Vasopressin Research Articles

Approach to the Patient: From Endocrinopathy to the Diagnosis of a Histiocytic Disorder.

Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim-Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and anterior pituitary dysfunction (APD) in 20% to 30% of cases, often as the first manifestation. Conversely, histiocytic disorders account for a notable proportion (10-15%) of all pituitary stalk lesions. The diagnosis of histiocytoses is often delayed in such cases due to the nonspecific presentation of endocrinopathies and pituitary involvement. Consequently, endocrinologists are at the frontline and uniquely positioned to achieve early diagnosis by recognizing the varied nonendocrine features of these disorders. This article provides an overview of the endocrine manifestations of histiocytic disorders and presents a simplified algorithm to guide the diagnostic workup in cases presenting with "idiopathic" AVP-D or APD. Such cases should be evaluated for histiocytic neoplasms with additional imaging studies and biopsies of suspected disease sites. If no disease site beyond the pituitary is identified, the risks and benefits of a pituitary stalk lesion biopsy must be carefully considered. While treatments of histiocytic neoplasms are highly efficacious, endocrinopathies are considered permanent and require long-term hormone replacement. It remains unclear whether early diagnosis and novel targeted therapies can reverse these endocrine disorders. Therefore, the role of the endocrinologist role is critical in the diagnosis and management of these rare diseases.

Can the Bladder Itself "Measure" Volume, and Thereby Help to Determine When Initiation of Voiding Should Occur? ICI-RS 2024.

To answer the question of whether the bladder itself can to any extent control or modulate the initiation of voiding. This subject was discussed at the International Consultation on Incontinence-Research Society (ICI-RS) 2024 conference in Bristol, UK in a proposal session. Cells in the bladder wall sense the local environment via a diverse array of ion channels and receptors which together provide input to motor-sensory and signal transduction mechanisms. A purinergic signal transduction system provides a high-gain mucosal chemosensitive transduction pathway between bladder wall stretch during filling and graded afferent activation. Recent studies established cross-species similarities in the regulation of urine storage which include the upregulation of aquaporin (water) channels during bladder filling/wall stretch, in the bladder. In addition to the endocrine hypothalamus/pituitary axis production, urothelial production of arginine vasopressin acts on urothelial vasopressin receptors in a paracrine manner causing aquaporin channel upregulation, reducing the bladder volume and delaying sensation of fullness. Bladder shape influences the sensory systems involved in the perception of bladder volume; moreover irregular bladder shapes may correlate with overactive bladder. Volume measuring and signaling threshold-determining mechanisms in the bladder along with shape and permeability act to influence the timing and type of signaling to the CNS; although this is not always followed by a consecutive action. The hierarchical grading of the signals originating from the bladder among other peripheral bodily or central signals are crucial factors that determine whether the bladder is "allowed" to initiate voiding.

Anaemia of inflammation preceding dyspnoea, dry cough and weight loss in primary pulmonary lymphoma

Introduction: There is little information in the literature on the early, sub-clinical stage and laboratory test results in patients with primary mucosa-associated lymphoid tissue (MALT) lymphoma of the lung, a rare disease. Case description: In a 75-year-old man, an open lung biopsy-confirmed diagnosis of primary pulmonary lymphoma was preceded by almost six months of anaemia of inflammatory disease and monocytosis without any pulmonary symptoms. When he developed a dry cough, increasing dyspnoea and marked weight loss, these changes deepened and became associated with reactive thrombocytosis; markedly increased ferritin and C-reactive protein (positive acute-phase reactants), as well as reduced albumin and transferrin (negative acute-phase reactants). Globulins increased, due to an increase in the alpha1, alpha2 and gamma fractions, and mild hyponatraemia developed due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) secondary to the intrathoracic disease. All these changes were completely reversible following successful treatment and complete remission. Conclusion: The previously unreported detailed laboratory features of early, sub-clinical and advanced primary pulmonary lymphoma are presented. When a potentially susceptible patient develops an unexplained anaemia of inflammatory disease, primary pulmonary lymphoma should be added to the differential diagnosis.

