α-1 Adrenoceptor Activation in the Dorsal Raphe Nucleus Decreases Food Intake in Fasted Rats

The dorsal raphe (DR) nucleus is involved in a myriad of physiological functions, such as the control of sleep-wake cycle, motivation, pain, energy balance, and food intake. We have previously demonstrated that in ad libitum fed rats the intra-DR administration of phenylephrine, an α-1 receptor agonist, does not affect food intake, whereas clonidine, an α-2 receptor agonist, potently stimulates food intake. These results indicated that in fed rats an increased adrenergic tonus blocked food intake, since the activation of α-2 auto-receptors, which decreases pre-synaptic release of adrenaline/noradrenaline, affected food intake. Thus, in this study we assessed whether the response to adrenergic stimuli would differ after overnight fasting, a situation of low adrenergic activity in the DR. Intra-DR administration of adrenaline and noradrenaline blocked food intake evoked by overnight fasting. Similarly, phenylephrine administration decreased hunger-induced food intake. These changes in food intake were accompanied by changes in other behaviors, such as increased immobility time and feeding duration. On the other hand, intra-DR administration of clonidine did not affect food-intake or associated behaviors. These results further support the hypothesis that in fed animals, increased adrenergic tonus in DR neurons inhibiting feeding, while in fasted rats the adrenergic tonus decreases and favors food intake. These data indicate a possible mechanism through which adrenergic input to the DRN contributes to neurobiology of feeding.

Predictors of Perioperative Vasoactive Drug Requirement During Retroperitoneal Adrenalectomy for Pheochromocytoma: A Retrospective Exploratory Study

The aim of the present study was to test a hypothesis that baseline systemic vascular resistance index (SVRI) assessed by method of transpulmonary thermodilution predicts perioperative requirement for vasoactive drugs. The primary outcomes were: (1) peak vasoactive-inotropic score (VIS) and (2) peak dose of hypotensive drugs at any stage of surgery. The main exposure variable was baseline SVRI. Hemodynamics were retrospectively assessed by transpulmonary thermodilution in 50 adults who had undergone posterior retroperitoneal surgery for pheochromocytoma. Univariate linear regression analysis showed predictive value of SVRI on VIS [regression coefficient, 95% CI; 0.024 (0.005, 0.4), p=0.015]. Other significant factors were the history of peak diastolic pressure, baseline MAP, baseline betablocker therapy, and history of coronary artery disease (CAD). After adjustment of SVRI for the history of CAD, its prognostic value became non-significant [0.018 (0.008, 0.03), p=0.063 and 29.6 (19, 40.2), p=0.007 for SVRI and history of CAD, respectively]. Requirements of vasodilators were predicted by baseline adrenergic activity [0.37 (0.005, 0.74), p=0.047]. In conclusion, baseline SVRI is associated with perioperative requirement of vasopressor drugs, but history of CAD is a stronger prognostic factor for vasopressor support. Perioperative requirement in vasodilators is associated with baseline adrenergic activity.

Severe diaphoresis and fever during alcohol withdrawal cause hypovolemic shock: case report

Background Several fatal medical complications have been associated with alcohol withdrawal, such as seizure, cardiac arrhythmia, and takotsubo cardiomyopathy. However, there have been no reports on hypovolemic shock during alcohol withdrawal, although two physical signs of alcohol withdrawal, i.e., diaphoresis and fever, can lead to hypovolemia and its medical consequences. Case presentation We describe a patient with alcohol use disorder who exhibited hypovolemic shock and its associated acute renal failure during alcohol withdrawal with severe diaphoresis and fever even though he had consumed almost the full amount of food he was offered. Given his excessive diaphoresis and fever that were related to alcohol withdrawal, his water intake was insufficient. Infusion with extracellular fluid resolved all these medical issues. Conclusions The increased adrenergic activity associated with alcohol withdrawal might substantially increase a patient’s water-intake requirement through diaphoresis and fever and may cause severe hypovolemia and its associated medical complications.

