic and HPA axis function in an animal model of chronic neuropathic pain.

Chronic pain can be considered a form of chronic stress, and chronic pain patients often have disturbances of the hypothalamic-pituitary-adrenal (HPA) axis, including abnormal cortisol levels. In addition, chronic pain patients have an increased incidence of depression and anxiety, stress-related disorders that are frequently accompanied by disturbances in the limbic system (e.g. hippocampus and amygdala) and the HPA axis. Despite the fact that the literature supports a strong link between chronic pain, stress disorders, and limbic dysfunction, the mechanisms underlying the effects of chronic

Effect of Agouti-related protein in regulation of the hypothalamic-pituitary-thyroid axis in the melanocortin 4 receptor knockout mouse.

Agouti-related protein (AGRP) is thought to be one of the neuropeptides mediating the effects of leptin on appetite and satiety. The central administration of AGRP not only stimulates food intake, but also inhibits the hypothalamic-pituitary-thyroid axis (HPT) axis, closely replicating the central hypothyroid state induced by fasting. AGRP binds as an endogenous antagonist or inverse agonist of the central melanocortin receptors but has also been hypothesized to have melanocortin receptor-independent effects. Thus, we determined whether the central effects of AGRP on the HPT axis are altered i

Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects.

A dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) system has been hypothesized to account for a myriad of cardinal symptoms of affective disorders. Specifically, increased CRH signalling via CRH type 1 receptors is thought to be an important factor in the pathogenesis of major depression and anxiety disorders. Consequently, a number of drugs have been developed in order to target the postulated increase in CRH/CRH 1 receptor signalling. One of these compounds, R121919, binds with high affinity to CRH1 receptors antagonising the action of CRH. R121919 was recently tested in an

Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity.

Recent evidence indicates that glucocorticoids and catecholamines, the major stress hormones, inhibit the production of proinflammatory cytokines, such as interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma, whereas they stimulate the production of antiinflammatory cytokines, such as IL-10, IL-4, and transforming growth factor (TGF)-beta. Thus, systemically, an excessive immune response, through activation of the stress system, stimulates an important negative feedback mechanism, which protects the organism from an "overshoot" of proinflammatory cytokines and oth

Hypothalamic-pituitary-adrenal axis and autonomic nervous system activity in disruptive children and matched controls.

OBJECTIVES: To investigate whether a pattern of lower autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis activity is found in children with disruptive behavior disorders (DBD) under nonstressful and stressful conditions, and whether such a pattern would correspond with their feelings of control and negative emotionality. METHOD: The effects of stress were studied by comparing cortisol response, heart rate (HR), skin conductance level (SCL), and subjective feelings of 26 children with DBD and 26 matched normal controls. An additional 12 normal control children were st

The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke.

OBJECTIVES: The hypothalamic-pituitary-adrenal (HPA) axis, the mediator of cortisol, plays a central role in the homeostatic processes. In this study, we addressed the potential impact of HPA axis activity on established anthropometric, metabolic and haemodynamic risk factors for cardiovascular disease (CVD), type 2 diabetes mellitus and stroke. DESIGN: A cross-sectional study. SUBJECTS: A subgroup of 284 men from a population sample of 1040 at the age of 51 years. MAIN OUTCOME MEASURES: Anthropometric measurements included body mass index (BMI, kg m-2), waist/hip circumference ratio (WHR)

A glucocorticoid receptor gene marker is associated with abdominal obesity, leptin, and dysregulation of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: Abdominal obesity has a key role in the pathogenesis of prevalent and serious diseases and has been shown to be associated with an altered hypothalamic-pituitary-adrenal (HPA) axis function, which is regulated by endocrine feedback mediated via hippocampal glucocorticoid receptors (GR). RESEARCH METHODS AND PROCEDURES: We examined the HPA axis function by repeated salivary samples for the assessment of cortisol, as well as other endocrine, anthropometric, metabolic, and circulatory variables in middle-aged Swedish men (n = 284). With the restriction enzyme BclI, variants of the GR

Patterns of growth deficiency in rats exposed in utero to undernutrition, ethanol, or the neuroteratogen methylazoxymethanol (MAM).

Children and experimental animals exposed to ethanol (EtOH) in utero commonly have low birthweights, and many remain small at maturity. Low body weight or small stature in adulthood may reflect an inability to recover from in utero growth retardation, or it may reflect a separate, postnatal growth deficiency. In this study, daily body weights (postnatal days 1 to 60) were compared among the offspring of the following groups of Long Evans rats: dams fed liquid diet containing 35% EtOH-derived calories; their pair-fed and chow-fed controls; and dams exposed to methylazoxymethanol (MAM) in two pr

Release of pro-thyrotropin-releasing hormone connecting peptides PS4 and PS5 from perifused rat hypothalamic slices.

Thyrotropin-releasing hormone prohormone contains five copies of the thyrotropin-releasing hormone progenitor sequence Gln-His-Pro-Gly, each flanked by pairs of basic amino acids and separated by intervening sequences (connecting peptides). Using a perifusion system for rat hypothalamic slices, we have studied the ionic mechanisms underlying the release of two connecting peptides originating from the thyrotropin-releasing hormone precursor: prepro-thyrotropin-releasing hormone-(160-169) (Ps4) and prepro-thyrotropin-releasing hormone-(178-199) (Ps5). Quantification of these two peptides in the

Disorders of prolactin and growth hormone secretion.

A large range of tests is now available to help us understand, diagnose and manage GH-related growth disorders. The traditional provocative tests of GH secretion will identify short children with severe GH deficiency. However, evidence is emerging that these pharmacological tests may not be sufficiently sensitive to identify some subjects with GH deficiency arising from neurosecretory disturbance of GH release. There is a need for a simple sensitive test that will detect subtle GH secretion of this type. hGRF administration is a reliable test of GH reserve and, when used in combination with co

Studies of the pituitary-Leydig cell axis in young men with hypogonadotropic hypogonadism and hyposmia: comparison with normal men, prepuberal boys, and hypopituitary patients.

