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Although deep frying is widely used, little is known about the effect of frying different meats on the frying oil. The aims of this study were to investigate whether the pork type influences the characteristics of the frying oil, to compare any effects with those of French fries, and to research whether the use of thermally damaged oil differentially affects those products. French fries and pork from pigs reared outdoors on acorns and grass (outdoor) or indoors on a concentrated feed (indoor) were deep-fried in either raw or previously heated olive oil. The type of product affected most color parameters, K 268 and the α-tocopherol content of the oil. The frying of outdoor pork hardly affected the α-tocopherol content, whereas the frying of indoor pork and especially French fries caused a significant decrease. This suggests that the meat type should be considered when setting the frying lifespan of olive oil. Regarding the fried products, L* , moisture (only French fries) and the malondialdehyde (MDA) content (only indoor pork) were the only parameters affected by the previous oil damage. The outdoor pork was less susceptible to oxidation than the indoor pork when the oil was severely damaged. Therefore, pig outdoor-based systems based on antioxidant-rich diets might be convenient to maintain oxidation at the lowest level after frying.

Aim: The aim of the present study was to review in VigiBase the reports of serious hepatic disorders associated with the use of ivermectin for COVID-19 in adults., Background: In the face of the global health emergency caused by SARS-CoV-2, ivermectin, among other drugs, has been repurposed in some Latin American countries to treat COVID-19. Studies are needed on the safety of ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all individual case safety reports (ICSRs) from more than 130 countries., Methods: We extracted the ICSRs of men or women aged ≥ 18 years and dated between 1 January 2020 and 7 March 2021 which included an association with the use of ivermectin., Results: Of 1393 ICSRs associated with ivermectin, 60 (4.3%) were registered as "serious." Ivermectin had been used for COVID-19 in 25 of those cases. Among the latter, 6 experienced hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and/or aspartate aminotransferase levels, abnormal liver function tests)., Conclusion: The safety of the use of ivermectin should be studied more exhaustively, especially as regards the possibility of hepatic disorders developing when the drug is used for COVID-19., Competing Interests: The authors declare no conflict of interest.

The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale-mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19-ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira . Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09-7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33-8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Moreira-Rosário, Marques, Pinheiro, Araújo, Ribeiro, Rocha, Mota, Pestana, Ribeiro, Pereira, de Sousa, Pereira-Leal, de Sousa, Morais, Teixeira, Rocha, Silvestre, Príncipe, Gatta, Amado, Santos, Maltez, Boquinhas, de Sousa, Germano, Sarmento, Granja, Póvoa, Faria and Calhau.)

Background: Anti-hypertensive medications may reduce the incidence of cognitive disorders. This may be due to reasons beyond their pure hypotensive effect. This study aimed to systematically review the association between the use of Angiotensin-Receptor Blockers (ARBs) and the incidence of Alzheimer's disease (AD)., Methods: We systematically searched studies reporting the association between ARB use and the incidence of AD., Results: Ten studies (1 RCT, 2 case-control and 7 cohort studies) met the inclusion criteria. When all observational studies (9) were analyzed, ARB use was associated with a reduced risk of incident AD (HR 0.72, 95% CI: 0.58-0.88, p<0.001). In the only RCT, decrease in the incidence of AD was also significant (HR= 0.31, 95% CI: 0.14-0.68)., Conclusion: ARB use may reduce the risk of incident AD. This association does not imply causation and further research is required to clarify potential mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: There is increasing scientific interest in the possible association between hypovitaminosis D and the risk of SARS-CoV-2 infection severity and/or mortality., Objective: To conduct a metanalysis of the association between 25-hydroxyvitamin D (25(OH)D) concentration and SARS-CoV-2 infection severity or mortality., Material and Methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for studies published between December 2019 and December 2020. Effect statistics were pooled using random effects models. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Targeted outcomes: mortality and severity proportions in COVID-19 patients with 25(OH)D deficiency, defined as serum 25(OH)D < 50 nmol/L., Results: In the 23 studies included (n = 2692), the mean age was 60.8 (SD ± 15.9) years and 53.8% were men. Results suggested that vitamin 25(OH)D deficiency was associated with increased risk of severe SARS-CoV-2 disease (RR 2.00; 95% CI 1.47-2.71, 17 studies) and mortality (RR 2.45; 95% CI 1.24-4.84, 13 studies). Only 7/23 studies reported C-reactive protein values, all of which were > 10 mg/L. Conclusions 25(OH)D deficiency seems associated with increased SARS-CoV-2 infection severity and mortality. However, findings do not imply causality, and randomized controlled trials are required, and new studies should be designed to determine if decreased 25(OH)D is an epiphenomenon or consequence of the inflammatory process associated with severe forms of SARS-CoV-2. Meanwhile, the concentration of 25(OH)D could be considered as a negative acute phase reactant and a poor prognosis in COVID-19 infection.