Early-life challenge enhances cortisol regulation in zebrafish larvae.

The hypothalamic-pituitary-adrenal (HPA) axis in mammals and the hypothalamic-pituitary-interrenal (HPI) axis in fish are open systems that adapt to the environment during development. Little is known about how this adaptation begins and regulates early stress responses. We used larval zebrafish to examine the impact of prolonged forced swimming at 5 days post-fertilization (dpf), termed early-life challenge (ELC), on cortisol responses, neuropeptide expression in the nucleus preopticus (NPO), and gene transcript levels. At 6 dpf, ELC-exposed larvae showed normal baseline cortisol but reduced reactivity to an initial stressor. Conversely, they showed increased reactivity to a second stressor within the 30-min refractory period, when cortisol responses are typically suppressed. ELC larvae had fewer corticotropin-releasing hormone (crh), arginine vasopressin (avp), and oxytocin (oxt)-positive cells in the NPO, with reduced crh and avp co-expression. Gene expression analysis revealed upregulation of genes related to cortisol metabolism (hsd11b2, cyp11c1), steroidogenesis (star), and stress modulation (crh, avp, oxt). These results suggest that early environmental challenge initiates adaptive plasticity in the HPI axis, tuning cortisol regulation to balance responsiveness and protection during repeated stress. Future studies should explore the broader physiological effects of prolonged forced swimming and its long-term impact on cortisol regulation and stress-related circuits.

The natural history of untreated X-linked nephrogenic diabetes insipidus with mutation in the vasopressin V2 receptor gene.

Nephrogenic diabetes insipidus (NDI) results from the kidneys' inability to concentrate urine. We describe a 6-month-old male with a history of poor weight gain who presented with an incidental finding of hypernatremia (155mEq/L) during an episode of acute gastroenteritis. The arginine vasopressin (AVP) test, along with molecular analysis revealing the M272R mutation in the AVP receptor 2 (AVPR2) gene, confirmed the diagnosis of congenital NDI. Interestingly, this mutation was also identified in the patient's maternal grandfather, who had never been diagnosed or treated for NDI despite a history of polydipsia, polyuria, and evidence of chronic kidney disease (CKD), severe bilateral hydronephrosis, hypertension, and severe bladder dysfunction. Early intervention with hydrochlorothiazide in the infant resulted in a significant reduction in urinary output and improved growth. The untreated grandfather's case highlights the potential severity of untreated NDI and the benefits of timely therapeutic intervention. This report contributes to the limited long-term data on congenital NDI, emphasizing the critical role of early detection and consistent management in preventing severe complications such as CKD, hydronephrosis, and bladder dysfunction. Regular follow-up, including renal ultrasound and monitoring of renal function, is essential for effectively managing NDI and improving patient outcomes.

Trends and Outcomes in Pituitary Apoplexy Management: A Spanish Observational Multicenter Study.

Currently, the management for pituitary apoplexy (PA) has been promoted toward a more conservative approach, particularly for patients with low-grade PA scores. Our aim was to investigate trends in PA management and compare clinical presentation, therapeutic approaches, and outcomes before and after 2017, additionally to evaluate long-term outcomes in conservatively treated patients. Spanish multicenter, retrospective study. Statistical analyses compared clinical presentation and outcomes between periods, adjusting for confounders. A total of 215 patients with PA and nonfunctioning pituitary adenoma were included, with the median age of 62.2 years and 68.4% were male patients. Of which 94 (43.7%) were diagnosed before 2017 and 121 (56.3%) in 2017 or later. Conservative treatment increased from 17% before to 30.6% in the recent period (odd ratio 0.47, 95% CI 0.24-0.90, P 0.02) This trend remained significant after adjusting for hospital, age, and Knosp grade (odd ratio 0.46, 95% CI 0.22-0.89, P = .03). However, surgery remained the most frequently used therapeutic option in both periods. There were no statistically significant differences in outcomes at 3 months between periods. Surgery compared with conservative management was associated with higher permanent arginine vasopressin deficiency in both periods (0 vs 17.9%, P = .07 before 2017; 0 vs 16.7%, P = .01 after). Up to 89.7% of patients treated conservatively, presented more than 25% spontaneous tumor shrinkage, and 74.4% had more than 50% tumor reduction. Although conservative management increased in the last years, surgery remains the predominant option. Patients managed conservatively experience a lower risk of permanent arginine vasopressin deficiency, and a high proportion exhibit clinically significant tumor shrinkage over time.