MEMBRANE-RECEPTOR COMPLEX DYSFUNCTION AS A NEW TARGET FOR THE NEUROTROPHIC THERAPY OF ISCHEMIC STROKE

The aim of the study was the β-adrenergic activity of peripheral blood erythrocyte membranes in the acute period of ischemic stroke (IS). Peripheral blood erythrocytes are the most informative biological tissue for studying many pathogenetic mechanisms, and the work of their membrane-receptor complex (MRC) can very well reflect the functional state of the whole organism, one of the most important criteria for assessing is the adrenergic activity of cytoplasmic membranes in the pathogenesis of IS. This study solves the problem of the finding of the features of changes in the adrenoceptors system in the acute period of IS in the dynamics of the treatment of humans cryopreserved cord blood serum (CCBS). The main scientific results: the obtained results indicate a reduced ability of adrenoceptors (ARs) on erythrocyte membranes to bind blockers due to the desensitisation effect, which is observed from the 1st day of the disease. In the onset of IS, there is a significant increase in the values of β-adrenergic activity of membranes (β-ARM) of erythrocytes in 2.4 times compared with the control. Maximum levels of the indicator (42.43±3.64 CU) are observed in patients with initially severe disease, which indicates significant stress of the sympathoadrenal system (SAS) in these patients. On the 10th day of the disease, there was a decrease in β-ARM relative to the values obtained during hospitalisation. Still, comparing the value of the indicator on the 10th day of IS in both groups, there was an apparent, more significant decrease in β-ARM in the 2nd group of patients, which additionally received CCBS. The use of CCBS contributes to a more pronounced degree of recovery in neurological functions (6.9%) and faster stabilisation of the structure of MRCs in erythrocytes in the form of reducing the values of β-ARM to 16.61±2.86 CU (p<0.05). The area of practical use of the research results: the results of the study can be used to diagnose and treat of the IS. An innovative technological product: A comprehensive approach to assess the β-ARM of peripheral blood erythrocytes in patients with IS by determining the degree of changes in osmotic resistance of erythrocytes (ORE) under the action of adrenergic drugs (AD) is informative and can be used to diagnose of IS. The use of neurotrophic factors is a potentially new method of treating this pathology. Scope of application of the innovative technological product: in the clinical practice of neurological departments for the treatment of patients with strokes

The effects of moderate alterations in adrenergic activity on acute appetite regulation in obese women: A randomised crossover trial

Background: Previous evidence has demonstrated that serum leptin is correlated with appetite in combination with, but not without, modest exercise. Aim: The present experiments investigated the effects of exogenous adrenaline and α/β adrenoceptor blockade in combination with moderate exercise on serum leptin concentrations, appetite/satiety sensations and subsequent food intake in obese women. Methods: A total of 10 obese women ((mean ± SEM), age: 50 (1.9) years, body mass index 36 (4.1) kg/m2, waist 104.8 (4.1) cm) participated in two separate, double-blind randomised experimental trials. Experiment 1: moderate exercise after α/β adrenergic blocker (labetalol, 100 mg orally) versus moderate exercise plus placebo; experiment 2: adrenaline infusion for 20 minutes versus saline infusion. Appetite/satiety and biochemistry were measured at baseline, pre- and immediately post-intervention, then 1 hour post-intervention (i.e., before dinner). Food intake was assessed via ad libitum buffet-style dinner. Results: No differences were found in appetite/satiety, subsequent food intake or serum leptin in any of the studies (experiment 1 or experiment 2). In experiment 1, blood glucose was higher ( p < 0.01) and plasma free fatty acids lower ( p = 0.04) versus placebo. In experiment 2, plasma free fatty acids ( p < 0.05) increased after adrenaline versus saline infusion. Conclusions: Neither inhibition of exercise-induced adrenergic activity by combined α/β adrenergic blockade nor moderate increases in adrenergic activity induced by intravenous adrenaline infusion affected acute appetite regulation.