Introduction: The need for parathyroidectomy to treat asymptomatic patients with primary hyperparathyroidism is controversial. The aim of this study was to assess the impact of parathyroidectomy vs. surveillance on skeletal outcomes such as bone mineral density (BMD) and incident fractures., Methods: This was a retrospective cohort study including 170 patients (112 treated with surgery and 58 subject to active surveillance) between 1991 and 2014. Changes in BMD in lumbar spine, femoral neck, total hip, and radius, and incidence of fractures, were monitored for 2-6 years., Results: Patients treated with surgery had BMD gains at 2years of 4.37%, as compared to 1.59% in non-operated patients (p<0.05) in the lumbar spine, 3.90% vs. 0.19% (p<0.05) in the femoral neck, and 2.70% vs. 0.14% (p<0.05) in total hip. Gain in BMD in the lumbar spine and femoral neck remained significant in operated patients at 4 and 6 years. No improvement was seen in the radius in operated patients. No significant difference was seen in fracture occurrence between operated and non-operated patients., Conclusion: Patients with primary hyperparathyroidism treated with surgery experience greater BMD gains than non-operated patients, especially in the lumbar spine and femoral neck. The risk of fracture does not decrease in the group of operated patients., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Major bleeding is a serious complication of acute coronary syndrome (ACS) and is associated with a worse prognosis. The CRUSADE bleeding score is used to stratify the risk of major bleeding in ACS., Objective: To assess the predictive ability of the CRUSADE score in a contemporary ACS population., Methods: In a single-center retrospective study of 2818 patients admitted with ACS, the CRUSADE score was calculated for each patient and its discrimination and goodness of fit were assessed by the area under the receiver operating characteristic curve (AUC) and by the Hosmer-Lemeshow test, respectively. Predictors of in-hospital major bleeding (IHMB) were determined., Results: The IHMB rate was 1.8%, significantly lower than predicted by the CRUSADE score (7.1%, p<0.001). The incidence of IHMB was 0.5% in the very low risk category (rate predicted by the score 3.1%), 1.5% in the low risk category (5.5%), 1.6% in the moderate risk category (8.6%), 5.5% in the high risk category (11.9%), and 4.4% in the very high risk category (19.5%). The predictive ability of the CRUSADE score for IHMB was only moderate (AUC 0.73). The in-hospital mortality rate was 4.0%. Advanced age (p=0.027), femoral vascular access (p=0.004), higher heart rate (p=0.047) and ticagrelor use (p=0.027) were independent predictors of IHMB., Conclusions: The CRUSADE score, although presenting some discriminatory power, significantly overestimated the IHMB rate, especially in patients at higher risk. These results question whether the CRUSADE score should continue to be used in the stratification of ACS., (Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Anxiety disorders are one of the most common mental health concerns with a major contribution to the global burden of disease. When not treated, anxiety can be aggravated to more serious and complicated health problems. Pharmacology and psychotherapy stand for the conventional treatment for anxiety disorders but these present limited efficacy, especially in the case of chronic anxiety, with high relapse rates and often causing adverse side effects. Clinical research studies render acupuncture as a valid treatment therapy for anxiety disorders without significant adverse effects. The objective of this paper is to review the literature on the effectiveness of acupuncture and electroacupuncture for the treatment of patients with anxiety disorders in order to find strong scientific evidence for its regular practice in Western culture. The systematic review of the clinical research was focused on published clinical trials (controlled, randomized and non-randomized) regarding the treatment of anxiety with acupuncture. Only clinical trials where anxiety was treated as the therapeutic target, and not as a secondary measurement or being associated with other health condition or disease, were considered. Two authors extracted the data independently and exclusion and inclusion criteria were set. The search rendered 1135 papers addressing anxiety as a primary therapeutic target. After review, 13 papers were identified to match exclusion and inclusion criteria and were selected for this analysis. Methodology, design, and quality of the research were highly variable and are discussed and