Disease control of acromegaly does not prevent excess mortality in the long term: results of a nationwide survey in Italy.

Objective: This study aimed to assess the long-term outcome of patients with acromegaly.

Design: This is a multicenter, retrospective, observational study which extends the mean observation period of a previously reported cohort of Italian patients with acromegaly to 15 years of follow-up.

Methods: Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included.

Clinical and Visual Outcomes of Dysthyroid Optic Neuropathy After Surgical Orbital Decompression.

Current guidelines suggest high-dose steroids as first-line treatment for dysthyroid optic neuropathy (DON). When steroids fail, decompressive surgery is mandatory. We conducted a single-center, retrospective cohort study in a tertiary care combined Thyroid-Eye clinic in Milan, Italy.

Is Encapsulated Medullary Thyroid Carcinoma Associated With a Better Prognosis? A Case Series and a Review of the Literature.

Context: Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine neoplasm that may spread to lymph nodes before the primary tumor is diagnosed; moreover, distant metastases are already present in about 10% of patients at diagnosis. Serum calcitonin (Ctn) usually reflects the spread of disease, thus orienting the extent of surgery and predicting the possibility of biochemical remission. Tumor size and vascular invasion are important prognostic factors, but little is known on the relationship between other histopathological features, such as the presence of a tumor capsule, and long term outcome of MTC.

Morphine reduces the interest for natural rewards.

Rationale: Alongside a pathological, excessive, motivation for substances of abuse, substance use disorder (SUD) patients often show a dramatic loss of interest for naturally rewarding activities, such as positive peer social interaction and food intake. Yet, pre-clinical evidence of the latter SUD features remains scarce and inconsistent.

Objectives: In the current study, we investigated the effect of non-rewarding and rewarding doses of morphine upon social behaviour, motivation for and intake of palatable food, in male and female C57BL/6J mice.

Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist d-serine.

Prefrontal control of cognitive functions critically depends upon glutamatergic transmission and N-methyl D-aspartate (NMDA) receptors, the activity of which is regulated by dopamine. Yet whether the NMDA receptor coagonist d-serine is implicated in the dopamine-glutamate dialogue in the prefrontal cortex (PFC) and other brain areas remains unexplored. Here, using electrophysiological recordings, we show that d-serine is required for the fine-tuning of glutamatergic neurotransmission, neuronal excitability, and synaptic plasticity in the PFC through the actions of dopamine at D and D receptors.

Octreotide and pasireotide effects on medullary thyroid carcinoma (MTC) cells growth, migration and invasion.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine neoplasm of the parafollicular thyroid C cells. Although somatostatin receptors are expressed by MTCs, treatment with octreotide has shown poor efficacy, whereas recently pasireotide has demonstrated antiproliferative effects in persistent postoperative MTCs. Aim of this study was to test the effects of octreotide and pasireotide on MTC cells proliferation, cell cycle proteins expression, MAPK activation, apoptosis, calcitonin secretion, migration and invasion in TT cell line as well as in primary MTC cultured cells.

The CRF receptor mediates social behavior deficits induced by opiate withdrawal.

Poor sociability and aggressive behavior are key clinical features of opioid use disorders. The corticotropin-releasing factor (CRF) system may mediate behavioral effects of substances of abuse but its implication in substance-induced social behavior deficits and outward-directed hostility remains largely unknown. CRF signaling is mediated by two receptor types, termed CRF and CRF .

Sex-linked roles of the CRF and the CRF receptor in social behavior.

Dysfunctional social behavior is a major clinical feature of mood, anxiety, autism spectrum, and substance-related disorders, and may dramatically contribute to the poor outcome of these diseases. Nevertheless, the mechanisms underlying social behavior deficits are still largely unknown. The corticotropin-releasing factor (CRF) system, a major coordinator of the stress response, has been hypothesized to modulate social behavior.

Long-lasting pseudo-social aggressive behavior in opiate-withdrawn mice.

Poor sociability and aggressive behavior are major clinical features of opiate use disorders that may contribute to the establishment and maintenance of these harmful diseases. The present study investigated the long-term effects of chronic morphine administration and withdrawal upon social and aggressive behavior as well as the interrelationship between these two behaviors. Thus, social behavior was measured in C57BL/6J male mice 7, 21, 35 and 49 days after cessation of escalating morphine doses (20-100 mg/kg, i.

Corticotropin-releasing factor receptor 2-deficiency eliminates social behaviour deficits and vulnerability induced by cocaine.

Background And Purpose: Poor social behaviour and vulnerability to stress are major clinical features of stimulant use disorders. The corticotropin-releasing factor (CRF) system mediates stress responses and might underlie substance use disorders; however, its involvement in social impairment induced by stimulant substances remains unknown. CRF signalling is mediated by two receptor types, CRF and CRF .

CRF receptor-deficiency increases cocaine reward.

Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood.

The CRF1 and the CRF2 receptor mediate recognition memory deficits and vulnerability induced by opiate withdrawal.