BIOPHYSICAL MARKERS OF ISCHEMIC STROKE

An important and influential factor that directly affects the severity of ischemic stroke (IS) and determines its outcome is the functional state of the membrane-receptor complex (MRC) of cells. One of the most important criteria for assessing this parameter is the β‑adrenergic activity of cytoplasmic membranes (β‑ARM), which plays a leading role in the pathogenesis of IS. The article presents the results of a comprehensive study of the peculiarities of changes in the structural and functional characteristics of brain tissue and β‑adrenoceptors in the acute period of IS to optimize diagnosis. Measurement of changes in the osmotic resistance of erythrocytes (ORE) under the action of β‑blockers was determined by photoelectron colorimetry. The work was based on the materials of a comprehensive examination of 350 patients with the new-onset IS on the 1st, 10th and 21st day of the disease. The severity of the condition and the degree of neurological deficit were objectified using the stroke scale of the National Institutes of Health (NIHSS) with a score in the first hours of the disease, in the dynamics of treatment on the 10th and 21st day. All patients were divided into 2 clinical groups: 1st (n = 183) – patients in moderate severity condition (mean score on the NIHSS scale 11.74 ± 0.33); 2nd (n = 167) – patients in severe condition (mean score on the NIHSS scale 24.06 ± 0.29). As a result of the study, the indicators of β‑ARM of the control group were within normal limits (15.3 ± 4.4 SU), which corresponds to normal β‑ARM. In patients with moderate IS, the indicator exceeded the control values by 1.97 times, which is typical for the average degree of β‑ARM (21–40 SU), and in severe – 2.8 times and was characterized by a low degree of β‑ARM (> 41 SU). An unfavorable sign for the prognosis of the acute period of IS was represented by a further increase in the levels of β‑ARM in the dynamics, which was observed in clinically severe patients. Keywords adrenergic activity, ischemia, erythrocyte, receptor.

Chromogranin A in the Laboratory Diagnosis of Pheochromocytoma and Paraganglioma

This work discusses the clinical performance of chromogranin A (CGA), a commonly measured marker in neuroendocrine neoplasms, for the diagnosis of pheochromocytoma/ paraganglioma (PPGL). Plasma CGA (cut-off value 150 µg/L) was determined by an immunoradiometric assay. Free metanephrine (cut-off value 100 ng/L) and normetanephrine (cut-off value 170 ng/L) were determined by radioimmunoassay. Blood samples were collected from PPGL patients preoperatively, one week, six months, one year and two years after adrenal gland surgery. The control patients not diagnosed with PPGL suffered from adrenal problems or from MEN2 and thyroid carcinoma. The clinical sensitivity in the PPGL group of patients (n = 71) based on CGA is 90% and is below the clinical sensitivity determined by metanephrines (97%). The clinical specificity based on all plasma CGA values after surgery (n = 98) is 99% and is the same for metanephrines assays. The clinical specificity of CGA in the control group (n = 85) was 92% or 99% using metanephrines tests. We can conclude that plasma CGA can serve as an appropriate complement to metanephrines assays in laboratory diagnosis of PPGL patients. CGA is elevated in PPGLs, as well as in other neuroendocrine or non-neuroendocrine neoplasia and under clinical conditions increasing adrenergic activity.

Nondiabetic Endocrine Emergencies 2: Hypoparathyroidism, Hyperparathyroidism, Myxedema Coma, And Thyroid Storm

Acute emergent presentations of the thyroid and parathyroids are rarer occurrences in the emergency department but essential to diagnose and treat early in the course of illness. Disorders of the parathyroids are typically related to circulating calcium levels and the metabolic effects thereof, whereas thyroid deficiency or excess can lead to profound shock, coma, hypothermia, hyperthermia, and death. The diagnosis of parathyroid disease should be considered in patients presenting with signs and symptoms consistent with hyper- or hypocalcemia. Myxedema coma should be considered in any patient presenting with evidence of severe sepsis or shock, particularly when there is a history of hypothyroidism. Thyroid storm should be suspected in any patient with unexplained increased adrenergic activity, hyperpyrexia, or multiorgan failure. Empirical treatment must begin prior to definitive diagnosis in all cases. This review demonstrates how to recognize and manage acute presentations of hypo- and hyperparathyroidism, myxedema coma, and thyroid storm in the emergency setting. Patients with nondiabetic endocrine emergencies may present in extremis, and immediate stabilization, typically without confirmatory testing, is necessary. Early intervention is key in treating such presentations. This review contains 3 figures, 8 tables and 28 references Key words: disorders of the parathyroids, hyperparathyroidism, hypoparathyroidism, hypothyroidism, myxedema coma, thyroid storm, thyrotoxicosis