compared. Overall, there is good scientific evidence encouraging acupuncture therapy to treat anxiety disorders as it yields effective outcomes, with fewer side effects than conventional treatment. More research in this area is however needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Anxiety disorders are a current public health issue, as an estimated 16.5% of the Portuguese population suffers from this condition. The goal of this descriptive study was to analyze the efficiency of the treatment of integrative medicine (acupuncture and therapeutic massage) to reduce anxiety disorders and to describe the sociodemographic characteristics of Integrative Medicine Institute (IMI) patients. To this end, a documental analysis from the data base of the clinical reports of IMI was performed, with the approval of the Ethics Committee of the Health Sciences Research Unit with informed consents being signed by all patients. Between January and August 2017, 259 IMI patients were treated. Of these, 30,5% had been diagnosed with an anxiety disorder. Ten sessions of Integrative Medicine (IM) using acupuncture techniques combined with therapeutic massage were applied. Each session consisted of an initial treatment of acupuncture for 30 min, followed by a therapeutic massage for another 30 min. Before starting all 10 treatments, anxiety levels were measured by a self-perception 5 points scale. Anxiety levels were also assessed at the end of the 5th and the 10th treatment. It was found that 75.29% of the patients looking for IM were female and 34.4% were professionals working in intellectual and scientific activities. Patients taking anxiolytic medication presented higher levels of anxiety in comparison with non-medicated ones (p = 0.000). After a maximum of ten treatments (acupuncture combined with massage), the levels of anxiety were reduced (98.39% after five sessions). Women at their tenth treatment reached lower anxiety levels than those of men. The therapies used are proved to be efficient and can be used as a complementary care to treat and relief the symptoms of anxiety disorders. This research is the basis for designing a future randomized control trial study of acupuncture efficiency in the treatment of anxiety disorders., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: CKD-EPIcr (Chronic Kidney Disease Epidemiology Collaboration creatinine) and BIS1 (Berlin Initiative Study) are two serum creatinine-based formulae for the estimation of glomerular filtration rate (GFR). However, their comparative accuracy in older people has not been well established. Our aim was to conduct a systematic comparative study of the accuracy of estimation of GFR in older people with these two formulae., Methods: We conducted a systematic search in Pubmed, EMBASE and Central databases on the validity of the CKD-EPIcr and BIS1 formulae in people aged 60 or more years. The search ranged from 2009 and 2012 for CKD-EPIcr and BIS1, respectively, until May 2017. The validity criterion for comparing the formulae was to have a P30 accuracy level equal to or greater than 80%., Results: Of 1295 identified studies, 16 met our inclusion criteria. Out of 16 studies reporting the accuracy of the CKD-EPIcr formula, only 5 (31.3%) had P30 scores ≥80% (mean P30 was 77.1 ± 7.711 range 55.5-91.7), and out of 9 studies on accuracy using the BIS1 formula, 6 (66.7%) were ≥80% (mean P30 was 83.88 ± 9.37, range 67.0-95.8)., Conclusion: Our results suggest that for the estimation of the GFR in older people, BIS1 formula may be more accurate than CKD-EPIcr., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The receptor of parathyroid hormone and parathyroid hormone-related-protein (PTH/PTHrp) is located in the cell membrane of target tissues - kidney and osteoblasts. It is a G protein-coupled-receptor whose G s α subunit is encoded by the GNAS gene. Our aim was to study whether the single nucleotide polymorphism (SNP) T393C of the GNAS gene is associated with renal stones, bone mineral density (BMD), or bone remodelling markers in primary hyperparathyroidism (PHPT)., Methods: An analysis was made of clinical and biochemical parameters and densitometric values in three areas and their relationship with the T393C SNP of the GNAS gene in 261 patients with primary hyperparathyroidism and in 328 healthy controls. Genotyping was performed using the Custom Taqman ® SNP Genotyping assay., Results: The genotype frequencies of GNAS T/C 393 were similar in the control and PHPT groups. No association was found between genotypes and clinical expression of PHPT (renal stones and bone fractures). A nonstatistically