Opiate use disorders are associated with impaired cognitive function and altered stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates stress responses via CRF1 and CRF2 receptors and may be implicated in substance use disorders. However, the specific role for each of the two known CRF receptor subtypes in cognitive impairment induced by opiate administration and withdrawal remains to be elucidated.

CRF2 Receptor Deficiency Eliminates the Long-Lasting Vulnerability of Motivational States Induced by Opiate Withdrawal.

Vulnerability to stressful life events is a hallmark of drug dependence that may persist long after cessation of drug intake and dramatically fuel key clinical features, such as deregulated up-shifted motivational states and craving. However, to date, no effective therapy is available for reducing vulnerability to stressful events in former drug users and drug-dependent patients, mostly because of poor knowledge of the mechanisms underlying it. In this study, we report that genetic inactivation of the stress-responsive corticotropin-releasing factor receptor-2 (CRF2-/-) completely eliminates the reemergence of increased nonrewarded nose-pokes, reflecting up-shifted motivational states, triggered by ethological environmental stressors long after cessation of morphine administration in mice.

The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms.

Objectives: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown.

Methods: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption.

CRF₂ receptor-deficiency reduces recognition memory deficits and vulnerability to stress induced by cocaine withdrawal.

Psychostimulant drug abuse, dependence and withdrawal are associated with cognitive dysfunction and impact stress-sensitive systems. The corticotropin-releasing factor (CRF) system orchestrates stress responses via CRF1 and CRF2 receptors and is implicated in substance use disorders. However, CRF2 role in psychostimulant drug-induced cognitive dysfunction remains to be elucidated.

CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine.

Rationale: The intake of psychostimulant drugs may induce cognitive dysfunction and negative affective-like states, and is associated with increased activity of stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates neuroendocrine, behavioural and autonomic responses to stressors, and might be implicated in substance-related disorders. CRF signalling is mediated by two receptor types, named CRF1 and CRF2.

The corticotropin-releasing factor receptor-2 mediates the motivational effect of opiate withdrawal.

Altered motivational processes are key features of drug dependence and withdrawal, yet their neural mechanisms remain largely unknown. The present study shows that genetic disruption of the corticotropin-releasing factor receptor-2 (CRF₂-/-) does not impair motivation for palatable food in drug-naïve mice. However, CRF₂ receptor-deficiency effectively reduces the increase in palatable food-driven motivation induced by opiate withdrawal.

Increased motivation to eat in opiate-withdrawn mice.

Rationale: In drug-dependent individuals, the primary excessive motivation is for drugs. Studies also indicate altered interest for "natural" rewarding activities associated with motivational disorders that may be relevant to drug dependence. However, to date, the impact of drug dependence and withdrawal upon motivation for "natural" rewards remains unclear.

CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress coping.

The opiate withdrawal syndrome is a severe stressor that powerfully triggers addictive drug intake. However, no treatment yet exists that effectively relieves opiate withdrawal distress and spares stress-coping abilities. The corticotropin-releasing factor (CRF) system mediates the stress response, but its role in opiate withdrawal distress and bodily strategies aimed to cope with is unknown.

Binge-like eating in mice.

Objective: Given the lack of reliable murine model of binge-like eating, we tried to induce this pathological behavior in mice.

Method: We used an experimental protocol mimicking the etiological factors involved in the development of binge eating in humans, that is, food restriction, refeeding (R-R) in presence of high palatable food, and stress (S).

Results: Mice subjected to at least three cycles of R-R plus S (forced swimming stress), showed a binge-like behavior evident as early as 4 h, persisting 24 h after stress application and not associated to depressive-like behavior.

Disruption of the CRF(2) receptor pathway decreases the somatic expression of opiate withdrawal.

Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF(1) and CRF(2).

Role of the corticotropin-releasing factor receptor type 2 in the control of food intake in mice: a meal pattern analysis.

The actions of corticotropin-releasing factor (CRF) and related peptides are mediated by two receptors (CRF(1) and CRF(2)). The respective role of each subtype in the control of food intake remains poorly known. In the present study, we examined the quantity and microstructure of ingestive behavior of knockout (KO) mice lacking CRF(2) receptors and their wild-type (WT) littermates.

Nitrous oxide (N2O) prevents latent pain sensitization and long-term anxiety-like behavior in pain and opioid-experienced rats.

Improving rehabilitation after a severe tissue injury does not only require a reduction in pain, but also requires alleviation of negative affects, particularly anxiety. Although opioids remain unsurpassed analgesics to relieve moderate to severe pain, it has been shown that they also induce latent pain sensitization leading to long-lasting hyperalgesia via N-methyl-D-aspartate-(NMDA)-dependent pronociceptive systems. The present study evaluated the ability of nitrous oxide (N2O), a gas with NMDA antagonist properties, to prevent latent pain sensitization and long-term anxiety-like behavior (ALB) in rats with pain and opioid experiences.