Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia.

PURPOSE: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. METHODS: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). RESULTS: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). CONCLUSIONS: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG.

The interferon in idiopathic inflammatory myopathies: Different signatures and new therapeutic perspectives. A literature review.

Idiopathic inflammatory myopathies (IIM), even though sharing common clinical manifestations, are characterized by diversified molecular pathogenetic mechanisms which may account for the partial inefficacy of currently used immunomodulatory drugs. In the last decades, the role of interferon (IFN) in IIM has been extensively elucidated thanks to genomic and proteomic studies which have assessed the molecular signature at the level of affected tissues or in peripheral blood across distinct IIM subtypes. A predominant type I IFN response has been shown in dermatomyositis (DM), being especially enhanced in anti-melanoma differentiation-associated gene 5 (MDA5)+ DM, while a type 2 IFN profile characterizes anti-synthetase syndrome (ASyS) and inclusion body myositis (IBM); conversely, a less robust IFN footprint has been defined for immune-mediated necrotizing myopathy (IMNM). Intracellular IFN signaling is mediated by the janus kinase/signal transducer and activator of transcription (JAK/STAT) through dedicated transmembrane receptors and specific cytoplasmic molecular combinations. These results may have therapeutic implications and led to evaluating the efficacy of new targeted drugs such as the recently introduced janus kinase inhibitors (JAKi), currently approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In this review we aim to summarize the most significant evidence of IFN role in IIM pathogenesis and to describe the current state of the art about the ongoing clinical trials on IFN-targeting drugs, with particular focus on JAKi.

Impact of the Italian Society of Anatomic Pathology and Diagnostic Cytology Classification of Thyroid Nodules in the Treatment of Indeterminate Follicular Lesions: Five-Year Results at a Single Center.

PURPOSE: Aim of the study was to assess the impact of the Italian Society of Anatomic Pathology and Diagnostic Cytology (SIAPEC) classification of 2014, on the treatment of indeterminate thyroid lesions (TIR3). METHODS: We retrospectively analyzed patients undergoing thyroid surgery for TIR3 lesions between 2013 and 2018, at the General Surgery Department of Trieste University Hospital. According to the SIAPEC classification, patients were divided into TIR3A and TIR3B groups. All patients treated before 2014 underwent surgical treatment, and surgical specimens were retrospectively classified after revision of fine-needle aspiration cytology. Starting 2014, TIR3A patients were treated only when symptomatic (i.e., coexistent bilateral thyroid goiter or growing TIR3A nodules), whereas TIR3B patients always received surgical treatment. Hemithyroidectomy (HT) was the procedure of choice. Total thyroidectomy (TT) was performed in case of concurrent bilateral goiter, autoimmune thyroid disease, and/or presence of BRAF and/or RAS mutation. Lastly, we analyzed the malignancy rate in the two groups. RESULTS: 29 TIR3A and 90 TIR3B patients were included in the study. HT was performed in 10 TIR3A patients and 37 TIR3B patients, respectively, with need for reoperation in 4 TIR3B (10.8%) patients due to histological findings of follicular thyroid carcinoma >1 cm. The malignancy rates were 17.2% in TIR3A and 31.1% in TIR3B, (p = 0.16). Predictability of malignancy was almost 89% in BRAF mutation and just 47% in RAS mutation. CONCLUSIONS: The new SIAPEC classification in association with biomolecular markers has improved diagnostic accuracy, patient selection, and clinical management of TIR3 lesions.