significant trend was seen to lower BMD in the lumbar spine, femoral neck, and total hip in both PHPT and control C homozygote subjects., Conclusion: Genetic susceptibility to PHPT related to the GNAS T393C polymorphism or a major influence in its development and clinical expression were found. A C allele-related susceptibility to lower BMD in trabecular bone in both PHPT and control subjects is not sufficient to suggest a more severe clinical expression of PHPT. This trend may be considered as a basis for further studies with larger sample sizes and complementary functional evaluation., (Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cardiogenic shock is characterized by a decrease in myocardial contractility, and presents a high mortality rate. Inotropic and vasopressor agents have been recommended and used for several years in the treatment of patients in shock, but they remain controversial. Despite its beneficial effect on myocardial contractility, the side effects of inotropic therapy (arrhythmias and increased myocardial oxygen consumption) may be associated with increased mortality. The pharmacodynamics of different inotropic agents suggest benefits in specific situations, but these differences have not been reflected in reduced mortality in most studies, making it difficult to formulate recommendations. This review integrates data from different studies on the use of inotropes and vasopressors in patients with cardiogenic shock, proposing a therapeutic scheme for the pharmacological treatment of patients in cardiogenic shock according to the patient's hemodynamic profile., (Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Anomalous aortic origin of coronary arteries (AAOCA) is one of the most frequent causes of cardiovascular sudden death among the young population. We aimed to determine the prevalence and anatomic characteristics of AAOCA in a population referred to computed tomography angiography (CTA) and to describe the clinical prognosis of these findings at middle term follow-up. From a total of 3539 CTA, 53 were found to have AAOCA. This population was compared to an age and gender matched control group (n = 106) from the same CTA list. A telephone follow-up to determine cardiac events was conducted, with a mean follow-up of 45.9 ± 28.2 months. Prevalence of AAOCA was 1.5 %. The most common AAOCA was an origin of the right coronary artery (RCA) from the left coronary sinus, followed by an origin of the left circumflex artery (LCX) arising from the right coronary sinus. All patients with an anomalous origin of the RCA had an interarterial course. Four additional patients were found to have an interarterial course: 1 with an anomalous origin of LCX and 3 with an anomalous origin of the left main coronary artery (LMCA). At follow-up there were 33 (21.2 %) cardiac events, 9 (17.6 %) on the AAOCA group and 24 (22.9 %) on the control group (p = 0.46). Cardiac events and cardiovascular deaths were not related to any particular AAOCA or to interarterial courses. Among an adult population referred to CTA, AAOCA were not related with worse middle term prognosis when compared to an age- and gender- matched population.

Aim: To investigate the plasma levels of betatrophin in patients with cirrhosis., Methods: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic, or histological criteria were included. The severity of cirrhosis was classified according to Pugh's modification of Child's classification and MELD score. Insulin resistance (IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects. Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay (DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%, respectively. The normal values were between 2 and 17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA (Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were < 6% and < 10%, respectively., Results: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects (P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B (P < 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation (P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification (r = 0.53; P < 0.01) or MELD score (r = 0.45; P < 0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin (r = 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin (r = -0.41; P < 0.01) or prothrombin time (r = -0.44; P <0.01). Moreover, insulin resistance was observed in 82.5% of the cirrhotic patients. In this group of patients, betatrophin levels were significantly higher than those in the group of patients without IR (P < 0.05)., Conclusion: Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance.