Neurohormonal activation pattern in patients with atrial septal defect

Atrial septal defects (ASD) divert flow from systemic to pulmonary circulation, and some degree of plasma volume expansion and neurohormonal activation are necessary to maintain the effective circulatory volume. The aim of the present study was to understand the patterns of neurohormonal activation in ASD patients. 16 ASD patients and 10 controls were enrolled. Fasting blood samples were collected prior to procedure and 48 h after defect closure. At baseline, renin (185.0(79.0—437.0 vs. 79.4(60.8—110.0), p = 0.04), aldosterone (20.2 ± 7.6 vs. 11.7 ± 2.8, p < 0.001), copeptin (43.6 ± 27.5 vs. 16.4 ± 8.7, p = 0.002) and both natriuretic peptides were higher in ASD patients, while noradrenaline (113.0 ± 61.3 vs. 178.0 ± 49.4, p = 0.009) and endothelin-1 (2.93 ± 2.00 vs. 5.06 ± 1.25, p = 0.006) were higher in controls. After ASD closure, only NT-proBNP reduced significantly (p = 0.02). There were negative correlations between defect area with noradrenaline (r=-0.73, p = 0.002) and with endothelin-1 (r=-0.59, p = 0.02). Present findings suggest that in patients with an ASD, there is an increase in neurohormones that are related to regulation of plasma volume (aldosterone and arginine vasopressin) with simultaneous reductions in neurohormones related to vasoconstriction in systemic and pulmonary beds (noradrenaline and endothelin-1).

The Syndrome of Inappropriate Antidiuresis

Abstract The syndrome of inappropriate antidiuresis (SIAD)–the most frequent cause of hypotonic hyponatremia–is mediated by nonosmotic release of arginine vasopressin (AVP), which promotes water retention by activating renal vasopressin type 2 (V2) receptors. There are numerous causes of SIAD, including malignancy, pulmonary and central nervous system diseases and medications. Rare activating mutations of the V2 receptor can also cause SIAD Determination of the etiology of SIAD is important because removal of the stimulus for inappropriate AVP secretion offers the most effective therapy. Treatment of SIAD is guided by symptoms and their severity as well as the level of plasma sodium. In the absence of severe symptoms which require urgent intervention, many clinicians focus on fluid restriction as a first-line treatment. Second-line therapeutic options include loop diuretics and salt tablets, urea, and V2 receptor antagonists.

Intestinal butyric acid-mediated disruption of gut hormone secretion and lipid metabolism in vasopressin receptor-deficient mice.

