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Presse Medicale (Paris, France : 1983) Dec 2021Diabetes insipidus (DI) is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of... (Review)
Review
Diabetes insipidus (DI) is a disorder characterized by a high hypotonic urinary output of more than 50ml per kg body weight per 24 hours, with associated polydipsia of more than 3 liters a day [1,2]. Central DI results from inadequate secretion and usually deficient synthesis of Arginine vasopressin (AVP) in the hypothalamus or pituitary gland. Besides central DI further underlying etiologies of DI can be due to other primary forms (renal origin) or secondary forms of polyuria (resulting from primary polydipsia). All these forms belong to the Polyuria Polydipsia Syndrom (PPS). In most cases central and nephrogenic DI are acquired, but there are also congenital forms caused by genetic mutations of the AVP gene (central DI) [3] or by mutations in the gene for the AVP V2R or the AQP2 water channel (nephrogenic DI) [4]. Primary polydipsia (PP) as secondary form of polyuria includes an excessive intake of large amounts of fluid leading to polyuria in the presence of intact AVP secretion and appropriate antidiuretic renal response. Differentiation between the three mentioned entities is difficult [5], especially in patients with Primary polydipsia or partial, mild forms of DI [1,6], but different tests for differential diagnosis, most recently based on measurement of copeptin, and a thorough medical history mostly lead to the correct diagnosis. This is important since treatment strategies vary and application of the wrong treatment can be dangerous [7]. Treatment of central DI consists of fluid management and drug therapy with the synthetic AVP analogue Desmopressin (DDAVP), that is used as nasal or oral preparation in most cases. Main side effect can be dilutional hyponatremia [8]. In this review we will focus on central diabetes insipidus and describe the prevalence, the clinical manifestations, the etiology as well as the differential diagnosis and management of central diabetes insipidus in the out- and inpatient setting.
Topics: Adult; Antidiuretic Agents; Aquaporin 2; Child; Deamino Arginine Vasopressin; Diabetes Insipidus; Diagnosis, Differential; Glycopeptides; Humans; Mutation; Neurophysins; Pituitary Gland; Polydipsia; Polyuria; Protein Precursors; Vasopressins
PubMed: 34718110
DOI: 10.1016/j.lpm.2021.104093 -
Medicina Aug 2022Guillain-Barré syndrome (GBS) is characterized by rapidly progressive and generally ascending symmetrical muscle weakness, accompanied by decreased or absent...
Guillain-Barré syndrome (GBS) is characterized by rapidly progressive and generally ascending symmetrical muscle weakness, accompanied by decreased or absent osteotendinous reflexes. The inflammatory process may affect the myelin or the axon. There are 4 clinical forms of GBS: 1) acute inflammatory demyelinating polyradiculoneuropathy, 2) acute motor axonal neuropathy, 3) acute sensory and motor axonal neuropathy, and 4) the Miller-Fisher variant, which is characterized by ophthalmoplegia, ataxia and areflexia, with little muscle weakness. Diagnosis is based on the albumin-cytological dissociation observed at the end of the first week after the onset of symptoms and may persist until the third week, as well as on the specific neurophysiological alterations of each clinical form. The treatment of GBS will depend on the degree of severity, if the patient presents grade IV or less according to the Paradiso scale, it will be treated with Ig IV, if it presents grade V, the use of plasmapheresis and/or immunoadbosorption is recommended. In severe axonal cases, the use of corticosteroid bolus is recommended in initial stages. There is a clinical picture that overlaps GBS and chronic demyelinating polyneuropathy related to antibodies against neurophysin and contactin, in this case the appropriate therapy is rituximab.
