Antonio Fraioli

Liver vitamin D receptor, CYP2R1, and CYP27A1 expression: relationship with liver histology and vitamin D3 levels in patients with nonalcoholic steatohepatitis or hepatitis C virus

Evidence suggests an association between low serum 25‐hydroxy‐vitamin D3 [25(OH)D3] levels and the presence and prognosis of liver disease. Vitamin D receptor (VDR) has been widely detected in the liver, but its expression in the course of liver disease has never been investigated. We evaluated the hepatic expression of VDR along with that of vitamin D 25‐hydroxylases in patients with nonalcoholic steatohepatitis (NASH) or chronic hepatitis C (CHC) and its relationship with hepatic histological features and serum 25(OH)D3 levels. We evaluated 61 patients (25 NASH and 36 CHC) who had undergone liver biopsy for clinical purposes and 20 subjects without liver disease. Serum 25(OH)D3 was measured via colorimetric assay. Expression of VDR, CYP2R1, and CYP27A1 was evaluated via immunohistochemistry in hepatocytes, cholangiocytes, and liver inflammatory cells. Parenchymal and inflammatory cells from liver biopsies of patients with NASH and CHC expressed VDR, CYP2R1, and CYP27A1. In NASH patients, VDR expression on cholangiocytes was inversely correlated with steatosis severity (P < 0.02), lobular inflammation (P < 0.01), and nonalcoholic fatty liver disease score (P < 0.03). Moreover, expression of CYP2R1 in hepatocytes correlated strongly with VDR positivity on liver inflammatory cells. In CHC subjects, fibrosis stage was associated with low hepatic CYP27A1 expression, whereas portal inflammation was significantly higher in patients with VDR‐negative inflammatory cells (P < 0.009) and low VDR expression in hepatocytes (P < 0.03). Conclusion: VDR is widely expressed in the liver and inflammatory cells of chronic liver disease patients and its expression is negatively associated with the severity of liver histology in both NASH and CHC patients. These data suggest that vitamin D/VDR system may play a role in the progression of metabolic and viral chronic liver damage. (HEPATOLOGY 2012;56:2180–2187)

Epidemiology of Nephrolithiasis

The main purpose of the study is to acquire useful information on nephrolithiasis in Italy, given the recent increase in its prevalence. The analysis was based on data from sample surveys of the Italian population carried out in 1983 and 1993–1994 as well as on data obtained from medical records of patients treated at the ASTIF in Fiuggi. An increase in the prevalence of the disease from 11.7 to 17.2 out of 1,000 inhabitants has been observed over the last 10 years; most patients are men and elderly, and the highest frequency is in southern and the lowest in northern Italy. The results of the study confirm the hereditary predisposition, since nephrolithiasis is very common among patients’ parents (22.5%) and siblings (14.1%). The patients eat more meat than others and are often overweight or obese; the latter represent 18% of these patients and 11% of the general population.

Hypovitaminosis D is independently associated with metabolic syndrome in obese patients.

Background Metabolic syndrome (MS) and hypovitaminosis D represent two of the most diffuse condition worldwide, reaching pandemic proportions in industrialized countries, and are both strongly associated with obesity. This study set out to evaluate the presence of an independent association between hypovitaminosis D and MS in an adult population of obese subjects with/without MS. Methods We recruited 107 consecutive obese subjects, 61 with MS (age(mean±SD) 45.3±13.3 years, BMI(mean±SD): 43.1±8.3 kg/m2) and 46 without MS (age: 41.8±11.5, p = n.s., BMI:41.6±6.5 kg/m2, p = n.s.) comparable for sex, BMI, waist circumference and body fat mass, evaluated by bioimpedentiometry. 25(OH) vitamin D3 levels were measured by colorimetric method. Insulin resistance was estimated by fasting blood insulin, HOMA-IR and ISI. Results Serum 25(OH)D3 levels were significantly lower in MS obese patients than in obese subjects without MS (median(range) 13.5(3.3–32) vs 17.4(5.1–37.4), p<0.007). Low 25(OH)D3 levels correlated with glycaemia (p<0.007), phosphate (p<0.03), PTH (p<0.003) and the MS (p<0.001). Multivariate model confirmed that low 25(OH)D3 levels were associated with the diagnosis of MS in obese patients independently from gender, age, serum PTH and body fat mass. After stratifying the study population according to 25(OH)D3 concentrations, patients in the lowest quartile showed a markedly increased prevalence of MS compared to those in the highest quartile (OR = 4.1, CI 1.2–13.7, p = 0.02). Conclusions A powerful association exists between hypovitaminosis D and MS in obese patients independently from body fat mass and its clinical correlates. This indicates that the association between low 25(OH) D3 levels and MS is not merely induced by vitamin D deposition in fat tissue and reinforces the hypothesis that hypovitaminosis D represent a crucial independent determinant of MS.

Clinical researches on the efficacy of spa therapy in fibromyalgia: a systematic review

BACKGROUND Fibromyalgia is characterized by chronic widespread pain, tenderness at muscle and tendon insertions point when digital pressure is applied, sleep disorders, chronic fatigue, depressive episodes, anxiety, and other functional somatic syndromes. OBJECTIVE The aim of this study was to determine whether balneotherapy with mineral waters and mineral-water containing mud is effective in the management of fibromyalgia. METHODS We conducted a systematic review of the literature regarding spa therapy in the treatment of the fibromyalgia. We searched many databases for articles published between 2000 and 2012 and we selected 7 studies among 65 articles retrieved. A total of 142 patients received balneotherapy and 129 were controls. CONCLUSION Study data confirms that spa therapy could improve the symptoms of fibromyalgia including pain, depression and minor symptoms.