Arginine vasopressin (AVP), known as an antidiuretic hormone, is also crucial in metabolic homeostasis. Although AVP receptor-deficient mice exhibit various abnormalities in glucose and lipid metabolism, the mechanism underlying these symptoms remains unclear. This study aimed to explore the involvement of the gut hormones including glucagon-like peptide-1 (GLP-1) and microbiota as essential mediators. We used the mouse GLP-1-secreting cell line, GLUTag, and performed live cell imaging to examine the contribution of V1a and V1b vasopressin receptors (V1aR and V1bR, respectively) to GLP-1 secretion. We next investigated the hormone dynamics of V1aR-deficient mice (V1aR-/- mice), V1bR-deficient mice (V1bR-/- mice), and V1aR/V1bR-double deficient mice (V1aR-/-V1bR-/-mice). AVP induced the increase in intracellular Ca2+ levels and GLP-1 secretion from GLUTag cells in a V1aR and V1bR-dependent manner. AVP receptor-deficient mice, particularly V1aR-/-V1bR-/- mice, demonstrated impaired secretion of GLP-1 and peptide YY secreted by enteroendocrine L cells. V1aR-/-V1bR-/-mice also exhibited abnormal lipid accumulation in the brown adipose tissue and skeletal muscle. We discovered that V1aR-/-V1bR-/- mice showed increased Paneth cell-related gene expression in the small intestine, which was attributed to increased fecal butyric acid levels. Exposure to butyric acid reduced GLP-1 secretion in L cell line. Additionally, human Paneth cell-related gene expressions negatively correlated with that of V1 receptor genes. The deficiency in V1 receptor genes may increase gut butyric acid levels and impair the function of L cells, thus dysregulating lipid homeostasis in the brown adipose tissue and skeletal muscle. This study highlights the importance of appropriate control of the gut microbiota and its metabolites, including butyric acid, for the optimum functioning of enteroendocrine cells.

Comparative study of the effectiveness of tolvaptan versus urea in patients with hyponatremia caused by SIADH

Background and objectivesHyponatraemia is common in elderly and hospitalised patients, often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study evaluates the efficacy and safety of tolvaptan and urea in patients with hyponatraemia and SIADH. Materials and methodsAn observational cohort study was conducted on 198 patients with SIADH and hyponatraemia (Na+ <135 mmol/L) at the Complejo Hospitalario Universitario de Pontevedra from January 2015 to May 2022. Of these, 86 were treated with tolvaptan (average dose of 7.5 mg) and 112 with urea (average dose of 15 g). The primary outcome was the normalisation of sodium levels (Na ≥ 135 mmol/L). ResultsThe tolvaptan group showed higher sodium concentrations at the end of therapy compared to the urea group (ME = 136, IQR = 135-137 vs. ME = 134, IQR = 132-137; p < 0.001). The time to normalise sodium was shorter with tolvaptan (4 ± 3.4 days) compared to urea (6 ± 3.6 days; p = 0.03). A higher percentage of patients achieved sodium normalisation with tolvaptan (83.72% vs. 59.82%; p = 0.005). Tolvaptan had more adverse effects, such as dry mouth, thirst, and sodium overcorrection, while urea caused dysgeusia, abdominal pain, and diarrhea. There were no significant differences in mortality between the groups. ConclusionsTolvaptan was more effective and quicker than urea in normalising sodium levels, though it showed a higher percentage of adverse effects, which did not require discontinuation of the drug.

Effect of Genetics on Autism Spectrum Disorders: A Review Study

Autism Spectrum Disorders (ASD) are intricate neurodevelopmental conditions marked by challenges in social interaction, communication, and repetitive behaviors. The etiology of ASD is multifaceted, involving genetic mutations, perinatal, nutritional and environmental factors. This review explores the various genetic mutations implicated in the development of ASD for the purpose of examining the diverse genetic factors contributing to the pathogenesis of ASD such as SHANK3, SCGN, ADNP, ARID1B, CHD8, DYRK1A, KMT2C, OT, AVP and zinc transporter genes. A comprehensive review of literature was conducted to gather information on genetic influences related to ASD. Studies investigating the complex interplay of those factors were analyzed to elucidate how they contribute to the development of ASD. Results found that genetic mutations in genes like Shank3 and SCGN have been identified as playing a role in the pathogenesis of ASD through their impact on glutamic excitatory pathways and oxytocin signaling. ADNP, ARID1B, CHD8, DYRK1A, KMT2C, OT, AVP and zinc transporter genes have also been linked to an increased risk of ASD and associated cognitive and neurological impairments. In conclusion, research on different genetic mutations and deletions affecting autism spectrum disorder (ASD) highlights the complexity of the disease. Key genes such as SHANK3, SCGN, ADNP, ARID1B, CHD8, DYRK1A, and KMT2C are implicated, each contributing uniquely to ASD. Genetic variations, mutations, and heritability play significant roles, with factors like zinc deficiency and advanced paternal age also linked to increased ASD risk. While genomic technology has identified specific markers and pathways, the effect of multiple genetic mutations on symptom severity remains unclear. Understanding these genetic factors is crucial for improving diagnostic precision and developing targeted therapies, necessitating continued interdisciplinary research.