Ambulatory blood pressure monitoring-derived short-term blood pressure variability in primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism is associated with a cluster of cardiovascular manifestations, including hypertension, leading to increased cardiovascular risk. PURPOSE: The aim of our study was to investigate the ambulatory blood pressure monitoring-derived short-term blood pressure variability in patients with primary hyperparathyroidism, in comparison with patients with essential hypertension and normotensive controls. METHODS: Twenty-five patients with primary hyperparathyroidism (7 normotensive,18 hypertensive) underwent ambulatory blood pressure monitoring at diagnosis, and fifteen out of them were re-evaluated after parathyroidectomy. Short-term-blood pressure variability was derived from ambulatory blood pressure monitoring and calculated as the following: 1) Standard Deviation of 24-h, day-time and night-time-BP; 2) the average of day-time and night-time-Standard Deviation, weighted for the duration of the day and night periods (24-h "weighted" Standard Deviation of BP); 3) average real variability, i.e., the average of the absolute differences between all consecutive BP measurements. RESULTS: Baseline data of normotensive and essential hypertension patients were matched for age, sex, BMI and 24-h ambulatory blood pressure monitoring values with normotensive and hypertensive-primary hyperparathyroidism patients, respectively. Normotensive-primary hyperparathyroidism patients showed a 24-h weighted Standard Deviation (P < 0.01) and average real variability (P < 0.05) of systolic blood pressure higher than that of 12 normotensive controls. 24-h average real variability of systolic BP, as well as serum calcium and parathyroid hormone levels, were reduced in operated patients (P < 0.001). A positive correlation of serum calcium and parathyroid hormone with 24-h-average real variability of systolic BP was observed in the entire primary hyperparathyroidism patients group (P = 0.04, P = 0.02; respectively). CONCLUSION: Systolic blood pressure variability is increased in normotensive patients with primary hyperparathyroidism and is reduced by parathyroidectomy, and may potentially represent an additional cardiovascular risk factor in this disease.

Partial thyroidectomy for papillary thyroid microcarcinoma: Is completion total thyroidectomy indicated?

AIM: Papillary thyroid microcarcinoma (PTMC) is increasing in incidence. Despite its excellent clinical outcomes, there is still debate regarding which surgical approach is more appropriate for PTMC, procedures including hemithyroidectomy (HT), total thyroidectomy (TT), and completion thyroidectomy (CT) after initial HT and histopathologic examination confirming a PTMC. Here we report our experience in the surgical management of PTMC. METHODS: We conducted a retrospective evaluation of all patients who received a postoperative diagnosis of PTMC between January 2001 and January 2016. Every patient was divided according to the type of surgery performed (TT or HT alone). Follow-up consisted of regular clinical and neck ultrasonographic examination. Clinical and histopathological parameters (e.g. age, sex, lesion size, histological features, multifocality, lymph node metastases, BRAF status when available) as well as clinical outcomes (e.g. complications rates, recurrence, overall survival) were analyzed. RESULTS: Group A consisted of 86 patients who underwent TT, whereas Group encompassed 19 patients who underwent HT. Mean follow-up period was 58.5 months. In Group A, one patient (1.2%) experienced recurrence in cervical lymph nodes with need for reoperation. In Group B, eight patients (42%) underwent completion thyroidectomy after histopathological examination confirming PTMC, while one patient (5.3%) developed PTMC in the contralateral lobe with need for reoperation at 2 years after initial surgery. Multifocality was found in 19 patients in Group A (22%). Of these, 14 presented bilobar involvement, whereas in 3 cases multifocality involved only one lobe. 1 patient in Group B (5.3%) presented with unilateral multifocal PTMC (p = 0.11). CONCLUSIONS: Low-risk patients with PTMC may benefit from a more conservative treatment, e.g. HT followed by close follow-up. However, appropriate selection of patients based on risk stratification is the key to differentiate therapy options and gain better results.

Rationality in prophylactic central neck dissection in clinically node-negative (cN0) papillary thyroid carcinoma: Is there anything more to say? A decade experience in a single-center.