Subclinical vascular alterations in young adults with type 1 diabetes detected by arterial tonometry

Diabetes mellitus is characterized by a very high prevalence of atherosclerotic disease. Aims of this study were to determine arterial compliance parameters in type 1 diabetes (T1D) patients as an expression of early pre‐clinical endothelial dysfunction and to evaluate the impact of glucose exposure parameters such as the duration of diabetes and glycosylated haemoglobin (HbA1c) on the risk of developing alterations in vascular compliance.

Chemical Analysis of Water of the Anticolana Valley: Isolation of Humic Compounds

The purpose of this study was to identify and characterize humic compounds in Anticolana Valley (Fiuggi) water. The capacity of this class of compounds to mobilize metals from solid phases could have an important role in calculi solubilization. Humic compounds were isolated, purified and characterised by FTIR, 1H-NMR and 13C-NMR spectroscopy, thermogravimetry and elemental analysis. Only fulvic acids were found. They are mainly composed of aliphatic chains, made of six –CH2O– groups and contain a number of carboxylic groups, responsible for their metal complexing capacity.

Appropriateness and efficacy of Spa therapy for musculoskeletal disorders. A Delphi method consensus initiative among experts in Italy

OBJECTIVE The aim of the study was to identify the main aspects concerning appropriateness and efficacy of Spa therapy for musculoskeletal pathologies. METHODS A committee of 8 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Clinicians from Italian medical centers specialized in rheumatology, rehabilitation and thermal medicine took part in a Delphi process aimed at obtaining consensus statements among the participants. RESULTS Large consensus was obtained for statements grouped under the following main themes: treatment indications; choice of treatment modality and treatment efficacy. CONCLUSIONS The experts developed a number of consensus statements which may be used as a practical reference to guide the choice of physicians to treat musculoskeletal diseases with Spa therapy.

Functional rs20417 SNP (–765G>C) of Cyclooxygenase-2 Gene Does Not Predict the Risk of Recurrence of Ischemic Events in Coronary Patients: Results of a 7-Year Prospective Study

Objectives: The –765G>C variation (rs20417 SNP) in the promoter of cyclooxygenase-2 (COX-2) gene has been demonstrated to lower COX-2 enzyme activity in the vasculature, thus affecting atherosclerotic plaque growth and stability. Therefore, this genetic variant may be a candidate influencing the residual risk. Methods: In 285 coronary patients the incidence of major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular deaths, non-fatal myocardial infarction and stroke, unstable angina and revascularization procedures, was monitored for a median of 7.8 years. The genotypes were obtained in 231 patients (81%) by PCR amplification and FAU I digestion. Results: 89 MACEs (38.5%) were recorded during the follow-up in genotyped patients. Their incidence was not different in patients with GC or CC when compared with those with GG genotype (46.2 vs. 35.5% respectively; p = 0.14). Kaplan-Meyer analysis did not demonstrate any influence of COX-2 genotypes on the event-free survival time (log-rank p = 0.55). After controlling for confounders, the –765G>C carrier status was not associated with significant variation in the risk of MACE or its individual components. Conclusions: These results suggest that the functional G–765C variant in the COX-2 gene is not a significant predictor of the recurrence of ischemic events in coronary patients.

Solvent effect in vitro of Anticolana Valley water on renal stones : Analytical-instrumental study

The presence of humic and fulvic acids in the Anticolana Valley (Fiuggi) water has been established. On the basis of this evidence we investigated the capacity of Anticolana Valley (Fiuggi) water to dissolve renal calculi in vitro. Crystals of calcium oxalate monohydrate to simulate a kidney stone were prepared. Human renal stones of calcium oxalate monohydrate were obtained by courtesy of the Division of Urology of ‘La Sapienza’ University (Rome), the Division of Urology of the University of Havana (Cuba) and the ASTIF of Fiuggi. The study was performed using the Anticolana Valley (Fiuggi) water, distilled water and tap water (ACEA, Rome), in a specially designed Perspex apparatus. Each calculus was subjected to a water flow of 2 liters/24 h. The capacity of the Anticolana Valley (Fiuggi) water to dissolve human and synthetic calculi was found to be much higher than that of distilled water which in turn was significantly more effective than tap (ACEA) water.

Comment on Elangovan H et al. Vitamin D in liver disease: Current evidence and potential directions. Biochim Biophys Acta 2017;1863(4):907-916

Please cite this article as: I. Barchetta, M. Del Ben, F. Angelico, M. Di Martino, A. Fraioli, G. La Torre, R. Saulle, L. Perri, S. Morini, C. Tiberti, L. Bertoccini, F.A. Cimini, F. Panimolle, C. Catalano, M.G. Baroni, M.G. Cavallo, Comment on Elangovan H et al. Vitamin D in liver disease: Current evidence and potential directions. Biochim Biophys Acta 2017;1863(4):907-916, BBA Molecular Basis of Disease (2017), doi:10.1016/j.bbadis.2017.04.023