Nebulized vasopressin penetrates CSF and improves social cognition without inducing aggression in a rhesus monkey model of autism

Low cerebrospinal (CSF) arginine vasopressin (AVP) concentration is a biomarker of social impairment in low-social monkeys and children with autism, suggesting that AVP administration may improve primate social functioning. However, AVP administration also increases aggression, at least in "neurotypical" animals with intact AVP signaling. Here, we tested the effects of a voluntary drug administration method in low-social male rhesus monkeys with high autistic-like trait burden. Monkeys received nebulized AVP or placebo, using a within-subjects design. Study 1 (N = 8) investigated the effects of AVP administration on social cognition in two tests comparing responses to social versus nonsocial stimuli. Test 1: Placebo-administered monkeys lacked face recognition memory, whereas face recognition memory was "rescued" following AVP administration. In contrast, object recognition memory was intact and did not differ between administration conditions. Test 2: Placebo-administered monkeys did not respond to conspecific social communication cues, whereas following AVP administration, they reciprocated affiliative communication cues with species-typical affiliative responses. Importantly, AVP administration did not increase aggressive responses to conspecific aggressive or affiliative overtures. Study 2 (N = 4) evaluated the pharmacokinetics of this administration method. Following AVP nebulization, we observed a linear increase in cisternal CSF AVP levels, and a quadratic rise and fall in blood AVP levels. These findings indicate that nebulized AVP likely penetrates the central nervous system, selectively promotes species-typical responses to social information, and does not induce aggression in low-social individuals. Nebulized AVP therefore may hold promise for managing similar social symptoms in people with autism, particularly in very young or lower functioning individuals.

Saline versus balanced crystalloids for hydration post-kidney biopsy.

Isotonic fluids are becoming the standard for hydration and maintenance fluid therapy, but there is no consensus on the optional choice among the different types of isotonic solution. This study is a single-center, non-randomized controlled trial at Kobe University Hospital, Japan, between April 2021 and March 2023. The study included pediatric patients aged 1-19years who underwent kidney biopsies. From April 2021 to March 2022, 0.9% sodium chloride (saline) was administered, and from April 2022 to March 2023, balanced crystalloids were used. The primary outcome was the occurrence of hyponatremia (< 137mEq/L) after a kidney biopsy. Secondary outcomes included other electrolyte balances, blood gas parameters, creatinine-based estimated glomerular filtration rate (Cr-eGFR), and arginine vasopressin concentrations (UMIN Clinical Trial Registry: UMIN 000044330). Of 61 patients enrolled, 2 were excluded, leaving 34 in the saline group and 25 in the balanced crystalloid group. No hyponatremia occurred, and serum sodium concentrations were similar between both groups (138.7 vs. 138.9mEq/L, P = 0.08). The saline group showed a greater increase in serum chloride (+ 1.7 vs. + 0.2, P < 0.01) and a greater decrease in HCO3- concentrations (- 0.6 vs. + 0.9, P < 0.01). There were minimal changes in pH (- 0.01 vs. - 0.01, P = 0.99) and Cr-eGFR (- 1.5 vs. + 1.1mL/min/1.73 m2, P = 0.96) in both groups. During pediatric kidney biopsy, both saline and balanced crystalloids were effective in preventing hyponatremia. Although saline infusion results in higher serum chloride concentrations and lower blood HCO3- concentrations than balanced crystalloids infusion, the clinical significance was minimal.