AIM: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Despite its extremely favorable prognosis, cervical lymph node metastases are a common feature of PTC and a known independent risk factor for local recurrence. However, the role of prophylactic central neck dissection (PCND) remains a matter of debate in patients with clinically node-negative (cN0) PTC. To better clarify the current role of PCND in the surgical treatment of PTC, evaluating advantages and disadvantages of PCND and outcome of cN0 PTC patients who have been treated with either total thyroidectomy alone or in combination with PCND. A review of recent literature data is performed. METHODS: Between January 2000 and December 2015, 186 consecutive patients with cN0 PTC were identified to be included in the present study. 74 of these underwent total thyroidectomy associated with PCND, while 112 patients underwent total thyroidectomy alone. The epidemiological and clinical-pathological data of all patients included were collected at diagnosis and during follow-up. RESULTS: Overall complication rate was significantly higher in the group of patients undergoing PCND (39.2% vs. 17.8%, p = 0.0006). To be specific, they presented a considerably increased risk of temporary recurrent laryngeal nerve injury (p = 0.009) and of permanent hypothyroidism (p = 0.016). Overall survival and recurrence rates did not differ between those undergoing PCND and those undergoing total thyroidectomy alone (p = 1.000 and p = 0.715, respectively). CONCLUSIONS: The results of the present study do not support the routine use of PCND in the treatment of cN0 PTC patients.

Radiofrequency ablation for benign thyroid nodules.

Benign thyroid nodules are an extremely common occurrence. Radiofrequency ablation (RFA) is gaining ground as an effective technique for their treatment, in case they become symptomatic. Here we review what are the current indications to RFA, its outcomes in terms of efficacy, tolerability, and cost, and also how it compares to the other conventional and experimental treatment modalities for benign thyroid nodules. Moreover, we will also address the issue of treating with this technique patients with cardiac pacemakers (PM) or implantable cardioverter-defibrillators (ICD), as it is a rather frequent occurrence that has never been addressed in detail in the literature.

Coexistence of chronic lymphocytic thyroiditis and papillary thyroid carcinoma. Impact on presentation, management, and outcome.

BACKGROUND: The association between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) has been investigated for several years from different perspectives. In spite of that, there were only few attempts to design a common frame of references to understand the complex mutual interactions between the various pathways of inflammatory response and of thyroid tumor induction and progression. This study compares two independent groups of patients aiming to determine the frequency and the prognostic significance of CLT in patients with PTC. MATERIAL AND METHODS: From January 2005 to September 2013, we conducted a retrospective study on 160 patients with PTC who underwent thyroidectomy. CLT was diagnosed histopathologically. Age, sex, tumor features (dimensions, angioinvasion, capsular infiltration, mono/multifocality and lymph node metastases) pathologic findings and outcome were considered. Mean follow-up (metastasis, completeness-of-resection, serum thyroglobulin levels, tumor recurrence) period was 61 months (ranged from 18 to 132 months). A p < 0.05 was considered statistically significant. RESULTS: Patients were divided in 2 groups. In group A there were 90 patients affected by PTC alone, and in group B there were 70 patients affected with PTC associated with CLT. Our data showed that the presence of CLT correlate with a lower grade of PTC (p < 0.05). Considering the sex of the patients there were a statistically significant correlation (p < 0.02) and the presence of CLT associated with PTC was most representative in female patients. CONCLUSIONS: The presence of CLT in patients with PTC correlated with a lower grade of PTC, but it does not affect the overall survival of papillary thyroid cancers.

Cross-sex hormone therapy for gender dysphoria.

PURPOSE: Gender identity is the sense one has of being male or female. Gender dysphoria (GD) refers to the distress caused by the incongruence between gender identity and biological sex in gender-nonconforming individuals. Cross-sex hormone therapy (CHT) aims at easing GD, improving well-being, and quality of life of gender-nonconforming individuals. This can be achieved by inducing and maintaining the desired-sex characteristics in accordance with the specific aspirations and expectations of each individual. Nevertheless, CHT can be associated with potentially serious long-term complications. METHODS: Here, we review when, how, and how long to prescribe CHT to adult transsexuals as well as what to expect and monitor once it has been initiated. RESULTS: In recent years, transsexualism has become more and more recognized and depathologized. To manage GD, National and International Standards of Care have been established. Nevertheless, the needs of transgender patients can still be ignored or dismissed. Moreover, some questions remain unanswered because of the lack of specific retrospective or prospective studies on CHT. CONCLUSION: Education and culturally sensitive training must be supplied to healthcare professionals to overcome the existing issues on GD management and change the perspectives of transsexual people.