Pituitary and gonadal function was studied in seven chromatin-negative men, ages 15-27 yr, with retarded sexual and somatic development, skeletal anomalies, and hyposmia. These hyposmic patients were compared with normal men, prepuberal boys and hypogonadal patients with hypopituitarism. The urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels of hyposmic subjects were the same as those of normal boys and hypopituitary patients but significantly lower than those of normal men. Clomiphene citrate did not cause an increase in plasma FSH and LH levels in either hypogonad

Functional pituitary adenoma imaging.

High-resolution pituitary MRI localises most pituitary neuroendocrine tumours (PitNETs), yet clinically important subgroups remain challenging: (i) very small functioning tumours, particularly corticotroph microadenomas, and (ii) post-operative remnants where scar, gland and tumour cannot be reliably separated. Functional imaging, specifically PET has matured into a problem-solving modality when conventional imaging is equivocal, provided it is used selectively and interpreted within a physiology-led framework. This review proposes an MRI-first, tiered imaging strategy and a pragmatic approach

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… Pituitary [ 18 F]FDG uptake has been reported to rise in the weeks preceding clinically apparent ICI-related hypophysitis, which occurs in up to ~ 10% of ICI-treated patients [ 81 , 128 – 130 ]. … Future studies should investigate a possible role of PET in predicting ICI-related hypophysitis and potentially identifying patients at risk of suffering an adrenal crisis after therapy. …

Immunotherapy-Associated Pancreatic Adverse Events: Current Understanding of Their Mechanism, Diagnosis, and Management.

Immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 (PD-1) and its ligand PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibodies, are involved in T cell-mediated immune response augmentation and promote anti-tumor immunity. Cancer patients treated with combination of immunotherapy, chemotherapy, radiotherapy, and targeted therapy exhibit superior clinical outcomes and tolerance compared with patients treated with monotherapies. However, immutherapy is associated with several concomitant immune-related adverse events (irAEs). For instance, IrAEs interfere

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… Despite the efficacy of immunotherapy, immune-related adverse events (irAEs), often involving endocrine tissues including pneumonitis, hypophysitis, thyroiditis, colitis, pancreatitis, and autoimmune diabetes, have emerged as potential challenges to patients ( 11 , 12 ). … NR | Pembrolizumab | 38.8 | DKA | 25.6 | 0.7 ng/ml | 7.8 | GAD | NR NR | Pembrolizumab | 94.4 | DKA | 23.8 | NR | 11.3 | NR | Dermatitis, Hypophysitis, Arthritis NR | Pembrolizumab | 12 | DKA | 23.7 | NR | 11.2 | NR | NR NR | Pembrolizumab | 2.8 | DKA | 77.2 | 0.4 ng/ml | 8.8 | NR | NR NR | Pembrolizumab …

The dark side of immunotherapy.

Immunotherapy has broadened the therapeutic scope and response for many cancer patients with drugs that are generally of higher efficacy and less toxicity than prior therapies. Multiple classes of immunotherapies such as targeted antibodies and immune checkpoint inhibitors (ICI), cell-based immunotherapies, immunomodulators, vaccines, and oncolytic viruses have been developed to help the immune system target and destroy malignant tumors. ICI targeting programmed cell death protein-1 (PD-1) or its ligand (PD-L1) are among the most effective immunotherapy agents and are a major focus of current

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… Subsequently, irAEs were identified in the liver (autoimmune hepatitis), non-thyroid endocrine glands (hypophysitis and adrenal insufficiency), lungs and nervous system (myasthenia gravis and encephalitis). … Immune-related endocrine toxicities such as thyroid dysfunctions, hypophysitis, adrenal insufficiency, and type 1 diabetes mellitus are irreversible in approximately 50% of patients ( 51 ). …

Neurologic adverse events of cancer immunotherapy.

Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system and have revolutionized oncological treatment in recent years, with approval for its use in more and more cancers. However, it is not without side effects. Several neurological adverse events have been recognized associated with immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapy, the two main classes of cancer immunotherapy. With the increase in the prevalence of oncological diseases and this type of therapy, it is improbable that neu

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… CSF examination is usually altered in most cases, and there may be an overlap with asseptic meningitis and hypophysitis. MRI may demonstrate contrast enhancement in the affected nerve. … Although best characterized as an endocrinologic adverse event, hypophysitis is often reported as a nirAE 3 , 11 . …

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR … ldi, Rosa Russo, Di Giulio Giovanni, Vincenzo Faiola, Pio Zeppa, Stefano Pepe P16 Immunotherapy and hypophysitis: a case report Elisabetta Gambale, Consiglia Carella, Alessandra Di Paolo, Michele De Tursi Tumor microenvironment and biomarkers P17 New immuno- histochemical markers for the differential diagnosis of atypical melanocytic lesions with uncertain mal …

Agarwood Essential Oil Ameliorates Restrain Stress-Induced Anxiety and Depression by Inhibiting HPA Axis Hyperactivity.

In our previous investigation, we found that agarwood essential oil (AEO) has a sedative-hypnotic effect. Sedative-hypnotic drugs usually have an anxiolytic effect, where concomitant anxiety and depression are a common comorbidity. Therefore, this study further investigated the anxiolytic and antidepressant effects of AEO using a series of animal behavior tests on a restraint stress-induced mice model. The elevated plus maze (EPM) test, the light dark exploration (LDE) test, and the open field (OF) test demonstrated that AEO has a significant anxiolytic effect. Simultaneously, the tail suspens