A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice.

The transcription factor MYT1L supports proper neuronal differentiation and maturation during brain development. MYT1L haploinsufficiency results in a neurodevelopmental disorder characterized by intellectual disability, developmental delay, autism, behavioral disruptions, aggression, obesity and epilepsy. While MYT1L is expressed throughout the brain, how it supports proper neuronal function in distinct regions has not been assessed. Some features of MYT1L Neurodevelopmental Syndrome suggest disruption of hypothalamic function, such as obesity and endocrine issues, and previous research showed changes in hypothalamic neuropeptide expression following knockdown in zebrafish. Here, we leveraged our heterozygous Myt1l mutant, previously shown to recapitulate aspects of the human syndrome such as hyperactivity, social challenges, and obesity, to examine the impact of MYT1L loss on hypothalamic function. Examining the molecular profile of the MYT1L haploinsufficient hypothalamus revealed a similar scale of disruption to previously studied brain regions, yet with region-specific roles for MYT1L, including regulation of neuropeptide systems. Alterations in oxytocin and arginine vasopressin cell numbers were also found. Behaviors studied included maternal care, social group hierarchies, and aggression, all of which were unchanged. Feeding and metabolic markers were also largely unchanged in MYT1L haploinsufficient mice, yet an interaction was observed between diet and MYT1L genotype on weight gain. Our findings here suggest that gross endocrine function was not altered by MYT1L haploinsufficiency, and that key sex-specific behaviors related to proper hypothalamic function remain intact. Further study is needed to understand the functional impact of the altered hypothalamic molecular profile and changes in neuropeptide cell numbers that result from MYT1L haploinsufficiency.

THE ETIOLOGICAL PROFILE AND ALTERATIONS IN CEREBROSPINAL FLUID CHARACTERISTICS IN PATIENTS WITH BACTERIAL MENINGITIS

Currently, bacterial meningitis (BM) remains a form of life-threatening infectious pathology, with a mortality rate ranging from 4% to 35% and poor prognosis often accompanied by diverse specific and non-specific complications, including infectious toxic shock, cerebral edema, ventricular inflammation, hydrocephalus, acute cerebrovascular accidents, venous sinus thrombosis, disseminated intravascular coagulation (DIC) syndrome, respiratory distress syndrome (RDS) syndrome, inappropriate secretion of antidiuretic hormone, and systemic inflammatory response syndrome. In clinical practice, the early identification of the causative microorganism and the implementation of proper antibiotic treatment, as well as a comprehensive assessment of the patient's status and management, are crucial for minimizing a risk of related severe complications and mortality. The BM etiology is characterized by a highly variable nature, contingent upon a multitude of factors such as geographic location, temporal context, patient age, immunological status, and other variables. Over the past two to three decades, advancements in conjugate vaccines and the use implementation of antibiotic treatment have brought about alterations in the spectrum of pathogens responsible for meningitis. The objective of this study was to delve into the etiological profile and prognostic implications of cerebrospinal fluid (CSF) parameters among patients with diagnosed meningitis admitted to the Neuroinfectious Diseases Division of the Infectious Clinical Hospital №2 (Moscow) between 2022 and 2023. A retrospective analysis of medical records of meningitis patients admitted to the Infectious Clinical Hospital №2 during 2022–2023 was conducted. The data were analyzed using the k-means clustering algorithm implemented in the Loginom analytics software to create a scenario, as well as OLAP cubes. The study involved the analysis of medical records for 110 patients aged 18-89 years old. Among the BM pathogens identified, Neisseria meningitidis emerged as the most prevalent in this patient cohort, accounting for 68.2% of cases. Within the group of meningococcal meningitis cases, serovariants A and W135 were the most frequently detected, accounting for 49.3% and 33.3%, respectively. Significant alterations in cerebrospinal fluid parameters, characterized by elevated cell counts and lowered glucose levels, were observed among patients with purulent meningitis resulting from serogroup A Neisseria meningitidis infections. A combination of elevated baseline cell level along with high concentrations of proteins, and lactate, coupled with the presence of D-dimer in cerebrospinal fluid, has been associated with a severe disease progression and the emergence of critical and life-threatening sequelae.

Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats.

In clinical practice, an increasing number of patients exhibit concurrent cardiac and renal dysfunction, known as "cardiorenal syndrome," where each condition exacerbates the other, resulting in poorer patient prognosis. Fluid and sodium retention can lead to excessive fluid overload in the body; therefore, correcting fluid and sodium metabolic disorders is crucial for alleviating patient symptoms. This study was to investigate the abnormalities in water and sodium metabolism, as well as the expression levels of arginine vasopressin receptor 1a (AVPR1a) and arginine vasopressin receptor 2 (AVPR2), in a rat model of chronic renal failure-chronic heart failure (CRF-CHF). One hundred male Sprague-Dawley rats were randomly assigned into four groups: the CG group (normal feeding), the CRF group (3/4 nephrectomy using a "two-step surgical method"), the CHF group (subcutaneous injection of isoproterenol at 100 mg/kg), and the CRF-CHF group (3/4 nephrectomy followed by a subcutaneous injection of isoproterenol at 100 mg/kg 1 week later). 4 weeks post-surgery, urine and blood samples were collected to measure 24 h urinary protein, sodium, and potassium levels. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were determined using assay kits. Left ventricular end diastolic pressure (LVEDP) and left ventricular systolic pressure (LVSP) were measured via left ventricular catheterization. The heart was weighed to calculate the left ventricular weight to body weight ratio (LVW/BW). The renal cortex and medulla were isolated to assess the relative mRNA and protein expression levels of AVPR1a and AVPR2. Compared to the CG group, the CRF and CRF-CHF groups exhibited significantly elevated levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla. The CHF and CRF-CHF groups showed significant increases in LVEDP and LVW/BW (P < 0.05). Additionally, compared to the CG group, the other three groups had significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Compared to the CRF and CHF groups, the CRF-CHF group exhibited significantly higher levels of 24 h urinary protein, SCr, BUN, and relative expression levels of AVPR1a and AVPR2 in the renal cortex and medulla, along with significantly increased LVEDP and LVW/BW, significantly reduced LVSP, significantly increased urinary sodium and blood potassium levels, and significantly decreased urinary potassium and blood sodium levels (P < 0.05). Rats with CRF-CHF experienced exacerbated renal and cardiac failure, characterized by significant disturbances in water and sodium metabolism and abnormal expression of AVPR1a and AVPR2.

Long-Term Persistence of Inappropriate Antidiuretic Hormone Secretion Following Minor Head Injury.

While the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is typically transient, it can persist after even minor head trauma, highlighting the importance of long-term follow-up in cases of post-traumatic hyponatremia.Urea therapy is effective and well-tolerated for managing chronic hyponatremia in SIADH, offering a sustainable long-term treatment option.Even mild hyponatremia can lead to subtle but impactful cognitive and motor symptoms.

Real-time intraoperative ultrasound imaging of the posterior pituitary gland during endoscopic endonasal approach.