Topics: Guillain-Barre Syndrome; Humans; Muscle Weakness; Plasmapheresis
PubMed: 36054864
DOI: No ID Found -
Neuropharmacology Jun 2020Neuropeptides play important modulatory roles throughout the nervous system, functioning as direct effectors or as interacting partners with other neuropeptide and... (Review)
Review
Neuropeptides play important modulatory roles throughout the nervous system, functioning as direct effectors or as interacting partners with other neuropeptide and neurotransmitter systems. Limbic brain areas involved in learning, memory and emotions are particularly rich in neuropeptides. This review will focus on the amygdala, a limbic region that plays a key role in emotional-affective behaviors and pain modulation. The amygdala is comprised of different nuclei; the basolateral (BLA) and central (CeA) nuclei and in between, the intercalated cells (ITC), have been linked to pain-related functions. A wide range of neuropeptides are found in the amygdala, particularly in the CeA, but this review will discuss those neuropeptides that have been explored for their role in pain modulation. Calcitonin gene-related peptide (CGRP) is a key peptide in the afferent nociceptive pathway from the parabrachial area and mediates excitatory drive of CeA neurons. CeA neurons containing corticotropin releasing factor (CRF) and/or somatostatin (SOM) are a source of long-range projections and serve major output functions, but CRF also acts locally to excite neurons in the CeA and BLA. Neuropeptide S (NPS) is associated with inhibitory ITC neurons that gate amygdala output. Oxytocin and vasopressin exert opposite (inhibitory and excitatory, respectively) effects on amygdala output. The opioid system of mu, delta and kappa receptors (MOR, DOR, KOR) and their peptide ligands (β-endorphin, enkephalin, dynorphin) have complex and partially opposing effects on amygdala function. Neuropeptides therefore serve as valuable targets to regulate amygdala function in pain conditions. This article is part of the special issue on Neuropeptides.
Topics: Affect; Amygdala; Animals; Chronic Pain; Corticotropin-Releasing Hormone; Emotions; Humans; Neuropeptides; Neurophysins; Oxytocin; Protein Precursors; Vasopressins
PubMed: 32188569
DOI: 10.1016/j.neuropharm.2020.108052 -
Alcohol Research & Health : the Journal... 2007The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are... (Review)
Review
The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date primarily have studied coding variants in the ADH1 B, ADH1C, and ALDH2 genes that are associated with altered kinetic properties of the resulting enzymes. For example, certain ADH1B and ADH1C alleles encode particularly active ADH enzymes, resulting in more rapid conversion of alcohol (i.e., ethanol) to acetaldehyde; these alleles have a protective effect on the risk of alcoholism. A variant of the ALDH2 gene encodes an essentially inactive ALDH enzyme, resulting in acetaldehyde accumulation and a protective effect. It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study.
Topics: Alcohol Dehydrogenase; Alcoholism; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Alleles; Ethanol; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Linkage Disequilibrium; Neurophysins; Protein Precursors; Retinal Dehydrogenase; Vasopressins
PubMed: 17718394
DOI: No ID Found -
Biophysics and Physicobiology 2023Some evidence suggests that oxytocin, which is a neuropeptide conventionally thought to be synthesized in the hypothalamus and released by the posterior pituitary, is...
Some evidence suggests that oxytocin, which is a neuropeptide conventionally thought to be synthesized in the hypothalamus and released by the posterior pituitary, is generated in peripheral keratinocytes, but the details are lacking and the mRNA analysis is further required. Oxytocin and neurophysin I are generated together as cleavage products after splitting the precursor molecule, preprooxyphysin. To confirm that oxytocin and neurophysin I are also generated in the peripheral keratinocytes, it must first be clarified that these molecules contained in peripheral keratinocytes did not originate in the posterior pituitary gland and then the expression of oxytocin and neurophysin I mRNAs must be established in keratinocytes. Therefore, we attempted to quantify preprooxyphysin mRNA in keratinocytes using various primers. Using real-time PCR, we observed that the mRNAs of both oxytocin and neurophysin I were located in keratinocytes. However, the mRNA amounts of oxytocin, neurophysin I, and preprooxyphysin were too small to confirm their co-existence in keratinocytes. Thus, we had to further determine whether the PCR-amplified sequence was identical to preprooxyphysin. The PCR products analyzed by DNA sequencing were identical to preprooxyphysin, finally determining the co-existence of both oxytocin and neurophysin I mRNAs in keratinocytes. In addition, the immunocytochemical experiments showed that oxytocin and neurophysin I proteins were located in keratinocytes. These results of the present study provided further support indicating that oxytocin and neurophysin I are generated in peripheral keratinocytes.
PubMed: 37234847
DOI: 10.2142/biophysico.bppb-v20.0003 -
Scientific Reports Aug 2022Sodium appetite is a motivational state involving homeostatic behavior, seeking the ingest of salty substances after sodium loss. There is a temporal dissociation...