Ambulatory arterial stiffness indices and non-alcoholic fatty liver disease in essential hypertension.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) has been found to be strongly related to an increased arterial stiffness in patients with essential hypertension, suggesting a pathophysiologic link between major cardiovascular and metabolic abnormalities associated with liver steatosis and the functional and structural alterations of the arterial wall. The aim of our study was to investigate, in a group of essential hypertensive patients without additional cardiovascular risk factors, the relationship between NAFLD and arterial stiffness. METHODS AND RESULTS: Sixty-eight consecutive patients with essential hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM) and were separated according to the presence (n = 40) or absence (n = 28) of NAFLD at liver ultrasonography. The Ambulatory Arterial Stiffness Index (AASI) and Symmetric AASI (Sym-AASI) were derived from ABPM tracings. Patients with diabetes, obesity, hyperlipidaemia or other risk factors for cardiovascular or liver disease were excluded. Hypertensive patients were compared with a normotensive control group.The two hypertensive groups had comparable age, sex distribution and clinic/ABPM blood pressure levels. In hypertensive patients with NAFLD, body mass index, fasting glucose, insulin, homeostasis model of assessment of insulin resistance index and triglyceride levels were higher, whereas plasma adiponectin was lower than in patients without NAFLD. In hypertensive patients, AASI and Sym-AASI were higher (P < 0.001) than in normotensive subjects, but both indices of vascular stiffness were comparable in patients with and without NAFLD. CONCLUSIONS: In essential hypertensive patients without additional cardiovascular risk factors, NAFLD is associated with insulin resistance but not with increased arterial stiffness.

Aldosterone does not modify gene expression in human endothelial cells.

The toxic effects of aldosterone on the vasculature, and in particular on the endothelial layer, have been proposed as having an important role in the cardiovascular pathology observed in mineralocorticoid-excess states. In order to characterize the genomic molecular mechanisms driving the aldosterone-induced endothelial dysfunction, we performed an expression microarray on transcripts obtained from both human umbilical vein endothelial cells and human coronary artery endothelial cells stimulated with 10 - 7 M aldosterone for 18 h. The results were then subjected to qRT-PCR confirmation, also including a group of genes known to be involved in the control of the endothelial function or previously described as regulated by aldosterone. The state of activation of the mineralocorticoid receptor was investigated by means of a luciferase-reporter assay using a plasmid encoding a mineralocorticoid and glucocorticoid-sensitive promoter. Aldosterone did not determine any significant change in gene expression in either cell type both in the microarray and in the qRT-PCR analysis. The luciferase-reporter assay showed no activation of the mineralocorticoid receptor following aldosterone stimulation. The status of nonfunctionality of the mineralocorticoid receptor expressed in cultured human umbilical and coronary artery endothelial cells does not allow aldosterone to modify gene expression and provides evidence against either a beneficial or harmful genomic effect of aldosterone on healthy endothelial cells.

Innate immunity, through late complement components activation, contributes to the development of early vascular inflammation and morphologic alterations in experimental diabetes.

OBJECTIVE: To verify if innate immunity, and namely the assembly of terminal complement complex (TCC) could be involved in the development of early diabetic vascular damage. METHODS AND RESULTS: At first in 2 groups of diabetic or non-diabetic Wistar rats the occurrence of basal or stimulated stable adherence to the endothelial layer and extravasation of circulating fluorescently-labelled leukocytes was assessed by using an in vivo videomicroscopy technique. In a second part of the study, the development of vascular damage in short term diabetes was studied in the genetically C6 deficient rats of the PVG strain, and compared with those observed in the wild-type C6 sufficient animals. Here, the analysis of mesentery vascular expression of mRNA for vascular cell adhesion molecule (VCAM)-1, transforming growth factor-ß (TGF-ß), connective tissue growth factor (CTGF), and platelet-derived growth factor (PDGF), the evaluation of intravascular protein levels of VCAM-1, TGF-ß, CTGF, proliferative cell nuclear antigen (PCNA), as well as the assessment of structural changes and Complement components deposition at the mesentery arterial vascular wall were also performed. CONCLUSIONS: Leukocyte trafficking, mesentery arteries hypertrophy, extracellular matrix deposition, local vascular gene and protein expression of VCAM-1, TGF-ß, CTGF and PCNA, as well as PGDF gene expression were all increased by short term diabetes, but all significantly reduced in the C6 deficient diabetic animals, thus suggesting an active role for TCC in the development of vascular inflammation in the early phases of experimental diabetes.