Introduction and Objectives: The aim of this study was to determine whether changes to referral protocols for cardiac surgery have had an impact on waiting times, hospitalizations and mortality during the waiting period and during the first year of follow-up after surgery., Methods: In this retrospective study of patients referred for cardiac surgery between January 1, 2008 and September 30, 2014, the study population was divided into two groups: those referred before (group A, January 1, 2008 to August 31, 2011) and after (group B, September 1, 2011 to September 30, 2014) the change in referral protocols. A telephone follow-up was conducted., Results: There were 864 patients referred for cardiac surgery, 557 in group A and 307 in group B. Patient characteristics were similar between groups. The mean waiting time for surgery was 10.6±18.5 days and 55.7±79.9 days in groups A and B, respectively (p=0.00). During the waiting period two patients (0.4%) were hospitalized in group A and 28 (9.1%) in group B (p=0:00); mortality was, respectively, 0% and 2.3% (p=0.00). During one-year follow-up 12.8% of group A patients and 16% of group B patients were hospitalized. Cardiovascular mortality in this period was around 5% in both groups (p>0.05)., Conclusion: Changes to referral protocols for cardiac surgery had an impact on waiting times, on the number of hospitalizations and on mortality in this period., (Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Background: The CLDN14 gene encodes a protein involved in the regulation of paracellular permeability or ion transport at epithelial tight junctions as in the nephron. The C allele of the rs219780 SNP (single nucleotide polymorphism) of CLDN14 has been associated with renal lithiasis, high levels of parathormone (PTH), and with low bone mineral density (BMD) in healthy women. Our aim is to study the relationship between rs219780 SNP of CLDN14 and renal lithiasis, fractures, and BMD in patients with primary hyperparathyroidism (PHPT)., Methods: We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analysed anthropometric data, history of fractures or kidney stones, biochemical parameters including markers for bone remodelling, abdominal ultrasound, and BMD and genotyping for the rs219780 SNP of CLDN14., Results: We did not find any difference in the frequency of fractures or renal lithiasis between the genotype groups in PHPT patients. Moreover, we did not find any relationship between the T or C alleles and BMD or biochemical parameters., Conclusions: rs219780 SNP of CLDN14 does not appear to be a risk factor for the development of PHPT nor does it seem to influence the clinical expression of PHPT.

Introduction and Objectives: Syncope is a common symptom that leads to 1% of admissions to hospital emergency departments, and is associated with high costs to the health system. The cardiology department of Faro Hospital has had a syncope unit since July 2007. The aim of this study is to analyze its results in terms of etiological diagnosis and treatment of syncope, using diagnostic flowcharts based on European Society of Cardiology (ESC) guidelines., Methods: We conducted a retrospective study of all patients referred to the syncope unit of Faro Hospital between July 2007 and August 2011. We analyzed demographic data, characteristics of syncopal episodes, diagnostic methods, etiology of syncope and treatment. The percentages of syncope of cardiac and uncertain etiology were compared with data from other international syncope units. Statistical analysis was performed using SPSS version 13.0., Results: Of the 304 patients referred to the syncope unit for loss of consciousness, 245 (80.7%) had syncope. Most had reflex syncope (52.2%), 20% had cardiac syncope, 15.6% had orthostatic hypotension, and in 12% of cases etiology remained undetermined. The percentages of cardiac and uncertain etiology were similar to data published by other syncope units., Conclusions: The Faro Hospital syncope unit obtained similar results to those published by other international syncope units through application of diagnostic flowcharts for etiological diagnosis of syncope. The flowcharts presented can be of value for the proper application of ESC guidelines on syncope., (Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

