Anna Neri

Incidence of metabolic syndrome among night-shift healthcare workers

Objective: Night-shift work is associated with ischaemic cardiovascular disorders. It is not currently known whether it may be causally linked to metabolic syndrome (MS), a risk condition for ischaemic cardiovascular disorders. The syndrome presents with visceral obesity associated with mild alterations in glucidic and lipidic homeostasis, and in blood pressure. The aim of this study was to assess whether a causal relationship exists between night-shift work and the development of MS. Methods: Male and female nurses performing night shifts, free from any component of MS at baseline, were evaluated annually for the development of the disorder during a 4-year follow-up. Male and female nurses performing daytime work only, visited during the same time period, represented the control group. Results: The cumulative incidence of MS was 9.0% (36/402) among night-shift workers, and 1.8% (6/336) among daytime workers (relative risk (RR) 5.0, 95% CI − 2.1 to 14.6). The annual rate of incidence of MS was 2.9% in night-shift workers and 0.5% in daytime workers. Kaplan–Meier survival curves of the two groups were significantly different (log-rank test; p<0.001). Multiple Cox regression analysis (forward selection method based on likelihood ratio) showed that among selected variables (age, gender, smoking, alcohol intake, familiar history, physical activity, and work schedule) the only predictors of occurrence of MS were sedentariness (hazard ratio (HR) 2.92; 95% CI 1.64 to 5.18; p = 0.017), and night-shift work (HR 5.10; 95% CI 2.15 to 12.11; p<0.001). Conclusions: The risk of developing MS is strongly associated with night-shift work in nurses. Medical counselling should be promptly instituted in night-shift workers with the syndrome, and in case of persistence or progression, a change in work schedule should be considered.

Systemic acute-phase response after laparoscopic and open cholecystectomy.

Background: Cytokines are the main mediators of inflammation and the response to trauma. The purpose of this study was to compare variations in cytokine levels following laparoscopic cholecystectomy (LC) and minilaparotomy cholecystectomy (OC), since these two types of operations were considered to be a unique model for examining the role of local tissue injury in postoperative inflammatory reactions. Methods: A total of 40 patients were studied. Eighteen of them underwent LC; the remaining 22 were operated on using the open technique. Systemic concentrations of interleukin- 6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor (TNF), and C-reactive protein (CRP) were measured before and after the operation. In addition, we compared pre- and postoperative white blood cell (WBC) counts, postoperative body temperature, and length of postoperative hospitalization. Results: There was no difference between the two groups in IL-1 and TNF response. The rise in plasma IL-6 levels (18.86 ± 9.61 vs 5.00 ± 0.0 pg/ml, p < 0.0001) and CRP (8.40 ± 5.81 vs 1.43 ± 1.30 mg/dl, p < 0.001) were more marked after open cholecystectomy than after the laparoscopic procedure. There was no correlation between serum CRP concentrations and the other postoperative parameters. Conclusion: The magnitude of the acute-phase response was less pronounced following laparoscopic cholecystectomy, consistent with a reduction in tissue trauma.

Thyroid function and morphology in patients affected by Williams syndrome

Objective  To evaluate the prevalence of abnormalities of thyroid function and morphology in a cohort of patients with Williams syndrome (WS).

p53 codon 72 polymorphism and coronary artery disease: Evidence of interaction with ACP1

Summary Background Common biological features between cancer and atherosclerosis suggest possible association of p53 with atherosclerotic diseases, but data on such a relationship are controversial, suggesting interactions with other variables. Acid phosphatase locus 1 (ACP1) is a polymorphic gene that controls the synthesis of an enzyme involved in important metabolic functions. Since ACP1 is associated with coronary artery disease (CAD), we searched for possible interactions between this enzyme and p53 codon 72 polymorphism with regard to their effects on susceptibility to CAD. Material/Methods The study included 381 patients admitted to the hospital for cardiovascular disease (232 patients with CAD and 149 with other cardiovascular problems) and 97 healthy newborns. Results The proportion of subjects carrying the *Pro allele of p53 codon 72 and the high activity *B*C genotype of ACP1 is higher in CAD (10.3%) than in non-CAD patients (2.0%) and in healthy newborns (6.2%). Conclusions The data suggest an interaction between p53 codon 72 and ACP1 wherein a positive effect of the p53 *Pro allele on susceptibility to CAD occurs, but only in the presence of the ACP1 genotype characterized by high enzymatic activity.