Sodium appetite is a motivational state involving homeostatic behavior, seeking the ingest of salty substances after sodium loss. There is a temporal dissociation between sodium depletion (SD) and the appearance of sodium appetite. However, the responsible mechanisms for this delay remain poorly elucidated. In the present study, we measured the temporal changes at two and 24 h after SD in the gene expression of key elements within excitatory, inhibitory, and sensory areas implicated in the signaling pathways involved in the onset of sodium appetite. In SD rats, we observed that the expression of critical components within the brain control circuit of sodium appetite, including Angiotensin-type-1 receptor (Agtr1a), Oxytocin-(OXT-NP)-neurophysin-I, and serotonergic-(5HT)-type-2c receptor (Htr2c) were modulated by SD, regardless of time. However, we observed reduced phosphorylation of mitogen-activated protein kinases (MAPK) at the paraventricular nucleus (PVN) and increased oxytocin receptor (Oxtr) mRNA expression at the anteroventral of the third ventricle area (AV3V), at two hours after SD, when sodium appetite is inapparent. At twenty-four hours after SD, when sodium appetite is released, we observed a reduction in the mRNA expression of the transient receptor potential channel 1gene (Trpv1) and Oxtr in the AV3V and the dorsal raphe nucleus, respectively. The results indicate that SD exerts a coordinated timing effect, promoting the appearance of sodium appetite through changes in MAPK activity and lower Trpv1 channel and Oxtr expression that trigger sodium consumption to reestablish the hydroelectrolytic homeostasis.
Topics: Animals; Appetite; Biomarkers; Oxytocin; RNA, Messenger; Rats; Receptor, Angiotensin, Type 1; Sodium; Sodium, Dietary
PubMed: 35987984
DOI: 10.1038/s41598-022-18220-w -
Animals : An Open Access Journal From... Mar 2022Leucyl and cystinyl aminopeptidase (LNPEP/oxytocinase) is an enzyme that metabolizes oxytocin in serum and tissues. The presence of oxytocin/neurophysin I (OXT),...
Leucyl and cystinyl aminopeptidase (LNPEP/oxytocinase) is an enzyme that metabolizes oxytocin in serum and tissues. The presence of oxytocin/neurophysin I (OXT), oxytocin and LNPEP and their relationship to other genes is unknown in the equine conceptus. Our objective was to characterize gene expression of LNPEP and OXT on D8, 10, 12, 14, 15, 16 and 21 conceptuses in relationship to other genes. Immunohistochemistry, western blot and liquid chromatography with tandem mass spectrometry (LC-MS/MS) were used for identification of oxytocin and LNPEP in D15, 16 and 18 conceptuses. LNPEP was increased at D15 compared to D10, was immunolocalized in the equine trophectoderm and endoderm, and protein was confirmed by LC-MS/MS. Maximal abundance of OXT was at D21, and lowest on D12 and D14, but no protein was identified. OXTR abundance was highest on D14 and D21. LNPEP was correlated with PTGFR and PTGES on D12 and D14-D15, and high expression of PTGES, PTGS2 was found on D14, D15 and D21; PTGFR was found on D8 and D12-21. LNPEP may have a role in prostaglandin regulation and conceptus fixation by decreasing the availability of oxytocin. Further investigation on the role embryonic LNPEP during pregnancy is warranted.
PubMed: 35405789
DOI: 10.3390/ani12070799 -
Psychopharmacology Dec 2018Arginine vasopressin (VP) has been implicated in a number of neuropsychiatric disorders with an emphasis on situations where stress increased the severity of the... (Review)
Review
BACKGROUND
Arginine vasopressin (VP) has been implicated in a number of neuropsychiatric disorders with an emphasis on situations where stress increased the severity of the disorder. Based on this hypothesized role for VP in neuropsychiatric disorders, much research is currently being undertaken in humans and animals to test VP as a target for treatment of a number of these disorders including alcohol abuse.
OBJECTIVES
To provide a summary of the literature regarding the role of VP in alcohol- and stress-related behaviors including the use of drugs that target VP in clinical trials.
RESULTS
Changes in various components of the VP system occur with alcohol and stress. Manipulating VP or its receptors can alter alcohol- and stress-related behaviors including tolerance to alcohol, alcohol drinking, and anxiety-like behavior. Finally, the hypothalamic-pituitary-adrenal axis response to alcohol is also altered by manipulating the VP system. However, clinical trials of VP antagonists have had mixed results.