Background and Objective: An adequate bowel cleansing is needed prior to radiologic and endoscopic procedures. However, it may have a number of adverse effects, including abnormalities of calcium-phosphorus homeostasis., Patients and Method: This was an observational prospective study in a hospital practice setting. We included consecutive inpatients (n = 47) subjected to a barium enema or colon endoscopy. Prior cleansing was done as indicated by the attending physician by using a low-salt oral poliethylenglicol (PEG) solution, oral sodium phosphate or a phosphate-containing enema., Results: PEG solution frequently caused mild increases in serum sodium, and decreases in serum potassium. Oral phosphate caused a significant increase in serum phosphorus and parathormone concentrations, whereas it decreased serum calcium. Mild hyperphosphatemia was found in 57% of cases, and hypocalcemia in 36%. Phosphate enema also increased serum phosphate, causing mild hyperphosphatemia (33% cases). Although in the whole subgroup of enema-treated patients there were no significant changes in serum calcium, mild hypocalcemia was found in 27% cases., Conclusions: Bowel cleansing procedures, particularly those using oral phosphate salts, frequently induce hyperphosphatemia and other abnormalities in serum electrolytes. Although usually transitory and without overt clinical consequences, clinicians should be aware of this potential risk, especially in elderly patients and those with impaired renal function.

Objective: The aromatization of androgenic precursors in peripheral tissues, including bone, is the main source of estrogens after the menopause. CYP19, the gene encoding aromatase, has a long 5'-untranslated region with several variants of exon I and specific promoters. The aim of this study was to investigate the possible relationship between a common biallelic (C/G) polymorphism located on exon I.2 and bone mineral density (BMD)., Design: This was designed to be an association study between CYP19 polymorphism and BMD and the risk of vertebral fractures in women., Methods: DNA was extracted from the peripheral blood of 299 women (116 premenopausal and 183 postmenopausal). CYP19 alleles were identified by a method based on the exonuclease activity of Taq-polymerase. BMD was determined by dual-energy absorptiometry., Results: In premenopausal women there were no genotype-related differences in BMD. However, postmenopausal women with the CC genotype had lower spine and hip BMD than those with the GG genotype. The association between CYP19 genotypes and BMD was independent of other variables, such as age, height, body weight, calcium intake or years since menopause. The CC genotype was also associated with an increased risk of osteoporotic vertebral fractures (odds ratio 2.0; P=0.03). Serum levels of estrone and estradiol were similar in women with CC and GG alleles., Conclusions: A common biallelic polymorphism in the 5'-untranslated region of the CYP19-aromatase gene was associated with significant differences in bone mass and the risk of vertebral fractures in postmenopausal women. Given the frequency of allelic variants, genotype-related differences appear to be important from the perspective of the individual as well as the general population. Further studies are needed to elucidate underlying mechanisms that may be dependent on differences in estrogen bioactivity at the bone tissue level.

A growing body of evidence indicates that ageing brings a progressive disruption in the immune and endocrine systems. However, very few reports have correlated the changes in the immune system with the endocrine function in the elderly. The aim of the present study was to investigate the changes occurring in the peripheral blood lymphocyte subpopulations with age and correlate them with the hypothalamic-pituitary-adrenal (HPA) function. We determined the peripheral blood lymphocyte phenotype and the T cell receptor usage by flow cytometry analysis. The HPA function was evaluated by the basal serum levels of adrenal steroids and the response to stimulation with a low-dose ACTH. In the elderly, we observed a decrease of major T subsets together with an increase of NK cells and activated T cells. With regard to the HPA function, the most significant decline was found in dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS). A close correlation between immune changes with ageing and DHEA response to ACTH stimulation was found. The present study showed an inverse correlation of lymphocyte changes with the plasma levels of steroids, especially DHEA and its metabolite, DHEAS. This association was not found for other steroids and points for the possibility of using DHEA to correct the immunological decline associated with ageing.