Atherosclerosis and PTPN22: A Study in Coronary Artery Disease

Objectives: Recently, it has been shown that PTPN22 genetic polymorphism is associated with phenotypes related to the risk of atherosclerosis. In the present note, we have searched for a possible association of PTPN22 polymorphism with coronary artery disease (CAD). Methods: One hundred and thirty-four non-diabetic subjects admitted to hospital for CAD and 174 healthy subjects (blood donors) were studied. PTPN22 genotypes were determined by DNA analysis. Statistical analyses were performed by SPSS programs. Results: In CAD patients, the proportion of carriers of the *T allele of PTPN22 is significantly higher compared to healthy controls (OR 2.66; 95% CI 1.07–6.72). Conclusions: The present observation confirms the association of PTPN22 phenotype with atherosclerosis and suggests a role of immune mechanism in the pathogenesis of CAD.

Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia

AIM To investigate the role of protein tyrosin phosphatase 22 (PTPN22), maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes (T1D) in Continental Italy and Sardinian populations. METHODS Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032 healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia. PTPN22 genotype was determined by DNA analysis. Maternal age at conception and age at onset of disease were obtained from clinical records. χ(2) test of independence, student t test for differences between means and odds ratio analysis were carried out by SPSS programs. Three way contingency table analysis was carried out according to Sokal and Rohlf. RESULTS The pattern of association between PTPN22 and T1D is similar in Continental Italy and Sardinia: the proportion of *T allele carriers is 13.6% in T1D vs 6.7% in controls in Continental Italy while in Sardinia is 7.3% in T1D vs 4.4% in controls. The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy: the proportion of newborn from mother aging more than 32 years is 89.3% in T1D vs 32.7% in consecutive newborn in Sardinia (P < 10(-6)) while in Continental Italy is 32.2% in T1D vs 19.1% in consecutive newborns (P = 0.005). This points to an important role of ethnicity. A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia. PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia. Maternal age does not influence significantly age at onset in Italy (8.2 years in T1D infants from mothers aging 32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years: P = 0.824) while in Sardinia a border line effect is observed (5.75 years in T1D infants from mothers aging 32 years or less vs 7.54 years in T1D infants from mothers aging more than 32 years: P = 0.062). No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males (8.07 years in males vs 6.3 years in females: P = 0.002). CONCLUSION The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.

ABH secretor genetic polymorphism: evidence of intrauterine selection.

OBJECTIVE Fucosyltransferase locus 2 (FUT2) controls the presence or absence of blood group substances (A, B, H) in the saliva and other body secretions. Secretor/non-secretor phenotypes are associated with some metabolic and infectious diseases. ABO and FUT2 contribute to build up oligosaccharide structures of the cell surface that are important for blastocyst adhesion and resistance to microbial invasion. We investigated a possible selection on ABH secretor phenotypes during intrauterine life. STUDY DESIGN Three hundred and fifty-six consecutive healthy puerperae and their newborn infants from the caucasian population of Rome were studied. Informed consent for study participation was obtained from the mothers to participate and the study was approved by the Institutional Review Board. ABH secretor Se phenotype was determined on saliva by standard laboratory procedure. RESULTS Symmetry analysis of mother infant Se phenotype revealed a deficit of mother Se+/newborn Se- with respect to expected values. The asymmetry is present only in infants carrying the A blood group antigen. The asymmetry was dependent on several maternal and neonatal parameters including maternal age, smoke, parity and gestational duration. CONCLUSIONS The data suggest intrauterine selection against Se- of the embryo carried by a Se+ mother. Such selection is dependent on factors influencing the maternal environment. The study could have practical importance in assessing the risk of infertility and success of artificial insemination.