Non-alcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in essential hypertension.

BACKGROUND AND AIM: Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found. We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in 86 never-treated essential hypertensive patients subdivided in two subgroups according to the presence (n = 48) or absence (n = 38) of NAFLD at ultrasonography. METHODS AND RESULTS: The two groups were similar as to sex, age and blood pressure levels. No patient had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease. Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), aspartate aminotransferase and alanine aminotransferase were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD, and were associated with NAFLD at univariate analysis. Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (62.5 vs 21.1%, P < 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (P = 0.040) and HOMA-IR (P = 0.012) remained independently associated with NAFLD at backward multivariate analysis. CONCLUSIONS: Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

Orally administered microencapsulated lysozyme downregulates serum AGE and reduces the severity of early-stage diabetic nephropathy.

AIM: Diabetic nephropathy is the leading cause of end-stage kidney disease in developed countries and is related to chronic hyperglycaemia. The increased production and tissue deposition of advanced glycation end products (AGE) are known to play a major role in the pathogenesis of diabetic kidney damage. This study was undertaken to determine if lysozyme (LZ), microencapsulated in orally administrable chitosan-coated alginate microspheres (MS), is effective against the early changes seen in the initial stages of diabetic nephropathy. METHODS: LZ-containing MS (MSLZ) and an equivalent dose (equidose) of nonencapsulated LZ were given as oral treatments. LZ was administered to Wistar rats for seven weeks after diabetes induction with streptozotocin. RESULTS: The results showed that microencapsulated LZ treatment significantly reduced the concentration of serum AGE in the circulation and their deposition in the kidneys. Likewise, MSLZ significantly prevented the development of microalbuminuria compared with untreated diabetic rats. Furthermore, MSLZ significantly prevented the development of glomerular and renal hypertrophy as well as overexpression of AGE receptors (RAGE). An equidose of free LZ had little or no effect whatsoever. CONCLUSION: Our study supports a relationship between serum AGE and nephropathy in diabetes, and suggests that orally administered microencapsulated LZ can exert kidney-protective activity in a diabetic animal model.

Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor.

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (P(alb)) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg. kg(-1). day(-1). Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of P(alb) in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced P(alb) significantly in concentration ranges from 10(-6) to 10(-14) mol/l compared with results in control glomeruli. The effect on P(alb) may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the P(alb) defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.

Mechanics of the carotid artery wall and baroreflex sensitivity after acute ethanol administration in young healthy volunteers.

The effects of ethanol administered orally (300 mg/kg in 250 ml of water) or intravenously (7.5 mg.min(-1).kg(-1) in 250 ml of saline over 40 min) on common carotid haemodynamics, wall mechanics and baroreflex sensitivity were compared with the effects of the intravenous infusion of 250 ml of saline. Ethanol or saline was administered to 10 healthy volunteers after 30 min of supine rest, and measurements were obtained 40 min (median; range 34-46 min) after administration. After ethanol administration, the plasma alcohol level rose from 0 to 0.3+/-0.07 g/l. Mean arterial blood pressure had risen slightly at 20 min, but was normalized by 40 min, the time at which the haemodynamic study was performed. Heart rate decreased after infusion of either saline or alcohol, but was unchanged after oral ethanol administration. Both oral and intravenous ethanol administration were associated with significant decreases in baroreflex sensitivity, carotid shear stress and blood velocity, compared with resting values, while the mean carotid artery diameter was increased, and blood viscosity and mean blood flow were unchanged. No changes were observed in these parameters after saline administration. Ethanol, administered either intravenously or orally, increased the stiffness of the carotid artery and decreased the pulsatility (systo-diastolic changes) of its diameter. A direct, statistically significant correlation was found between the decrease in shear stress and the decrease in baroreflex heart rate control sensitivity after both modes of alcohol administration, while no such correlation was found between the increase in the Peterson elastic modulus and the decrease in carotid diameter pulsatility on the one hand or the decrease in baroreflex sensitivity on the other. In conclusion, reduced shear stress associated with vasodilatation of the carotid artery wall may contribute to the decrease in baroreflex sensitivity observed after acute ethanol administration.