Pituitary adenomas are amongst the most common benign central nervous system tumors, and often require resection via an endoscopic endonasal approach (EEA). Two of the most common associated complications are central diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both are thought to be caused by manipulation of the posterior pituitary gland (PPG), making intraoperative visualization and preservation of this structure critical. Intraoperative endoscopic endonasal ultrasound (IEUS) may present an optimal tool for this purpose. This study aims to describe the appearance and morphology of the PPG on IEUS. This study included all pituitary adenoma surgeries during which IEUS was utilized and the PPG was visualized between 1/1/2022, and 12/31/2023. Demographic, clinical, pathological, and radiological data were retrospectively collected. The PPG was described as either hypoechoic, isoechoic, or hyperechoic as compared to the anterior pituitary gland and adenoma, and the morphology of the PPG was further classified as ellipse or crescent shaped. The PPG was hypoechoic in all 43 cases included in our final cohort (100.0%). Morphologically, the PPG appeared elliptical in 27 cases (62.8%), and crescent shaped in 16 cases (37.2%). The PPG can typically be visualized by IEUS as a hypoechoic structure immediately anterior to the posterior wall of the sella turcica, with elliptical morphology being the most common appearance. These characteristics can be used by the skull base surgeon to more confidently identify the position and morphology of the PPG intraoperatively for its' preservation.

Hyponatremia Associated with the Use of Common Antidepressants in the All of Us Research Program.

Selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), and norepinephrine-dopamine reuptake inhibitor (NRI) antidepressants can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH). This study assesses the differential risks of hyponatremia associated with commonly prescribed SSRIs (fluoxetine, paroxetine, sertraline, citalopram, escitalopram), SNRIs (duloxetine, venlafaxine) and NRI (bupropion), as well as omeprazole as a reference, with a retrospective observational cohort study in the All of Us Research Program, a national multicenter research cohort containing de-identified electronic health records (EHR). Participants who had been prescribed monotherapy with any of eight common antidepressants were included, with each drug considered as a separate arm indexed with a start date. Events were defined as the first occurrence of a low plasma sodium measurement or a clinical diagnosis recorded for either hyponatremia or SIADH. Those who did not have events were censored at their last plasma sodium measurement. A total of 17,439 individuals were exposed to one of the eight antidepressants as monotherapy. The overall incidences for hyponatremia were 0.87% in the first 30 days and 10.5% in the first 3 years in the antidepressant arms. Compared to sertraline, duloxetine (hazard ratio [HR] = 1.37 [1.19-1.58]) and escitalopram (HR = 1.16 [1.01-1.33]) were associated with the highest overall risk of hyponatremia, and bupropion (HR = 0.83 [0.73-0.94]) and paroxetine (HR = 0.78 [0.65-0.93]) were associated with the lowest risk. The risks were unchanged after adjusting for comorbidity and polypharmacy. Such information could help guide providers in managing patients and their risks of hyponatremia when on common antidepressants.

Correlation Between Serum Copeptin and NTproBNP Levels in Heart Failure

Introduction: Heart Failure is a leading cause of morbidity and mortality worldwide. It is associated with upregulation and dysfunction of the renin-angiotensin aldosterone system, the sympathetic nervous system and the vasopressin system. In heart failure, the levels of vasopressin are elevated and out of sync with the osmotic status. Arginine Vasopressin has a half-life of only 20 minutes and is bound to circulating platelets. Hence, it is not useful as a biomarker. Copeptin, a by-product of vasopressin metabolism has been used as a surrogate marker for Arginine Vasopressin in clinical practice. Thus, our study aims to find the use of copeptin in studying heart failure and its use in predicting severity. We also sought to correlate copeptin with NTproBNP the standard biomarker used in heart failure. Methods: Our study was a single-centre cross-sectional observational study involving 90 admitted heart failure patients over 18 months. NYHA Class was used to assess the severity of heart failure. Copeptin levels were measured using Human Copeptin ELISA Kit. Results: In these patients, elevated levels of copeptin and NTproBNP were found. In patients with higher NYHA Class, a greater rise in serum copeptin and NTproBNP levels was noted. Moreover, a strong positive correlation between NTproBNP and copeptin (rho = 0.7) was found in our study. Conclusion: Our study puts forward copeptin as a simple additional cost-effective biomarker for predicting the severity of heart failure.