Correlation between birth weight and placental weight in healthy and diabetic puerperae

OBJECTIVE The birth weight/placental weight ratio has an important predictive value for perinatal mortality and morbidity and for cardiovascular diseases in adult life. In this study, we compared the birth weight/placental weight (BW/PW) ratio and the correlation between the two parameters in diabetic women with that observed in healthy women. MATERIALS AND METHODS A total of 347 consecutive newborn infants from healthy puerperae, 164 newborns from puerperae with gestational diabetes, 148 newborns from puerperae with preexisting type 1 diabetes, and 40 newborns from puerperae with preexisting type 2 diabetes have been studied from the White population of Rome. The research project was approved by the Institutional Review Board and informed written consent was obtained from the participating mothers. RESULTS The BW/PW ratio is higher, and the correlation between the two parameters is lower in all classes of diabetes as compared to healthy puerperae. A remarkably low correlation is observed in preexisting diabetes pointing to a dissociation of fetal growth from placental growth. DISCUSSION In diabetic pregnancy the BW/PW ratio is higher, and the correlation between birth weight and placental weight is lower in all classes of diabetic as compared to healthy puerperae pointing to a relative dissociation between the two parameters. It has been suggested that the increase of glycemic levels in diabetic pregnancy predisposes to important diseases in adult life. The dissociation of BW from PW in infants of diabetic pregnancy could be a predictor of the risk for such diseases of adult life.

Ak1 genetic polymorphism and season of conception

OBJECTIVE The season of conception affects human reproduction, intrauterine growth, neonatal parameters, sex ratio, cognitive development and, in adult life, performance in many fields. Associations between polymorphic enzymes and season of conception have been also reported. In this study we searched for a possible association between season of conception and adenylate kinase locus 1 (Ak(1)). STUDY DESIGN Two samples of 381 and 248 consecutively newborn infants from two Italian cities with different geographical positions and climatic conditions were considered. Three way contingency table analysis and Student t-test analysis were performed. RESULTS Ak(1)2-1 phenotype is more frequent in males conceived in the summer-autumn period than in those conceived in winter-spring and this association depends on maternal Ak(1) phenotype (p=0.001). There is also an interaction between season of conception and Ak(1) phenotype concerning their effects on sex ratio and birth weight. CONCLUSION The present data suggest a complex interaction involving seasonal cycles, maternal and foetal Ak(1) genotype and sex of foetus concerning their effects on intrauterine selection and neonatal parameters.

Genetic variability within Adenosine Deaminase gene and uterine leiomyomas

OBJECTIVE The recent observation of an association of colon cancer with two polymorphic sites within the Adenosine Deaminase (ADA) gene suggests an involvement of these polymorphisms in the development of solid tumors. This prompted us to search for a similar association in uterine leiomyomas. STUDY DESIGN We have studied 181 women admitted to the hospital for leiomyomas requiring surgical intervention and 248 women of comparable age without clinical signs of leiomyomas. All women were from the White population of Rome and gave verbal consent to participate in the study. The genotypes of three polymorphic sites (ADA1, ADA2, ADA6) of ADA gene were determined by DNA analysis. RESULTS A higher proportion of ADA2*1/*1 genotype and of carriers of the ADA6*1 allele was observed in women with leiomyomas as compared to controls. This parallels the association found in colon cancer. CONCLUSIONS This pattern is identical to that previously observed in colon cancer making the possibility of mere sample chance artifact unlikely and supporting the hypothesis that genetic polymorphisms within the ADA gene could be involved in the susceptibility to solid tumors. Genetic variability within the ADA gene may influence adenosine concentration and in turn the immune response by lymphocytes in solid tumors. On the other hand ADA molecules acting as ecto-enzyme may be involved in the transduction of signals in the cell surface with important effects on tumor development.