Haemoconcentration, shear-stress increase and carotid artery diameter regulation after furosemide administration in older hypertensives.

The aim of the present study was to determine whether changes of carotid wall shear stress induced by changes in blood viscosity after diuretic administration cause carotid arterial dilatation in elderly hypertensives, as reported in the cat. Arterial wall shear rate (ultrasound technique, profilmeter FRP III), the systo-diastolic diameter (echotracking technique) and the mean blood flow velocity and volume of the common carotid artery, the blood viscosity (rotational viscometer) and the finger arterial blood pressure (Finapress Ohmeda) were measured in 12 young volunteers (aged 25+/-2 years) and in 12 elderly hypertensives (aged 80+/-4 years) treated with short-acting calcium antagonists up to 24h before the study, both at baseline and after intravenous furosemide infusion (0.5mg/min), when the haematocrit had increased by at least two percentage points. After furosemide administration the mean arterial blood pressure decreased and blood viscosity and carotid systolic shear stress increased in both groups. However, common carotid artery diameter increased only in the young controls but not in the elderly hypertensives. These data show that an increase in carotid shear stress caused by haemoconcentration induces carotid vasodilatation only in young healthy subjects, and not in elderly hypertensives. This effect may be related to impaired endothelium function and/or arterial wall mechanics.

Effects of prolonged high-altitude exposure on peripheral adrenergic receptors in young healthy volunteers.

The regulation of adrenergic receptors during hypoxia is complex, and the results of published reports have not been consistent. In the present study blood cell adrenoceptor characteristics at sea level (SL) before and after prolonged exposure to high altitude (HA) were measured in seven trained young male lowlanders. Sympathoadrenal activity and clinical haemodynamic parameters were also evaluated before departure (SLB), after 1 week (HA1) and 4 weeks (HA4) at HA and 1 week after return to sea level (SLA). As compared to pre-departure sea level values, urinary norepinephrine excretion increased significantly during altitude exposure [SLB: 10.26 (3.04) microg x 3 h(-1); HA1: 23.2 (4.19) microg x 3 h(-1); HA4: 20.3 (8.68) microg x 3 h(-1)] and fell to pre-ascent values 1 week after return to sea level [SLA: 9 (2.91) microg x 3 h(-1)]. In contrast, mean urinary epinephrine levels did not increase over time at HA. Both systolic and diastolic blood pressures, as well as heart rate, were increased during HA exposure. The circadian blood pressure and heart rate rhythms were preserved during all phases of altitude exposure. Mean maximal binding (Bmax) of the alpha2-adrenoceptor antagonist [3H]rauwolscine to platelet membranes was significantly reduced (P < 0.001) after exposure to chronic hypoxia [SLB: 172.6 (48.5) fmol x mg(-1) protein versus SLA: 136.8 (56.1) fmol x mg(-1) protein] without change in the dissociation constant (K(D)). Neither the lymphomonocyte beta2-adrenoceptor Bmax [SLB: 38.5 (13.6) fmol x mg(-1) protein, versus SLA: 32.4 (12.1) fmol mg(-1) protein] nor the K(D) for [3H]dihydroalprenolol was affected by chronic hypoxia. Cyclic AMP (adenosine 3',5'-cyclic monophoshate) generation in lymphomonocytes by maximal isoproterenol stimulation was not modified after prolonged HA exposure. In conclusion, the down-regulation of alpha2-adrenoceptors appears to be an important component of the adrenergic system response to HA exposure.