CONCLUSIONS
A review of VP's involvement in alcohol's actions demonstrates that there is much to be learned about brain regions involved in VP-mediated effects on behavior. Thus, future work should focus on elucidating relevant brain regions. By using previous knowledge of the actions of VP and determining the brain regions and/or systems involved in its different behavioral effects, it may be possible to identify a specific receptor subtype target, drug treatment combination, or specific clinical contexts that may point toward a more successful treatment.
Topics: Alcohol Drinking; Alcoholism; Animals; Antidiuretic Hormone Receptor Antagonists; Anxiety; Arginine Vasopressin; Ethanol; Humans; Hypothalamo-Hypophyseal System; Neurophysins; Pituitary-Adrenal System; Protein Precursors; Stress, Psychological; Vasopressins
PubMed: 30392132
DOI: 10.1007/s00213-018-5099-x -
International Journal of Molecular... Oct 2021The neurons secreting oxytocin (OXY) and vasopressin (AVP) are located mainly in the supraoptic, paraventricular, and suprachiasmatic nucleus of the brain. Oxytocinergic... (Review)
Review
The neurons secreting oxytocin (OXY) and vasopressin (AVP) are located mainly in the supraoptic, paraventricular, and suprachiasmatic nucleus of the brain. Oxytocinergic and vasopressinergic projections reach several regions of the brain and the spinal cord. Both peptides are released from axons, soma, and dendrites and modulate the excitability of other neuroregulatory pathways. The synthesis and action of OXY and AVP in the peripheral organs (eye, heart, gastrointestinal system) is being investigated. The secretion of OXY and AVP is influenced by changes in body fluid osmolality, blood volume, blood pressure, hypoxia, and stress. Vasopressin interacts with three subtypes of receptors: V1aR, V1bR, and V2R whereas oxytocin activates its own OXTR and V1aR receptors. AVP and OXY receptors are present in several regions of the brain (cortex, hypothalamus, pons, medulla, and cerebellum) and in the peripheral organs (heart, lungs, carotid bodies, kidneys, adrenal glands, pancreas, gastrointestinal tract, ovaries, uterus, thymus). Hypertension, myocardial infarction, and coexisting factors, such as pain and stress, have a significant impact on the secretion of oxytocin and vasopressin and on the expression of their receptors. The inappropriate regulation of oxytocin and vasopressin secretion during ischemia, hypoxia/hypercapnia, inflammation, pain, and stress may play a significant role in the pathogenesis of cardiovascular diseases.
Topics: Axons; Brain; Cardiovascular Abnormalities; Cardiovascular System; Humans; Hypertension; Lung; Myocardial Infarction; Neurons; Neurophysins; Oxytocin; Protein Precursors; Receptors, Oxytocin; Vasopressins
PubMed: 34768894
DOI: 10.3390/ijms222111465 -
Seminars in Dialysis Nov 2017Homeostatic regulation of plasma osmolality (POsm) is critical for normal cellular function in humans. Arginine vasopressin (AVP) is the major hormone responsible for... (Review)
Review
Homeostatic regulation of plasma osmolality (POsm) is critical for normal cellular function in humans. Arginine vasopressin (AVP) is the major hormone responsible for the maintenance of POsm and acts to promote renal water retention in conditions of increased POsm. However, AVP also exerts pressor effects, and its release can be stimulated by the development of effective arterial blood volume depletion. Patients with end-stage renal disease on hemodialysis, particularly those with minimal or no residual renal function, have impaired ability to regulate water retention in response to AVP. While hemodialysis can assist with this task, patients are subject to relatively rapid shifts in volume and electrolytes during the procedure. This can result in the development of transient osmotic gradients that lead to the movement of water from the extracellular to the intracellular space. Hypotension may result-both as a consequence of water movement out of the intravascular compartment, but also from impaired AVP release and inadequate vascular tone. In this review, we explore the evidence for POsm changes during hemodialysis, associations with adverse outcomes, and methods to minimize the rapidity of changes in POsm in an effort to reduce patient symptoms and minimize intra-dialytic hypotension.
Topics: Blood Pressure; Hemodialysis Solutions; Humans; Hypotension; Kidney Failure, Chronic; Neurophysins; Osmolar Concentration; Protein Precursors; Renal Dialysis; Vasopressins; Water-Electrolyte Balance
PubMed: 28691402
DOI: 10.1111/sdi.12629